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No description available.

Friedreich ataxia (FRDA) is an autosomal recessive, neurodegenerative disorder with severely debilitating effects and no current cure. FRDA is mainly caused by the hyper-expansion of a GAA repeat present in intron 1 of the FXN gene, which results in decreased gene expression and consequently a deficiency of the mitochondrial protein frataxin. In the first instance, frataxin deficiency renders an impaired protection from oxidative stress. Antioxidant therapy with cannabinoids (CBD and THC) and CTMIO was investigated in GAA repeat FXN YAC transgenic mouse models of FRDA, but no significant improvements were detected on functional measurements such as rotarod performance and locomotor activity. Additionally such compounds failed to protect the brain of treated mice from oxidative insults. Therefore, the use of such antioxidant compounds cannot be advocated for FRDA therapy. Recent findings indicate that FXN silencing in FRDA may be mediated by repressive heterochromatin, suggesting the use of histone deacetylase inhibitors (HDACi) as FXN up-regulators. Therefore, therapy with a benzamide-type HDACi (106) was similarly investigated on the FXN YAC GAA mouse model. No significant improvements were detected by functional and histochemical analysis. However, significant changes were produced in global acetylation levels of H3 and H4 in the brain of treated mice, suggesting that the drug is capable of crossing the blood-brain barrier and producing an effect. Additionally, significant increases in frataxin expression were detected in the brain of treated mice. To identify further FRDA disease mechanisms, characterization of the FXN gene for the presence of the CCCTC-binding factor (CTCF) was also performed on FRDA patient cerebellum samples. Overall, lower levels of CTCF were detected in FRDA-associated FXN alleles, suggesting the potential involvement of CTCF in the regulation of FXN transcription.

The first measurement of the ratio of the W and Z cross sections in association with a single jet, known as the R_{Jets} measurement, is presented. The measurement was performed using 33pb^-1 of integrated luminosity, recorded during the year 2010 by the ATLAS detector at the LHC. At this time the LHC was operating at a center-of-mass energy of 7 TeV. The measurement is made as a function of the threshold on the jet transverse momentum, from 30 GeV up to a value of 200 GeV. The motivation for this measurement is outlined in terms of providing a stringent test of the Standard Model of particle physics, as well as a model independent tool for searching for new physics. Data driven tools are developed to perform the measurement and their performance is discussed. The result of the measurement is compared with the predictions of Next-to-Leading order perturbative QCD and found to be in good agreement over the entire range of transverse momenta considered.

This thesis explores the modelling for Internal Rating Based (IRB) of Credit Risk for Small and Medium Enterprises (SMEs) as required for implementation of Basel II Accord. There has been limited previous research for this important sector of the economy. There are two major approaches: Accounting Based and Merton Type, and these are compared. To make the comparison initially a small sample is considered and simulation is used to explore the use of the two approaches. The study indicates some of the limitation of analysis for both Accounting Based and Merton Type approaches, for example the issue of colinearity for the Accounting Based approach and lack of trading of SMEs’ equity affecting the Merton Type approach. A large sample is then investigated using standard Credit Scoring approaches for the Accounting Based modelling. Different definitions of default and distress are considered to overcome the problem of low number of defaults. These approaches are found to be viable. Merton Type model is then compared to benchmark models from the Accounting Based approach. The predictions are compared over differing time horizons. It is found that Merton Type models perform well within a limited period compared to the Accounting Base approach. Overall, credit scoring models demonstrated better performance when the sample group included a considerable number of ‘Bad’ firms or cutoff point was selected so that an acceptance rate was relatively low, otherwise model’s predictive accuracy would decline. Merton model presented better predictive accuracy with higher acceptance rates. Credit scoring models was able to give early signs of default year. In addition, one may take into consideration that if the company is going to decline credit quality or raise default probability this year, Merton type models can be helpful in adjusting credit rating. When considering a loan to a company, a bank wants to know the likelihood default for duration of loan. In this sense Merton models is only useful for a relatively short loan terms.

Large mass splittings between new scalars in two-Higgs-doublet models (2HDM) open a key avenue to search for these new states via exotic heavy Higgs decays. We discuss in detail the different search channels for these new scalars at the LHC in the presence of a sizable mass splitting, i.e. a hierarchical 2HDM scenario, taking into account the theoretical and experimental constraints. We provide benchmark planes to exploit the complementarity among these searches, analyzing their potential to probe the hierarchical 2HDM parameter space during LHC Run 2.

The Eady problem is modified to allow for a non-zero ß parameter but retaining a zero meridional gradient of potential vorticity. Two different basic states are examined for which analytical solutions of the linearized quasi-geostrophic potential vorticity equation were obtained. As has to be expected in addition to the short wave cutoff to instability a non-zero ß parameter implies a long wave cutoff, too. In both cases the solutions turn out to converge towards the classical Eady solution if ß-70. lt is found that the qualitative structure of the phase speed diagramm and also the qualitative shape of the vertical structure of the unstable solutions turned out to be rather insensitive to the specific settings of the basic state. / Das klassische Eadyproblem wird auf die ß-Ebene verlagert, wobei der Grundstrom so modifiziert wird, daß der meridionalen Gradienten der potentiellen Vorticity nach wie vor verschwindet. Zwei verschiedene Grundzustände werden untersucht, für die analytische Lösungen der linearisierten potentiellen Vorticitygleichung erhalten werden konnten. Wie man erwarten konnte, bedingt die Einführung eines von Null verschiedenen ß-Parameters das Auftreten einer Langwelleninstabilitätsgrenze zusätzlich zu der Kurzwelleninstabilitätsgrenze des klassischen Problems. In beiden Fällen konnte weiterhin gezeigt werden, daß die Lösungen für ß-70 gegen die klassischen Eadylösungen konvergieren. Ferner stellte sich heraus, daß die qualitative Struktur des Phasengeschwindigkeitsdiagramms und die qualitative Gestalt der Vertikalstruktur der instabilen Lösungen relativ unempfindlich gegenüber der genauen funktionalen Darstellung des Grundzustandes sind.

To evaluate and test control systems designed for heavy duty hydraulic excava-tor, it is important to simulate the force acting on the bucket during its excavation process. The study of soil-tool interaction contributes to the prediction and simula-tion of resistive forces experienced at the tool during digging. Even though many different finite element (FE) models have been developed in the past to study soil-tool interaction process, there is still needs to study the effects of soil-tool friction coefficient. The main objective of this thesis is to utilize finite element model to simulate the soil-tool interaction process, with the focus on the application of excavation, to study the effects of soil-tool friction coefficient on soil failure zone, soil resistive force, and stress distribution on the cutting tool by utilizing finite element model to simulate the soil-tool interaction process. / October 2016

In this article, I introduce a novel airborne network mobility model, called the Smooth Turn Mobility Model, that captures the correlation of acceleration for airborne vehicles across time and spatial coordinates. E?ective routing in airborne networks (ANs) relies on suitable mobility models that capture the random movement pattern of airborne vehicles. As airborne vehicles cannot make sharp turns as easily as ground vehicles do, the widely used mobility models for Mobile Ad Hoc Networks such as Random Waypoint and Random Direction models fail. Our model is realistic in capturing the tendency of airborne vehicles toward making straight trajectory and smooth turns with large radius, and whereas is simple enough for tractable connectivity analysis and routing design.