Crystallization and preliminary x-ray diffraction analysis of the unliganded human growth hormone receptor

The crystal structure of the extracellular domain of growth hormone receptor complexed to its ligand, growth hormone, has been known since 1992. However, no information exists for the unliganded form of the receptor. The human growth hormone receptor's extracellular ligand-binding domain, encompassing amino-acid residues 1 - 238, has been expressed in Escherichia coli, purified by anion ion-exchange chromatography and crystallized in its unliganded state by the hanging-drop vapour-diffusion method in 100 mM HEPES pH 7.0 containing 27.5%(w/v) PEG 5000 monomethyl ether and 200 mM ammonium sulfate as the co-precipitants. The crystals belong to the othorhombic space group C222(1), have unit-cell parameters a = 99.7, b = 112.2, c = 93.2 Angstrom and diffract to 2.5 Angstrom resolution using synchrotron radiation. The crystal structure will shed light on the nature of any conformation changes that occur upon ligand binding and will provide information to develop potential low-molecular-weight agonists/antagonists to treat clinical diseases in which the growth hormone receptor is implicated.

A preliminary investigation of the effectiveness of a sleep apnea education program

Objectives: This study aimed to evaluate a standardised sleep apnea patient education program and develop a study design that may be used to evaluate other such education programs. Method: Thirty-four adults diagnosed with obstructive sleep apnea hypopnea syndrome (OSAHS) underwent a standard sleep apnea education program and completed measures of knowledge of and beliefs about sleep apnea before, after, and 3 months following education. Two outcome measures were used: the Apnea Knowledge Test (AKT) and the Apnea Beliefs Scale (ABS). Results: AKT results showed significant knowledge gains posteducation, which were maintained at follow-up. Patients also reported more positive beliefs about their ability to change their behaviour and comply with continuous positive airway pressure (CPAP) treatment recommendations after education. Discussion: Findings from this preliminary investigation suggest that the education program used in this study may improve patients' knowledge of CPAP and promote functional beliefs about OSAHS treatment. This program clearly warrants further research, and ultimately such programs may prove important in improving CPAP compliance. (C) 2004 Elsevier Inc. All rights reserved.

The design of planar gradient coils. Part ll: A weighted superposition method

In this work a superposition technique for designing gradient coils for the purpose of magnetic resonance imaging is outlined, which uses an optimized weight function superimposed upon an initial winding similar to that obtained from the target field method to generate the final wire winding. This work builds on the preliminary work performed in Part I on designing planar insertable gradient coils for high resolution imaging. The proposed superposition method for designing gradient coils results in coil patterns with relatively low inductances and the gradient coils can be used as inserts into existing magnetic resonance imaging hardware. The new scheme has the capacity to obtain images faster with more detail due to the deliver of greater magnetic held gradients. The proposed method for designing gradient coils is compared with a variant of the state-of-the-art target field method for planar gradient coils designs, and it is shown that the weighted superposition approach outperforms the well-known the classical method.

A metacognitive contextual intervention to enhance error awareness and functional outcome following traumatic brain injury: A single-case experimental design

Very few empirically validated interventions for improving metacognitive skills (i.e., self-awareness and self-regulation) and functional outcomes have been reported. This single-case experimental study presents JM, a 36-year-old man with a very severe traumatic brain injury (TBI) who demonstrated long-term awareness deficits. Treatment at four years post-injury involved a metacognitive contextual intervention based on a conceptualization of neuro-cognitive, psychological, and socio-environmental factors contributing to his awareness deficits. The 16-week intervention targeted error awareness and self-correction in two real life settings: (a) cooking at home: and (b) volunteer work. Outcome measures included behavioral observation of error behavior and standardized awareness measures. Relative to baseline performance in the cooking setting, JM demonstrated a 44% reduction in error frequency and increased self-correction. Although no spontaneous generalization was evident in the volunteer work setting, specific training in this environment led to a 39% decrease in errors. JM later gained paid employment and received brief metacognitive training in his work environment. JM's global self-knowledge of deficits assessed by self-report was unchanged after the program. Overall, the study provides preliminary support for a metacognitive contextual approach to improve error awareness and functional Outcome in real life settings.

A preliminary investigation of parenting attributes of Australian foster carers

Utilising a comparison research design of mothers involved in fostering (N= 28) and their peers (N =28), the major findings were that within the fostering group, those who had been fostering the longest had the lowest sense of efficacy, reflecting that the experience of providing foster care eroded parents' sense of their own skill. In terms of attachment to the children, the data suggested that foster carers may resist becoming too close to the children in their care in order to limit the emotional cost of subsequent separation. Importantly, there was no significant correlation between the length of time in providing foster care and marital satisfaction, which supports the notion that providing foster care does not, in itself cause marital stress. While formal support services were more utilised by foster carers there was some indication that this group is not well integrated into the broader community. Collectively, these findings demonstrate that over the long- term providing fostering care has some negative consequences for the carers in terms of their self-confidence. Agencies designated to work with carers need to consider proactive strategies to reduce this consequence.

A systematic review of successes and failures in home telehealth: preliminary results

We conducted a systematic review of the literature to identify studies in home telehealth that compared a home telehealth intervention with a non-telehealth standard/usual care alternative in terms of administrative changes, patient management decisions, patient outcomes, caregiver outcomes, economic impact or social impact on patients. A search of various databases produced 6643 references. Of these 769 papers were selected for more detailed investigation. These papers, combined with hand searching of relevant telehealth journals and cross-referencing of citations in identified publications, resulted in 138 papers referring to 130 projects for review. In this preliminary analysis we used a quality appraisal approach that took into account the study design. An additional analysis of patient numbers was then used to calculate a net evidence score. A large proportion of studies (80%) were randomised controlled trials. Only 22 projects (17%) reported economic data deemed to be sufficient for appraisal. Evidence exists for the clinical effectiveness of home telehealth in diabetes, the general area of mental health, high risk pregnancy monitoring, heart failure and cardiac disease.

Design and characterisation of novel blends of poly(lactic acid)

This thesis is concerned with the effect of polymer structure on miscibility of the three component blends based on poly(lactic acid) (PLA) with using blending techniques. The examination of novel PLA homologues (pre-synthesised poly(a-esters)), including a range of aliphatic and aromatic poly(a-esters) is an important aspect of the work. Because of their structural simplicity and similarity to PLA, they provide an ideal system to study the effect of polyester structures on the miscibility of PLA polymer blends. The miscibility behaviour of the PLA homologues is compared with other aliphatic polyesters (e.g. poly(e-caprolactone) (PCL), poly(hydroxybutyrate hydroxyvalerate) (P(HB-HV)), together with a series of cellulose-based polymers (e.g. cellulose acetate butyrate (CAB)). The work started with the exploration the technique used for preliminary observation of the miscibility of blends referred to as “a rapid screening method” and then the miscibility of binary blends was observed and characterised by percent transmittance together with the Coleman and Painter miscibility approach. However, it was observed that symmetrical structures (e.g. a1(dimethyl), a2(diethyl)) promote the well-packing which restrict their chains from intermingling into poly(L-lactide) (PLLA) chains and leads the blends to be immiscible, whereas, asymmetrical structures (e.g. a4(cyclohexyl)) behave to the contrary. a6(chloromethyl-methyl) should interact well with PLLA because of the polar group of chloride to form interactions, but it does not. It is difficult to disrupt the helical structure of PLLA. PLA were immiscible with PCL, P(HB-HV), or compatibiliser (e.g. G40, LLA-co-PCL), but miscible with CAB which is a hydrogen-bonded polymer. However, these binary blends provided a useful indication for the exploration the novel three component blends. In summary, the miscibility of the three-component blends are miscible even if only two polymers are miscible. This is the benefit for doing the three components blend in this thesis, which is not an attempt to produce a theoretical explanation for the miscibility of three components blend system.

The design and piloting of an eBusiness design studio

This paper describes the establishment and early use of an eBusiness Design Studio in Aston Business School at Aston University which is located in Birmingham in the UK. It was originally conceived as an R&D aid as much as a teaching resource. However the bulk of its use to date has been in the support of Masters level modules (courses) and this description will focus on that application in the first instance. We have less experience of its use in an R&D context but we will make some preliminary comments on this in a later section.

A naturally shaped silicone ventricle evaluated in a mock circulation loop: a preliminary study

Mock circulation loops are used to evaluate the performance of cardiac assist devices prior to animal and clinical testing. A compressible, translucent silicone ventricle chamber that mimics the exact size, shape and motion of a failing heart is desired to assist in flow visualization studies around inflow cannulae during VAD support. The aim of this study was therefore to design and construct a naturally shaped flexible left ventricle and evaluate its performance in a mock circulation loop. The ventricle shape was constructed by the use of CT images taken from a patient experiencing cardiomyopathic heart failure and used to create a 3D image and subsequent mould to produce a silicone ventricle. Different cardiac conditions were successfully simulated to validate the ventricle performance, including rest, left heart failure and VAD support.

Design and construction of an ultrasonic probe for use in a Cryo-Magnet NMR Spectrometer

SINNMR (Sonically Induced Narrowing of the Nuclear Magnetic Resonance spectra of solids), is a novel technique that is being developed to enable the routine study of solids by nuclear magnetic resonance spectroscopy. SINNMR aims to narrow the broad resonances that are characteristic of solid state NMR by inducing rapid incoherent motion of solid particles suspended in a support medium, using high frequency ultrasound in the range 2-10 MHz. The width of the normal broad resonances from solids are due to incomplete averaging of several components of the total spin Hamiltonian caused by restrictions placed on molecular motion within a solid. At present Magic Angle Spinning (MAS) NMR is the classical solid state technique used to reduce line broadening, but: this has associated problems, not least of which is the appearance of many spinning side bands which confuse the spectra. It is hoped that SlNNMR will offer a simple alternative, particularly as it does not reveal spinning sidebands The fundamental question concerning whether the use of ultrasound within a cryo-magnet will cause quenching has been investigated with success, as even under the most extreme conditions of power, frequency and irradiator time, the magnet does not quench. The objective of this work is to design and construct a SINNMR probe for use in a super conducting cryo-magnet NMR spectrometer. A cell for such a probe has been constructed and incorporated into an adapted high resolution broadband probe. It has been proved that the cell is capable of causing cavitation, up to 10 MHz, by running a series of ultrasonic reactions within it and observing the reaction products. It was found that the ultrasound was causing the sample to be heated to unacceptable temperatures and this necessitated the incorporation of temperature stabilisation devices. Work has been performed on the investigation of the narrowing of the solid state 23Na spectrum of tri-sodium phosphate using high frequency ultrasound. Work has also been completed on the signal enhancement and T1 reduction of a liquid mixture and a pure compound using ultrasound. Some preliminary "bench" experiments have been completed on a novel ultrasonic device designed to help minimise sample heating. The concept involves passing the ultrasound through a temperature stabilised, liquid filled funnel that has a drum skin on the end that will enable the passage of ultrasound into the sample. Bench experiments have proved that acoustic attenuation is low and that cavitation in the liquid beyond the device is still possible.

The molecular design of a new solvent for the absorption of carbon dioxide

Gas absorption, the removal of one or more constitutents from a gas mixture, is widely used in chemical processes. In many gas absorption processes, the gas mixture is already at high pressure and in recent years organic solvents have been developed for the process of physical absorption at high pressure followed by low pressure regeneration of the solvent and recovery of the absorbed gases. Until now the discovery of new solvents has usually been by expensive and time consuming trial and error laboratory tests. This work describes a new approach, whereby a solvent is selected from considerations of its molecular structure by applying recently published methods of predicting gas solubility from the molecular groups which make up the solvent molecule. The removal of the acid gases of carbon dioxide and hydrogen sulfide from methane or hydrogen was used as a commercially important example. After a preliminary assessment to identify promising moecular groups, more than eighty new solvent molecules were designed and evaluated by predicting gas solubility. The other important physical properties were also predicted by appropriate theoretical procedures, and a commercially promising new solvent was chosen to have a high solubility for acid gases, a low solubility for methane and hydrogen, a low vapour pressure, and a low viscosity. The solvent chosen, of molecular structure Ch3-COCH2-CH2-CO-CH3, was tested in the laboratory and shown to have physical properties, except for vapour pressures, close to those predicted. That is gas solubilities were within 10% but lower than predicted. Viscosity within 10% but higher than predicted and a vapour pressure significantly lower than predicted. A computer program was written to predict gas solubility in the new solvent at the high pressures (25 bar) used in practice. This is based on the group contribution method of Skold Jorgensen (1984). Before using this with the new solvent, Acetonyl acetone, the method was show to be sufficiently accurate by comparing predicted values of gas solubility with experimental solubilities from the literature for 14 systems up to 50 bar. A test of the commercial potential of the new solvent was made by means of two design studies which compared the size of plant and approximate relative costs of absorbing acid gases by means of the new solvent with other commonly used solvents. These were refrigerated methanol(Rectisol process) and Dimethyl Ether or Polyethylene Glycol(Selexol process). Both studies showed in terms of capital and operating cost some significant advantage for plant designed for the new solvent process.

Some studies relating to the design of shallow, fluidized bed boilers

The concept of shallow fluidized bed boilers is defined and a preliminary working design for a gas-fired package boiler has been produced. Those areas of the design requiring further study have been specified. Experimental investigations concerning these areas have been carried out. A two-dimensional, conducting paper analog has been developed for the specific purpose of evaluating sheet fins. The analog has been generalised and is presented as a simple means of simulating the general, two-dimensional Helmholtz equation. By recording the transient response of spherical, calorimetric probes when plunged into heated air-fluidized beds, heat transfer coefficients have been measured at bed temperatures up to 1 100°C. A correlation fitting all the data to within ±10% has been obtained. A model of heat transfer to surfaces immersed in high temperature beds has been proposed. The model solutions are, however, only in qualitative agreement with the experimental data. A simple experimental investigation has revealed that the effective, radial, thermal conductivities of shallow fluidized beds are an order of magnitude lower than the axial conductivities. These must, consequently, be taken into account when considering heat transfer to surfaces immersed within fluidized beds. Preliminary work on pre-mixed gas combustion and some further qualitative experiments have been used as the basis for discussing the feasibility of combusting heavy fuel oils within shallow beds. The use of binary beds, within which the fuel could be both gasified and subsequently burnt, is proposed. Finally, the consequences of the experimental studies on the initial design are considered, and suggestions for further work are made.

User interface design support for the development of knowledge-based systems

The present scarcity of operational knowledge-based systems (KBS) has been attributed, in part, to an inadequate consideration shown to user interface design during development. From a human factors perspective the problem has stemmed from an overall lack of user-centred design principles. Consequently the integration of human factors principles and techniques is seen as a necessary and important precursor to ensuring the implementation of KBS which are useful to, and usable by, the end-users for whom they are intended. Focussing upon KBS work taking place within commercial and industrial environments, this research set out to assess both the extent to which human factors support was presently being utilised within development, and the future path for human factors integration. The assessment consisted of interviews conducted with a number of commercial and industrial organisations involved in KBS development; and a set of three detailed case studies of individual KBS projects. Two of the studies were carried out within a collaborative Alvey project, involving the Interdisciplinary Higher Degrees Scheme (IHD) at the University of Aston in Birmingham, BIS Applied Systems Ltd (BIS), and the British Steel Corporation. This project, which had provided the initial basis and funding for the research, was concerned with the application of KBS to the design of commercial data processing (DP) systems. The third study stemmed from involvement on a KBS project being carried out by the Technology Division of the Trustees Saving Bank Group plc. The preliminary research highlighted poor human factors integration. In particular, there was a lack of early consideration of end-user requirements definition and user-centred evaluation. Instead concentration was given to the construction of the knowledge base and prototype evaluation with the expert(s). In response to this identified problem, a set of methods was developed that was aimed at encouraging developers to consider user interface requirements early on in a project. These methods were then applied in the two further projects, and their uptake within the overall development process was monitored. Experience from the two studies demonstrated that early consideration of user interface requirements was both feasible, and instructive for guiding future development work. In particular, it was shown a user interface prototype could be used as a basis for capturing requirements at the functional (task) level, and at the interface dialogue level. Extrapolating from this experience, a KBS life-cycle model is proposed which incorporates user interface design (and within that, user evaluation) as a largely parallel, rather than subsequent, activity to knowledge base construction. Further to this, there is a discussion of several key elements which can be seen as inhibiting the integration of human factors within KBS development. These elements stem from characteristics of present KBS development practice; from constraints within the commercial and industrial development environments; and from the state of existing human factors support.

What Google Maps can do for Biomedical Data Dissemination: Examples and a Design Study

Background: Biologists often need to assess whether unfamiliar datasets warrant the time investment required for more detailed exploration. Basing such assessments on brief descriptions provided by data publishers is unwieldy for large datasets that contain insights dependent on specific scientific questions. Alternatively, using complex software systems for a preliminary analysis may be deemed as too time consuming in itself, especially for unfamiliar data types and formats. This may lead to wasted analysis time and discarding of potentially useful data. Results: We present an exploration of design opportunities that the Google Maps interface offers to biomedical data visualization. In particular, we focus on synergies between visualization techniques and Google Maps that facilitate the development of biological visualizations which have both low-overhead and sufficient expressivity to support the exploration of data at multiple scales. The methods we explore rely on displaying pre-rendered visualizations of biological data in browsers, with sparse yet powerful interactions, by using the Google Maps API. We structure our discussion around five visualizations: a gene co-regulation visualization, a heatmap viewer, a genome browser, a protein interaction network, and a planar visualization of white matter in the brain. Feedback from collaborative work with domain experts suggests that our Google Maps visualizations offer multiple, scale-dependent perspectives and can be particularly helpful for unfamiliar datasets due to their accessibility. We also find that users, particularly those less experienced with computer use, are attracted by the familiarity of the Google Maps API. Our five implementations introduce design elements that can benefit visualization developers. Conclusions: We describe a low-overhead approach that lets biologists access readily analyzed views of unfamiliar scientific datasets. We rely on pre-computed visualizations prepared by data experts, accompanied by sparse and intuitive interactions, and distributed via the familiar Google Maps framework. Our contributions are an evaluation demonstrating the validity and opportunities of this approach, a set of design guidelines benefiting those wanting to create such visualizations, and five concrete example visualizations.