Part I: Syntheses, Characterizations, and Investigations of Molecular Micelles and Imidazolium-Based Ionic Liquids for Protein Separations in Electrophoresis PART II: Investigating the Mentoring Canon Through Exploration of Thirty Years of Mentoring by an Exemplar

The research reported in this dissertation is presented in two parts. The first part is the Syntheses, Characterizations, and Investigations of Molecular Micelles and Imidazolium-Based Ionic Liquids for Protein Separations in Electrophoresis, and the second part is a case study entitled Investigating the Mentoring Canon through Exploration of Thirty Years of Mentoring by an Exemplar. Protein separations in the gel electrophoretic format are ubiquitous analyses used on a daily basis throughout biochemistry, analytical chemistry, and biotechnology. The goal of the research reported in the first part of this dissertation is to synthesize and characterize molecular micelles and ether-functionalized imidazolium-based ionic liquids and investigate their relevance and practical utility for protein separations in polyacrylamide gel electrophoresis (PAGE). Four experimental parameters were optimized for poly (sodium N-undecanoyl sulfate) (poly-SUS) protein separations. The analytical techniques, fluorescence spectroscopy and circular dichroism, proved useful for investigating the extent and mechanism of interaction that the molecular micelles and ionic liquids had with a combination of globular and glycosylated proteins. Based on the spectroscopic results, postulations were made and experiments were designed using validation samples in one-dimensional PAGE. Poly-SUS binding to p53, a major target for anticancer therapy, was highly efficient. The addition of 20% v/v 1-methoxyethoxyethyl-3-methyl imidazolium bromide and 1- methoxyethoxyethyl-3-butyl imidazolium bromide to the sample buffer containing poly-SUS resulted in significant gel band shifting of transferrin, a well known biomarker for chronic alcoholism and congenital disorders of glycosylation (CDG). The goal of the research reported in part two of this dissertation was to investigate the mentoring of an exemplar over a thirty year period to determine why his mentoring ‘works’ as evidenced by the many invited talks, publications as well as local and national mentoring awards received. Study participants’ conceptions of what made the exemplar an effective mentor and why his mentoring philosophy worked were determined by item analysis of 40 mentor interview questions, 3080 protégé in-depth survey responses, and 2 mentoring award nomination packages. A theory of why the exemplar’s mentoring ‘worked’ was determined using constructivist grounded theory analysis. The theory that was constructed consisted of three stages: intra-psychological positioning, inter-psychological exchange, and intra-psychological transformation

Fermi Large Area Telescope Constraints on the Gamma-ray Opacity of the Universe

The Extragalactic Background Light (EBL) includes photons with wavelengths from ultraviolet to infrared, which are effective at attenuating gamma rays with energy above ~10 GeV during propagation from sources at cosmological distances. This results in a redshift- and energy-dependent attenuation of the gamma-ray flux of extragalactic sources such as blazars and Gamma-Ray Bursts (GRBs). The Large Area Telescope onboard Fermi detects a sample of gamma-ray blazars with redshift up to z~3, and GRBs with redshift up to z~4.3. Using photons above 10 GeV collected by Fermi over more than one year of observations for these sources, we investigate the effect of gamma-ray flux attenuation by the EBL. We place upper limits on the gamma-ray opacity of the Universe at various energies and redshifts, and compare this with predictions from well-known EBL models. We find that an EBL intensity in the optical-ultraviolet wavelengths as great as predicted by the "baseline" model of Stecker et al. (2006) can be ruled out with high confidence.Comment: 42 pages, 12 figures, accepted version (24 Aug.2010) for publication in ApJ; Contact authors: A. Bouvier, A. Chen, S. Raino, S. Razzaque, A. Reimer, L.C. Reye

Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Methods: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. Results: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. Conclusions: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses

Entry and Exit Strategies in Migration Dynamics

This work is devoted to study the role of combined entry and exit strategies in the migration process. We develop a real option model in which the community of immigrants in the host country is described as a club and the immigrants benefits is a U-shaped function, depending on the dimension of the district. There exist two threshold levels: the first one triggers the migration choice, while the second triggers the return to the country of origin. The theoretical results show that the phenomenon of hysteresis is amplified by the existence of a community both in the entry case and in the exit case. Furthermore, the community can reduce the minimum wage level required to trigger both exit and entry: this fact could explain why in some cases we observe migration inflows with a low wage differential and also with underunemployment. We show also some possible further extensions of the model: in one case we introduce a possible way to select the entrants skills and in another case we show some theoretical implementations to include possible policy shocks in the migrants choice

DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

Background: The discovery of robust and trans-ethnically replicated DNA methylation markers of metabolic phenotypes, has hinted at a potential role of epigenetic mechanisms in lipid metabolism. However, DNA methylation and the lipid compositions and lipid concentrations of lipoprotein sizes have been scarcely studied. Here, we present an epigenome-wide association study (EWAS) (N = 5414 total) of mostly lipid-related metabolic measures, including a fine profiling of lipoproteins. As lipoproteins are the main players in the different stages of lipid metabolism, examination of epigenetic markers of detailed lipoprotein features might improve the diagnosis, prognosis, and treatment of metabolic disturbances.Results: We conducted an EWAS of leukocyte DNA methylation and 226 metabolic measurements determined by nuclear magnetic resonance spectroscopy in the population-based KORA F4 study (N = 1662) and replicated the results in the LOLIPOP, NFBC1966, and YFS cohorts (N = 3752). Follow-up analyses in the discovery cohort included investigations into gene transcripts, metabolic-measure ratios for pathway analysis, and disease endpoints. We identified 161 associations (p value -10), covering 16 CpG sites at 11 loci and 57 metabolic measures. Identified metabolic measures were primarily medium and small lipoproteins, and fatty acids. For apolipoprotein B-containing lipoproteins, the associations mainly involved triglyceride composition and concentrations of cholesterol esters, triglycerides, free cholesterol, and phospholipids. All associations for HDL lipoproteins involved triglyceride measures only. Associated metabolic measure ratios, proxies of enzymatic activity, highlight amino acid, glucose, and lipid pathways as being potentially epigenetically implicated. Five CpG sites in four genes were associated with differential expression of transcripts in blood or adipose tissue. CpG sites in ABCG1 and PHGDH showed associations with metabolic measures, gene transcription, and metabolic measure ratios and were additionally linked to obesity or previous myocardial infarction, extending previously reported observations.Conclusion: Our study provides evidence of a link between DNA methylation and the lipid compositions and lipid concentrations of different lipoprotein size subclasses, thus offering in-depth insights into well-known associations of DNA methylation with total serum lipids. The results support detailed profiling of lipid metabolism to improve the molecular understanding of dyslipidemia and related disease mechanisms.</p

The Role of Risk Aversion and Lay Risk in the Probabilistic Externality Assessment for Oil Tanker Routes to Europe

Oil spills are a major cause of environmental concern, in particular for Europe. However, the traditional approach to the evaluation of the expected external costs of these accidents fails to take into full account the implications of their probabilistic nature. By adapting a methodology originally developed for nuclear accidents to the case of oil spills, we extend the traditional approach to the assessment of the welfare losses borne by potentially affected individuals for being exposed to the risk of an oil spill. The proposed methodology differs from the traditional approach in three respects: it allows for risk aversion; it adopts an ex-ante rather than an ex-post perspective; it allows for subjective oil spill probabilities (held by the lay public) higher than those assessed by the experts in the field. In order to illustrate quantitatively this methodology, we apply it to the hypothetical (yet realistic) case of an oil spill in the Aegean Sea. We assess the risk premiums that potentially affected individuals would be willing to pay in order to avoid losses to economic activities such as tourism and fisheries, and non-use damages resulting from environmental impacts on the Aegean coasts. In the scenarios analysed, the risk premiums on expected losses for tourism and fisheries turn out to be substantial when measured as a percentage of expected losses; by contrast, they are quite small for the case of damages to the natural environment

Cost Effectiveness in River Management: Evaluation of Integrated River Policy System in Tidal Ouse

The River Ouse forms a significant part of Humber river system, which drains about one fifth the land area of England and provides the largest fresh water source to the North Sea from UK. The river quality in the tidal river suffered from sag of dissolved oxygen (DO) during last few decades, deteriorated by the effluent discharges. The Environment Agency (EA) proposed to increase the water quality of Ouse by implementing more potent environmental policies. This paper explores the cost effectiveness of water management in the Tidal Ouse through various options by taking into account the variation of assimilative capacity of river water, both in static and dynamic scope of time. Reduction in both effluent discharges and water abstraction were considered along side with choice of effluent discharge location. Different instruments of environmental policy, the emission tax-subsidy (ETS) scheme and tradable pollution permits (TPP) systems were compared with the direct quantitative control approach. This paper at the last illustrated an empirical example to reach a particular water quality target in the tidal Ouse at the least cost, through a solution of constrained optimisation problem. The results suggested significant improvement in the water quality with less cost than current that will fail the target in low flow year

A Future for the Dead Sea Basin: Water Culture among Israelis, Palestinians and Jordanians

The Dead Sea basin plays a major role for regional economic development (industry, tourism and agriculture) in the Middle East. This potential is threatened by the steady disappearance of the Dead Sea. Since around 1930 the water level of the Dead Sea has fallen by about 25 m, about half of this alone in the last 20 years. The Dead Sea is a transboundary resource shared by Israel, the Palestinian Authority and Jordan. The Dead Sea is the terminal point of the Jordan River watershed and as such, it serves as a barometer for the health of the overall system. Its rapid decline reflects the present water management strategies of the riparian and upstream countries. This includes the different water cultures of the three countries. Throughout history, the Dead Sea basin has served as a source of refuge and inspiration for followers of Judaism, Christianity and Islam. Today, the religious significance of the Dead Sea is being overshadowed by its rapid disappearance. This may be explained in part by the water cultures of the three countries that influence water policy in the region. Ideology, together with culture and tradition, such as that of Zionism in Israel, has played a central role in water development in the region. In many cases, this has been at the expense of the environment. Elements pertaining to environmental security and water culture and tradition, whereby a sustainably managed environment provides for social, economic as well as environmental benefits are evident with regards the Dead Sea. The decline for example, undermines its potential as a tourist destination, despite the enormous investment in hotel and resort infrastructures in Israel and in Jordan. The decline also raises ethical issues about the exploitation of water resources by present generations at the expense of this natural heritage to future generations. This paper provides an analysis of a European Union funded project whose aims are to synthesize and assess existing physical and socio-economic data and to assess options for a better future for the Dead Sea. It will identify the patterns of water supply and use in the region, and the factors that control these patterns, including those of water culture. The underlying assumption is that solutions for a more sustainable development than todays scenario will not come from simply providing more water for more development, but from a new land and water management system, indeed ethic, that is sensitive to social, cultural and ecological resources thereby providing security and stability across cultures, economic sectors and nations

Technology Transfers and the Clean Development Mechanism in a North-South General Equilibrium Model

This paper analyzes the potential welfare gains of introducing a technology transfer from Annex I to non-Annex I in order to mitigate greenhouse gas emissions. Our analysis is based on a numerical general equilibrium model for a world economy comprising two regions, North (Annex I) and South (non-Annex I). As our model allows for labor mobility between the formal and informal sectors in the South, we are also able to capture additional aspects of how the transfer influences the Southern economy. In a cooperative equilibrium, a technology transfer from the North to the South is clearly desirable from the perspective of a global social planner, since the welfare gain for the South outweighs the welfare loss for the North. However, if the regions do not cooperate, then the incentives to introduce the technology transfer appear to be relatively weak from the perspective of the North; at least if we allow for Southern abatement in the pre-transfer Nash equilibrium. Finally, by adding the emission reductions associated with the Kyoto agreement to an otherwise uncontrolled market economy, the technology transfer leads to higher welfare in both regions