国立情報学研究所で電子化したコンテンツを使用している。

Transglutaminase II (TG2) is a complex protein with five different reported activities. Increases in TG2 expression and TGase activity have previously been observed during wound healing in rat studies; however, it has been unclear whether these phenomena were directly involved in the healing process or if they were simply a by-product of it. The aims of this thesis were, thus, to determine if TG2 plays a role in wound healing in vivo and to elucidate the mechanism of any effects TG2 may have at the cellular level. TG2 ablation resulted in delayed wound healing. To gain mechanistic insight into this abnormality, primary fibroblast cultures from TG2-knockout and wildtype mouse embryos were analysed. TG2-null fibroblasts displayed decreased adhesion and integrin signalling during initial stages of adhesion. Intriguingly, TG2-null cells showed faster activation of Rac1 and RhoA in response to adhesion. Long-term adhesion of TG2-null fibroblasts resulted in increased basal phosphorylation of FAK and number of paxillin-stained focal adhesions, enhanced PI3-kinase signalling, faster actin dynamics and altered activation of p44/42 MAPK. These results are indicative of futile cycling of intracellular signalling pathways resulting from reduced focal adhesion turnover in the TG2-knockout fibroblasts. Rescue experiments demonstrated that TG2-mediated effects on cell adhesion occurred in the extracellular environment and that neither GTP-binding nor TGase activity is required for these effects. Results further showed that a ???compact??? conformation of TG2 was not required for this role of TG2. Interestingly, addition of recombinant TG2 to the extracellular environment increased cell spreading of TG2-null cells to a level far greater than that seen in wildtype cells, which did not increase their spreading in response to exogenous TG2. Demonstration of faster activation of the small GTPases in the TG2-null MEFs, and the apparent inhibition of exogenous TG2???s extracellular effects on cell spreading by endogenous protein in the wildtype cells, provide tantalising evidence for a role for intracellular TG2 in regulating activation of the small GTPases to promote efficient fibroblast migration. This work identifies TG2 as a facilitator of efficient wound closure through extracellular effects on integrin-mediated signalling and intracellular effects on activation of the small GTPases.

Thesis (Ph. D.)--University of Hawaii at Manoa, 2005. / Includes bibliographical references (leaves 150-166).

Thesis (Ph. D.)--Stanford University, 1982. / Includes bibliographical references (leaves 200-211).

Thesis (Ph. D.)--Massachusetts Institute of Technology and Woods Hole Oceanographic Institution, 1979. / Vita. Grant no.: N00014-74-C-0262, NR 083-004, N00014-75-C-0291 (MIT). Includes bibliographical references.

Thesis (Ph. D.)--Columbia University, 1982. / Includes bibliographical references.

Thesis (Ph. D.)--Massachusetts Institute of Technology and Woods Hole Oceanographic Institution, 1979. / Vita. Grant no.: N00014-74-C-0262, NR 083-004, N00014-75-C-0291 (MIT). Includes bibliographical references.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Earth and Planetary Sciences, 1979. / Supervised by J.G. Sclater. Vita. Includes bibliographical references.

Master of Science / Department of Electrical and Computer Engineering / Caterina M. Scoglio / West Nile virus (WNV) ---a mosquito-borne arbovirus--- entered the USA through New York City in 1999 and spread to the contiguous USA within three years while transitioning from epidemic outbreaks to endemic transmission. The virus is transmitted by vector competent mosquitoes and maintained in the avian populations. WNV spatial distribution is mainly determined by the movement of residential and migratory avian populations. We developed an individual-level heterogeneous network framework across the USA with the goal of understanding the long-range spatial distribution of WNV. To this end, we proposed three distance dispersal kernels model: 1) exponential ---short-range dispersal, 2) power-law ---long-range dispersal in all directions, and 3) power-law biased by flyway direction ---long-range dispersal only along established migratory routes. To select the appropriate dispersal kernel we used the human case data and adopted a model selection framework based on approximate Bayesian computation with sequential Monte Carlo sampling (ABC-SMC). From estimated parameters, we find that the power-law biased by flyway direction kernel is the best kernel to fit WNV human case data, supporting the hypothesis of long-range WNV transmission is mainly along the migratory bird flyways. Through extensive simulation from 2014 to 2016, we proposed and tested hypothetical mitigation strategies and found that mosquito population reduction in the infected states and neighboring states is potentially cost-effective.

Master of Science / Department of Electrical and Computer Engineering / Faryad Darabi Sahneh / A significant number of processes we observe in nature can be described as a spreading process; any agent which is compelled to survive by replicating through a population, examples include viruses, opinions, and information. Accordingly, a significant amount of thought power has been spent creating tools to aid in understanding spreading processes: How do they evolve? When do they thrive? What can we do to control them? Often times these questions are asked with respect to processes in isolation, when agents are free to spread to the maximum extent possible given topological and characteristic constraints. Naturally, we may be interested in considering the dynamics of multiple processes spreading through the same population, examples of which there are no shortage; we frequently characterize nature itself by the interaction and competition present at all scales of life. Recently the number of investigations into interacting processes, particularly in the context of complex networks, has increased. The roles of interaction among processes are varied from mutually beneficial to hostel, but the goals of these investigations has been to understand the role of topology in the ability of multiple processes to co-survive. A consistent feature of all present works -- within the current authors knowledge -- is that conclusions of coexistence are based on marginal descriptions population dynamics. It is the main contribution of this work to explore the hypothesis that purely marginal population descriptions are insufficient indicators of co-survival between interacting processes. Specifically, evaluating coexistence based on non-zero marginal populations is an over-simplistic definition. We randomly generate network topologies via a community based algorithm, the parameters of which allow for trivially controlling possibility of coexistence. Both marginal and conditional probabilities of each process surviving is measured by stochastic simulations. We find that positive marginal probabilities for both processes existing long term does not necessarily imply coexistence, and that marginal and conditional measurements only agree when layers are strongly anti-correlated (sufficiently distinct). In addition to the present thesis, this work is being prepared for a journal article publication. The second portion of this thesis presents numerical simulations for the Adaptive Contact - Susceptible Alert Infected Susceptible model. The dynamics of interaction between an awareness process and an infectious process are computed over a multilayer network. The rate at which nodes "switch" their immediate neighbors (contacts) when exposed to the infection is varied and numerical solutions to the epidemic threshold are computed according to mean-field approximation. We find two unexpected cases where certain parameter configurations allow the epidemic threshold to either increase above or decrease below the theoretical limits of the layers when considered individually. These computations were performed as part of a separate journal article that has been accepted for publication.