Showing papers by "Imperial College London published in 1995"

Polycystic ovary syndrome.

Abstract: Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age. The classical symptoms are those of hyperandrogenism (hirsutism, persistant acne, androgen dependent alopecia) together with symptoms of anovulation (infertility, amenorrhoea, irregular dysfunctional uterine bleeding).1In the last 10 to 15 years, the use of high resolution pelvic ultrasonography has greatly facilitated identification of polycystic ovaries in women with hirsutism or menstrual disturbance. It is now clear that the range of presenting symptoms of women with polycystic ovaries includes not only non-hirsute women with oligomenorrhoea or amenorrhoea but also hirsute subjects with regular, ovulatory cycles. PCOS occurs in nearly 75% of cases of anovulatory infertility and over 80% of subjects with hirsutism.1 The typical biochemical features of PCOS include hyperandrogenaemia and an increase of serum luteinising hormone (LH) (with normal follicle stimulating hormone) but PCOS is also associated with a characteristic metabolic syndrome that includes hyperinsulinaemia, insulin resistance, and dyslipidaemia.1-4 These features are linked to a significantly increased risk of type II (non-insulin-dependent) diabetes in later life and women with PCOS may also have a greater chance of developing premature cardiovascular disease.3 5 6 The presence of polycystic ovaries is necessary for the development of the syndrome but not all women with polycystic ovaries have PCOS. The typical …

Synchronized oscillations in interneuron networks driven by metabotropic glutamate receptor activation

Abstract: Partially synchronous 40-Hz oscillations of cortical neurons have been implicated in cognitive function. Specifically, coherence of these oscillations between different parts of the cortex may provide conjunctive properties to solve the 'binding problem': associating features detected by the cortex into unified perceived objects. Here we report an emergent 40-Hz oscillation in networks of inhibitory neurons connected by synapses using GABAA (gamma-aminobutyric acid) receptors in slices of rat hippocampus and neocortex. These network inhibitory postsynaptic potential oscillations occur in response to the activation of metabotropic glutamate receptors. The oscillations can entrain pyramidal cell discharges. The oscillation frequency is determined both by the net excitation of interneurons and by the kinetics of the inhibitory postsynaptic potentials between them. We propose that interneuron network oscillations, in conjunction with intrinsic membrane resonances and long-loop (such as thalamocortical) interactions, contribute to 40-Hz rhythms in vivo.

Quantum Gravity and Minimum Length

Abstract: The existence of a fundamental scale, a lower bound to any output of a position measurement, seems to be a model-independent feature of quantum gravity. In fact, different approaches to this theory lead to this result. The key ingredients for the appearance of this minimum length are quantum mechanics, special relativity and general relativity. As a consequence, classical notions such as causality or distance between events cannot be expected to be applicable at this scale. They must be replaced by some other, yet unknown, structure.

Defective myosin VIIA gene responsible for Usher syndrome type 1B

Abstract: USHER syndrome represents the association of a hearing impairment with retinitis pigmentosa1 and is the most frequent cause of deaf–blindness in humans. It is inherited as an autosomal recessive trait which is clinically and genetically heterogeneous2,3. Some patients show abnormal organization of microtubules in the axoneme of their photoreceptors cells (connecting cilium)4–6, nasal ciliar cells7 and sperm cells5, as well as widespread degeneration of the organ of Corti8. Usher syndrome type 1 (USH1) is characterized by a profound congenital sensorineural hearing loss, constant vestibular dysfunction and prepubertal onset of retinitis pigmentosa. Of three different genes responsible for USH19–11,USH1B maps to 11q13.5 (ref. 10) and accounts for about 75% of USH1 patients2,3. The mouse deafness shaker-1 (shl) mutation has been localized to the homologous murine region12,13. Taking into account the cytoskeletal abnormalities in USH patients, the identification of a gene encoding an unconventional myosin as a candidate for shaker-1(ref. 14) led us to consider the human homo-logue as a good candidate for the gene that is defective in USH1B. Here we present evidence that a gene encoding myosin VIIA is responsible for USH1B. Two different premature stop codons, a six-base-pair deletion and two different missense mutations were detected in five unrelated families. In one of these families, the mutations were identified in both alleles. These mutations, which are located at the amino-terminal end of the motor domain of the protein, are likely to result in the absence of a functional protein. Thus USH IB appears as a primary cytoskeletal protein defect. These results implicate the genes encoding other unconventional myosins and their interacting proteins as candidates for other genetic forms of Usher syndrome.

Matrix techniques for modeling ultrasonic waves in multilayered media

Abstract: Research into ultrasonic NDE techniques for the inspection of multilayered structures relies strongly on the use of modeling tools which calculate dispersion curves and reflection and transmission spectra. These predictions are essential to enable the best inspection strategies to be identified and their sensitivities to be evaluated. General purpose multilayer modeling tools may be developed from a number of matrix formulations which have evolved in the latter half of this century and there is now a formidable number of publications on the subject. This paper presents a review of the main developments of the matrix techniques, and their use in response and modal models, with emphasis on ultrasonics applications. >

Specifying Distributed Software Architectures

Abstract: There is a real need for clear and sound design specifications of distributed systems at the architectural level This is the level of the design which deals with the high-level organisation of computational elements and the interactions between those elements The paper presents the Darwin notation for specifying this high-level organisation Darwin is in essence a declarative binding language which can be used to define hierarchic compositions of interconnected components Distribution is dealt with orthogonally to system structuring The language supports the specification of both static structures and dynamic structures which may evolve during execution The central abstractions managed by Darwin are components and services Services are the means by which components interact

Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis.

Abstract: We report the results of a double-blind, placebo-controlled trial in nine cystic fibrosis (CF) subjects receiving cationic liposome complexed with a complementary DNA encoding the CF transmembrane conductance regulator (CFTR), and six CF subjects receiving only liposome to the nasal epithelium. No adverse clinical effects were seen and nasal biopsies showed no histological or immuno-histological changes. A partial restoration of the deficit between CF and non-CF subjects of 20% was seen for the response to low Cl- perfusion following CFTR cDNA administration. This was maximal around day three and had reverted to pretreatment values by day seven. In some cases the response to low Cl- was within the range for non-CF subjects. Plasmid DNA and transgene-derived RNA were detected in the majority of treated subjects. Although these data are encouraging, it is likely that transfection efficiency and the duration of expression will need to be increased for therapeutic benefit.

Electron acceleration from the breaking of relativistic plasma waves

Abstract: ELECTRONS in a plasma undergo collective wave-like oscillations near the plasma frequency. These plasma waves can have a range of wavelengths and hence a range of phase velocities1. Of particular note are relativistic plasma waves2,3, for which the phase velocity approaches the speed of light; the longitudinal electric field associated with such waves can be extremely large, and can be used to accelerate electrons (either injected externally or supplied by the plasma) to high energies over very short distances2a¤-4. The maximum electric field, and hence maximum acceleration rate, that can be obtained in this way is determined by the maximum amplitude of oscillation that can be supported by the plasma5a¤-8. When this limit is reached, the plasma wave is said to a¤˜breaka¤™. Here we report observations of relativistic plasma waves driven to breaking point by the Raman forward-scattering instability9,10 induced by short, high-intensity laser pulses. The onset of wave-breaking is indicated by a sudden increase in both the number and maximum energy (up to 44 MeV) of accelerated plasma electrons, as well as by the loss of coherence of laser light scattered from the plasma wave.

The Sry-related gene Sox9 is expressed during chondrogenesis in mouse embryos

Abstract: Mutations in the human SRY-related gene, SOX9, located on chromosome 17, have recently been associated with the sex reversal and skeletal dysmorphology syndrome, campomelic dysplasia. In order to clarify the role of this gene in skeletal development, we have studied the expression of mouse Sox9 during embryogenesis. Sox9 is expressed predominantly in mesenchymal condensations throughout the embryo before and during the deposition of cartilage, consistent with a primary role in skeletal formation. Interspecific backcross mapping has localized mouse Sox9 to distal chromosome 11. The expression pattern and chromosomal location of Sox9 suggest that it may be the gene defective in the mouse skeletal mutant Tail-short, a potential animal model for campomelic dysplasia.

A type VII myosin encoded by the mouse deafness gene shaker-1.

Abstract: GENETIC deafness is common, affecting about 1 in 2,000 births1. Many of these show primary abnormalities of the sensory neuro-epithelia of the inner ear, as do several hearing-impaired mouse mutants, suggesting that genes involved in sensory transduction could be affected. Here we report the identification of one such gene, the mouseshaker-1(shl) gene. Shaker-1 homozygotes show hyperactivity, head-tossing and circling due to vestibular dysfunction, together with typical neuroepithelial-type cochlear defects involving dysfunction and progressive degeneration of the organ of Corti2–7. The shl gene encodes an unconventional myosin molecule of the type VII family. Three mutations are described, two mis-sense mutations and a splice acceptor site mutation, all in the region encoding the myosin head. The myosin type VII molecule encoded byshl is the first molecule to be identified that is known, by virtue of its mutations, to be involved in auditory transduction.

Nonsynaptic modulation of neuronal activity in the brain: electric currents and extracellular ions

Abstract: Nonsynaptic interactions between neurons have been eclipsed by our increasingly detailed understanding of chemical synapses, but they do play significant roles in the nervous system. This review considers four classes of nonsynaptic interaction, mainly in mammalian brain. 1) Electrotonic (and chemical) coupling through gap junctions has effects during development and under some, often pathological, conditions in the mature brain. 2) Ephaptic transmission is mediated by electrical coupling between specific neuronal elements in the absence of specialized contacts, notably in the cerebellum, and in axon tracts affected by demyelination. 3) Field effect interactions are mediated by large extracellular currents and potential fields generated by the hippocampus and other cortical structures. Both endogenous and applied electric fields alter neuronal excitability at field strengths over a few millivolts per millimeter. Weaker fields have more subtle effects, for instance, on axonal growth during development and repair and, more controversially, in behavioral responses to environmental fields. 4) There are fluctuations in extracellular ions such as K+, which are released during neuronal activity and which alter neuronal excitability. Field effects and ion fluctuations probably have modest effects during physiological activity but have a significant impact on epileptic seizures, and can sustain them in the absence of synaptic transmission.

Applied analysis of the Navier-Stokes equations

Abstract: The Navier–Stokes equations are a set of nonlinear partial differential equations comprising the fundamental dynamical description of fluid motion. They are applied routinely to problems in engineering, geophysics, astrophysics, and atmospheric science. This book is an introductory physical and mathematical presentation of the Navier–Stokes equations, focusing on unresolved questions of the regularity of solutions in three spatial dimensions, and the relation of these issues to the physical phenomenon of turbulent fluid motion. Intended for graduate students and researchers in applied mathematics and theoretical physics, results and techniques from nonlinear functional analysis are introduced as needed with an eye toward communicating the essential ideas behind the rigorous analyses.

The mathematics of financial derivatives : a student introduction

Abstract: Finance is one of the fastest growing areas in the modern banking and corporate world. This, together with the sophistication of modern financial products, provides a rapidly growing impetus for new mathematical models and modern mathematical methods; the area is an expanding source for novel and relevant 'real-world' mathematics. In this book the authors describe the modelling of financial derivative products from an applied mathematician's viewpoint, from modelling through analysis to elementary computation. A unified approach to modelling derivative products as partial differential equations is presented, using numerical solutions where appropriate. Some mathematics is assumed, but clear explanations are provided for material beyond elementary calculus, probability, and algebra. Over 140 exercises are included. This volume will become the standard introduction to this exciting new field for advanced undergraduate students.

17β-Estradiol Attenuates Acetylcholine-Induced Coronary Arterial Constriction in Women but Not Men With Coronary Heart Disease

Abstract: Background Women are protected from coronary artery disease until the menopause. Ovarian hormones are vasoactive substances that influence both hemodynamic parameters and atheroma formation. Intravenous ethinyl estradiol has been shown to reverse acetylcholine-induced vasoconstriction in cynomolgus monkeys and humans, and 17β-estradiol improves exercise-induced myocardial ischemia in female patients. We investigated the effect of the naturally occurring estrogen 17β-estradiol on the coronary circulation in postmenopausal women and men with coronary artery disease. Methods and Results We studied nine postmenopausal women 59±3 years old, mean±SEM, and seven men 52±4 years old with proven coronary artery disease. They underwent measurement of coronary artery diameter and coronary blood flow after intracoronary infusion of acetylcholine 1.6 and 16 μg/min before and 20 minutes after intracoronary administration of 2.5 μg of 17β-estradiol into atherosclerotic, nonstenotic coronary arteries. Changes in coronary ...

Standard Reference Data for the Thermal Conductivity of Water

Abstract: New experimental data on the thermal conductivity of liquid water along the saturation line have been obtained recently, using the bare and coated transient hot wire technique, with high accuracy. The quality of the data is such that new standard reference values can be proposed with confidence limits of 0.7% at a 95% confidence level. These data and the correlation herein presented revise a previous correlation endorsed by IUPAC.

The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families

Abstract: Genetic linkage studies place a gene causing early onset familial Alzheimer's disease (FAD) on chromosome 14q24.3 (refs 1–4). Five mutations within the S182 (Presenilin 1: PS–1) gene, which maps to this region, have recently been reported in several early onset FAD kindreds5. We have localized the PS-1 gene to a 75 kb region and present the structure of this gene, evidence for alternative splicing and describe six novel mutations in early onset FAD pedigrees all of which alter residues conserved in the STM26 (Presenilin 2: PS-2) gene.

Determining Teaching and Research Efficiencies

Abstract: In this paper we consider the problem of determining teaching and research efficiencies for university departments concerned with the same discipline. Considering this problem highlights the issue of how to determine efficiencies when resources are shared between different activities, and a non-linear approach to this issue based upon data envelopment analysis is presented. Computational results are given for chemistry and physics departments in the United Kingdom.

Association between an MHC Class II Allele and Clearance of Hepatitis B Virus in the Gambia

Abstract: Background The course of hepatitis B virus (HBV) infection does not appear to be determined by variations in viral virulence and may be influenced by the host immune response. We studied the distribution of human leukocyte antigens in children and adult men in the Gambia who spontaneously recovered from HBV infection as compared with the distribution of these antigens in subjects with persistent infection. Methods In a two-stage, case –control study, we analyzed the frequency of MHC class I antigens and class II haplotypes in subjects with either transient or persistent HBV infection. MHC class I typing was performed by microlymphocytotoxicity assays. MHC class II typing was performed with analysis of restriction-fragment–length polymorphisms (RFLPs), supplemented by other techniques. Results In the first stage (the study of children up to the age of 10 years), the RFLP pattern 25-1, which includes the class II allele HLA-DRB1*1302, was found in 58 of 218 subjects with transient HBV infection (26.6 percen...

Evolutionary theory of parent-offspring conflict

Abstract: Natural selection can act in different ways on genes expressed in parents and their young, giving rise to parent-offspring conflict. The way in which this genetic conflict manifests itself at the behavioural level is unclear, and there has been widespread dissatisfaction that the theory has provided few testable predictions. A recent shift in emphasis from models that define the possible extent of conflict to those that predict its resolution offers greater hope of a testable theory of parent-offspring conflict.

Empirical Evidence that Declining Species Diversity May Alter the Performance of Terrestrial Ecosystems

Abstract: We examined experimentally the association between species diversity and ecosystem processes in a series of terrestrial mesocosms. We developed and maintained 14 mesocosms whose biota were assembled from a single pool of plant and animal species and whose environmental conditions were identically controlled. Each community contained four trophic levels: primary producers (annual herbs), consumers (herbivorous molluscs and phloem sucking insects), secondary consumers (parasitoids) and decomposers (earthworms, Collembola and microbes). All mesocosms received the same diurnal pattern of light, temperature, relative humidity and water. The initial volume of soil, soil structure, composition, nutrient content and inocula of both soil microbes and nematodes were also identical among replicates. The only experimentally manipulated factor was the number of plant and animal species within each trophic level. High, medium and low diversity communities had nine, 15 or 31 plant and animal species, respectively. We measured five ecosystem processes as response variables in these mesocosms over the course of 206 days: (i) community respiration; (ii) productivity; (iii) decomposition; (iv) nutrient retention; and (v) water retention. The manipulation of diversity produced communities that differed significantly in their ecosystem processes. Our results provide the first evidence (obtained by a direct manipulation of diversity under controlled environmental conditions) that ecosystem processes may be affected by loss of diversity.

The relationship between knowledge and attitudes in the public understanding of science in Britain

Abstract: The belief that greater understanding leads to more positive attitudes informs many practical initiatives in the public understanding of science. However, there has been comparatively little empirical study of the justification for this belief. This paper explores the relationship between understanding of science and levels of support for science using a national sample of over 2000 British respondents. The analysis indicates that the internal consistency of attitudes towards science is poor, and that the links between attitudes towards science in general and attitudes towards specific areas of scientific research are weak. Understanding of science is weakly related to more positive attitudes in general: but, more significantly, it is also associated with more coherent and more discriminating attitudes. Of particular importance is the finding that while knowledgeable members of the public are more favourably disposed towards science in general, they are less supportive of morally contentious areas of rese...

Performance of the ALEPH detector at LEP

Abstract: The performance of the ALEPH detector at the LEP e+e− collider is reviewed. The accuracy of the tracking detectors to measure the impact parameter and momentum of charged tracks is specified. Calorimeters are used to measure photons and neutral hadrons, and the accuracy obtained in energy and angle is given. An essential property of the detector is its ability to identify particles; the performance in identification of electrons, muons, neutrinos (from missing energy), charged hadrons, π0's and V0's is described.