Engineering design applications of surrogate-assisted optimization techniques

The construction of models aimed at learning the behaviour of a system whose responses to inputs are expensive to measure is a branch of statistical science that has been around for a very long time. Geostatistics has pioneered a drive over the last half century towards a better understanding of the accuracy of such ‘surrogate’ models of the expensive function. Of particular interest to us here are some of the even more recent advances related to exploiting such formulations in an optimization context. While the classic goal of the modelling process has been to achieve a uniform prediction accuracy across the domain, an economical optimization process may aim to bias the distribution of the learning budget towards promising basins of attraction. This can only happen, of course, at the expense of the global exploration of the space and thus finding the best balance may be viewed as an optimization problem in itself. We examine here a selection of the state of-the-art solutions to this type of balancing exercise through the prism of several simple, illustrative problems, followed by two ‘real world’ applications: the design of a regional airliner wing and the multi-objective search for a low environmental impact hous

Spectroscopic analysis of finite size effects around a Kondo quantum dot

We consider a simple setup in which a small quantum dot is strongly connected to a finite size box. This box can be either a metallic box or a finite size quantum wire.The formation of the Kondo screening cloud in the box strongly depends on the ratio between the Kondo temperature and the box level spacing. By weakly connecting two metallic reservoirs to the quantum dot, a detailed spectroscopic analysis can be performed. Since the transport channels and the screening channels are almost decoupled, such a setup allows an easier access to the measure of finite-size effects associated with the finite extension of the Kondo cloud.Comment: contribution to Les Houches proceeding, ``Quantum magnetism'' 200

Effects of Ursolic Acid and its Analogues on Soybean 15-Lipoxygenase Activity and the Proliferation Rate of A human Gastric Tumour Cell Line

The authors have previously isolated and purified ursolic acid from heather flowers (Calluna vulgarts). This terpene was found to inhibit HL-60 leukaemic cell proliferation and arachidonic acid oxidative metabolism in various cell species. The effects of ursolic acid and its analogues on soybean 15-lipoxygenase activity and on the proliferation of a human gastric tumour cell line (HGT), have been assessed. These triterpenes inhibited soybean 15-lipoxygenase at its optimal activity (pH 9). The proliferation ofHGT was decreased in a dose-dependent manner. At 20 μM the rank order is: ursolic acid > uvaol > oleanolic acid > methyl ursolate. The carboxylic group at the C28 position of ursolic acid appears to be implicated in the inhibition of both lipoxygenase activity and cell proliferation. Thus methylation of this group decreases these two inhibitory properties. Oleanolic acid, which differs by the position of one methyl group (C20 instead of C19) is less inhibitory than ursolic acid. The lipophilicity of the terpene is also implicated since uvaol appears to be more inhibitory than methyl ursolate

Multisteroid LC-MS/MS assay for glucocorticoids and androgens, and its application in Addison’s disease

Objective: Liquid chromatography–tandem mass spectrometry (LC–MS/MS) offers superior analytical specificity compared with immunoassays, but it is not available in many regions and hospitals due to expensive instrumentation and tedious sample preparation. Thus, we developed an automated, high-throughput LC–MS/MS assay for simultaneous quantification of ten endogenous and synthetic steroids targeting diseases of the hypothalamic–pituitary–adrenal axis and gonads. Methods: Deuterated internal standards were added to 85 μl serum and processed by liquid–liquid extraction. Cortisol, cortisone, prednisolone, prednisone, 11-deoxycortisol, dexamethasone, testosterone, androstenedione and progesterone were resolved by ultra-high-pressure chromatography on a reversed-phase column in 6.1 min and detected by triple-quadrupole mass spectrometry. The method was used to assess steroid profiles in women with Addison's disease (AD, n=156) and blood donors (BDs, n=102). Results: Precisions ranged from 4.5 to 10.1% relative standard deviations (RSD), accuracies from 95 to 108% and extraction recoveries from 60 to 84%. The method was practically free of matrix effects and robust to individual differences in serum composition. Most postmenopausal AD women had extremely low androstenedione concentrations, below 0.14 nmol/l, and median testosterone concentrations of 0.15 nmol/l (interquartile range 0.00–0.41), considerably lower than those of postmenopausal BDs (1.28 nmol/l (0.96–1.64) and 0.65 nmol/l (0.56–1.10) respectively). AD women in fertile years had androstenedione concentrations of 1.18 nmol/l (0.71–1.76) and testosterone concentrations of 0.44 nmol/l (0.22–0.63), approximately half of those found in BDs of corresponding age. Conclusion: This LC–MS/MS assay provides highly sensitive and specific assessments of glucocorticoids and androgens with low sample volumes and is suitable for endocrine laboratories and research. Its utility has been demonstrated in a large cohort of women with AD, and the data suggest that women with AD are particularly androgen deficient after menopause.publishedVersio

Exploring the polarization of gluons in the nucleon

We give an overview of the current status of investigations of the polarization of gluons in the nucleon. We describe some of the physics of the spin-dependent gluon parton distribution and its phenomenology in high-energy polarized hadronic scattering. We also review the recent experimental results.Comment: 10 pages, 13 figures. Talk presented at the "Second Meeting of the APS Topical Group on Hadronic Physics", Nashville, Tennessee, October 22-24, 2006. Reference adde

Population assessment of future trajectories in coronary heart disease mortality.

Background: Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s, largely reflecting improvements in cardiovascular risk factors. The purpose of this study was to predict future CHD mortality in Iceland based on potential risk factor trends. Methods and findings: The previously validated IMPACT model was used to predict changes in CHD mortality between 2010 and 2040 among the projected population of Iceland aged 25–74. Calculations were based on combining: i) data on population numbers and projections (Statistics Iceland), ii) population risk factor levels and projections (Refine Reykjavik study), and iii) effectiveness of specific risk factor reductions (published meta-analyses). Projections for three contrasting scenarios were compared: 1) If the historical risk factor trends of past 30 years were to continue, the declining death rates of past decades would level off, reflecting population ageing. 2) If recent trends in risk factors (past 5 years) continue, this would result in a death rate increasing from 49 to 70 per 100,000. This would reflect a recent plateau in previously falling cholesterol levels and recent rapid increases in obesity and diabetes prevalence. 3) Assuming that in 2040 the entire population enjoys optimal risk factor levels observed in low risk cohorts, this would prevent almost all premature CHD deaths before 2040. Conclusions: The potential increase in CHD deaths with recent trends in risk factor levels is alarming both for Iceland and probably for comparable Western populations. However, our results show considerable room for reducing CHD mortality. Achieving the best case scenario could eradicate premature CHD deaths by 2040. Public health policy interventions based on these predictions may provide a cost effective means of reducing CHD mortality in the future

Comparison of usefulness of computer assisted continuous 48-h 3-lead with 12-lead ECG ischaemia monitoring for detection and quantitation of ischaemia in patients with unstable angina

AIMS: The selection of ECG leads used for ST monitoring may influence detection and quantitation of ischaemia. METHODS: We compared on-line continuous 48-h 12-lead against 3-lead ST monitoring in 130 unstable angina patients (Mortara. ELI-100). Onset and offset of ST episodes were defined by the lead with the first > or = 100 microV ST change relative to baseline and the lead with the latest return to baseline ST level, respectively. ST episodes were calculated for 12 leads and 3 leads (V2, V5, III) separately. RESULTS: ST episodes were detected in 88 patients (77%) by 12-lead and in 71 patients (62%) by 3-lead ST monitoring (P < 0.02). The median number (25.75%) of episodes/patient was 1 (0.3) for 3-lead and 2 (1.6) for 12-lead (P < 0.0001). The total duration of ischaemia detected during 12-lead far exceeded 3-lead monitoring: 12.3 (1, 58.2) and 1.7 (0, 23.3) min respectively (P < 0.0001). The probability of recurrent ischaemia declined most during the first 24 h of monitoring. After a period without ST changes of 1, 12, 24 and 36 h, the probabilities of recurrent ischaemia were 63, 31, 14 and 9%, respectively. CONCLUSIONS: Continuous 12-lead ST monitoring increases detection rate and duration of ST episodes compared to 3-lead ST monitoring. The use of continuous 12-lead ECG monitoring devices on emergency wards and coronary care units is recommended

Quantum Memories. A Review based on the European Integrated Project "Qubit Applications (QAP)"

We perform a review of various approaches to the implementation of quantum memories, with an emphasis on activities within the quantum memory sub-project of the EU Integrated Project "Qubit Applications". We begin with a brief overview over different applications for quantum memories and different types of quantum memories. We discuss the most important criteria for assessing quantum memory performance and the most important physical requirements. Then we review the different approaches represented in "Qubit Applications" in some detail. They include solid-state atomic ensembles, NV centers, quantum dots, single atoms, atomic gases and optical phonons in diamond. We compare the different approaches using the discussed criteria.Comment: 22 pages, 12 figure