Showing papers by "Imperial College London published in 1996"

Extremely Low Frequency Plasmons in Metallic Mesostructures

Abstract: The plasmon is a well established collective excitation of metals in the visible and near UV, but at much lower frequencies dissipation destroys all trace of the plasmon and typical Drude behavior sets in. We propose a mechanism for depression of the plasma frequency into the far infrared or even GHz band: Periodic structures built of very thin wires dilute the average concentration of electrons and considerably enhance the effective electron mass through self-inductance. Computations replicate the key features and confirm our analytic theory. The new structure has novel properties not observed before in the GHz band, including some possible impact on superconducting properties.

Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD

Abstract: Strains of transmissible spongiform encephalopathies are distinguished by differing physicochemical properties of PrPSc, the disease-related isoform of prion protein, which can be maintained on transmission to transgenic mice. 'New variant' Creutzfeldt-Jakob disease (CJD) has strain characteristics distinct from other types of CJD and which resemble those of BSE transmitted to mice, domestic cat and macaque, consistent with BSE being the source of this new disease. Strain characteristics revealed here suggest that the prion protein may itself encode disease phenotype.

Computer Architecture: A Quantitative Approach, 2nd Edition

Abstract: The computing world today is in the middle of a revolution: mobile clients and cloud computing have emerged as the dominant paradigms driving programming and hardware innovation today. The Fifth Edition of Computer Architecture focuses on this dramatic shift, exploring the ways in which software and technology in the cloud are accessed by cell phones, tablets, laptops, and other mobile computing devices. Each chapter includes two real-world examples, one mobile and one datacenter, to illustrate this revolutionary change. Updated to cover the mobile computing revolution Emphasizes the two most important topics in architecture today: memory hierarchy and parallelism in all its forms. Develops common themes throughout each chapter: power, performance, cost, dependability, protection, programming models, and emerging trends ("What's Next") Includes three review appendices in the printed text. Additional reference appendices are available online. Includes updated Case Studies and completely new exercises.

Molecular Cloning and Disease Association of Hepatitis G Virus: A Transfusion-Transmissible Agent

Abstract: An RNA virus, designated hepatitis G virus (HGV), was identified from the plasma of a patient with chronic hepatitis. Extension from an immunoreactive complementary DNA clone yielded the entire genome (9392 nucleotides) encoding a polyprotein of 2873 amino acids. The virus is closely related to GB virus C (GBV-C) and distantly related to hepatitis C virus, GBV-A, and GBV-B. HGV was associated with acute and chronic hepatitis. Persistent viremia was detected for up to 9 years in patients with hepatitis. The virus is transfusion-transmissible. It has a global distribution and is present within the volunteer blood donor population in the United States.

A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection.

Abstract: BACKGROUND Genetic differences in immune responses may affect susceptibility to mycobacterial infection, but no specific genes have been implicated in humans. We studied four children who had an unexplained genetic susceptibility to mycobacterial infection and who appeared to have inherited the same recessive mutation from a common ancestor. METHODS We used microsatellite analysis, immunofluorescence studies, and sequence analysis to study the affected patients, unaffected family members, and normal controls. RESULTS A genome search using microsatellite markers identified a region on chromosome 6q in which the affected children were all homozygous for eight markers. The gene for interferon-gamma receptor 1 maps to this region. Immunofluorescence studies showed that the receptor was absent on leukocytes from the affected children. Sequence analysis of complementary DNA for the gene for interferon-gamma receptor 1 revealed a point mutation at nucleotide 395 that introduces a stop codon and results in a truncated protein that lacks the transmembrane and cytoplasmic domains. CONCLUSIONS Four children with severe mycobacterial infections had a mutation in the gene for interferon-gamma receptor 1 that leads to the absence of receptors on cell surfaces and a functional defect in the up-regulation of tumor necrosis factor alpha by macrophages in response to interferon-gamma. The interferon-gamma pathway is important in the response to intracellular pathogens such as mycobacteria.

Population dynamics of immune responses to persistent viruses.

Abstract: Mathematical models, which are based on a firm understanding of biological interactions, can provide nonintuitive insights into the dynamics of host responses to infectious agents and can suggest new avenues for experimentation. Here, a simple mathematical approach is developed to explore the relation between antiviral immune responses, virus load, and virus diversity. The model results are compared to data on cytotoxic T cell responses and viral diversity in infections with the human T cell leukemia virus (HTLV-1) and the human immunodeficiency virus (HIV-1).

Hydraulic conductivity of rock fractures

Abstract: The flow of a single-phase fluid through a rough-walled rock fracture is discussed within the context of fluid mechanics. The derivation of the ‘cubic law’ is given as the solution to the Navier-Stokes equations for flow between smooth, parallel plates - the only fracture geometry that is amenable to exact treatment. The various geometric and kinematic conditions that are necessary in order for the Navier-Stokes equations to be replaced by the more tractable lubrication or Hele-Shaw equations are studied and quantified. In general, this requires a sufficiently low flow rate, and some restrictions on the spatial rate of change of the aperture profile. Various analytical and numerical results are reviewed pertaining to the problem of relating the effective hydraulic aperture to the statistics of the aperture distribution. These studies all lead to the conclusion that the effective hydraulic aperture is less than the mean aperture, by a factor that depends on the ratio of the mean value of the aperture to its standard deviation. The tortuosity effect caused by regions where the rock walls are in contact with each other is studied using the Hele-Shaw equations, leading to a simple correction factor that depends on the area fraction occupied by the contact regions. Finally, the predicted hydraulic apertures are compared to measured values for eight data sets from the literature for which aperture and conductivity data were available on the same fracture. It is found that reasonably accurate predictions of hydraulic conductivity can be made based solely on the first two moments of the aperture distribution function, and the proportion of contact area.

Collective Theory for Surface Enhanced Raman Scattering.

Abstract: We present an implementation of Maxwell's equations on adaptive meshes in order to study interaction of light with metal surfaces. For the first time it is possible to handle surfaces consisting of complex particles close enough to interact strongly. A fully retarded implementation allows treatment of large particles as well as small. By way of example we model a rough silver surface as an array of half-cylinders embedded in a silver surface. Very localized plasmon modes, created by strong electromagnetic coupling between touching metallic objects, dominate the surface enhanced Raman scattering response.

Hierarchical Generalized Linear Models

Abstract: We consider hierarchical generalized linear models which allow extra error components in the linear predictors of generalized linear models. The distribution of these components is not restricted to be normal; this allows a broader class of models, which includes generalized linear mixed models. We use a generalization of Henderson's joint likelihood, called a hierarchical or h-likelihood, for inferences from hierarchical generalized linear models. This avoids the integration that is necessary when marginal likelihood is used. Under appropriate conditions maximizing the h-likelihood gives fixed effect estimators that are asymptotically equivalent to those obtained from the use of marginal likelihood; at the same time we obtain the random effect estimates that are asymptotically best unbiased predictors. An adjusted profile h-likelihood is shown to give the required generalization of restricted maximum likelihood for the estimation of dispersion components. A scaled deviance test for the goodness of fit, a model selection criterion for choosing between various dispersion models and a graphical method for checking the distributional assumption of random effects are proposed. The ideas of quasi-likelihood and extended quasi-likelihood are generalized to the new class. We give examples of the Poisson-gamma, binomial-beta and gamma-inverse gamma hierarchical generalized linear models. A resolution is proposed for the apparent difference between population-averaged and subject-specific models. A unified framework is provided for viewing and extending many existing methods.

Quantitative determination of the stability of the implant‐tissue interface using resonance frequency analysis

Abstract: Bone anchored implants are now being used in dentistry for supporting intraoral and craniofacial prostheses. Although high success rates have been reported, a small number of implants may fail during the early healing phase or lateral in function. Currently available clinical methods to determine implant stability and osseointegration are relatively crude and may entail percussing a fixture with a blunt instrument. Radiographs are of value, but a standardised technique is necessary to ensure repeatability. This investigation was designed to study the application of a non-invasive test method using resonance frequency analysis to make quantitative measurements of the stability of the implant tissue interface in-vitro and in-vivo. The resonance frequency of a small transducer was measured when attached to implants embedded at different heights in an aluminum block. A strong correlation (r = 0.94, p < 0.01) was observed between the observed frequency and the height of implantation fixture exposed. The change in stiffness observed in the bone surrounding an implant during healing was modelled by embedding implants in self-curing polymethylmethacrylate and measuring the resonance frequency at periods during polymerisation. A significant increase in resonance frequency was observed related to the increase in stiffness. Resonance frequency measurements were also made on implants in-vivo and the results correlated well with the in-vitro findings.

Intersalt revisited: further analyses of 24 hour sodium excretion and blood pressure within and across populations

Abstract: Objectives: To assess further the relation in Intersalt of 24 hour urinary sodium to blood pressure of individuals and populations, and the difference in blood pressure from young adulthood into middle age Design: Standardised cross sectional study within and across populations Setting: 52 population samples in 32 countries Subjects: 10 074 men and women aged 20-59 Main outcome measures: Association of sodium and blood pressure from within population and cross population multiple linear regression analyses with multivariate correction for regression dilution bias Relation of sample median daily urinary sodium excretion to difference in blood pressure with age Results: In within population analyses (n=10 074), individual 24 hour urinary sodium excretion higher by 100 mmol (for example, 170 v 70 mmol) was associated with systolic/diastolic blood pressure higher on average by 3/0 to 6/3 mm Hg (with and without body mass in analyses) Associations were larger at ages 40-59 In cross population analyses (n=52), sample median 24 hour sodium excretion higher by 100 mmol was associated with median systolic/diastolic pressure higher on average by 5-7/2-4 mm Hg, and estimated mean difference in systolic/diastolic pressure at age 55 compared with age 25 greater by 10-11/6 mm Hg Conclusions: The strong, positive association of urinary sodium with systolic pressure of individuals concurs with Intersalt cross population findings and results of other studies Higher urinary sodium is also associated with substantially greater differences in blood pressure in middle age compared with young adulthood These results support recommendations for reduction of high salt intake in populations for prevention and control of adverse blood pressure levels Key messages The within population findings were previously underestimated because of incomplete correction for the regression dilution problem Revised estimates of the within population association of sodium to blood pressure in Intersalt are concordant with the cross population findings for 52 samples Estimates of the effect of median sodium excretion higher by 100 mmol/day over a 30 year period (age 55 minus age 25) were a greater difference of 10-11 mm Hg in systolic blood pressure and 6 mm Hg in diastolic blood pressure These results lend further support to recommendations for mass reduction of high salt intake for the prevention and control of adverse blood pressure levels and high blood pressure in populations

Plasma Brain Natriuretic Peptide as an Indicator of Left Ventricular Systolic Function and Long-term Survival After Acute Myocardial Infarction Comparison With Plasma Atrial Natriuretic Peptide and N-Terminal Proatrial Natriuretic Peptide

Abstract: Background Elevated plasma levels of atrial natriuretic peptide (ANP) and the N-terminal fragment of the ANP prohormone (N-ANP) are associated with decreased left ventricular function and decreased long-term survival after acute myocardial infarction (AMI). Previous data suggest that plasma brain natriuretic peptide (BNP) may increase proportionally more than plasma ANP after AMI and in chronic heart failure. The diagnostic and prognostic value of plasma BNP as an indicator of left ventricular dysfunction and long-term survival after AMI, relative to that of ANP and N-ANP, remain to be established. Methods and Results Venous blood samples for analysis of ANP, N-ANP, and BNP were obtained on day 3 after symptom onset from 131 patients with documented AMI. Left ventricular ejection fraction was determined by echocardiography in a subsample of 79 patients. Twenty-eight cardiovascular and 3 noncardiovascular deaths occurred during the follow-up period (median, 1293 days). All three peptides proved to be power...

Insects in fragmented forests: a functional approach

Abstract: Insects are highly susceptible to the adverse effects of forest fragmentation. It is now beyond any doubt that fragmentation-induced changes in abundance and species richness occur in many insect groups. However, the study of insects in fragmented forests is still in its infancy and lacks real direction. Simple empirical studies are not answering the questions we most want to answer about fragmented systems. Are we in the midst of a mass-extinction crisis? What is the functional significance of the immense insect biodiversity? Does biodiversity loss affect ecosystem functioning? A more focused, functional approach to the study of forest fragmentation is required to move beyond the description of pattern and to determine how changes in insect communities affect ecosystem processes in fragmented forests.

Prediction of horizontal response spectra in europe

Abstract: A large and uniform dataset is used to find equations for the prediction of absolute spectral acceleration ordinates in Europe and adjacent areas, in terms of magnitude, source-distance and site geology. The dataset used is shown to be representative of European strong motion in terms of the attenuation of peak ground acceleration. The equations are recommended for use in the range of magnitudes from M s 4.0 to 7.5 and for source-distances of up to 200 km.

A mechanism for generation of long-range synchronous fast oscillations in the cortex.

Abstract: Synchronous neuronal oscillations in the 30-70 Hz range, known as gamma oscillations, occur in the cortex of many species. This synchronization can occur over large distances, and in some cases over multiple cortical areas and in both hemispheres; it has been proposed to underlie the binding of several features into a single perceptual entity. The mechanism by which coherent oscillations are generated remains unclear, because they often show zero or near-zero phase lags over long distances, whereas much greater phase lags would be expected from the slow speed of axonal conduction. We have previously shown that interneuron networks alone can generate gamma oscillations; here we propose a simple model to explain how an interconnected chain of such networks can generate coherent oscillations. The model incorporates known properties of excitatory pyramidal cells and inhibitory interneurons; it predicts that when excitation of interneurons reaches a level sufficient to induce pairs of spikes in rapid succession (spike doublets), the network will generate gamma oscillations that are synchronized on a millisecond time-scale from one end of the chain to the other. We show that in rat hippocampal slices interneurons do indeed fire spike doublets under conditions in which gamma oscillations are synchronized over several millimetres, whereas they fire single spikes under other conditions. Thus, known properties of neurons and local synaptic circuits can account for tightly synchronized oscillations in large neuronal ensembles.

The Impact of Solar Variability on Climate

Abstract: A general circulation model that simulated changes in solar irradiance and stratospheric ozone was used to investigate the response of the atmosphere to the 11-year solar activity cycle. At solar maximum, a warming of the summer stratosphere was found to strengthen easterly winds, which penetrated into the equatorial upper troposphere, causing poleward shifts in the positions of the subtropical westerly jets, broadening of the tropical Hadley circulations, and poleward shifts of the storm tracks. These effects are similar to, although generally smaller in magnitude than, those observed in nature. A simulation in which only solar irradiance was changed showed a much weaker response.

Dynamic structure in software architectures

Abstract: Much of the recent work on Architecture Description Languages (ADL) has concentrated on specifying organisations of components and connectors which are static When the ADL specification is used to drive system construction, then the structure of the resulting system in terms of its component instances and their interconnection is fixed This paper examines ADL features which permit the description of dynamic software architectures in which the organisation of components and connectors may change during system executionThe paper outlines examples of language features which support dynamic structure These examples are taken from Darwin, a language used to describe distributed system structure An operational semantics for these features is presented in the π-calculus, together with a discussion of their advantages and limitations The paper discusses some general approaches to dynamic architecture description suggested by these examples

Laws of Software Evolution Revisited

Abstract: Data obtained during a 1968 study of the software process [8] led to an investigation of the evolution of OS/360 [13] and and, over a period of twenty years, to formulation of eight Laws of Software Evolution. The FEAST project recently initiated (see sections 4–6 below) is expected to throw additional light on the phenomenology underlying these laws, to increase understanding of them, to explore their finer detail, to expose their wider relevance and implications and to develop means for their beneficial exploitation. This paper is intended to trigger wider interest in the laws and in the FEAST study of feedback and feedback control in the context of the software process and its improvement to ensure beneficial exploitation of their potential.

Stimulation of the Stress-Activated Mitogen-Activated Protein Kinase Subfamilies in Perfused Heart: p38/RK Mitogen-Activated Protein Kinases and c-Jun N-Terminal Kinases Are Activated by Ischemia/Reperfusion

Abstract: It has recently been recognized that cellular stresses activate certain members of the mitogen-activated protein kinase (MAPK) superfamily. One role of these “stress-activated” MAPKs is to increase the transactivating activity of the transcription factors c-Jun, Elk1, and ATF2. These findings may be particularly relevant to hearts that have been exposed to pathological stresses. Using the isolated perfused rat heart, we show that global ischemia does not activate the 42- and 44-kD extracellular signal–regulated (protein) kinase (ERK) subfamily of MAPKs but rather stimulates a 38-kD activator of MAPK-activated protein kinase-2 (MAPKAPK2). This activation is maintained during reperfusion. The molecular characteristics of this protein kinase suggest that it is a member of the p38/reactivating kinase (RK) group of stress-activated MAPKs. In contrast, stress-activated MAPKs of the c-Jun N-terminal kinase (JNK/SAPKs) subfamily are not activated by ischemia alone but are activated by reperfusion following ischemia. Furthermore, transfection of ventricular myocytes with activated protein kinases (MEKK1 and SEK1) that may be involved in the upstream activation of JNK/SAPKs induces increases in myocyte size and transcriptional changes typical of the hypertrophic response. We speculate that activation of multiple parallel MAPK pathways may be important in the responses of hearts to cellular stresses.

A Formal Characterisation of Institutionalised Power

Abstract: It is a standard feature of norm-governed institutions that designated agents are empowered to create particular kinds of states of aaairs by means of the performance of speciied types of actions. Frequently, the states of affairs are of a normative kind, in the sense that they pertain to rights and obligations, as for instance when a Head of Department signs a purchase agreement and thereby creates an obligation on his employer to pay for goods received. We use the term institutionalised power to stand for the notion of power we here seek to explicate. Following a lead from jurispru-dential discussions of legal power, we distinguish institutionalised power from permission and practical possibility. We deene a conditional connective intended to capture the consequence relation implicit in statements of the form: according to the constraints operative in institution s, the performance of some act A by agent x counts as a means of creating state of aaairs B. When combined with deontic and action logics, the new connective facilitates the analysis of a number of notions crucial to the understanding of organised interaction in institutions, such as authorisation and delegation. We conclude with some illustrations of the expressive power of the new logical language.

Refraction and geometry in Maxwell's equations

Abstract: Computational studies of Maxwell's equations in complex geometries encountered in photonic band structure calculations run into difficulties when several length scales occur, such as the wavelength of light in free space and the skin depth in metal. These problems are remedied by using an adaptive co-ordinate system which expands or contracts length scales as necessary. Here we show that moving to a general co-ordinate transformation is equivalent to renormalizing e and μ. This is an huge simplification because now we need only write one computer code in a Cartesian system, and we can use this same code to handle any co-ordinate system by adjusting the e and μ we feed into the calculation.

The Life-cycle

Abstract: This chapter is concerned with approaches and techniques used in studying those aspects of parasitoid and predator life cycles that have an important bearing on the major topics covered by other chapters in this book. To illustrate what we mean, consider the female reproductive system of parasitoids which we discuss in some detail (section 2.3). As pointed out by Donaldson and Walter (1988), at least some knowledge of its function/in particular of ovarian dynamics, is crucial to a proper understanding of foraging behaviour in parasitoids. The physiological status of the ovaries may determine: (a) the duration of any preoviposition period following eclosion; (b) the rate of oviposition, (c) the frequency and duration of non-ovipositional activities, e.g. host-feeding; and (d) the insect’s response to external stimuli, e.g. odours, hosts (Collins and Dixon, 1986) (subsection 1.5.1). Note that egg load (defined in subsection 1.2.2) is now being incorporated into foraging models, as it is becoming increasingly clear that certain foraging decisions depend importantly upon the insect’s reproductive state (Jervis and Kidd, 1986; Mangel, 1989a; Chan and Godfray, 1993). It also follows from the above that a female parasitoid’s searching efficiency depends upon the functioning of its reproductive system (subsection 5.3.7), and this may in turn influence parasitoid and host population processes.

Comparison of The Replication of Positive-Stranded Rna Viruses of Plants and Animals

Abstract: Publisher Summary It is clear from the experimental data that there are some similarities in RNA replication for all eukaryotic positive-stranded RNA viruses—that is, the mechanism of polymerization of the nucleotides is probably similar for all. It is noteworthy that all mechanisms appear to utilize host membranes as a site of replication. Membranes appear to function not only as a way of compartmentalizing virus RNA replication but also appear to have a central role in the organization and functioning of the replication complex, and further studies in this area are needed. Within virus supergroups, similarities are evident between animal and plant viruses—for example, in the nature and arrangements of replication genes and in sequence similarities of functional domains. However, it is also clear that there has been considerable divergence, even within supergroups. For example, the animal alpha-viruses have evolved to encode proteinases which play a central controlling function in the replication cycle, whereas this is not common in the plant alpha-like viruses and even when it occurs, as in the tymoviruses, the strategies that have evolved appear to be significantly different. Some of the divergence could be host-dependent and the increasing interest in the role of host proteins in replication should be fruitful in revealing how different systems have evolved. Finally, there are virus supergroups that appear to have no close relatives between animals and plants, such as the animal coronavirus-like supergroup and the plant carmo-like supergroup.

Inhibition of NF-κB DNA Binding by Nitric Oxide

Abstract: It has been suggested that the NF-kappaB transcription factor family may mediate expression of the gene encoding the cytokine-inducible form of nitric oxide synthase (iNOS). To establish if nitric oxide (NO) could in turn affect activity of NF-kappaB, the ability of NO-donor compounds to influence NF-kappaB DNA binding activity in vitro was investigated. NO-donor compounds sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) both inhibited the DNA binding activity of recombinant NF-kappaB p50 and p65 homodimers and of p50-p65 heterodimers. Inhibition of NF-kappaB p50 DNA binding by NO-donor compounds involved modification of the conserved redox-sensitive C62 residue, as a C62S p50 mutant was significantly more resistant to SNP-mediated inactivation. Non-reducing SDS-polyacrylamide gel electrophoresis demonstrated that SNP could inhibit p50 DNA binding by mechanisms other than the formation of intersubunit disulphide bonds involving p50 residue C62. Electrospray ionization mass spectrometry of a synthetic NF-kappaB p5O peptide containing the C62 residue suggested that NO gas can modify C62 by S-nitrosylation. This study indicates that NO-donors can directly inhibit the DNA binding activity of NF-kappaB family proteins, suggesting that cellular NO provides another control mechanism for modulating the expression of NF-kappaB-responsive genes.

Clinical studies of multiple endocrine neoplasia type 1 (MEN1)

Abstract: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid, pancreatic islet and anterior pituitary tumours. To facilitate a screening programme for MEN1, we investigated 709 people (364 males and 345 females, age range 1-84 years) from 62 MEN1 families, and 36 non-familial MEN1 patients. Of those investigated, 220 (95 males and 125 females, age range 8-79 years) suffered from MEN1. Parathyroid, pancreatic and pituitary tumours occurred in 95%, 41% and 30% of the patients, respectively. Parathyroid tumours were the first manifestation of MEN1 in 87% of patients, and amongst the pituitary and pancreatic tumours, somatotrophinomas and gastrinomas were more common in patients above the age of 40 years, whilst insulinomas occurred more frequently in patients below the age of 40 years. Biochemical screening indicated that the penetrance of MEN1 by the ages of 20, 35 and 50 years was 43%, 85% and 94%, respectively, and that the development of MEN1 was confined to first-degree relatives in 91% of patients and to second-degree relatives in 9% of patients. These findings have helped to define a proposed screening programme for MEN1.

High sensitivity collisionally-activated decomposition tandem mass spectrometry on a novel quadrupole/orthogonal-acceleration time-of-flight mass spectrometer.

Abstract: Consideration of the special problems encountered in ultra-high sensitivity biopolymer sequencing studies has led to the development of a novel quadrupole/erthogonal-acceleration time-of-flight tandem mass spectrometer described for the first time here. The performance characteristics of this new geometry are demonstrated, including fully resolved daughter-ion spectra with mass accuracies of 0.1 dalton, which allow removal of interpretation ambiguities and easy differentiation of charge states even in weak collisionally-activated decomposition tandem mass spectra. The instrument has been applied to a variety of biopolymer research problems, including the structure determination of major histocompatibility complex peptide antigens using liquid chromatography/electrospray mass spectrometry and nanoflow-electrospray tandem mass spectrometry, and sequencing capability in the low-femtomole and attomole ranges is demonstrated.