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"Os franciscanos da reconciliação e o ecumenismo na arquidiocese de São Paulo (1977-1994)" / The franciscan friars of the atonement and the ecumenism at archdiocese of Sao Paulo (1977-1994)Edison Minami 23 June 2005 (has links)
O presente trabalho busca analisar a atuação dos Franciscanos da Reconciliação(Atonement) em São Paulo entre os anos 1977 a 1994. Fundados em 1898 pela iniciativa do então reverendo Episcopal Anglicano Paul James Francis (Pe. Paul Wattson) e da Irmã Lurana White passam a pregar a união entre as Igrejas Católica, Episcopal Anglicana e Ortodoxa Grega. Em 1909 a conversão dos membros ao catolicismo não interrompeu as atividades ecumênicas, que prosseguem mesmo após a morte de Paul Wattson em 1940. Iniciam a Missão no Brasil nas Dioceses de Jataí e Rio Verde (GO) em 1963. Em São Paulo o trabalho teve início no ano de 1977 a convite do então arcebispo de São Paulo D.Paulo Evaristo Arns ampliando o trabalho ecumênico na Arquidiocese. Em 1994 decidiram encerrar sua presença no Brasil. / The objective of the present work is to analyse the ecumenical task performed by Franciscan Friars and Sisters of Atonement in Sao Paulo City in the period from 1977 to 1994. Founded in 1898 by Anglican Episcopal reverend Paul James Francis (Father Paul Wattson) and Mother Lurana White started the movement preaching the union of Catholic, Anglican Episcopal and Greek Orthodox Churches. The conversion of those members to Catholicism in 1909 did not interrupt the ecumenical activities, which continued after the death of Paul Wattson in 1940. They created in 1963 the mission at Jataí and Rio Verde Diocese in Goias State. In Sao Paulo City the action took place in 1977 by invitation of archbishop D. Paulo Evaristo Arns, expanding the ecumenical work inArchdiocese . In 1994 they decided their departure from Brazil.
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Inibição do sistema NF-KB durante a lactação promove hipertensão na vida adulta / Inhibition of NF-kB system during lactation promotes hypertension in adult lifeDaniele Canale 21 September 2009 (has links)
Em roedores, a administração de Losartan (LO) durante a nefrogênese (primeiras duas semanas de vida) leva à insuficiência renal progressiva e, mais tardiamente, à hipertensão, indicando que a Angiotensina II (AII) é indispensável a uma nefrogênese adequada. Os mediadores intracelulares desse efeito são desconhecidos. Nós investigamos se o sistema NF-kB, que tem influência na embriogênese de outros tecidos, poderia ser um desses mediadores. Trinta e duas ratas Munich Wistar, cada uma amamentando 6 filhotes, foram divididas em dois grupos: C, sem tratamento, e PDTC, que receberam o inibidor do NF-kB Pirrolidina Ditiocarbamato (PDTC), 280 mg/kg/dia na água de beber durante 21 dias. A prole (C e PDTC), constituída de ratos machos, foi acompanhada até 10 meses de vida sem qualquer tratamento. Diferentemente do observado anteriormente com o LO, o PDTC não promoveu redução do número de néfrons nem albuminúria, indicando que o sistema NF-kB não participa crucialmente da nefrogênese. No entanto, os ratos que receberam o PDTC durante a lactação apresentaram hipertensão persistente, associada a hipertrofia de miócitos e a fibrose miocárdica. Para investigar a patogênese da hipertensão (que não se pode explicar por uma redução no número de néfrons), as expressões renais dos componentes do sistema renina-angiotensina (SRA) e dos transportadores tubulares foram determinadas por PCR em tempo real (qRT-PCR) aos 3 e 10 meses de vida. Aos 3 meses, a expressão de angiotensinogênio (AGT) e renina foram significativamente aumentadas no grupo PDTC vs C, indicando que uma ativação local do SRA pode explicar o desenvolvimento da hipertensão no grupo PDTC. No entanto, a expressão de todos os componentes do SRA examinados nos animais que receberam o PDTC durante a nefrogênese estava diminuída aos 10 meses, possivelmente devido a um mecanismo compensatório, sugerindo que a hipertensão foi mantida por outros mecanismos. No túbulo proximal, observou-se um aumento da expressão do transportador sódio/glicose isoforma 1 (SGLT1) (luminal) e sódio/bicarbonato (NBC) (basolateral), bem como um aumento numérico na expressão do trocador luminal sódio/hidrogênio isoforma 3 (NHE3), sugerindo que essas anormalidades podem estar envolvidas na patogênese da hipertensão nesses animais. Aos 10 meses, a expressão de todas as moléculas estava diminuída, sugerindo a participação de outros mecanismos na manutenção da hipertensão em longo prazo. A administração de PDTC pode representar um novo modelo de hipertensão essencial, possivelmente iniciada pela ativação local do SRA e por anormalidades no transporte de sódio no túbulo proximal e mantida em longo prazo por outros mecanismos. / Losartan treatment during late murine nephrogenesis (first 2 weeks of extrauterine life) causes progressive renal injury in adult life and, at more advanced stages, hypertension, indicating a physiologic action of angiotensin II on nephrogenesis. The possible intracellular pathways that might mediate this effect are unknown. We investigated the possibility that the NF-kB system, known to participate in the embryogenesis of other tissues, could be one of these mediators. Soon after delivery, thirty-two Munich-Wistar dams, each nursing 6 male pups, were divided in 2 groups: C, untreated, and PDTC, receiving the NF-kB inhibitor pyrrolidine dithiocarbamate (PDTC), 280 mg/kg/day in drinking water during 21 days. After weaning (at 25 days), the offspring (C and PDTC) were followed until 10 months of age with no further treatment. Unlike Losartan, neonatal PDTC treatment promoted no reduction in the number of nephrons and no abnormal albuminuria, indicating that the NF-kB system does not participate decisively in nephrogenesis. Nevertheless, rats that received PDTC during lactation exhibited stable hypertension associated with myocardial hypertrophy and fibrosis. To investigate the pathogenesis of hypertension, which cannot be ascribed to number of nephrons reduction, the renal expressions of the renin-angiotensin system (RAS) components and of several molecules involved in sodium transport were determined by qRT-PCR at 3 and 10 months of life. The renal expression of renin and angiotensinogen in PDTC-treated rats at 3 months of age was significantly higher in comparison with control, but lower than age-matched controls at 10 months of age, suggesting that, although hypertension may be initiated by a derangement in the RAS, it was maintained by other mechanisms in the long run. At 3 months of age, there was upregulation of the luminal sodium/glucose transporter and the basolateral sodium/bicarbonate transporter at the proximal tubule, as well as a numerically higher expression of the luminal sodium/hydrogen exchanger, suggesting that these abnormalities might also be related to the pathogenesis of hypertension in these rats. At 10 months of age, however, the expression of all these transporters was reduced, suggesting that none of them was responsible for the long-term maintenance of high blood pressure. Neonatal PDTC administration represents a new model of essential hypertension, possibly related to local renal activation of the RAS and to deranged sodium transport at the proximal tubule. In the long run, hypertension must be maintained by other mechanisms.
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Avaliação da concentração de metais pesados (Zn, Cd, Pb e Cu) em água de chuva visando sua aplicação como fonte alternativa de água potável na cidade de Juiz de Fora/MGCerqueira, Marcos Rodrigues Facchini 02 March 2012 (has links)
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Previous issue date: 2012-03-02 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais / Muitas pessoas sofrem da falta crônica de água potável para necessidades pessoais e, nesse contexto, a água de chuva surge como uma possível fonte alternativa. Em cima disso, foi proposto um método simples e efetivo para a determinação de cobre(II), cádmio(II), zinco(II) e chumbo(II) em 64 amostras de água de chuva de Juiz de Fora/MG/Brasil utilizando a técnica de redissolução potenciométrica. Um potenciostato μ-AUTOLAB foi utilizado para a aquisição dos dados e a célula eletroquímica consistia de um eletrodo de trabalho de carbono vítreo modificado com filme de mercúrio, um eletrodo de Ag/AgCl(sat) como eletrodo de referência e um de eletrodo de platina como eletrodo auxiliar. Foi realizada uma avaliação do pH do meio variando de 0-3 para uma determinação simultânea de Cd, Pb e Cu e de 0-6 para a determinação de Zn. Um Planejamento Estrela 22 foi realizado para a otimização das condições eletroquímicas das determinações. Para as determinações de Cd, Pb e Cu foram estudados níveis entre -1,06 e -0,64 V para o potencial de deposição (Ed), com tempo de deposição (td) entre 239 s e 662 s. Para a determinação de Zn os níveis estudados para o Ed foram entre -1,70 V e -1,10 V, com td entre 239 s e 662 s. A condição ótima encontrada para o pH do meio foi de pH = 4 para a determinação de Zn e um pH = 0 para a determinação de Cd, Pb e Cu. De acordo com as superfícies de resposta obtidas, foi estipulado para a determinação de Zn um Ed = -1,40 V e um td = 300 s e para a determinação de Cd, Pb e Cu um Ed = -1,00 V e um td = 300 s. Foram construídas curvas analíticas para verificar a linearidade do método. Os limites de detecção e quantificação foram de 1,26 e 3,83 μg L-1 para Zn, 0,38 e 1,26 μg L-1 para Cd, 0,41 e 1,36 μg L-1 para Pb e 0,96 e 3,20 μg L-1 para Cu, respectivamente. O método mostrou valores de recuperação entre 86 e 113%. As amostras de água de chuva também foram analisadas por espectroscopia de absorção atômica em forno de grafite (GFAAS), como método de referência, demonstrando uma boa correlação entre os resultados. Foram encontrados valores entre 3,93 e 13,8 μg L-1 de Zn, 3,11 e 7,51 μg L-1 de Cu, enquanto que nenhuma concentração significativa foi observada para Pb e Cd. Conforme os valores estipulados na Portaria nº 2914, de 12 de dezembro de 2011, do Ministério da Saúde, a água de chuva da região de Juiz de Fora pode ser considerada como potável com relação os parâmetros avaliados. / Many people suffer from a chronicle lack of potable water for their personal needs and, in this context, the rainwater arises as a possible alternative source. Upon this, an effective and simple method to determine copper(II), cadmium(II), zinc(II) and lead(II) in 64 rainwater samples from Juiz de Fora/MG/Brazil, using potentiometric stripping analysis (PSA), is proposed. A μ-AUTOLAB potentiostat was used for data acquisition and the electrochemical cell consisted of a working glassy carbon electrode modified with a thin mercury film, an Ag/AgCl(sat) as reference electrode and a platinum as auxiliary electrode. The pH of the medium was evaluated in the range of 0-3 for the simultaneous determination of Cd, Pb and Cu, and in the range of 0-6 for Zn. A 22 Star Design was run to optimize the analytical conditions. For Cd, Pb and Cu determination the studied levels for deposition potential (Ed) were between -1.06 V and -0.64 V, with deposition time (td) between 239 s and 662 s. For Zn determination the studied levels for Ed were between -1.70 V and -1.10 V, with td between 239 s and 662 s. The optimum medium pH conditions found were of pH = 4 for Zn determination and pH = 0 for Cd, Pb and Cu determination. According to the obtained response surfaces it was stipulated for Zn determination a Ed = -1.40 V and a td = 300 s and for Cu, Pb and Cd determination a Ed = -1.00 V and a td = 300 s. Analytical curves were constructed to verify the method linearity. The detection and quantification limits were of 1.26 and 3.83 μg L-1 for Zn, 0.378 and 1.26 μg L-1 for Cd, 0.407 and 1.36 μg L-1 for Pb and 0.960 and 3.20 μg L-1 for Cu, respectively. The method showed recovery values between 86 and 113%. The rainwater samples were also analyzed by graphite furnace atomic absorption spectrometry (GFAAS), as reference method, showing a good correlation between the results. Values between 3.93 and 13.8 μg L-1 of Zn, 3.11 and 7.51 μg L-1 of Cu were found, while no significant concentrations of Pb and Cd were found. According to the stipulated values on Portaria nº 2914, of december 12 of 2011, from Ministério da Saúde, the Juiz de Fora region rainwater can be considered potable, with respect to the evaluated parameters.
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Estudo das mutações no gene COL2A1 em uma coorte de pacientes com displasias esqueléticas do grupo colagenopatia tipo II segundo critérios clínico-radiológicos / Study of mutations in the COL2A1 gene in a cohort of patients with skeletal dysplasias of type 2 collagenopathy group according to clinical and radiological criteriaSilveira, Karina da Costa, 1989- 24 August 2018 (has links)
Orientadores: Denise Pontes Cavalcanti, Luciana Cardoso Bonadia / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T20:03:03Z (GMT). No. of bitstreams: 1
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Previous issue date: 2014 / Resumo: As displasias esqueléticas ou osteocondrodisplasias são doenças genéticas que afetam o crescimento e o desenvolvimento do tecido ósseo e cartilaginoso produzindo, em geral, baixa estatura. Mutações em heterozigose no gene COL2A1 são responsáveis por uma série de displasias esqueléticas conhecidas como colagenopatias do tipo II que geralmente apresentam um padrão espondiloepifisário típico. Apesar das mutações no COL2A1 serem, em geral, "privadas", o estudo molecular desse gene em pacientes com fenótipos sugestivos de colagenopatia do tipo II pode contribuir seja para um melhor entendimento das colagenopatias do tipo II seja para refinar, quando possível, a correlação genótipo-fenótipo. O objetivo desse estudo foi investigar o gene COL2A1 numa coorte de pacientes com fenótipo de colagenopatia do tipo II de modo a melhorar o conhecimento sobre essas colagenopatias. Foram estudados 33 pacientes com fenótipo de colagenopatia do tipo II. A análise molecular foi feita por sequenciamento automático bidirecional direto do gene COL2A1, começando pelos domínios relacionados a cada fenótipo seguido de sequenciamento completo das regiões codificantes do gene quando as primeiras foram negativas. Foram identificadas alterações potencialmente deletérias em heterozigose em 23 dos 33 pacientes (69,7%): 18 alterações do tipo missense (11 inéditas, 7 descritas), 4 alterações que alteram sítio de splice (2 inéditas, 2 descritas) e uma deleção inédita. Das mutações do tipo missense encontradas, duas foram recorrentes em 5 pacientes: p.G594E e p.R989C. Ambas as mutações recorrentes foram associadas a fenótipos graves: a p.R989C foi observada em displasia espondiloepifisária congênita (SEDC) grave enquanto que a p.G594E foi associadaa 2 recém-nascidos com fenótipo de SEDC-letal. Para todas as mutações novas, a análise in silico, estudo em controles e/ou dos pais confirmaram a patogenicidade de todas elas. Concluindo, os resultados deste estudo permitiram a identificação de 14 mutações novas no gene COL2A1 e um melhor refinamento da correlação genótipo-fenótipo / Abstract: Skeletal dysplasias are genetic disorders that affect the growth and development of the bone and cartilage tissues producing, in general, short stature. Heterozygous mutations in the COL2A1 gene are responsible for a number of skeletal dysplasias that usually exhibit a pattern spondyloepiphyseal and are called type II collagenopathies. Although the mutations in COL2A1 are usually privates, molecular studies of this gene in patients with suggestive phenotypes can contribute to a better understanding of the type II collagenopathies. The aim of this study was to sequence the COL2A1 in a cohort of patients with type II collagenopathy phenotypes in order to refine the knowledge regarding the genotype-phenotype correlation. Thus, 33 patients with suggestive phenotype were studied. The molecular analysis was performed by automated Sanger bidirectional sequencing of the COL2A1 gene, starting with the domains related to each phenotype followed by whole sequencing of the gene coding regions when the first ones were negative. Potentially deleterious changes in heterozygosity were identified in 23 of 33 patients (69.7 %): 18 missense changes (11 undescribed), 4 changes that modify the splice site (2 undescribed) and a new deletion. The pathogenicity of the undescribed changes were confirmed by in silico analysis, study of control individuals and/or of the respective parents. Among the found missense mutations, two were recurrent and associated with severe phenotypes. These mutations, p.G594E and p.R989C, were found in five patients. The R989C change was observed in three children presenting a phenotype of spondyloepiphyseal dysplasia congenita (SEDC), which follow up showed a pattern of severe SEDC featured by severe disproportioned short stature with coxa vara and kyphoscoliosis. The G594E change was associated with two newborns presenting also a SEDC phenotype, however with lethal evolution. In conclusion, the results of this study allowed the identification of 14 new mutations in COL2A1 gene and a better refinement of the genotype-phenotype correlation / Mestrado / Ciencias Biomedicas / Mestra em Ciências Médicas
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[en] SYNTHESIS AND CHARACTERIZATION OF BINUCLEATING LIGANDS DERIVED FROM THE ISONIAZID AND THEIR DINUCLEAR COPPER(II) COMPLEXES / [pt] SÍNTESE E CARACTERIZAÇÃO DE LIGANTES BINUCLEANTES DERIVADOS DA ISONIAZIDA E SEUS COMPLEXOS BINUCLEARES DE COBRE (II)RAFAELA DOS SANTOS MORAES 28 July 2011 (has links)
[pt] Diante das limitações e dos efeitos colaterais indesejáveis observados na terapia do câncer com os derivados de platina, muitos esforços têm sido feitos com o objetivo de obter novas drogas mais eficazes e menos tóxicas, capazes de promover a clivagem oxidativa ou hidrolítica da cadeia do DNA e de outras estruturas subcelulares fundamentais. Até o presente momento, alguns complexos de cobre já foram desenvolvidos, e mostraram excelente atividade in vitro contra uma variedade de tumores. Assim, o conhecimento sobre a citotoxidade e seletividade dos complexos de cobre(II) contendo ponte de hidróxido é, portanto, de importância na busca por novos fármacos para o tratamento do câncer. Além disso, por se tratar de um metal fisiológico, os compostos de cobre costumam ser menos tóxicos que os derivados de platina, diminuindo assim efeitos colaterais indesejados e com isso possibilitando o aumento do arsenal quimioterápico disponível para o tratamento da doença. Neste contexto, foram desenvolvidos no presente trabalho dois ligantes binucleantes derivados da isoniazida (INH). Um desses ligantes, o não-simétrico N-isonicotinoil-2-hidroxi-3-{[(2-hidroxibenzil)(2-piridilmetil)amino]-metil}-5-metilbenzaldeído hidrazona, é inédito. Já o outro, o ligante simétrico N,N’-diisonicotinoil-2-hidroxi-5-metilisoftaldeído diidrazona, foi originalmente sintetizado por uma equipe liderada por Chen, em 1992. A partir destes ligantes, quatro novos complexos binucleares de Cu(II) contendo pontes exógenas hidroxo e acetato, todos eles contendo uma ponte do tipo -hidroxo entre os metais, foram sintetizados e caracterizados por diversas técnicas instrumentais de análise. Além disso, foram feitos cálculos teóricos com o objetivo de auxiliar as propostas quanto à estrutura dos compostos. Trabalhos futuros serão realizados a fim de investigar a atividade biológica destes complexos. / [en] Considering the limitations and undesirable side effects observed in cancer therapy with platinum derivatives, many efforts have been made with the aim of obtaining new drugs more effective and less toxic, able to promote the hydrolytic cleavage or oxidative DNA chain other subcellular structures critical. Until now, some copper complexes have been developed and showed excellent in vitro activity against a variety of experimental tumors. Thus, knowledge on the cytotoxicity and selectivity compounds of copper (II) containing bridging hydroxide is therefore of importance in the search for new drugs for cancer treatment. Moreover, because it is a physiological metal, its compounds are usually less toxic than platinum derivatives, thus reducing unwanted side effects and thereby enabling the increase of chemotherapeutic arsenal available for treatment of the disease. In this context, were developed in this work binucleantes two ligands derived from isoniazid (INH). One of these ligands, the non-symmetrical N-isonicotinoil-2-hydroxy-3-{[(2-hydroxybenzyl) (2-piridilmetil) amino]-methyl}-5-hydrazone methylbenzaldehyde, is new. But the other, the symmetrical ligand N, N -diisonicotinoyl-2-hydroxy-5-methylisophthalaldehyde dihydrazone, was originally synthesized by a team led by Chen in 1992. From these ligands, four new binuclear complexes of Cu (II) bridges containing exogenous hydroxo and acetate, all of which contain a hydroxo-bridge type between the metals were synthesized and characterized by various instrumental techniques of analysis. In addition, theoretical calculations were made with the aim of helping the proposals regarding the structure of the compounds. Future works will be performed to investigate the biological activity of these complexes.
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Some properties of superconductorsFrench, Robin A. January 1966 (has links)
No description available.
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Changes in the Rpb3 Interactome Caused by the Deletion of RPB9 in Saccharomyces cerevisiaeTalbert, Eric A. 02 August 2016 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / RNA Polymerase II (Pol II) is the primary actor in the transcription of mRNA from genes. Pol II is a complex composed of twelve protein subunits. This study focused on the changes in the interactome of Rbp3 in S. cerevisiae when the Pol II subunit Rpb9 is removed. Rpb3 is one of the core subunits of Pol II, and any significant changes to the Rpb3 incteractome due to the loss of Rpb9 can be used to infer new information about Rpb9’s role in the Pol II complex.
Rpb3 was pulled down using FLAG purification from both wild type and rpb9Δ S. cerevisiae cultures. Rpb3 and the proteins complexed with it were then analyzed using multi-dimensional protein identification technology (MudPIT), a form of liquid chromatography-mass spectrometry (LC-MS). This data was searched using the SEQUEST database search algorithm, and the results were further analyzed for likelihood of interaction using Significance Analysis of INTeractome (SAINT), as well as for post-translational phosphorylation. Deletion of rpb9 did not present any changes in Pol II phosphorylation however it did cause several changes in the interaction network. The rpb9Δ strain showed new interactions with Rtr1, Sen1, Vtc4, Pyc1, Tgl4, Sec61, Tfb2, Hfd1, Erv25, Rib4, Sla1, Ubp15, Bbc1, and Hxk1. The most prominent of these hits are Rtr1, an Rpb1 C-terminal domain phosphatase linked to transcription termination, and Sen1, an RNA/DNA nuclease that terminates transcription. In addition, this mutant showed no interaction with Mtd1, an interaction that is present in the wild type. In all cases, these hits should be considered fuel for future research, rather than conclusive evidence of novel interactions.
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Probing the Redox and Photophysical Properties of Ru(II)-Pt(II) Supramolecular Complexes as Efficient Photodynamic Therapy AgentsHiggins, Samantha Lake Hopkins 02 April 2012 (has links)
Mixed-metal Ru(II)-Pt(II) supramolecular complexes having the [(Ph₂phen)₂Ru(BL)PtCl₂]₂+ (Ph₂phen = 4,7-diphenyl-1,10-phenanthroline, and BL (bridging ligand) = dpp = 2,3-bis(2-pyridyl)pyrazine, or dpq = 2,3-bis(2-pyridyl)quinoxaline) structural motif were synthesized and their redox, photophysical, and photochemical properties studied. Subsequently the application of the Ru(II)-Pt(II) bimetallic complexes in light activated DNA modification and cytotoxicity were evaluated. The supramolecular design entails covalently coupling an efficient Ru(II) chromophore for photodynamic therapy (PDT) activity through a polyazine bridging ligand (dpp or dpq) to a cis-PtCl₂ bioactive site for covalent binding to biological substrates. The bioactive site is comparable to the first generation Pt-based chemotherapy agent cisplatin, cis-[PtCl₂(NH₃)₂]. The Ph₂phen ligand is known in [Ru(Ph₂phen)₃]²+ to provide enhanced excited state lifetime and increase quantum efficiency for singlet oxygen generation in comparison to the phen analog (Φ₁₀₂ = 0.97, Ph₂phen and Φ₁₀₂ = 0.54, phen). The redox and photophysical properties were analyzed at each synthetic step providing systematic evaluation of the complex properties. The [(Ph₂phen₂2Ru(BL)PtCl₂](PF₆)₂ complexes display reversible RuII/III oxidations at +1.61 (dpp) and +1.63 (dpq) V vs. Ag/AgCl with an irreversible PtII/IV oxidation occurring prior at +1.51 V vs. Ag/AgCl. Four reversible ligand reductions occur at -0.45 (dpp0/-), -1.15 (dpp-/2-), -1.33 (Ph₂phen0/-), and -1.52 (Ph₂phen0/-) V vs. Ag/AgCl. For the [(Ph₂phen)₂Ru(dpq)PtCl₂](PF₆)₂ complex, the first two reductions shift to more positive potentials at -0.19 and -0.95 V vs. Ag/AgCl, while the TL reductions remain generally unperturbed. The electronic absorption spectroscopy for the [(Ph₂phen)₂Ru(dpq)PtCl₂](PF₆)₂, BL = dpp or dpq, complexes is dominated in the UV region by Ph₂phen (274 nm) and BL-based (310-320 nm) π⟶ π* transitions and in the visible region by metal-to-ligand charge transfer (MLCT) transitions at 424 nm (Ru(dπ)→ Ph₂phen(π*) 1CT) and 517 nm (Ru(dπ)→ dpp(π*) 1CT) or 600 nm (Ru(dπ)→ dpq(π*) 1CT). Steady-state and time-resolved emission spectroscopy shows that upon attaching Pt to the Ru monometallic precursor the λmaxem shifts from 664 nm for [(Ph₂phen)2Ru(dpp)](PF₆)₂ to 740 nm for [(Ph₂phen)₂Ru(dpp)PtCl₂](PF₆)₂ and the excited state lifetime is reduced from 820 ns to 44 ns in accordance with the energy gap law. The τ = 44 ns for the Ru(dπ)→ dpp(π*) 3CT excited state was somewhat unexpected upon TL variation given the lack of formal involvement of Ph₂phen in the emissive state. This likely results from the Ph₂phen contribution to the formally Ru(dπ) donor orbital. Although not typically done, given the complexity of the study the Φ₁₀₂ was quantified for the [(Ph₂phen)₂Ru(BL)PtC₂]Cl₂ (BL = dpp, Φ₁₀₂ = 0.07 or dpq, Φ₁₀₂ = 0.03) complexes supporting 1O2 generation via energy transfer from the 3MLCT excited state.
The thermal and photochemical interactions of the [(Ph₂phen₂2Ru(BL)PtCl₂]Cl₂ (BL = dpp or dpq) supramolecular complexes were studied in the presence of DNA and U87MG cancer cells. Thermal binding at the cis-PtCl₂ BAS in the Ru(II)-Pt(II) architecture was compared to cisplatin displaying similar reduced migration through the gel attributed to covalent binding to DNA. DNA photocleavage studies provided evidence of efficient strand cleavage when excited at 455 nm likely enhanced by producing 1O2 locally at the DNA target. DNA photobinding by the [(Ph₂phen)₂Ru(dpp)PtCl₂]Cl₂ complex was observed utilizing low energy light where typical Pt(II) agents do not absorb. This is the first example of MLCT excitation of a Ru(II)-Pt(II) complex to induce a photobinding event. MLCT excitation enhances electron density on the dpp making the Pt(II) a weaker Lewis acid and promoting halide loss. In addition, this system is photoactivated with low energy red light in the therapeutic window. These studies validate the supramolecular design and show that coupling a Ru(II) chromophore for PDT activity and a cis- PtCl₂ binding moiety for covalent DNA targeting affords a complex applicable in photochemotherapies. Analysis of cytotoxicity in the dark for [(Ph₂phen)₂Ru(dpp)PtCl₂]Cl₂ and cisplatin afforded LC50 values of 100 μM, which are confirmed by previous reports for cisplatin and the currently used chemotherapy, TMZ in U87MG cells. Photolysis of the [(Ph₂phen)₂Ru(dpp)PtCl₂]Cl₂ resulted in substantial reduction in the observed LC50 values to approximately 5 μM. The enhanced cytotoxicity via excitation into the formally Ru(dπ)→ BL(π*) CT excited state of [(Ph₂phen)2Ru(dpp)PtCl2]Cl2 indicates that the bimetallic complex undergoes an efficient light activated mechanism of action. The Ru(II)-Pt(II) complex displays substantially lower LC50 values through PDT action than currently used clinical treatments with LC50 values of 100 μM.
The [(Ph₂phen)₂Ru(BL)PtCl₂]₂+ (BL = dpp or dpq) mixed-metal supramolecules utilizing the Ph₂phen TL have displayed surprising results. The direct coupling of the cis-PtCl₂ moiety to the (Ph₂phen)₂Ru(BL) chromophore display dramatically enhanced photophysical properties, relative to the bpy and phen systems with a longer excited state lifetime and improved light activated interactions with DNA, which was not previously observed for directly coupled Ru(II)- Pt(II) systems. The Ph₂phen TL positively influence the bioactivity compared to the typical deactivation observed in the bpy and phen systems. Probing the [(Ph₂phen)₂Ru(BL)PtCl₂]₂+ (BL = dpp or dpq) biological interactions confirms the importance of coupling an efficient light absorbing and 1O2 generating PDT-type unit with a cis-PtCl2 DNA binding unit for applications in covalent DNA photomodification, DNA photocleavage, and photocytotoxicity. It is proposed that excitation using visible light into the formally Ru(dπ)→ BL(π*) CT excited state leads to enhanced electron density on the BL and weakened Lewis acidity at the Pt(II) center, which facilitates halide loss for efficient biological substrate modification. Upon coordination of the Ru(II)-Pt(II) complexes at the biological substrate, 1O2 is localized providing effective targeting of the highly reactive oxygen species. The visible light induced activity of the [(Ph₂phen)₂Ru(BL)PtCl₂]₂+ (BL = dpp or dpq) supramolecules suggests a new mode of action in relation to cisplatin, which was further supported by the enhanced photocytotoxicity observed in the presence of U87MG cells. The results indicate that the Ru(II)-Pt(II) supramolecular structural motif hold great promise as a future photochemotherapy agent. / Ph. D.
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The establishment and initial development of a British airborne force, June 1940-January 1942Buckingham, William Frederick January 2001 (has links)
The following thesis is an examination of the establishment and initial development of a British airborne force. Beginning with an examination of airborne development outside the UK up to 1940, it traces the growing British use of air transport as a tool for imperial policing in the inter-war period, and examines why this did not lead to the logical step of creating a dedicated British airborne force. The impact of German airborne operations and the defeat at Dunkirk in 1940 on British attitudes is then analysed, followed by a detailed examination of the mechanics of the establishment of a British airborne force, ending with the British 1st Parachute Brigade attaining operational status in January 1942.
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Lone-pair effects in tin (II) materialsChristoforou, M. January 1988 (has links)
No description available.
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