Scaffold searching: automated identification of similar ring systems for the design of combinatorial libraries

Rigid ring systems can be used to position receptor-binding functional groups in 3D space and they thus play an increasingly important role in the design of combinatorial libraries. This paper discusses the use of shape-similarity methods to identify ring systems that are structurally similar to, and aligned with, a user-defined target ring system. These systems can be used as alternative scaffolds for the construction of a combinatorial library

Issues of partial credit in mathematical assessment by computer

The CALM Project for Computer Aided Learning in Mathematics has operated at Heriot‐Watt University since 1985. From the beginning CALM has featured assessment in its programs (Beevers, Cherry, Foster and McGuire, 1991), and enabled both students and teachers to view progress in formative assessment The computer can play a role in at least four types of assessment: diagnostic, self‐test, continuous and grading assessment. The TLTP project Mathwise employs the computer in three of these roles. In 1994 CALM reported on an educational experiment in which the computer was used for the first time to grade, in part, the learning of a large class of service mathematics students (Beevers, McGuire, Stirling and Wild ,1995), using the Mathwise assessment template. At that time the main issues identified were those of ‘partial credit’ and communication between the student and the computer. These educational points were addressed in the next phase of the CALM Project in which the commercial testing program Interactive PastPapers was developed. The main aim of this paper is to describe how Interactive Past Papers has been able to incorporate some approaches to partial credit which has helped to alleviate student worries on these issues. Background information on other features in Interactive Past Papers is also included to provide context for the discussion

High angular resolution mm- and submm-observations of dense molecular gas in M82

Researchers observed CO(7-6), CO(3-2), HCN(3-2) and HCO+(3-2) line emission toward the starburst nucleus of M82 and have obtained an upper limit to H13CN(3-2). These are the first observations of the CO(7-6), HCN(3-2) and HCO+(3-2) lines in any extragalactic source. Researchers took the CO(7-6) spectrum in January 1988 at the Infrared Telescope Facility (IRTF) with the Max Planck Institute for Extraterrestrial Physics/Univ. of California, Berkeley 800 GHz Heterodyne Receiver. In March 1989 researchers used the Institute for Radio Astronomy in the Millimeter range (IRAM) 30 m telescope to observe the CO(3-2) line with the new MPE 350 GHz Superconductor Insulator Superconductor (SIS) receiver and the HCN(3-2) and HCO+(3-2) lines with the (IRAM) 230 GHz SIS receiver (beam 12" FWHM, Blundell et al. 1988). The observational parameters are summarized

Stability of condensate in superconductors

According to the BCS theory the superconducting condensate develops in a single quantum mode and no Cooper pairs out of the condensate are assumed. Here we discuss a mechanism by which the successful mode inhibits condensation in neighboring modes and suppresses a creation of noncondensed Cooper pairs. It is shown that condensed and noncondensed Cooper pairs are separated by an energy gap which is smaller than the superconducting gap but large enough to prevent nucleation in all other modes and to eliminate effects of noncondensed Cooper pairs on properties of superconductors. Our result thus justifies basic assumptions of the BCS theory and confirms that the BCS condensate is stable with respect to two-particle excitations

Cosmological constraints from galaxy clustering

In this manuscript I review the mathematics and physics that underpins recent work using the clustering of galaxies to derive cosmological model constraints. I start by describing the basic concepts, and gradually move on to some of the complexities involved in analysing galaxy redshift surveys, focusing on the 2dF Galaxy Redshift Survey (2dFGRS) and the Sloan Digital Sky survey (SDSS). Difficulties within such an analysis, particularly dealing with redshift space distortions and galaxy bias are highlighted. I then describe current observations of the CMB fluctuation power spectrum, and consider the importance of measurements of the clustering of galaxies in light of recent experiments. Finally, I provide an example joint analysis of the latest CMB and large-scale structure data, leading to a set of parameter constraints.Comment: 30 pages, 13 figures. Lecture given at Third Aegean Summer School, The invisible universe: Dark matter and Dark energ

Integrated cardiopulmonary MRI assessment of pulmonary hypertension

Pulmonary hypertension (PH) is a heterogeneous condition that can affect the lung parenchyma, pulmonary vasculature, and cardiac chambers. Accurate diagnosis often requires multiple complex assessments of the cardiac and pulmonary systems. MRI is able to comprehensively assess cardiac structure and function, as well as lung parenchymal, pulmonary vascular, and functional lung changes. Therefore, MRI has the potential to provide an integrated functional and structural assessment of the cardiopulmonary system in a single exam. Cardiac MRI is used in the assessment of PH in most large PH centers, whereas lung MRI is an emerging technique in patients with PH. This article reviews the current literature on cardiopulmonary MRI in PH, including cine MRI, black-blood imaging, late gadolinium enhancement, T1 mapping, myocardial strain analysis, contrast-enhanced perfusion imaging and contrast-enhanced MR angiography, and hyperpolarized gas functional lung imaging. This article also highlights recent developments in this field and areas of interest for future research including cardiac MRI-based diagnostic models, machine learning in cardiac MRI, oxygen-enhanced 1H imaging, contrast-free 1H perfusion and ventilation imaging, contrast-free angiography and UTE imaging

Stability analysis of agegraphic dark energy in Brans-Dicke cosmology

Stability analysis of agegraphic dark energy in Brans-Dicke theory is presented in this paper. We constrain the model parameters with the observational data and thus the results become broadly consistent with those expected from experiment. Stability analysis of the model without best fitting shows that universe may begin from an unstable state passing a saddle point and finally become stable in future. However, with the best fitted model, There is no saddle intermediate state. The agegraphic dark energy in the model by itself exhibits a phantom behavior. However, contribution of cold dark matter on the effective energy density modifies the state of teh universe from phantom phase to quintessence one. The statefinder diagnosis also indicates that the universe leaves an unstable state in the past, passes the LCDM state and finally approaches the sable state in future.Comment: 15 pages, 12 figure

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research