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.

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.

Balancing expectations in engineering education:enhancing student experiences through empirical research - a comparative analysis

This paper draws upon the findings of an empirical study comparing the expectations and concerns of engineering students with students enrolled on business and management programs. It argues that whilst the two groups of students have very similar expectations, motivations and concerns before their start their studies, once at university, engineering students are twice as likely to drop-out than are their compatriots in business studies. Drawing upon the study findings, recommendations are made as to what might be done to counteract this. The conclusion argues that there is a need for more in-depth research to be conducted in this area in order to identify the reasons behind the different attrition rates and to further enhance engineering undergraduate experience.

Applicability of contact angle techniques used in the analysis of contact lenses, part 1:comparative methodologies

Objectives and Methods: Contact angle, as a representative measure of surface wettability, is often employed to interpret contact lens surface properties. The literature is often contradictory and can lead to confusion. This literature review is part of a series regarding the analysis of hydrogel contact lenses using contact angle techniques. Here we present an overview of contact angle terminology, methodology, and analysis. Having discussed this background material, subsequent parts of the series will discuss the analysis of contact lens contact angles and evaluate differences in published laboratory results. Results: The concepts of contact angle, wettability and wetting are presented as an introduction. Contact angle hysteresis is outlined and highlights the advantages in using dynamic analytical techniques over static methods. The surface free energy of a material illustrates how contact angle analysis is capable of providing supplementary surface characterization. Although single values are able to distinguish individual material differences, surface free energy and dynamic methods provide an improved understanding of material behavior. The frequently used sessile drop, captive bubble, and Wilhelmy plate techniques are discussed. Their use as both dynamic and static methods, along with the advantages and disadvantages of each technique, is explained. Conclusions: No single contact angle technique fully characterizes the wettability of a material surface, and the application of complimenting methods allows increased characterization. At present, there is not an ISO standard method designed for soft materials. It is important that each contact angle technique has a standard protocol, as small protocol differences between laboratories often contribute to a variety of published data that are not easily comparable. © 2013 Contact Lens Association of Ophthalmologists.

Efficacy and safety of second-generation antipsychotic long-acting injections (SGA LAIs) in maintenance treatment of bipolar disorder:protocol for a systematic review and meta-analysis

INTRODUCTION: Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder. METHODS AND ANALYSIS: The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy.

Application of Naïve Bayesian sequential analysis to primary care optometry

The objective of this study was to investigate the effects of circularity, comorbidity, prevalence and presentation variation on the accuracy of differential diagnoses made in optometric primary care using a modified form of naïve Bayesian sequential analysis. No such investigation has ever been reported before. Data were collected for 1422 cases seen over one year. Positive test outcomes were recorded for case history (ethnicity, age, symptoms and ocular and medical history) and clinical signs in relation to each diagnosis. For this reason only positive likelihood ratios were used for this modified form of Bayesian analysis that was carried out with Laplacian correction and Chi-square filtration. Accuracy was expressed as the percentage of cases for which the diagnoses made by the clinician appeared at the top of a list generated by Bayesian analysis. Preliminary analyses were carried out on 10 diagnoses and 15 test outcomes. Accuracy of 100% was achieved in the absence of presentation variation but dropped by 6% when variation existed. Circularity artificially elevated accuracy by 0.5%. Surprisingly, removal of Chi-square filtering increased accuracy by 0.4%. Decision tree analysis showed that accuracy was influenced primarily by prevalence followed by presentation variation and comorbidity. Analysis of 35 diagnoses and 105 test outcomes followed. This explored the use of positive likelihood ratios, derived from the case history, to recommend signs to look for. Accuracy of 72% was achieved when all clinical signs were entered. The drop in accuracy, compared to the preliminary analysis, was attributed to the fact that some diagnoses lacked strong diagnostic signs; the accuracy increased by 1% when only recommended signs were entered. Chi-square filtering improved recommended test selection. Decision tree analysis showed that accuracy again influenced primarily by prevalence, followed by comorbidity and presentation variation. Future work will explore the use of likelihood ratios based on positive and negative test findings prior to considering naïve Bayesian analysis as a form of artificial intelligence in optometric practice.

An analysis of the labor market situation of vocational students based on national and international data

The article focuses on the labour market situation and opportunities of the Hungarian vocational students. After briefly placing the topic in an international context, the study introduces the findings of the Hungarian empirical researches. Due to the differences between the various national education systems, it is not easy to make international comparisons; therefore I chose former socialist countries with characteristics similar to those of Hungary. When comparing the relevant data, it became clear that obtaining a diploma provides more advantages in Hungary. Hungarian researches suggest that vocational schools mostly attract students with poor competence test scores at the end of primary school. Also a significant proportion of these students are disadvantaged. Vocational students are the most likely to drop out of the system and their return to the school later is sporadic at best. Although a completed VET improves their employment conditions and prospects, many of the graduates will leave their profession or do unskilled labour. Their labour income varies greatly depending on their type of trade and experience gained.

Headspace analysis of smokeless powders: Development of mass calibration methods using microdrop printing for chromatographic and ion mobility spectrometric detection

Smokeless powder additives are usually detected by their extraction from post-blast residues or unburned powder particles followed by analysis using chromatographic techniques. This work presents the first comprehensive study of the detection of the volatile and semi-volatile additives of smokeless powders using solid phase microextraction (SPME) as a sampling and pre-concentration technique. Seventy smokeless powders were studied using laboratory based chromatography techniques and a field deployable ion mobility spectrometer (IMS). The detection of diphenylamine, ethyl and methyl centralite, 2,4-dinitrotoluene, diethyl and dibutyl phthalate by IMS to associate the presence of these compounds to smokeless powders is also reported for the first time. A previously reported SPME-IMS analytical approach facilitates rapid sub-nanogram detection of the vapor phase components of smokeless powders. A mass calibration procedure for the analytical techniques used in this study was developed. Precise and accurate mass delivery of analytes in picoliter volumes was achieved using a drop-on-demand inkjet printing method. Absolute mass detection limits determined using this method for the various analytes of interest ranged between 0.03–0.8 ng for the GC-MS and between 0.03–2 ng for the IMS. Mass response graphs generated for different detection techniques help in the determination of mass extracted from the headspace of each smokeless powder. The analyte mass present in the vapor phase was sufficient for a SPME fiber to extract most analytes at amounts above the detection limits of both chromatographic techniques and the ion mobility spectrometer. Analysis of the large number of smokeless powders revealed that diphenylamine was present in the headspace of 96% of the powders. Ethyl centralite was detected in 47% of the powders and 8% of the powders had methyl centralite available for detection from the headspace sampling of the powders by SPME. Nitroglycerin was the dominant peak present in the headspace of the double-based powders. 2,4-dinitrotoluene which is another important headspace component was detected in 44% of the powders. The powders therefore have more than one headspace component and the detection of a combination of these compounds is achievable by SPME-IMS leading to an association to the presence of smokeless powders.

Headspace Analysis of Smokeless Powders: Development of Mass Calibration Methods using Microdrop Printing for Chromatographic and Ion Mobility Spectrometric Detection

Smokeless powder additives are usually detected by their extraction from post-blast residues or unburned powder particles followed by analysis using chromatographic techniques. This work presents the first comprehensive study of the detection of the volatile and semi-volatile additives of smokeless powders using solid phase microextraction (SPME) as a sampling and pre-concentration technique. Seventy smokeless powders were studied using laboratory based chromatography techniques and a field deployable ion mobility spectrometer (IMS). The detection of diphenylamine, ethyl and methyl centralite, 2,4-dinitrotoluene, diethyl and dibutyl phthalate by IMS to associate the presence of these compounds to smokeless powders is also reported for the first time. A previously reported SPME-IMS analytical approach facilitates rapid sub-nanogram detection of the vapor phase components of smokeless powders. A mass calibration procedure for the analytical techniques used in this study was developed. Precise and accurate mass delivery of analytes in picoliter volumes was achieved using a drop-on-demand inkjet printing method. Absolute mass detection limits determined using this method for the various analytes of interest ranged between 0.03 - 0.8 ng for the GC-MS and between 0.03 - 2 ng for the IMS. Mass response graphs generated for different detection techniques help in the determination of mass extracted from the headspace of each smokeless powder. The analyte mass present in the vapor phase was sufficient for a SPME fiber to extract most analytes at amounts above the detection limits of both chromatographic techniques and the ion mobility spectrometer. Analysis of the large number of smokeless powders revealed that diphenylamine was present in the headspace of 96% of the powders. Ethyl centralite was detected in 47% of the powders and 8% of the powders had methyl centralite available for detection from the headspace sampling of the powders by SPME. Nitroglycerin was the dominant peak present in the headspace of the double-based powders. 2,4-dinitrotoluene which is another important headspace component was detected in 44% of the powders. The powders therefore have more than one headspace component and the detection of a combination of these compounds is achievable by SPME-IMS leading to an association to the presence of smokeless powders.

Multi-Scale Dynamic Study of Secondary Impact During Drop Testing of Surface Mount Packages

This dissertation focuses on design challenges caused by secondary impacts to printed wiring assemblies (PWAs) within hand-held electronics due to accidental drop or impact loading. The continuing increase of functionality, miniaturization and affordability has resulted in a decrease in the size and weight of handheld electronic products. As a result, PWAs have become thinner and the clearances between surrounding structures have decreased. The resulting increase in flexibility of the PWAs in combination with the reduced clearances requires new design rules to minimize and survive possible internal collisions impacts between PWAs and surrounding structures. Such collisions are being termed ‘secondary impact’ in this study. The effect of secondary impact on board-level drop reliability of printed wiring boards (PWBs) assembled with MEMS microphone components, is investigated using a combination of testing, response and stress analysis, and damage modeling. The response analysis is conducted using a combination of numerical finite element modeling and simplified analytic models for additional parametric sensitivity studies.

Analysis of N-nitrosames in water using micellar electrokinetic chromatography (MEKC) and development of online and offline methods of extraction and enrichment of neutral polar analytes

Evaluation of the quality of the environment is essential for human wellness as pollutants in trace amounts can cause serious health problem. Nitrosamines are a group of compounds that are considered potential carcinogens and can be found in drinking water (as disinfection byproducts), foods, beverages and cosmetics. To monitor the level of these compounds to minimize daily intakes, fast and reliable analytical techniques are required. As these compounds are relatively highly polar, extraction and enrichment from environmental samples (aqueous) are challenging. Also, the trend of analytical techniques toward the reduction of sample size and minimization of organic solvent use demands new methods of analysis. In light of fulfilling these requirements, a new method of online preconcentration tailored to an electrokinetic chromatography is introduced. In this method, electroosmotic flow (EOF) was suppressed to increase the interaction time between analyte and micellar phase, therefore the only force to mobilize the neutral analytes is the interaction of analyte with moving micelles. In absence of EOF, polarity of applied potential was switched (negative or positive) to force (anionic or cationic) micelles to move toward the detector. To avoid the excessive band broadening due to longer analysis time caused by slow moving micelles, auxiliary pressure was introduced to boost the micelle movement toward the detector using an in house designed and built apparatus. Applying the external auxiliary pressure significantly reduced the analysis times without compromising separation efficiency. Parameters, such as type of surfactants, composition of background electrolyte (BGE), type of capillary, matrix effect, organic modifiers, etc., were evaluated in optimization of the method. The enrichment factors for targeted analytes were impressive, particularly; cationic surfactants were shown to be suitable for analysis of nitrosamines due to their ability to act as hydrogen bond donors. Ammonium perfluorooctanoate (APFO) also showed remarkable results in term of peak shapes and number of theoretical plates. It was shown that the separation results were best when a high conductivity sample was paired with a BGE of lower conductivity. Using higher surfactant concentrations (up to 200 mM SDS) than usual (50 mM SDS) for micellar electrokinetic chromatography (MEKC) improved the sweeping. A new method for micro-extraction and enrichment of highly polar neutral analytes (N-Nitrosamines in particular) based on three-phase drop micro-extraction was introduced and its performance studied. In this method, a new device using some easy-to-find components was fabricated and its operation and application demonstrated. Compared to conventional extraction methods (liquid-liquid extraction), consumption of organic solvents and operation times were significantly lower.

Application of the latency insertion method (LIM) to the analysis of large circuit interconnect networks

The focus of this research is to explore the applications of the finite difference formulation based on the latency insertion method (LIM) to the analysis of circuit interconnects. Special attention is devoted to addressing the issues that arise in very large networks such as on-chip signal and power distribution networks. We demonstrate that the LIM has the power and flexibility to handle various types of analysis required at different stages of circuit design. The LIM is particularly suitable for simulations of very large scale linear networks and can significantly outperform conventional circuit solvers (such as SPICE).

Statistical Analysis of Sea Surface Temperature and Chlorophyll-a Concentration Patterns in the Gulf of Tadjourah (Djibouti)

The sea surface temperature (SST) and chlorophyll-a concentration (CHL-a) were analysed in the Gulf of Tadjourah from two set of 8-day composite satellite data, respectively from 2008 to 2012 and from 2005 to 2011. A singular spectrum analysis (SSA) shows that the annual cycle of SST is strong (74.3% of variance) and consists of warming (April-October) and cooling (November-March) of about 2.5C than the long-term average. The semi-annual cycle captures only 14.6% of temperature variance and emphasises the drop of SST during July-August. Similarly, the annual cycle of CHL-a (29.7% of variance) depicts high CHL-a from June to October and low concentration from November to May. In addition, the first spatial empirical orthogonal function (EOF) of SST (93% of variance) shows that the seasonal warming/cooling is in phase across the whole study area but the southeastern part always remaining warmer or cooler. In contrast to the SST, the first EOF of CHL-a (54.1% of variance) indicates the continental shelf in phase opposition with the offshore area in winter during which the CHL-a remains sequestrated in the coastal area particularly in the south-east and in the Ghoubet Al-Kharab Bay. Inversely during summer, higher CHL-a quantities appear in the offshore waters. In order to investigate processes generating these patterns, a multichannel spectrum analysis was applied to a set of oceanic (SST, CHL-a) and atmospheric parameters (wind speed, air temperature and air specific humidity). This analysis shows that the SST is well correlated to the atmospheric parameters at an annual scale. The windowed cross correlation indicates that this correlation is significant only from October to May. During this period, the warming was related to the solar heating of the surface water when the wind is low (April-May and October) while the cooling (November-March) was linked to the strong and cold North-East winds and to convective mixing. The summer drop in SST followed by a peak of CHL-a, seems strongly correlated to the upwelling. The second EOF modes of SST and CHL-a explain respectively 1.3% and 5% of the variance and show an east-west gradient during winter that is reversed during summer. This work showed that the seasonal signals have a wide spatial influence and dominate the variability of the SST and CHL-a while the east-west gradient are specific for the Gulf of Tadjourah and seem induced by the local wind modulated by the topography.

Economic well-being and poverty among the elderly: an analysis based on a collective consumption model

We apply the collective consumption model of Browning, Chiappori and Lewbel (2006) to analyse economic well-being and poverty among the elderly. The model focuses on individual preferences, a consumption technology that captures the economies of scale of living in a couple, and a sharing rule that governs the intra-household allocation of resources. The model is applied to a time series of Dutch consumption expenditure surveys. Our empirical results indicate substantial economies of scale and a wifeís share that is increasing in total expenditures. We further calculated poverty rates by means of the collective consumption model. Collective poverty rates of widows and widowers turn out to be slightly lower than traditional ones based on a standard equivalence scale. Poverty among women (men) in elderly couples, however, seems to be heavily underestimated (overestimated) by the traditional approach. Finally, we analysed the impact of becoming a widow(er). Based on cross-sectional evidence, we find that the drop (increase) in material well-being following the husbandís death is substantial for women in high (low) expenditure couples. For men, the picture is reversed.

Analysis of the impact of stationary energy storage systems in trolleybus grids using Simulink-based modelling

The voltage profile of the catenary between traction substations (TSSs) is affected by the trolleybus current intake and by its position with respect to the TSSs: the higher the current requested by the bus and the further the bus from the TSSs, the deeper the voltage drop. When the voltage drops below 500V, the trolleybus is forced to decrease its consumption by reducing its input current. This thesis deals with the analysis of the improvements that the installation of an BESS produces in the operation of a particularly loaded FS of the DC trolleybus network of the city of Bologna. The stationary BESS is charged by the TSSs during off-peak times and delivers the stored energy when the catenary is overloaded alleviating the load on the TSSs and reducing the voltage drops. Only IMC buses are considered in the prospect of a future disposal of all internal combustion engine vehicles. These trolleybuses cause deeper voltage drops because they absorb enough current to power their traction motor and recharge the on board battery. The control of the BESS aims to keep the catenary voltage within the admissible voltage range and makes sure that all physical limitations are met. A model of FS Marconi Trento Trieste is implemented in Simulink environment to simulate its daily operation and compare the behavior of the trolleybus network with and without BESS. From the simulation without BESS, the best location of the energy storage system is deduced, and the battery control is tuned. Furthermore, from the knowledge of the load curve and the battery control trans-characteristic, it is formulated a prediction of the voltage distribution at BESS connection point. The prediction is then compared with the simulation results to validate the Simulink model. The BESS allows to decrease the voltage drops along the catenary, the Joule losses and the current delivered by the TSSs, indicating that the BESS can be a solution to improve the operation of the trolleybus network.