A Model of Physician Goal Commitment

The Physician Goal Commitment Model provides a framework, based on prior research, in which to explore the resulting conflicts between physicians' personal goals and the organizational goals of managed care providers. The utility of this model is to provide information regarding total commitment and to identify specific conflict situations, using group specific scenarios, presented in survey or questionnaire form. Successful resolution of conflicts by physicians will indicate areas contributing significantly to higher overall commitment, while unsuccessful resolution of conflicts suggest barriers to a cooperative, efficient, and effective care delivery system.Master of Public AdministrationPublic AdministrationUniversity of Michigan-Flinthttps://deepblue.lib.umich.edu/bitstream/2027.42/143441/1/Hardy.pd

Computationally-Guided Thermostabilization of the Primary Endoglucanase from Hypocrea jerorina for Cellulosic Biofuel Production

The creation of thermostable enzymes has wide-ranging applications in industrial, scientific, and pharmaceutical settings. As various stabilization techniques exist, it is often unclear how to best proceed. To this end, we have redesigned Cel5A (HjCel5A) from Hypocrea jecorina (anamorph Trichoderma reesei) to comparatively evaluate several significantly divergent stabilization methods: 1) consensus design, 2) core repacking, 3) helix dipole stabilization, 4) FoldX ΔΔG approximations, 5) Triad ΔΔG approximations, and 6) entropy reduction through backbone stabilization. As several of these techniques require structural data, we initially solved the first crystal structure of HjCel5A to 2.05 Å. Results from the stabilization experiments demonstrate that consensus design works best at accurately predicting highly stabilizing and active mutations. FoldX and helix dipole stabilization, however, also performed well. Both methods rely on structural data and can reveal non-conserved, structure-dependent mutations with high fidelity. HjCel5A is a prime target for stabilization. Capable of cleaving cellulose strands from agricultural waste into fermentable sugars, this protein functions as the primary endoglucanase in an organism commonly used in the sustainable biofuels industry. Creating a long-lived, highly active thermostable HjCel5A would allow cellulose hydrolysis to proceed more efficiently, lowering production expenses. We employed information gleaned during the survey of stabilization techniques to generate HjCel5A variants demonstrating a 12-15 °C increase in the temperature at which 50% of the total activity persists, an 11-14 °C increase in optimal operating temperature, and a 60% increase over the maximal amount of hydrolysis achievable using the wild type enzyme. We anticipate that our comparative analysis of stabilization methods will prove useful in future thermostabilization experiments.</p

Dialogic Dissensus: The Postmodern Sideshow

In the United States, the sideshow occupies a marginal and often controversial space in popular culture. Despite a decline of the sideshow during the early twentieth century, its postmodern reinvention in 1980 has inspired a proliferation of the aesthetics of the sideshow within mass media and culture as a highly profitable commodity. The current existence of the sideshow as a thriving genre can sometimes be met with surprise, disbelief, or disgust because of the history of sideshow and existing codes of “normality.” Although there is pre-existing scholarship on Bakhtin and the sideshow, what is missing is an exploration of Bakhtin’s dialogism in relation to the art of the postmodern sideshow. This dissertation argues that the postmodern sideshow as an art form is an example of a reinvention of intersubjectivity through Bakhtin’s dialogic and still relevant for understanding contemporary aesthetics. Furthermore, I propose that the carnivalesque is an aspect of the dialogic because the carnivalesque renews hope for a better future which reverberates through unfinalizable time. Instead, I will propose an intertextual genealogy between philosophical thought and the first-hand voices of sideshow performers and related show people in the spirit of dialogism. However, I assert that the dialogic is nearly impossible without a dissensus because of precarization and our permanent cellular connection as a result of our technological progress, which did not exist at the height of postmodernism. This new tyranny of normality has depersonalized our time, dissolved our friendships and communities, our ability to communicate, and our social consciousness to empathize with others in a fundamental shift to our notions of exploitation. A revolution of the aesthetic regime through the maternal will create a new paradigm that reorganizes our senses, our social consciousness, and the conditions for possibility in the dialogic.https://digitalmaine.com/academic/1022/thumbnail.jp

Culture Moderates the Relationship between Family Obligation Values and the Outcomes of Korean and European American College Students

Family obligation values have been described as an important element of collectivistic cultures that are related to the development of positive emotional well-being and motivation in high school and college students. The present study tested the hypothesis that culture moderates the relationship between family obligation values and the outcomes of Korean (n = 249) and European American (n = 251) college students. The results provided support for this hypothesis. Specifically, for Koreans, family obligation values were significantly and positively correlated with descriptions of parents as being more supportive of the self-determination of their children, which was found to mediate the relationship between family obligation values and student outcomes. Furthermore, family obligation values were more strongly associated with the motivation, self-esteem, and depression of Koreans than European Americans. European American students expressed lower family obligation values and the intensity of these values were unrelated to their emotional well-being. Family obligation values were positively correlated with reports of self-determined motivation for Korean students, and negatively correlated with reports of self-determined motivation for European American students. The results are discussed in terms of cultural moderation and self-determination theory

Sexual Violence Against the Outsiders of Society in The Round House, Bitter in the Mouth, and The Color Purple

This thesis will examine why the outsiders to society are more susceptible to violence, particularly sexual violence. America has been led predominantly by white males, white males who have oppressed individuals who do not fit into the white male majority for years. It is my argument that when women of color are born, they are automatically labeled as outsiders due to their race and gender. An outsider is simply one who does not fit into a particular group, the group in this case being white males. While some white women experience sexual violence, their socioeconomic status and race often allows them to receive justice, especially if their perpetrator is a man of color. I will also examine other factors that lead to sexual violence, particularly rape for these outsiders, such as social class and age. This thesis analyzes three primary texts: the 2010 novel Bitter in the Mouth by Monique Truong, the 2012 novel The Round House by Louise Erdrich, and the 1982 novel The Color Purple by Alice Walker. The women in these novels, Linda, Geraldine, and Celie, respectively are sexually assaulted. It is my argument that women of color's race/ethnicity make them more susceptible to violence, both physical and sexual, from others. These texts showcase how women are labelled as outsiders because of their races and their gender, creating a dual outsider status in the white male dominated America; thus, making them more vulnerable to sexual assault and less likely to receive justice

The clinical spectrum of SMA-PME and in vitro normalization of its cellular ceramide profile

OBJECTIVE: The objectives of this study were to define the clinical and biochemical spectrum of spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and to determine if aberrant cellular ceramide accumulation could be normalized by enzyme replacement. METHODS: Clinical features of 6 patients with SMA-PME were assessed by retrospective chart review, and a literature review of 24 previously published cases was performed. Leukocyte enzyme activity of acid ceramidase was assessed with a fluorescence-based assay. Skin fibroblast ceramide content and was assessed by high performance liquid chromatography, electrospray ionization tandem mass spectroscopy. Enzyme replacement was assessed using recombinant human acid ceramidase (rhAC) in vitro. RESULTS: The six new patients showed the hallmark features of SMA-PME, with variable initial symptom and age of onset. Five of six patients carried at least one of the recurrent SMA-PME variants observed in two specific codons of ASAH1. A review of 30 total cases revealed that patients who were homozygous for the most common c.125C \u3e T variant presented in the first decade of life with limb-girdle weakness as the initial symptom. Sensorineural hearing loss was associated with the c.456A \u3e C variant. Leukocyte acid ceramidase activity varied from 4.1%-13.1% of controls. Ceramide species in fibroblasts were detected and total cellular ceramide content was elevated by 2 to 9-fold compared to controls. Treatment with rhAC normalized ceramide profiles in cultured fibroblasts to control levels within 48 h. INTERPRETATION: This study details the genotype-phenotype correlations observed in SMA-PME and shows the impact of rhAC to correct the abnormal cellular ceramide profile in cells

Engineered thermostable fungal cellulases exhibit efficient synergistic cellulose hydrolysis at elevated temperatures

A major obstacle to using widely available and low-cost lignocellulosic feedstocks to produce renewable fuels and chemicals is the high cost and low efficiency of the enzyme mixtures used to hydrolyze cellulose to fermentable sugars. One possible solution entails engineering current cellulases to function efficiently at elevated temperatures in order to boost reaction rates and exploit several other advantages of a higher temperature process. Here we describe the creation of the most stable reported fungal endoglucanase, a derivative of Hypocrea jecorina (anamorph Trichoderma reesei) Cel5A, by combining stabilizing mutations identified using consensus design, chimera studies, and structure-based computational methods. The engineered endoglucanase has an optimal temperature that is 17 °C higher than wild type H. jecorina Cel5A, and hydrolyzes 1.5 times as much cellulose over 60 h at its optimum temperature compared to the wild type enzyme at its optimal temperature.This enzyme complements previously-engineered highly-active, thermostable variants of the fungal cellobiohydrolases Cel6A and Cel7A in a thermostable cellulase mixture that hydrolyzes cellulose synergistically at an optimum temperature of 70 °C over 60 h.The thermostable mixture produces three times as much total sugar as the best mixture of the wild type enzymes operating at its optimum temperature of 60 °C, clearly demonstrating the advantage of higher-temperature cellulose hydrolysis

Effects of early life trauma are dependent on genetic predisposition: a rat study

<p>Abstract</p> <p>Background</p> <p>Trauma experienced early in life increases the risk of developing a number of psychological and/or behavioural disorders. It is unclear, however, how genetic predisposition to a behavioural disorder, such as attention-deficit/hyperactivity disorder (ADHD), modifies the long-term effects of early life trauma. There is substantial evidence from family and twin studies for susceptibility to ADHD being inherited, implying a strong genetic component to the disorder. In the present study we used an inbred animal model of ADHD, the spontaneously hypertensive rat (SHR), to investigate the long-term consequences of early life trauma on emotional behaviour in individuals predisposed to developing ADHD-like behaviour.</p> <p>Methods</p> <p>We applied a rodent model of early life trauma, maternal separation, to SHR and Wistar-Kyoto rats (WKY), the normotensive control strain from which SHR were originally derived. The effects of maternal separation (removal of pups from dam for 3 h/day during the first 2 weeks of life) on anxiety-like behaviour (elevated-plus maze) and depressive-like behaviour (forced swim test) were assessed in prepubescent rats (postnatal day 28 and 31). Basal levels of plasma corticosterone were measured using radioimmunoassay.</p> <p>Results</p> <p>The effect of maternal separation on SHR and WKY differed in a number of behavioural measures. Similar to its reported effect in other rat strains, maternal separation increased the anxiety-like behaviour of WKY (decreased open arm entries) but not SHR. Maternal separation increased the activity of SHR in the novel environment of the elevated plus-maze, while it decreased that of WKY. Overall, SHR showed a more active response in the elevated plus-maze and forced swim test than WKY, regardless of treatment, and were also found to have higher basal plasma corticosterone compared to WKY. Maternal separation increased basal levels of plasma corticosterone in SHR females only, possibly through adaptive mechanisms involved in maintaining their active response in behavioural tests. Basal plasma corticosterone was found to correlate positively with an active response to a novel environment and inescapable stress across all rats.</p> <p>Conclusion</p> <p>SHR are resilient to the anxiogenic effects of maternal separation, and develop a non-anxious, active response to a novel environment following chronic mild stress during the early stages of development. Our findings highlight the importance of genetic predisposition in determining the outcome of early life adversity. SHR may provide a model of early life trauma leading to the development of hyperactivity rather than anxiety and depression. Basal levels of corticosterone correlate with the behavioural response to early life trauma, and may therefore provide a useful marker for susceptibility to a certain behavioural temperament.</p

Mental Health Disorders as Predictors of Relapse in Previously Detoxified Individuals

Researchers have shown a relationship between mental health disorders and alcohol dependence. However, only 5-10% of individuals with substance use problems co-occurring with mental health problems are correctly identified. The purpose of this research was to identify predictors of relapse using three different instruments of varying complexity: the Patient Health Questionnaire-9 (PHQ-9), the Modified Mini Screen (MMS), and the Millon Clinical Multiaxial Inventory-III (MCMI-III). Researchers have found that using alcohol produces relief, similar to a pharmacological intervention, from troublesome mental health symptoms that individuals experience. Considering this association, the self-medication hypothesis was the conceptual lens used for the study as it provides a practical framework for analyzing the relationship between mental health disorders and relapse. At the request of this researcher, data were collected on 45 individuals who were provided detoxification services at a public treatment facility in central Wisconsin. Regression analyses were conducted and identified a statistically significant, although weak, predictive relationship between relapse and the variable of depression as measured by the PHQ-9 (R = .311a, R2 = .097, p = .037), and depression as measured by the MCMI-III (R = .364a, R2 = .133, p = .014). The implications for positive social change from this study include the potential to increase the effectiveness and efficiency in identifying co-occurring mental health disorders among individuals who are treated for alcohol detoxification, enhancing the accuracy of referrals for aftercare, and reducing readmissions for detoxification amongst the individuals served

Iterative approach to computational enzyme design

A general approach for the computational design of enzymes to catalyze arbitrary reactions is a goal at the forefront of the field of protein design. Recently, computationally designed enzymes have been produced for three chemical reactions through the synthesis and screening of a large number of variants. Here, we present an iterative approach that has led to the development of the most catalytically efficient computationally designed enzyme for the Kemp elimination to date. Previously established computational techniques were used to generate an initial design, HG-1, which was catalytically inactive. Analysis of HG-1 with molecular dynamics simulations (MD) and X-ray crystallography indicated that the inactivity might be due to bound waters and high flexibility of residues within the active site. This analysis guided changes to our design procedure, moved the design deeper into the interior of the protein, and resulted in an active Kemp eliminase, HG-2. The cocrystal structure of this enzyme with a transition state analog (TSA) revealed that the TSA was bound in the active site, interacted with the intended catalytic base in a catalytically relevant manner, but was flipped relative to the design model. MD analysis of HG-2 led to an additional point mutation, HG-3, that produced a further threefold improvement in activity. This iterative approach to computational enzyme design, including detailed MD and structural analysis of both active and inactive designs, promises a more complete understanding of the underlying principles of enzymatic catalysis and furthers progress toward reliably producing active enzymes