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Mihalas, Stephanie Tamara University of South Florida 2008 해외공개박사
This study explored the relationship between relational victimization and depression among middle school students (n = 153) in an urban school in Florida. The majority of participants were African-American and Hispanic at-risk youth. This study is one of the first to study how positive protective factors (i.e., hope, spirituality, perceived social support) moderate the relationship between victim status and depression. A mixed methods design was used to gain further insight into the survey data collected. Findings from the study indicated that hope and perceived social support were statistically significant moderator variables. Additionally, results from the qualitative interviews suggested that teachers, parents, and siblings play an important role in supporting victimized students. Implications for gender and culturally sensitive interventions are discussed. Possible avenues for future research are also outlined.
Quantitative model of calcium/calmodulin-dependent protein kinase II activation
Mihalas, Stefan California Institute of Technology 2006 해외박사(DDOD)
Calcium/calmodulin-dependent protein kinase II (CaMKII) is a key element in the Ca2+ second messenger cascades that lead to long term potentiation (LTP) of synaptic strength. In this thesis, I have constructed kinetic models of activation of CaMKII and measured some of the unknown parameters of the model. I used the models to elucidate mechanisms of activation of CaMKII and to study the kinetics of its activation under conditions similar to those in dendritic spines. In chapter 2, I developed a new experimental method to rapidly stop the autophosphorylation reaction. I used this method to measure the catalytic turnover number of CaMKII. To quantitatively characterize CaMKII atophosphorylation in nonsaturating Ca2+, I also measured the autophosphorylation turnover number when CaMKII is activated by calmodulin mutants that can bind Ca2+ only in either the amino or the carboxyl lobes. Previous models of CaMKII activation assumed that binding of calmodulins to individual CaMKII subunits is independent and that autophosphorylation occurs within a ring of 6 subunits. However, a recent structure of CaMKII suggests that pairs of subunits cooperate in binding calmodulin and raises the possibility that the autophosphorylation occurs within pairs of subunits. In chapter 3, I constructed a model in which CaMKII subunits cooperate in binding calmodulin. This model reconciled previous experimental results from the literature that appeared contradictory. In chapter 4, I constructed two models for CaMKII autophosphorylation, in which autophosphorylation can occur either in rings or pairs, and used them to design experiments aimed at differentiating between these possibilities. Previously published measurements and the measurements that I performed are more consistent with autophosphorylation occurring within pairs. In chapter 5, I constructed a model for simultaneous interactions among Ca2+, calmodulin, and CaMKII, and I used an automatic parameter search algorithm to fit the parameters for this model. I used it to characterize which of the parameters of Ca2+ transients are critical for CaMKII activation. This modeling work is part of a continuing effort to realistically model the spatial and temporal aspects of Ca2+ second messenger signaling in dendritic spines.