Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Physics, 1982. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE / Bibliography: leaves 29-30. / by Rupert LaWendell Seals. / M.S.

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Rett syndrome (RTT) is an X-linked neurological disorder primarily caused by mutations in the MECP2 gene. The majority of RTT mutations disrupt the interaction of MeCP2 with DNA or TBL1X/TBL1XR1, which forms the scaffold of NCoR/SMRT co-repressor complex. Patients with RTT show no signs of neuronal death, although they have abnormal neuronal morphology, indicating that it is a neurodevelopmental rather than a neurodegenerative disease. It has been shown that reactivation of silenced MeCP2 in mice rescues the RTT phenotype, which implies that the disease is treatable. The RTT mutations in MeCP2 cluster to two regions - the methyl-CpG-binding domain (MBD) and NCoR/SMRT Interaction Domain (NID). While the interaction between MBD and DNA has been biochemically and structurally characterised, there are no structural data about the interaction between MeCP2 NID and TBL1XR1. The aim of this work was to understand how mutations in the NID cause RTT by characterising the interaction between MeCP2 and TBL1XR1. I have solved the structure of MeCP2 NID bound to TBL1XR1 WD40 domain. I show that a small region of the MeCP2 NID makes extensive contacts with TBL1XR1, and that these contacts are mediated primarily by MeCP2 residues known to be mutated in RTT. I also measured the affinities between TBL1XR1 and MeCP2-derived peptides using fluorescence anisotropy and surface plasmon resonance assays. I determined the affinity between MeCP2 NID peptide and TBL1XR1 to be around 10- 20 μM, and show that mutations in either MeCP2 or TBL1XR1 can abolish this interaction. Taken together, these data strongly suggest that the abolition of the interaction between MeCP2 NID and TBL1XR1 WD40 domain is sufficient to cause RTT. This knowledge can help with the rational design of small drug-like molecules that might be able to mediate the interaction between mutated MeCP2 and TBL1XR1, potentially helping to treat the disease.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Medicine in Diagnostic Radiology Johannesburg, 2014 / INTRODUCTION South Africa presents a complex scenario with regard to patients consenting for medical procedures, because of the differing profiles of the population and the health care workers who perform the consenting procedures. AIM To evaluate consenting practice for CT scanning, within the South African tertiary referral setting and to determine if there are any associations between patient demographic profile and the level of understanding with the adequacy of consent. METHOD A prospective survey regarding consenting practices for CT scanning was performed in a form of an interview questionnaire in patients presenting to Chris Hani Baragwanath Academic and Charlotte Maxeke Johannesburg Academic hospitals. Determination of any associations between patient age, racial group, language and education was made with the level of understanding and adequacy of consent. RESULTS The survey was conducted on 117 patients; 86 from Charlotte Maxeke Johannesburg Academic Hospital and 31 from Chris Hani Baragwanath Academic Hospital. We found no significant association between gender and age category (p=0.11), racial group (p=0.17), education (p=0.26), home language (p=0.21) or residential area type (p=0.70). vi There was a significant, weak, association between age category and education (p=0.043; Cramer’s V=0.29). There was a significant, moderate association between the understanding of the language of consent and the home language of the patients (p=0.0013; phi coefficient=0.43). There was also some association between education and age. Just over 50% of patients felt that they had been given enough information and had had an opportunity to ask questions and only 33% had been offered an alternative to the CT scan. There was a significant difference in the mean adequacy of consent score with regards to racial group (p<0.0001), home language (p=0.0073), residential area type (p<0.0001) and level of education (p<0.0001). CONCLUSION Language differences between patients and personnel performing the consent procedure proved to be a major barrier in offering adequate consenting for CT Scans.

Thesis(M. Med (Anaesthesiology)--University of Limpopo(Medunsa Campus), 2010. / The purpose of this study was to interrogate the clinical relevance and cost effectiveness of the routine preoperative chest X-rays at DGMH. It was conducted as a descriptive cross-sectional prospective study of radiographic films in the Radiology department. A review of patients’ files and chest X-rays performed during a 6-month period from January to June 2008. Data from 100 patients’ files were included in the analysis. The age of patients ranged from 45 to 84years, the median age was 57years. The majority of patients younger than 50years were female, while the majority of male patients were over 50years. From a total of 100 patients only 8%(8 patients) were deemed unfit and consequently postponed or cancelled for further investigation and optimization. The cost for performing one routine chest X-ray was estimated to be R393 manpower, time and film inclusive, the total costs for the 100 patients included in this study being R39300. This study has provided some evidence that the routine preoperative chest X-rays can help in uncovering some abnormalities that were not apparent on clinical examination, it has pointed out that the impact of these uncovered abnormalities is very minimal on the planned surgery and that the costs associated with doing routine pre-operative chest X-rays can be substantial.

The beginning of X-ray astronomy is based on two accidental discoveries made in 1962. A single point source, Scorpio X-1 and remarkable discovery of the diffuse background radiation, three years before the microwave background was discovered. Over the past four decades, X-ray astronomy has matured into a major branch of astronomy, contributing to our understanding of the physical processes operating in many different types of sources, from stars to high redshift quasars. In 1990, the launch of the ROSAT satellite offered to unique opportunity to investigate the radio properties of X-ray emitters. A sample of faint X-ray emitters from a deep pointed observation is used in this thesis to investigate the prediction that sub-mJy radio source are a major contributor to the X-ray background. Another sample of 695 bright X-ray emitters were selected from ROSAT All Sky Survey for optical follow-up as a European Southern Observatory key project. The radio follow-up of the sample was undertaken for this thesis. The aim is to construct a catalogue of radio emitting X-ray (REX) sources to study their quantitative statistical properties and to select out a sample of BL-Lac objects for further study. Based on previous surveys approximately 19% or 130 of the X-ray sources should be directly associated with a radio emitter, of which 90% will be positionally coincident with the most plausible optical candidate for an X-ray source. This increases the efficiency of the optical identification program by about 15 percent. / Doctor of Philosophy (PhD)

More than 90% of human genes undergo a processing step called splicing, whereby non-coding introns are removed from initial transcripts and coding exons are ligated together to yield mature messenger RNA. Roughly 50% of human genetic diseases correspond to aberrant splicing. Splicing is catalyzed by an RNA/protein machine called the spliceosome. RNA components of the spliceosome are at least partly responsible for splicing catalysis. In addition, in vitro analyses implicate an essential and very highly conserved protein, Prp8, in orchestrating key steps in spliceosome assembly and possibly catalysis. Interestingly, mutant alleles of Prp8 are the cause of retinitis pigmentosa, an inherited form of retinal degeneration. A key goal is elucidation of the precise role of Prp8 in the spliceosome by high resolution structural analysis. The large size of Prp8 and its insolubility hinder progress in this regard. Instead, structural understanding of Prp8 can be gained by investigating domains in isolation; however there is only limited information as to what domain boundaries are and few hints about the functional relevance of putative domains. Here we have further defined the previously proposed domain IV in Prp8, and identified the domain IV core. Structural determination of the domain IV core reveals an RNase H fold, which could not be predicted based on primary sequence alone. RNase H recognizes A-form nucleic acid duplexes, which strongly suggests the domain IV core interacts with double-stranded RNA in the context of the spliceosome. Characterizing the binding preferences of the domain IV revealed the highest affinity is for a 4-helix junction structure adopted by the very RNAs at the spliceosome active site. Our characterization of the protein/RNA binding interface by complementary footprinting techniques currently provides the best model of how RNA interacts with an essential protein component at the heart of the spliceosome.

Thesis (Ph. D.)--University of Delaware, 2006. / Principal faculty advisor: Tatyana Polenova, Dept. of Chemistry & Biochemistry. Includes bibliographical references.

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 152-164).

Thesis (Ph. D.)--University of Chicago, Dept. of Astronomy and Astrophysics, August 2000. / Includes bibliographical references. Also available on the Internet.