DNA Mutation of the progranulin (GRN) gene in familial frontotemporal lobar degeneration (FTLD):a study of the pathology of nine cases

Frontotemporal lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) proteinopathy (FTLD-TDP) is a neurodegenerative disease characterized by variable neocortical and allocortical atrophy principally affecting the frontal and temporal lobes. Histologically, there is neuronal loss, microvacuolation in the superficial cortical laminae, and a reactive astrocytosis. A variety of TDP-43 immunoreactive changes are present in FTLD-TDP including neuronal cytoplasmic inclusions (NCI), neuronal intranuclear inclusions (NII), dystrophic neurites (DN) and, oligodendroglial inclusions (GI). Many cases of familial FTLD-TDP are caused by DNA mutations of the progranulin (GRN) gene. Hence, the density, spatial patterns, and laminar distribution of the pathological changes were studied in nine cases of FLTD-TDP with GRN mutation. The densities of NCI and DN were greater in cases caused by GRN mutation compared with sporadic cases. In cortical regions, the commonest spatial pattern exhibited by the TDP-43 immunoreactive lesions was the presence of clusters of inclusions regularly distributed parallel to the pia mater. In approximately 50% of cortical gyri, the NCI exhibited a peak of density in the upper cortical laminae while the GI were commonly distributed across all laminae. The distribution of the NII and DN was variable, the most common pattern being a peak of NII density in the lower cortical laminae and DN in the upper cortical laminae. These results suggest in FTLD-TDP caused by GRN mutation: 1) there are greater densities of NCI and DN than in sporadic cases of the disease, 2) there is degeneration of the cortico-cortical and cortico-hippocampal pathways, and 3) cortical degeneration occurs across the cortical laminae, the various TDP-43 immunoreactive inclusions often being distributed in different cortical laminae.

A study of liquid-liquid extraction in a sieve plate column

The literature relating to sieve plate liquid extraction columns and relevant hydrodynamic phenomena have been surveyed. Mass transfer characteristics during drop formation, rise and coalescence, and related models were also reviewed. Important design parameters i.e. flooding, dispersed phase hold-up, drop size distribution, mean drop size, coalescence/flocculation zone height beneath a plate and jetting phenomena were investigated under non-mass transfer and mass transfer conditions in a 0.45m diameter, 2.3m high sieve plate column. This column had provision for four different plate designs, and variable plate spacing and downcomer heights, and the system used was Clairsol `350' (dispersed) - acetone - deionised water (continuous) with either direction of mass transfer. Drop size distributions were best described by the functions proposed by Gal-or, and then Mugele-Evans. Using data from this study and the literature, correlations were developed for dispersed phase hold-up, mean drop size in the preferred jetting regime and in the non-jetting regime, and coalescence zone height. A method to calculate the theoretical overall mass transfer coefficient allowing for the range of drop sizes encountered in the column gave the best fit to experimental data. This applied the drop size distribution diagram to estimate the volume percentage of stagnant, circulating and oscillating drops in the drop population. The overall coefficient Kcal was then calculated as the fractional sum of the predicted individual single drop coefficients and their proportion in the drop population. In a comparison between the experimental and calculated overall mass transfer coefficients for cases in which all the drops were in the oscillating regime (i.e. 6.35mm hole size plate), and for transfer from the dispersed(d) to continuous(c) phase, the film coefficient kd predicted from the Rose-Kintner correlation together with kc from that of Garner-Tayeban gave the best representation. Droplets from the 3.175mm hole size plate, were of a size to be mainly circulating and oscillating; a combination of kd from the Kronig-Brink (circulating) and Rose-Kintner (oscillating) correlations with the respective kc gave the best agreement. The optimum operating conditions for the SPC were identified and a procedure proposed for design from basic single drop data.

A study of adaptive load balancing algorithms for distributed systems

With the advent of distributed computer systems with a largely transparent user interface, new questions have arisen regarding the management of such an environment by an operating system. One fertile area of research is that of load balancing, which attempts to improve system performance by redistributing the workload submitted to the system by the users. Early work in this field concentrated on static placement of computational objects to improve performance, given prior knowledge of process behaviour. More recently this has evolved into studying dynamic load balancing with process migration, thus allowing the system to adapt to varying loads. In this thesis, we describe a simulated system which facilitates experimentation with various load balancing algorithms. The system runs under UNIX and provides functions for user processes to communicate through software ports; processes reside on simulated homogeneous processors, connected by a user-specified topology, and a mechanism is included to allow migration of a process from one processor to another. We present the results of a study of adaptive load balancing algorithms, conducted using the aforementioned simulated system, under varying conditions; these results show the relative merits of different approaches to the load balancing problem, and we analyse the trade-offs between them. Following from this study, we present further novel modifications to suggested algorithms, and show their effects on system performance.

Differences in market-oriented behaviour levels across firms' domestic and export marketing operations:a study of antecedents and consequences

Researchers are beginning to recognise that organisations often have different levels of market orientation across different aspects of their operations. Focusing on firms involved in export marketing, this study examines how market-oriented behaviour differs across firms' domestic and export marketing operations. In this respect, the study is the first of its kind since it investigates three main issues: (1) to what extent do differences exist in firms' levels of market-oriented behaviour in their domestic markets (i.e., their domestic market-oriented behaviour) and in their export markets (i.e., their export market-oriented behaviour), (2) what are the key drivers of such differences, and (3) what are the performance implications for firms of having different levels of domestic and export market-oriented behaviour. To shed light on these research questions, data were collected from 225 British exporting firms using a mail questionnaire. Structural equation modelling techniques were used to develop and purify measures of all construct of interest, and to test the theoretical models developed. The results indicate that many of businesses sampled have very different levels of market orientation in their domestic and exporting operations: typically, firms tend to be more market-oriented in their domestic markets relative to their export markets. Several key factors were identified as drivers of differences in market orientation levels across firms' domestic and export markets. In particular, it was found that differences were more pronounced when: (i) interfunctional interactions between domestic marketing and export marketing are rare, (ii) when domestic and export marketing follow asymmetric business strategies, (iii) when mutual dependence between the functions is low, (iv) when one or other of the functions dominates the firm's sales, and (v) when there are pronounced differences in the degree to which the domestic and the export markets are experiencing environmental turbulence. The consequences of differences in market-oriented behaviour across firms' domestic and export markets were also studied. The results indicate that overall sales performance of firms (as determined by the composite of firms' domestic sales and export sales performance) is positively related to levels of domestic market-oriented behaviour under high levels of environmental turbulence in firms' domestic markets. However, as domestic market turbulence decreases, so to does the strength of this positive relationship. On the other hand, export market-oriented behaviour provides a positive contribution to firms' overall sales success under conditions of relatively low export market turbulence. As the turbulence in export markets increases, this positive relationship becomes weaker. These findings indicate that there are numerous situations in which it is sub-optimal for firms to have identical levels of market-oriented behaviour in their domestic and exporting operations. The theoretical and practical implications of these findings are discussed.

A simulation study of a localised computer network

An investigation is carried out into the design of a small local computer network for eventual implementation on the University of Aston campus. Microprocessors are investigated as a possible choice for use as a node controller for reasons of cost and reliability. Since the network will be local, high speed lines of megabit order are proposed. After an introduction to several well known networks, various aspects of networks are discussed including packet switching, functions of a node and host-node protocol. Chapter three develops the network philosophy with an introduction to microprocessors. Various organisations of microprocessors into multicomputer and multiprocessor systems are discussed, together with methods of achieving reliabls computing. Chapter four presents the simulation model and its implentation as a computer program. The major modelling effort is to study the behaviour of messages queueing for access to the network and the message delay experienced on the network. Use is made of spectral analysis to determine the sampling frequency while Sxponentially Weighted Noving Averages are used for data smoothing.

Translation strategies and cross-cultural contraints : a case study of the translation of advertising texts

Since the transfer of a message between two cultures very frequently takes place through the medium of a written text qua communicative event, it would seem useful to attempt to ascertain whether there is any kind of pattern in the use of strategies for the effective interlingual transfer of this message. Awareness of potentially successful strategies, within the constraints of context, text type, intended TL function and TL reader profile will enhance quality and cost-effectiveness (time, effort, financial costs) in the production of the target text. Through contrastive analysis of pairs of advertising texts, SL and TL, French and English, this study will attempt to identify the nature of some recurring choices made by different translators in the attempt to recreate ST information in the TL in such a manner as to reproduce as closely as possible the informative, persuasive and affective functions of the text as advertising material. Whilst recurrence may be seen to be significant in terms of illustrating tendencies with regard to the solution of problems of translation, this would not necessarily be taken as confirmation of the existence of pre-determined or prescriptive rules. These tendencies could, however, be taken as a guide to potential solutions to certain kinds of context-bound and text-type specific problem. Analysis of translated text-pairs taken from the field of advertising should produce examples of constraints posed by the need to select the content, tone and form of the Target Text, in order to ensure maximum efficacy of persuasive effect and to ensure the desired outcome, as determined by the Source Text function. When evaluating the success of a translated advertising text, constraints could be defined in terms of the culture-specific references or assumptions on which a Source Text may build in order to achieve its intended communicative function within the target community.

Combining an enterprise resource planning system and informality:a study of efficiency and flexibility complmentarity [sic]

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT One of the current research trends in Enterprise Resource Planning (ERP) involves examining the critical factors for its successful implementation. However, such research is limited to system implementation, not focusing on the flexibility of ERP to respond to changes in business. Therefore, this study explores a combination system, made up of an ERP and informality, intended to provide organisations with efficient and flexible performance simultaneously. In addition, this research analyses the benefits and challenges of using the system. The research was based on socio-technical system (STS) theory which contains two dimensions: 1) a technical dimension which evaluates the performance of the system; and 2) a social dimension which examines the impact of the system on an organisation. A mixed method approach has been followed in this research. The qualitative part aims to understand the constraints of using a single ERP system, and to define a new system corresponding to these problems. To achieve this goal, four Chinese companies operating in different industries were studied, all of which faced challenges in using an ERP system due to complexity and uncertainty in their business environments. The quantitative part contains a discrete-event simulation study that is intended to examine the impact of operational performance when a company implements the hybrid system in a real-life situation. Moreover, this research conducts a further qualitative case study, the better to understand the influence of the system in an organisation. The empirical aspect of the study reveals that an ERP with pre-determined business activities cannot react promptly to unanticipated changes in a business. Incorporating informality into an ERP can react to different situations by using different procedures that are based on the practical knowledge of frontline employees. Furthermore, the simulation study shows that the combination system can achieve a balance between efficiency and flexibility. Unlike existing research, which emphasises a continuous improvement in the IT functions of an enterprise system, this research contributes to providing a definition of a new system in theory, which has mixed performance and contains both the formal practices embedded in an ERP and informal activities based on human knowledge. It supports both cost-efficiency in executing business transactions and flexibility in coping with business uncertainty.This research also indicates risks of using the system, such as using an ERP with limited functions; a high cost for performing informally; and a low system acceptance, owing to a shift in organisational culture. With respect to practical contribution, this research suggests that companies can choose the most suitable enterprise system approach in accordance with their operational strategies. The combination system can be implemented in a company that needs to operate a medium amount of volume and variety. By contrast, the traditional ERP system is better suited in a company that operates a high-level volume market, while an informal system is more suitable for a firm with a requirement for a high level of variety.

A corpus-assisted study of the discourse marker well as an indicator of judges' institutional roles in court cases with litigants in person

In this paper, I concentrate on court cases with litigants in person (lay people who act on their own behalf in legal proceedings without a counsel or solicitor) and discuss the challenges of building a corpus of courtroom discourse where it is crucial to distinguish between speakers due to their distinct institutional roles. The corpus incorporates seven sub-corpora of verbatim transcripts from different court cases with litigants in person and comprises over eleven-million tokens. The focus of this paper is on the interplay between the legal and lay discourse types and how judges project their institutional roles through well-initiated turns directed at litigants in person and counsels. As a versatile discourse marker, well provides a good opportunity to explore how judges have to adapt their roles to ensure lay litigants in person receive the necessary support and that their lack of competence does not impede on the fairness of the proceedings. Given the breadth and importance of the topic of litigation in person, I discuss how the tools and approaches of corpus linguistics can be helpful in this multi-disciplinary area where multiple functions and uses of individual linguistic features need to be explored in depth.

Contesting human rights through institutional reform:a case study of the reform of the UK Equality and Human Rights Commission

This article presents a case study of the recent reform of the United Kingdom Equalities and Human Rights Commission, to address a critical gap in the literature on national human rights institutions (NHRIs) concerning the power of governments to exert control over these institutions through reform processes. Through this analysis, the article demonstrates, first, that NHRIs are affected by contextual factors not only related to the popularity of the human rights agenda but also to wider policy agendas which impact on their status and functions; and second, that attempts by government to exert more administrative control can be significantly problematic for the operational independence of NHRIs.