Common structural basis for central nervous system drug design

The main theme of this thesis is that there is a common structural basis for drugs acting on the central nervous system (CNS), and that this concept may be used to design new CNS-active drugs which have greater specificity and hence less side-effects. To develop these ideas, the biological basis of how drugs modify CMS neurotransmission is described, and illustrated using dopaminergic pathways. An account is then given of the use of physicochemical concepts in contemporary drug design. The complete conformational analysis of several antipsychotic drugs is used to illustrate some of these techniques in the development of a model for antipsychotic drug action. After reviewing current structure-activity studies in several classes of CNS drugs (antipsychotics, anti-depressants, stimulants, hal1ucinogens, anticonvulsants and analgesics), a hypothesis for a common structural basis of CNS drug action is proposed- This is based on a topographical comparison of the X-ray structures of eight representative CNS-active drugs, and consists of three parts: 1.there is a common structural basis for the activity of many different CNS-active drug classes; 2. an aromatic ring and a nitrogen atom are the primary binding groups whose topographical arrangement is fundamental to the activity of these drug classes; 3. the nature and placement of secondary binding determines different classes of CNS drug activity. A four-Point model for this common structural basis is then defined using 14- CNS-active drug structures that include the original eight used in proposing the hypothesis. The coordinates of this model are: R1 (0. 3.5, 0), R2 (0, -3.5, O), N (4.8. -0.3, 1.4), and R3 (6.3, 1.3, 0), where R1 and R2 represent the point locations of a hydrophobic interaction of the common aromatic ring with a receptor, and R3 locates the receptor point for a hydrogen bond involving the common nitrogen, N. Extended structures were used to define the receptor points R1, R2 and R3, and the complete conformational space of each of the 14 molecules was considered. It is then shoun that the model may be used to predict whether a given structure is likely to show CNS activity: a search over 1,000 entries in the current Merck Index shows a high probability (82%) of CNS activity in compounds fitting the structural model. Analysis of CNS neurotransmitters and neuropeptides shows that these fit the common model well. Based on the available evidence supporting chemical evolution, protein evolution, and the evolution of neurotransmitter functions, it is surmised that the aromatic ring/nitrogen atom pharmacophore proposed in the common model supports the idea of the evolution of CNS receptors and their neurotransmitters, possibly from an aromatic amine or acety1cho1ine acting as a primaeval communicating molecule. The third point in the hypothesis trilogy is then addressed. The extensive conformation-activity analyses that have resulted in well-defined models for five separate CNS drug classes are used to map out the locations of secondary binding groups relative to the common model for anti-psychotics, antidepressants, analgesics, anticholinergics, and anticonvulsants. With this information, and knowledge derived from receptor-binding data, it is postulated that drugs having specified activity could be designed. In order to generate novel structures having a high probability of CNS-activity, a process of drug design is described in which known CNS structures are superimposed topographically using the common model as a template. Atoms regarded as superfluous may be selectively deleted and the required secondary binding groups added in predicted locations to give novel structures. It is concluded that this process provides the basis for the rational design of new lead compounds which could further be optimized for potent and specific CNS activity.

Human-computer interaction in ubiquitous computing environments

Purpose – The purpose of this paper is to explore characteristics of human-computer interaction when the human body and its movements become input for interaction and interface control in pervasive computing settings.

Design/methodology/approach – The paper quantifies the performance of human movement based on Fitt's Law and discusses some of the human factors and technical considerations that arise in trying to use human body movements as an input medium.

Findings – The paper finds that new interaction technologies utilising human movements may provide more flexible, naturalistic interfaces and support the ubiquitous or pervasive computing paradigm.

Practical implications – In pervasive computing environments the challenge is to create intuitive and user-friendly interfaces. Application domains that may utilize human body movements as input are surveyed here and the paper addresses issues such as culture, privacy, security and ethics raised by movement of a user's body-based interaction styles.

Originality/value – The paper describes the utilization of human body movements as input for interaction and interface control in pervasive computing settings.

Customer-product interaction : a model for new product development in entrepreneurial firms

Use of New Product Development (NPD) methods may benefit New Zealand SMEs and entrepreneurial firms in gaining greater market share. In this paper we review the literature on New Product Development, NPD theory and methods for early stage product design and development. Our reading suggests that product design has greater success when the customer is involved in the design effort. It also recommends methods of approach to new markets in the (NPD) life cycle. The literature further elucidates methods for identification of product design criteria based on customer needs identification. In essence, customer-product interaction in the early stages of product development is important to product success in new markets for entrepreneurial firms and SMEs. Of particular interest are early-stage NPD research methods and their influence on the company’s marketing strategy.

Design and analysis of a cantilever biosensor based on a boron nitride nanotube

In this paper, we introduce a single-walled boron nitride nanotube (SWBNNT)-based cantilever biosensor, and investigate its bending deformation. The BNNT-based cantilever is modelled by accounting that the surface of the cantilever beam is coated with the antibody molecule. We have considered two main approaches for the mechanical deformation of the BNNT beam. The first one is differential surface stress produced by the binding of biomolecules onto its surface, and the second one is the charge released from the biomolecular interaction. In addition, other parameters including length of beam, variation of beam’s location and chiralities of the BNNT have been taken into consideration to design the cantilever biosensor. The computed results are in good agreement with the well known electrostatic equations that govern the deformation of the cantilever.

The psychological and physical needs of workers impacting office design

Office design needs to be based on the needs of the most important producers of profit and value for any organisation – the workforce. Drivers affecting office design have been economics – space being often viewed as a cost-centre rather than a business enabler; and more recently, ideas that office design can impact organisational culture – resulting in the adoption of more collaborative working spaces in an attempt to force interaction. What is not always considered are the actual working styles
of the individuals and their motivations nor the requirements of the work itself. There is a need to profile not only the workforce, but also the work carried out. Recent research into space requirements for work is reviewed and reported with recommendations for better consideration of the psychological and physical needs of workers for office design.

On the influence of building design, occupants and heat waves on comfort and greenhouse gas emissions in naturally ventilated offices. A study based on the EN 15251 adaptive thermal comfort model in Athens, Greece

According to the Intergovernmental Panel on Climate Change the buildings sector has the largest mitigation potential for CO2 emissions. Especially in office buildings, where internal heat loads and a relatively high occupant density occur at the same time with solar heat gains, overheating has become a common problem. In Europe the adaptive thermal comfort model according to EN 15251 provides a method to evaluate thermal comfort in naturally ventilated buildings. However, especially in the context of the climate change and the occurrence of heat waves within the last decade, the question arises, how thermal comfort can be maintained without additional cooling, especially in warm climates. In this paper a parametric study for a typical cellular naturally ventilated office room has been conducted, using the building simulation software EnergyPlus. It is based on the Mediterranean climate of Athens, Greece. Adaptive thermal comfort is evaluated according to EN 15251. Variations refer to different building design priorities, and they consider the variability of occupant behaviour and internal heat loads by using an ideal and worst case scenario. The influence of heat waves is considered by comparing measured temperatures for an average and an exceptionally hot year within the last decade. Since the use of building controls for shading affects thermal as well as visual comfort, daylighting and view are evaluated as well. Conclusions are drawn regarding the influence and interaction of building design, occupants and heat waves on comfort and greenhouse gas emissions in naturally ventilated offices, and related optimisation potential.

The effect of planning design on thermal comfort in outdoor spaces

Urban outdoor spaces are considered essential elements of cities, where the greatest amount of human contact and interaction takes place. That is the reason why there is increasing public interest in the quality of open urban spaces as they can contribute to the quality of life within cities, or contrarily increase isolation and social exclusion. There are a lot of factors influencing the success of the outdoor spaces; one of the principal factors is the microclimatic comfort. In the hot areas, the outdoor thermal comfort conditions during the daytime are often far above acceptable comfort standards due to intense solar radiation and high solar elevations. The variation of the urban spaces' configuration can generate significant modifications of the microclimatic parameters. Design decisions such as street and sidewalk widths, shading structures, materials, landscaping, building heights, and inducing air flow have a significant impact on the pedestrian thermal comfort and subsequently on the use of the urban environment. Although it has been established that the vegetation elements should be considered as one of the main tools that can be used in improving the thermal comfort in outdoor spaces, the integration of the climate dimension in the planting design process in urban spaces is lacking because of insufficient interdisciplinary work between urban climatology, urban design and landscape architecture. The primary aim of this research is to study the influence of some of the design decision for the plantation elements in outdoor spaces on the thermal comfort of its users. This will provide landscape designers and decision makers with the appropriate tools for effectively assessing the development of urban environment while considering the microclimate of outdoor spaces. A special emphasis is put on summertime conditions in Egypt. Findings of this research will contribute to sustainable urban design of outdoor spaces.

A generic virtual reality interaction system and its extensions using the common object request broker architecture (CORBA)

The paper describes the design and implementation of an immersive Virtual Reality (VR) interaction system. The system aims to provide a flexible mechanism for programmers to implement interaction in their VR applications, making good use of all accepted practices in the field. The paper further describes how the system was extended to a multi-user system using the CORBA middleware layer.

User-centered design and evaluation of an interactive visual-haptic-auditory interface : a user study on assembly

Utilizing user-centred system design and evaluation method has become an increasingly important tool to foster better usability in the field of virtual environments (VEs). In recent years, although it is still the norm that designers and developers are concerning the technological advancement and striving for designing impressive multimodal multisensory interfaces, more and more awareness are aroused among the development team that in order to produce usable and useful interfaces, it is essential to have users in mind during design and validate a new design from users' perspective. In this paper, we describe a user study carried out to validate a newly developed haptically enabled virtual training system. By taking consideration of the complexity of individual differences on human performance, adoption and acceptance of haptic and audio-visual I/O devices, we address how well users learn, perform, adapt to and perceive object assembly training. We also explore user experience and interaction with the system, and discuss how multisensory feedback affects user performance, perception and acceptance. At last, we discuss how to better design VEs that enhance users perception, their interaction and motor activity.

Occupant interaction with interior environment in Greek dwellings during summer

User behaviour significantly affects energy consumption simulation estimates, which can consequently influence architectural design decisions at an early stage. Different regional behavioural patterns could, therefore, hinder the applicability of certain architectural and environmental strategies. Through questionnaires analysis and field studies, this study investigates the pattern use of manual control of windows, shading and air condition units, in residential buildings in Greece, during summer. Initial findings of the analysis indicate significant interaction of Greek residents with the building shell, in their effort to maintain comfort.

The social network virtual design studio : integrated design learning using blended learning environments

Online communications, multimedia, mobile computing and face-to-face learning create blended learning environments to which some Virtual Design Studios (VDS) have reacted to. Social Networks (SN), as instruments for communication, have provided a potentially fruitful operative base for VDS. These technologies transfer communication, leadership, democratic interaction, teamwork, social engagement and responsibility away from the design tutors to the participants. The implementation of Social Network VDS (SNVDS) moved the VDS beyond its conventional realm and enabled students to develop architectural design that is embedded into a community of learners and expertise both online and offline. Problem-based learning (PBL) becomes an iterative and reflexive process facilitating deep learning. The paper discusses details of the SNVDS, its pedagogical implications to PBL, and presents how the SNVDS is successful in enabling architectural students to collaborate and communicate design proposals that integrate a variety of skills, deep learning, knowledge and construction with a rich learning experience.

How social is the virtual design studio? A case study of a third year design studio

With the advent of social networks, it became apparent that the social aspect of designing and learning plays a crucial role in students’ education. Technologies and skills are the base on which learners interact. The ease of communication, leadership opportunity, democratic interaction, teamwork, and the sense of community are some of the aspects that are now in the centre of design interaction. The paper examines Virtual Design Studios (VDS) that used media-rich platforms and analyses the influence the social aspect plays in solving all problems on the sample of a design studio at Deakin University. It studies the effectiveness of the generated social intelligence and explores the facilitation of students’ self-directed learning. Hereby the paper studies the construction of knowledge via social interaction and how blended learning environments foster motivation and information exchange. It presents its finding based on VDS that were held over the past three years.

Constructing a t-way interaction test suite using the Particle Swarm Optimization approach

This paper presents the design and implementation of a new t-way test generation strategy, known as the Particle Swarm Test Generator (PSTG). Complementing the existing work on t-way testing strategies, PSTG serves as our research vehicle to investigate the applicability of Particle Swarm Optimization for t-way test data generation. The experimental results demonstrate that PSTG is capable of outperforming some of the existing strategies as far as the test size is concerned. Additionally, the evaluation also indicates the effectiveness of PSTG in generating an efficient test suite for testing consideration.

Finding common ground: enhancing interaction between domestic and international students in higher education

A feature of Australian Higher Education over the last 10 years has been the increased numbers of international students. This feature has been perceived to have great potential for enhanced learning for all students – both international and domestic. Yet, student surveys and research clearly indicate that there is very little interaction occurring between domestic and international students. This article reports on a study that investigated the extent to which university teaching can promote interaction between students from diverse cultural and linguistic background. Using an innovative video-analysis methodology, the research found that academics engage in a variety of activities to encourage interaction between student groups. In order to assist academics in planning interaction, one of the main findings of the study was the development of ‘The Interaction for Learning Framework (ILF)’, that identifies key dimensions for curriculum design that can be used by academics to inform ways that they can enhance interaction between diverse student groups within teaching and learning contexts.

Virtual design studio within a blended social network

Online interactions, multimedia, mobile computing and face-to-face learning create blended learning environments to which some Virtual Design Studios (VDS) have reacted. Social Networks (SN), as instruments for communication, have provided a potentially fruitful operative base for VDS. These technologies transfer communication, leadership, democratic interaction, teamwork, social engagement and responsibility away from the design tutors to the participants. The implementation of a Social Network VDS (SNVDS) moved the VDS beyond its conventional realm and enabled students to develop architectural design that is embedded into a community of learners and their expertise both online and offline. Problem-based learning (PBL) becomes an iterative and reflexive process facilitating deep learning. The paper discusses details of the SNVDS, its pedagogical implications to PBL, and presents how the SNVDS is successful in empowering architectural students to collaborate and communicate design proposals that integrate a variety of skills, deep learning, knowledge and construction with a rich learning experience.