NMDARs are indispensable for developmental plasticity in the mammalian brain, but their roles in vivo are difficult to ascertain as NMDAR-knockouts are lethal. To circumvent this problem, we utilized NR1-knockdown mice to examine plasticity at the calyx of Held-MNTB synapse in the auditory brainstem. Previous work shows NMDARs at this synapse are rapidly down-regulated following the onset of hearing (P12), leading to the hypothesis that transient NMDAR expression is indispensable for modulating functional and morphological remodelling during development. We tested this by performing electrophysiological recordings, fluorescence tracing in vitro, and auditory brainstem responses in vivo, and surprisingly found that reducing postsynaptic NMDARs appears to promote functional maturation via presynaptic mechanisms in the absence of morphological and acoustic transmission differences in the mature calyx. This suggests a novel role for NMDARs to function as an activity-dependent control for setting the pace of consolidation and maturation in the calyx of Held synapse.

The study uses Moving Average, On Balance Volume, and KD (Stochastic Oscillator) to analyze that the technical analysis in which the bull or bear stock markets is efficiency. Also, verifies the changes of market efficiency before and after the financial crisis and whether it can earn excess returns or not by using technical analysis. That is, the returns earned by using technical analysis significantly greater than buy and hold which means the efficiency of technical analysis. Nevertheless, the study also aims to realize that whether the returns of the portfolio of technical indicators better than unit indicator. The companies in our samples are selected by the size of market value top 30 companies in the industries of electronic and finance in order to avoid the effect of market micro structure. Our results are as follows: (1) The returns in bear market are significantly higher than bull market by using MA6-144. (2) The MA6-72 and MA6-144 of financial stock before financial crisis, the returns of technical analysis are significantly better than buy and hold. In the other hand, in the electronic stock, we can use MA6-22-250, KD, and OBV to beat the buy and hold strategy and verify that the market efficiency does not exist. (3) The returns which combine of KD and OBV indicators are significantly higher than KD.

Judicial discretion is at the heart of a humane criminal justice system, but the latitude exercisable in the UK juvenile courts allowed constructive treatment at one end of the spectrum and penal custody the other. Official acknowledgement of the different culpability of adult and juvenile offenders really began in the middle of the 19th century, and Parliament finally made provision early in the 20th century for this ‘welfare principle’, that reform and welfare rather than punishment were to guide judicial discretion in the decisions and conduct of juvenile criminal courts. This thesis offers an explanation for the varying emphasis given to this principle in England/Wales and Scotland, concentrating on the last 40 years of the 20th century. The lack of implementation of earlier reforms was confronted in two major reports, chaired by Kilbrandon in Scotland and Longford in England and Wales. Although they came to similar conclusions about the causes and the remedies for juvenile delinquency, and their subsequent legislation shared the same general philosophy, the implementation took diametrically different routes in the two jurisdictions. It is argued that deep-seated cultural and historical differences played a significant role both in legislative reforms and their application, coupled in Scotland with a conjunction of agency and political pragmatism that produced radical reforms. Significant factors implicated in the failure of the English reforms were political ambivalence towards the legislation; judicial/magisterial resistance or lack of training, particularly on child development; the absence of accountability in the magistracy; and the influence exercised by the Magistrates' Association. The research draws on archival papers and research literature, supplemented by interviews with key people. It has sought to find the origin of some influential ideas and explain their acceptance or rejection by the lay justices, through their exercise of judicial discretion. As there were further Acts related to juvenile defendants in both jurisdictions in the 1990s, the research was concluded with a consideration of their implementation.

Glucocorticoids are widely used in clinical therapy. However, they cause adverse effects including insulin resistance and Type 2 diabetes, which are characterised by decreased glucose transport into the muscles and fat. How glucocorticoids inhibit glucose transport remains unclear. Insulin stimulates glucose uptake via the insulin receptor substrate (IRS)-1 / phosphoinositide-3-kinase (PI3K) / protein kinase B (AKT) pathway and promotes the redistribution of GLUT4 from intracellular storage compartments to the plasma membrane (PM). Insulin-stimulated phosphorylation of AKT substrate of 160 kDa (AS160), a Rab-GTPase activating protein is downstream of AKT and appears to be essential for exposure of GLUT4 at the PM and glucose uptake. This is mediated through the association of phosphorylated AS160 (at the key residue T642) with 14-3-3 in the cytosol. The mildly insulin-responsive GLUT1 mediates basal glucose uptake in adipocytes. It is also subject to regulated trafficking like GLUT4. This study aimed to determine the level at which glucocorticoids inhibit glucose uptake in adipocytes. Effects of the synthetic glucocorticoid dexamethasone (Dex) and the natural glucocorticoid cortisol, on GLUT1 and GLUT4 function were examined. Candidates for the glucocorticoid-mediated inhibition of GLUT1- and GLUT4-mediated glucose uptake were investigated. These were glycogen synthase kinase (GSK) 3β (an AKT substrate) for GLUT1-mediated glucose transport; and adaptor protein containing PH domain, PTB domain, and leucine zipper motif (APPL)-1 (an AKT-interacting protein) and AS160 for GLUT4-mediated glucose transport. Dex and cortisol significantly decreased basal glucose uptake by 50% (p<0.05) in SGBS and 3T3-L1 adipocytes. Similarly, insulin-stimulated glucose uptake was decreased by 50% (p<0.001 for SGBS; p<0.05 for 3T3-L1) and 30% (p<0.05 for both) at 1 nM and 100 nM insulin respectively. Similar results were observed with differentiated primary human preadipocytes and human adipose explants. Dex-mediated inhibition of basal glucose uptake was limited to insulin-sensitive cell types implying that glucocorticoids may regulate GLUTs at steps common to GLUT1 and GLUT4 trafficking. Dex-mediated reduction in glucose uptake correlated with the reduction in basal and insulin-stimulated expression of GLUT1 and GLUT4 to the PM without changes in total GLUT1/4 expression. Dex did not alter total expression or phosphorylation of proximal insulin-signalling molecules up to and including AKT but increased FOXO1 expression, and modified GSK3β-S9 phosphorylation. Dex did not alter total APPL1 expression or subcellular distribution. Dex significantly decreased 1nM-insulin stimulated AS160-T642 phosphorylation by 50% (p<0.05) in SGBS and 3T3-L1 adipocytes via the glucocorticoid repector (GR). This correlated with reduced AS160:14-3-3 interaction. Similar results were obtained for AS160-T642 basal phosphorylation. At 1nM insulin, AS160-T642 phosphorylation is maximal at sub-maximal glucose uptake, i.e. AS160 phosphorylation significantly contributes to glucose uptake. RU486 significantly prevented but did not fully abrogate the Dex-mediated reduction in glucose uptake suggesting additional Dex-induced defects. In conclusion, glucocorticoids inhibit glucose uptake at a level distal to AKT by GR-dependent mechanisms. A role for GSK3β or APPL1 in glucocorticoid-mediated inhibition of glucose uptake requires further investigations. FOXO1 represents a suitable candidate for mediating the Dex-induced defects. Of significance, perturbation in AS160-T642 phosphorylation contributes to Dex-mediated inhibition of glucose uptake. Thus, AS160 presents a novel therapeutic target in the improvement of glucocorticoid-mediated inhibition of glucose uptake.

The study will examine the introduction of the computerisation of crime and intelligence recording in three police forces in the United Kingdom in the decade 1976-1986. The thesis will critique the roles and actions of the main players in this decade, The Home Office in London England, three provincial police forces, Kent County Constabulary, Humberside Police and Lothian and Borders Police, and the computer supply industry. The study will consider the concept of ‘crime' from a jurisprudential viewpoint and will consider the legal imposition on chief officers of police to collect, store and distribute certain crime based data. The study will also examine and analyse in detail three computer projects in different police forces. The use of new, complex and expensive computer programs is highlighted with the introduction of free text searching of large data sources and the need for large scale mainframe computers to handle the analysis and storage of that data. The limited success of two police projects will question the requirement for central government control of publicly funded new technology. The study will examine strategic planning in the process, as well as the rush to be the first police force to embrace the new technology. Further the study will review central government control over public spending, in the first police force based computerisation projects. In conclusion, the thesis will suggest that new police systems should be scaled to local needs and guided by expert central advice. Additionally, chief police officers should be encouraged to use new technology in a strategic manner, sharing outcomes in open fora. Possible new research problems are listed and evaluated.

Police around the world present evidence to suspects at different points during the interview. Some psychologists suggest that police should strategically delay disclosing evidence and test the truthfulness of a suspect’s account by comparing it with the evidence. Moreover, psychologists suggest interviewers who plan strategic evidence disclosure might be less guilt-presumptive about the suspect because they must consider alternative explanations of the evidence as part of their planning. In contrast, many lawyers argue that police should not strategically disclose evidence as it undermines a suspect’s fair trial rights and prevents lawyers from advising suspects effectively before the interview. To address these conflicting perspectives from the domains of psychology and law, this thesis takes an interdisciplinary approach and considers strategic evidence disclosure within the broader legal context of a suspect’s custodial detention. First, a field study of police disclosure briefings with lawyers, lawyer-client consultations, and police interviews, and a survey of lawyers highlights how lawyers rely upon the police’s evidence to advise suspects in custody. When police strategically disclose evidence, lawyers cannot provide informed legal advice and tend to advise suspects to not answer police questions. Second, three experiments and a mini meta-analysis show that generating alternative evidential explanations for criminal cases, as interviewers planning strategic evidence disclosure might do, has a very small effect, or plausibly no effect, on people’s beliefs about the suspect’s guilt. Finally, a mock crime experiment shows that, even two months after a crime, truthful suspects’ accounts fit evidence that was strategically withheld more than deceptive suspects’ accounts did. Independent laypeople from a follow-up experiment could distinguish between these truthful and deceptive accounts. Together, these findings suggest that strategic evidence disclosure could help deception detection even months after a crime, but it also impinges upon suspects’ legal rights and is unlikely to make interviewers less guilt-presumptive.

Chapter 1 introduces the topic of third party funding of litigation which is a recent phenomenon in academic circles. Few of the existing papers on commercial litigation funding are empirically based and those that are, with one exception, use surveys and interviews to collect data. Within the legal boundaries of litigation funding, economic theory predicts that in perfectly competitive markets consumers control what is supplied, prices cover costs without excessive profits and inefficient producers are eliminated. However reality rarely conforms to prediction, and regulation may be appropriate in the public interest to overcome market failures arising from information asymmetries. The research focus is: ‘How effectively are commercial third party litigation funders governed and/or regulated?’ Chapter 2 proceeds to consider the literature on regulation, it’s applicability to litigation funding and the interests of stakeholders. A major concern is the ability of a litigation funder to pay the costs of a winning defendant. The conclusion reached in Chapter 3 is that litigation funders have too much choice in the way they report and disclose information and what they actually report and disclose is deficient in meeting the needs of investors. In Chapter 4, using single firm event study methodology I discover that the stock exchange market does not always react as predicted to disclosure by litigation funders and consequently the market is not an adequate proxy for a regulator. Chapter 5 extends chapter 3 on the solvency issue and also considers other stakeholder issues e.g. ethical ones which may require regulation. The conclusion reached is that a light touch independent regulator overseen by the legal services board would be appropriate. This work narrows the literature gap for empirically based economic research and augments and extends the existing literature by examining third party funding of heterogeneous high value, low volume cases in contrast to homogenous, low value, high volume cases. It is the first work on the accounting regulation of litigation funding. This work will also assist investors, the judiciary and other stakeholders to better evaluate the risks of this new industry.

Denna studie gick ut på att jämföra tre olika algoritmer som har använts för bred kollisionsdetektering, dessa algoritmer var Kd-tree, Octree och Sweep and prune. Kd-tree och Octree är spatiala datastrukturer, d.v.s. att de hanterar objekt inom specifika volymer. Sweep and prune använder istället listor för att ta reda på om objekt kolliderar. Fokus låg på att se hur stor skillnad algoritmernas exekveringstid hade jämfört med ’brute force’-implementationen och jämfört med varandra. Det utfördes ett antal olika experiment på algoritmerna med ett antal olika inställningar för att kunna utvärdera hur de presterar i olika situationer. Dessa inställningar var t.ex. antalet boids, deras hastighet och hur långt de kunde se. Resultatet visade att Sweep and prune presterade bäst med en liten mängd boids medans de andra algoritmerna kom ikapp och presterade bättre när antalet objekt ökade, då Kd-tree presterade bäst överlag. Studien kan vara till hjälp med att välja vilken bred kollisionsdetekteringsalgoritm som kan tänkas implementeras för en applikation.

Context. Ray tracing has always been a simple but effective way to create a photorealistic scene but at a greater cost when expanding the scene. Recent improvements in GPU and CPU hardware have made ray tracing faster, making more complex scenes possible with the same amount of time needed to process the scene. Despite the improvements in hardware ray tracing is still rarely run at a interactive speed. Objectives. The aim of this experiment was to implement a new kdtree generation algorithm using DirectX 11 compute shaders. Methods. The implementation created during the experiment was tested using two platforms and five scenarios where the generation time for the kd-tree was measured in milliseconds. The results where compared to a sequential implementation running on the CPU. Results. In the end the kd-tree generation algorithm implemented did not run within our definition of real-time. Comparing the generation times from the implementations shows that there is a speedup for the GPU implementation compared to our CPU implementation, it also shows linear scaling for the generation time as the number of triangles in the scene increase. Conclusions. Noticeable limitations encountered during the experiment was that the handling of dynamic structures and sorting of arrays are limited which forced us to use less memory efficient solutions.

The principle of equality in the workplace, enshrined in the Sex Discrimination Act 1975, applies to a wide category of workers. However, there are certain exceptions to the legislation. Ministers of religion are not protected by the Act where employment is limited to one sex. Historically "employment" as a Church of England priest was limited to one sex. Then in 1993, following the momentous General Synod vote, legislation was passed which allowed women to be ordained as priests. A significant change had taken place regarding the theology of the Church. This shift in theology also brought the legal position of priests, in relation to sex discrimination, into question. An initial question was, should such priests be protected by secular employment legislation? if so, what are the legal difficulties of inclusion under the Sex Discrimination Act, and what are the practical difficulties of accommodation under the Act? These questions form the foundation stones of this thesis. A four stage process was used to answer these questions. First, a philosophical analysis of the theory behind sex discrimination law was undertaken, focusing on the concepts of equality and difference. Secondly, the position of the Church of England in relation to sex discrimination law was assessed with special reference to the employment status of ministers of religion. Thirdly, drawing on the theoretical work of stages one and two, an empirical investigation into the treatment of Church of England priests was conducted. The fourth stage built upon the empirical findings and the theoretical framework. British and European Community sex discrimination law was critically analysed, as was the relevant ecclesiastical law, and recommendations for law reform were made.