Thesis (MEng (Electrical and Electronic Engineering))--University of Stellenbosch, 2002. / An efficient radiating strucllire was needed for borehole pulsed radar applications in the 10-100 MHz frequency band. Both resistively loaded and insulated wire antennas were investigated and an active antenna is proposed as a fmal solution. The study proceeded from the characterization of the origin of radiation on a conductive dipole wire antenna when excited with a transient. Different radiation mechanisms were identified when the antenna was excited with a current or voltage source. The wire antenna in insulated surroundings was modelled using transmission line theory to simulate the antenna in the borehole environment. The transmission line model proved to be useful for investigating conducting and resistively loaded antennas for the dimensions associated with borehole surveys. From the modelling results, it became apparent that the asymmetric resistively loaded antenna might provide the best practical solution. This antenna displays reasonably stable input impedance and low far-field variations for different theta angles across the desired frequency band. Different percentage Wu-King resistive profiles were studied to show that a 50% reduction in the normal Wu-King resistor values will add only a little ringing but have better amplitude response than the 100% Wu-King loading. The asymmetric resistively loaded antenna has better sensitivity to receiving transients when combined with a high impedance source load than when symmetrically loading the antenna. An active antenna incorporating the asymmetric resistively loaded antenna and a low noise current feedback front end amplifier was built and measured in an air environment. The results show that the active antenna has a flat transfer function and reacts as a wide band electric field probe with better resolution than in the conventional 50 Q loaded case

Thesis (MScEng (Electrical and Electronic Engineering))--University of Stellenbosch, 2008. / Modern technology is reducing the cost of electronic devices. The speed of these devices and their reliability is improving. They can be used to implement low cost systems without compromising performance. The design of two linear FM-CW radars using direct digital synthesis (DDS) is discussed. The use of the DDS simplifies the generation of the linear frequency sweep that is required. The systems are analysed mathematically and by computer simulation, before being implemented in hardware. The first system is to be used to measure the position of pedestrians, at short range. The other system is to be used as a ground penetrating radar to measure the depth of objects located close to the surface. The design of a micro-strip patch array with a corporate feed network is also discussed. The antenna is constructed, measured and used in the pedestrian measurement system. Both systems are tested and used for initial radar measurements and the results obtained are presented.

Thesis (MScEng (Electrical and Electronic Engineering))--University of Stellenbosch, 2006. / The successful operation of a pulsed monostatic borehole radar system requires that cur- rent on the antenna due to transmitter pulses subsides quickly. Deterioration of the radar antenna feed-point current settling times when deployed in water-¯lled boreholes showed that the radar system's performance is highly environmentally sensitive. Electromagnetic models are used to investigate this e®ect, since measuring the feed-point and radiative characteristics of an insulated antenna deployed in a borehole is practically impossible at present. A transmission line model for insulated antennas is utilized to model the borehole radar antenna in electrically dense media. Predicted input impedance values however do not correspond well to those from numerical ¯eld simulation software and the model is shown to be inadequate for modelling insulated antennas in environments of low conductivity. Radiated ¯eld results are however found to be accurate. A study of the feed-point and radiative characteristics of the borehole radar antenna in a range of di®erent borehole environment is performed using electromagnetic ¯eld simulation software. Results con¯rm that the borehole radar antenna has longer feed- point current settling times and degraded radiated pulse waveforms when deployed in water-¯lled boreholes. Simple lumped element networks with driving-port impedances approximately equal to antenna input impedances are synthesized from simulated input impedance results for a range of borehole environments. This allows diagnostics on the radar system to be performed in the laboratory, with the antenna load appearing as if the system were deployed in a borehole. The use of an antenna with distributed resistive and capacitive loading is proposed as a modi¯cation that would result in improved feed-point characteristics in water-¯lled boreholes. Results from simulations and experiments are presented that con¯rm that the new antenna design substantially reduces feed-point current settling times after the transmitter ¯res.

Thesis (MScEng (Electrical and Electronic Engineering))--University of Stellenbosch, 2000. / South Africa has an immensely rich reserve of minerals which still has to be exploited. The problem with these reserves is that they exist in reefs where the mining environment is extremely hazardous, and where mining is very expensive. These are only two of the reasons why borehole radar has recently become a very important field of research in the South African mining industry. These radars have to operate in rock, which has a number of electromagnetically problematic characteristics, which greatly complicate modelling and design of suitable radars. The goal of this project is to demonstrate how the Finite Difference Time Domain (FDTD) method may be used to electromagnetically model and simulate borehole radars and subterranean environments.

Le transport de substances dotées de propriétés pharmacologiques au travers de la membrane plasmique ainsi que leur accès aux divers compartiments intracellulaires, en particulier le compartiment cytoplasmique et nucléaire, demeure un obstacle pour la recherche biotechnologique et biomédicale et pour l'industrie pharmaceutique. Parmi les moyens actuellement connus pour introduire des substances dans les cellules, les peptides de translocation également dénommés CPPs (Cell- Penetrating-Peptides) qui représentent des vecteurs particulièrement intéressants. Dans le présent travail, nous avons utilisé trois CPPs, Tat, penétratine et un analogue de la maurocalcine (MCaAbu) pour la délivrance de la doxorubicine (Dox), une drogue utilisée en chimiothérapie anticancéreuse et dont son effet est limité par la résistance des cellules tumorales. Afin d'évaluer l'efficacité des trois complexes formés (Dox-CPPs), deux modèles cellulaires du cancer mammaire ont été utilisés; les cellules MDA-MB 231 et les cellules MCF7 qui présentent une sensibilité différente à la drogue seule. Notre étude nous a permis de monter en premier lieu que les trois CPPs utilisés représentent de puissants vecteurs pour l'entrée de la Dox à l'intérieur des cellules et que la conjugaison de la drogue a contourné la résistance des cellules MDA-MB 231 à la Dox. Nous avons également montré que la distribution de la Dox est plutôt nucléaire à l'état libre et cytoplasmique lorsqu'elle est couplée aux CPPs. Dans la deuxième partie de notre travail, nous avons montré que la Dox ainsi que les Dox-CPPs induisent l'apoptose des cellules MDA-MB 231 et que cet effet est observé en traitant les cellules avec une dose cinq fois plus faible de Dox-CPPs par rapport à la Dox. Cette mort est dépendante des caspases et implique la voie mitochondriale. De plus, l'apoptose induite par la Dox est médiée par les radicaux oxygénés (ROS). Ceux-ci sont en partie impliqués lors de l'apoptose induite par les Dox-CPPs puisque l'utilisation d'un inhibiteur de ROS inhibe partiellement l'apoptose induite par ces composés. Nous avons montré également que la surexpression de Bcl-2 protège l'apoptose induite par la Dox et partiellement par les Dox-CPPs, ce qui suggère qu'une autre voie est impliquée dans l'apoptose induite par les Dox-CPPs et qui expliquerait la plus forte toxicité de ces composés. Concernant cette deuxième voie nous avons pu montré que les récepteurs de mort TRAIL sont bien impliqués dans l'apoptose induite par les Dox-CPPs via la clustérisation membranaire des récepteurs de mort DR4 et DR5. Cette clustérisation modifie le taux d'expression de ces récepteurs membranaires et à l'origine d'une sensibilisation des cellules MDA-MB 231 au TRAIL endogène au cours de l'apoptose induite par les Dox-CPPs. Une telle sensibilisation au TRAIL est à l'origine de la génération de céramide, qui constitue une autre voie d'induction d'apoptose par les Dox-CPPs en plus de la voie mitochondriale. L'ensemble de ces résultats devraient nous permettre à valoriser la stratégie de couplage des CPPs à des agents antitumoraux afin d'améliorer leur effet et de mieux comprendre les voies de signalisation de la mort induite suite au couplage. Ceci pourrait à terme conduire à la conception de nouveaux analogues d'index thérapeutique plus élevé. Mots clés : Cell- Penetrating-Peptides, Doxorubicine, résistance cellulaire, apoptose, ROS, récepteurs de mort, céramide.

<p>Polythermal glaciers, i.e. glaciers with a combination of ice at and below the freezing point, are widespread in arctic and subarctic environments. The polythermal structure has major implications for glacier hydrology, ice flow and glacial erosion. However, the interplay of factors governing its spatial and temporal variations such as net mass balance, ice advection and water content in the ice is poorly investigated and as yet not fully understood. This study deals with a thorough investigation of the polythermal regime on Storglaciären, northern Sweden, a small valley glacier with a cold surface layer in the ablation area. Extensive field work was performed including mapping of the cold surface layer using ground-penetrating radar, ice temperature measurements, mass balance and ice velocity measurements. Analyses of these data combined with numerical modelling were used specifically to investigate the spatial and temporal variability of the cold surface layer, the spatial distribution of the water content just below the cold surface layer transition, the effect of radar frequency on the detection of the surface layer, and the sensitivity of the cold surface layer to changes in forcing.</p><p>A comparison between direct temperature measurements in boreholes and ground-penetrating surveys shows that the radar-inferred cold-temperate transition depth is within ±1 m from the melting point of ice at frequencies above ~300 MHz. At frequencies below ~155 MHz, the accuracy degrades because of reduced scattering efficiency that occurs when the scatterers become much smaller compared to the wavelength. The mapped spatial pattern of the englacial cold-temperate transition boundary is complex. This pattern reflects the observed spatial variation in net loss of ice at the surface by ablation and vertical advection of ice, which is suggested to provide the predominant forcing of the cold surface layer thickness pattern. This is further supported by thermomechanical modeling of the cold surface layer, which indicates high sensitivity of the cold surface layer thickness to changes in vertical advection rates.</p><p>The water content is the least investigated quantity that is relevant for the thermal regime of glaciers, but also the most difficult to assess. Spatial variability of absolute water content in the temperate ice immediately below the cold surface layer on Storglaciären was determined by combining relative estimates of water content from ground-penetrating radar data with absolute determination from temperature measurements and the thermal boundary condition at the freezing front. These measurements indicate large-scale spatial variability in the water content, which seems to arise from variations in entrapment of water at the firn-ice transition. However, this variability cannot alone explain the spatial pattern in the thermal regime on Storglaciären.</p><p>Repeated surveys of the cold surface layer show a 22% average thinning of the cold surface layer on Storglaciären between 1989 and 2001. Transient thermomechanical modeling results suggest that the cold surface layer adapts to new equilibrium conditions in only a few decades after a perturbation in the forcing is introduced. An increased winter air temperature since mid-1980s seems to be the cause of the observed thinning of the cold surface layer. Over the last decades, mass balance measurements indicate that the glacier has been close to a steady state. The quasi-steady state situation is also reflected in the vertical advection, which shows no significant changes during the last decades. Increased winter temperatures at the ice surface would result in a slow-down of the formation of cold ice at the base of the cold surface layer and lead to a larger imbalance between net loss of ice at the surface and freezing of temperate ice at the cold-temperate transition.</p>

The Wanganui-Wilberg landslide lies between Hokitika and Franz Josef townships, at the entrance of Harihari, on the true left bank of the Wanganui River, by State Highway 6. This apparently co-seismic landslide belongs to the class of events called rock avalanches - powerful destructive agents (Keefer, 1984) in the landscape. Other rock avalanches are numerous (Whitehouse, 1983), and widespread over the Southern Alps of New Zealand, and many appear to be co-seismic. De Mets et al. (1994) used the model NUVEL-1A to characterize the motion of the Alpine fault: 37 mm/year at an azimuth of 071° for the strike-slip and a dip-slip of 10 mm/year normal to the strike direction. Although linear when seen from the sky, the detailed morphology of the fault is more complex, called en échelon (Norris and Cooper, 1997). It exhibits metamorphosed schists (mylonite series) in its hanging wall (McCahon, 2007; Korup, 2004). Earthquakes on the Alpine fault have a recurrence time of c. 200-300 years and a probability of occurrence within 100 years of 88% (Rhoades and Van Dissen, 2002). Thought to have been triggered by the AD1220 event (determined by dendrochronology), the Wanganui-Wilberg rock avalanche deposit represents only 20% of its original volume, which was c. 33 million cubic metres. The deposit probably dammed the Wanganui River and, as a result, created a small and short-lived lake upstream. The next earthquake capable of triggering such events is likely to occur fairly soon (Yetton, 1998). Knowledge of historic catastrophic events such as the Wanganui-Wilberg rock avalanche is of crucial importance in the development of future hazard and management plans.

Development of chimeric, recombinant peptides, proteins and enzymes expands the availability of protein/enzyme–based tools for cellular analysis and new assay platforms. Ideal protein reagents for cellular analysis must translocate into a variety of cells with minimum cell damage, retain stability and biological activity within the cell during analysis, and provide a reliable, measurable signal. This work focused on development, characterization and utilization of chimeric recombinant peptide, protein and enzyme reagents for cellular analysis and immunoassays. A cell-penetrating, fluorescent protein substrate (PKAS) was developed to monitor intracellular protein kinase A activity in cells without the need for cellular transfection. PKAS translocated into HeLa cells, βTC-3 cells and pancreatic islets with minimal toxicity. Upon cellular loading, glucose dependent phosphorylation of PKAS was observed in both βTC-3 and pancreatic islets via capillary zone electrophoresis. In pancreatic islets, maximal PKAS phosphorylation (83 ± 6 %) was observed at 12 mM glucose, whereas maximal PKAS phosphorylation (86 ± 4 %) in βTC-3 cells was with 3 mM glucose indicating a left-shifted glucose sensitivity. A cell-penetrating luciferase chimera (Luc-TAT) and a cell-penetrating phospholipid nanoshell entrapped luciferase (Luc-PPN) was constructed to monitor dynamic changes in intracellular ATP levels in mammalian cells. Upon cellular loading, the activity of Luc-TAT and Luc-PPN was monitored with time. Luc-TAT lost approximately 50% activity within one hour, and decreased rapidly over time. In contrast Luc-PPNs retain approximately 95% activity in 1 hour and 77% after 12 hours showing longer biological lifetime. Luc-PPNs were able to detect dynamic ATP changes in intact HeLa cells in the presence of KCN and NaN3. The bioluminescence returned to background levels within 8-10 minutes after treatment with KCN, whereas NaN₃ showed ~ 40% reduction. Two novel recombinant human parathyroid hormone (hPTH) analogs hPTHEGFP and hPTH-Cys were prepared to develop immunoassays for PTH detection in clinical samples. Initial experiments show promise for these analogs for use in CZELIF based immunoassays. The analogs present a number of distinctive advantages for clinical assays and can be used to develop several immunoassay platforms.

The mitochondrion is an important therapeutic target due to its roles in energy metabolism, reactive oxygen species production, and activation of cell death. The connection of these cellular processes with diabetes, obesity, neurodegenerative disorders, and cancer makes this organelle a potential control point for treatment of these diseases. The advancement of mitochondrial medicine will be accelerated by the development of organelle-specific cellular transporters as well as by strategies to enhance the activity of mitochondrially-active drugs. Here, the discovery and development of a new class of mitochondria-specific agents, mitochondria-penetrating peptides (MPPs), is described. These peptides, exemplified by the sequences (FXY)3 and (FXY)4 where FX=cyclohexylalanine and Y=basic arginine or lysine residues, display hydrophobic and cationic residues critical for access to this organelle, and appear to accumulate within cells and mitochondria through membrane potential-dependent mechanisms. Subcellular localization of the peptides was determined by the interplay of hydrophobicity and positive charge, and necessary lipophilicity “thresholds” for access to the mitochondrion. MPPs can be engineered to have minimal mitochondrial disruptive activity and cytotoxicity through minimization of hydrophobicity and length. Furthermore, MPPs appear to accumulate predominantly in the mitochondrial matrix, a feature which places them within an exclusive class of mitochondria-specific transporters and may enable delivery applications for a number of therapeutically-relevant cargoes. Information gained from MPP studies on the physiochemical parameters that drive mitochondrial localization were applied to improve the activity of the anticancer peptide d-(KLAKLAK)2, an agent that activates apoptosis through mitochondrial disruption. Residue substitutions that increased peptide hydrophobicity, regardless of changes to secondary structure, enhanced mitochondrial localization, activity, and cytotoxicity induced by the peptide. In conclusion, these studies provide important guidelines for how to drive the subcellular localization and activity of peptides, and expand the possibilities for mitochondrially-targeted therapeutics.

The “green agenda” combined with highway congestion has accelerated the demand for increased freight and passenger travel on the world’s railways. These increases have driven demand for more efficient and rapid investigation of trackbed ballast. Network Rail and other rail infrastructure operators spend significant financial sums on inspecting, tamping, adjusting, cleaning, and replacing trackbed ballast. Such maintenance is often to the detriment of normal network operation. Industry requires a method of ballast evaluation that is non-intrusive, cheap, can appraise long stretches of track in a short period of time, and give a fingerprinting result from which time-to-maintenance can be calculated and planned. Thus, the aim was to develop evaluation methods using non-destructive testing techniques. A 10-year old full-scale trackbed composed of variously fouled ballast was re-visited and used for experimentation. The condition of the ballast was calculated using the Ionescu Fouling Index. Earlier research at the University of Edinburgh enabled researchers worldwide to characterise ballast using ground penetrating radar (GPR). This research was repeated, validated and taken forward in a series of GPR experiments on the trackbed using a range of antennas from 500MHz to 2.6GHz. New "scatter" metrics were developed to determine ballast condition from the GPR waveforms. These metrics were then used to predict the Ionescu Fouling Index with a correlation coefficient greater than 0.9. One of the current approaches to evaluating the stiffness of railway ballast is to use a Falling Weight Deflectometer (FWD). The viability of using a Prima 100 mini-FWD on railways to measure stiffness was determined and deemed to be ineffective on ballast. The applicability of the impulse response technique on railways was determined. An instrumented hammer was used to excite the ballast, with a geophone measuring the response. The Frequency Response Function of this was successfully correlated with the Ionescu Fouling Index with a correlation coefficient also greater than 0.9. Finally, using GPR data and measured stiffness data collected by Banverket, Sweden, a numerical model to successfully relate radar responses to stiffness was developed.