This work aims to study the pressure dependence of the thickness of the epitaxial silicon carbide SiC film growing from crystalline silicon Si due to the heterogeneous reaction with gaseous carbon monoxide CO.

Background The Breast Cancer Resistance Protein (BCRP) drug transporter is important for drug disposition and plays a critical role in regulating drug entry into the brain. Its substrate spectrum overlaps with substrates of Multi Drug Resistance Protein 1 (MDR1, P-gp), which influences and complicates the interpretation of data on drug distribution into tissues (e.g. brain). Distinguishing BCRP mediated transport from the transport by the MDR1 is often problematic. However, with new in vitro tools, this is now possible. In this project, two drug compounds, i.e. Dantrolene and Ritonavir, were investigated using these new in vitro models. The results from the experimental in vitro assay were matched with molecular dynamics (MD) simulations. Using coarse-grained (CG) simulations, a model of the BCRP transporter in a lipid bilayer was built, this model is based on the human BCRP structure revealed by Taylor et al (2017). Simulations were run for Dantrolene (a known substrate of BCRP) independently three times, and another with Ritonavir (a non-substrate) three times. Aim To determine substrate specificity for the BCRP transporter for two compounds, and to construct a CG model of BCRP transporter to see whether in silico methods can be used as an alternative for assessing substrate specificity.  Methods Madin-Darby canine kidney (MDCK) II cell line with no endogenous canine MDR1 (cMDR1) expression (MDCKcMDR1-KO), overexpressing human MDR1 (hMDR1) (MDCK-hMDR1cMDR1-KO) and stable expression of human BCRP (hBCRP) (MDCK-hBCRPcMDR1-KO) cells were cultured and used in Transwell experiments. Samples were analyzed using LC-MS/MS to determine the substrate concentrations. Apparent permeability and efflux ratio was calculated and evaluated.  MD simulations used the Martini 3 CG force field, and were run with Gromacs (version 2020.4). Tools including MODELLER, INSANE and others were used to construct the initial model (Webster, 2000; Wassenaar et al., 2015), for parameterization of substrate and non-substrate molecules. And visual inspection was done with the visual molecular dynamics (VMD) program and PyMOL. Results In vitro transport experiment confirmed that Dantrolene is a BCRP specific substrate, and Ritonavir is MDR1 specific substrate. Following simulations of these two compounds, Dantrolene is observed to stay in the transmembrane domains (TMD) for a certain period (on average several hundreds of nanoseconds), while Ritonavir is not found to bind in the TMD, which provides a proof of concept for future studies.

In this work, an innovative approach for effective modeling of substrate integrated waveguide (SIW) devices is firstly proposed. Next, a novel substrate integrated waveguide power splitter is proposed to feed antenna array elements in series. This feed network inherently provides uniform output power to eight quadrupole antennas. More importantly, it led to a compact configuration since the feed network can be integrated inside the elements without increasing the overall array size. Its design procedure is also presented. Then, a series feed network was used to feed a novel compact omnidirectional antenna array. Targeting the 5G 26 GHz mm-wave frequency band, simulated results showed that the proposed array exhibits a broad impedance bandwidth of 4.15 GHz and a high gain of 13.6 dBi, which agree well with measured results. Its attractive features indicate that the proposed antenna array is well suitable for millimeter-wave wireless communication systems.

Proteinase-activated receptor-2 (PAR-2) is a member of a family of G-protein-coupled, seven-transmembrane domain receptors that are activated by proteolytic cleavage. The receptor is expressed in a number of different tissues and potential physiological activators identified thus far include trypsin and mast cell tryptase. Acrosin, a trypsin-like serine proteinase found in spermatozoa of all mammals, was found to cleave a model peptide fluorescent quenched substrate representing the cleavage site of PAR-2. This substrate was cleaved with kinetics similar to those of the known PAR-2 activators, trypsin and mast cell tryptase. Acrosin was also shown to induce significant intracellular calcium responses in Chinese hamster ovary cells stably expressing intact human PAR-2, most probably due to activation of the receptor. Immunohistochemical studies using PAR-2 specific antibodies indicated that the receptor is expressed by mouse oocytes, which suggests that acrosin may play additional role(s) in the fertilization process via the activation of PAR-2 on oocytes.

Flavonoid glycosides are required for a number of crucial roles in planta and have the potential for development in a variety of agricultural, medicinal, and biotechnological applications. A number of recent advancements have been made in characterizing glycosyltransferases, the enzymes that are responsible for the synthesis of these important molecules. In this review, glycosyltransferases are considered with regard to biochemical properties, expression patterns, levels of enzyme activity during development, and structure/function relationships. This is presented with historical context to highlight critical findings, particularly with regard to the innovative work that has come from research on citrus species. The plant glycosyltransferase crystal structures that have been solved over the past decade, either alone or in complex with sugar donor and/or acceptor molecules, are discussed. The application of results from these structures to inform current structure/function work as well as implications and goals for future crystallography and tertiary modeling studies are considered. A thorough understanding of the properties of glycosyltransferases will be a critical step in any future biotechnological application of these enzymes in areas such as crop improvement and custom design of enzymes to produce desired compounds for nutritional and/or medicinal usage.

The Insulin Receptor Substrate (IRS) proteins IRS-1 and IRS-2 are cytoplasmic adaptor proteins that organize and propagate intracellular signaling downstream of specific growth factor receptors, including the Insulin and Insulin-Like Growth Factor-1 Receptors (IR and IGF-1R, respectively). Despite sharing a high level of homology and the ability to stimulate Phosphotidylinositol-3-Kinase (PI3K) and Mitogen-Activated Protein Kinase (MAPK) signaling, IRS-1 and IRS-2 play distinct roles in mammary tumor progression. Specifically, IRS-1 promotes growth and proliferation, whereas IRS- 2 promotes motility, invasion, survival, aerobic glycolyis, and metastasis. To further understand the differences between IRS-1 and IRS-2, I investigated the mechanistic basis of IRS-2-mediated PI3K activation. I identified tyrosines in IRS-2 that mediate its recruitment and activation of PI3K in response to insulin and IGF-1 stimulation. Using a PI3K-binding deficient IRS-2 mutant, I demonstrated that IRS-2-dependent PI3K signaling promotes aerobic glycolysis through its ability to selectively regulate the phosphorylation of the Akt effector Glycogen Synthase Kinase-3β (Gsk-3β). I also performed a rigorous comparison of IRS-1 and IRS-2 signal transduction and their ability to regulate functions associated with tumor progression. These studies required the generation of a novel model system where IRS-1 and IRS-2 function could be compared in a genetically identical background. Using this model, I confirmed a role for IRS-1 in growth regulation and IRS-2 in tumor cell invasion, as well as expanded the understanding of differential IRS protein function by showing that IRS-2 more vi effectively promotes Akt activation. The model system I have established can be used for further characterization of IRS-1 and IRS-2-specific functions.

>Magister Scientiae - MSc / Mining has a lengthy history in South Africa, and subsequent beneficiation processes have been conducted with little regard for the environment, thus leaving the land with un-rehabilitated abandoned mines. Currently, most of these abandoned mine sites are no longer operational and they continuously contaminate soil, air and water resources in various areas where mining took place. This study looks at the treatment of contaminated mine water using the Dispersed Alkaline Substrates (DAS) which is a new South African technology that uses a variety of substrates to neutralize and raise the pH of mine water while lowering the solubility of potentially dangerous metals.

Membrane-based filtration technologies have seen rapid inclusion in a variety of industrial processes, especially production of drinking water by desalination. Biological fouling of membranes is a challenge that leads to increased costs from efficiency reductions, membrane damage, and ultimately, membrane replacement over time. Such costs can be mitigated by monitoring and optimizing cleaning processes for better prognosis. A fluorescence-based sensor for early biofouling detection capable of measuring extracellular enzyme activity was developed. The selected fluorogen and fluorogen-substrate were characterized and down selected by in vitro screening for compatibility in seawater and profiled over relevant Red Sea desalination parameters (pH and temperature). ATP measurements are currently regarded as start-of-the-art when assessing biomass accumulation in membrane-based filtration systems Therefore, the fluorescence sensor response was measured for a range of bacterial concentrations and validated using an ATP assay. We demonstrate the efficacy of the proposed approach for the quantitative assessment of bacteria activity in seawater rapidly and sensitively. Following in vitro testing, the method was employed in a lab-scale seawater reverse osmosis (SWRO) system for suitability in monitoring biofouling formation. The sensor successfully measured bacterial biomass accumulation rapidly and non-invasively using exogenously applied fluorogen-substrates. The sensor response was corroborated with real-time in situ non-destructive imaging of the membrane surface. This approach demonstrates the practicality of prototyping an early-detection biofouling sensor in membrane based processes using extracellular enzyme activity as a measure of bacterial abundance.

Les circuits intégrés (CI) de puissance sont utilisés dans les systèmes embarqués automobiles en raison de leur capacité à réunir sur la même puce des dispositifs basse tension et haute tension (HV). Dans de tels systèmes, le bruit de couplage électrique induit par la commutation des étages de puissance est un problème majeur. Pendant la commutation, les tensions et les courants parasites produisent un décalage local de la tension de substrat allant jusqu'à une centaine de millivolt, perturbant ainsi le circuit basse tension. Ces signaux parasites entraînent des dysfonctionnements. Les solutions existantes reposent sur le layout et sont difficiles à optimiser par simulation électrique. L'absence d'une stratégie de modélisation interdit de fait une stratégie de conception s'appuyant sur la prédiction de ces perturbations. Nous présentons ici une méthode d'extraction et de simulation post-layout pour la modélisation des parasites de substrats. Nous avons développé un logiciel (CAO) pour l'extraction du substrat fondé sur la reconnaissance de forme. L'extraction utilise un algorithme de maillage pour la génération du modèle du substrat. Les courants de substrat peuvent être pris en compte lors de la simulation post-layout, autorisant l'analyse des dysfonctionnements éventuels induits par les couplages à travers le substrat. Ce travail a été validé par plusieurs cas d'études industriels, une configuration en miroir de courant, et un test automobile standard en technologie amsHV. Cette méthodologie est aussi appliquée à une technologie HV BCD de STMicroelectronics. Ainsi, en utilisant notre approche, il devient possible de simuler des bruits de substrat avant fabrication. / Smart Power Integrated Circuits (ICs) are intensively used in automotive embedded systems due to their unique capabilities to merge low power and high voltage (HV) devices on the same chip. In such systems, induced electrical coupling noise due to switching of the power stages is a big issue. During switching, parasitic voltages and currents, lead to a local shift of the substrate potential that can reach hundreds of millivolts, and can severely disturb low voltage circuits. Such parasitic signals are known to represent the major cause of failure and costly circuit redesign in power ICs. Most solutions are layout dependent and are thus difficult to optimize using available electrical simulator. The lack for a model strategy prohibits an efficient design strategy and fails at giving clear predictions of perturbations in HV ICs. Here, we present a post-layout extraction and simulation methodology for substrate parasitic modeling. We have developed a Computer-Aided-Design (CAD) tool for substrate extraction from layout patterns. The extraction employs a meshing algorithm for substrate model generation. The behavior of the substrate currents can be taken into account in post-layout simulation, and enables an exhaustive failure analysis due to substrate coupling. Several industrial test cases are considered to validate this work, the interferences of substrate currents in a current mirror configuration, and a standard automotive test in amsHV technology. This methodology is also applied to a HV BCD technology of STMicroelectronics. Eventually, by using the proposed CAD tool, it becomes possible to simulate the behaviors of substrate noises before fabrication.

A substrate was developed for measuring the milk clotting strength of rennet preparations on an automatic clot-timer . The substrate contained 8 percent pasteurized skim milk solids, 1 percent chloroform, 0.3 percent 200 bloom gelatin, 0.03 M added CaCl2 and was buffered to pH 6.6 with 0.057 M cacodylic acid and 0.042 M triethanolamine. The substrate was shelf-stable for 18 days at room temperatures. It was found that rennet preparations could be standardized to within 1 percent of each other, in terms of milk clotting strength, by use of the substrate on the automatic clot-timer. The method appears to have advantages over conventional rennet standardizing procedures. The research included studies on the effect of chloroform, nonfat dry milk and CaCl2 concentrations; heat and ionizing radiation on the substrate coagulation time.