Showing papers by "Imperial College London published in 2001"

Materials for fuel-cell technologies

Abstract: Fuel cells convert chemical energy directly into electrical energy with high efficiency and low emission of pollutants. However, before fuel-cell technology can gain a significant share of the electrical power market, important issues have to be addressed. These issues include optimal choice of fuel, and the development of alternative materials in the fuel-cell stack. Present fuel-cell prototypes often use materials selected more than 25 years ago. Commercialization aspects, including cost and durability, have revealed inadequacies in some of these materials. Here we summarize recent progress in the search and development of innovative alternative materials.

Biodiversity and Ecosystem Functioning: Current Knowledge and Future Challenges

Abstract: The ecological consequences of biodiversity loss have aroused considerable interest and controversy during the past decade. Major advances have been made in describing the relationship between species diversity and ecosystem processes, in identifying functionally important species, and in revealing underlying mechanisms. There is, however, uncertainty as to how results obtained in recent experiments scale up to landscape and regional levels and generalize across ecosystem types and processes. Larger numbers of species are probably needed to reduce temporal variability in ecosystem processes in changing environments. A major future challenge is to determine how biodiversity dynamics, ecosystem processes, and abiotic factors interact.

Minimum information about a microarray experiment (MIAME)-toward standards for microarray data.

Abstract: Microarray analysis has become a widely used tool for the generation of gene expression data on a genomic scale. Although many significant results have been derived from microarray studies, one limitation has been the lack of standards for presenting and exchanging such data. Here we present a proposal, the Minimum Information About a Microarray Experiment (MIAME), that describes the minimum information required to ensure that microarray data can be easily interpreted and that results derived from its analysis can be independently verified. The ultimate goal of this work is to establish a standard for recording and reporting microarray-based gene expression data, which will in turn facilitate the establishment of databases and public repositories and enable the development of data analysis tools. With respect to MIAME, we concentrate on defining the content and structure of the necessary information rather than the technical format for capturing it.

Partitioning selection and complementarity in biodiversity experiments

Abstract: The impact of biodiversity loss on the functioning of ecosystems and their ability to provide ecological services has become a central issue in ecology. Several experiments have provided evidence that reduced species diversity may impair ecosystem processes such as plant biomass production. The interpretation of these experiments, however, has been controversial because two types of mechanism may operate in combination. In the 'selection effect', dominance by species with particular traits affects ecosystem processes. In the 'complementarity effect', resource partitioning or positive interactions lead to increased total resource use. Here we present a new approach to separate the two effects on the basis of an additive partitioning analogous to the Price equation in evolutionary genetics. Applying this method to data from the pan-European BIODEPTH experiment reveals that the selection effect is zero on average and varies from negative to positive in different localities, depending on whether species with lower- or higher-than-average biomass dominate communities. In contrast, the complementarity effect is positive overall, supporting the hypothesis that plant diversity influences primary production in European grasslands through niche differentiation or facilitation.

Ghrelin enhances appetite and increases food intake in humans.

Abstract: Ghrelin is a recently identified endogenous ligand for the growth hormone secretagogue receptor. It is synthesized predominantly in the stomach and found in the circulation of healthy humans. Ghrelin has been shown to promote increased food intake, weight gain and adiposity in rodents. The effect of ghrelin on appetite and food intake in man has not been determined. We investigated the effects of intravenous ghrelin (5.0 pmol/kg/min) or saline infusion on appetite and food intake in a randomised double-blind cross-over study in nine healthy volunteers. There was a clear-cut increase in energy consumed by every individual from a free-choice buffet (mean increase 28 ± 3.9%, p<0.001) during ghrelin compared with saline infusion. Visual analogue scores for appetite were greater during ghrelin compared to saline infusion. Ghrelin had no effect on gastric emptying as assessed by the paracetamol absorption test. Ghrelin is the first circulating hormone demonstrated to stimulate food intake in man. Endogenous ghr...

Classical, quantum and total correlations

Abstract: We discuss the problem of separating consistently the total correlations in a bipartite quantum state into a quantum and a purely classical part. A measure of classical correlations is proposed and its properties are explored.

A Simple Generalisation of the Area Under the ROC Curve for Multiple Class Classification Problems

Abstract: The area under the ROC curve, or the equivalent Gini index, is a widely used measure of performance of supervised classification rules. It has the attractive property that it side-steps the need to specify the costs of the different kinds of misclassification. However, the simple form is only applicable to the case of two classes. We extend the definition to the case of more than two classes by averaging pairwise comparisons. This measure reduces to the standard form in the two class case. We compare its properties with the standard measure of proportion correct and an alternative definition of proportion correct based on pairwise comparison of classes for a simple artificial case and illustrate its application on eight data sets. On the data sets we examined, the measures produced similar, but not identical results, reflecting the different aspects of performance that they were measuring. Like the area under the ROC curve, the measure we propose is useful in those many situations where it is impossible to give costs for the different kinds of misclassification.

Quantum Monte Carlo simulations of solids

Abstract: This article describes the variational and fixed-node diffusion quantum Monte Carlo methods and how they may be used to calculate the properties of many-electron systems. These stochastic wave-function-based approaches provide a very direct treatment of quantum many-body effects and serve as benchmarks against which other techniques may be compared. They complement the less demanding density-functional approach by providing more accurate results and a deeper understanding of the physics of electronic correlation in real materials. The algorithms are intrinsically parallel, and currently available high-performance computers allow applications to systems containing a thousand or more electrons. With these tools one can study complicated problems such as the properties of surfaces and defects, while including electron correlation effects with high precision. The authors provide a pedagogical overview of the techniques and describe a selection of applications to ground and excited states of solids and clusters.

Maternal obesity and pregnancy outcome: a study of 287 213 pregnancies in London

Abstract: OBJECTIVE: To examine the maternal and foetal risks of adverse pregnancy outcome in relation to maternal obesity, expressed as body mass index (BMI, kg/m2) in a large unselected geographical population. DESIGN: Retrospective analysis of data from a validated maternity database system which includes all but one of the maternity units in the North West Thames Region. A comparison of pregnancy outcomes was made on the basis of maternal BMI at booking. SUBJECTS: A total of 287 213 completed singleton pregnancies were studied including 176 923 (61.6%) normal weight (BMI 20–24.9), 79 014 (27.5%) moderately obese (BMI 25–29.9) and 31 276 (10.9%) very obese (BMI≥30) women. MEASUREMENTS: Ante-natal complications, intervention in labour, maternal morbidity and neonatal outcome were examined and data presented as raw frequencies and adjusted odds ratios with 99% confidence intervals following logistic regression analysis to account for confounding variables. RESULTS: Compared to women with normal BMI, the following outcomes were significantly more common in obese pregnant women (odds ratio (99% confidence interval) for BMI 25–30 and BMI≥30 respectively): gestational diabetes mellitus (1.68 (1.53–1.84), 3.6 (3.25–3.98)); proteinuric pre-eclampsia (1.44 (1.28–1.62), 2.14 (1.85–2.47)); induction of labour (2.14 (1.85–2.47), 1.70 (1.64–1.76)); delivery by emergency caesarian section (1.30 (1.25–1.34), 1.83 (1.74–1.93)); postpartum haemorrhage (1.16 (1.12–1.21), 1.39 (1.32–1.46)); genital tract infection (1.24 (1.09–1.41), 1.30 (1.07–1.56)); urinary tract infection (1.17 (1.04–1.33), 1.39 (1.18–1.63)); wound infection (1.27 (1.09–1.48), 2.24 (1.91–2.64)); birthweight above the 90th centile (1.57 (1.50–1.64), 2.36 (2.23–2.50)), and intrauterine death (1.10 (0.94–1.28), 1.40 (1.14–1.71)). However, delivery before 32 weeks' gestation (0.73 (0.65–0.82), 0.81 (0.69–0.95)) and breastfeeding at discharge (0.86 (0.84–0.88), 0.58 (0.56–0.60)) were significantly less likely in the overweight groups. In all cases, increasing maternal BMI was associated with increased magnitude of risk. CONCLUSION: Maternal obesity carries significant risks for the mother and foetus. The risk increases with the degree of obesity and persists after accounting for other confounding demographic factors. The basis of many of the complications is likely to be related to the altered metabolic state associated with morbid obesity.

Theory of extraordinary optical transmission through subwavelength hole arrays.

Abstract: We present a fully three-dimensional theoretical study of the extraordinary transmission of light through subwavelength hole arrays in optically thick metal films. Good agreement is obtained with experimental data. An analytical minimal model is also developed, which conclusively shows that the enhancement of transmission is due to tunneling through surface plasmons formed on each metal-dielectric interface. Different regimes of tunneling (resonant through a ``surface plasmon molecule,'' or sequential through two isolated surface plasmons) are found depending on the geometrical parameters defining the system.

Mass-loss predictions for O and B stars as a function of metallicity

Abstract: We have calculated a grid of massive star wind models and mass-loss rates for a wide range of metal abundances between 1/100 and 10 Z/Zsun. The calculation of this grid completes the Vink et al. (2000) mass-loss recipe with an additional parameter Z. We have found that the exponent of the power law dependence of mass loss vs. metallicity is constant in the range between 1/30 and 3 Z/Zsun. The mass-loss rate scales as Mdot \propto Z^0.85 Vinf^p with p = -1.23 for stars with Teff \ga 25000 K, and p = -1.60 for the B supergiants with Teff \la 25000 K. Taking also into account the metallicity dependence of Vinf, using the power law dependence Vinf \propto Z^0.13 from Leitherer et al. (1992), the overall result of mass loss as a function of metallicity can be represented by Mdot \propto Z^0.69 for stars with Teff \ga 25000 K, and Mdot \propto Z^0.64 for B supergiants with Teff \la 25000 K. Our mass-loss predictions are successful in explaining the observed mass-loss rates for Galactic and Small Magellanic Cloud O-type stars, as well as in predicting the observed Galactic bi-stability jump. Hence, we believe that our predictions are reliable and suggest that our mass-loss recipe be used in future evolutionary calculations of massive stars at different metal abundance. A computer routine to calculate mass loss is publicly available.

Molecular states of water in room temperature ionic liquids

Abstract: ATR and transmission IR spectroscopy have been used to investigate the state of water in room temperature ionic liquids (RTILs) based on the 1-alkyl-3-methylimidazolium cation with the anions: [PF6]−, [SbF6]−, [BF4]−, [ClO4]−, [CF3SO3]−, [(CF3SO2)2N]−, [NO3]− and [CF3CO2]−. It has been shown that in these RTILs water molecules absorbed from the air are present mostly in the “free” (not self-associated) state, bound via H-bonding with [PF6]−, [BF4]−, [SbF6]−, [ClO4]−, [CF3SO3]−, [(CF3SO2)2N]− with the concentrations of dissolved water in the range 0.2–1.0 mol dm−3. It has been concluded that most of the water molecules at these concentrations exist in symmetric 1 : 2 type H-bonded complexes: anion...HOH...anion. Additional evidence that the preferred sites of interaction with water molecules are the anions has been obtained from the experiments with RTILs of the 1-butyl-2,3-dimethylimidazolium and 1-butyl-2,3,4,5-tetramethylimidazolium cations. Water molecules can also form associated liquid-like formations in RTILs with anions of stronger basicity such as [NO3]− and [CF3CO2]−. When these RTILs are exposed to air the water concentrations exceed 1.0 mol dm−3. The strength of H-bonding between water molecules and anions increases in the order [PF6]− < [SbF6]− < [BF4]− < [(CF3SO2)2N]− < [ClO4]− < [CF3SO3]− < [NO3]− < [CF3CO2]−. The energies of this H-bonding were estimated from spectral shifts, with the resulting enthalpies being in the range 8–13 kJ mol−1. ATR-IR spectroscopy has also been used to study H-bonding between methanol and RTILs.

The Ponder Policy Specification Language

Abstract: The Ponder language provides a common means of specifying security policies that map onto various access control implementation mechanisms for firewalls, operating systems, databases and Java. It supports obligation policies that are event triggered condition-action rules for policy based management of networks and distributed systems. Ponder can also be used for security management activities such as registration of users or logging and auditing events for dealing with access to critical resources or security violations. Key concepts of the language include roles to group policies relating to a position in an organisation, relationships to define interactions between roles and management structures to define a configuration of roles and relationships pertaining to an organisational unit such as a department. These reusable composite policy specifications cater for the complexity of large enterprise information systems. Ponder is declarative, strongly-typed and object-oriented which makes the language flexible, extensible and adaptable to a wide range of management requirements.

Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer.

Abstract: Defective dendritic cell (DC) function caused by abnormal differentiation of these cells is an important mechanism of tumor escape from immune system control. Previously, we have demonstrated that the number and function of DC were dramatically reduced in cancer patients. This effect was closely associated with accumulation of immature cells (ImC) in peripheral blood. In this study, we investigated the nature and functional role of those ImC. Using flow cytometry, electron microscopy, colony formation assays, and cell differentiation in the presence of different cell growth factors, we have determined that the population of ImC is composed of a small percentage (<2%) of hemopoietic progenitor cells, with all other cells being represented by MHC class I-positive myeloid cells. About one-third of ImC were immature macrophages and DC, and the remaining cells were immature myeloid cells at earlier stages of differentiation. These cells were differentiated into mature DC in the presence of 1 microM all-trans-retinoic acid. Removal of ImC from DC fractions completely restored the ability of the DC to stimulate allogeneic T cells. In two different experimental systems ImC inhibited Ag-specific T cell responses. Thus, immature myeloid cells generated in large numbers in cancer patients are able to directly inhibit Ag-specific T cell responses. This may represent a new mechanism of immune suppression in cancer and may suggest a new approach to cancer treatment.

Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned?

Abstract: Rheumatoid arthritis (RA), a systemic disease, is characterized by a chronic inflammatory reaction in the synovium of joints and is associated with degeneration of cartilage and erosion of juxta-articular bone. Many pro-inflammatory cytokines including TNFα, chemokines, and growth factors are expressed in diseased joints. The rationale that TNFα played a central role in regulating these molecules, and their pathophysiological potential, was initially provided by the demonstration that anti-TNFα antibodies added to in vitro cultures of a representative population of cells derived from diseased joints inhibited the spontaneous production of IL-1 and other pro-inflammatory cytokines. Systemic administration of anti-TNFα antibody or sTNFR fusion protein to mouse models of RA was shown to be anti-inflammatory and joint protective. Clinical investigations in which the activcity of TNFα in RA patients was blocked with intravenously administered infliximab, a chimeric anti-TNFα monoclonal antibody (mAB), has prov...

Prion Diseases of Humans and Animals: Their Causes and Molecular Basis

Abstract: ▪ Abstract Prion diseases are transmissible neurodegenerative conditions that include Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE) and scrapie in animals. Prions appear to be composed principally or entirely of abnormal isoforms of a host-encoded glycoprotein, prion protein. Prion propagation involves recruitment of host cellular prion protein, composed primarily of α-helical structure, into a disease specific isoform rich in β-sheet structure. The existence of multiple prion strains has been difficult to explain in terms of a protein-only infections agent, but recent studies suggest that strain specific phenotypes can be encoded by different prion protein conformations and glycosylation patterns. The ability of a protein to encode phenotypic information has important biological implications. The appearance of a novel human prion disease, variant CJD, and the clear experimental evidence that it is caused by exposure to BSE has highlighted the need to understand the ...

Allergy and allergic diseases.

Abstract: Allergic Diseases and Their Treatment Allergic Rhinitis Allergic rhinitis is characterized by episodes of sneezing, itching, rhinorrhea, and nasal obstruction. Perennial allergic rhinitis should be distinguished from nonallergic, noninfectious forms of rhinitis, such as idiopathic (“vasomotor”) rhinitis, nonallergic rhinitis with eosinophilia syndrome, hormonal rhinitis, drug-induced rhinitis, and food-induced rhinitis. The treatment of allergic rhinitis (and other allergic diseases) consists of allergen avoidance (whenever possible and practical), antiallergic medication, and immunotherapy for specific allergens, which is also called hyposensitization or desensitization. Currently, the drugs usually used to treat allergic rhinitis are antihistamines and anticholinergic agents (for the relief of symptoms) and . . .

The Cluster Magnetic Field Investigation: overview of in-flight performance and initial results

Abstract: . The accurate measurement of the magnetic field along the orbits of the four Cluster spacecraft is a primary objective of the mission. The magnetic field is a key constituent of the plasma in and around the magnetosphere, and it plays an active role in all physical processes that define the structure and dynamics of magnetospheric phenomena on all scales. With the four-point measurements on Cluster, it has become possible to study the three-dimensional aspects of space plasma phenomena on scales commeasurable with the size of the spacecraft constellation, and to distinguish temporal and spatial dependences of small-scale processes. We present an overview of the instrumentation used to measure the magnetic field on the four Cluster spacecraft and an overview the performance of the operational modes used in flight. We also report on the results of the preliminary in-orbit calibration of the magnetometers; these results show that all components of the magnetic field are measured with an accuracy approaching 0.1 nT. Further data analysis is expected to bring an even more accurate determination of the calibration parameters. Several examples of the capabilities of the investigation are presented from the commissioning phase of the mission, and from the different regions visited by the spacecraft to date: the tail current sheet, the dusk side magnetopause and magnetosheath, the bow shock and the cusp. We also describe the data processing flow and the implementation of data distribution to other Cluster investigations and to the scientific community in general. Key words. Interplanetary physics (instruments and techniques) – magnetospheric physics (magnetospheric configuration and dynamics) – space plasma physics (shock waves)

Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18

Abstract: Salmonella enterica serovar Typhi (S. typhi) is the aetiological agent of typhoid fever, a serious invasive bacterial disease of humans with an annual global burden of approximately 16 million cases, leading to 600,000 fatalities. Many S. enterica serovars actively invade the mucosal surface of the intestine but are normally contained in healthy individuals by the local immune defence mechanisms. However, S. typhi has evolved the ability to spread to the deeper tissues of humans, including liver, spleen and bone marrow. Here we have sequenced the 4,809,037-base pair (bp) genome of a S. typhi (CT18) that is resistant to multiple drugs, revealing the presence of hundreds of insertions and deletions compared with the Escherichia coli genome, ranging in size from single genes to large islands. Notably, the genome sequence identifies over two hundred pseudogenes, several corresponding to genes that are known to contribute to virulence in Salmonella typhimurium. This genetic degradation may contribute to the human-restricted host range for S. typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis.

Genome sequence of Yersinia pestis , the causative agent of plague

Abstract: The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague (nineteenth century to the present day). The recent identification of strains resistant to multiple drugs and the potential use of Y. pestis as an agent of biological warfare mean that plague still poses a threat to human health. Here we report the complete genome sequence of Y. pestis strain CO92, consisting of a 4.65-megabase (Mb) chromosome and three plasmids of 96.2 kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion sequences and displays anomalies in GC base-composition bias, indicating frequent intragenomic recombination. Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins). The genome contains around 150 pseudogenes, many of which are remnants of a redundant enteropathogenic lifestyle. The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve.

Finite element interface models for the delamination analysis of laminated composites: mechanical and computational issues

Abstract: The finite element analysis of delamination in laminated composites is addressed using interface elements and an interface damage law. The principles of linear elastic fracture mechanics are indirectly used by equating, in the case of single-mode delamination, the area underneath the traction/relative displacement curve to the critical energy release rate of the mode under examination. For mixed-mode delamination an interaction model is used which can fulfil various fracture criteria proposed in the literature. It is then shown that the model can be recast in the framework of a more general damage mechanics theory. Numerical results are presented for the analyses of a double cantilever beam specimen and for a problem involving multiple delamination for which comparisons are made with experimental results. Issues related with the numerical solution of the non-linear problem of the delamination are discussed, such as the influence of the interface strength on the convergence properties and the final results, the optimal choice of the iterative matrix in the predictor and the number of integration points in the interface elements. Copyright © 2001 John Wiley & Sons, Ltd.

Gene-expression profiling of human osteoblasts following treatment with the ionic products of Bioglass 45S5 dissolution.

Abstract: The effect of the ionic products of Bioglass 45S5 dissolution on the gene-expression profile of human osteoblasts was investigated by cDNA microarray analysis of 1,176 genes. Treatment with the ionic products of Bioglass 45S5 dissolution increased the levels of 60 transcripts twofold or more and reduced the levels of five transcripts to one-half or less than in control. Markedly up-regulated genes included RCL, a c-myc responsive growth related gene, cell cycle regulators such as G1/S specific cyclin D1, and apoptosis regulators including calpain and defender against cell death (DAD1). Other significantly up-regulated genes included the cell surface receptors CD44 and integrin beta1, and various extracellular matrix regulators including metalloproteinases-2 and -4 and their inhibitors TIMP-1 and TIMP-2. The identification of differentially expressed genes by cDNA microarray analysis has offered new insights into the mode of action of bioactive glasses and has proven to be an effective tool in evaluating their osteoproductive properties.

Ghrelin Causes Hyperphagia and Obesity in Rats

Abstract: Ghrelin, a circulating growth hormone-releasing peptide derived from the stomach, stimulates food intake. The lowest systemically effective orexigenic dose of ghrelin was investigated and the resulting plasma ghrelin concentration was compared with that during fasting. The lowest dose of ghrelin that produced a significant stimulation of feeding after intraperitoneal injection was 1 nmol. The plasma ghrelin concentration after intraperitoneal injection of 1 nmol of ghrelin (2.83 +/- 0.13 pmol/ml at 60 min postinjection) was not significantly different from that occurring after a 24-h fast (2.79 +/- 0.32 pmol/ml). After microinjection into defined hypothalamic sites, ghrelin (30 pmol) stimulated food intake most markedly in the arcuate nucleus (Arc) (0-1 h food intake, 427 +/- 43% of control; P < 0.001 vs. control, P < 0.01 vs. all other nuclei), which is potentially accessible to the circulation. After chronic systemic or intracerebroventricular (ICV) administration of ghrelin for 7 days, cumulative food intake was increased (intraperitoneal ghrelin 13.6 +/- 3.4 g greater than saline-treated, P < 0.01; ICV ghrelin 19.6 +/- 5.5 g greater than saline-treated, P < 0.05). This was associated with excess weight gain (intraperitoneal ghrelin 21.7 +/- 1.4 g vs. saline 10.6 +/- 1.9 g, P < 0.001; ICV ghrelin 15.3 +/- 4.3 g vs. saline 2.2 +/- 3.8 g, P < 0.05) and adiposity. These data provide evidence that ghrelin is important in long-term control of food intake and body weight and that circulating ghrelin at fasting concentrations may stimulate food intake.

Inequality and Happiness: Are Europeans and Americans Different?

Abstract: The answer to the question posed in the title is 'yes.' Using a total of 128,106 answers to a survey question about happiness,' we find that there is a large, negative and significant effect of inequality on happiness in Europe but not in the US. There are two potential explanations. First, Europeans prefer more equal societies (inequality belongs in the utility function for Europeans but not for Americans). Second, social mobility is (or is perceived to be) higher in the US so being poor is not seen as affecting future income. We test these hypotheses by partitioning the sample across income and ideological lines. There is evidence of inequality generated' unhappiness in the US only for a sub-group of rich leftists. In Europe inequality makes the poor unhappy, as well as the leftists. This favors the hypothesis that inequality affects European happiness because of their lower social mobility (since no preference for equality exists amongst the rich or the right). The results help explain the greater popular demand for government to fight inequality in Europe relative to the US.

Indices of multilocus linkage disequilibrium

Abstract: Linkage disequilibrium is an ubiquitous biological phenomenon. However a common metric for disequilibrium – the index of association or IA– is dependent on sample size. In this paper we present a modification of IA that removes this dependency. This method has been implemented in a software package.