ミトコンドリア脱共役薬を投与されたラットおよび心不全ラットにおけるテクネチウムセスタミビ集積の測定

京都大学0048新制・課程博士博士(医学)甲第19175号医博第4017号新制||医||1010(附属図書館)32167京都大学大学院医学研究科医学専攻(主査)教授 渡邊 直樹, 教授 松原 和夫, 教授 横出 正之学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Polyakov loop effects on the phase diagram in strong-coupling lattice QCD

We investigate the Polyakov loop effects on the QCD phase diagram by using the strong-coupling (1/g^2) expansion of the lattice QCD (SC-LQCD) with one species of unrooted staggered quark, including O}(1/g^4) effects. We take account of the effects of Polyakov loop fluctuations in Weiss mean-field approximation (MFA), and compare the results with those in the Haar-measure MFA (no fluctuation from the mean-field). The Polyakov loops strongly suppress the chiral transition temperature in the second-order/crossover region at small chemical potential, while they give a minor modification of the first-order phase boundary at larger chemical potential. The Polyakov loops also account for a drastic increase of the interaction measure near the chiral phase transition. The chiral and Polyakov loop susceptibilities have their peaks close to each other in the second-order/crossover region. In particular in Weiss MFA, there is no indication of the separated deconfinement transition boundary from the chiral phase boundary at any chemical potential. We discuss the interplay between the chiral and deconfinement dynamics via the bare quark mass dependence of susceptibilities.Comment: 17 pages, 17 figure

Phase diagram evolution at finite coupling in strong coupling lattice QCD

We investigate the chiral phase transition in the strong coupling lattice QCD at finite temperature and density with finite coupling effects. We adopt one species of staggered fermion, and develop an analytic formulation based on strong coupling and cluster expansions. We derive the effective potential as a function of two order parameters, the chiral condensate sigma and the quark number density $\rho_q$, in a self-consistent treatment of the next-to-leading order (NLO) effective action terms. NLO contributions lead to modifications of quark mass, chemical potential and the quark wave function renormalization factor. While the ratio mu_c(T=0)/Tc(mu=0) is too small in the strong coupling limit, it is found to increase as beta=2Nc/g^2 increases. The critical point is found to move in the lower T direction as beta increases. Since the vector interaction induced by $\rho_q$ is shown to grow as beta, the present trend is consistent with the results in Nambu-Jona-Lasinio models. The interplay between two order parameters leads to the existence of partially chiral restored matter, where effective chemical potential is automatically adjusted to the quark excitation energy.Comment: 17 pages, 9 figure

Targeting the BCL9/B9L Binding Interaction with B-catenin as a Potential Anticancer Strategy.

Wnt signaling plays a critical role in numerous cellular processes including embryonic development, cell proliferation and tissue homeostasis. The multifunctional protein β-catenin is the primary mediator of canonical Wnt signaling and acts as a transcriptional activator in this context. Dysregulated Wnt signaling is a hallmark of many human cancers and results in the stabilization and accumulation of β-catenin, leading to the increased transcription and expression of Wnt target genes. The transcriptional activation function of β-catenin requires the formation of a nuclear super-complex with protein cofactors including BCL9/B9L, TCF and CBP. It has been demonstrated that binding to these cofactors is essential for transcriptional. Of these critical cofactors, BCL9 and its homolog B9L are the most recently identified and their exact roles are not fully understood. To explore the consequences of the BCL9/B9L-β-catenin binding interaction we developed and optimized a quantitative, reliable and high throughput fluorescence polarization (FP) binding assay along with a surface plasmon resonance (SPR)-based secondary assay. Using our FP assay, we performed extensive mutational analysis of four key hydrophobic residues in BCL9 and determined their contribution to the interaction with β-catenin. We also mapped the precise region of BCL9 required for high affinity binding to β-catenin. With our optimized FP assay, we performed high throughput screening (HTS) for small molecule inhibitors and identified one molecule that warrants further characterization in cell-based assays. We also synthesized BCL9 peptides tagged with cell penetrating peptides (CPPs), but found that their usefulness was limited by their poor solubility. We then explored the design and synthesis of stabilized α-helical BCL9 peptides by three different methods and determined that triazole-stapling, mediated by the Huisgen 1,3-dipolar cycloaddition reaction, was the most robust and highest yielding method in our hands. Our detailed study of this stapling technique defined the optimal azido and alkynyl linker combinations required for stabilizing one turn of the BCL9 α-helix. In summary, we confirmed the requirement for BCL9/B9L in β-catenin transcriptional activation, identified a potentially druggable site around the BCL9 F374 binding pocket and demonstrated that triazole stapling can increase helicity and binding affinity of our BCL9 peptides.Ph.D.Medicinal ChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/75846/1/kawamoto_1.pd

Mathematical aspects of the Digital Annealer's simulated annealing algorithm

The Digital Annealer is a CMOS hardware designed by Fujitsu Laboratories for high-speed solving of Quadratic Unconstrained Binary Optimization (QUBO) problems that could be difficult to solve by means of existing general-purpose computers. In this paper, we present a mathematical description of the first-generation Digital Annealer's Algorithm from the Markov chain theory perspective, establish a relationship between its stationary distribution with the Gibbs-Boltzmann distribution, and provide a necessary and sufficient condition on its cooling schedule that ensures asymptotic convergence to the ground states

UMA AVALIAÇÃO PRELIMINAR DO DESEMPENHO DOS CLUBES DE INVESTIMENTO EM AÇÕES BRASILEIROS

Este trabalho faz uma avaliação do desempenho dos clubes de investimento em ações no Brasil, a partir de uma amostra composta por 113 clubes. Especificamente, com apoio da literatura de avaliação de desempenho de fundos de investimento, foi testada a hipótese de que clubes com elevado patrimônio obtêm desempenho superior aqueles com patrimônio reduzido, além de se investigar a existência de um nível patrimonial ótimo para a gestão de clubes. A avaliação foi realizada através de regressões pelo método dos mínimos quadrados ordinários, utilizando os índices de Sharpe, Treynor e Modigliani trimestrais, de 25 carteiras construídas com base em seus patrimônios médios. Os resultados sugerem que os clubes não obtiveram desempenho satisfatório, entre 2004 e 2008, quando comparados ao índice Bovespa. Como os clubes possuem gestores não-profissionais, o resultado anda em linha com a hipótese de que gestões profissionais agregam valor, alcançando melhores relações risco-retorno. Ainda mais, com base nos resultados, foi possível corroborar a existência de um nível de patrimônio ótimo para os clubes, situado entre R$1,79 milhões a R$4,98 milhões.Palavras-chave: Clube de Investimento em Ações. Índice de Sharpe. Índice de Treynor. Índice de Modigliani