Building functional thin-film-transistor (TFT) circuits is crucial for applications such as wearable, implantable and transparent electronics. Therefore, developing a compact model of an emerging semiconductor material for accurate circuit simulation is the most fundamental requirement for circuit design. Further, unique analogue building blocks are needed due to the specific properties and non-idealities of TFTs. This dissertation reviews the major developments in thin-film transistor (TFT) modelling for the computer-aided design (CAD) and simulation of circuits and systems. Following the progress in recent years on oxide TFTs, we have successfully developed a Verilog-AMS model called the CAMCAS model, which supports computer-aided circuit simulation of oxide-TFTs, with the potential to be extended to other types of TFT technology families. For analogue applications, an accurate small signal model for thin film transistors (TFTs) is presented taking into account non-idealities such as contact resistance, parasitic capacitance, and threshold voltage shift to exhibit higher accuracy in comparison with the adapted CMOS model. The model is used to extract the zeros and poles of the frequency response in analogue circuits. In particular, we consider the importance of device-circuit interactions (DCI) when designing thin film transistor circuits and systems and subsequently examine temperature- and process-induced variations and propose a way to evaluate the maximum achievable intrinsic performance of the TFT. This is aimed at determining when DCI becomes crucial for a specific application. Compensation methods are reviewed to show examples of how DCI is considered in the design of AMOLED displays. Based on these design considerations, analogue building blocks including voltage and current references and differential amplifier stages have been designed to expand the analogue library specifically for TFT circuit design. The $V_T$ shift problem has been compensated based on unique circuit structures. For a future generation of application, where ultra low power consumption is a critical requirement, we investigate the TFT’s subthreshold operation through examining several figures of merit including intrinsic gain ($A_i$), transconductance efficiency ($g_m/I_{DS}$) and cut-off frequency ($f_T$). Here, we consider design sensitivity for biasing circuitry and the impact of device variations on low power circuit behaviour.

The instability behaviour of detonation waves are studied using Fickett's model with a 2-step reaction model with separately controlled induction and reaction zones. This model acts as a simplified toy-model to the reactive Euler equations allowing for more clarity of the detonation phenomenon. We numerically simulate a 1D self-supported detonation and investigate the pulsating instability behaviour. We are able to clarify the governing mechanism behind the pulsations through a characteristic analysis describing the coupling that takes place between the amplification of the compressions waves and the alteration to the induction timing. We examine the acceleration phase of the pulsations and determine an analytical solution to describe the strength of the amplification. Fickett's model is as well shown to reproduce the same period doubling bifurcation with increasing sensitivity of the induction rate, and route to chaos as seen in the full reactive Euler equations.

The work of this thesis is guided by the Analogue Gravity research programme, in which condensed matter systems are used as analogues of the physics of curved spacetimes to obtain new perspectives on open problems of gravitational physics. Here we use this idea to investigate the phenomenon of superradiance, most famously occurring in rotating black hole spacetimes, using as an analogue system atomic Bose-Einstein condensates (BECs). Superradiance is a radiation enhancement phenomenon in which waves of different kind are scattered with an increased amplitude by extracting energy from the object they are scattering on. In this thesis on the one hand we use the gravitational analogy to understand better superradiance starting from easier analogue setups, and on the other hand we use concepts coming from superradiance to learn something about the physics of BECs. We first present a (possibly realizable) toy model, built using the tools of synthetic gauge fields for neutral atoms, to provide a new and conceptually simple illustration of superradiant scattering. This toy model allows to disentangle the different elements at play and highlight the basic mechanisms of superradiance and has also the interesting feature of being exactly mappable to a scattering problem of a charged scalar field on an electrostatic potential. We also show how at the quantum level, superradiance implies the spontaneous emission of pairs of excitations. The low temperatures of atomic condensates can make these quantum features visible and we propose a way of detecting them via correlation measurements. Another realization of this toy model can also be built using periodic trapping potentials for the atoms. By changing the boundary conditions of the acoustic excitations of the condensate we show how superradiance can give rise to dynamical instabilities. Our toy model gives a simple illustration of superradiant instabilities occurring in rotating gravitational spacetimes, in particular ergoregion instabilities and black hole bombs. It also provides a realization of the analogous instabilities involving a charged scalar field, called the Schiff-Snyder-Weinberg effect. Our approach naturally shows how amplified scattering can also occur in the presence of dynamical instabilities, a point often object of confusion in the literature. Moreover, we add an acoustic horizon to our toy model and show that, differently from what happens in general relativity, horizons do not always prevent the presence of ergoregion instabilities. We then apply these concepts to the study of the stability of quantized vortices in two-dimensional BECs. With a careful account of boundary conditions, we show that the dynamical instability of multiply quantized vortices in trapped condensates persists in untrapped, spatially homogeneous geometries and has an ergoregion nature with some modification due to the peculiar dispersion of Bogoliubov sound. Our results open new perspectives to the physics of vortices in trapped condensates, where multiply quantized vortices can be stabilized by interference effects and singly charged vortices can become unstable in suitably designed trap potentials. We show how superradiant scattering can be observed also in the short-time dynamics of dynamically unstable systems, providing an alternative point of view on dynamical (in)stability phenomena in spatially finite systems. Finally we consider the equivalent of a shear layer between parallel flows in hydrodynamics, but in a BEC. In the present case the shear layer is constituted by and array of quantized vortices that are shown to develop an instability analogous to the Kelvin-Helmholtz instability. When the relative velocity between the two parallel flow is sufficiently large however, this instability is quenched and substituted by a slower instability that has the features of the superradiant instabilities we studied. Differently from superradiant instabilities, this one also remains with open boundary conditions on the two sides of the shear layer, and manifests itself as a continuous emission of phonons in both directions; we call this new regime radiative instability.

No / The azinomycins are potent antitumour antibiotics that are able to crosslink DNA, but are relatively unstable and unlikely to progress as therapeutic candidates. A prototype analogue 4 with more clinical potential has been designed and synthesised and incorporates the epoxide function of the azinomycins and a nitrogen mustard. Two further analogues 5 and 6 that can alkylate DNA but cannot crosslink the duplex have also been synthesised. Compound 4 crosslinks DNA efficiently at nM concentrations. Compounds 4¿6 were submitted to the NCI 60 cell line screen and have similar antitumour activity, although 4 is slightly less active than the non-crosslinking compounds. These observations will be important in the design of further azinomycin analogues with antitumour activity.

Les analogues de choline constituent une nouvelle classe d'antipaludiques qui inhibent la biosynthèse de la phosphatidylcholine (PC) de Plasmodium, parasite responsable du paludisme. Les études conduites ont mis en relief des particularités uniques de ces composés. Nous avons élucidé le mécanisme d'action biochimique de l'albitiazolium, actuel candidat clinique, caractérisant chacune des 5 étapes conduisant à la biosynthèse de PC. L'albitiazolium affecte en premier lieu l'entrée de choline dans le parasite intraerythrocytaire, choline et albitiazolium utilisant le même transporteur et affecte de façon différentielle les autres étapes de synthèse. L'activité antipaludique est fortement antagonisée par la choline indiquant que le mécanisme d'action primaire est bien l'inhibition de la synthèse de PC. L'accumulation des analogues de choline dans le parasite intracellulaire leur permet de restreindre leur toxicité aux seuls érythrocytes infectés. Des études comparatives réalisées chez Plasmodium et Babesia montrent une double compartimentation de l'albitiazolium uniquement chez Plasmodium, l'une d'elles correspondant à la vacuole digestive. L'accumulation chez Plasmodium est glucose-dépendante et exige aussi le maintien des gradients ioniques dans la cellule. Bien que les analogues de choline exercent leur effet antiparasitaire dès les premières heures de contact, l'effet dit « cheval de Troie » exige des conditions particulières pour les mesures d'activités pharmacologiques, nous amenant à comparer différents tests d'activité. Seuls les tests isotopiques basés sur l'incorporation d'hypoxanthine ou d'éthanolamine après un cycle parasitaire entier et le test fluorescent au SYBR green appliqué après 72h obtiennent des résultats fiables quel que soit le mécanisme d'action des antipaludiques. Enfin, des études de pharmacocinétique / pharmacodynamie montrent une exposition plasmatique supérieure chez les souris infectées par Plasmodium, due au recyclage de l'albitiazolium après son accumulation dans l'érythrocyte infecté. / Choline analogues form a new class of antimalarial drugs that inhibit the biosynthesis of phosphatidylcholine (PC) in Plasmodium, the malaria-causing parasite. The studies presented here highlighted the unique features of these compounds. We elucidated the biochemical mechanism of action of albitiazolium, the current clinical candidate, characterizing each of the 5 steps leading to the biosynthesis of PC. Albitiazolium primarily affects the entry of choline into the intraerythrocytic parasite and choline and albitiazolium use the same carrier. The other steps of synthesis are differentially affected. Antimalarial activity is strongly antagonized by choline indicating that the primary mechanism of action is the inhibition of PC synthesis Accumulation of choline analogs in the intracellular parasite allows them to restrict their toxicity to infected erythrocytes. Comparative studies in Plasmodium and Babesia show a double compartmentalization of albitiazolium only in Plasmodium, one of them corresponding to the food vacuole. Accumulation in Plasmodium is glucose-dependent and requires maintaining ionic gradients in the cell.Although choline analogues exert their antiparasitic effect in the first hours of contact, the “Trojan horse effect” requires specific conditions for the determination of pharmacological activity, leading us to evaluate various tests of activity. Only the isotopic tests based on hypoxanthine or ethanolamine incorporation after one parasite cycle and the fluorescent SYBR green assay applied after 72 hours give reliable results regardless of the mode of action of the tested antimalarials. Finally, pharmacokinetics/pharmacodynamics studies in Plasmodium-infected mice revealed that albitiazolium is recycled after its accumulation in the infected erythrocyte leading to increased plasma levels.

The resistor ladder (R/2R) digital-to-analogue converter (DAC) architecture is often used in high performance audio solutions due to its low-noise performance. Even high-end R/2R DACs suffer from static nonlinearity distortions. It was suspected that compensating for these nonlinearities would be possible. It was also suspected that this could improve audio quality in audio systems using R/2R DACs for digital-to-analogue (A/D) conversion. Through the use of models of the resistor ladder architecture a way of characterizing and measuring the faults in the R/2R DAC was created. A compensation algorithm was developed in order to compensate for the nonlinearities. The performance of the algorithm was simulated and an implementation of it was evaluated using an audio evaluation instrument. The results presented show that it is possible to increase linearity in R/2R DACs by compensating for static nonlinearity distortions. The increase in linearity can be quite significant and audible for the trained ear.

Le projet de recherche consiste à observer en laboratoire la radiation de Hawking, cette prédiction stupéfiante de l'astrophysicien anglais Stephen Hawking faite en 1974 : les trous noirs ne sont pas noirs. Autrement dit, ils n'absorbent pas tout ce qui est à leur portée mais émettent un rayonnement. En plus des complications du fait que ces objets célestes sont à des milliers d'années-lumière, ce rayonnement est tellement faible que cela reviendrait à essayer d'entendre un murmure dans un concert de rock. Mais William Unruh, en 1981, a proposé une solution : utiliser des systèmes hydrodynamiques qui présentent les mêmes équations mathématiques qu'en astrophysique. Plus précisément, dans notre cas, nous utilisons la correspondance entre la propagation des ondes lumineuses au voisinage d'un trou noir et celles des ondes de surface dans un contre-courant rendu inhomogène par la présence d'un obstacle immergé. Pour cela, une compréhension approfondie de la mécanique des ondes de surface est nécessaire (bathymétrie variable, vorticité, non-linéarités…). Du côté technique, une méthode de mesure de surface libre a été développée et optimisée. / The aim of the PhD is the observation the Hawking radiation in the laboratory, this astounding prediction of the English astrophysicist Stephen Hawking made in 1974: black holes are not black. In other words, they do not absorb anything within reach but emit a radiation. In addition to the complications of the fact that these celestial objects are thousands of light years away, this radiation is so weak that it would be like trying to hear a whisper in a rock concert. But William Unruh, in 1981, proposed a solution: to use hydrodynamic systems which have the same mathematical equations as in astrophysics. More precisely, in our case, we use the correspondence between the propagation of light in the vicinity of a black hole and surface waves propagation on a inhomogeneous countercurrent (due to the presence of a submerged obstacle). For this, a thorough understanding of the surface waves physics is necessary (variable bathymetry, vorticity, non-linearities ...). On the technical side, a free surface measurement method has been developed and optimized.

This thesis consists of 3 studies: 1. Determination of the minimal important difference (MID) of the visual analogue scale for dyspnoea (VASD): Determining the MID of the VASD is essential to interpret the results of trials in patients with malignant pleural effusions (MPEs). Patients undergoing a pleural procedure assessed the change in their VASD and the degree of change in their symptoms on a Likert scale. The mean VASD in patients experiencing a ‘small but just worthwhile’ decrease in their symptoms is the MID for the VASD and was found to be 22mm (95% CI 16 - 27mm). 2. Development of a thoracic ultrasound septation score (TUSS): A TUSS is important for objectively assessing the degree of septation within a pleural effusion. An iterative process was used to demonstrate that degree of septation predicts clinical outcome, to identify candidate factors for inclusion in a TUSS and to determine which factors predicted the degree of septation. The final TUSS consisted of an assessment of the degree of homogeneity of septation distribution and number of septations at the most septated area. 3. Effect of an indwelling pleural catheter (IPC) versus standard care for relieving dyspnoea in patients with MPEs: the TIME2 randomised controlled trial (RCT). The objective of this unblinded RCT was to determine whether IPCs are more effective than chest drains and talc pleurodesis at relieving dyspnoea in patients with MPEs. 106 patients were randomised to either IPC or standard care in a 1:1 ratio. The primary outcome was daily VASD over 42 days post intervention. Dyspnoea improved in both groups with no significant difference in mean dyspnoea in the first 42 days (mean score: IPC 25mm (95% CI 19 – 30), standard care 24mm (95% CI 19 – 29)).

Les glycanes présents à la surface des cellules cancéreuses sont souvent modifiés par rapport à ceux d’une cellule saine. Or ces antigènes glucidiques n’induisent pas de réponse immune efficace. La GalNAc est le premier sucre fixé lors de la O-glycosylation de type mucine et ainsi ce sucre entre dans la composition de nombreux antigènes tumoraux. Le but de notre travail était de préparer des analogues synthétiques de la GalNAc susceptibles d’être incorporés à la surface de cellules cancéreuses et dans les mucines synthétisées par les tumeurs, afin d’augmenter la réponse immune vis-à-vis des glycanes tumoraux. Nous avons synthétisé chimiquement des analogues de la GalNAc afin de les tester in vitro en tant que substrats de la voie de « sauvetage » de la GalNAc chez les mammifères et donc d’enzymes impliquées dans cette voie : une kinase (GK2) et une UDP-pyrophosphorylase (AGX1) humaines. Les meilleurs candidats ont permis la synthèse de différents UDP-sucres et une GalNAc-transférase (ppGalNAc T1) bovine a pu être utilisée in vitro pour transférer certains de ces analogues, à partir de leur forme activée en UDP-sucre, sur des peptides. Nous avons donc pu montrer que certains des analogues synthétisés étaient capables de s’intégrer dans la voie de sauvetage et d’être incorporés dans des peptides. Le pouvoir immunologique des glycoconjugués de type mucine ainsi formés a été étudié chez la souris après couplage de ces glycoprotéines à une protéine immunostimulante (KLH). D’autre part, des cellules de mammifères ont également été cultivées en présence de ces analogues afin de vérifier leur incorporation au niveau des glycoconjugués de la surface des cellules. / Glycans are often present at the cancerous cell surface in a modified form compared to healthy cells. However, these carbohydrate antigens don’t lead to an effective immune response. GalNAc is the first sugar attached to mucin type O-glycans and is thus a component of numerous tumor antigens. The aim of our work was to prepare synthetic GalNAc analogs able to be incorporated at the surface of cancer cell and into mucins synthesized by tumors in order to increase the immune response toward tumor glycans. We chemically synthesized GalNAc analogs to test them in vitro as substrates of enzymes involved in the mammalian GalNAc salvage pathway: a human galactokinase (GK2) and a human UDP-pyrophosphorylase (AGX1). The best candidates allowed the synthesis of the corresponding UDP-sugars further used to test the transfer of those analogs onto peptides using a bovine GalNAc transferase (ppGalNAc T1). We have shown that some synthetic analogs could be integrated in the GalNAc salvage pathway and O-linked to peptides. Immunological properties of the glycoconjugates thus formed were studied in mice after coupling to an immunostimulant protein (KLH). Moreover, mammalian cells were cultivated in the presence of these analogs in order to check their incorporation into glycoconjugates at the cell surface.

Student Number: 0416806D MA Art and Culture Management 2004 Faculty of Humanities / British broadcasting has undergone significant change in recent years, as the nation prepares to switch from analogue to digital broadcasting. This process has already begun, with the full switch over to the digital platform scheduled in Britain for 2012. Appropriately, at the forefront of the development of digital broadcasting in Britain is its public broadcaster: The BBC. In line with both government, and organisational objectives, the BBC has developed a range of new television, and radio channels aimed at providing a service that will continue to be appropriate to audiences further into the twenty-first century. This research examines the output of two BBC music radio stations, Radio One and 1xtra, considering how changes to management, policy, and strategy in each station can affect the output they broadcast. Radio One and 1xtra both use a strategy of broadcasting new music to target a youth audience. However, Radio One is a mixed-genre station broadcasting on analogue radio, while 1xtra is a niche station broadcasting on the digital platform. By comparing the stations I attempt to draw conclusions about the BBC’s digital strategy, and what implications these have for the output of both Radio One and 1xtra in the digital age. Discussion in the first half of the research focuses on the internal operations of the BBC. I consider the BBC’s approach to the diversity of the content it broadcasts, and what this approach reveals about the different priorities of the organisation. Close examination of the management changes made at both an organisational, and individual station level provide further insight into the context guiding priorities and policy decisions made in the BBC, Radio One, and 1xtra. The second half of the research pays greater attention to the actual output broadcast by Radio One and 1xtra, using content analysis methodology to measure similarities, and differences between the two stations. Through the simultaneous examination of management and policy changes, and of the output broadcast by the two stations, I aim to make conclusions about how changes made internally have had a direct impact on the diversity of music broadcast on Radio One and 1xtra.