Integrins are transmembrane heterodimeric proteins that link extracellular matrix (ECM) to cytoskeleton and have been shown to function as mechanotransducers in non-muscle cells. Synthetic integrin-binding peptide triggers Ca2+ mobilization and contraction in vascular smooth muscle cells (VSMCs) from rat afferent arteriole, indicating that interactions between ECM and integrins modulate vascular tone. RGD, an integrin binding peptide, triggered contraction in cultured VSMCs as observed by Electric Cell-Substrate Impedance Sensing technique. To examine whether integrins transduce extracellular mechanical stress into intracellular Ca2+ signaling events in VSMCs, unidirectional mechanical force was applied to freshly isolated renal VSMCs through paramagnetic beads coated with fibronectin (FN, natural ligand of α5β1 integrin in VSMCs). Pulling of fibronectin-coated beads with electromagnet triggered Ca2+ sparks, followed by global Ca2+ mobilization. Paramagnetic beads coated with low-density lipoprotein (LDL), whose receptors are not linked to cytoskeleton, were minimally effective in triggering Ca2+ sparks and global Ca2+ mobilization. Pre-incubation with ryanodine, cytochalasin-D, or colchicine substantially reduced the occurrence of Ca2+ sparks triggered by fibronectin-coated beads. Binding of VSMCs with antibodies specific to the extracellular domains of alpha5 and beta1 integrins triggered Ca2+ sparks simulating the effects of fibronectin-coated beads. Anti-β2- integrin antibody served as the negative control. Traction force microscopy studies showed that only the force transduced via integrins could potentially trigger cytoskeletal remodeling in cultured VSMCs. Atomic force microscopy revealed a significant increase in surface roughness in VSMCs when treated with RGD peptide though there was no difference in the maximum deflection of the force curves. Pre-incubation of microperfused afferent arterioles with ryanodine or integrin specific binding peptide inhibited pressure-induced myogenic constriction. In conclusion, integrins transduce mechanical force into intracellular Ca2+ signaling events in renal VSMCs. Integrin-mediated mechanotransduction is probably involved in myogenic response of afferent arterioles. Thus, integrins can potentially act as sensors for myogenic response phenomenon and affect the autoregulatory mechanism in the vasculature.

Thesis (doctoral)--Universität Erlangen.

The Reno-Sparks community is in a seismically hazardous area. Recent research indicates that a Richter 7.0 or greater magnitude earthquake could affect the area. Many of the emergency and essential facilities are situated in dangerous geological locations and are housed in outdated structures which could be severely damaged in the event of a major earthquake. Detailed site evaluations need to be made with respect to location of new structures and of existing building safety. The 1979 Unified Building Code seismic provisions should be adopted without exception; Nevada Revised Statute 278 .160 needs to be revised to require a seismic safety plan; Alquist-Priolo legislation should be implemented, and creation of a comprehensive civil defense plan for seismic hazards is essential.

京都大学 / 新制・課程博士 / 博士(医科学) / 甲第24533号 / 医科博第147号 / 新制||医科||10(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 篠原 隆司, 教授 松田 道行, 教授 伊藤 貴浩 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Grassland fuels quickly respond to moisture changes in the environment, and successfully ignite more readily compared with other wildland fuel types. In recent years in New Zealand grasslands, wildfire ignitions have increased due to recreational activities on public conservation land. Ignition sources have included off-road vehicles, sparks from machinery, and campfires, cooking stoves, etc. This research investigated ignition thresholds for fully cured tussock (Festuca novae-zelandiae) and exotic (Agrostis capillaris) grasses, with the aim of providing a scientific basis for wildfire prevention through decision-support tools for activity controls. Five ignition sources of concern to the Department of Conservation were tested in the laboratory, and results were validated against field experiments. Experiments were innovative, and were designed to simulate ignitions from: hot exhaust systems on off-road vehicles (hot metal); sparks from vehicle exhausts (carbon emissions); grinding operations (metal sparks); smouldering debris dropped onto grass fuels from hot vehicle parts (organic embers); and ordinary cigarette lighters (open flame). Fuel moisture content (MC), and wind speed were varied, but ambient temperature and relative humidity were kept relatively constant in the laboratory. Logistic regression was used to analyse data for each ignition source, except organic embers because no ignitions occurred. Ignition thresholds were determined for a probability of ignition success of 50%, and all models were statistically significant. The thresholds are listed in terms of model accuracy for each experiment: open flame was 28% MC without wind, and 55% MC with light wind (1 m/s); metal sparks was 37% MC; hot metal, with a wind speed of 2 m/s and MC of 1%, was 398ºC hot metal temperature; and carbon emissions was 65% MC. The results represent a significant contribution to knowledge of the ignition behaviour of grassland fuels. Further research is required to verify and extend the results; but, initial findings provide a scientific basis for management, investigations of wildfire causes, and decisions around controls on recreational activities to protect highly sensitive ecosystems and natural areas from damaging wildfires.

Atrial fibrillation (AF), the most common arrhythmia encountered in clinical practice, is a major source of morbidity and mortality, and is highly associated with inflammation and oxidative stress. In the present study, we show that acute exposure of mice atrial tissue to tumor necrosis factor-α (TNF-α) increases susceptibility to AF. We further show that acute exposure to TNF-α led to increased spontaneous sarcoplasmic reticulum (SR) calcium release and generated triggered activities in isolated mice atrial myocytes. This increase in spontaneous SR calcium activity was found to be due to elevated reactive oxygen species production from mitochondria and NADPH oxidase sources triggered by TNF-α. Hence we concluded that acute exposure to TNF-α leads to elevated oxidative stress that increases spontaneous SR Ca2+ release and triggered activity through which it can lead to AF induction and maintenance

Atrial fibrillation (AF), the most common arrhythmia encountered in clinical practice, is a major source of morbidity and mortality, and is highly associated with inflammation and oxidative stress. In the present study, we show that acute exposure of mice atrial tissue to tumor necrosis factor-α (TNF-α) increases susceptibility to AF. We further show that acute exposure to TNF-α led to increased spontaneous sarcoplasmic reticulum (SR) calcium release and generated triggered activities in isolated mice atrial myocytes. This increase in spontaneous SR calcium activity was found to be due to elevated reactive oxygen species production from mitochondria and NADPH oxidase sources triggered by TNF-α. Hence we concluded that acute exposure to TNF-α leads to elevated oxidative stress that increases spontaneous SR Ca2+ release and triggered activity through which it can lead to AF induction and maintenance

Critics and readers often consider Nicholas Sparks’ novel The Notebook to be a romance novel, while Sparks himself considers it a love story. Sparks claims that there are no similarities between the two genres. Therefore, this paper investigates the differences and similarities between the romance genre and the love story genre, while simultaneously exploring The Notebook’s storyline, the characterization, and the marketing surrounding the book in order to understand the novel’s classification. The purpose is to discover if The Notebook can be identified as a romance even if it never was Sparks’ intention. The only aspect that differs between the genres is how the ending is written, other than that there are no remarkable differences. There are also several elements that validates that The Notebook has romantic features. Both of the protagonists have romance characteristics, the cover of the novel is a characteristic romance cover, and the storyline itself is based on a romance structure and it follows all of the essential romance elements. The conclusion of this paper is that The Notebook has romance elements and therefore can be placed in the romance genre even if that never was Sparks’ intention.

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Made available in DSpace on 2014-10-09T12:49:48Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:02:20Z (GMT). No. of bitstreams: 1 09811.pdf: 7739701 bytes, checksum: 322f7fce8713f27550b470eff5575b73 (MD5) / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP