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The contraction of skeletal muscle during exercise that occurs in the absence of muscle damage has been demonstrated to yield a significant increase in the release of potentially anti-inflammatory myokine interleukin-6 (IL-6). Increased generation of IL-6 may be valuable in managing inflammatory states, such as chronic kidney disease (CKD). However, the IL-6 output of CKD patients during muscular exercise may be unusually weak, due to factors such as metabolic acidosis. In CKD, physical exertion has been reported to lower levels of amino acids in muscles in vivo. This effect may be attributable to uraemic metabolic acidosis and exercise-induced acidosis impairing mitogen-activated protein kinases (MAPKs) such as p38, which normally activate the amino acid transporter SNAT2. The SNAT2 transporter protein is also known to be directly and rapidly inhibited by low pH. The resulting intracellular amino acid depletion could, in turn, result in inhibited protein synthesis, and hence reduced production of IL-6. This study sought to test the following hypotheses: (1) higher levels of IL-6 expression occur in mechanically stressed skeletal muscle cells following in vitro mechanical stretch, arising from the activation of MAPKs, followed by activation of SNAT2; and (2) low pH blocks this process. Experiments on L6 rat skeletal muscle cells showed that drug inhibition of MAPKs inhibited SNAT2 transport activity, confirming that MAPKs play a role in the regulation of SNAT2 and, by extension, in the availability of amino acids for protein synthesis. Interestingly, while P-p38 and P-JNK activation significantly increased after cyclic stretching of 1-10 minutes duration, SNAT2 activity significantly increased only transiently i.e. after periods of stretching lasting 1 minute, suggesting that this transporter may paradoxically be inhibited by prolonged stretching. In addition, mRNA of IL-6 was increased after 30 minutes of intermittent stretching and, (as previously reported elsewhere) by 6 hours of Ca2+ loading of the cells with ionomycin which activates p38. The siRNA silencing of SNAT2 in L6 myoblasts decreased gene expression of the mRNA of IL-6, suggesting that SNAT2 can influence IL-6 expression. As SNAT2 and MAPKs, particularly p38 and JNK, are inhibited at low pH, it would be predicted that low pH (pH 7.1) would decrease IL-6 expression. However, both with and without ionomycin, low pH failed to decrease IL-6 mRNA; indeed with ionomycin low pH strongly activated IL-6 expression. It is concluded that even though the acidosis-sensing amino acid transporter SNAT2 may play some role in regulating IL-6 expression (as previously hypothesised), a distinct and novel stimulatory effect of low pH over-rides this and maybe a more important regulator of IL-6 expression in L6 skeletal muscle cells.

The purpose of this thesis is to present new different spaces as attempts to generalize the concept of topological vector spaces. A topological vector space, a well-known concept in mathematics, is a vector space over a field \mathbb{F} with a topology that makes the addition and scalar multiplication operations of the vector space continuous functions. The field \mathbb{F} is usually \mathbb{R} or \mathbb{C} with their standard topologies. Since every vector space is a finitary matroid, we define two spaces called finite matroidal spaces and matrological spaces by replacing the linear structure of the topological vector space with a finitary matroidal structure. The idea is to combine a finitary matroidal closure operator like the linear closure operator with a topological closure operator into a single closure operator called a common closure operator. Therefore, one may take a set with a finitary matroidal closure operator and a topological closure operator like the topological vector space. The study starts with basic definitions, some fundamental properties and a collection of examples. The finite matroidal spaces and matrological spaces are then presented. Furthermore, the idea of a common closure operator is introduced and then a discussion is given of when to obtain from a set and a common closure operator a finite matroidal space or a matrological space. Finally, relationships of topological vector spaces with both finite matroidal spaces and topological vector spaces are presented.

High temperature oxidation of fuel cladding materials, during the loss of coolant accident (LOCA), is of utmost importance for next-generation nuclear energy systems. Ti2AlC is a promising candidate material for nuclear applications due to its outstanding properties such as thermal stability at high temperatures, oxidation resistance in air, thermal shock resistance, low neutron absorption cross-section, and the resistance to irradiation-induced amorphization. In this research, high temperature steam oxidation experiments were conducted to evaluate the oxidation resistance of Ti2AlC in LOCA conditions. After oxidation in 100% steam at 600 and 800˚C, the oxidation kinetics followed a parabolic rate law while it followed a cubic rate law at 1000˚C. The oxide microstructure initially consisted of a thin, discontinuous outer layer of TiO2 and a continuous inner layer of Al2O3. As the temperature was increased, the concentration of Al2O3 increased in the outer scale, resulting in an excellent oxidation resistance. The steam flow rate accelerates the oxidation kinetics, and this effect is the greatest at 600˚C, at which the oxide scale is porous and cracked. This was likely attributed to stresses generated in the oxide scale due to the phase transformation of TiO2 from anatase to rutile phase. Advisor: Bai Cui