Multisubstrate adduct inhibitors: Drug design and biological tools

In drug discovery, different methods exist to create new inhibitors possessing satisfactory biological activity. The multisubstrate adduct inhibitor (MAI) approach is one of these methods, which consists of a covalent combination between analogs of the substrate and the cofactor or of the multiple substrates used by the target enzyme. Adopted as the first line of investigation for many enzymes, this method has brought insights into the enzymatic mechanism, structure, and inhibitory requirements. In this review, the MAI approach, applied to different classes of enzyme, is reported from the point of view of biological activity.

Agitating for a design and regeneration agenda in a postconflict city: the case of Belfast

Introduction

Belfast has been a focus of academic attention for the last forty years with most interest centred on various aspects of ‘the Troubles’. Where there has been interest in the built environment, it has largely been about how the ‘security situation’ impacted directly on architecture and on the design and layout of social housing. This paper seeks to go beyond this to explore how the political- administrative culture of ‘the Troubles’ interacted with ‘normal’ market forces to shape the central area of the city, and to consider the responses of a recently formed activist group, known as the Forum for Alternative Belfast (hereafter referred to as the Forum). The paper is written by three of the directors of the Forum.1 Moreover, the empirical research presented here was undertaken by the Forum as part of a campaign to address issues relating to the design, layout and quality of Belfast’s built environment. In the longstanding tradition of participant observation working within an action-research paradigm, the participants have attempted to offer an account that is evidentially and purposefully selfcritical and reflective. It is of course recognised that while this approach offers many positive attributes, such as phenomenological access through immersion in the project, it also has the potential to bring compromise on research detachment and objectivity.2 To address the latter, the authors have attempted
to avoid polemical argument, and to support claims with primary or secondary research evidence. The authors also acknowledge that action-research has a chequered history; however, they would argue
that their approach is faithful to a concept that sees ‘research’ defined as understanding and ‘action’ defined as seeking change. The Forum’s very purpose is to seek change, but to do this requires evidence, collaboration and demonstration. And in this sense, it is a learning process for all participants, including the research activists, government officials, community organisations and students. The authors also recognise the complexity of factors that affect urban management and change, particularly in a city such as Belfast, which has had to cope with political violence for over thirty years. And they appreciate that in the context of conflict, governance is skewed to cope with political realities. Hamdi reminds us, however, that in practice there is an ‘important dialectic between top-down planning, with its formal and designed laws and structures, and bottom-up selforganizing collectivism—those “quantum and emergent systems” which Jane Jacobs argued long ago give cities their life and order.’3

Application of Internet techniques into online collaborative design and manufacture

A research project in Web-enabled collaborative design and manufacture has been conducted. The major tasks of the project include the development of a Web-enabled environment for collaboration, online collaborative CAD/CAM, remote execution of large size programs (RELSP), and distributed product design. The tasks and Web/Internet techniques involved are presented first, followed by detail description of two approaches developed for implementation of the research: (1) a client-server approach for RELSP, where the following Internet techniques are utilized: CORBA, Microsoft’s Internet information server, Tomcat server, JDBC and ODBC; (2) Web-Services supported collaborative CAD which enables geographically dispersed designers jointly conduct a design task in the way of speaking and seeing each other and instantaneously modifying the CAD drawing online.

Group Design-Build-Test Projects as the Core of an Integrated Curriculum in Product Design and Development

The School of Mechanical and Aerospace Engineering at Queen’s University Belfast introduced a new degree programme in Product Design and Development (PDD) in 2004. As well as setting out to meet all UK-SPEC requirements, the entirely new curriculum was developed in line with the syllabus and standards defined by the CDIO Initiative, an international collaboration of universities aiming to improve the education of engineering students. The CDIO ethos is that students are taught in the context of conceiving, designing, implementing and operating a product or system. Fundamental to this is an integrated curriculum with multiple Design-Build-Test (DBT) experiences at the core. Unlike most traditional engineering courses the PDD degree features group DBT projects in all years of the programme. The projects increase in complexity and challenge in a staged manner, with learning outcomes guided by Bloom’s taxonomy of learning domains. The integrated course structure enables the immediate application of disciplinary knowledge, gained from other modules, as well as development of professional skills and attributes in the context of the DBT activity. This has a positive impact on student engagement and the embedding of these relevant skills, identified from a stakeholder survey, has also been shown to better prepare students for professional practice. This paper will detail the methodology used in the development of the curriculum, refinements that have been made during the first five years of operation and discuss the resource and staffing issues raised in facilitating such a learning environment.

Design and Evaluation of a "Pharmacists in Schools" Community Outreach Programme: A Pilot Study.

Aims: To design, evaluate and pilot a novel programme that would allow school children to become “pharmacists for the day”,encouraging them to recognise the importance of science, to contribute to the Department of Health‟s Building the Community Partnership strategy and University Outreach to the community and to provide undergraduate pharmacy students with teaching experience and an opportunity to build their CV.

Methods: Concept and formulation development, branding work,schools visits,questionnaires and semi-structured interviews.

Results: Suitable formulations were developed and prepared by school children on visits to their schools. The children seemed to enjoy the experience and their teachers gave both positive and constructive feedback. Pharmacy undergraduate students felt they had gained valuable experience that will benefit their future careers.

Conclusion: The Pharmacists in Schools outreach programme has now been successfully piloted and launched and will now be fully implemented in 20 schools in the local community.

Design and evaluation of tinnitus synthesis methods: From spectral to spatial matching

Purpose
This study was designed to investigate methods to help patients suffering from unilateral tinnitus synthesizing an auditory replica of their tinnitus.

Materials and methods
Two semi-automatic methods (A and B) derived from the auditory threshold of the patient and a method (C) combining a pure tone and a narrow band-pass noise centred on an adjustable frequency were devised and rated on their likeness over two test sessions. A third test evaluated the stability over time of the synthesized tinnitus replica built with method C, and its proneness to merge with the patient's tinnitus. Patients were then asked to try and control the lateralisation of this single percept through the adjustment of the tinnitus replica level.

Results
The first two tests showed that seven out of ten patients chose the tinnitus replica built with method C as their preferred one. The third test, performed on twelve patients, revealed pitch tuning was rather stable over a week interval. It showed that eight patients were able to consistently match the central frequency of the synthesized tinnitus (presented to the contralateral ear) to their own tinnitus, which leaded to a unique tinnitus percept. The lateralisation displacement was consistent across patients and revealed an average range of 29dB to obtain a full lateral shift from the ipsilateral to the contralateral side.

Conclusions
Although spectrally simpler than the semi-automatic methods, method C could replicate patients' tinnitus, to some extent. When a unique percept between synthesized tinnitus and patients' tinnitus arose, lateralisation of this percept was achieved.