Discovery and Development of a Potent and Highly Selective Small Molecule Muscarinic Acetylcholine Receptor Subtype I (mAChR 1 or M-1) Antagonist In Vitro and In Vivo Probe

This article describes the discovery and development of the first highly selective, small molecule antagonist of the muscarinic acetylcholine receptor subtype I (mAChR1 or M-1). An M-1 functional, cell-based, calcium-mobilization assay identified three distinct chemical series with initial selectivity for M-1 versus M-4. An iterative parallel synthesis approach was employed to optimize all three series in parallel, which led to the development of novel microwave-assisted chemistry and provided important take home lessons for probe development projects. Ultimately, this effort produced VU0255035, a potent (IC50 = 130 nM) and selective (>75-fold vs. M-2-M-5 and >10 mu M vs. a panel of 75 GPCRs, ion channels and transporters) small molecule M-1 antagonist. Further profiling demonstrated that VU0255035 was centrally penetrant (Brain(AUC)/Plasma(AUC) of 0.48) and active in vivo, rendering it acceptable as both an in vitro and in vivo MLSCN/MLPCN probe molecule for studying and dissecting M-1 function.

Towards optimal software engineering: learning from agile practice

In essence, optimal software engineering means creating the right product, through the right process, to the overall satisfaction of everyone involved. Adopting the agile approach to software development appears to have helped many companies make substantial progress towards that goal. The purpose of this paper is to clarify that contribution from comparative survey information gathered in 2010 and 2012. The surveys were undertaken in software development companies across Northern Ireland. The paper describes the design of the surveys and discusses optimality in relation to the results obtained. Both surveys aimed to achieve comprehensive coverage of a single region rather than rely on a voluntary sample. The main outcome from the work is a collection of insights into the nature and advantages of agile development, suggesting how further progress towards optimality might be achieved.

Metodologia híbrida de desenvolvimento centrado no utilizador: aplicada ao software educativo

No panorama atual do desenvolvimento de software educativo é importante que os processos de desenvolvimento sejam adequados e compatíveis com o contexto em que serão utilizados este tipo de recursos. Desta forma, é importante melhorar continuamente os processos de desenvolvimento bem como se proceder à avaliação de forma a garantir a sua qualidade e viabilidade económica. Este estudo propõe uma Metodologia Híbrida de Desenvolvimento Centrado no Utilizador (MHDCU) aplicada ao software educativo. Trata-se de um processo de desenvolvimento simples, iterativo e incremental que tem como “alicerces” princípios do Design Centrado no Utilizador, especificados na International Organization for Standardization - ISO 13407. Na sua base encontra-se a estrutura disciplinada de processos de desenvolvimento, bem como práticas e valores dos métodos ágeis de desenvolvimento de software. O processo é constituído por 4 fases principais: planeamento (guião didático), design (storyboard), implementação e manutenção/operação. A prototipagem e a avaliação são realizadas de modo transversal a todo o processo. A metodologia foi implementada numa Pequena e Média Empresa de desenvolvimento de recursos educacionais, com o objetivo de desenvolver recursos educacionais com qualidade reconhecida e simultaneamente viáveis do ponto de vista económico. O primeiro recurso que teve por base a utilização desta metodologia foi o Courseware Sere – “O Ser Humano e os Recursos Naturais”. O trabalho seguiu uma metodologia de investigação & desenvolvimento, de natureza mista, em que se pretendeu descrever e analisar/avaliar uma metodologia de desenvolvimento de software educativo, i.e., o processo, bem como o produto final. O estudo é fundamentalmente descritivo e exploratório. A metodologia de desenvolvimento do software (primeira questão de investigação) foi proposta, essencialmente, com base na revisão integrativa da literatura da especialidade e com base nos resultados que emergiram das Fases 2 e 3. Do ponto de vista exploratório, foi avaliado, por um lado, o potencial técnico e didático da 1ª versão do software inserido no Courseware Sere (segunda questão de investigação), e, por outro lado, analisar os pontos fortes e as fragilidades da metodologia utilizada para o seu desenvolvimento (terceira questão de investigação). Como técnicas de recolha de dados recorreu-se a dois inquéritos por questionário e à observação direta participante (mediada pela plataforma moodle). Quanto às técnicas de análise de dados optou-se pela análise estatística descritiva e pela análise de conteúdo. Os resultados indicam que o recurso desenvolvido possui qualidade técnica e didática. Relativamente a análise da Metodologia Híbrida de desenvolvimento Centrado no Utilizador foram propostas algumas melhorias relacionadas com o envolvimento do utilizador e introdução de novos métodos. Apesar de identificadas algumas limitações, este projeto permitiu que a empresa melhorasse significativamente os processos de desenvolvimento de recursos (mesmo os que não são informatizados), bem como permitiu o aumento do seu portefólio com o desenvolvimento do Courseware Sere.

Self-organization for scheduling in agile manufacturing

Agility refers to the manufacturing system ability to rapidly adapt to market and environmental changes in efficient and cost-effective ways. This paper addresses the development of self-organization methods to enhance the operations of a scheduling system, by integrating scheduling system, configuration and optimization into a single autonomic process requiring minimal manual intervention to increase productivity and effectiveness while minimizing complexity for users. We intend to conceptualize real manufacturing systems as interacting autonomous entities in order to build future Decision Support Systems (DSS) for Scheduling in agile manufacturing environments.

Analysis of the domain of applicability of an algorithm for a resources system selection problem for Distributed/Agile/Virtual Enterprises integration

The process of resources systems selection takes an important part in Distributed/Agile/Virtual Enterprises (D/A/V Es) integration. However, the resources systems selection is still a difficult matter to solve in a D/A/VE, as it is pointed out in this paper. Globally, we can say that the selection problem has been equated from different aspects, originating different kinds of models/algorithms to solve it. In order to assist the development of a web prototype tool (broker tool), intelligent and flexible, that integrates all the selection model activities and tools, and with the capacity to adequate to each D/A/V E project or instance (this is the major goal of our final project), we intend in this paper to show: a formulation of a kind of resources selection problem and the limitations of the algorithms proposed to solve it. We formulate a particular case of the problem as an integer programming, which is solved using simplex and branch and bound algorithms, and identify their performance limitations (in terms of processing time) based on simulation results. These limitations depend on the number of processing tasks and on the number of pre-selected resources per processing tasks, defining the domain of applicability of the algorithms for the problem studied. The limitations detected open the necessity of the application of other kind of algorithms (approximate solution algorithms) outside the domain of applicability founded for the algorithms simulated. However, for a broker tool it is very important the knowledge of algorithms limitations, in order to, based on problem features, develop and select the most suitable algorithm that guarantees a good performance.

Agile Game: A Project Management Game for Agile Methods

Since mid-1990s, companies have adopted agile methods and incorporated them in their development methodologies. For this reason, future project managers and developers need to have a full understanding of these methods. At present, the university’s approach to agile methods is theoretical and is not reflected during the development of a product and their practical use. The purpose of this project is the creation of a software system in the form of a game, named Agile Game, which simulates their use. The system is designed for use as supplementary material in lectures, to help students understand agile methods, to present their use within a project, and to demonstrate how they differ from traditional project management methodologies. The final system, which is web based, was implemented using PHP, MySQL and JavaScript. It was fully tested against the requirements and evaluated by peer students. The evaluation showed that the majority of users were satisfied with the system but they thought that it should contain more detailed information at every step of the game. For this reason, some parts of the design and the content were reviewed to meet user requirements.

Agile methodologies

Outlines of both Scrum and Dynamic Systems Development Model

Software Development: Testing

This presentation discusses the role and purpose of testing in the systems/Software Development Life Cycle. We examine the consequences of the 'cost curve' on defect removal and how agile methods can reduce its effects. We concentrate on Black Box Testing and use Equivalence Partitioning and Boundary Value Analysis to construct the smallest number of test cases, test scenarios necessary for a test plan.

TIDT's Development Process

This presentation gives an overview of TIDT's development process at time of writitng in March 2016. We were and still are developing our process. It is an agile process based on DSDM and Scrum.

Goal sketching: towards agile requirements engineering

This paper describes a technique that can be used as part of a simple and practical agile method for requirements engineering. The technique can be used together with Agile Programming to develop software in internet time. We illustrate the technique and introduce lazy refinement, responsibility composition and context sketching. Goal sketching has been used in a number of real-world development projects, one of which is described here.

Goal sketching: an agile approach to clarifying requirements

This paper describes a technique that can be used as part of a simple and practical agile method for requirements engineering. It is based on disciplined goal-responsibility modelling but eschews formality in favour of a set of practicality objectives. The technique can be used together with Agile Programming to develop software in internet time. We illustrate the technique and introduce lazy refinement, responsibility composition and context sketching. Goal sketching has been used in a number of real-world development.

British pharmacy professionals’ beliefs and participation in continuing professional development: a review of the literature.

Objectives Continuing professional development (CPD) has potential to be useful in pharmacy revalidation but past uptake and attitudes to CPD in Great Britain (GB) need to be mapped. This review examines published literature to chart the participation and beliefs of pharmacy professionals towards CPD in GB in a decade that had seen a formal transition from continuing education to CPD. Methods A comprehensive review of the published literature was conducted to identify studies of the uptake of, or attitudes towards, CPD cross different sectors of pharmacy in GB from 2000 to 2010. Key findings Twenty-two studies were included and analysed, including 13 research papers, six conference papers, two news items reporting survey outcomes and one commissioned study. Eight barriers to CPD were identified as: time, financial costs and resource issues, understanding of CPD, facilitation and support for CPD, motivation and interest in CPD, attitudes towards compulsory CPD, system constraints, and technical problems. Pharmacy professionals on the whole agreed with the principle of engaging with CPD but there was little evidence to suggest widespread and wholehearted acceptance and uptake of CPD, essential for revalidation. Conclusions If CPD is to succeed, people's beliefs and attitudes must be addressed by recognising and modifying perceived barriers through a combination of regulatory, professional, work-related and personal channels. A number of recommendations are made. Direct experience of effective CPD in the absence of perceived barriers could impact on personal development, career development and patient benefit thus strengthening personal beliefs in the value of CPD in an iterative manner.

British pharmacy professionals' beliefs and participation in continuing professional development: a review of the literature

Objectives:  Continuing professional development (CPD) has potential to be useful in pharmacy revalidation but past uptake and attitudes to CPD in Great Britain (GB) need to be mapped. This review examines published literature to chart the participation and beliefs of pharmacy professionals towards CPD in GB in a decade that had seen a formal transition from continuing education to CPD. Methods:  A comprehensive review of the published literature was conducted to identify studies of the uptake of, or attitudes towards, CPD cross different sectors of pharmacy in GB from 2000 to 2010. Key findings:  Twenty-two studies were included and analysed, including 13 research papers, six conference papers, two news items reporting survey outcomes and one commissioned study. Eight barriers to CPD were identified as: time, financial costs and resource issues, understanding of CPD, facilitation and support for CPD, motivation and interest in CPD, attitudes towards compulsory CPD, system constraints, and technical problems. Pharmacy professionals on the whole agreed with the principle of engaging with CPD but there was little evidence to suggest widespread and wholehearted acceptance and uptake of CPD, essential for revalidation. Conclusions:  If CPD is to succeed, people's beliefs and attitudes must be addressed by recognising and modifying perceived barriers through a combination of regulatory, professional, work-related and personal channels. A number of recommendations are made. Direct experience of effective CPD in the absence of perceived barriers could impact on personal development, career development and patient benefit thus strengthening personal beliefs in the value of CPD in an iterative manner.