Doctor of Philosophy

dissertationThe Heck reaction is an important tool in target-directed syntheses, but its full potential has yet to be realized due to limited substrate compatibility. This limitation arises from poor behavior of the selectivity-determining steps of migratory insertion and -hydride elimination when using electronically nonbiased substrates. The inability to accommodate nonbiased alkenes is due to chemist's poor understanding of the controlling factors in these two key mechanistic steps. Herein are described Pd0 and PdII catalysts that exhibit unique selectivity in these electronically nonbiased molecular systems. Chapter 1 describes the use of an electrophilic PdII catalyst to install two identical aryl groups upon terminal aliphatic olefins. The use of the same system, with a different aryl source, led to the discovery that electrophilic PdII catalysts are capable of selectively delivering (E)-styrenyl products from electronically nonbiased olefins. Chapter 2 details optimization of the PdII system to selectively deliver traditionally inaccessible (E)-styrenyl products, and evaluation of substrate scope. Mechanistic experiments are performed, suggesting that the unique selectivity observed is attributable to the cationic nature of the catalyst, that the ligand on Pd is required for catalyst stability, and that the catalyst distinguishes between B-hydrogens on the basis of C-H bond strength. These findings are applied to rational design of a Pd0-catalyzed Heck reaction of similar substrates. The Pd0-catalyzed system exhibits greater functional group tolerance than the oxidative system, is operationally simple, and requires no added stabilizing ligand. The design and study of this reaction is the subject of Chapter 3. Mechanistic studies suggest that solvent choice is crucial in allowing the metal center to distinguish between - hydrogens on the basis of their relative hydridic nature. The insight gained in the work described in Chapters 2 and 3 allowed for the rational design of a system enabling enantioselective Heck reactions using acyclic substrates. This methodology, described in Chapter 4, was intended to deliver optically active -aryl ketones from allylic alcohol substrates. After establishing that the reaction performs as anticipated, it was applied to the unprecedented single-step enantioselective synthesis of y-aryl ketones, and aldehydes, and a d-aryl aldehyde

Cooperative action in eukaryotic gene regulation: physical properties of a viral example

The Epstein-Barr virus (EBV) infects more than 90% of the human population, and is the cause of several both serious and mild diseases. It is a tumorivirus, and has been widely studied as a model system for gene (de)regulation in human. A central feature of the EBV life cycle is its ability to persist in human B cells in states denoted latency I, II and III. In latency III the host cell is driven to cell proliferation and hence expansion of the viral population, but does not enter the lytic pathway, and no new virions are produced, while the latency I state is almost completely dormant. In this paper we study a physico-chemical model of the switch between latency I and latency III in EBV. We show that the unusually large number of binding sites of two competing transcription factors, one viral and one from the host, serves to make the switch sharper (higher Hill coefficient), either by cooperative binding between molecules of the same species when they bind, or by competition between the two species if there is sufficient steric hindrance.Comment: 7 pages, 6 figures, 1 tabl

China's economic transition : from working dragon to consuming panda

published_or_final_versionInternational and Public AffairsMasterMaster of International and Public Affair

The Joint ESA/NASA Galileo/GPS Receiver Onboard the ISS the GARISS Project

ESA and NASA conducted a joint Galileo/GPS space receiver experiment on-board the International Space Station (ISS). The objectives (Enderle 2017) of the joint project were to demonstrate the robustness of a combined Galileo/GPS waveform uploaded to NASA hardware already operating in the challenging space environment - the SCaN (Space Communications and Navigation) software defined radio (SDR) testbed (FPGA) - on-board the ISS. These activities data included the analysis of the Galileo/GPS signal and on-board Position/Velocity/Time (PVT) performance, processing of the Galileo/GPS raw data (code- and carrier phase) for Precise Orbit Determination (POD), and validate the added value of a space-borne dual GNSS receiver compared to a single-system GNSS receiver operating under the same conditions. This paper will provide a general overview of the Galileo/GPS experiment called GARISS - on-board the ISS, describe design, test and validation and also the operations of the experiment. Further, the various analysis conducted in the con is joint project and also the results obtained will be presented with a focus on the (Precise) Orbit Determination results

Individualized quality of life in patients with low back pain: reliability and validity of the Patient Generated Index

Objective: To evaluate the reliability and validity of the improved version of the Patient Generated Index (PGI) in patients with low back pain. Methods: The PGI was administered to 90 patients attending care in 1 of 6 institutions in Norway and evaluated for reliability and validity. The questionnaire was given out to 61 patients for re-test purposes. Results: The PGI was completed correctly by 80 (88.9%) patients and, of the 61 patients responding to the re-test, 50 (82.0%) completed both surveys correctly. PGI scores were approximately normally distributed, with a median of 40 (range 80), where 100 is the best possible quality of life. There were no floor or ceiling effects. The 5 most frequently listed areas affecting quality of life were pain, sleep, stiffness, socializing and housework. The test-retest intraclass correlation coefficient was 0.73. The smallest detectable changes for individual and group purposes were 32.8 and 4.6, respectively. The correlations between PGI scores and other instrument scores followed a priori hypotheses of low to moderate correlations. Discussion: The PGI has evidence for reliability and validity in Norwegian patients with low back pain at the group level and may be considered for application in intervention studies when a comprehensive evaluation of quality of life is important. However, the smallest detectable change, of approximately 30 points, may be considered too large for individual purposes in clinical application

Some pain, no gain: experiences with the no-claim rebate in the Dutch health care system

To contain expenditures in an increasingly demand driven health care system, in 2005 a no-claim rebate was introduced in the Dutch health insurance system. Since demand-side cost sharing is a very controversial issue, the no-claim rebate was launched as a consumer friendly bonus system to reward prudent utilization of health services. Internationally, the introduction of a mandatory no-claim rebate in a social health insurance scheme is unprecedented. Consumers were entitled to an annual rebate of 255 eruos if no claims were made. During the year, all health care expenses except fo

Mercury, silver and selenium in serum before and after removal of amalgam restorations: results from a prospective cohort study in Norway

Objective A prospective cohort study on changes of health complaints after removal of amalgam restorations was carried out at the request of the Norwegian Directorate of Health. The aim was to provide and evaluate experimental treatment to patients with health complaints attributed to dental amalgam fillings. Methods Patients (n = 32) with medically unexplained physical symptoms (MUPS), which were attributed to dental amalgam restorations had all their amalgam restorations removed and replaced with other dental restorative materials. Samples of blood were collected before and 1 year after removal of the fillings, and concentration of inorganic mercury (I-Hg), methylmercury (MeHg), silver (Ag) and selenium (Se) in serum was determined by inductively coupled plasma–sector field mass spectrometry. The comparison groups (one with MUPS but without attribution to amalgam [n = 28] and one group of healthy individuals [n = 19]) received no treatment. The participants responded to questionnaires at baseline and at follow-up after 1 and 5 years. Results Concentration of I-Hg and Ag in serum decreased significantly after removal of all amalgam restorations. Concentration of MeHg and Se in serum were not changed. Intensity of health complaints was significantly reduced after amalgam removal, but there were no statistically significant correlations between exposure indicators and health complaints. Conclusions Removal of all amalgam restorations is followed by a decrease of concentration of I-Hg and Ag in serum. The results support the hypothesis that exposure to amalgam fillings causes an increase of the daily dose of both I-Hg and Ag. Even though intensity of health complaints decreased after removal of all amalgam restorations there was no clear evidence of a direct relationship between exposure and health complaints