The displacement damage induced by primary recoils of fusion neutrons in tungsten and alloys has been studied with self-ion irradiations, followed by damage characterization with electron microscopy. Tungsten and alloys (≤ 5 wt.% Re, Ta, V) were implanted with 2 MeV W+ ions over a dose range of 3.3×1017 - 2.5×1019 W+m-2 at temperatures ranging from 300 to 750°C. Dislocation loops of b = ½<111> (> 60%) and b = <100> were identified, and that ½<111> loops were found more thermally stable. Among loops that were large enough for nature determination, at least 50% were found to be of interstitial type, with larger fractions in high-temperature and high-dose conditions. The diameter of loops did not exceed 20 nm, with the majority being ≤ 5 nm. The loop number density varied between 1022 and 1023 m-3. The effects of ion dose, irradiation temperature, composition and grain orientation on damage microstructure were investigated. In-situ irradiations (150 keV W+ ions) were carried out as a complement to the bulk implantations. Qualitative trends in loop size, geometry and nature with irradiation dose and temperature were similar to bulk irradiated specimens. Also, the dynamics of defects and their effects on the damage evolution were explored. In-situ annealing of irradiated thin foils was performed to investigate the thermal stability of radiation damage in tungsten. The majority of microstructure transformations were completed within 15 min of annealing. However, extended durations did favour the increase of loop size and the fraction of ½<111> loops.

No description available.

<p>Mitochondria are responsible for producing the vast majority of cellular ATP, and are therefore critical to organismal health [1]. They contain thir own genomes (mtDNA) which encode 13 proteins that are all subunits of the mitochondrial respiratory chain (MRC) and are essential for oxidative phosphorylation [2]. mtDNA is present in multiple copies per cell, usually between 103 and 104 , though this number is reduced during certain developmental stages [3, 4]. The health of the mitochondrial genome is also important to the health of the organism, as mutations in mtDNA lead to human diseases that collectively affect approximately 1 in 4000 people [5, 6]. mtDNA is more susceptible than nuclear DNA (nucDNA) to damage by many environmental pollutants, for reasons including the absence of Nucleotide Excision Repair (NER) in the mitochondria [7]. NER is a highly functionally conserved DNA repair pathway that removes bulky, helix distorting lesions such as those caused by ultraviolet C (UVC) radiation and also many environmental toxicants, including benzo[a]pyrene (BaP) [8]. While these lesions cannot be repaired, they are slowly removed through a process that involves mitochondrial dynamics and autophagy [9, 10]. However, when present during development in C. elegans, this damage reduces mtDNA copy number and ATP levels [11]. We hypothesize that this damage, when present during development, will result in mitochondrial dysfunction and increase the potential for adverse outcomes later in life.</p><p>To test this hypothesis, 1st larval stage (L1) C. elegans are exposed to 3 doses of 7.5J/m2 ultraviolet C radiation 24 hours apart, leading to the accumulation of mtDNA damage [9, 11]. After exposure, many mitochondrial endpoints are assessed at multiple time points later in life. mtDNA and nucDNA damage levels and genome copy numbers are measured via QPCR and real-time PCR , respectively, every 2 day for 10 days. Steady state ATP levels are measured via luciferase expressing reporter strains and traditional ATP extraction methods. Oxygen consumption is measured using a Seahorse XFe24 extra cellular flux analyzer. Gene expression changes are measured via real time PCR and targeted metabolomics via LC-MS are used to investigate changes in organic acid, amino acid and acyl-carnitine levels. Lastly, nematode developmental delay is assessed as growth, and measured via imaging and COPAS biosort.</p><p>I have found that despite being removed, UVC induced mtDNA damage during development leads to persistent deficits in energy production later in life. mtDNA copy number is permanently reduced, as are ATP levels, though oxygen consumption is increased, indicating inefficient or uncoupled respiration. Metabolomic data and mutant sensitivity indicate a role for NADPH and oxidative stress in these results, and exposed nematodes are more sensitive to the mitochondrial poison rotenone later in life. These results fit with the developmental origin of health and disease hypothesis, and show the potential for environmental exposures to have lasting effects on mitochondrial function.</p><p>Lastly, we are currently working to investigate the potential for irreparable mtDNA lesions to drive mutagenesis in mtDNA. Mutations in mtDNA lead to a wide range of diseases, yet we currently do not understand the environmental component of what causes them. In vitro evidence suggests that UVC induced thymine dimers can be mutagenic [12]. We are using duplex sequencing of C. elegans mtDNA to determine mutation rates in nematodes exposed to our serial UVC protocol. Furthermore, by including mutant strains deficient in mitochondrial fission and mitophagy, we hope to determine if deficiencies in these processes will further increase mtDNA mutation rates, as they are implicated in human diseases.</p> / Dissertation

Techniques of performance-based design in fire safety have developed notably in the past two decades. One of the reasons for departing from the prescriptive methods is the ability of performance-based methods to form a scientific basis for the cost-risk-benefit analysis of different fire safety alternatives. Apart from few exceptions, observation of past fires has shown that the structure’s contribution to the overall fire resistance was considerably underestimated. The purpose of this research is to outline a risk-based design approach for structures in fire. Probabilistic methods are employed to ascertain uniform reliability indices in line with the classical trend in code development. Modern design codes for complex phenomena such as fire have been structured to facilitate design computations. Prescriptive design methods specify fire protection methods for structural systems based on laboratory controlled and highly restrictive testing regimes. Those methods inherently assume that the tested elements behave similarly in real structures irrespective of their loading, location or boundary conditions. This approach is contested by many researchers, and analyses following fire incidents indicated alarming discrepancy between anticipated and actual structural behaviour during real fires. In formulating design and construction codes, code writers deal with the inherent uncertainties by setting a ceiling to the potential risk of failure. The latter process is implemented by specifying safety parameters, that are derived via probabilistic techniques aimed at harmonising the risks ensuing different load scenarios. The code structure addresses the probability of failure with adequate detail and accuracy. The other component of the risk metric, namely the consequence of failure, is a subjective field that assumes a multitude of variables depending on the context of the problem. In codified structural design, the severity of failure is implicitly embodied in the different magnitudes of safety indices applied to different modes of structural response. This project introduces a risk-based method for the design of structures in fire. It provides a coherent approach to a quantified treatment of risk elements that meets the demands of performance-based fire safety methods. A number of proposals are made for rational acceptable risk and reliability parameters in addition to a damage index with applications in structural fire safety design. Although the example application of the proposed damage index is a structure subjected to fire effects, the same rationale can be easily applied to the assessment of structural damage due to other effects.

Thesis (MSc)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: The aim of the study was to investigate skeletal muscle changes induced by an acute bout of plyometric exercise before and after plyometric training. The study consisted of an acute study and training intervention study. The acute study, investigated whether direct evidence of ultrastructural damage and identification of indirect factors were more evident in subjects presenting with rhabdomyolysis. Moreover the training intervention study investigated whether plyometric training would protect the muscle from ultrastructural damage and rhabdomyolysis. During the acute intervention, twenty six healthy untrained individuals completed an acute bout of plyometric exercise (10 x 10 squat-jumps, 1 min rest). After, thirteen subjects continued with the training intervention. Eight of these subjects completed 8 weeks of plyometric jump training, while five subjects were instructed to rest from physical activity for 8 weeks. Seven days after the final training session the training and rest group repeated a second acute bout of plyometric exercise. Acute Study: Creatine kinase (CK) activity increased significantly following the single bout of plyometric exercise in all subjects (baseline: 129 to day 4: 5348 U/l). This was accompanied by an increase in perceived pain, C-reactive protein (CRP) a marker of inflammation as well as white blood cells (WBCs). Electron micrographs of muscle biopsies taken 3 days post exercise showed evidence of ultrasructural damage and membrane damage was apparent by immunofluorescence by the loss of dystrophin staining. A stretch of the c-terminus of titin was observed by immunogold, and western blot analysis indicated an increase in calpain-3 autolysis. Based on individual CK responses (CK range: 153-71,024 U/L at 4days after exercise) the twenty six subjects were divided into two groups, namely the high (n=10) and low responders (n=16). Training intervention: Following training the trained group did not experience: a rise of CK activity (110.0 U/l), perceived pain, CRP, WBCs, Z-line streaming, a stretch of titin or calpain-3 activation; while in the control group only two subjects presented with Z-line streaming. The results indicate that high responders have a more pronounced inflammatory response compared to low responders after eccentric exercise, therefore more WBCs and more specifically neutrophils are recruited to damaged areas resulting in greater membrane damage by respiratory burst in high responders. This damage can be limited with training by remodelling sarcomeric proteins via calpain activation resulting in the stable assembly of proteins in the sarcomere preventing the release of proteins. / AFRIKAANSE OPSOMMING: Die doel van die studie was om skeletspier veranderinge wat teweeggebring is deur voor en na afloop van akute pleometriese oefening, te ondersoek. Die studie bestaan uit ‘n akute intervensie en ‘n oefeningsintervensie gedeelte. Die akute intervensie het ondersoek ingestel na die direkte bewyse van ultrastrukturele skade en identifikasie van indirekte faktore meer sigbaar is in proefpersone wat met rhabdomiolose presenteer. Meerso het die oefningsintervensie die moontlikheid dat pleometriese oefening die spier van ultrastrukturele skade en rhabdomiolose beskerm, ondersoek. Tydens die akute intervensie is 26 gesonde ongeoefende individue die akute pleometriese oefeningsessie (10 x 10 hurkspronge, 1 min rus) voltooi. Hierna het 13 proefpersone voortgegaan met die oefeningsintervensie. Agt van hierdie proefpersone het agt weke pleometriese sprongsessie oefeninge voltooi, terwyl vyf proefpersone gevra is om vir 8 weke geen oefeninge te doen nie. Sewe dae na afloop van die finale oefeningssessie het die oefening en kontrole groep in ‘n tweede herhaalde akute pleometriese oefeningsessie deelgeneem. Akute intervensie: kreatienkinase (KK) aktiwiteit het betekenisvol verhoog na die enkel pleometriese oefeningsessie in all proefpersone (basislyn: 129 tot op dag vier: 5348 U/l). Hierdie is vergesel met ‘n toename in die persepsie van pyn, c-reaktiewe proteïen (CRP) ‘n merker van inflammasie sowel as witbloedselle (WBS). Elektronmikrograwe van spierbiopsies wat geneem is drie dae na afloop van die oefeninge, het tekens van ultrastrukturele skade en membraanskade getoon wat ook deur immunofluoresensie duidelik warneembaar was deur die verlies van distrofienverkleuring. ‘n Verrekking van die c-terminus van titin is ook waargeneem deur middel van immunogold. Westernblot analyse het ‘n toename in calpain-3 outolise getoon. Gegrond op individuele KK response (KK grense: 153-71,024 U/L na vier dae post oefening) is 26 proefpersone verdeel in twee groepe naamlik ‘n hoë (n=10) en lae responders (n=16). Oefeningintervensie:: Na oefening het die geoefende groep nie ‘n toename in KK aktiwiteit getoon nie (KK aktiwiteit (110.0 U/l)), pynervaring, CRP, WBS, Z-lynstroming, ‘n strekking van titin of calpain-3 aktivering; terwyl in die kontrole groep daar slegs twee proefpersone met Z-lynstroming geïdentifiseer is. Die resultate wyse daarop dat hoë responders ‘n meer uitgesproke inflammatoriese reaksie toon vergeleke met die lae responders na afloop van essentriese oefening. Daar word dus meer WBS en spesifiek meer neutrofiele na beskadigde areas gelokaliseer wat in grootter membraanskade deur respiratoriese inspanning in die hoë responders. Hierdie skade kan beperk word deur oefening waardeur hermodulering van sarkomeriese proteïene via calpain aktivering tot stabiele rangskiking van proteïene in die sarcomere lei en daardeur proteïen vrystelling verhinder. / The NRF for financial assistance

It is well documented that engaging in resistance exercise can lead to further improvements in endurance performance. Whilst, not fully understood, it is speculated that increased motor unit recruitment, improved muscle coordination and enhanced utilisation of stored elastic energy after resistance-based exercise improves exercise economy. Nevertheless, while prolonged exposure to resistance training improves endurance performance in the long-term, a consequence of such training when unaccustomed is the appearance of exercise-induced muscle damage (EIMD). Exercise-induced muscle damage is well known to affect athletic performance requiring muscular strength and power; however, its effects on markers of endurance exercise are unclear. Therefore, the aim of this thesis was to investigate the effects of EIMD on endurance performance, with an emphasis on the physiological (oxygen uptake; , minute ventilation; ), metabolic (blood lactate; [La]), perceptual (rating of perceived exertion; RPE) and kinematic (stride length; SL, stride frequency; SF) responses during sub-maximal endurance exercise.

Every year the Eurasian crane travel from northern Africa to northern Europe and Asia. On their migration route they need to rest and often choose places around shallow lakes in agriculture landscapes. During their time in these resting sites the cranes forage in agriculture fields surrounding the lakes, which often cause crop-damage and thereof also financial loses. The last 30 years the population has increased radically, resulting in more extensive crop-damage. This study was set out to gain a better understanding how these migrating cranes choose sites to forage, based on four environment factors: roads, water, buildings, trees and shrub. A study-area in north of Lake Tåkern was selected and during six days in the spring all the cranes in the area were counted and marked on a map. The results showed that the factors affected the occurrence of cranes in the fields. They wanted to be close to shallow water and keep a distance to buildings, roads, trees and shrub. The cranes often spend the night in shallow water and search for food in the area close by to not lose too much energy, which probably was the main reason for the birds to stay close to the water. The distance to buildings and roads suggests that the cranes want to avoid interference from humans and the distance to trees and shrub that they want to have a good awareness of their surroundings. Through this understanding, areas with higher risk to attract groups of cranes can more easily be identified.

The aims of this project were (1) to investigate two forms of event perception: perception of movement and perception of sudden appearance, (2) to develop event perception procedures which could be applied to testing clinical populations, and (3) to relate event perception to abnormalities shown by neuroimaging. In addition issues relevant to each of the particular clinical populations involved were addressed. Event perception tasks used stimuli consisting of a background of randomly selected dots of light. In one task a dot was added to the display (appearance), in the other a dot started to move (movement onset). Four laboratory experiments were conducted examining the ability to detect and locate these events under varying conditions in healthy controls. Results indicated that neuronal coding strategies were different for appearances and movement onset. Laboratory tasks were adapted for clinical application and administered to groups of patients with different neurological conditions. Five studies were conducted to assess sensitivity and specificity of the Event Perception tasks in clinical settings. The groups studied were chronic solvent abusers, detoxified alcoholics, patients suffering from optic neuritis, and patients with traumatic brain injury. Event Perception tasks were found to be differentially sensitive to neurological conditions and showed dissociations and double dissociations both within and between neurological conditions. Relationships with Magnetic Resonance Imaging (MRI) and Single Photon Emission Computed Tomography (SPECT) were investigated in patients with head injury. Patterns of brain damage differed significantly for patients with impaired performance on the movement task. It is concluded that Event Perception tasks are of value in the assessment of neurological patients: They allow assessment of functions which are not usually evaluated in neuropsychological examinations, facilitate detection of subtle deficits and deficits which may present at an early stage, and offer greater specificity and sensitivity than many traditional neuropsychological test procedures. Event Perception tasks are easy to administer and do not suffer from training effects on repeated administration to the same degree as many traditional measures. It is also argued that tests with a theoretical basis are better suited to clinical research in neuropsychology than many traditional tasks because they potentially allow a more precise explanation and assessment of the abnormal processes under investigation.

published_or_final_version / Community Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Anatomy / Doctoral / Doctor of Philosophy