Human congenital heart disease (CHD) is the most common cause of non-infectious neonatal death affecting 1-2% of live births (Hoffman and Kaplan, 2002). Treatment of CHD requires major surgery and quality of life is often significantly reduced despite treatment. With the discovery of single gene mutations that cause CHD in model animals (Lyons et al., 1995), the role of genetics in CHD has become appreciated. The genetic basis of CHD is poorly understood, with different members of the same family presenting with different types of CHD (Schott et al., 1998), suggesting the causes of CHD are multifactorial. Cardiogenesis is intimately associated with the establishment of the left-right (L-R) body axis, with the two processes sharing several important transcription factors. Heart looping, in which the heart turns dextrally, is the earliest physical manifestation of L-R asymmetry. L-R patterning disorders are associated with an increased risk of CHD; heterotaxy (in which L-R asymmetry is neither normal nor mirror image) accounts for about 3% of all CHD (Zhu et al., 2006).Investigating cardiogenesis and the causes of CHD necessitates the use of animal models, typically mice, chicks, zebrafish and Xenopus. Recently a strain of mouse with a mutation in a gene essential for cardiac development was isolated from an ENU mutagenesis screen (Kile et al., 2003) using mice carrying a balancer chromosome. It has been subsequently found that the most likely candidate gene codes for the protein Prpf8, an integral component of the spliceosome. The mutation is homozygous lethal, with homozygous mice having a grossly deformed heart, developmental delay and a high incidence of heart looping reversal, indicative of a L-R patterning disorder. In depth characterisation of homozygous mutant embryos revealed defects in the morphology of the embryonic node, nodal cilia and the expression pattern of L-R axis genes. We also investigated the expression of Prpf8 during embryogenesis, and the effect that the point mutation we found in our homozygous embryos has on splicing kinetics.

The measure-multiplicity-invariant for masas in II_1 factors was introduced by Dykema, Smith and Sinclair to distinguish masas that have the same Pukanszky invariant. In this dissertation, the measure class (left-right-measure) in the measuremultiplicity- invariant is studied, which equivalent to studying the structure of the standard Hilbert space as an associated bimodule. The focal point of this analysis is: To what extent the associated bimodule remembers properties of the masa. The structure of normaliser of any masa is characterized depending on this measure class, by using Baire category methods (Selection principle of Jankov and von Neumann). Measure theoretic proofs of Chifan's normaliser formula and the equivalence of weak asymptotic homomorphism property (WAHP) and singularity is presented. Stronger notions of singularity is also investigated. Analytical conditions based on Fourier coefficients of certain measures are discussed, that partially characterize strongly mixing masas and masas with nontrivial centralizing sequences. The analysis also provide conditions in terms of operators and L2 vectors that characterize masas whose left-right-measure belongs to the class of product measure. An example of a simple masa in the hyperfinite II1 factor whose left-right-measure is the class of product measure is exhibited. An example of a masa in the hyperfinite II1 factor whose leftright- measure is singular to the product measure is also presented. Unitary conjugacy of masas is studied by providing examples of non unitary conjugate masas. Finally, it is shown that for k greater than/equal to 2 and for each subset S \subseteq N, there exist uncountably many non conjugate singular masas in L(Fk) whose Pukanszky invariant is S u {1}.

Networks at various levels of the nervous system coordinate different motor patterns such as respiration, eye or hand movements and locomotion. Intrinsic rhythm-generating networks that are located in the spinal cord generate motor behaviors that underlie locomotion in vertebrates. These networks give a continuous and measurable coordinated rhythmic motor output and are referred to as locomotor central pattern generators (CPGs). Characterization of the mammalian locomotor CPG and its molecular control is depending on the identification of participating neurons and neuronal populations. In this thesis I present work where we have studied the significance of subpopulations of neurons in the formation and function of the left-right circuitry. In summary, we show that the axon guidance receptor DCC has a central role in the formation of spinal neuronal circuitry underlying left-right coordination, and that both Netrin-1 and DCC are required for normal function of the locomotor CPG. Commissural interneurons (CINs), which send their axons across the ventral midline in the spinal cord, play a critical role in left–right coordination during locomotion. A complete loss of commissural axons in the spinal cord, as seen in the Robo3 null mutant mouse, resulted in uncoordinated fictional locomotor activity. Removing CIN connections from either dorsal or ventral neuronal populations led to a shift from alternation to strict synchronous locomotor activity. Inhibitory dI6 CIN have been suggested as promising candidate neurons in coordinating bilateral alternation circuitry. We have identified that Dmrt3, expressed in inhibitory dI6 CINs, is a crucial component for the normal development of coordinated locomotor movements in both horses and mice. We have also concluded that the prominent hopping phenotype seen in hop/hop mice is a result of abnormal developmental processes including induction from the notochord and Shh signaling. Together, these findings increase our knowledge about the flexibility in neuronal circuit development and further confirm the role of dI6 neurons in locomotor circuits.

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Since its birth at the time of the French Revolution, Left/Right has been a key tool for understanding politics. This thesis investigates how we think about politics using Left/Right: how it shapes, constrains and interacts with our most deeply-held conceptions of politics, how its meaning and implications have developed historically and in the British context, and why it might warrant the attention of the student of ideologies. After outlining the methodological underpinnings of the study and histories of Left/Right, the thesis examines uses of Left/Right in a range of contexts of actual thinking about politics. Left/Right is widely used in both the academic study of politics and popular commentary on British politics. The early New Left in Britain in the late 1950s and early 1960s is studied as a group attempting to influence the discourse around the political label “the Left”; a section of the neo-conservative New Right in Britain in the 1980s, around The Salisbury Review, is analysed as a political group with a complicated relationship to the political label “the Right”. Left/Right emerges as an element of the contested “common sense” of politics. Further, it is argued that some elements of common sense, such as Left/Right, may be expressed through narratives. Left/Right is theorized as a political narrative, or as a story about politics. The concept of political narrative explores the possibility that Left/Right may be susceptible to “interpretation”, both in terms of the assumptions about how politics is done and how politics should be done that underlie it, and more complexly in its relationship with a master narrative of political conflict understood as class struggle. Students of ideologies can learn much about how we think about and do our politics by attending to Left/Right.

Political scientists have sought to unify under a single theoretical umbrella the explanations for the patterns of public opinion in the electorate and the patterns of party policy. Yet, these models have not taken account of potential differences between left-wingers and right-wingers in the ways that policy preferences are bundled together across multiple dimensions of political disagreement. The dissertation examines the origins and structure of political opinions on three dimensions of left/right disagreement: wealth redistribution, social morality, and immigration. The overall argument is that the content and structure of opinions are fundamentally intertwined. As a result, left/right disagreement is multidimensional and asymmetrical. Left-wingers and right-wingers derive from different sources, and structure in different ways, their opinions about policy. These asymmetries appear in the patterns of public opinion, the preferences of party activists, and in the positioning of political parties.

Political scientists have sought to unify under a single theoretical umbrella the explanations for the patterns of public opinion in the electorate and the patterns of party policy. Yet, these models have not taken account of potential differences between left-wingers and right-wingers in the ways that policy preferences are bundled together across multiple dimensions of political disagreement. The dissertation examines the origins and structure of political opinions on three dimensions of left/right disagreement: wealth redistribution, social morality, and immigration. The overall argument is that the content and structure of opinions are fundamentally intertwined. As a result, left/right disagreement is multidimensional and asymmetrical. Left-wingers and right-wingers derive from different sources, and structure in different ways, their opinions about policy. These asymmetries appear in the patterns of public opinion, the preferences of party activists, and in the positioning of political parties.

The left-right concept is considered to facilitate communication and orientation in the political world. It has a long tradition in European politics due to its capacity to absorb different associations over time. However, this dynamic nature of the concept requires periodical reassessments in order to assure that a common conceptualisation endures. This dissertation focuses on reassign what individual left-right orientation means. Usually, this is measured by asking people to place themselves on a scale labelled ‘left’ and ‘right’ at its endpoints. The first empirical analysis of this dissertation shows that this measure is comparable across groups and countries. Thereafter, the relationship between an individual’s issue preference and left-right orientation is considered. The second empirical analysis shows that this relationship is conditioned by the importance people assign to the respective issues. The final analysis demonstrates that what explains left-right orientation is contingent on individual and contextual factors. This implies that in order to understand left-right orientation, it is not enough to identify what has an impact on a person’s position but also account for all those factors that predict variation between individuals. Given this complexity, my conclusion is that the left-right concept runs the risk of becoming too complicated to serve as an analytical tool to shed light on political attitudes and behaviour. / El concepte esquerra-dreta és considerat com un factor facilitador de la comunicació en el món polític. Té una llarga tradició’ en la política europea degut a la seva capacitat d’absorbir diferents associacions a través del temps. Tanmateix, aquesta natura dinàmica del concepte requereix revisions periòdiques per assegurar que persisteix una conceptualització comuna. La present tesi es centra en resignar el que significa l’orientació esquerra-dreta. Normalment, es mesura tot demanant als enquestats posicionar-se a ells mateixos en una escala que va de l’esquerra a la dreta. El primer anàlisi empíric de la present tesi mostra que aquesta mesura és comparable entre grups i països. Seguidament, es considera la relació entre les preferències temàtiques dels individus i llur orientació esquerra-dreta. El segon anàlisi empíric mostra que aquesta relació està condicionada per la importància que les persones assignen als temes respectius. L’anàlisi final demostra que el que explica l’orientació esquerra-dreta depèn de factors contextuals i individuals. Això implica que per entendre l’orientació esquerra-dreta no és suficient identificar què té un impacte en la posició d’una persona sinó també una explicació per a tots aquells factors que preveuen la variació entre individus. Donada aquesta complexitat, la meva conclusió és que el concepte esquerra-dreta corre el risc de convertir-se en massa complicat per a servir com a eina analítica per a l’estudi de les actituds i el comportament politics.

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