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Besides collagen, elastin is the most common connective tissue structural protein in vertebrates and similar to collagen relatively resistant to non-specific degradation. Typical elastolytic proteases are the serine-dependent pancreatic and leukocyte elastases, the Zn-dependent matrix metalloproteinase 12, and several lysosomal cysteine proteases. Among the cysteine cathepsins, cathepsins S, K and V are highly potent elastases with cathepsin V displaying the highest activity among all known mammalian elastases. Despite a shared amino acid sequence identity of over 80% between cathepsins V and L and very similar subsite specificities, only cathepsin V has a potent elastase activity whereas cathepsin L lacks it. A series of chimera mutants containing various proportions of cathepsin V and cathepsin L were constructed in an attempt to define a specific region needed for elastin degradation. It was found that retaining the peptide sequence region from amino acids 89 to 119 of cathepsin V preserves the mutant’s elastolytic activity against elastin-Rhodamine conjugates whereas the region FTVVAPGK (amino acids 112-119) contributes approximately 60% of activity retention. Several additional mutant proteins involving mutual swapping of residues VDIPK (amino acids 113-117) of cathepsin L with residues TVVAPGK (amino acids 113-119) of cathepsin V, deletion of Glyl 18 from cathepsin V, and insertion of Gly between Prol 16 and Lysi 17 in cathepsin L were constructed and evaluated for their elastolytic activities. The results obtained with those mutant cathepsin proteins support the importance of the amino acid region spanning the residues from 112 to 119 in cathepsin V. Based on the 3-D structure of cathepsin V, this peptide region is located below subsite binding pocket S2 and forms a wall-like barrier which may act as an exosite for the productive binding of cross-linked elastin. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

The potential for using RMP (refiner mechanical process) pulp mill fibre waste as a soil amendment was investigated by determining levels of net carbon mineralization. Under optimum conditions (laboratory incubation study), the pulp fibre waste, being a relatively homogeneous substrate, was found to mineralize at one rate of -0.0078 d⁻¹. In field applications the rate of net mineralization was slower, with rates of -0.0034 d⁻¹ and -0.0037 d⁻¹, as determined by soil respiration and litter bag trials, respectively. A loading effect was noted for this amendment, where increasing the levels of application was found to cause decreases in the mineralization rate. Using pulp fibre waste in forest landing rehabilitation appears to increase the levels of microbial activity in the surface horizon. The higher levels of productivity should lead to improvements in soil structure, and would be a better alternative to only tilling and fertilizing the soil. / Land and Food Systems, Faculty of / Graduate

Nanocellulosics, often found in the form of cellulose nanocrystals (CNCs) and nanofibrillated cellulose (NFCs), provide promise as rheological modifiers and reinforcement fillers for composite materials. The biological origin of CNCs promises a bio-renewable resource with the potential to expedite degradation times compared to synthetic polymer species. Additionally, the surface functional groups provide a route for both hydrogen bonding and further chemical modification. While much research is currently investigating the possible uses of these materials, they offer limited aid if their use is not scalable to industrial processing techniques. Common processing techniques such as injection molding subject materials to high temperatures and strain rates upwards of 100000 s-1. Thermal stability is a known challenge that can be increased via chemical modifications, but little is known about the effects of high or extended shear stresses typical of those experienced during typical polymer processing. High shear rates, which proportionally result in high shear stresses, have the potential to influence the alignment, degradation, and overall usability of these materials when employed in consumer applications. In this work, we investigate the rheology and processing of aqueous CNC suspensions at concentrations up to 12.1 wt% and of aqueous NFC suspensions at concentrations up to 20 wt% under capillary shear stresses. Traditional capillary rheology corrections, including the Weissenberg-Rabinowitsch-Mooney (WRM) correction for non-Newtonian fluids, and the Bagley correction for entrance pressure effects, have been applied to determine the true rheological behaviors of these suspensions. Additional analysis using atomic force microscopy (AFM), wide-angle x-ray scattering (WAXS), and conductometric titration assist identification of morphological and chemical changes that affect the CNMs after they have been subjected to industry-relevant shear rates. These studies demonstrate that processing conditions can significantly affect the size and shape of the post-processed nanomaterials by fracturing the CNCs and unwinding the larger bundles of the NFCs. Given the importance of the final aspect ratio of filler and reinforcement materials, the impact of this discovery will substantially influence how these materials are used and processed to create consumer products. / Doctor of Philosophy / As the world struggles with the problem of plastic waste and climate change, it is important to develop biologically friendly solutions to combat these issues. Filler materials such as carbon fibers and glass fibers can help create lightweight materials for cars and transportation containers. However, carbon fibers can be hazardous and expensive to obtain. Glass fibers offer a more cost-effective option, but they often break during processing and are heavy in comparison to carbon fibers. Cellulose nanomaterials (CNMs) can provide a lightweight and more bio-friendly alternative to these fillers. These CNMs can come from a wide variety of sources, such as hardwood trees, bacteria, or tunicates (a type of marine animal). This makes them abundantly available, relatively cheap to produce, and easy for the environment to break down fully. Using these as fillers instead of glass fibers, carbon fibers or other materials could help reduce much of our waste, but we need to be able to process them in the same ways we currently handle other composite materials. This work focuses on characterizing the effect of high-speed flows and the forces those flows put on the cellulose nanomaterials. The following document will show that the smaller, more rigid, cellulose nanocrystals (CNCs) often break under these stresses, while the longer nanofibrillated cellulose (NFCs) unwind and disperse.

The hallmark oncoprotein Myc is a major driver of tumorigenesis in various human cancer entities. However, Myc’s structural features make it challenging to develop small molecules against it. A promising strategy to indirectly inhibit the function of Myc is by targeting its interactors. Many Myc-interacting proteins have reported scaffolding functions which are difficult to target using conventional occupancy- driven inhibitors. Thus, in this thesis, the proteolysis targeting chimera (PROTAC) approach was used to target two oncoproteins interacting with Myc which promote the oncogenicity of Myc, Aurora-A and WDR5. PROTACs are bifunctional small molecules that bind to the target protein with one ligand and recruit a cellular E3- ligase with the other ligand to induce target degradation via the ubiquitin- proteasome system. So far, the most widely used E3-ligases for PROTAC development are Cereblon (CRBN) and von Hippel–Lindau tumor suppressor (VHL). Furthermore, there are cases of incompatibility between some E3-ligases and proteins to bring about degradation. Hence there is a need to explore new E3- ligases and a demand for a tool to predict degradative E3-ligases for the target protein in the PROTAC field. In the first part, a highly specific mitotic kinase Aurora-A degrader, JB170, was developed. This compound utilized Aurora-A inhibitor alisertib as the target ligand and thalidomide as the E3-ligase CRBN harness. The specificity of JB170 and the ternary complex formation was supported by the interactions between Aurora-A and CRBN. The PROTAC-mediated degradation of Aurora-A induced a distinct S- phase defect rather than mitotic arrest, shown by its catalytic inhibition. The finding demonstrates that Aurora-A has a non-catalytic role in the S-phase. Furthermore, the degradation of Aurora-A led to apoptosis in various cancer cell lines. In the second part, two different series of WDR5 PROTACs based on two protein- protein inhibitors of WDR5 were evaluated. The most efficient degraders from both series recruited VHL as a E3-ligase and showed partial degradation of WDR5. In addition, the degradation efficiency of the PROTACs was significantly affected by the linker nature and length, highlighting the importance of linker length and composition in PROTAC design. The degraders showed modest proliferation defects at best in cancer cell lines. However, overexpression of VHL increased the degradation efficiency and the antiproliferative effect of the PROTACs. In the last part, a rapamycin-based assay was developed to predict the degradative E3-ligase for a target. The assay was validated using the WDR5/VHL and Aurora- A/CRBN pairs. The result that WDR5 is degraded by VHL but not CRBN and Aurora-A is degraded by CRBN, matches observations made with PROTACs. This technique will be used in the future to find effective tissue-specific and essential E3-ligases for targeted degradation of oncoproteins using PROTACs. Collectively, the work presented here provides a strategy to improve PROTAC development and a starting point for developing Aurora-A and WDR5 PROTACs for cancer therapy. / Das Onkoprotein Myc ist ein wichtiger Faktor bei der Tumorentstehung in verschiedenen menschlichen Krebsarten. Die strukturellen Merkmale von Myc machen es jedoch schwierig, kleine Moleküle gegen dieses Protein zu entwickeln. Eine vielversprechende Strategie zur indirekten Hemmung der Funktion von Myc besteht darin, auf seine Interaktoren abzuzielen. Viele Proteine, die mit Myc interagieren, haben Gerüstfunktionen, die mit herkömmlichen Inhibitoren nur schwer zu hemmen sind. Daher wurde in dieser Arbeit der PROTAC-Ansatz (Proteolysis Targeting Chimera) verwendet, um zwei Onkoproteine, die mit Myc interagieren und die Onkogenität von Myc fördern, ins Visier zu nehmen: Aurora-A und WDR5. PROTACs sind bifunktionale kleine Moleküle, die mit einem Liganden an das Zielprotein binden und mit dem anderen Liganden eine zelluläre E3-Ligase rekrutieren, um den Abbau des Zielproteins über das Ubiquitin-Proteasom-System einzuleiten. Die bisher am häufigsten verwendeten E3-Ligasen für die Entwicklung von PROTACs sind Cereblon (CRBN) und der von Hippel-Lindau-Tumorsuppressor (VHL). Außerdem gibt es Fälle von Inkompatibilität zwischen einigen E3-Ligasen und Proteinen, die abgebaut werden sollen. Daher besteht die Notwendigkeit, neue E3-Ligasen zu erforschen und Werkzeuge zur Vorhersage abbauender E3-Ligasen für das Zielprotein zu entwickeln. Im ersten Teil wurde ein hochspezifischer Degrader der mitotischen Kinase Aurora-A, JB170, entwickelt. Bei dieser Verbindung wurde der Aurora-A-Inhibitor Alisertib als Zielligand und Thalidomid als Binder für die E3-Ligase CRBN verwendet. Die Spezifität von JB170 und die ternäre Komplexbildung wurden durch die Wechselwirkungen zwischen Aurora-A und CRBN unterstützt. Der durch PROTAC vermittelte Abbau von Aurora-A führte zu einem deutlichen Defekt in der S-Phase und nicht zu einem mitotischen Stillstand, wie es für dessen katalytische Hemmung beobachtet wurde. Dies zeigt, dass Aurora-A eine nicht-katalytische Funktion in der S-Phase hat. Außerdem führte der Abbau von Aurora-A in verschiedenen Krebszelllinien zur Apoptose. Im zweiten Teil wurden zwei verschiedene Serien von WDR5 PROTACs auf der Grundlage von zwei Protein-Protein-Inhibitoren von WDR5 untersucht. Die effizientesten Degrader aus beiden Serien rekrutierten VHL als E3-Ligase und zeigten einen teilweisen Abbau von WDR5. Darüber hinaus wurde die Abbaueffizienz der PROTACs erheblich von der Art und Länge des Linkers beeinflusst, was die Bedeutung der Linkerlänge und -zusammensetzung bei der Entwicklung von PROTACs unterstreicht. Die Abbauprodukte zeigten bestenfalls bescheidene Proliferationsdefekte in Krebszelllinien. Eine Überexpression von VHL erhöhte jedoch die Abbaueffizienz und den antiproliferativen Effekt der PROTACs. Im letzten Teil wurde ein auf Rapamycin basierender Assay entwickelt, um die abbauende E3-Ligase für ein Target vorherzusagen. Der Assay wurde anhand der Paare WDR5/VHL und Aurora-A/CRBN validiert. Das Ergebnis, dass WDR5 von VHL, aber nicht von CRBN abgebaut wird und Aurora-A von CRBN abgebaut wird, stimmt mit den Beobachtungen überein, die mit PROTACs gemacht wurden. Diese Technik wird in Zukunft eingesetzt werden, um wirksame gewebespezifische und essentielle E3-Ligasen für den gezielten Abbau von Onkoproteinen mit Hilfe von PROTACs zu finden. Insgesamt bieten die hier vorgestellten Arbeiten eine Strategie zur Verbesserung der PROTAC-Entwicklung und einen Ausgangspunkt für die Entwicklung von Aurora-A- und WDR5-PROTACs für die Krebstherapie.

In this work, we demonstrate the mechanism for etching exfoliated graphene on SiO2 and other technological important substrates (Si, SiC and ITO), using low-energy electron sources. Our mechanism is based on helium ion sputtering and vacancy formation. Helium ions instead of incident electrons cause the defects that oxygen reacts with and etches graphene. We found that etching does not occur on low-resistivity Si and ITO. Etching occurs on higher resistivity Si and SiC, although much less than on SiO2. In addition, we studied the degradation mechanism of MoS2 under ambient conditions using as-grown and preheated mono- and thicker-layered MoS2 films. Thicker-layered MoS2 do not exhibit the growth of dendrites that is characteristic of monolayer degradation. Dendrites are observed to stop at the monolayer-bilayer boundary. Raman and photoluminescence spectra of the aged bilayer and thicker-layered films are comparable to those of as-grown films. We found that greater stability of bilayers and thicker layers supports a previously reported mechanism for monolayer degradation involving Förster resonance energy transfer. As a result, straightforward and scalable 2D materials integration, or air stable heterostructure device fabrication may be easily achieved. Our proposed mechanisms for etching graphene and ambient degradation of MoS2 could catalyze research on realizing new devices that are more efficient, stable, and reliable for practical applications.

Absorption-stripping with aqueous, concentrated piperazine (PZ) is a viable retrofit technology for post-combustion CO2 capture from coal-fired power plants. The rate of thermal degradation and oxidation of PZ was investigated over a range of temperature, CO2 loading, and PZ concentration. At 135 to 175 °C, degradation is first order in PZ with an activation energy of 183.5 kJ/mole. At 150 °C, the first order rate constant, k1, for thermal degradation of 8 m PZ with 0.3 mol CO2/mol alkalinity is 6.12 × 10-9 s-1. After 20 weeks of degradation at 165 °C, 74% and 63%, respectively, of the nitrogen and carbon lost in the form of PZ and CO2 was recovered in quantifiable degradation products. N-formylpiperazine, ammonium, and N-(2-aminoethyl) piperazine account for 57% and 45% of nitrogen and carbon lost, respectively. Thermal degradation of PZ likely proceeds through SN2 substitution reactions. In the suspected first step of the mechanism, 1-[2-[(2-aminoethyl) amino]ethyl] PZ is formed from a ring opening SN2 reaction of PZ with H+PZ. Formate was found to be generated during thermal degradation from CO2 or CO2-containing molecules. An analysis of k1 values was applied to a variety of amines screened for thermal stability in order to predict a maximum recommended stripper temperature. Morpholine, piperidine, PZ, and PZ derivatives were found to be the most stable with an allowable stripper temperature above 160 °C. Long-chain alkyl amines or alkanolamines such as N-(2-hydroxyethyl)ethylenediamine and diethanolamine were found to be the most unstable with an allowable stripper temperature below 120 °C. Iron (Fe2+) and stainless steel metals (Fe2+, Ni2+, and Cr3+) were found to be only weak catalysts for oxidation of PZ, while oxidation was rapidly catalyzed by copper (Cu2+). In a system with Fe2+ or SSM, 5 kPa O2 in the inlet flue gas, a 55 °C absorber, and one-third residence time with O2, the maximum loss rate of PZ is expected to 0.23 mol PZ/kg solvent in one year of operation. Under the same conditions but with Cu2+ present, the loss rate of PZ is predicted to be 1.23 mole PZ/kg solvent in one year of operation. Inhibitor A was found to be effective at decreasing PZ loss catalyzed by Cu2+. Ethylenediamine, carboxylate ions, and amides were the only identified oxidation products. Total organic carbon analysis and overall mass balances indicate a large concentration of unidentified oxidation products. / text

The lighting retrofit method is adopted as one of the solutions to reduce lighting energy consumption and improve lighting quality in existing buildings. Lighting controls and energy-efficient light sources are used to achieve the goals of the lighting retrofit. Nowadays, Light-Emitting Diodes (LEDs) are replacing traditional lighting technology owing to their high efficiency and longevity. One of the advantages of LEDs is the controllability function, which allows users to set the light level according to their preferences. This saves more energy and satisfies users’ lighting needs. However, over time, the performance of lighting retrofit projects deteriorates subject to failure of the retrofitted lights. Therefore, to maintain the performance of lighting retrofit projects, maintenance must be planned and performed. The impacts of the users’ lighting level requirements on LEDs’ life characteristics and lighting system performance are investigated by using lighting controls. Light and occupancy sensors adjust artificial light to the light level required by users and detect the presence of users in the zones, respectively. Light sensors measure the average illuminance in the zones. The measured illuminance is compared to the users’ set illuminance; if the measured illuminance is higher than the users’ set illuminance, lamps are dimmed to meet users’ lighting preference, when the measured illuminance is less than the users’ set illuminance, lamps in the zone are replaced by new ones. The dimming level in each zone at each sampling interval is used to estimate the operating junction temperature, thereafter the degradation rate and luminous flux are calculated. Light levels at workspace are modelled using the lumen method. This model helps to quantify energy savings and predict when lamps will fail to deliver the required light levels. In existing studies, users’ lighting level requirements are neglected when investigating the lifetime of the lighting system; however, users’ profile and driving schemes affect the operating conditions of a lighting system. From the simulation results, it is noted that lumen output degradation increases when the user’s set illuminance is above the illuminance required under normal operating conditions and decreases when the user’s set illuminance is below the illuminance required under normal operating conditions. Increased lumen output degradation shortens the lifetime of LEDs and reduces energy savings, while decreased lumen output degradation extends the lifetime and increases energy savings. Generally, lighting retrofit projects contain a large lighting population; investigating when each lamp will fail can be time-consuming and costly. In this research, a mathematical model is formulated to model LEDs’ failure by analysing the statistical properties of the lumen degradation rates. Based on the statistical properties of the degradation rates, the cumulative probability of failure distribution and the survival function are modelled. The formulated survival function is incorporated into the lighting maintenance optimization problem to balance energy savings and maintenance costs. A case study carried out shows that, in 10 years, the optimal lighting maintenance plan would save up to 59% of lighting energy consumption with acceptable maintenance costs. It is found that the proposed maintenance plan is more cost-effective than full maintenance. It is concluded that lumen degradation failure should be considered when investigating the performance of lighting retrofit projects, as this may not only affect energy savings but also reduce the level of illumination, which can cause visual discomfort. The initial investment costs of LEDs are still a barrier to the implementation of LED lighting systems in residential buildings. Energy-efficiency projects often face hurdles to access capital investments because decision-makers and funders do not have enough information about operational savings the project can provide and specific financial requirements applied to efficiency investment. In this research, an optimization model is formulated to give decision-makers and funders detailed information about the performance and operational savings that a LED lighting retrofit project can offer and its economic viability. The lumen degradation failure model developed is used to monitor and estimate the energy savings, and the optimal maintenance plan is scheduled to replace failed lamps. In the existing studies, the economic analysis of the lighting retrofit projects is assessed based on lighting population decay due to burnout failure while in this research economic analysis is assessed by considering the lumen degradation failure. The case study results show that the substitution of halogen light bulbs with LED light bulbs could save up to 291.4 GWh of energy consumption, and reduce 273:92 103 tons of CO2 emissions over 10-year period. The optimization model formulated is effective to help the decision-makers and funders to quantify the savings and assess the economic viability of the LED lighting retroïnˇA˛t project. This optimization model can help the decision-makers and funders to make an informed decision. / Thesis (PhD (Electrical Engineering))--University of Pretoria, 2020. / Electrical, Electronic and Computer Engineering / PhD (Electrical Engineering) / Unrestricted

Land degradation in communal rangelands is one of the problems that lowers land / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2009.

Thesis (M. Dev. (Planning and Management)) -- University of Limpopo, 2021 / Sand mining has grown popular in South African rural communities due to its increasing demand for building purposes in and around the surrounding villages as well as a source of income to the rural communities. Sand is an indispensable natural resource of any society around the world. For instance, the government has to deal with the frequent sand mining environmental effects and implement various strategies on how to deal with these effects to protect the environment. Although the National Environmental Management Act (NEMA) 107 of 1998 regulates sand mining, the illegal and unregulated rural sand mining is causing land degradation, creating unpleasant appearances, causing vulnerability to floods and pointing out the need for rehabilitation. Given the circumstances surrounding the issue of illegal sand mining in rural communities, this research is aimed at investigating the impact of illegal or legal sand mining on the environment looking at the land degradation and the importance of rehabilitating the area after use in Mentz village. The main objective of this research was to explore how sand mining causes land degradation and examining the significance of rehabilitation in sand mining. The methodology of the study was carried out using both quantitative and qualitative research design in a form of questionnaire surveys, oral interviews and field observations to collect the data. The sample was composed of the general members of the community, the chief and the sand miners. For data analysis, the study used the Statistical Package for the Social Sciences (SPSS), IBM SPSS Statistics 25. The results indicated that sand mining causes 54.76% of the land degradation in South Africa. Furthermore, the research revealed that 30.95% of the land degradation was due to deforestation and 11.90% of Mentz land degradation was caused by overgrazing. Besides, an overwhelming 76.58% of the respondents agreed that land should be rehabilitated after sand mining processes.