The effect of X-rays on mouse normal femoral bone marrow GM-CFC was compared using two different in vitro cell culture techniques - the agar colony assay and the radioisotope uptake assay (125IUdR or 3HTdR). The values obtained with the agar colony assay was 1.00 +/- 0.09 Gy and 2.10 +/- 0.10 Gy as measured by the radioisotope assay. Similar values were observed when the bone marrow cells were irradiated to vitro or to vivo. It was observed that the concentration of WEHI-3B conditioned medium (CSA) used in the agar colony assay would affect GM-CFC content of irradiated or normal bone marrow cells. But when optimum or greater levels of CSA were used the survival parameters plateaus. Pre-trypsinisation of bone marrow cells was not demonstrated to have modified the radiation survival characteristics of GM-CFC to X-rays and Do were not significantly different from GM-CFC from untreated bone marrow cells. Two distinct subpopulations of GM-CPC were observed based on their sensitivity to trypsin. One was survival-dose dependent and the other totally unaffected by increasing trypsin concentrations. Their ratio was approximately 1:1. Trypsin permeabilised murine bone marrow cells were treated with restriction endonucleases Pvu II and Bam HI. It was postulated that these endonucleases generated blunt-ended and cohesive-erided double-strand breaks (dsb), respectively. The cells were then assayed for their clonogenic ability to simulate GM-CFC death following X-ray exposure and to test the hypothesis that cell death arises from the induction of dsb in DNA via the formation of chromosomal aberrations. The results reported here show that Pvu II simulates X-ray exposure in causing a dose-dependent loss of the reproductive integrity of mouse femoral bone narrow GM-CPC, whilst Bam HI was found not to reduce cell survival even when concentrations greater than Pvu II were employed. These results support the idea that X-irradiated mammalian cells undergo a mode of death in which dsb in the DNA are lethal resulting in the loss of clonogenic ability. In contrast to previous experiments using inactivated Sendai virus, 0.001% trypsin was used to permeabilise the cells before treatment with the restriction endonucleases. However, when 0.05% trypsin was used Pvu II was shown not to further reduce the survival fraction of GM-CFC. The storage buffer containing the restriction endonucleases were found to be toxic but a region of tolerance was observed when the lower trypsin concentration was used. This had enabled the study of the effect of the restriction endonucleases on GM-CFC without the complicating presence of other forms of damage. From the D37 values, a dose of 142 +/- 4 units of Pvu II was equivalent to 1.20 Gy of X-rays (ie. 100 units = 0.85 Gy).

With the intention of preparing long chain esters containing a carbocyclic system, methyl linoleate and related esters were subjected to strongly acidic reaction conditions. The major product of the reaction, however, was shown to be a mixture of isomeric 1,4-epoxidea (tetrahydrofurans) and for comparison, a mixture of the cis and trans 9,12-epoxidos was prepared by an unambiguous synthesis. The discovery of those hotorocyclic fatty esters prompted further investigations into their methods of preparation. The cyclodehydration of some trihydroxyacids containing a 1,4-diol system was examined and the mechanism of the reaction elucidated. Those studies led to the formulation of the absolute configurations of the 9,12,13-tri-hydroxystearic acids. Methyl ricinoleate and methyl 9-hydroxyoctadec-cis-12- enoate were found to give different types of product when epexidised, The former yielded the expected 1,2-epoxide, whilst the latter furnished a mixture of hydroxytetrahydrofurans (90%). Since it was evident that the second reaction involved participation by the hydroxyl function, other epoxidation Reactions of various hydroxy, oxo and acetylenic ostors were investigated. The results indicated that oxo and hydroxy functions can interact with a proformed epoxide to yield cyclic products. Finally, various unsubstiuted 1,4-opoxidos were prepared by free radical oxidations of some hydroxyostors. Both load totraacotate and metal oxido-halogon mixtures were used as oxidising agents.

No description available.

Machine-assisted formal proofs are becoming commonplace in certain fields of mathematics and theoretical computer science. New formal systems and variations on old ones are constantly invented. The meta-theory of such systems, i.e. proofs about the system as opposed to proofs within the system, are mostly done informally with a pen and paper. Yet the meta-theory of deductive systems is an area which would obviously benefit from machine support for formal proof. Is the software currently available sufficiently powerful yet easy enough to use to make machine assistance for formal meta-theory a viable proposition? This thesis presents work done by the author on formalizing proof theory from [DP97a] in various formal systems: SEQUEL [Tar93, Tar97], Isabelle [Pau94] and Coq [BB+96]. SEQUEL and Isabelle were found to be difficult to use for this type of work. In particular, the lack of automated production of induction principles in SEQUEL and Isabelle undermined confidence in the resulting formal proofs. Coq was found to be suitable for the formalisation methodology first chosen: the use of nameless dummy variables (de Bruijn indices) as pioneered in [dB72]. A second approach (inspired by the work of McKinna and Pollack [vBJMR94, MP97]) formalising named variables was also the subject of some initial work, and a comparison of these two approaches is presented. The formalisation was restricted to the implicational fragment of propositional logic. The informal theory has been extended to cover full propositional logic by Dyckhoff and Pinto, and extension of the formalisation using de Bruijn indices would appear to present few difficulties. An overview of other work in this area, in terms of both the tools and formalisation methods, is also presented. The theory formalised differs from other such work in that other formalisations have involved only one calculus. [DP97a] involves the relationships between three different calculi. There is consequently a much greater requirement for equality reasoning in the formalisation. It is concluded that a formalisation of any significance is still difficult, particularly one involving multiple calculi. No tools currently exist that allow for the easy representation of even quite simple systems in a way that fits human intuitions while still allowing for automatic derivation of induction principles. New work on integrating higher order abstract syntax and induction may be the way forward, although such work is still in the early stages.

GUIMARÃES, Larissa Alves. Potencial anticâncer de actinomicetos recuperados do sedimento da praia da Pedra Rachada, Paracuru, Ceará. 2013. 70 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2013. / Submitted by denise santos (denise.santos@ufc.br) on 2014-06-03T12:54:32Z No. of bitstreams: 1 2013_dis_laguimarães.pdf: 1916575 bytes, checksum: 246be3ea6464010f766e0f2d14c7e46e (MD5) / Approved for entry into archive by denise santos(denise.santos@ufc.br) on 2014-06-03T12:55:35Z (GMT) No. of bitstreams: 1 2013_dis_laguimarães.pdf: 1916575 bytes, checksum: 246be3ea6464010f766e0f2d14c7e46e (MD5) / Made available in DSpace on 2014-06-03T12:55:35Z (GMT). No. of bitstreams: 1 2013_dis_laguimarães.pdf: 1916575 bytes, checksum: 246be3ea6464010f766e0f2d14c7e46e (MD5) Previous issue date: 2013 / The sea sediment is an important source of microorganisms that synthesize secondary metabolites with biomedical proprieties. During the past 10 years, the coast of Ceará has been prospected for the pharmacological potential housed in sponges, tunicates and corals, but little data are available regarding that of the microorganisms. In the present study, crude extracts from actinomycetes recovered from sediment collected at Pedra Rachada Beach, Paracuru, Ceará State, were evaluated for their cytotoxicity against tumor cells in culture. Among the 26 extracts, 16 inhibited more than 65% of growth of HCT-116 cells. The extract derived from the strain BRA-090, which exhibited the highest percentage of cell growth inhibition (98.38%), showed IC50 of 0.19 µg/mL and was grown in large scale in order to isolate active principles. Chemical fractionation techniques, such as flash chromatography and HPLC, were applied to this extract, which led to identification of three known chromomycins (chromomycins A2, A3 and desmetilchromomycin A2) and also two molecular masses regarding probable new molecules of the same class. Chromomycin A2 (C-A2) was isolated and the cytotoxic activity was evaluated across a panel of cell lines, with IC50 ranging from 7.8 to 49.5 nM for exposures of 48 and 72h. For 24h exposure period, none of the IC50 values were found to be below 50 nM. C-A2 was also tested against the non-tumor line MRC-5 with IC50 of 109 nM. The MALME-3M cells, which showed the best activity after 48h incubation, was chosen to investigate the potent cytotoxic effect of C-A2 at concentrations of 10, 20, 30 and 40 nM. C- A2 reduced viability of MALME-3M cells in concentration dependent manner and increased the number of non-viable cells in the two highest concentrations tested. As for changes in the cell cycle, C-A2 induced, particularly for treatment with 40 nM, reduction of S phase and increase in G0/G1 phase. Morphological analysis of MALME-3M cells treated with C-A2, mainly at 30 and 40 nM, presented membrane blebs, cellular volume reduction and DNA fragmentation, which are features suggestive of apoptosis. Treatment with 30 nM also induced the appearance of several cell fragments resembling autophagosomes, may suggest the occurrence of autophagy. / O sedimento marinho é uma importante fonte de microrganismos produtores de metabólitos secundários com propriedades biomédicas. Os actinomicetos são bactérias Gram-positivas e filamentosas bem conhecidas como profícuos produtores de produtos naturais com diversas atividades biológicas. A costa do Ceará vem sendo investigada, há pouco mais de 10 anos, quanto ao potencial farmacológico abrigado em esponjas, tunicados e corais, porém há ainda poucos registros de microrganismos como foco da prospecção de produtos naturais bioativos. No presente trabalho, os extratos brutos produzidos a partir dos 26 actinomicetos recuperados do sedimento coletado na Praia da Pedra Rachada, no município do Paracuru, Ceará, foram testados quanto a sua citotoxicidade em células tumorais em cultura. Dos 26 estratos brutos testados, 16 inibiram mais que 65% do crescimento de células HCT-116. A cepa denominada BRA-090, cujo extrato teve o maior porcentual de inibição do crescimento celular (98,38%), apresentou CI50 de 0,19 µg/mL e foi selecionada para crescer em larga escala a fim de isolar o(s) princípio(s) ativo(s). O fracionamento químico utilizando técnicas como cromatografia flash e CLAE levaram a identificação de três cromomicinas conhecidas (cromomicinas A2, A3 e desmetilcromomicina A2) além de duas massas referentes a prováveis novas moléculas da mesma classe. A cromomicina A2 (C-A2) foi isolada e teve a sua atividade citotóxica avaliada para outras seis linhagens tumorais, com CI50 variando de 7,8 a 49,5 nM para exposições durante 48 e 72h de duração. Com 24h, não foi encontrado valor CI50 abaixo de 50 nM. A C-A2 também foi testada contra a linhagem não tumoral MRC-5, com CI50 de 109nM. As células MALME-3M, para qual se obteve a melhor atividade no tempo de 48h de incubação, foi a escolhida para investigar o potente efeito citotóxico de C-A2 nas concentrações de 10, 20, 30 e 40 nM de C-A2. A C-A2 mostrou reduzir a viabilidade de células MALME-3M de forma concentração-dependente, e aumentou o número de células não viáveis nas duas maiores concentrações testadas. Quanto as alterações no ciclo celular, C-A2 apresentou, em particular para o tratamento com 40 nM, redução da fase S e aumento da fase G0/G1. Na análise morfológica das células MALME-3M, sobremaneira aquelas expostas a concentrações de 30 e 40 nM, foram observadas diversas alterações, tais como blebs de membrana plasmática, redução do volume celular e fragmentação de DNA, características sugestivas de apoptose. No tratamento com 30 nM, diversos fragmentos celulares similares a autofagossomos estavam presentes, sugerindo, ainda, a ocorrência de autofagia.

The exploration and application of nanomaterials have been attracting researchers’ attention in recent decades. Nanocatalysts, as one of the very important classes of nanomaterials, have been developed for several generations. Nanotechnology makes light be possibly utilized in catalysis rather than only heat and allows multifunctional parts to be assembled in one catalyst. The TiO2 (as the representative of hetero-photocatalyst) and iron-based magnetic catalysts (as multifunctional catalyst) will be discussed in detail in this thesis. The first chapter will introduce the background of catalysts and nanomaterials. TiO2, especially black TiO2, will be mainly discussed in the aspects of properties, synthesis, and applications. Another part of the chapter will talk about the separation-friendly catalyst – magnetic heterogenous catalysts’ synthesis and applications. Chapter 2 focuses on the synthetic route we used and the characterization of black TiO2 catalysts and magnetic catalysts. Both anatase and rutile black TiO2 catalysts were successfully prepared originally from Degussa P25 using the ethanol reduction method. The re-whitening treatment was also examined on both black TiO2 catalysts. All catalysts were characterized and compared by diffuse reflectance (DR), powder X-ray diffraction (XRD), and X-ray photoelectron spectroscope (XPS). Tauc plot results show that black TiO2 has smaller band gap than white TiO2. XPS revealed the existence of surface -OH species and Ti3+ in black TiO2. Furthermore, these two characterization techniques and XRD all proved that the blackening and re-whitening treatment does not change the crystalline phase of the catalysts, and the blackening treatment is reversible. For magnetic catalysts, we synthesized magnetic Fe2O3, Fe2O3@TiO2, copper/iron oxide magnetic TiO2, and black magnetic catalysts. Other than diffuse reflectance spectroscopy, Raman spectroscopy, scanning electron microscopy, and energy-dispersive X-ray elemental mapping analysis were used for determining the light-absorption properties, composition, and morphology of all synthesized magnetic catalysts. In addition, the magnetic separation was also achieved by simply applying an external magnetic field. Chapter 3 will discuss and compare the decarboxylation reaction activities of pristine, black, and re-whited TiO2 catalysts. The reactions were carried under the UV, blue, red, green, and white light irradiation. Unfortunately, the reaction was found only working under UV-light irradiation. The best solvent was dioxane which may be due to the proton affinity of the oxygen atom in dioxane molecule, which facilitates the deprotonation of the carboxylic acid. The optimal catalyst amount was found as 10 mg per 5 mL reaction mixture, and the kinetic study shows that the reaction is a pseudo-first order reaction. It is a pity that the performance of black TiO2 catalysts is worse than the pristine and re-whitened TiO2. Chapter 4 will talk about the sol-gel synthesized magnetic catalysts. These catalysts were used for aldehyde-alkyne-amine (A3) coupling reaction. The reaction was tested by light irradiating or traditional heating, but only heating can make the reaction proceed. Results also show that the coupling reaction requires copper to finish. The best solvent was found as toluene and the optimal reaction time is 6 hours at 120 ̊C. Sadly, the reactivity of copper/iron oxide magnetic TiO2 decreases a lot after three reaction cycles because of the copper leaching problem.

A presente dissertação de mestrado descreve estudos sobre as reações multicomponentes A3 na versão assimétrica. Diversas metodologias foram empregadas visando a obtenção de propargilaminas opticamente ativas, que são blocos sintéticos versáteis na preparação de compostos bioativos. O trabalho foi dividido em duas partes. Na primeira parte, estudou-se a utilização de aminas opticamente puras como materiais de partida para a reação tricomponente A3. Neste caso, foi utilizada a 2-metilpropan-2-sulfinamida como amina principal, no entanto, o produto de acoplamento não foi obtido, mesmo em diversas condições testadas. Outras aminas opticamente puras, como a (S)- metilbenzilamina e aminas derivadas de amino ácidos, também foram testadas. Os resultados, quanto às razões diastereoisoméricas e rendimento, foram satisfatórios quando aminas derivadas de amino ácidos foram utilizadas, principalmente quando o éster metílico da L-polina foi empregado como fonte de amina, que levou a formação do produto em bom rendimento e uma razão enantiomérica de 15:85. Na segunda parte do trabalho estudou-se a utilização de auxiliares quirais, na reação de A3, como indutores de assimetria. Para tanto, diversos compostos foram testados como oxazolinas opticamente puras e derivados de L-prolina. / This masters thesis describes studies for the asymmetric version of A3 multicomponent reactions. Several methodologies were employed in order to obtain optically active propargylamines, which are versatile synthetic building blocks on the preparation of bioactive compounds. The work was divided into two parts. In the first part, we investigated the use of optically pure amines as starting materials for the A3-coupling reaction. In this case, we used the 2-methylpropan-2-sulfinamide as the main amine, however, the coupling product was not obtained, even under several reaction conditions. Other optically pure amines such as (S)-methylbenzylamine and amines derived from amino acids, were also tested. The yields and diastereomeric excess were satisfactory when amines derived from amino acids were employed, especially when the methyl ester of L-poline was used as amine source, which led to the formation of the product in good yield and diastereoisomeric ratio. In the second part we studied the use of chiral auxiliaries in the A3-coupling reaction to induce the asymmetry. Therefore, several compounds were tested as optically pure oxazolines and L-proline derivatives.

A presente dissertação de mestrado descreve estudos sobre as reações multicomponentes A3 na versão assimétrica. Diversas metodologias foram empregadas visando a obtenção de propargilaminas opticamente ativas, que são blocos sintéticos versáteis na preparação de compostos bioativos. O trabalho foi dividido em duas partes. Na primeira parte, estudou-se a utilização de aminas opticamente puras como materiais de partida para a reação tricomponente A3. Neste caso, foi utilizada a 2-metilpropan-2-sulfinamida como amina principal, no entanto, o produto de acoplamento não foi obtido, mesmo em diversas condições testadas. Outras aminas opticamente puras, como a (S)- metilbenzilamina e aminas derivadas de amino ácidos, também foram testadas. Os resultados, quanto às razões diastereoisoméricas e rendimento, foram satisfatórios quando aminas derivadas de amino ácidos foram utilizadas, principalmente quando o éster metílico da L-polina foi empregado como fonte de amina, que levou a formação do produto em bom rendimento e uma razão enantiomérica de 15:85. Na segunda parte do trabalho estudou-se a utilização de auxiliares quirais, na reação de A3, como indutores de assimetria. Para tanto, diversos compostos foram testados como oxazolinas opticamente puras e derivados de L-prolina. / This masters thesis describes studies for the asymmetric version of A3 multicomponent reactions. Several methodologies were employed in order to obtain optically active propargylamines, which are versatile synthetic building blocks on the preparation of bioactive compounds. The work was divided into two parts. In the first part, we investigated the use of optically pure amines as starting materials for the A3-coupling reaction. In this case, we used the 2-methylpropan-2-sulfinamide as the main amine, however, the coupling product was not obtained, even under several reaction conditions. Other optically pure amines such as (S)-methylbenzylamine and amines derived from amino acids, were also tested. The yields and diastereomeric excess were satisfactory when amines derived from amino acids were employed, especially when the methyl ester of L-poline was used as amine source, which led to the formation of the product in good yield and diastereoisomeric ratio. In the second part we studied the use of chiral auxiliaries in the A3-coupling reaction to induce the asymmetry. Therefore, several compounds were tested as optically pure oxazolines and L-proline derivatives.

This thesis is an attempt to introduce the governor of to-day to the work of their earliest predecessors, in the belief that it will prove to be, if not always an example, at least of considerable relevance to the problems of modern administration. The purpose of the thesis is to construct a history of the governorship (al-wilaya) and the governors (al-wulat).

Yu, Po Ting. / Thesis M.Phil. Chinese University of Hong Kong 2014. / Includes bibliographical references (leaves 193-199). / Abstracts also in Chinese. / Title from PDF title page (viewed on 15, September, 2016).