Resumé This diploma thesis deals with compensation for damage under the civil law. The work gives a detailed explanation regarding this institution and highlights the most significant changes that have been brought by the new Civil Code. The aim is mainly to introduce different methods of compensation and basic procedures, that are used in determining the extent of compensation. This thesis is composed of six chapters. In the introductory chapter, the attention is given to the most significant changes that occurred in the area of tort law in comparison with the previous legislation. Moreover, there is discussed the change in the concept of liability for damage and its basic functions in more details. The following parts are focused on the analyze of duty of care and the limitation of the rights to compensation. The main topic of the second chapter is the definition of the basic assumptions leading to the obligation to compensate for damage. These assumptions include tort, damage, causation and the fault. In the following passages there is closer outlined the issue of strict liability. Special attention is paid to the damage that was caused by accident or solidary liability to compensation and the contributory negligence of a victim. In the final part of the second chapter there is explained the essence of...

A dissertation submitted to the Faculty of Arts, University of the Witwatersrand, in partial fulfilment of the requirements for the degree of Master of Arts in Clinical Psychology / This study investigated the emotional functioning of people who had been diagnosed as having traumatic brain injuries (TBI) of the frontal lobes. This was done with a view to examining whether there were changes in the emotional functioning of people with TBI in the period following their injuries. The pre-injury (or premorbid) emotional functioning of the respondents with TBI was assessed retrospectively through self-reports, which were compared with the ratings by the primary and secondary care-givers of these respondents. The current (post-injury) emotional functioning of the participants with TBI was also assessed through self-reports and the ratings by the primary and secondary care-givers. (abbreviation abstract) / Andrew Chakane 2019

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Huntington’s disease is an autosomal dominantly inherited neurodegenerative disorder characterized by degeneration of striatal and cortical neurons. The neurons in these regions are particularly energy-demanding and need to maintain high levels of oxidative phosphorylation to support cellular activities. Reactive oxygen species are generated as a byproduct of oxidative phosphorylation and can damage DNA and other biomolecules if not properly metabolized. In HD, there is elevated oxidative DNA damage and impaired DNA damage repair, likely due to impaired function of the mutant huntingtin protein in base excision repair (BER). Previous studies have shown that mutant huntingtin is hypo-phosphorylated at serines 13 and 16 in the N17 domain, and that restoring phosphorylation can reestablish normal protein function and is protective in HD. In this thesis, we show that a metabolite of the DNA damage product N6- furfuryladenine (N6FFA), kinetin triphoshate (KTP) increases N17 phosphorylation through casein kinase 2 (CK2) by acting as an ATP analog, with protective effects in cell and animal models of disease. We additionally show N6FFA increases the activity of CK2 on other substrates, specifically p53. We hypothesize that in times of ATP stress CK2 can utilize KTP as an alternate energy source, promoting DNA repair and cell viability. In HD, inefficient BER inhibits generation of KTP and promotes hypo- phosphorylation of CK2 substrates, which can be overcome by exogenous addition of N6FFA. Additionally, we show that another DNA-responsive kinase, PKCζ, can also phosphorylated N17, potentially priming this domain for CK2 phosphorylation. Finally, we propose that the protective effects of N6FFA may be via a two-pronged pathway, involving both CK2 and the mitochondrial quality control kinase, PINK1. Thus, this thesis presents a novel mechanism where a product of DNA damage acts as a phosphate source for critical kinases in DNA repair and mitochondrial maintenance in conditions where ATP levels are low. / Thesis / Doctor of Philosophy (PhD)

京都大学 / 新制・課程博士 / 博士(工学) / 甲第25240号 / 工博第5199号 / 新制||工||1992(附属図書館) / 京都大学大学院工学研究科建築学専攻 / (主査)准教授 倉田 真宏, 教授 西山 峰広, 教授 聲高 裕治 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

Chromosomal rearrangements can lead to loss of heterozygosity (LOH) and oncogene activation, both of which represent possible causative events in cancer development. Such outcomes can result from the misrepair of DNA damage arising from a variety of events including DNA double-strand breaks (DSBs), collapsed replication forks, and dysfunctional telomeres. In response to a DSB, chromosomal stability is principally maintained through the two major DNA repair pathways; non- homologous DNA end-joining (NHEJ) and homologous recombination (HR). The objective of this thesis was to identify novel factors functioning in prevention of chromosomal instability in response to a DSB in Schizosaccharomyces pombe. To achieve this, a central aim was to identify the genes mutated in a number of radiation-sensitive mutants in fission yeast, previously isolated by the laboratory. These include the ‘loh’ mutants loh-2, loh-5, loh-6 and loh-7, which were found to harbour mutations in known DNA repair genes rad3, rad17, and rad57. Further, a pan-genomic screen for novel HR repair factors was carried out. The Bioneer Version 2 deletion-library, consisting of 3308 haploid deletion strains, was screened for strains displaying hypersensitivity to the DNA damaging agents MMS, bleomycin and camptothecin. This screen yielded 209 hits which were further characterised, utilising a set of non-essential Ch¹⁶ minichromosomes . The minichromosome Ch¹⁶-LMYAU harbours an HO endonuclease recognition sequence and a centromere-distal ade6-M216 heteroallele. Following break-induction, failed repair of the DSB leads to loss of the ade6 allele, indicated by pink sectoring on low adenine plates. 39 sectoring hits were identified and further characterised to quantify levels of gene conversion via HR in response to a DSB, utilising Ch¹⁶-RMYAH. As a result of this study, a group of novel genes functioning in HR repair were identified. Finally, one of these hits, putative RNA metabolism protein Nrl1, was subjected to further characterisation, associating this protein with DNA damage repair for the first time. The work presented here, documents the approaches taken to successfully identify novel DNA repair factors in fission yeast.

The major target of ionising radiation has been determined as cellular DNA. Damage to DNA, as detected at 77K under conditions of direct damage by ESR, is localised on the bases thymine and guanine. This damage leads to single and double strand breaks, precursors of cell death and mutagenesis. In an attempt to intercept the damage at the bases, before formation of strand breaks, the use of polycations as potential drug delivery systems to DNA has been examined. Magnetic resonance techniques have been used to establish that polyamines used are present almost completely as polyammonium cations at pH 7 and to probe the interactions of a number of polycations with DNA. Sodium-NMR was used to investigate the affinity of polyamines, poly- aminothiols and transition-metal complexes for DNA, via sodium ion displacement from the DNA region. It was found that small metal complexes displace a greater number of sodium ions than polyamines of similar charge. Application of the counterion condensation theory led to a model of the counterions existing within a cylinder around the DNA of approximate radius 20A. The mode of interaction of polyammonium cations was studied using proton magnetic resonance. Linewidths, related to the transverse relaxation rate, give information on the motion of compounds close to DNA. Comparison of linewidths in the presence and absence of DNA revealed no significant broadening. This was interpreted as indicative of a loose, electrostatic interaction, not significantly hindering motion of the cations close to DNA, suggesting rapid motion of polyammonium ions along the DNA. The radioprotection of DNA by various transition-metal complexes was studied using ESR. Certain compounds exhibited protection via electron transfer, resulting in a decreased radical yield.

published_or_final_version / Mechanical Engineering / Doctoral / Doctor of Philosophy

published_or_final_version / Paediatrics / Doctoral / Doctor of Philosophy

A study has been made of creep damge accumulation in two casts of l%.Cr-1/2%i.Mo low alloy steel. Creep tests and creep crack growth tests have been carried out at 823K to determine the nature of the damage accumulation and to attempt to relate microscopic damage mechanisms to the macroscopic fracture parameters. Four types of specimen were tested and failure of all occurred by the continuous nucleation. growth and coalescence of grain boundary cavities. A mechanism for the growth of cavities is suggested. based on grain boundary diffusion coupled with geometric constraint. The influence of continuous cavity nucleation has also been considered and it is suggested that this phenomenon initially increases the rate of diffusive cavity growth. However continuous nucleation decreases the growth rate once the latter becomes constrained. The effect of stress-state is also considered and increasing triaxiality is shown to have little effect on the unconstrained diffusive growth but it decreases the constrained growth rate by increasing the overall constraint in the specimen. Predicted growth rates give good agreement to those observed experimentally for both notched and un-notched creep specimens. Reasonable agreement is also observed to the predicted rupture lives although the predictions suggest notch strengthening whilst experimentally notch weakening is observed. This is thought to be due to non-uniform damage formation on loading. Based on the above concepts of cavity growth, constitutive equations are presented to predict the time dependence of creep strain. These are found to give good agreement to the experimentally determined strain rates, lending further support for the development of continuum damage mechanics as a means of assessing creep crack growth behaviour.