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Continuum Modeling and Finite Element Analysis of Cell Motility
Hodge, Neil Eugene University of California, Berkeley 2011 해외박사(DDOD)
Cell motility, and in particular crawling, is a complex process, with many as yet unknown details (e.g., sources of viscosity in the cell, precise structure of focal adhesions). However, various models of the motility of cells are emerging. These models concentrate on different aspects of cellular behavior, from the motion of a single cell itself, to -taxis behaviors, to population models. Models of single cells seem to vary significantly in their intended scope and the level of detail included. Most single cells are far too large and complex to be globally amenable to fine-scale modeling. At the same time, cells are subject to external and internal influences that are connected to their fine-scale structure. This work presents a continuum model, including the use of a continuum theory of surface growth, that will predict the crawling motion of the cell, with consideration made for the appropriate fine-scale dependencies. This research addresses several modeling aspects. At the continuum level, the relationships between force and displacement in the bulk of the cell are modeled using the balance laws developed in continuum mechanics. Allowances are made for the treatment of and interaction between multiple protein species, as well as for the addition of various terms into the balance laws ( e.g., stresses generated by protein interactions). Various assumptions regarding the nature of cell crawling itself and its modeling are discussed. For instance, the extension of the lamellipod/detachment of the cell is viewed as a growth/resorption process. The model is derived without reference to dimensionality. The second component of the presentation concerns the numerical implementation of the cell motility model. This is accomplished using finite elements, with special features (i.e., ALE, discontinuous elements) being used to handle certain stages of the motility. In particular, the growth assumption used to model the crawling motility is represented using ALE, while the strong discontinuities that arise out of the growth model are represented using the discontinuous elements. Results from representative finite element simulations are shown to illustrate the modeling capabilities.
Optimization of high solids lignocellulosic biomass conversion for ethanol production
Hodge, David Colorado State University 2005 해외박사(DDOD)
Dilute acid pretreatment followed by enzymatic hydrolysis of cellulose and sugar fermentation is a promising technology for converting lignocellulosic biomass to fuel ethanol. Two of these steps, enzymatic hydrolysis and fermentation, are ultimately catalyzed by protein. The broad goal of this study is to develop a more definite understanding of the physical barriers to performing these two process steps economically. The major foci of this work are high-solids enzymatic saccharification of pretreated lignocellulosic biomass (corn stover) and protein expression profiling of a metabolically engineered bacterium fermenting glucose and xylose, the major biomass sugars. While high-solids enzymatic hydrolysis of cellulose is advantageous for reducing capital and operating costs, operating an enzymatic saccharification reactor at high insoluble solids levels presents a unique set of physical and reactor-dependent challenges such as mass transfer, temperature control, mixing, pH control, and sugar inhibition. This work partially focused on characterizing the effects of these problems. It was determined in saccharification characterization studies that slurries of pretreated corn stover (PCS) containing between 10% and 15% insoluble solids by weight represent the approximate upper limit for enzymatically hydrolyzing cellulose in a stirred tank reactor (2--10 L scale fermenter). As this work demonstrates, this maximum limit is ultimately derived from mixing limitations that cause difficulties with temperature control, as well with uniformly distributing enzymes. Using an offline optimal control algorithm in conjunction with a process model, a bench-scale stirred tank reactor was operated at 15% insoluble solids in fed-batch mode, while demonstrating sugar concentrations and yields equivalent to what would be found if operating at 25% initial insoluble solids. Further work applied 2-D gel electrophoresis and hierarchical cluster analysis to track transient protein abundance levels in during the course of mixed substrate fermentation of the two principle sugars contained in lignocellulosic biomass. Of particular significance the saccharification work was able to demonstrate for the first time that high glucose concentrations (>140 g/L or 80% cellulose conversion) are achievable in high-solids enzymatic saccharification reaction systems, and that high-solids enzymatic saccharification presents a viable reaction step option in lignocellulosic biomass conversion technologies.
Expatriate modernisms: Border crossing in the 1920s
Hodge, Deckard Francis University of California, Riverside 2005 해외박사(DDOD)
Expatriate Modernisms: Border Crossing in the 1920s focuses on some of the ways Ernest Hemingway, Hart Crane, Nella Larsen, Gertrude Stein, F. Scott Fitzgerald, James Joyce, and Sadakichi Hartmann reveal borderlands as rhizomatic sites of potential, as places where possibility is created rather than limited. This project examines how Hemingway's In Our Time blurs distinctions between genres, genders, and fates; how Crane's The Bridge offers a postmodern notion of history and time, erasing boundaries of difference between past and present; how Larsen's Quicksand highlights the contingency and social-constructedness of race; and how some of the works by Stein, Fitzgerald, Joyce, and Hartmann (Stein's Tender Buttons and "Composition as Explanation," Fitzgerald's 1920s novels: This Side of Paradise, The Beautiful and Damned, and The Great Gatsby, Joyce's "Oxen of the Sun" episode in Ulysses, and Hartmann's newly-anthologized poems) share an emphasis on simultaneous presence and absence. By proposing ways in which all of these texts traditionally regarded as "high modern" might be read as participants in today's burgeoning discourse on borderlands, I suggest rich possibilities for rereading not only these works, but also others from the modernist period.
Settlement dispersal, economic disintensification, and human health at Moundville (Alabama)
Hodge, Shannon Chappell Tulane University 2005 해외박사(DDOD)
This research proposes a model of economic disintensification, applied to the Mississippi period chiefdom of Moundville, in Alabama. I hypothesized the post-A.D. 1300 population dispersal from Moundville to outlying sites would have resulted in economic disintensification. To evaluate this model, I proposed subsistence, settlement pattern, and health correlates of disintensification, and tested these correlates against data from the Moundville site. I reviewed the existing literature on Moundville subsistence, and found that the published data were insufficient for determining if disintensification had occurred. Next, I performed a settlement pattern analysis of the number, mean size, distribution and density of Moundville phase sites, and found that although population dispersal occurred, there was no firm evidence of disintensification. I also collected primary demographic and paleopathological data from Moundville phase human skeletal remains, and made a diachronic comparison of skeletal samples before and after population dispersal, to see if there were any differences in health or nutrition that would signal disintensification. I found no statistically significant differences in rates of disease, trauma, degenerative joint disease, dental pathology or dental wear between pre-dispersal and post-dispersal populations, indicating that disintensification did not take place. The model of disintensification is upheld, and most of the archaeological correlates I proposed for disintensification are valid tests of the model. However, disintensification did not occur within the Moundville chiefdom. Instead, Moundville and the outlying communities in the chiefdom appear to have maintained close ties, and continued to act as a single entity in terms of subsistence and social connections, thereby leaving open the vectors of disease at consistent low levels throughout the Moundville era. I believe this low-level exposure partially accounts for the lack of clear distinctions in health between the subphases. Overall, people appear to have maintained good health and an adequate diet across time, regardless of population movements and political change. The dispersal of Moundville's population after A.D. 1300 in no way represents "the beginning of the end" of the chiefdom, but rather an organizational improvement that maintained the social and salutary status quo to the benefit of outlying communities and the residents of Moundville alike.
Hodge, Sharon McWhirter University of Georgia 2001 해외박사(DDOD)
Identification of cognitive variables that affect how welfare recipients process employment information, make occupational decisions, and solve work problems is important to the design of appropriate job training interventions for this population. This study developed a profile of individuals who receive Temporary Aid to Needy Families (TANF). It also examined the contribution of selected social indicators and four cognitive constructs to variation in work role participation. Three instruments were administered—the demographic profile and Participation scale of the <italic>Salience Inventory</italic> (Super & Nevill, 1985), the <italic>Career Thoughts Inventory</italic> (Sampson, Peterson, Lenz, Reardon, & Saunders, 1996a), and the <italic> Career Decision-Making Self-Efficacy Scale-Short Form</italic> (Betz, Klein, & Taylor, 1996)—to determine how well race, education level, dysfunctional career thoughts (decision-making confusion, commitment anxiety, external conflict), and career decision-making self-efficacy predicted work role participation in a sample of 104 individuals receiving TANF assistance. The sample of TANF individuals did not conform to the stereotypical image of welfare recipients in that they were older, better educated, and more heterogeneous than is typically thought. A majority of participants indicated at least some problem with dysfunctional career thoughts with external conflict being the highest level of difficulty. Levels of career decision-making self-efficacy were lower than levels of career self-efficacy in a normative sample of college females with the lowest levels of confidence in career planning and problem-solving tasks. <italic>T</italic>-tests revealed that Black recipients spent more significant time in work activities than White recipients, and non-high school completers indicated more significant decision-making confusion and commitment anxiety but less career decision-making self-efficacy than high school completers. Multiple regression analysis revealed that 11.8 percent of the variance in work role participation could be explained by the social indicators and cognitive variables combined. Supplementary analyses revealed that career decision-making self-efficacy was the single most important predictor of the variables studied. Results contribute to research literature describing cognitive variables and vocational behavior of socio-economically disadvantaged individuals. Findings may also assist job training practitioners in interventions designed to effect more satisfactory employment outcomes.
Hodge, Lucy Sahr University of Minnesota 2010 해외박사(DDOD)
Gemcitabine is a nucleoside analog used as a radiosensitizer for the treatment of locally advanced cervical carcinoma. Yet, despite its efficacy when administered concomitantly with radiation, gemcitabine therapy is not without side effects. The utility of delivering gemcitabine directly to the cervix was explored through the use of a novel drug delivery device, CerviPrep(TM). Local administration to the cervix led to clinically relevant concentrations of gemcitabine in cervical tissue and plasma, while no gemcitabine was detected in the systemic circulation and no side effects were reported. Our data suggest that targeting gemcitabine delivery to the cervix can limit systemic exposure and toxicity while achieving cytotoxic concentrations of drug at the target site. Despite its widespread use in cervical carcinoma, little is known about the disposition of gemcitabine in this tissue. As a nucleoside analog, gemcitabine is a substrate for the equilibrative nucleoside transporters (hENT), and patient response to gemcitabine therapy has been associated with the expression of these proteins. A characterization of hENT1 and hENT2 in both malignant and normal cervical tissue was undertaken, and while no effect of malignancy was observed on hENT1 protein expression, hENT2 protein was nearly three-fold higher in malignant cervical tissue when compared to normal tissue. Expression of hENT mRNA was highly variable and not associated with malignancy. We also examined the effect of dFdU on gemcitabine disposition, as this relatively inactive metabolite is present at much higher concentrations in the plasma than gemcitabine following intravenous administration of the parent compound. We report a novel interaction between dFdU and gemcitabine whereby dFdU competes with gemcitabine for transport via hENT1 and hENT2. The presence of dFdU appears to enhance the retention of gemcitabine intracellularly leading to an increase in the amount of active gemcitabine triphosphate. As more gemcitabine is phosphorylated in the presence of dFdU, a "metabolic sink" is created, further increasing gemcitabine uptake into the cell via hENT1 and hENT2. These data suggest that both transport and intracellular metabolism are equally important components of gemcitabine disposition and cytotoxic potential, and that the presence of dFdU increases intracellular exposure to this nucleoside analog.
Mental accounting and subsequent purchases: Consumer responses to price surprises
Hodge, Sharon K The University of North Carolina at Chapel Hill 2001 해외박사(DDOD)
This research investigates how aspects of initial purchasing decisions affect subsequent purchasing decisions. Most past research has focused on single purchases—typically the selection of a single alternative from some choice set. In contrast, this dissertation focuses on how consumers' responses to savings and losses on an initial purchase impact spending decisions for a subsequent purchase. It specifically examines how these responses are moderated by: (1) consumer control, (2) product relatedness, and (3) savings magnitude. Four experimental studies address these issues. Study 1 examined whether consumers respond asymmetrically to savings and losses when spending on a subsequent purchase. Subjects responded asymmetrically, but not significantly in one direction or the other. Qualitative data revealed the directionality of consumers' responses was largely a function whether the buyer was quality-driven, savings-driven, or “product interest”-driven. Study 2 examined how consumer control affects subsequent purchasing decisions for savings and losses. Subjects were more responsive to savings from sources outside their control, but more sensitive to losses inside their control. Qualitative data for savings suggest buyers have already allocated an amount to spend before they shop to a mental “spend account,” facilitating transfer of unanticipated savings to subsequent purchases. For losses inside their control, buyers are likely to pay a price in terms of quality or consumption to atone for their mistake. When losses are outside their control, buyers are less likely to feel a responsibility toward reducing subsequent spending. Study 3 examined savings under different degrees of product relatedness. Subjects spent more of a savings on a subsequent purchase when that purchase was related to the initial purchase. Qualitative data suggest savings for related products tend to be viewed in the same mental budget, facilitating transfer of savings on one purchase to subsequent spending on the other. Study 4 examined different levels of savings magnitude on subsequent purchasing decisions. Subjects spent proportionally more of a savings on a subsequent purchase when the savings was of small rather than large magnitude. Qualitative data suggest small savings are more available to “spend now,” while portions of large savings are stored as “assets” for future use.
Colonization of the Cuban body: Nationalism, economy, and masculinity of male sex work in Havana
Hodge, G. Derrick City University of New York 2005 해외박사(DDOD)
Survival of the extreme economic austerity of the Special Period---both national and personal---has required a dramatic bending of social, cultural, and political norms established during the first forty years of the Revolution. The turn to capitalism and tourism has a produced new groups of street hustlers and sex workers who call themselves pingueros. The pingueros and their bodies are sites at which converge four potentially contradictory processes: traditional Cuban masculinity, revolutionary nationalism, the exigencies of material survival, and the global capitalist imperative to consume. Personal desire is interactive with the collective processes of economy, politics, culture, and nation-building; the pingueros' desires (both sexual and material) are being configured according to the needs of the new capitalist market, but the youth are also faithful repositories of both Cuban masculinity and revolutionary citizenship. Though the state criminalizes the pingueros, they are nonetheless faithful reproducers of revolutionary ideology in terms of gender norms and expectations of economic justice. But since the youth revere designer clothing and look to consumer capitalism as their salvation from poverty, they are global capitalist consumers as much as they are revolutionary citizens. This dual location---as both reproducers of (socialist) revolutionary values and as criminalized youth who enthusiastically proclaim the triumph of capitalism---is a window into the social and cultural effects of both capitalism and (post)socialism. Ultimately, Cuba is being recolonized through the aggressive introduction of a new imperative to consume. The introduction of capitalism has saved the Cuban economy, but it has also had the consequence of transforming perceptions of need among the youth. This implantation of capitalist cultural forms is at end more powerful and longer-lasting than any particular regime. The Revolutionary government still enjoys considerable legitimacy, but the lure of consumption is powerful, and this may well become the ultimate triumph of a global capitalism over the Revolution. The children and grandchildren of the 1960--62 emigrants never got the military invasion for which they still so vehemently lobby, but the lure of things may well erode the values of fairness, justice, and equality for which the Revolution fought.
Analysis of the Saccharomyces cerevisiae cyclin-dependent kinase inhibitor Sic1
Hodge, Amy Elizabeth Yale University 1999 해외박사(DDOD)
The <italic>Saccharomyces cerevisiae</italic> cyclin-dependent kinase inhibitor Sic1 prevents premature initiation of S phase by binding to and inhibiting the activity of Clb•Cdc28 kinase complexes. Through deletion analysis this work has identified the C-terminal 70 amino acids of Sic1 to be necessary and sufficient for in vivo inhibitory activity. In addition, mutagenesis was used to show that simultaneous mutation of R261 and L263 abolished in vivo inhibition of both the full-length protein and the minimal inhibitory fragment. These two residues fall within a motif that is conserved near the N-termini of inhibitors that bind to the mammalian cclinA•Cdk2 complexes. Alignment of Sic1 with its functional homolog from <italic>Schizosaccharomyces pombe</italic> Rum1 shows no conservation of this particular sequence but rather of another more degenerate form of the motif found at the C-termini of cyclinA•Cdk2 substrates. It is proposed that Sic1 inhibits Clb•Cdc28 kinase complexes by binding in a manner similar to that of cyclinA•Cdk2 substrates. A specific cleavage event within the minimal inhibitory fragment of Sic1 has also been identified in this work, but the in vivo significance, if any, of this cleavage is unknown. In vitro kinase assays were performed to attempt to corroborate the in vivo data with a quantitative analysis but were inconclusive.