破壊指向性効果と震源の不均質性を考慮した地震スペクトル比解析

京都大学新制・課程博士博士(工学)甲第24572号工博第5078号新制||工||1973(附属図書館)京都大学大学院工学研究科建築学専攻(主査)教授 池田 芳樹, 教授 竹脇 出, 教授 松島 信一学位規則第4条第1項該当Doctor of Philosophy (Engineering)Kyoto UniversityDFA

Polimorfismo XmnI está associado com os níveis de hemoglobina fetal em hipoplasias medulares

CONTEXT AND OBJECTIVE: Acquired fetal hemoglobin (HbF) elevation has been implicated as a prognostic factor in dyserythropoietic disorders. Our objectives were to examine acquired HbF increases in aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) patients, and to evaluate whether there is an association between the presence of XmnI and 5' hypersensitive site locus control region (LCR-HS2) polymorphisms and the HbF levels. DESIGN AND SETTING: Cross-sectional study at the Hematology and Blood Transfusion Service of Universidade Federal de São Paulo (UNIFESP) - Escola Paulista de Medicina. METHODS: We studied a group of 37 patients with AA and/or PNH. Polymerase chain reaction (PCR) and enzymatic digestion were utilized to analyze XmnI polymorphisms; and PCR, cloning and automated sequencing for the HS2 polymorphisms. RESULTS: The mean HbF level was 2.32%, but there was no significant difference in HbF level between the AA and PNH groups (p = 0.46). HbF levels of less than 1.0% showed a significant correlation with absence of the XmnI (+) polymorphism (p = 0.02). The presence of the XmnI allele was greater in the AA group (p = 0.007). CONCLUSIONS: XmnI polymorphism absence reduction is associated with acquired HbF elevation. Further studies are required to confirm these observations and make treatment, prognosis and survival comparisons.CONTEXTO E OBJETIVO: O aumento adquirido da hemoglobina fetal (HbF) já foi implicado como fator prognóstico em distúrbios diseritropoiéticos. Nossos objetivos foram de examinar elevações adquiridas na HbF em pacientes com anemia aplástica (AA) e hemoglobinúria paroxística noturna (PNH), e de avaliar se há associação entre a presença de polimorfismos XmnI e de região de controle de locus gênico 5' (LCR-HS2) e os níveis de HbF. TIPO DE ESTUDO E LOCAL: Estudo longitudinal no Serviço de Hematologia e Transfusão de Sangue da Universidade Federal de São Paulo (UNIFESP) - Escola Paulista de Medicina. MÉTODOS: Estudamos um grupo de 37 pacientes com AA e/ou PNH. Reação de polimerase em cadeia (PCR) e digestão enzimática foram usadas para analisar polimorfismos XmnI; e PCR para clonagem e sequenciamento automático dos polimorfismos HS2. RESULTADOS: O nível médio de HbF foi de 2,32%, mas não houve diferença significativa entre o nível de HbF dos pacientes AA e PNH (p = 0.46). Os níveis de HbF menores que 1,0% mostraram correlação estatisticamente significativa com ausência do polimorfismo XmnI (+) (p = 0.007). CONCLUSÕES: Ausência de polimorfismo XmnI está associado com diminuição de HbF. Mais estudos são necessários para confirmar estas observações e fazer comparações sobre tratamento, prognóstico e sobrevida.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Hematology and Blood Transfusion ServiceUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPM, Hematology and Blood Transfusion ServiceUNIFESP, EPMSciEL

Checkpoint-Dependent and -Independent Roles of Swi3 in Replication Fork Recovery and Sister Chromatid Cohesion in Fission Yeast

Multiple genome maintenance processes are coordinated at the replication fork to preserve genomic integrity. How eukaryotic cells accomplish such a coordination is unknown. Swi1 and Swi3 form the replication fork protection complex and are involved in various processes including stabilization of replication forks, activation of the Cds1 checkpoint kinase and establishment of sister chromatid cohesion in fission yeast. However, the mechanisms by which the Swi1–Swi3 complex achieves and coordinates these tasks are not well understood. Here, we describe the identification of separation-of-function mutants of Swi3, aimed at dissecting the molecular pathways that require Swi1–Swi3. Unlike swi3 deletion mutants, the separation-of-function mutants were not sensitive to agents that stall replication forks. However, they were highly sensitive to camptothecin that induces replication fork breakage. In addition, these mutants were defective in replication fork regeneration and sister chromatid cohesion. Interestingly, unlike swi3-deleted cell, the separation-of-functions mutants were proficient in the activation of the replication checkpoint, but their fork regeneration defects were more severe than those of checkpoint mutants including cds1Δ, chk1Δ and rad3Δ. These results suggest that, while Swi3 mediates full activation of the replication checkpoint in response to stalled replication forks, Swi3 activates a checkpoint-independent pathway to facilitate recovery of collapsed replication forks and the establishment of sister chromatid cohesion. Thus, our separation-of-function alleles provide new insight into understanding the multiple roles of Swi1-Swi3 in fork protection during DNA replication, and into understanding how replication forks are maintained in response to different genotoxic agents

State-Dependent Fragility Curves for Aftershock Seismic Risk Assessment of Japanese Steel Frames

Probabilistic seismic risk assessment of civil infrastructures has been at tracting attention in Japan, especially after recent mega - earthquakes with a long - lasting series of aftershocks capable of accumulating building damage; e.g., the 2011 Tohoku earthquake. To this aim , it is valuable to be able to assess the failure probabil ity of a particular structure and its evolution in time due to sequential earthquake events, which may cause a difficulty for stakeholders to perform consistent decision making to warrant business continuity. This kind of risk analysis may require state - de pendent fragility curves, which in the study were developed for a Japanese steel frame . To construct the curves , a numerical model of a t hree - story steel moment - resisting frame was first constructed and calibrated acc ording to the results of shake table te st s for a typical Japanese steel structure . This model was subsequently transformed in an equivalent single degree of freedom (ESDOF) system , based on the results of the nonlinear static (pushover) analysis. The probabilistic damage model was then construc ted via nonlinear dynamic analys i s of the ESDOF system . The spectral acceleration of the elastic period of the ESDOF system was selected as the ground motion intensity measure while the drift angle was selected as response measure. All the records used in the analysis were selected from the Japanese strong - motion network, K - N et. Finally , the state - dependent fragility curves were developed for five levels of damage: As - New (AN), Immediate Occupancy (IO), Life Safety (LS), Collapse Prevention (CP) and Failure ( F ). The limit state value for each damage state (DS) was set in compliance with the results of the shake table tes t s . After computing the damage state probability due to the mainshock, t he time - variant aftershock risk of the steel structure was quantifie d integrating the developed state - dependent fragility curves with the seismic hazard, followin g a Markov chain model already available in the literature, which makes use of aftershock probabilistic seismic hazard analysis (APSHA) . Hazard was computed assum ing that the structure was located in Osaka, a site that may be affected by a mega - earthquake at the Nankai Trough subduction - zone . In particular, in the considered exercise, the most probable damage state due to the considered mainshock scenario was found to be IO, followed, in probability terms, by LS, F, AN, and CP. Given the probability distribution of the mainshock - induced damage, the daily evolution of aftershock damage was computed, and it was found that the most likely DS after two m onths since the mainshock was still IO followed by F, LS, CP and AN