Showing papers by "Imperial College London published in 2004"

Metamaterials and negative refractive index.

Abstract: Recently, artificially constructed metamaterials have become of considerable interest, because these materials can exhibit electromagnetic characteristics unlike those of any conventional materials. Artificial magnetism and negative refractive index are two specific types of behavior that have been demonstrated over the past few years, illustrating the new physics and new applications possible when we expand our view as to what constitutes a material. In this review, we describe recent advances in metamaterials research and discuss the potential that these materials may hold for realizing new and seemingly exotic electromagnetic phenomena.

Architecture of the Photosynthetic Oxygen-Evolving Center

Abstract: Photosynthesis uses light energy to drive the oxidation of water at an oxygen-evolving catalytic site within photosystem II (PSII). We report the structure of PSII of the cyanobacterium Thermosynechococcus elongatus at 3.5 angstrom resolution. We have assigned most of the amino acid residues of this 650-kilodalton dimeric multisubunit complex and refined the structure to reveal its molecular architecture. Consequently, we are able to describe details of the binding sites for cofactors and propose a structure of the oxygen-evolving center (OEC). The data strongly suggest that the OEC contains a cubane-like Mn 3 CaO 4 cluster linked to a fourth Mn by a mono-μ-oxo bridge. The details of the surrounding coordination sphere of the metal cluster and the implications for a possible oxygen-evolving mechanism are discussed.

Law, Finance, and Economic Growth in China

Abstract: China is an important counterexample to the findings in the law, institutions, finance, and growth literature: neither its legal nor financial system is well developed by existing standards, yet it has one of the fastest growing economies. We examine 3 sectors of the economy: the State Sector (state-owned firms), the Listed Sector (publicly listed firms), and the Private Sector (all other firms with various types of private and local government ownership). The law-finance-growth nexus established by existing literature applies to the State and Listed Sectors: with poor legal protections of minority and outside investors, external markets are weak, and the growth of these firms is slow or negative. However, with arguably poorer applicable legal and financial mechanisms, the Private Sector grows much faster than the State and Listed Sectors, and provides most of the economy's growth. This suggests that there exist effective alternative financing channels and governance mechanisms, such as those based on reputation and relationships, to support this growth.

Mimicking Surface Plasmons with Structured Surfaces

Abstract: Metals such as silver support surface plasmons: electromagnetic surface excitations localized near the surface that originate from the free electrons of the metal. Surface modes are also observed on highly conducting surfaces perforated by holes. We establish a close connection between the two, showing that electromagnetic waves in both materials are governed by an effective permittivity of the same plasma form. The size and spacing of holes can readily be controlled on all relevant length scales, which allows the creation of designer surface plasmons with almost arbitrary dispersion in frequency and in space, opening new vistas in surface plasmon optics.

Infliximab Maintenance Therapy for Fistulizing Crohn's Disease

Abstract: BACKGROUND: Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an effective maintenance therapy for patients with fistulas. METHODS: We performed a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn's disease and one or more draining abdominal or perianal fistulas of at least three months' duration. Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0, 2, and 6. A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then randomly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54. The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent randomization. RESULTS: The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance (more than 40 weeks vs. 14 weeks, P<0.001). At week 54, 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas, as compared with 36 percent of patients in the infliximab maintenance group (P=0.009). CONCLUSIONS: Patients with fistulizing Crohn's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks.

The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited

Abstract: The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving or = 50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions]. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.

BRIEF COMMUNICATION ARISING: Gut hormone PYY3-36 physiologically inhibits food intake

Abstract: Food intake is regulated by the hypothalamus, including the melanocortin and neuropeptide Y (NPY) systems in the arcuate nucleus. The NPY Y2 receptor (Y2R), a putative inhibitory presynaptic receptor, is highly expressed on NPY neurons in the arcuate nucleus, which is accessible to peripheral hormones. Peptide YY3-36 (PYY3-36), a Y2R agonist, is released from the gastrointestinal tract postprandially in proportion to the calorie content of a meal. Here we show that peripheral injection of PYY3-36 in rats inhibits food intake and reduces weight gain. PYY3-36 also inhibits food intake in mice but not in Y2r-null mice, which suggests that the anorectic effect requires the Y2R. Peripheral administration of PYY3-36 increases c-Fos immunoreactivity in the arcuate nucleus and decreases hypothalamic Npy messenger RNA. Intra-arcuate injection of PYY3-36 inhibits food intake. PYY3-36 also inhibits electrical activity of NPY nerve terminals, thus activating adjacent pro-opiomelanocortin (POMC) neurons. In humans, infusion of normal postprandial concentrations of PYY3-36 significantly decreases appetite and reduces food intake by 33% over 24 h. Thus, postprandial elevation of PYY3-36 may act through the arcuate nucleus Y2R to inhibit feeding in a gut–hypothalamic pathway.

Model Predictive Control

Abstract: This paper recalls a few past achievements in Model Predictive Control, gives an overview of some current developments and suggests a few avenues for future research.

eBURST: Inferring Patterns of Evolutionary Descent among Clusters of Related Bacterial Genotypes from Multilocus Sequence Typing Data

Abstract: The introduction of multilocus sequence typing (MLST) for the precise characterization of isolates of bacterial pathogens has had a marked impact on both routine epidemiological surveillance and microbial population biology. In both fields, a key prerequisite for exploiting this resource is the ability to discern the relatedness and patterns of evolutionary descent among isolates with similar genotypes. Traditional clustering techniques, such as dendrograms, provide a very poor representation of recent evolutionary events, as they attempt to reconstruct relationships in the absence of a realistic model of the way in which bacterial clones emerge and diversify to form clonal complexes. An increasingly popular approach, called BURST, has been used as an alternative, but present implementations are unable to cope with very large data sets and offer crude graphical outputs. Here we present a new implementation of this algorithm, eBURST, which divides an MLST data set of any size into groups of related isolates and clonal complexes, predicts the founding (ancestral) genotype of each clonal complex, and computes the bootstrap support for the assignment. The most parsimonious patterns of descent of all isolates in each clonal complex from the predicted founder(s) are then displayed. The advantages of eBURST for exploring patterns of evolutionary descent are demonstrated with a number of examples, including the simple Spain(23F)-1 clonal complex of Streptococcus pneumoniae, "population snapshots" of the entire S. pneumoniae and Staphylococcus aureus MLST databases, and the more complicated clonal complexes observed for Campylobacter jejuni and Neisseria meningitidis.

Monoenergetic beams of relativistic electrons from intense laser–plasma interactions

Abstract: High-power lasers that fit into a university-scale laboratory can now reach focused intensities of more than 10(19) W cm(-2) at high repetition rates. Such lasers are capable of producing beams of energetic electrons, protons and gamma-rays. Relativistic electrons are generated through the breaking of large-amplitude relativistic plasma waves created in the wake of the laser pulse as it propagates through a plasma, or through a direct interaction between the laser field and the electrons in the plasma. However, the electron beams produced from previous laser-plasma experiments have a large energy spread, limiting their use for potential applications. Here we report high-resolution energy measurements of the electron beams produced from intense laser-plasma interactions, showing that--under particular plasma conditions--it is possible to generate beams of relativistic electrons with low divergence and a small energy spread (less than three per cent). The monoenergetic features were observed in the electron energy spectrum for plasma densities just above a threshold required for breaking of the plasma wave. These features were observed consistently in the electron spectrum, although the energy of the beam was observed to vary from shot to shot. If the issue of energy reproducibility can be addressed, it should be possible to generate ultrashort monoenergetic electron bunches of tunable energy, holding great promise for the future development of 'table-top' particle accelerators.

Evaluated kinetic and photochemical data for atmospheric chemistry: Volume I - gas phase reactions of O x , HO x , NO x and SO x species

Abstract: . This article, the first in the series, presents kinetic and photochemical data evaluated by the IUPAC Subcommittee on GasKinetic Data Evaluation for Atmospheric Chemistry. It covers the gas phase and photochemical reactions of Ox, HOx, NOx and SOx species, which were last published in 1997, and were updated on the IUPAC website in late 2001. The article consists of a summary sheet, containing the recommended kinetic parameters for the evaluated reactions, and five appendices containing the data sheets, which provide information upon which the recommendations are made.

A Chiral Route to Negative Refraction

Abstract: Negative refraction is currently achieved by driving the magnetic permeability and electrical permittivity simultaneously negative, thus requiring two separate resonances in the refracting material. The introduction of a single chiral resonance leads to negative refraction of one polarization, resulting in improved and simplified designs of negatively refracting materials and opening previously unknown avenues of investigation in this fast-growing subject.

Terahertz magnetic response from artificial materials.

Abstract: We show that magnetic response at terahertz frequencies can be achieved in a planar structure composed of nonmagnetic conductive resonant elements. The effect is realized over a large bandwidth and can be tuned throughout the terahertz frequency regime by scaling the dimensions of the structure. We suggest that artificial magnetic structures, or hybrid structures that combine natural and artificial magnetic materials, can play a key role in terahertz devices.

Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial.

Abstract: ContextTenofovir disoproxil fumarate (DF) is a once-daily nucleotide analogue reverse transcriptase inhibitor.ObjectiveTo evaluate the efficacy and safety of tenofovir DF compared with stavudine in antiretroviral-naive patients.Design, Setting, and ParticipantsA prospective, randomized, double-blind study conducted at 81 centers in the United States, South America, and Europe from June 9, 2000, to January 30, 2004. A total of 753 patients infected with HIV who were antiretroviral naive were screened and 602 patients entered the study.InterventionPatients were randomized to receive either tenofovir DF (n = 299) or stavudine (n = 303), with placebo, in combination with lamivudine and efavirenz.Main Outcome MeasureProportion of patients with HIV RNA levels of less than 400 copies/mL at week 48.ResultsIn the primary intent-to-treat analysis in which patients with missing data or who added or switched antiretroviral medications before week 48 were considered as failures, the proportion of patients with HIV RNA of less than 400 copies/mL at week 48 was 239 (80%) of 299 in patients receiving tenofovir DF and 253 (84%) of 301 in patients receiving stavudine (95% confidence interval, −10.4% to 1.5%), exceeding the predefined −10% limit for equivalence. However, equivalence was demonstrated in the secondary analyses (HIV RNA <50 copies/mL) at week 48 and through 144 weeks. Virologic failure was associated most frequently with efavirenz and lamivudine resistance. Through 144 weeks, the K65R mutation emerged in 8 and 2 patients in the tenofovir DF and stavudine groups, respectively (P = .06). A more favorable mean change from baseline in fasting lipid profile was noted in the tenofovir DF group at week 144: for triglyceride levels (+1 mg/dL for tenofovir DF [n = 170] vs +134 mg/dL for stavudine [n = 162], P<.001), total cholesterol (+30 mg/dL [n = 170] vs +58 mg/dL [n = 162], P<.001), direct low-density lipoprotein cholesterol (+14 mg/dL [n = 169] vs +26 mg/dL [n = 161], P<.001), and high-density lipoprotein cholesterol (+9 mg/dL [n = 168] vs +6 mg/dL [n = 154], P = .003). Investigator-reported lipodystrophy was less common in the tenofovir DF group compared with the stavudine group (9 [3%] of 299 vs 58 [19%] of 301, P<.001). The number of bone fractures and the renal safety profile were similar between the 2 groups.ConclusionsThrough 144 weeks, the combination of tenofovir DF, lamivudine, and efavirenz was highly effective and comparable with stavudine, lamivudine, and efavirenz in antiretroviral-naive patients. However, tenofovir DF appeared to be associated with better lipid profiles and less lipodystrophy.

Advanced anodes for high-temperature fuel cells

Abstract: Fuel cells will undoubtedly find widespread use in this new millennium in the conversion of chemical to electrical energy, as they offer very high efficiencies and have unique scalability in electricity-generation applications. The solid-oxide fuel cell (SOFC) is one of the most exciting of these energy technologies; it is an all-ceramic device that operates at temperatures in the range 500–1,000 °C. The SOFC offers certain advantages over lower temperature fuel cells, notably its ability to use carbon monoxide as a fuel rather than being poisoned by it, and the availability of high-grade exhaust heat for combined heat and power, or combined cycle gas-turbine applications. Although cost is clearly the most important barrier to widespread SOFC implementation, perhaps the most important technical barriers currently being addressed relate to the electrodes, particularly the fuel electrode or anode. In terms of mitigating global warming, the ability of the SOFC to use commonly available fuels at high efficiency, promises an effective and early reduction in carbon dioxide emissions, and hence is one of the lead new technologies for improving the environment. Here, we discuss recent developments of SOFC fuel electrodes that will enable the better use of readily available fuels.

Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004—BHS IV

Abstract: Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004—BHS IV

Nearly 5000 Distant Early-Type Galaxies in COMBO-17: A Red Sequence and Its Evolution since z ~ 1

Abstract: We present the rest-frame colors and luminosities of ~25,000 mR 24 galaxies in the redshift range 0.2 < z ≤ 1.1 drawn from 0.78 deg2 of the COMBO-17 survey (Classifying Objects by Medium-Band Observations in 17 Filters). We find that the rest-frame color distribution of these galaxies is bimodal at all redshifts out to z ~ 1. This bimodality permits a model-independent definition of red early-type galaxies and blue late-type galaxies at any given redshift. The colors of the blue peak become redder toward the present day, and the number density of blue luminous galaxies has dropped strongly since z ~ 1. Focusing on the red galaxies, we find that they populate a color-magnitude relation. Such red sequences have been identified in galaxy cluster environments, but our data show that such a sequence exists over this redshift range even when averaging over all environments. The mean color of the red galaxy sequence evolves with redshift in a way that is consistent with the aging of an ancient stellar population. The rest-frame B-band luminosity density in red galaxies evolves only mildly with redshift in a Λ-dominated cold dark matter universe. When we account for the change in stellar mass-to-light ratio implied by the redshift evolution in red galaxy colors, the COMBO-17 data indicate an increase in stellar mass on the red sequence by a factor of 2 since z ~ 1. The largest source of uncertainty is large-scale structure, implying that considerably larger surveys are necessary to further refine this result. We explore mechanisms that may drive this evolution in the red galaxy population, finding that both galaxy merging and truncation of star formation in some fraction of the blue star-forming population are required to fully explain the properties of these galaxies.

Embryonic stem cells.

Abstract: Embryonic stem cells have huge potential in the field of tissue engineering and regenerative medicine as they hold the capacity to produce every type of cell and tissue in the body. In theory, the treatment of human disease could be revolutionized by the ability to generate any cell, tissue, or even organ, 'on demand' in the laboratory. This work reviews the history of murine and human ES cell lines, including practical and ethical aspects of ES cell isolation from pre-implantation embryos, maintenance of undifferentiated ES cell lines in the cell culture environment, and differentiation of ES cells in vitro and in vivo into mature somatic cell types. Finally, we discuss advances towards the clinical application of ES cell technology, and some of the obstacles which must be overcome before large scale clinical trials can be considered.

Turbulent amplification of magnetic field and diffusive shock acceleration of cosmic rays

Abstract: The diffusive shock acceleration of cosmic rays by supernova remnants depends upon the generation of magnetic fluctuations by cosmic rays upstream of the shock. Strongly driven, non-resonant, nearly purely growing modes grow more rapidly than the resonant Alfven waves usually considered. Non-linear simulation shows that the magnetic field can be amplified from its seed value by orders of magnitude. The consequences for the maximum attainable cosmic ray energy in supernova remnants are explored.

Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2

Abstract: Coumarin derivatives such as warfarin represent the therapy of choice for the long-term treatment and prevention of thromboembolic events. Coumarins target blood coagulation by inhibiting the vitamin K epoxide reductase multiprotein complex (VKOR). This complex recycles vitamin K 2,3-epoxide to vitamin K hydroquinone, a cofactor that is essential for the post-translational gamma-carboxylation of several blood coagulation factors. Despite extensive efforts, the components of the VKOR complex have not been identified. The complex has been proposed to be involved in two heritable human diseases: combined deficiency of vitamin-K-dependent clotting factors type 2 (VKCFD2; Online Mendelian Inheritance in Man (OMIM) 607473), and resistance to coumarin-type anticoagulant drugs (warfarin resistance, WR; OMIM 122700). Here we identify, by using linkage information from three species, the gene vitamin K epoxide reductase complex subunit 1 (VKORC1), which encodes a small transmembrane protein of the endoplasmic reticulum. VKORC1 contains missense mutations in both human disorders and in a warfarin-resistant rat strain. Overexpression of wild-type VKORC1, but not VKORC1 carrying the VKCFD2 mutation, leads to a marked increase in VKOR activity, which is sensitive to warfarin inhibition.

Factors that make an infectious disease outbreak controllable.

Abstract: The aim of this study is to identify general properties of emerging infectious agents that determine the likely success of two simple public health measures in controlling outbreaks, namely (i) isolating symptomatic individuals and (ii) tracing and quarantining their contacts. Because these measures depend on the recognition of specific disease symptoms, we investigate the relative timing of infectiousness and the appearance of symptoms by using a mathematical model. We show that the success of these control measures is determined as much by the proportion of transmission occurring prior to the onset of overt clinical symptoms (or via asymptomatic infection) as the inherent transmissibility of the etiological agent (measured by the reproductive number R0). From published studies, we estimate these quantities for two moderately transmissible viruses, severe acute respiratory syndrome coronavirus and HIV, and for two highly transmissible viruses, smallpox and pandemic influenza. We conclude that severe acute respiratory syndrome and smallpox are easier to control using these simple public health measures. Direct estimation of the proportion of asymptomatic and presymptomatic infections is achievable by contact tracing and should be a priority during an outbreak of a novel infectious agent.

Identifying adaptive genetic divergence among populations from genome scans

Abstract: The identification of signatures of natural selection in genomic surveys has become an area of intense research, stimulated by the increasing ease with which genetic markers can be typed. Loci identified as subject to selection may be functionally important, and hence (weak) candidates for involvement in disease causation. They can also be useful in determining the adaptive differentiation of populations, and exploring hypotheses about speciation. Adaptive differentiation has traditionally been identified from differences in allele frequencies among different populations, summarised by an estimate of FST. Low outliers relative to an appropriate neutral population-genetics model indicate loci subject to balancing selection, whereas high outliers suggest adaptive (directional) selection. However, the problem of identifying statistically significant departures from neutrality is complicated by confounding effects on the distribution of FST estimates, and current methods have not yet been tested in large-scale simulation experiments. Here, we simulate data from a structured population at many unlinked, diallelic loci that are predominantly neutral but with some loci subject to adaptive or balancing selection. We develop a hierarchical-Bayesian method, implemented via Markov chain Monte Carlo (MCMC), and assess its performance in distinguishing the loci simulated under selection from the neutral loci. We also compare this performance with that of a frequentist method, based on moment-based estimates of FST. We find that both methods can identify loci subject to adaptive selection when the selection coefficient is at least five times the migration rate. Neither method could reliably distinguish loci under balancing selection in our simulations, even when the selection coefficient is twenty times the migration rate.

Exercise training meta-analysis of trials in patients with chronic heart failure (ExTraMATCH).

Abstract: Objective To determine the effect of exercise training on survival in patients with heart failure due to left ventricular systolic dysfunction. Design Collaborative meta-analysis. Inclusion criteria Randomised parallel group controlled trials of exercise training for at least eight weeks with individual patient data on survival for at least three months. Studies reviewed Nine datasets, totalling 801 patients: 395 received exercise training and 406 were controls. Main outcome measure Death from all causes. Results During a mean (SD) follow up of 705 (729) days there were 88 (22%) deaths in the exercise arm and 105 (26%) in the control arm. Exercise training significantly reduced mortality (hazard ratio 0.65, 95% confidence interval, 0.46 to 0.92; log rank χ2 = 5.9; P = 0.015). The secondary end point of death or admission to hospital was also reduced (0.72, 0.56 to 0.93; log rank χ2 = 6.4; P = 0.011). No statistically significant subgroup specific treatment effect was observed. Conclusion Meta-analysis of randomised trials to date gives no evidence that properly supervised medical training programmes for patients with heart failure might be dangerous, and indeed there is clear evidence of an overall reduction in mortality. Further research should focus on optimising exercise programmes and identifying appropriate patient groups to target.