Showing papers by "University of Leicester published in 2003"

Regulation of cell death: the calcium-apoptosis link.

Abstract: To live or to die? This crucial question eloquently reflects the dual role of Ca2+ in living organisms--survival factor or ruthless killer. It has long been known that Ca2+ signals govern a host of vital cell functions and so are necessary for cell survival. However, more recently it has become clear that cellular Ca2+ overload, or perturbation of intracellular Ca2+ compartmentalization, can cause cytotoxicity and trigger either apoptotic or necrotic cell death.

Accretion leading to collision and the Permian Solonker suture, Inner Mongolia, China: Termination of the central Asian orogenic belt

Abstract: [1] The Solonker suture records the termination of the central Asian Orogenic Belt (CAOB). However, tectonic development of the Solonker suture is poorly understood. We report new field data for the Ondor Sum melange in the Ulan valley, and present a new evaluation of the orogenic belt extending from the southern Mongolia cratonic boundary to the north China craton within the context of a new geological framework and tectonic model, which incorporates relevant data from the literature. The southern accretionary zone between the north China craton and the Solonker suture is characterized by the Mid-Ordovician-Early Silurian Ulan island arc-Ondor Sum subduction-accretion complex and the Bainaimiao arc. This zone was consolidated by the Carboniferous-Permian when it evolved into an Andean-type magmatic margin above a south dipping subduction zone. The northern accretionary zone north of the Solonker suture extends southward from a Devonian to Carboniferous active continental margin, through the Hegenshan ophiolite-arc accretionary complex to the Late Carboniferous Baolidao arc associated with some accreted Precambrian blocks. This northern zone had consolidated by the Permian when it developed into an Andean-type magmatic margin above a north dipping subduction zone. Final subduction of the central Asian ocean caused the two opposing active continental margins to collide, leading to formation of the Solonker suture in the end-Permian. Predominant northward subduction during final formation of the suture gave rise in the upper northern plate to a large-scale, postcollisional, south directed thrust and fold belt in the Triassic-Jurassic. In summary, the CAOB underwent three final stages of tectonic development: early Japanese-type accretion, Andean-type magmatism, and Himalayan-type collision.

On characterizing the variability properties of X-ray light curves from active galaxies

Abstract: We review some practical aspects of measuring the amplitude of variability in 'red noise' light curves typical of those from active galactic nuclei (AGN). The quantities commonly used to estimate the variability amplitude in AGN light curves, such as the fractional rms variability amplitude, F v a r , and excess variance, σ 2 XS, are examined. Their statistical properties, relationship to the power spectrum and uses for investigating the nature of the variability processes are discussed. We demonstrate that σ 2 XS (or similarly F v a r ) shows large changes from one part of the light curve to the next, even when the variability is produced by a stationary process. This limits the usefulness of these estimators for quantifying differences in variability amplitude between different sources or from epoch to epoch in one source. Some examples of the expected scatter in the variance are tabulated for various typical power spectral shapes, based on Monte Carlo simulations. The excess variance can be useful for comparing the variability amplitudes of light curves in different energy bands from the same observation. Monte Carlo simulations are used to derive a description of the uncertainty in the amplitude expected between different energy bands (due to measurement errors). Finally, these estimators are used to demonstrate some variability properties of the bright Seyfert 1 galaxy Markarian 766. The source is found to show a strong, linear correlation between rms amplitude and flux, and to show significant spectral variability.

Hot L1s account for the bulk of retrotransposition in the human population

Abstract: Although LINE-1 (long interspersed nucleotide element-1, L1) retrotransposons comprise 17% of the human genome, an exhaustive search of the December 2001 “freeze” of the haploid human genome working draft sequence (95% complete) yielded only 90 L1s with intact ORFs. We demonstrate that 38 of 86 (44%) L1s are polymorphic as to their presence in human populations. We cloned 82 (91%) of the 90 L1s and found that 40 of the 82 (49%) are active in a cultured cell retrotransposition assay. From these data, we predict that there are 80–100 retrotransposition-competent L1s in an average human being. Remarkably, 84% of assayed retrotransposition capability was present in six highly active L1s (hot L1s). By comparison, four of five full-length L1s involved in recent human insertions had retrotransposition activity comparable to the six hot L1s in the human genome working draft sequence. Thus, our data indicate that most L1 retrotransposition in the human population stems from hot L1s, with the remaining elements playing a lesser role in genome plasticity.

The human Y chromosome: an evolutionary marker comes of age

Abstract: Until recently, the Y chromosome seemed to fulfil the role of juvenile delinquent among human chromosomes — rich in junk, poor in useful attributes, reluctant to socialize with its neighbours and with an inescapable tendency to degenerate. The availability of the near-complete chromosome sequence, plus many new polymorphisms, a highly resolved phylogeny and insights into its mutation processes, now provide new avenues for investigating human evolution. Y-chromosome research is growing up.

On characterising the variability properties of X-ray light curves from active galaxies

Abstract: We review some practical aspects of measuring the amplitude of variability in `red noise' light curves typical of those from Active Galactic Nuclei (AGN). The quantities commonly used to estimate the variability amplitude in AGN light curves, such as the fractional rms variability amplitude, F_var, and excess variance, sigma_XS^2, are examined. Their statistical properties, relationship to the power spectrum, and uses for investigating the nature of the variability processes are discussed. We demonstrate that sigma_XS^2 (or similarly F_var) shows large changes from one part of the light curve to the next, even when the variability is produced by a stationary process. This limits the usefulness of these estimators for quantifying differences in variability amplitude between different sources or from epoch to epoch in one source. Some examples of the expected scatter in the variance are tabulated for various typical power spectral shapes, based on Monte Carlo simulations. The excess variance can be useful for comparing the variability amplitudes of light curves in different energy bands from the same observation. Monte Carlo simulations are used to derive a description of the uncertainty in the amplitude expected between different energy bands (due to measurement errors). Finally, these estimators are used to demonstrate some variability properties of the bright Seyfert 1 galaxy Markarian 766. The source is found to show a strong, linear correlation between rms amplitude and flux, and to show significant spectral variability.

Black Holes, Galaxy Formation, and the MBH-σ Relation

Abstract: Recent X-ray observations of intense high-speed outflows in quasars suggest that supercritical accretion on to the central black hole may have an important effect on a host galaxy. I revisit some ideas of Silk & Rees and assume that such flows occur in the final stages of building up the black hole mass. It is now possible to model explicitly the interaction between the outflow and the host galaxy. This is found to resemble a momentum-driven stellar wind bubble, implying a relation MBH = (fgκ/2πG2)σ4 1.5 × 108σ M☉ between black hole mass and bulge velocity dispersion (fg = gas fraction of total matter density, κ = electron scattering opacity), without free parameters. This is remarkably close to the observed relation in both slope and normalization. This result suggests that the central black holes in galaxies gain most of their mass in phases of super-Eddington accretion, which are presumably obscured or at high redshift. Observed super-Eddington quasars are apparently late in growing their black hole masses.

Black Holes, Galaxy Formation, and the M_BH-sigma Relation

Abstract: Recent X-ray observations of intense high-speed outflows in quasars suggest that supercritical accretion on to the central black hole may have an important effect on a host galaxy. I revisit some ideas of Silk and Rees, and assume such flows occur in the final stages of building up the black hole mass. It is now possible to model explicitly the interaction between the outflow and the host galaxy. This is found to resemble a momentum-driven stellar wind bubble, implying a relation M_BH = (f_g kappa/2 pi G^2) sigma^4 = 1.5 10^8 sigma_200^4 Msun between black hole mass and bulge velocity dispersion (f_g = gas fraction of total matter density, kappa = electron scattering opacity), without free parameters. This is remarkably close to the observed relation in both slope and normalization. This result suggests that the central black holes in galaxies gain most of their mass in phases of super-Eddington accretion, which are presumably obscured or at high redshift. Observed super-Eddington quasars are apparently late in growing their black hole masses.

Reply to ``Comment on `Performance of different synchronization measures in real data: A case study on electroencephalographic signals' ''

Abstract: We agree with the Comment by Duckrow and Albano [Phys. Rev. E 67, 063901 (2003)] that mutual information, estimated with an optimized algorithm, can be a useful tool for studying synchronization in real data. However, we point out that the improvement they found is mainly due to an interesting but nonstandard embedding technique used, and not so much due to the algorithm used for the estimation of mutual information itself. We also address the issue of stationarity of electroencephalographic (EEG) data.

Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes

Abstract: Although ischaemic heart disease is the predominant cause of mortality in older people with diabetes, age-specific mortality rates have not been published for patients with Type 1 diabetes. The Diabetes UK cohort, essentially one of patients with Type 1 diabetes, now has sufficient follow-up to report all heart disease, and specifically ischaemic heart disease, mortality rates by age. A cohort of 23,751 patients with insulin-treated diabetes, diagnosed under the age of 30 years and from throughout the United Kingdom, was identified during the period 1972 to 1993 and followed for mortality until December 2000. Age- and sex-specific heart disease mortality rates and standardised mortality ratios were calculated. There were 1437 deaths during the follow-up, 536 from cardiovascular disease, and of those, 369 from ischaemic heart disease. At all ages the ischaemic heart disease mortality rates in the cohort were higher than in the general population. Mortality rates within the cohort were similar for men and women under the age of 40. The standardised mortality ratios were higher in women than men at all ages, and in women were 44.8 (95%CI 20.5–85.0) at ages 20–29 and 41.6 (26.7–61.9) at ages 30–39. The risk of mortality from ischaemic heart disease is exceptionally high in young adult women with Type 1 diabetes, with rates similar to those in men with Type 1 diabetes under the age of 40. These observations emphasise the need to identify and treat coronary risk factors in these young patients.

Kinetically inert transition metal complexes that reversibly bind to DNA

Abstract: Transition metal complexes that reversibly bind to DNA have been studied for almost 30 years. In the last few years a variety of new systems have been developed, employing a range of metal ions and ligand architectures. In many cases, high affinity binding and specific selectivities have been observed. These complexes display properties that make them attractive as probes of DNA structure and function, suggesting that they may find a role as prototypical tools for a spectrum of applications, from basic molecular biology to medicine. This review presents an overview of some of the structures and properties of such complexes.

Rankings of academic journals and institutions in economics

Abstract: We conducted a worldwide ranking of academic institutions that produce research in a list of thirty top research journals in economics. We also computed journal rankings for the same period and hence we do not rely on weights that were computed for research carried out in earlier periods. The United States is clearly the dominant force in the top-fifty group, but European academic institutions are well represented in the group of the top 200 universities worldwide as are universities from Asia and the Far East in particular. (JEL: A14, A10)

Dynamic Contrast-Enhanced Magnetic Resonance Imaging As a Biomarker for the Pharmacological Response of PTK787/ZK 222584, an Inhibitor of the Vascular Endothelial Growth Factor Receptor Tyrosine Kinases, in Patients With Advanced Colorectal Cancer and Liver Metastases: Results From Two Phase I Studies

Abstract: Purpose: PTK787/ZK 222584 (PTK/ZK), an orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, inhibits VEGF-mediated angiogenesis. The pharmacodynamic effects of PTK/ZK were evaluated by assessing changes in contrast-enhancement parameters of metastatic liver lesions using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced colorectal cancer treated in two ongoing, dose-escalating phase I studies. Patients and Methods: Twenty-six patients had DCE-MRI performed at baseline, day 2, and at the end of each 28-day cycle. Doses of oral PTK/ZK ranged from 50 to 2000 mg once daily. Tumor permeability and vascularity were assessed by calculating the bidirectional transfer constant (Ki). The percentage of baseline Ki (% of baseline Ki) at each time point was compared with pharmacokinetic and clinical end points. Results: A significant negative correlation exists between the % of baseline Ki and increase in PTK/ZK oral dose and plasma leve...

White Cell Telomere Length and Risk of Premature Myocardial Infarction

Abstract: Objective— Biological age may be distinct from chronological age and contribute to the pathogenesis of age-related diseases. Mean telomeres lengths provide an assessment of biological age with shorter telomeres, indicating increased biological age. We investigated whether subjects with premature myocardial infarction (MI) had shorter leukocyte telomeres. Methods and Results— Mean terminal restriction fragment (TRF) length, a measure of average telomere size, was compared in leukocyte DNA of 203 cases with a premature MI ( P P Conclusions— The findings support the concept that biological age may play a role in the etiology of coronary heart disease and have potentially important implications for our understanding of its genetic etiology, pathogenesis, and variable age of onset.

Learning as Apprentices in the Contemporary UK Workplace: creating and managing expansive and restrictive participation

Abstract: Situated learning theory provides a rich conceptual framework for analysing the processes by which apprentices become (full) participants in a community of practice. This article uses case study evidence from the UK?s Modern Apprenticeship programme to show how this framework can be developed by identifying features of expansive and restrictive participationwhich help distinguish between different approaches to apprenticeship. We suggest that three inter-related themes (participation, personal development and institutional arrangements) underpin an expansive/restrictive continuum. The analysis is used to categorise company approaches to apprenticeship according to their expansive and restrictive characteristics, and to illustrate the variable learning opportunities that are being created for apprentices under the Modern Apprenticeship.

Antiwindup for stable linear systems with input saturation: an LMI-based synthesis

Abstract: This paper considers closed-loop quadratic stability and L/sub 2/ performance properties of linear control systems subject to input saturation. More specifically, these properties are examined within the context of the popular linear antiwindup augmentation paradigm. Linear antiwindup augmentation refers to designing a linear filter to augment a linear control system subject to a local specification, called the "unconstrained closed-loop behavior." Building on known results on H/sub /spl infin// and LPV synthesis, the fixed order linear antiwindup synthesis feasibility problem is cast as a nonconvex matrix optimization problem, which has an attractive system theoretic interpretation: the lower bound on the achievable L/sub 2/ performance is the maximum of the open and unconstrained closed-loop L/sub 2/ gains. In the special cases of zero-order (static) and plant-order antiwindup compensation, the feasibility conditions become (convex) linear matrix inequalities. It is shown that, if (and only if) the plant is asymptotically stable, plant-order linear antiwindup compensation is always feasible for large enough L/sub 2/ gain and that static antiwindup compensation is feasible provided a quasi-common Lyapunov function, between the open-loop and unconstrained closed-loop, exists. Using the solutions to the matrix feasibility problems, the synthesis of the antiwindup augmentation achieving the desired level of L/sub 2/ performance is then accomplished by solving an additional LMI.

Social inequalities and the common mental disorders: a systematic review of the evidence.

Abstract: Background: Of two large-scale government-commissioned studies of common mental disorders in the UK, one found occupational social class to be the strongest marker of risk while the other showed no clear relationship. This study reviews the published evidence on the links between conventional markers of social position and the common mental disorders in developed countries. Methods: Inclusion criteria covered general population based studies with broad social class variation; samples of 3,000 or more adults of working age; identification of mental illness by validated instruments; social position identified by explicit standard markers; fieldwork undertaken since 1980; published output on key areas of interest. Incompatible study methods and concepts made statistical pooling of results invalid. Results: Of nine studies, eight provide evidence of an association between one or more markers of less privileged social position and higher prevalence of common mental disorders. For some individual indicators in particular studies, no clear trend was evident, but no study showed a contrary trend for any indicator. The more consistent associations were with unemployment, less education and low income or material standard of living. Occupational social class was the least consistent marker. Conclusions: Common mental disorders are significantly more frequent in socially disadvantaged populations. More precise indicators of education, employment and material circumstances are better markers of increased rates than occupational social class.

The Labour of Aesthetics and the Aesthetics of Organization

Abstract: This article develops the conceptualization and analysis of aesthetic labour in two parts. The first part focuses on conceptualizing aesthetic labour. We critically revisit the emotional labour literature, arguing that the analysis of interactive service work is impeded by the way in which its corporeal aspects are retired and that, by shifting the focus from emotional to aesthetic labour, we are able to recuperate the embodied character of service work. We then explore the insights provided by the sociological perspectives on the body contained in the works of Goffman and Bourdieu in order to conceptualize aesthetic labour as embodied labour. In the second part, we develop our analysis of aesthetic labour within the context of a discussion of the aesthetics of organization. We discern three ways in which aesthetics is recognized to imbue organization: aesthetics of organization, aesthetics in organization and aesthetics as organization. We contend that employees are increasingly seen not simply as 'software' but as 'hardware', in the sense that they too can be corporately moulded to portray the organizational aesthetic. We ground this analysis in a case study from research conducted by the authors.

Comparative Analysis of the Arabidopsis Pollen Transcriptome

Abstract: We present a genome-wide view of the male gametophytic transcriptome in Arabidopsis based on microarray analysis. In comparison with the transcriptome of the sporophyte throughout development, the pollen transcriptome showed reduced complexity and a unique composition. We identified 992 pollen-expressed mRNAs, nearly 40% of which were detected specifically in pollen. Analysis of the functional composition of the pollen transcriptome revealed the over-representation of mRNAs encoding proteins involved in cell wall metabolism, cytoskeleton, and signaling and under-representation of mRNAs involved in transcription and protein synthesis. For several gene families, we observed a common pattern of mutually exclusive gene expression between pollen and sporophytic tissues for different gene family members. Our results provide a 50-fold increase in the knowledge of genes expressed in Arabidopsis pollen. Moreover, we also detail the extensive overlap (61%) of the pollen transcriptome with that of the sporophyte, which provides ample potential to influence sporophytic fitness through gametophytic selection.

A high-velocity ionized outflow and XUV photosphere in the narrow emission line quasar PG1211+143

Abstract: The definitive version is available from www.blackwell-synergy.com. Erratum published in Monthly Notices of the Royal Astronomical Society, 2005, 356, p.1599

Sliding mode observers for robust detection and reconstruction of actuator and sensor faults

Abstract: This paper describes a method for designing sliding mode observers for detection and reconstruction of actuator and sensor faults, that is robust against system uncertainty. The method uses ℋ∞ concepts to design the sliding motion so that an upper bound on the effect of the uncertainty on the reconstruction of the faults will be minimized. The design method is first applied to the case of actuator faults, and then by some appropriate filtering, the method is extended to the case of sensor faults. A VTOL aircraft example taken from the fault detection literature is used to demonstrate the method and its effectiveness. Copyright © 2003 John Wiley & Sons, Ltd.

Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin

Abstract: Mechanical forces on matrix–integrin–cytoskeleton linkages are crucial for cell viability, morphology and organ function1. The production of force depends on the molecular connections from extracellular-matrix–integrin complexes to the cytoskeleton2,3. The minimal matrix complex causing integrin–cytoskeleton connections is a trimer of fibronectin's integrin-binding domain FNIII7-10 (ref. 4). Here we report a specific, molecular slip bond that was broken repeatedly by a force of 2 pN at the cellular loading rate of 60 nm s-1; this occurred with single trimer beads but not with monomer. Talin1, which binds to both integrins and actin filaments in vitro, is required for the 2-pN slip bond and rapid cytoskeleton binding. Further, inhibition of fibronectin binding to αvβ3 and deletion of β3 markedly decreases the 2-pN force peak. We suggest that talin1 initially forms a molecular slip bond between closely packed fibronectin–integrin complexes and the actin cytoskeleton, which can apply a low level of force to fibronectin until many bonds form or a signal is received to activate a force response.

Black hole winds

Abstract: Also available at http://www.blackwell-synergy.com/doi/abs/10.1046/j.1365-8711.2003.06980.x. The definitive version is available at www.blackwell-synergy.com.

A high velocity ionised outflow and XUV photosphere in the narrow emission line quasar PG1211+143

Abstract: We report on the analysis of a ~60 ksec XMM observation of the bright, narrow emission line quasar PG 1211+143. Absorption lines are seen in both EPIC and RGS spectra corresponding to H- and He-like ions of Fe, S, Mg, Ne, O, N and C. The observed line energies indicate an ionised outflow velocity of ~24000 km s^-1. The highest energy lines require a column density of N_H ~ 5 x 10^23 cm^-2, at an ionisation parameter of log(xi) ~ 3.4. If the origin of this high velocity outflow lies in matter being driven from the inner disc, then the flow is likely to be optically thick within a radius ~130 Schwarzschild radii, providing a natural explanation for the Big Blue Bump (and strong soft X-ray) emission in PG 1211+143.

Common-Pb corrected in situ U–Pb accessory mineral geochronology by LA-MC-ICP-MS

Abstract: LA-MC-ICP-MS is shown to be a rapid, precise and accurate method for determination of U–Pb ages of accessory minerals. For the protocol described, total analysis time is <3 min with a main acquisition sequence of only 30 s. Using a raster ablation protocol, within-run inter-element fractionation can be effectively eliminated and an external ablation standard used to quantify an overall error for the analysis. Reproducibilities of 206Pb/238U = ca. 3% and 207Pb/206Pb = <1% (2 σ) are achieved, with the resulting age accurate to within 1% as determined using in-house samples previously characterised by TIMS. A key control on the Pb/Pb reproducibility is shown to be the size of the 207Pb peak and an error propagation curve is determined for the accurate representation of this data. Propagation of these errors allows each individual sample analysis to be considered a stand-alone result, removing the need for statistical averaging of multiple data points. Simultaneous collection of flat-topped peaks enables precise measurement and correction of isobaric interference from 204Hg and a procedure for the consistent correction of common-Pb using 204Pb is described. Determination and correction of the common-Pb component is shown to be critical to the reliable interpretation of the data for certain minerals including those phases where a correction is often deemed unnecessary. Combined with time-resolved analysis of the data, this allows the Pb-loss history and nature of discordance within individual crystal domains to be ascertained. Successful analyses of zircons using a non-matrix matched (monazite) standard are also demonstrated suggesting that particle size distribution, ionisation efficiency and plasma loading, are more important issues in controlling inter-element fractionation in the plasma than absolute matrix matching.