Defining the metabolic effect of peroxisome proliferator-activated receptor δ activation

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that function as ligand activated transcription factors. There are three identified isotypes: PPAR alpha, PPAR gamma and PPAR delta, together controlling the expression of genes involved in inflammation, cell differentiation, proliferation, lipid and carbohydrate metabolism and energy homeostasis. The PPARs are potential targets for the treatment of dyslipidaemia, type II diabetes mellitus and the metabolic syndrome. This thesis uses a multi-platform metabolomics approach, 13C-isotope substrate flux analysis, respirometry and transcriptomics to determine the role PPAR delta and PPAR gamma play in metabolic control both in adipose tissue and systemically. To achieve this, the metabolic phenotype of the 3T3-L1 adipocyte cell line was defined to generate a metabolically phenotyped in vitro model of adipose tissue. The importance of fatty acid alpha-oxidation in the differentiation of adipocytes was emphasised The effects of PPAR delta and PPAR gamma activation in white adipose tissue from the ob/ob mouse model of insulin resistance, and in the phenotyped 3T3-L1 adipocyte model, were investigated. PPAR delta activation was distinguished by oxidative catabolism of fatty acids and citric acid cycle intermediates. Conversely, PPAR gamma activation was identified by the sequestration of lipids into adipose tissue. Moreover, to address the systemic influence of PPAR activation, with a focus on the Cori cycle and the interactions of the liver and skeletal muscle, the metabolic changes that occur in these tissues following PPAR delta and PPAR gamma activation in the ob/ob mouse were examined. PPAR delta activation was characterised by the mobilisation and release of triacylglycerols (TAGs) into circulation as an energy source for peripheral tissues whereas PPAR gamma activation was defined by a reduction and sequestration of circulating TAGs. This thesis has better characterised the role of the PPARs as master regulators of metabolism and emphasised their potential as therapeutic targets for metabolic diseases of global importance.This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC)and GlaxoSmithKline plc

Analysis of selected problems involving vortical flows

Three selected problems involving vortical flows are analyzed and discussed including: the trailing vortex behind a wing; rotor blade-vortex interaction; and the leading edge vortex on a flat plate

Two blowing concepts for roll and lateral control of aircraft

Two schemes to modulate aerodynamic forces for roll and lateral control of aircraft have been investigated. The first scheme, called the lateral blowing concept, consists of thin jets of air exiting spanwise, or at small angle with the spanwise direction, from slots at the tips of straight wings. For this scheme, in addition to experimental measurements, a theory was developed showing the analytical relationship between aerodynamic forces and jet and wing parameters. Experimental results confirmed the theoretically derived scaling laws. The second scheme, which was studied experimentally, is called the jet spoiler concept and consists of thin jets exiting normally to the wing surface from slots aligned with the spanwise direction

Searching for physics beyond the Standard Model through the dipole interaction

The magnetic dipole interaction played a central role in the development of QED, and continued in that role for the Standard Model. The muon anomalous magnetic moment has served as a benchmark for models of new physics, and the present experimental value is larger than the standard-model value by more than three standard deviations. The electric dipole moment (EDM) violates parity ({$P$}) and time-reversal ({$T$}) symmetries, and in the context of the $CPT$ theorem, the combination of charge conjugation and parity ($CP$). Since a new source of {$CP$} violation outside of that observed in the $K$ and $B$ meson systems is needed to help explain the baryon asymmetry of the universe, searches for EDMs are being carried out worldwide on a number of systems. The standard-model value of the EDM is immeasurably small, so any evidence for an EDM would signify the observation of new physics. Unique opportunities exist for EDM searches using polarized proton, deuteron or muon beams in storage rings. This talk will provide an overview of the theory of dipole moments, and the relevant experiments. The connection to the transition dipole moment that could produce lepton flavor violating interactions such as $\mu^+ \rightarrow e^+ \gamma$ is also mentioned.Comment: Invited Plenary talk at the 19th International Spin Physics Symposium, Juelic

Electrospun Nanofiber Coating of Fiber Materials: A Composite Toughening Approach

Textile-based composites could significantly benefit from local toughening using nanofiber coatings. Nanofibers, thermoplastic or otherwise, can be applied to the surface of the fiber tow bundle, achieving toughening of the fiber tow contact surfaces, resulting in tougher and more damage-resistant/tolerant composite structures. The same technique could also be applied to other technologies such as tape laying, fiber placement, or filament winding operations. Other modifications to the composite properties such as thermal and electrical conductivity could be made through selection of appropriate nanofiber material. Control of the needle electric potential, precursor solution, ambient temperature, ambient humidity, airflow, etc., are used to vary the diameter and nanofiber coating morphology as needed. This method produces a product with a toughening agent applied to the fiber tow or other continuous composite precursor material where it is needed (at interfaces and boundaries) without interfering with other composite processing characteristics

Method for Coating a Tow with an Electrospun Nanofiber

Method and apparatus for enhancing the durability as well as the strength and stiffness of prepreg fiber tows of the sort used in composite materials are disclosed. The method involves adhering electrospun fibers onto the surface of such composite materials as filament-wound composite objects and the surface of prepreg fiber tows of the sort that are subsequently used in the production of composite materials of the filament-wound, woven, and braided sorts. The apparatus performs the methods described herein

The Government needs to catch up with early years professionals

Last month, at the height of the pandemic, we were asked by the STA (Standards and Testing Agency) to review Test Items for its third attempt at Reception Baseline Assessment (RBA) in September 2023

Status of the Fermilab Muon (g-2) Experiment

The New Muon $(g-2)$ Collaboration at Fermilab has proposed to measure the anomalous magnetic moment of the muon, $a_\mu$, a factor of four better than was done in E821 at the Brookhaven AGS, which obtained $a_\mu = [116 592 089 (63)] \times 10^{-11}$ $\pm 0.54$ ppm. The last digit of $a_{\mu}$ is changed from the published value owing to a new value of the ratio of the muon-to-proton magnetic moment that has become available. At present there appears to be a difference between the Standard-Model value and the measured value, at the $\simeq 3$ standard deviation level when electron-positron annihilation data are used to determine the lowest-order hadronic piece of the Standard Model contribution. The improved experiment, along with further advances in the determination of the hadronic contribution, should clarify this difference. Because of its ability to constrain the interpretation of discoveries made at the LHC, the improved measurement will be of significant value, whatever discoveries may come from the LHC.Comment: Proceedings of the PhiPsi09, Oct. 13-16, 2009, Beijing, China, 4 pages 2 figures. Version 2 includes Fermilab report number, minor corrections and one additional referenc

Control of threshold voltage in E-mode and D-mode GaN-on-Si metal-insulator-semiconductor heterostructure field effect transistors by in-situ fluorine doping of atomic layer deposition Al2O3 gate dielectrics

We report the modification and control of threshold voltage in enhancement and depletion mode AlGaN/GaN metal-insulator-semiconductor heterostructure field effect transistors through the use of in-situ fluorine doping of atomic layer deposition Al2O3. Uniform distribution of F ions throughout the oxide thickness are achievable, with a doping level of up to 5.5 × 1019 cm−3 as quantified by secondary ion mass spectrometry. This fluorine doping level reduces capacitive hysteretic effects when exploited in GaN metal-oxide-semiconductor capacitors. The fluorine doping and forming gas anneal also induces an average positive threshold voltage shift of between 0.75 and 1.36 V in both enhancement mode and depletion mode GaN-based transistors compared with the undoped gate oxide via a reduction of positive fixed charge in the gate oxide from +4.67 × 1012 cm−2 to −6.60 × 1012 cm−2. The application of this process in GaN based power transistors advances the realisation of normally off, high power, high speed devices