Advantaged by the challenges: Life histories of high achieving first generation college women of color

German, Raechel Elizabeth Nan Michigan State University 2008 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

This study of the academic life histories of four high achieving first generation college women of color at a predominantly White Midwestern university explored factors in the formative and collegiate educational experiences that have led to the women's exceptional academic success. The questions that provided direction for the research were: (a) What are the defining moments in the pre-college and college experiences of gifted first generation college women of color? (b) What facilitates or provides an obstacle to high achieving women in the pre-college years and while in college? (c) To what or whom do high achieving first generation women of color attribute their academic success and finally, (d) What are some interventions that could serve as catalysts to enable the positive academic identity development of other first generation college students?. Each woman's history uniquely contributes to the discussion of ways in which early academic and non-academic challenges can fuel subsequent academic achievement. By using aspects of cultural identity and heritage, learning the language of the academy, applying lessons learned in other non-academic environments, and making decisions based on a strong internal foundation, the women's histories chronicled in this research provide a counternarrative to existing research that nearly uniformly claims the academic German frailty of first generation students and students of color. Family, school, and peer support are cited as critical to the success of the young women but their influence is moderated by each student's internal drive and ability to make independent decisions. As such, the women show signs of self-authorship as they make meaning of their school experiences and academic paths. Findings suggest that middle school interventions, intensive secondary school relationships with teachers and administrators, college enrichment programs and the peer relationships they foster may be particularly facilitative of academic success for these talented young women. The life histories presented are instructive regarding how a student can build and negotiate a positive academic identity development during their K-16 school career without the benefit of having an immediate family member who is personally familiar with what it is like to attend college. They also suggest strategies for educational institutions and practitioners seeking to improve the school experiences for first generation college women of color.

Studies on vitamin E and myoinositol nutrition for parrot fish (Oplegnathus fasciatus)

Galaz, German Bueno Cheju National Univ. 2008 국내박사

Parrot fish, Oplegnathus fasciatus, has been identified as one of the candidate for marine intensive aquaculture in Korea, China and Japan. However, little information in nutrition is available for the fish. Particularly, dietary requirements of vitamin E and inositol, which have been reported as the most expensive ingredients for normal growth of fish (Gaylord et al., 1998). Therefore, the aim of the first feeding trial was to determine the dietary requirement of vitamin E and its effects on innate immune responses and disease resistance of juvenile parrot fish. The second feeding trial aimed to elucidate essentiality of inositol in diet for juvenile parrot fish, and its effects on liver lipid metabolism. The present work consists of two chapters. The first chapter covers the requirement of vitamin E and its effect on immune responses in parrot fish. The second chapter covers the requirement of dietary myo-inositol and its physiological nutrition in parrot fish. In the first chapter, a 12-week feeding trial was conducted using a flow-through system to determine the dietary requirement of vitamin E for parrot fish in relation to growth performance, and to examine the effects of vitamin E on immune responses and disease resistance. Six semi-purified diets (E0, E25, E50, E75, E100 and E500) supplemented with 0, 25, 50, 75, 100 and 500 mg DL--tocopheryl acetate/kg diet, respectively, were fed to triplicate groups of parrot fish juveniles (mean body weight 20.15±0.09 g). At the end of feeding trial, growth performance and feed utilization and vitamin E deposition in liver were evaluated. Respiratory burst, lysozyme and myeloperoxidase (MPO) activities were analyzed. The fish fed with graded dietary vitamin E levels were challenged with Vibrio anguillarum. Significant higher weight gain, specific growth rate, protein efficiency ratio and lower feed conversion ratio were observed in fish fed diet E25. Survival did not differ among the treatments. Addition of vitamin E to the basal diet did not significantly affect whole body protein, crude fat, ash and moisture. An increase in the supplementation of vitamin E in the diet caused an increment in the deposition of vitamin E in liver tissue. Respiratory burst and MPO activities significantly increased with increment of dietary vitamin E levels. Serum lysozyme activity was not significant different among experimental diets. In challenge test, the dietary treatments E500, E100, E75 registered the highest survival of 13.89, 5.56 and 5.56%, respectively. In the second chapter was conducted a study to estimate the essentiality and requirement of myo-inositol (MI) for juvenile parrot fish, Oplegnathus fasciatus. MI was supplemented 0, 100, 200, 400 and 800 mg/kg diet in the basal diet providing 0, 83, 212, 410 and 943 mg MI/kg diet respectively. Each diet was fed to triplicate groups of juvenile parrot fish (initial body weight, 11.5 g). After 18 weeks of a feeding trial, fish fed diets with supplementation of MI had significantly higher weight gain and specific growth rate than those of fish fed the basal diet. Supplementation of dietary MI did not affect survival of parrot fish. Dietary MI affected blood hematocrit, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, while plasma triglyceride and myeloperoxidase (MPO) activity were not affected. Liver MI concentration of the fish fed the experimental diets was significantly increased by dietary supplementation of MI. The liver MI concentrations were highest in fish fed the ≥212 mg MI/kg diet and lowest in fish fed the MI free diet. Liver lipid concentrations were significantly decreased as increment of dietary MI supplementation. The dietary requirement of MI based on weight gain percentage and liver MI concentrations were analyzed by broken-line regression and indicated that the requirement for dietary MI in juvenile parrot fish is about 94 and 121 mg/kg diet, respectively. Therefore, we recommend the addition of myo-inositol approximately 100 mg/kg diet to prevent a potential problem by an abnormal lipid metabolism and to maximize the growth performances in juvenile parrot fish. In conclusion, the findings in this study suggest that an optimum level of the dietary vitamin E would be approximately 40 mg/kg for the maximum growth performances. It is suggested that over 500 mg vitamin E/kg diet could improve the immune responses of the fish. Also, the dietary supplementation of myo-inositol is needed to maximise the growth performance and to prevent abnormal lipid metabolism in juvenile parrot fish. The suggested dietary requirement of myo-inositol is about 100 mg/kg diet. 최근 양식산업에 있어서 새로운 양식대상어종으로 각광받고 있는 돌돔(Oplegnathus fasciatus)은 넙치와 조피볼락에 비해 성장이 다소 느린 단점을 가지고 있으나 질병에 대한 내병성이 강한 고부가가치의 유망한 양식대상 어종이다. 따라서 이 연구는 돌돔사료 내 비타민의 적정함량 규명을 통한 돌돔양식에 대한 기초연구자료 제공과 양식에 소요되는 비용 절감을 위해 수행되었다. 이 연구는 Part Ⅰ과 Ⅱ로 나누어 수행되어졌으며, Part Ⅰ에서는 돌돔치어 사료 내 비타민 E 적정함량과 비타민 E의 단계적인 첨가에 따른 어류의 면역력에 미치는 영향을 알아보기 위해 수행되었다. Part Ⅱ에서는 돌돔치어 사료 내 myo-inositol 단계적인 첨가에 따른 어류 성장 및 면역력에 미치는 영향을 알아보기 위해 수행되었다. 돌돔치어 사료 내 비타민 E 요구량과 비타민 E 첨가에 따른 면역력을 알아보기 위해 수행한 사양실험(Part Ⅰ)은 12동안 수행되었으며, 반 정제 사료원이 기초인 총 6개의 실험사료는 비타민 E 함량을 각각 0, 25, 50, 75, 100, 500 mg/kg diet으로 기초사료에 첨가하였다. 12동안의 사양실험 결과, 비타민 E가 25ppm 첨가되어진 실험구는 대조구에 비해 유의적으로 높은 성장률과 사료효율을 나타내었으나, 생존률과 전어체 함량은 사료 내 비타민 E 첨가에 유의적인 영향을 받지 않았다. 실험어류의 간 내 비타민 E 함량은 사료 내 비타민 E 첨가 함량의 증가에 따라 유의적인 증가를 보였으며, 실험사료를 섭취한 어류의 면역력을 알아보기위해 수행한 respiratory burst, myeloperoxidase 활성 분석 결과에서도 사료 내 비타민 E 첨가 함량의 증가에 따라 유의적으로 높은 할성을 나타내었다. 한편, Vibrio anguillarum을 이용한 공격 실험의 결과에서는 75ppm 이상의 비타민 E를 섭취한 실험구들에서 다른 실험구들에 비해 높은 생존률을 나타내었다. 돌돔 치어 사료 내 myo-inositol 첨가에 따른 어류의 성장 및 면역력에 미치는 영향을 알아보기 위해 수행한 사양실험(Part Ⅱ)은 18주동안 수행되었다. 실험사료 내 myo-inositol은 0, 100, 200, 400, 800 mg/kg diet으로 첨가되어졌으며, 사양실험은 3반복으로 수행되었다. 18주 동안의 사양실험 결과, myo-inositol이 첨가되어진 실험구들은 myo-inositol 첨가되어지지않은 대조구에 비해 유의적으로 높은 성장률과 사료효율을 나타내었다. 그러나 사료 내 myo-inositol의 첨가는 어류의 생존률에는 유의적인 영향을 미치지 않았으며, 혈액학적 분석 (hematocrit, asparatate aminotransferase, alanine aminotransferase, plasma triglyceride, cholesterol)과 면역학적 분석 (myeloperoxidase activity) 결과에서도 모든 실험구에서 유의적인 차이를 발견하지 못했다. 한편, 실험어류 간 내 myo-inositol 농도는 사료 내 myo-inositol 함량 증가와 함께 높아지는 경향을 나타내었으며, 사료 내 200ppm 첨가 실험구에서 가장 높은 값을 나타내었다. 어류 간 내 지방함량에 있어서는 사료 내 myo-inositol 함량이 증가함에 따라 유의적으로 낮은 지방함량을 나타내었다. Broken-line regression 모델을 이용하여 어류의 성장률과 간 내 myo-inositol 농도를 기초로 한 돌돔 치어 사료 내 myo-inositol 요구량은 약 94와 121 mg/kg으로 각각 분석되어졌다. 이와 같은 연구 결과를 바탕으로 할 때 돌돔 치어에 있어서 최적의 성장과 원활한 지방대사를 위한 사료 내 myo-inositol 요구량은 대략적으로 100mg/kg으로 사료되어진다. 결론적으로, 돌돔치어 사료 내 최적의 성장을 위한 비타민 E 요구량은 약 40 mg/kg으로 판단되어지며, 돌돔치어 사료 내 고농도(500 mg/kg)의 비타민 E 첨가는 어류의 면역력을 향상 시킬 수 있을 것으로 여겨진다. 또한, 돌돔치어에 있어서 최적의 성장과 원활한 지방대사를 위한 사료 내 myo-inositol 요구량은 대략적으로 100mg/kg으로 여겨진다.

Computation and Modification of Materials Interfaces for Sustainable Electrochemical and Electromechanical Systems

German, Lazarus Nigel ProQuest Dissertations & Theses The University of 2022 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

The ever-increasing demand for energy and environmental sustainability has promoted the exploration of many green and renewable energy alternatives to fossil fuels. These alternatives—solar, mechanical, thermal, nuclear, hydro, and wind are expected to account for more than 50% of installed power generation in the U.S. by 2050. About one third of that is expected to be solar energy, a portion of which is employed for direct conversion of sunlight to chemical fuel through photoelectrochemistry (PEC). To achieve practical use, these applications must exhibit efficient light absorption, rapid charge separation, and excellent corrosion resistance in harsh chemical environments. Other sustainability efforts include reducing the need for batteries and maximizing safety for implantable medical devices (IMDs) which has implications for the overall quality of life the IMD users and health costs associated with conventional IMDs. Additionally, the development of powerless wireless sensors for the Internet of Things (IoT) for smart building and manufacturing have great potential through smart lighting and heating/ventilation/air condition, and smart diagnostics to improved maintenance and manufacturing efficiency. This dissertation focuses on my work done in computational and interfacial band engineering for efficient and corrosion resistant PEC cells for hydrogen production, the use of piezoelectrics in IMDs and considerations for electrochemical safety therein, and the technological and commercial development of green triboelectric nanogenerators (TENGs) for powerless, wireless IoT sensors. Chapter 1 is a general overview of the basic principles that govern electrochemical systems, solar energy harvesting, piezoelectrics, and the interrelationships of those three as it pertains to the development for PEC, piezotronic PEC, and piezocatalysis. I also review atomic layer deposition (ALD) and recent progress on amorphous oxides as effective protection layers for less stable, high performance photoelectrodes, the discovery and role of structural metastable intermediates, and what has been done thus far to control these intermediates to improve overall lifetime. In the interest of IMDs, I address the safety concerns of piezocatalysis as piezoelectrics are developed more for direct nerve stimulation. Lastly, I discuss the use of cellulose and functionalized cellulose derivatives for high performance, inexpensive, green triboelectric nanogenerators and their development for commercialization directed through market research. Chapter 2 builds up a model for calculating energy band diagrams, particularly those for piezotronic and electrochemical systems. This first approximation approach was designed to be computationally accessible, highly modular, and free for the public to use—a tool to provide quantifiable support for experimental data and/or materials choice designing new interfaces to direct new research. Here, I demonstrate the significance of piezotronic modulation in metal/insulator/semiconductor junctions, p-i-n junctions, and semiconductor/insulator/solution interfaces. These computations also highlight an often-overlooked phenomenon at the semiconductor/solution interface, wherein the isoelectric point (IEP) of the solution-facing solid and its relationship with the pH of solution can have significant effects on the band bending in the semiconductor. Chapter 3 introduces a modified version of the model built up in Chapter 2 combined with experimental results. I demonstrate that we can modify the band bending for charge collection at back electrode for a TiO2 photoanode to improve its overall photocurrent density. This is done by using single-layer graphene as the charge collector sandwiched between ferroelectric lead magnesium niobate-lead titanate (PMN-PT) and TiO2. The limited free charge density in graphene is unable to fully screen the ferroelectric polarization which is then compensated by piezotronic band bending in the TiO2 photoactive material. The direction of ferroelectric poling effectively gates the charge collection efficiency which is evident experimentally and supported through the band bending calculations. By contrast, a 5-nm Au electrode is shown to have enough free charge such that charge collection is independent of the ferroelectric polarization. Piezoelectrics, as with conventional IMDs, can drive electrochemical reactions in the body which have implications for long-term safety. There are currently no guidelines for choosing piezoelectric materials in the interest of mitigating piezocatalysis as a function of their electromechanical properties. Chapter 4 discusses the advent of piezoelectrics as self-sufficient IMDs for direct nerve stimulation, and builds up a model for determining piezocatalytic trends between different piezoelectric/metal couplings. I compare different combinations of piezoelectrics: BaTiO3 (oxide), polyvinylidene fluoride (PVDF; polymer), and γ-glycine (biodegradable biocrystal); and typical metal electrodes used for IMDs: Au, Pt, Ir, and Mg, the latter of which is a popular biodegradable metal electrode. I then discuss other considerations such as corrosion resistance of electrodes, interfacial modification, and packaging to make a recommendation on materials choice. In Chapter 5, I make a case for controlling metastable intermediates in amorphous TiO2 ALD films by introducing a monolayer of Al2O3. The inclusion of the monolayer shows little change in photocurrent density while improving overall stability, supporting the hypothesis that metastable intermediates play a significant role in the corrosion of TiO2. I then provide a structural argument (based on Zacharisen’s rules for glass formation) on how the Al2O3 disrupts the growth of the intermediates. This, of course, comes with the caveat that it is still crucial that we observe these effects more directly and explain them through more fundamental and computational approaches. Chapter 6 and 7 discuss the technical and commercial development of cellulosic TENGs as powerless, wireless IoT sensors through the startup EWPanel. The work in Chapter 6 focuses on modifying commercial cellulosic papers for improved TENG output, demonstrating the recyclability and abundance of TENG resources. These TENGs were integrated into a cellulosic material-based energy harvesting floor (CEHF) which resulted in the first demonstration of wireless transmission achieved by a cellulosic TENG. Chapter 7 focuses on the commercialization efforts that directed the research for Chapter 6. I also discuss developments and consequences of the COVID-19 on the market landscape, the need to pivot from IoT for large scale occupancy analytics, and the additional customer discovery that went in to validating other potential customer segments. Customer interviews revealed that IoT for wander management in nursing homes/assisted living, particularly for seniors living with dementia or Alzheimer’s, is a viable customer segment. Secondary research also suggests a use case in industrial IoT (IIoT; Industry 4.0) for asset tracking or smart analytics for process controls and preventative maintenance. Finally, Chapter 8 summarizes the conclusions of my dissertation work with outlooks for the design of electrochemical systems involving piezotronics, piezocatalysis, interface engineering, and ALD protective oxides. Although my time with EWPanel has ended, I also include next steps for continuing the technical and commercial development of the cellulosic TENGs.

Social stability and HIV risk: Exploring the role of multidimensional social vulnerability

German, Danielle The Johns Hopkins University 2009 해외공개박사

Background. Social stability is an understudied construct with promise for understanding the extent and types of vulnerability experienced among urban populations. Social stability also offers a useful framework to understand the synergy of social vulnerabilities that form the context for and contribute to HIV transmission risk among urban populations. This study: (1) synthesized the existing literature on social stability; (2) investigated prevalence and patterns of co-occurrence among a set of social stability characteristics; (3) evaluated the possibility of underlying sub-groups of social stability; and (4) examined the extent to which indicators of social stability and two measures of multidimensional social stability were associated with HIV-related risk variables among a sample of primarily African-American, low-income women at risk for HIV. Methods. Data were from comprehensive baseline interviews with women and their female social network members (n=635) enrolled in an HIV prevention intervention in Baltimore, MD. Analysis included exploratory statistics, logistic regression, latent class analysis, and latent class regression accounting for clustered data using Stata and Mplus software. Stata version 10 and Mplus version 5 were used for analysis. Results. Literature review identified a set of six common domains of social stability: housing, residential mobility, employment, partner relationship, income, and incarceration. Analytic results supported the premise that this set of characteristics represents a single construct with identifiable underlying sub-groups. Individual indicators varied in their association with HIV-related outcomes and supported investigation of the cumulative impact of stability across domains. Both a cumulative and latent class measure of multidimensional social stability was associated with HIV-related risks, with differing implications. Conclusions. Results reinforce that instability characteristics tend to co-occur, but with heterogeneity. Findings also indicate that the co-occurrence of instability contributes to HIV risk. Future research should investigate socio-demographic and health characteristics associated with social stability. These findings add to the calls for attention to structural health determinants and provide a framework for evaluating social and contextual factors in social service and HIV prevention programs.

HEDGING OPTIONS WITH SMALL TRANSACTION COSTS (LELAND LIMIT)

GERMAN, ILYA CORNELL UNIVERSITY 1999 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

Nonzero proportional transaction costs make perfect replication impossible in the Black-Scholes model. We find the distribution of the replication error caused by readjustments of the hedging portfolio at discrete time intervals. Taking a Leland type limit, we find the limiting behavior of transaction costs being paid. Using these two results, we suggest a method for finding the optimal rebalancing interval.

Contributions of negative affect and empathy to the enjoyment of television drama: A eudaimonic approach

German, Tom The Ohio State University 2008 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

This study aimed to elucidate the role that emotional processes play in the enjoyment of television drama. Of primary interest was negative affect, which is a primary component in all drama, but has not been fully understood in entertainment research. A 2 (CONTEXT: Present, Absent) x 2 (ENDING: Happy, Sad) fully factorial between-individual design was employed to test the effects of empathy toward protagonist and viewers' affective states on entertainment of a dramatic television program. Participants viewed a specially-constructed episode of the program "LOST," which manipulated the availability of the protagonist's back story and the hedonic valence of his eventual outcome through a happy or sad ending. Eudaimonic preference for film was measured as a covariate due to the expectation that people who prefer programs that provide opportunities for them to better know their true selves might enjoy negative endings more than those with higher hedonic preferences. Results showed that the empathy induced by providing character context interacted with ending type, resulting in sad endings being enjoyed differently, suggesting that sad endings could be more entertaining than previous theory would predict. Additionally, eudaimonic preference predicted greater entertainment of sad endings only when context was present. Another contribution of this study was the examination of entertainment, empathy, positive and negative affect as situational effects that evolve over time. To address this research question, a 2 (CONTEXT: Present, Absent) x 2 (ENDING: Happy, Sad) x 3 (TIME: t1, t2, t3) mixed design was used to tease out the temporal characteristics. Correlational analysis of dependent variables over time also showed empathy for the protagonist at Time1 was associated with negative affect and entertainment at other time points, but only when character context was presented. Results support the idea that entertainment and emotion are temporal processes that are subject to both situational and dispositional variables.

Nucleus accumbens encoding of conditioned place preference

German, Paul Walter University of California, San Francisco 2005 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

Conditioned Place Preference (CPP) is a behavioral measure of learning and reward widely used in studies of addiction. CPP is generally measured as the cumulative time an animal spends in a location previously paired with reward. However, this measure masks the different behavioral strategies that an animal could use. To discover the specific behavioral change underlying CPP, we used continuous video tracking of animals before and after morphine CPP training. Using a three room apparatus we analyzed room visit frequency and duration, and room transition profiles. We discovered that the rats have two distinct room transition profiles, simple and complex, that correspond to the rat's intended destination, suggesting that room transitions are discrete, location-directed actions. A computational model that included location-directed room transitions revealed an effect of conditioning on morphine room behavior. Specifically, conditioning increased the probability of direct saline to morphine room transitions. Therefore, the expression of CPP is explained by an increase in the probability of spontaneous location-directed transitions into the morphine room. Nucleus Accumbens (NAc) neurons are required for the expression of CPP. To determine how they contribute we recorded their activity during CPP testing. During test sessions, when the rats freely explored all rooms, 26% of neurons were preferentially excited or inhibited while in one of the three rooms. Most of these neurons also showed transient responses during room transitions. Some room transition responses were selective for transitions in only one direction or to a particular room. Prior to conditioning, approximately equal populations of NAc neurons encoded excitations or inhibitions to each room (morphine paired, center or saline paired). Conditioning increased two of these populations, those inhibited while the rat was in the morphine room and those excited in the saline room. Thus, the increase in proportion of NAc neurons that code for excitation in the saline room and inhibition in the morphine room correlate with the observed behavioral bias to exit the saline room toward the morphine room during expression of morphine CPP. These results suggest a potential mechanism by which activity in NAc neurons could lead to increased time in the morphine paired room.

Assessment of Disharmony and Disaffection

German, Nicole Marie ProQuest Dissertations & Theses Auburn University 2013 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

Intimate relationship researchers’ need to accurately assess conflict resolution and emotional connection has driven the development of instruments measuring disharmony and disaffection, constructs that assess these respective processes. Research on existing measures provides a basis of empirical support for disharmony and disaffection, as well as their association with relationship distress; however, these measures lack a theoretical underpinning and evidence of construct validity. The current study empirically examines a theoretically-guided higher-order model of disharmony and disaffection within a sample of students at a large, Southeastern university. The hypothesized model of both constructs was largely supported. Notably, the retained model suggests that disharmony and disaffection share a cognitive component; specifically, each includes a factor indicative of the belief that one is misunderstood and criticized by one’s partner. Further, disharmony and disaffection independently contribute to lower positive relationship satisfaction, as well as higher negative relationship satisfaction. Overall, findings suggest that two distinct patterns of relationship function, each contributing to evaluations characterized by dissatisfaction.

Investigating and exploiting metabolic vulnerabilities in cancer

German, Natalie Janelle Harvard University 2015 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

Fuel metabolism in healthy cells is not sufficient to sustain the biosynthetic and energetic demands of cancer. For a normal cell to transform to a rapidly dividing tumor cell, metabolism must be dramatically altered in a process called metabolic reprogramming, characterized by increased nutrient uptake and re-purposing. As we move toward a future of personalized medicine, there is new opportunity in targeting the metabolic requirements specific to an individual's tumor. To this end, it is critical to understand molecular drivers that cancer cells hijack to modify metabolism. In this dissertation, I describe three studies on enzymes and metabolic pathways that shed light on molecular regulation of metabolic reprogramming in cancer. First, we screened for substrates of SIRT4, a mitochondrial sirtuin that promotes metabolic homeostasis and suppresses cancer by mechanisms not well understood. We used proteomics to identify hyperacetylated mitochondrial proteins in SIRT4 knockout mouse tissues compared to wildtype. We find SIRT4 binds and inhibits pyruvate carboxylase, an enzyme important for refueling the TCA cycle in cancer, indicating SIRT4 may target this node in tumor metabolism. Second, we reveal a role for prolyl hyrdoxylase domain (PHD) 3 in coordinating cancer cell addition to fat catabolism. In biochemical and cellular studies, we find PHD3 hydroxylates and activates acetyl-CoA carboxylase (ACC2) to repress fatty acid oxidation (FAO). Loss of this regulatory axis in leukemia enables greater utilization of fatty acids as fuel, and also serves as a liability by rendering cells susceptible to FAO inhibition. Finally, we used metabolomics to define alterations caused by the diabetes drugs metformin and phenformin to better understand their anti-cancer properties. We analyzed the drugs' effects on cells undergoing neoplastic transformation and on cancer stem cells (CSCs), a small population that possesses predominant tumor-initiation capacity and is selectively inhibited by metformin. We show metformin and phenformin induce changes that oppose cancer cell survival by eliciting a nutrient crisis during transformation and depleting nucleotide triphosphates in CSCs. In sum, these findings contribute to the future potential to impede nutrient switches in cancer, thus turning the metabolic dependencies of cancer cells into metabolic vulnerabilities.

Epidemiology of cocaine use and dependence

Alvarado, German F Michigan State University 2012 해외박사(DDOD)

소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.

The following dissertation presents original research on selected topics in the epidemiology of cocaine use and dependence. The research consists of inter-related studies that deal with gaps in scientific knowledge about the topics pertinent to drug dependence. The dissertation is focused on four studies. In study one, I seek to estimate a suspected causal association between cocaine use and the occurrence of panic during adolescence and young adulthood, building upon prior study results based upon adult samples. The data are from an epidemiological sample of young adults, observed longitudinally from primary school to that time. The main finding is a modest but generally statistically robust association linking cocaine use and the occurrence of a panic attack-like experience. In study two, I attempt to estimate a suspected causal association linking earlier onset of cocaine use with later risk of newly incident panic attack in adults. The data are from an epidemiological sample of Americans aged 18-44 years at the time of cross-sectional and retrospective assessment. The main findings of this study confirm prior evidence on the suspected causal association linking cocaine use with subsequent panic attack-like events. In this study, temporal sequencing of the association has been assured to the extent possible in retrospective age of onset data, with a conservative approach when the first cocaine and panic occurred in the same year. In study three, the aim is to estimate the risk of becoming cocaine dependent in the first months and years after onset of cocaine use, and to study suspected determinants of becoming dependent within 24 months after cocaine use starts, based on nationally representative samples of non-institutionalized citizens of the United States aged 12 years and older. The main findings of this study are as follows. First, an estimated 6-7% of recent-onset users develop cocaine dependence. Excess risk of cocaine dependence was found for females. Occurrence of cocaine dependence was greater among newly incident users who had started to smoke crack cocaine, as compared to those who had not smoked crack. No remarkable associations were found with the other variables under study (e.g., age, race-ethnicity). In study four, I seek to provide epidemiological evidence on predictors of who has started cocaine use in the last four years but has stopped using cocaine. The data for this research also are from nationally representative samples. The approach starts with exploratory analyses of data from calendar year 2003 (CY2003). Then, the model is re-evaluated using data from an independent sample drawn in CY2008. The main findings are as follows. First, among those whose onset of cocaine use was within the four years prior to the date of the survey assessment, an estimated 13-16% had remained cocaine users within the prior 30 days; and an estimated 34% used cocaine within past 12 months but not in the past 30 days. An estimated 50-53% had not used cocaine in the previous 12 months before the assessment. It was found that people with age of cocaine onset at 20 years old or greater are twofold more likely to stop; this is the only finding from the CY2003 analysis that could be replicated in the CY2008 analysis. Cocaine cessation was not found to be reliably associated with sex, education, or using crack-cocaine.