Mutations of beta-arrestin 2 that limit self-association also interfere with interactions with the beta2-adrenoceptor and the ERK1/2 MAPKs:implications for beta2-adrenoceptor signalling via the ERK1/2 MAPKs

FRET (fluorescence resonance energy transfer) and co-immunoprecipitation studies confirmed the capacity of beta-arrestin 2 to self-associate. Amino acids potentially involved in direct protein-protein interaction were identified via combinations of spot-immobilized peptide arrays and mapping of surface exposure. Among potential key amino acids, Lys(285), Arg(286) and Lys(295) are part of a continuous surface epitope located in the polar core between the N- and C-terminal domains. Introduction of K285A/R286A mutations into beta-arrestin 2-eCFP (where eCFP is enhanced cyan fluorescent protein) and beta-arrestin 2-eYFP (where eYFP is enhanced yellow fluorescent protein) constructs substantially reduced FRET, whereas introduction of a K295A mutation had a more limited effect. Neither of these mutants was able to promote beta2-adrenoceptor-mediated phosphorylation of the ERK1/2 (extracellular-signal-regulated kinase 1/2) MAPKs (mitogen-activated protein kinases). Both beta-arrestin 2 mutants displayed limited capacity to co-immunoprecipitate ERK1/2 and further spot-immobilized peptide arrays indicated each of Lys(285), Arg(286) and particularly Lys(295) to be important for this interaction. Direct interactions between beta-arrestin 2 and the beta2-adrenoceptor were also compromised by both K285A/R286A and K295A mutations of beta-arrestin 2. These were not non-specific effects linked to improper folding of beta-arrestin 2 as limited proteolysis was unable to distinguish the K285A/R286A or K295A mutants from wild-type beta-arrestin 2, and the interaction of beta-arrestin 2 with JNK3 (c-Jun N-terminal kinase 3) was unaffected by the K285A/R286A or L295A mutations. These results suggest that amino acids important for self-association of beta-arrestin 2 also play an important role in the interaction with both the beta2-adrenoceptor and the ERK1/2 MAPKs. Regulation of beta-arrestin 2 self-association may therefore control beta-arrestin 2-mediated beta2-adrenoceptor-ERK1/2 MAPK signalling.

Antecedents and consequences of service quality in consumer evaluation of self-service internet technologies

Advances in technology coupled with increasing labour costs have caused service firms to explore self-service delivery options. Although some studies have focused on self-service and use of technology in service delivery, few have explored the role of service quality in consumer evaluation of technology-based self-service options. By integrating and extending the self-service quality framework the service evaluation model and the Technology Acceptance Model the authors address this emerging issue by empirically testing a comprehensive model that captures the antecedents and consequences of perceived service quality to predict continued customer interaction in the technology-based self-service context of Internet banking. Important service evaluation constructs like perceived risk, perceived value and perceived satisfaction are modelled in this framework. The results show that perceived control has the strongest influence on service quality evaluations. Perceived speed of delivery, reliability and enjoyment also have a significant impact on service quality perceptions. The study also found that even though perceived service quality, perceived risk and satisfaction are important predictors of continued interaction, perceived customer value plays a pivotal role in influencing continued interaction.

The relationship between parental perceptions of diabetes and glycaemic control

Aim: To measure the relationship between perceived child competence, parental self-efficacy, and children's glycaemic control. Methods: Cross-sectional outpatient based questionnaire survey of 78 parents of children aged 6-12 years with insulin dependent diabetes mellitus, diagnosed for at least one year. Parental perceptions of their child's competence were assessed, together with parental perceptions of their own self-efficacy in managing their child's diabetes. Glycaemic control was assessed by the average annual HbA 1C level. Results: The response rate was 64.5% (51 parents); 82% were mothers and the socioeconomic class and ethnicity spread was representative of the general population. The mean age of the children was 10 years and duration of diabetes 4.4 years. Poorer glycaemic control was associated with higher perceived child competence, together with lower perceived age of responsibility, lower perceived seriousness, and less frequent blood tests. Higher parental self-efficacy and higher perceived child competence predicted a higher level of normalisation, as did lower perceived seriousness, a lower perceived parental responsibility for management, and a less protective style of parenting. Conclusion: Parents' perceptions of their children's diabetes are significantly related to glycaemic control; however, those who appear more competent at managing diabetes may overestimate their child's capabilities, leading to poorer glycaemic control.

Blood glucose self-monitoring in non-insulin-treated type 2 diabetes:a qualitative study of patients' perspectives

Background: Self-monitoring of blood glucose is controversial in the management of type 2 diabetes. Some research suggests that self-monitoring improves glycaemic control, whereas other research is sceptical about its value for people with type 2 diabetes who are not on insulin. Although blood glucose meters are widely available and used by this group, patients' own views are absent from the debate. Aim: To explore the pros and cons of glucose monitoring from the patients' perspectives. Design of study: Qualitative repeat-interview study. Setting: Patients were recruited from 16 general practices and three hospital clinics within four local healthcare cooperatives in Lothian, Scotland. Method: Interview data from 40 patients diagnosed with type 2 diabetes within the previous 6 months were analysed using thematic analysis informed by grounded theory. We report findings from round 1 and round 2 interviews. Results: Glucose monitoring can heighten patients' awareness of the impact of lifestyle; for example, dietary choices, on blood glucose levels. Glucose monitoring amplifies a sense of 'success' or 'failure' about self-management, often resulting in anxiety and self-blame if glucose readings remain consistently high. Moreover, monitoring can negatively effect patients' self-management when readings are counter-intuitive. Conclusion: Our analysis highlights the importance of understanding the meanings that newly diagnosed patients attach to glucose self-monitoring. To maximise the positive effects of self-monitoring, health professionals should ensure that patients understand the purpose of monitoring and should clarify with patients how readings should be interpreted. © British Journal of General Practice.

The role of self-regulation as a meta-competency in developing leaders: a longitudinal field experimental study

The question of how to develop leaders so that they are more effective in a variety of situations, roles and levels has inspired a voluminous amount of research. While leader development programs such as executive coaching and 360-degree feedback have been widely practiced to meet this demand within organisations, the research in this area has only scratched the surface. Drawing from the past literature and leadership practices, the current research conceptualised self-regulation, as a metacompetency that would assist leaders to further develop the specific competencies needed to perform effectively in their leadership role, leading to an increased rating of leader effectiveness and to enhanced group performance. To test this conceptualisation, a longitudinal field experimental study was conducted across ten months with a pre- and two post-test intervention designs with a matched control group. This longitudinal field experimental compared the difference in leader and team performance after receiving self-regulation intervention that was delivered by an executive coach. Leaders in experimental group also received feedback reports from 360-degree feedback at each stage. Participants were 40 leaders, 155 followers and 8 supervisors. Leaders’ performance was measured using a multi-source perceptual measure of leader performance and objective measures of team financial and assessment performance. Analyses using repeated measure of ANCOVA on pre-test and two post-tests responses showed a significant difference between leader and team performance between experimental and control group. Furthermore, leader competencies mediated the relationship between self-regulation and performance. The implications of these findings for the theory and practice of leadership development training programs and the impact on organisational performance are discussed.

AC self-bearing motors with a bridge configured winding

Magnetic levitation bearings eliminate friction, wear and the need for lubrication and so have high speed capability and potential for vibration control. One noteworthy development in the realm of magnetic levitation is the self-bearing or bearingless motor - an electromagnetic machine that supports its own rotor by way of magnetic forces generated by windings on its stator. Accordingly, various winding schemes have been proposed to accomplish the task of force production. This thesis proposes a novel concept of winding based on a bridge connection for polyphase self-bearing rotating electrical machines with the following advantages: • the connection uses a single set of windings and thus power loss is relatively low when compared with self-bearing motors with conventional dual set of windings. • the motor and levitation controls are segregated such that only one motor inverter is required for the normal torque production and levitation forces are produced by using auxiliary power supplies of relatively low current and voltage rating. The usual way of controlling the motor is retained. • there are many variant winding schemes to meet special needs. • independent power supplies for levitation control offer redundancy for fault tolerance. This thesis dwells specifically on the conceptual design and implementation of the proposed single set of windings scheme. The new connection has been verified to exhibit characteristics of a self-bearing motor via coupled-field finite element analysis: results are crosschecked analytically. Power loss and other aspects such as cost, design implementation are compared to support the newly proposed connection as a potential alternative to present designs.

Targets and self monitoring in hypertension: randomised controlled trial and cost effectiveness analysis

OBJECTIVES: To assess whether blood pressure control in primary care could be improved with the use of patient held targets and self monitoring in a practice setting, and to assess the impact of these on health behaviours, anxiety, prescribed antihypertensive drugs, patients' preferences, and costs. DESIGN: Randomised controlled trial. SETTING: Eight general practices in south Birmingham. PARTICIPANTS: 441 people receiving treatment in primary care for hypertension but not controlled below the target of < 140/85 mm Hg. INTERVENTIONS: Patients in the intervention group received treatment targets along with facilities to measure their own blood pressure at their general practice; they were also asked to visit their general practitioner or practice nurse if their blood pressure was repeatedly above the target level. Patients in the control group received usual care (blood pressure monitoring by their practice). MAIN OUTCOME MEASURES: Primary outcome: change in systolic blood pressure at six months and one year in both intervention and control groups. Secondary outcomes: change in health behaviours, anxiety, prescribed antihypertensive drugs, patients' preferences of method of blood pressure monitoring, and costs. RESULTS: 400 (91%) patients attended follow up at one year. Systolic blood pressure in the intervention group had significantly reduced after six months (mean difference 4.3 mm Hg (95% confidence interval 0.8 mm Hg to 7.9 mm Hg)) but not after one year (mean difference 2.7 mm Hg (- 1.2 mm Hg to 6.6 mm Hg)). No overall difference was found in diastolic blood pressure, anxiety, health behaviours, or number of prescribed drugs. Patients who self monitored lost more weight than controls (as evidenced by a drop in body mass index), rated self monitoring above monitoring by a doctor or nurse, and consulted less often. Overall, self monitoring did not cost significantly more than usual care (251 pounds sterling (437 dollars; 364 euros) (95% confidence interval 233 pounds sterling to 275 pounds sterling) versus 240 pounds sterling (217 pounds sterling to 263 pounds sterling). CONCLUSIONS: Practice based self monitoring resulted in small but significant improvements of blood pressure at six months, which were not sustained after a year. Self monitoring was well received by patients, anxiety did not increase, and there was no appreciable additional cost. Practice based self monitoring is feasible and results in blood pressure control that is similar to that in usual care.

'Urine testing is a waste of time': newly diagnosed Type 2 diabetes patients' perceptions of self-monitoring

Aims To date, there is no convincing evidence that non-insulin treated patients who undertake self-blood glucose monitoring (SBGM) have better glycaemic control than those who test their urine. This has led to a recommendation that non-insulin dependent patients undertake urine testing, which is the cheaper option. This recommendation does not take account of patients' experiences and views. This study explores the respective merits of urine testing and SBGM from the perspectives of newly diagnosed patients with Type 2 diabetes. Methods Qualitative study using repeat in-depth interviews with 40 patients. Patients were interviewed three times at 6-monthly intervals over 1 year. Patients were recruited from hospital clinics and general practices in Lothian, Scotland. The study was informed by grounded theory, which involves concurrent data collection and analysis. Results Patients reported strongly negative views of urine testing, particularly when they compared it with SBGM. Patients perceived urine testing as less convenient, less hygienic and less accurate than SBGM. Most patients assumed that blood glucose meters were given to those with a more advanced or serious form of diabetes. This could have implications for how they thought about their own disease. Patients often interpreted negative urine results as indicating that they could not have diabetes. Conclusions Professionals should be aware of the meanings and understandings patients attach to the receipt and use of different types of self-monitoring equipment. Guidelines that promote the use of consistent criteria for equipment allocation are required. The manner in which negative urine results are conveyed needs to be reconsidered.

Establishing a framework for dynamic risk management in 'intelligent' aero-engine control

The behaviour of control functions in safety critical software systems is typically bounded to prevent the occurrence of known system level hazards. These bounds are typically derived through safety analyses and can be implemented through the use of necessary design features. However, the unpredictability of real world problems can result in changes in the operating context that may invalidate the behavioural bounds themselves, for example, unexpected hazardous operating contexts as a result of failures or degradation. For highly complex problems it may be infeasible to determine the precise desired behavioural bounds of a function that addresses or minimises risk for hazardous operation cases prior to deployment. This paper presents an overview of the safety challenges associated with such a problem and how such problems might be addressed. A self-management framework is proposed that performs on-line risk management. The features of the framework are shown in context of employing intelligent adaptive controllers operating within complex and highly dynamic problem domains such as Gas-Turbine Aero Engine control. Safety assurance arguments enabled by the framework necessary for certification are also outlined.

Mode control in multimode optical fibre and its applications

This thesis describes an investigation into methods for controlling the mode distribution in multimode optical fibres. The major contributions presented in this thesis are summarised below. Emerging standards for Gigabit Ethernet transmission over multimode optical fibre have led to a resurgence of interest in the precise control, and specification, of modal launch conditions. In particular, commercial LED and OTDR test equipment does not, in general, comply with these standards. There is therefore a need for mode control devices, which can ensure compliance with the standards. A novel device consisting of a point-load mode-scrambler in tandem with a mode-filter is described in this thesis. The device, which has been patented, may be tuned to achieve a wide range of mode distributions and has been implemented in a ruggedised package for field use. Various other techniques for mode control have been described in this work, including the use of Long Period Gratings and air-gap mode-filters. Some of the methods have been applied to other applications, such as speckle suppression and in sensor technology. A novel, self-referencing, sensor comprising two modal groups in the Mode Power Distribution has been designed and tested. The feasibility of a two-channel Mode Group Diversity Multiplexed system has been demonstrated over 985m. A test apparatus for measuring mode distribution has been designed and constructed. The apparatus consists of a purpose-built video microscope, and comprehensive control and analysis software written in Visual Basic. The system may be fitted with a Silicon camera or an InGaAs camera, for measurement in the 850nm and 130nm transmission windows respectively. A limitation of the measurement method, when applied to well-filled fibres, has been identified and an improvement to the method has been proposed, based on modelled Laguerre Gauss field solutions.

Self-seeded gain-switched operation of an InGaN MQW laser diode

Self-seeded, gain-switched operation of an InGaN multi-quantum-well laser diode has been demonstrated for the first time. An external cavity comprising Littrow geometry was implemented for spectral control of pulsed operation. The feedback was optimized by adjusting the external cavity length and the driving frequency of the laser. The generated pulses had a peak power in excess of 400mW, a pulse duration of 60ps, a spectral linewidth of 0.14nm and maximum side band suppression ratio of 20dB. It was tunable within the range of 3.6nm centered at a wavelength of 403nm.

Comparing methods to separate treatment from self-selection effects in an online banking setting

The literature discusses several methods to control for self-selection effects but provides little guidance on which method to use in a setting with a limited number of variables. The authors theoretically compare and empirically assess the performance of different matching methods and instrumental variable and control function methods in this type of setting by investigating the effect of online banking on product usage. Hybrid matching in combination with the Gaussian kernel algorithm outperforms the other methods with respect to predictive validity. The empirical finding of large self-selection effects indicates the importance of controlling for these effects when assessing the effectiveness of marketing activities.

A language for self-adaptive system requirements

Self-adaptive systems have the capability to autonomously modify their behaviour at run-time in response to changes in their environment. Such systems are now commonly built in domains as diverse as enterprise computing, automotive control systems, and environmental monitoring systems. To date, however, there has been limited attention paid to how to engineer requirements for such systems. As a result, selfadaptivity is often constructed in an ad-hoc manner. In this paper, we argue that a more rigorous treatment of requirements relating to self-adaptivity is needed and that, in particular, requirements languages for self-adaptive systems should include explicit constructs for specifying and dealing with the uncertainty inherent in self-adaptive systems. We present some initial thoughts on a new requirements language for selfadaptive systems and illustrate it using examples from the services domain. © 2008 IEEE.

The role of self-regulation in developing leaders:a longitudinal field experiment

A longitudinal field experiment examined a leader self-regulation intervention in teams engaged in a Business Strategy Module (BSM) of a University course. The BSM, which is an integral part of the degree programme, involved teams of four or five individuals, under the direction of a leader, working on a (simulated) car manufacturing task over a period of 24. weeks. Various aspects of team performance contributed towards module assessment. All leaders received multi-source feedback of leader task-relevant capabilities (from the leader, followers and module tutor). Leaders were randomly allocated into a self-regulation intervention (15 leaders, 46 followers) or control (25 leaders, 109 followers) conditions. The intervention, which was run by an independent coach, was designed to improve leaders' use of self-regulatory processes to aid the development of task-relevant leadership competencies. Survey data was collected from the leaders and followers (on three occasions: pre- and two post-test intervention), team financial performance (three occasions: post-test) and a final team report (post-test). The leader self-regulation intervention led to increased followers' ratings of leader's effectiveness, higher team financial performance and higher final team grade compared to the control (non-intervention) condition. Furthermore, the benefits of the self-regulation intervention were mediated by leaders' attaining task-relevant competencies. © 2013.