The second intracellular loop of the calcitonin gene-related peptide receptor provides molecular determinants for signal transduction and cell surface expression

The calcitonin gene-related peptide (CGRP) receptor is a heterodimer of a family B G-protein-coupled receptor, calcitonin receptor-like receptor (CLR), and the accessory protein receptor activity modifying protein 1. It couples to Gs, but it is not known which intracellular loops mediate this. We have identified the boundaries of this loop based on the relative position and length of the juxtamembrane transmembrane regions 3 and 4. The loop has been analyzed by systematic mutagenesis of all residues to alanine, measuring cAMP accumulation, CGRP affinity, and receptor expression. Unlike rhodopsin, ICL2 of the CGRP receptor plays a part in the conformational switch after agonist interaction. His-216 and Lys-227 were essential for a functional CGRP-induced cAMP response. The effect of (H216A)CLR is due to a disruption to the cell surface transport or surface stability of the mutant receptor. In contrast, (K227A)CLR had wild-type expression and agonist affinity, suggesting a direct disruption to the downstream signal transduction mechanism of the CGRP receptor. Modeling suggests that the loop undergoes a significant shift in position during receptor activation, exposing a potential G-protein binding pocket. Lys-227 changes position to point into the pocket, potentially allowing it to interact with bound G-proteins. His-216 occupies a position similar to that of Tyr-136 in bovine rhodopsin, part of the DRY motif of the latter receptor. This is the first comprehensive analysis of an entire intracellular loop within the calcitonin family of G-protein-coupled receptor. These data help to define the structural and functional characteristics of the CGRP-receptor and of family B G-protein-coupled receptors in general. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

Accessing networked services : a user interface design problem

This research investigates the general user interface problems in using networked services. Some of the problems are: users have to recall machine names and procedures to. invoke networked services; interactions with some of the services are by means of menu-based interfaces which are quite cumbersome to use; inconsistencies exist between the interfaces for different services because they were developed independently. These problems have to be removed so that users can use the services effectively. A prototype system has been developed to help users interact with networked services. This consists of software which gives the user an easy and consistent interface with the various services. The prototype is based on a graphical user interface and it includes the following appJications: Bath Information & Data Services; electronic mail; file editor. The prototype incorporates an online help facility to assist users using the system. The prototype can be divided into two parts: the user interface part that manages interactlon with the user; the communicatIon part that enables the communication with networked services to take place. The implementation is carried out using an object-oriented approach where both the user interface part and communication part are objects. The essential characteristics of object-orientation, - abstraction, encapsulation, inheritance and polymorphism - can all contribute to the better design and implementation of the prototype. The Smalltalk Model-View-Controller (MVC) methodology has been the framework for the construction of the prototype user interface. The purpose of the development was to study the effectiveness of users interaction to networked services. Having completed the prototype, tests users were requested to use the system to evaluate its effectiveness. The evaluation of the prototype is based on observation, i.e. observing the way users use the system and the opinion rating given by the users. Recommendations to improve further the prototype are given based on the results of the evaluation. based on the results of the evah:1ation. . .'. " "', ':::' ,n,<~;'.'

An empirical investigation of the effect of rights issue announcements on share returns and the determinants of abnormal returns on the Kuala Lumpur Stock Exchange

This thesis examines the effect of rights issue announcements on stock prices by companies listed on the Kuala Lumpur Stock Exchange (KLSE) between 1987 to 1996. The emphasis is to report whether the KLSE is semi strongly efficient with respect to the announcement of rights issues and to check whether the implications of corporate finance theories on the effect of an event can be supported in the context of an emerging market. Once the effect is established, potential determinants of abnormal returns identified by previous empirical work and corporate financial theory are analysed. By examining 70 companies making clean rights issue announcements, this thesis will hopefully shed light on some important issues in long term corporate financing. Event study analysis is used to check on the efficiency of the Malaysian stock market; while cross-sectional regression analysis is executed to identify possible explanators of the rights issue announcements' effect. To ensure the results presented are not contaminated, econometric and statistical issues raised in both analyses have been taken into account. Given the small amount of empirical research conducted in this part of the world, the results of this study will hopefully be of use to investors, security analysts, corporate financial managements, regulators and policy makers as well as those who are interested in capital market based research of an emerging market. It is found that the Malaysian stock market is not semi strongly efficient since there exists a persistent non-zero abnormal return. This finding is not consistent with the hypothesis that security returns adjust rapidly to reflect new information. It may be possible that the result is influenced by the sample, consisting mainly of below average size companies which tend to be thinly traded. Nevertheless, these issues have been addressed. Another important issue which has emerged from the study is that there is some evidence to suggest that insider trading activity existed in this market. In addition to these findings, when the rights issue announcements' effect is compared to the implications of corporate finance theories in predicting the sign of abnormal returns, the signalling model, asymmetric information model, perfect substitution hypothesis and Scholes' information hypothesis cannot be supported.

An extensive laboratory investigation of the use of bio-oil modified bitumen in road construction

Several roads in Iceland with bio-oil modified surface dressings exhibited severe distresses such as bleeding, binder drain down, and eventually as surface dressing sticking to tires. Samples from six road sections were evaluated in the laboratory to determine the causes of the failure. Binders with and without bio-oil, rapeseed oil and fish oil, were evaluated through a comprehensive rheological and chemical characterization. Both oils, exhibited solubility issues with the bitumen; consequently, the oils covered the aggregates, preventing bonding between binder and stones. It appears that fish oil worked a little better than rapeseed oil for binder modification.

Unique reporter-based sensor platforms to monitor signalling in cells

Introduction - In recent years much progress has been made in the development of tools for systems biology to study the levels of mRNA and protein, and their interactions within cells. However, few multiplexed methodologies are available to study cell signalling directly at the transcription factor level. Methods - Here we describe a sensitive, plasmid-based RNA reporter methodology to study transcription factor activation in mammalian cells, and apply this technology to profiling 60 transcription factors in parallel. The methodology uses two robust and easily accessible detection platforms; quantitative real-time PCR for quantitative analysis and DNA microarrays for parallel, higher throughput analysis. Findings - We test the specificity of the detection platforms with ten inducers and independently validate the transcription factor activation. Conclusions - We report a methodology for the multiplexed study of transcription factor activation in mammalian cells that is direct and not theoretically limited by the number of available reporters.

A stage-oriented model (SOM) for e-commerce adoption:a study of Saudi Arabian organisations

Purpose - The purpose of this paper is to construct a new e-commerce innovation and adoption model that takes into account various stages of e-commerce adoption (interactive, non-interactive and stabilised) and covers technological, organisational and environmental factors. This was tested using data collected from manufacturing and service companies in Saudi Arabia (SA) to reveal inhibitors and catalysts for e-commerce adoption. Design/methodology/approach - This study uses new data from surveys from 202 companies and then uses exploratory factor analysis and structural equation modelling for analyses. Findings - This study shows that the new stage-oriented model (SOM) is valid and can reveal specific detailed nuances of e-commerce adoption within a particular setting. Surprising results show that SA is not so very different to developed western countries in respect to e-commerce adoption. However there are some important differences which are discussed in detail. Research limitations/implications - A new SOM for e-commerce adoption is provided which may be used by other IS adoption researchers. Practical implications - Managers responsible for the adoption of e-commerce in SA, the Middle East and beyond can learn from these findings to speed up adoption rates and make e-commerce more effective. Social implications - This work may help spread e-commerce use throughout SA, the Middle East and to other developing nations. Originality/value - The results add to the extremely limited number of empirical studies that has been conducted to investigate e-commerce adoption in the context of Arabic countries.

An investigation into the factors affecting e-commerce adoption decisions by SMEs:a study in Saudi Arabia

Electronic commerce (e-commerce) has become an increasingly important initiative among Small and Medium Enterprises (SMEs) as both a great opportunity and as a source of competition. The factors affecting adoption decisions of e-commerce by SMEs have been well documented, but there is a paucity of empirical studies that examine the adoption of e-commerce in the Arab world. The aim of this chapter is to provide insights into the salient e-commerce adoption issues by focusing on Saudi Arabian businesses. This chapter investigates the state of e-commerce adoption and analyses the factors that determine the extent to which SMEs in Saudi Arabia are inclined towards deploying e-commerce technologies. This research was designed using a qualitative approach through exploratory case studies selected from firms in Saudi Arabia. The findings contribute towards a better conceptual and practical understanding of the main factors driving SMEs to adopt e-commerce. The study has found that the level of e-commerce implementation has yet to mature and customer readiness for Internet shopping has to improve before e-commerce reaches the levels of maturity seen in other regions of the world. This study highlights several directions for future inquiry and implications for policymakers and managers who are involved in efforts to introduce complex innovations such as e-commerce into their organisations or are interested in expanding their e-commerce applications and generating more revenue.

An investigation into the adoption of electronic commerce among Saudi Arabian SMEs

Despite the proliferation of e-commerce adoption by SMEs and the world-wide growth of e-commerce, in general there is a paucity of empirical studies that examine the adoption of e-commerce by SMEs in the Middle East. In this paper, the authors provide insights into the salient e-commerce adoption issues by focusing on Saudi Arabian SMEs. This research was designed using a qualitative approach through in-depth case studies selected from firms in Saudi Arabia. The findings contribute toward a better conceptual and practical understanding of the main factors driving SMEs to adopt e-commerce. The authors find that the level of e-commerce implementation has yet to mature and customer readiness for Internet shopping must improve before e-commerce reaches the levels of maturity seen in other regions of the world. This study highlights directions for future inquiry and implications for information and technology managers and policymakers in developing Arab nations.