Showing papers by "Imperial College London published in 1982"

Relation of Body Fat Distribution to Metabolic Complications of Obesity

Abstract: The importance of body fat distribution as a predictor of metabolic aberrations was evaluated in 9 nonobese and 25 obese, apparently healthy women. Plasma glucose and insulin levels during oral glucose loading were significantly higher in women with predominantly upper body segment obesity than in women with lower body segment obesity. Of the former group, 10 of 16 subjects had diabetic glucose tolerance results, while none of the latter group was diabetic. Fasting plasma triglyceride levels were also significantly higher in the upper body segment obese women. The site of adiposity in the upper body segment obese women was comprised of large fat cells, while in the lower body segment obese subjects, it was formed of normal size cells. In both types of obesity, abdominal fat cell size correlated significantly with postprandial plasma glucose and insulin levels. Thigh fat cell size gave no indication as to the presence of metabolic complications. Thigh adipocytes were also resistant to epinephrine-stimulated lipolysis, presumably due to an increase in alpha-adrenergic receptors. Thus, in women, the sites of fat predominance offer an important prognostic marker for glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. This association may be related to the disparate morphology and metabolic behavior of fat cells associated with different body fat distributions.

Coevolution of hosts and parasites.

Abstract: The coevolution of parasites and their hosts has both general biological interest and practical implications in agricultural, veterinary and medical fields Surprisingly, most medical, parasitological and ecological texts dismiss the subject with unsupported statements to the effect that ‘successful’ parasite species evolve to be harmless to their hosts Recently, however, several people have explored theoretical aspects of the population genetics of host-parasite associations; these authors conclude that such associations may be responsible for much of the genetic diversity found within natural populations, from blood group polymorphisms (Haldane, 1949) to protein polymorphisms in general (Clarke, 1975, 1976) and to histocompatibility systems (Duncan, Wakeland & Klein, 1980) It has also been argued that pathogens may constitute the selective force responsible for the evolution and maintenance of sexual reproduction in animal and plant species (Jaenike, 1978; Hamilton, 1980, 1981, 1982; Bremermann, 1980)

Machine-component group formation in group technology: review and extension

Abstract: The paper provides a comprehensive review of the various approaches that have been adopted in an attempt to solve the problem of forming machines into groups and components into associated families in Group Technology, A new and more efficient version of the previously published ROC algorithm, implemented interactively, is described together with a new relaxation procedure for bottleneck machines.

Processes influencing the distribution of parasite numbers within host populations with special emphasis on parasite-induced host mortalities

Abstract: The paper examines the factors which generate various patterns of dispersion in the distribution of parasites within their host populations. Particular emphasis is placed on the role played by chance elements in the growth and decay of parasite populations and on the influence of different types of demographic processes. It is argued that observed distributions are dynamic, rather than static, entities generated by opposing forces, some acting to create over-dispersion and others acting to generate under-dispersion. Monte Carlo simulation experiments, based on probability models of the growth and decay of host and parasite populations, are used to study the dynamics of parasite dispersion. Attention is specifically focused on the role played by parasite-induced host mortality. It is shown that, for certain types of host–parasite associations, convex curves of mean parasite abundance in relation to age (age-intensity curves), concomitant with a decline in the degree of dispersion in the older age classes of hosts, may be evidence of the induction of host mortality by parasite infection. Empirical evidence is examined in light of this prediction. In general, however, simulation studies highlight the technical difficulties inherent in establishing clear evidence of parasite-induced host mortality from ecological studies of hosts and parasites in their natural habitats.

Molecular mechanisms of general anaesthesia

Abstract: Important constraints on possible molecular mechanisms of general anaesthesia are derived from a quantitative reappraisal of data on the potency of general anaesthetics on whole animals. Despite their popularity, theories that invoke lipids as the prime target do not look at all promising, and available data point much more plausibly to a direct effect on particularly sensitive proteins. Structural changes of proteins on binding general anaesthetics are probably small but may be sufficient to perturb normal function; alternatively, anaesthetics may compete with an endogenous ligand. The phenomenon of pressure reversal of anaesthesia may simply be due to anaesthetics being squeezed away from their target sites.

Inherent Stress Biaxiality in Various Fracture Specimen Geometries

Abstract: Previous work by the authors has indicated that crack behaviour in PMMA (and thus probably in other materials as well) shows a secondary dependence on the degree of in-plane stress biaxiality, in addition to its established primary dependence on K1, the elastic stress intensity factor. Data published here shows the crack-length dependence of a parameter expressing the degree of stress biaxiality inherent to a number of standard specimen geometries. This should help to determine to what, if any, extent a given material's sensitivity to stress biaxiality is responsible for K1-independent variations in crack behaviour between specimens.

An experimental study of pressure fluctuations on fixed and oscillating square-section cylinders

Abstract: Measurements are presented of the pressure fluctuations acting on a stationary squaresection cylinder, with the front face normal to the flow, and one forced to oscillate, transverse to a flow, at amplitudes up to 25% of the length of a side. The range of reduced velocities investigated, 4–13, includes the vortex lock-in regime. At lock-in the amplification of the coefficient of fluctuating lift is found to be much less than that found for a circular cylinder. The variation of the phase angle, between lift and displacement, is also different from that measured on a circular cylinder, and vortex-induced oscillations are possible only at the high-reduced-velocity end of the lock-in range. At reduced velocities sufficiently far below lock-in the natural vortex-shedding mode is suppressed and vortices are found to form over the side faces at the body frequency. Intermittent reattachment occurs over the side faces and, for an amplitude of oscillation equal to 10% of the length of a side face, the time-mean drag coefficient can be reduced to 60% of its fixed-cylinder value.

An Analysis of Transformations Revisited, Rebutted

Abstract: : In a paper written in 1964, Box and Cox described a method for estimating transformations and showed how in suitable cases valuable increases in simplicity and efficiency were possible. Since that time, this technique has enjoyed wide practical use and considerable success. However, a recent theoretical paper by Bickel and Doksum (1981) seems to suggest that serious dangers are associated with the employment of this method, and speaks of 'instability' and 'cost' of estimation of the transformation. These difficulties seem to be associated with (1) examples which common sense would rule out, namely situations where the effect of transformation on the data is almost linear, so that it is a matter of indifference which transformation is used; (2) the idea that it makes sense to state conclusions in terms of a number measured on an arbitrary scale; (3) failure to take proper account of the Jacobian of the transformation.

Redesigning enzyme structure by site-directed mutagenesis: tyrosyl tRNA synthetase and ATP binding

Abstract: We describe here a general method for systematically replacing amino acids in an enzyme. This allows analysis of their molecular roles in substrate binding or catalysis and could eventually lead to the engineering of new enzymatic activities. The gene encoding the enzyme is first cloned into a vector from which the enzyme is expressed and is then mutated in vitro to change a particular nucleotide and hence the amino acid sequence of the enzyme. We have cloned the gene for the tyrosyl tRNA synthetase of Bacillus stearothermophilus into a vector derived from the single-stranded bacteriophage M13 to facilitate mutagenesis with mismatched synthetic oligodeoxynucleotide primers. From the recombinant M13 clone we have obtained high levels of the enzyme (∼50% of soluble protein) expressed in the Escherichia coli host and have converted cysteine (Cys35) at the enzyme's active site to serine. This leads to a reduction in enzymatic activity that is largely attributable to a lower Km for ATP.

Linkage relationship of a cloned DNA sequence on the short arm of the X chromosome to Duchenne muscular dystrophy

Abstract: Duchenne muscular dystrophy (DMD) is one of the most common and serious human X-linked disorders. It occurs at a frequency of up to 1 in 5,000 newborn males in most populations studied, with about one-third of all cases due to new mutations1. The primary biochemical defect remains unknown, and no proven prenatal diagnostic test exists, although raised serum creatine kinase levels act as a somewhat equivocal guide to carrier females2. Previous studies have shown no measurable genetic linkage of the DMD locus with any X-chromosome marker3,4. Therefore, if a cloned sequence of the X chromosome could be used to define the locus, and to provide a closely linked set of markers, it would be of considerable importance in the prediction and prevention of DMD, as well as a step towards identifying the basic biochemical defect causing the disease. We present here evidence of an X-chromosome sequence, defined by its restriction enzyme polymorphism, that is loosely linked to DMD, at a distance of approximately 10 centimorgans, as determined by studies on nine informative families. The polymorphism occurs in 29% of women in a control London population and in 22% of carriers for DMD. The linkage data support cytogenetic evidence that DMD is on the short arm of the X chromosome. The object of this letter is to encourage others to make use of our probe, which seems to be linked to the DMD locus.

Two‐dimensional convection in non‐constant shear: A model of mid‐latitude squall lines

Abstract: Numerical simulations of two-dimensional deep convection are analysed using analytical models extended to include shallow downdraughts and non-constant shear. The cumulonimbus are initiated by low-level convergence created by a finite amplitude downdraught. These experiments have constant low-level shear and differ only in the profile of mid-and upper-level winds. Quasi-steady convenction is produced if the mid- and upper-level flow has small shear and the low-level shear is large. The surface precipitation ismaximized for no intial relative relative flow aloft, if stationary, this storm (P(O)) can give prodigious locilized rainfall; P(O) is the two-dimentisonal equivalent of the supercell. These results are placed in context with previous two-dimensional simulations. Attention is drawn to the similiarity with previous two-dimensional simulations. Attention is drawn to the similarity with squall lines in central and eastern U.S.A. Storm P(O) is analysed by construction of time-averaged fields of streamfunction, vorticity, teperature, and height deviation. The smoothness of these fields suggests a conceptual model of the storm dynamics which involves cooperation between distinct charcteristic flows; an overturning updraught, a jump type updraught, a shallow downdraught, a low-level rotor, and a boundary layer. An idealized analytical model is described by solution of the equations for steady convection. These solutions, for the remote flow, are derived from energy conversation, mass continuity and a momentum budget, and they give relationships between the non-dimensional parameteres of the problem. It is apparent that the convection is a high Froude (or low Richardson) number flow demanding the existence of a cross-storm pressure gradient. Inherent in this idealized model is a vortex sheet between updraught and down-draught and it is considered that the dynamical instability of this sheet is related to complexities in the numerical simulation. Furthermore, these results show that in two-dimensions both non-constant shear and a shallow downdraught are necessary to maintain steady convection.

Population dynamics of human helminth infections: control by chemotherapy

Abstract: An analysis is presented of the population dynamics of the major helminth parasites of man with the aim of understanding observed patterns in the age-specific prevalence and intensity of infection Mathematical models are used to investigate the possibility of controlling helminth diseases by mass chemotherapy, and to explore the advantages of selective treatment of the most heavily infected individuals in a community

Optimum biased coin designs for sequential clinical trials with prognostic factors

Abstract: Patients in a clinical trial arrive sequentially and are assigned to one of t treatments. This assignment should maintain a balance between the numbers receiving each treatment, yet should be sufficiently random to avoid any suspicion of conscious or unconscious cheating. To balance these requirements Efron (1971) introduced biased coin designs for the comparison of two treatments in which allocation of the treatment is determined probabilistically, but with a bias towards the underrepresented treatment. One disadvantage of Efron's scheme is that it does not include balance over covariates or prognostic factors which may affect the response of the patient to the treatment. Biased coin schemes which do force balance over both treatments and prognostic factors are given by Pocock & Simon (1975) and Efron (1980). The properties of the designs have been elucidated by numerical studies and they are now being increasingly used in clinical trials. Reviews of the literature and discussions of the practical implications of the designs are given by Pocock (1979) and Simon (1979). However, the designs suffer from the disadvantage that they rely on arbitrary functions to achieve the desired balance. The procedures thus lack a firm theoretical framework. An alternative approach in the presence of prognostic factors (Begg & Iglewicz, 1980) uses optimum design theory to suggest a deterministic design criterion, which is then modified for computational convenience. In this paper I use optimum design theory to provide a procedure of the biased coin type for an arbitrary number of treatments in the presence, or absence, of prognostic factors. This has the theoretical advantage of obviating dependence on a series of arbitrary functions. The necessary optimum design theory is presented in ? 2 and, in ? 3, applied to biased coin experiments. The simplest case, that of two treatments in the absence of prognostic factors, is studied in ? 4. The extension to three or more treatments is in ? 5, followed, in ? 6, by the allowance for prognostic factors. Although, in the biased coin designs, allocation of treatments is made probabilistically, the results of the paper can be used for the sequential construction of DA-optimum designs in which randomization is not introduced by the experimenter. All the designs mentioned so far are sequential, but not adaptive. In the useful distinction made by Pericchi (1981), they are data-dependent but not outcomedependent: each allocation depends on the previous allocations and prognostic factors,

Taylor—Gortler vortices in fully developed or boundary-layer flows: linear theory

Abstract: The stability characteristics of some fluid flows at high Taylor or Gortler numbers are determined using perturbation methods. In particular, the stability characteristics of some fully developed flows between concentric cylinders driven either by a pressure gradient or the motion of the inner cylinder are investigated. The asymptotic structure of short-wavelength disturbances to these flows is obtained and used as a basis for a formal perturbation solution to the corresponding stability problem appropriate to a developing boundary layer. The non-parallel effect of the basic flow on the condition for neutral stability is discussed. The results obtained suggest that the disturbances are concentrated in internal viscous or critical layers well away from the wall and the free stream. The stability of a boundary layer on a concave wall to Gortler vortices that propagate downstream is also considered. These modes are found to be more stable than the usual time-independent modes and they propagate downstream with the speed of the basic flow in the critical layer. Some comparison with previous experimental and theoretical work is given.

Variability in the abundance of animal and plant species

Abstract: A striking and consistent observation in ecology is that variability in population abundance of a species and average population density are related in both space and time1,2. Taylor and his colleagues have shown that this relationship between variance (V) and mean (M) conforms well to a simple power law for a very wide range of animal and plant species, with the logarithms of sample variance and average sample density following a linear relationship1–3 (V = âMb where â and b are constants). They suggest that the slope of this line, b, which generally falls within the range 1 to 2, is a species-specific characteristic reflecting the balance between the opposing behavioural tendencies to aggregate within, and migrate from, centres of population density4. Taylor and co-workers1–6 have stressed that migration between patches is rarely a random process, on the evidence of the observed ‘density-dependent’ relationships between the degree of dispersion (the variance to mean ratio, V/M and mean abundance per patch). We show here that the relationship between variability and average abundance can be a simple, and inevitable, consequence of chance demographic events in the dynamics of population growth and decline. The precise form of these relationships is determined by the relative magnitude of the various rate processes which govern the dynamics of population change (the birth, death, immigration and emigration rates), and by the degree of spatial and temporal heterogeneity. We do not need to invoke any complex behavioural mechanisms to explain observed patterns.

Walls bounded by strings

Abstract: Extended structures consisting of walls bounded by strings appear in some unified gauge theories. The Spin(10) grand-unified-theory model provides the simplest example, provided the symmetry breaking proceeds via SU(4)\ifmmode\times\else\texttimes\fi{}SU(2)\ifmmode\times\else\texttimes\fi{}SU(2). It is shown that the presence of such structures may cause conflict with standard cosmology.