Showing papers by "University of Glasgow published in 1986"

Singular perturbation methods in control : analysis and design

Abstract: From the Publisher: Singular perturbations and time-scale techniques were introduced to control engineering in the late 1960s and have since become common tools for the modeling, analysis, and design of control systems. In this SIAM Classics edition of the 1986 book, the original text is reprinted in its entirety (along with a new preface), providing once again the theoretical foundation for representative control applications. This book continues to be essential in many ways. It lays down the foundation of singular perturbation theory for linear and nonlinear systems, it presents the methodology in a pedagogical way that is not available anywhere else, and it illustrates the theory with many solved examples, including various physical examples and applications. So while new developments may go beyond the topics covered in this book, they are still based on the methodology described here, which continues to be their common starting point. Audience Control engineers and graduate students who seek an introduction to singular perturbation methods in control will find this text useful. The book also provides research workers with sketches of problems in the areas of robust, adaptive, stochastic, and nonlinear control. No previous knowledge of singular perturbation techniques is assumed. About the Authors Petar Kokotovic is Director of the Center for Control Engineering and Computation at the University of California, Santa Barbara. Hassan K. Khalil is Professor of Electrical and Computer Engineering at Michigan State University. John O'Reilly is Professor of Electronics and Electrical Engineering at the University of Glasgow, Scotland.

The complete DNA sequence of varicella-zoster virus.

Abstract: Summary The entire DNA sequence of varicella-zoster virus (VZV) was determined using the M13-dideoxynucleotide technology. The genome is variable in size, but the sequence which was obtained comprises 124884 bp. Analysis of the sequence indicated that the genome contains 70 genes distributed about equally between the two DNA strands. The genes are organized compactly, but regions of overlap between protein-coding regions are not extensive. Many of the genes are arranged in 3′-coterminal families, and at least one is spliced. The discerned organization of VZV genes and that deduced for herpes simplex virus type 1 (HSV-1) from published transcript mapping data indicate that these two members of the Alphaherpesvirinae are very similar in gene layout. Comparisons of the predicted amino acid sequences of VZV proteins with those available for HSV-1 proteins generally suggest evolution from an ancestral genome, and allow the functions of several VZV genes to be deduced, although limited regions where the genomes differ in functional organization were also identified.

Activation of two signal-transduction systems in hepatocytes by glucagon

Abstract: The ability of glucagon to stimulate glycogen breakdown in liver played a key part in the classic identification of cyclic AMP and hormonally stimulated adenylate cyclase1. But several observations indicate that glucagon can exert effects independent of elevating intracellular cAMP concentrations2–7. These effects are probably mediated by an elevation8,9 of the intracellular concentration of free Ca2+ although the mechanism by which this occurs is unknown. We show here that glucagon, at the low concentrations found physiologically, causes both a breakdown of inositol phospholipids and the production of inositol phosphates. Indeed, we show that the glucagon analogue, (1-N-α-trinitrophenylhistidine,12-homo-arginine)glucagon (TH-glucagon), which does not activate adenylate cyclase or cause any increase in cAMP in hepatocytes yet can fully stimulate glycogenolysis, gluconeogenesis and urea synthesis10, stimulates the production of inositol phosphates. This stimulation of inositol phospholipid metabolism by low concentrations of glucagon provides a mechanism11,12 whereby glucagon can exert cAMP-independent actions on target cells. We suggest that hepatocytes possess two distinct receptors for glucagon, a GR-1 receptor coupled to stimulate inositol phospholipid breakdown and a GR-2 receptor coupled to stimulate adenylate cyclase activity.

Normal p21N-ras couples bombesin and other growth factor receptors to inositol phosphate production.

Abstract: Many receptors, in response to ligand activation, trigger inositol phospholipid breakdown, which leads to rapid intracellular responses. The sustained activation of this pathway is believed to be at least one of the factors involved in the stimulation of cell growth and there has been much speculation that certain oncogenes use this pathway to effect uncontrolled cellular proliferation. It has been suggested, by analogy with the receptor-mediated control of adenylate cyclase, that the receptor stimulation of inositol phospholipid metabolism is mediated through a guanine nucleotide regulatory protein (G-protein) called Gp (or Np). Although such a species has not been identified, there is now strong experimental evidence that this process is mediated by a G-protein distinct from the stimulatory and inhibitory G-proteins (Gs and Gi, respectively). The ras genes code for a plasma membrane protein, p21, whose only known biochemical property is a high-affinity GTPase activity. We show here that the expression of normal p21N-ras in NIH 3T3 fibroblasts leads to the coupling of certain growth factor receptors to stimulated inositol phosphate production. We propose that the N-ras proto-oncogene encodes a protein which couples the receptors for certain growth factors to the stimulation of phospholipase C. Thus, N-ras p21 may be the putative Gp or a functionally related protein.

The Central Metabolic Pathways of Escherichia coli: Relationship between Flux and Control at a Branch Point, Efficiency of Conversion to Biomass, and Excretion of Acetate

Abstract: Publisher Summary This chapter focuses on the central metabolic pathways of Escherichia coli . The chapter reviews the relationship between flux and control at a branch point, efficiency of conversion to biomass, and excretion of acetate. Provided that the metabolic routes through the central pathways are known, the carbon input and the outputs to biosynthesis, CO 2 , and excreted products can be used to compute the throughput of each step employed. The product of each throughput and growth rate gives the net flux through each individual enzyme of the system. Futile or useful cycles do not affect fluxes through other reactions in the pathways, and fluxes to maintain pool sizes are quantitatively insignificant. The central pathways are divided into two parts which utilize phosphorylated compounds and carboxylic acids, respectively. Carbon sources which feed into the phosphorylated pathways sustain a more efficient conversion to biomass because, in contrast with other carbon sources, they use the central pathways in the manner for which they were originally selected.

Intraspecific variation in competitive ability and food intake in salmonids: consequences for energy budgets and growth rates

Abstract: The interactions between dominance status, feeding rate and growth in rainbow trout, Salmo gairdneri Richardson, were analyzed using published data on experimental populations. There was a positive correlation between metabolic expenditure and food intake in both dominant and subordinate fish, but dominants obtained a greater intake for a given expenditure than did subordinates. Subordinates that adopted a high–return/high–cost foraging strategy actually expended more energy than they acquired, whereas those that minimized energy expenditure obtained a net energy gain. This led to the surprising finding that the growth rate of subordinates was negatively correlated with food intake.

Preliminary conclusions of the Royal Society and Academia Sinica 1985 geotraverse of Tibet

Abstract: The 1985 Chinese/British expedition to the Tibetan Plateau attempted to solve the question of the origin of the very thick crustal rocks in this region. Continuing northwards movement of the Indian plate over the past 38 Myr has given rise to severe folding and thrust faulting, causing crustal thickening by internal deformation. Previous collisions of microplate terranes derived from Gondwanaland occurred during Mesozoic times but the Kun Lun terrane of northern Tibet was already part of Laurasia by the Carboniferous

An energy budget for Porites porites (Scleractinia)

Abstract: An energy budget for Porites porites (Pallas) was determined for specimens from 10 m depth on the Fore Reef of Discovery Bay, Jamaica, between July 1984 and July 1985. Evidence for habitual zooplankton ingestion was not obtained, and P. porites appears to be largely autotrophic. Out of the daily photosynthetically fixed energy, 26% is used for animal respiration and growth, 22% for zooxanthellae respiration and growth, and <1% for colony reproduction as mature planulae; 45% remains unaccounted for. Colony respiration, net photosynthesis, colony skeleton and tissue growth, zooplankton ingestion, reproductive effort and energy content of tissues were measured. Energy loss as continuous mucus secretion was not detected, but may occur by an alternative route via mucus tunics, which occur periodically in situ and in the laboratory. The energy budget suggests that a considerable excess of photosynthetically fixed energy is produced on an ideal sunny day at 10 m depth. This surplus may be required for periodic rather than continuous energy demands, or may be essential to survive “less-than-ideal” days, when net photosynthetic input is reduced.

Specific inhibition of herpesvirus ribonucleotide reductase by synthetic peptides

Abstract: Ribonucleotide reductase is an essential enzyme for DNA synthesis in all prokaryotic and eukaryotic cells; it catalyses the reductive conversion of ribonucleotides to deoxyribonucleotides. Several herpesviruses including herpes simplex virus type 1 (HSV-1)1, HSV-22, pseudorabies virus (PRV)3, equine herpesvirus type 1 (EHV-1)4 and Epstein–Barr virus (EBV)5 have been found to induce novel ribonucleotide reductase activities. There is evidence that the HSV-1 ribonucleotide reductase activity is virus-encoded6 and essential for virus replication7. This makes herpesvirus ribonucleotide reductases potential targets for antiviral chemotherapy. The HSV-1-encoded enzyme consists of two summits8,9,18: V136, the large subunit of relative molecular mass (Mr) 136,000 (136K) (RR1), which has been shown to be essential for enzyme activity7, and V38, the small subunit (RR2) which forms a complex with the large subunit and is also likely to be essential for enzyme activity9. Two particular features of the enzyme make it an attractive antiviral target. First, there is evidence for a common, highly conserved herpesvirus ribonucleotide reductase and second, the interaction between the large and small subunits may itself be exploitable. Here we identify a synthetic peptide which specifically inhibits the activity of virus-induced enzyme. We deduce that the mechanism of inhibition involves interference with the normal interaction between the two types of subunit.

Human Papillomavirus in Clinically and Histologically Normal Tissue of Patients with Genital Cancer

Abstract: To study the association of human papillomavirus (HPV) and herpes simplex virus (HSV) with genital cancer, we collected specimens of cervical, vulvar, endometrial, and vaginal tumors at the time of operation in patients with cancer. In some patients, matched internalcontrol (histologically normal) tissue was also collected. DNA extracted from the tissue was probed with Radio-labeled HPV type 16 DNA, HPV type 18 DNA, and cloned fragments of HSV type 2 DNA. Hybridization to the HindIIIa clone of HSV-2 was detected in only 1 cervical tumor and 1 vulvar tumor (9 percent) among the 22 tumors tested. However, DNA sequences hybridizing to HPV-16 were detected in 21 of 25 tumors (84 percent) and in 8 of 11 (73 percent) of the DNA samples from clinically and histologically normal, paired, internal-control tissues from the patients with cancer. HPV-16 DNA was found in one of nine normal cervixes (11 percent) of women without genital neoplastic disease or abnormal cytology. HPV-18 DNA was detected in only 2...

Nucleotide sequences of a feline leukemia virus subgroup A envelope gene and long terminal repeat and evidence for the recombinational origin of subgroup B viruses.

Abstract: Molecular clones of the subgroup A feline leukemia virus FeLV-A/Glasgow-1 have been obtained. Nucleotide sequence analysis of the 3' end of the proviral genome and comparison with the published sequence of FeLV-B/Gardner-Arnstein showed that the most extensive differences are located within the 5' domain of the env gene. Within this domain, several divergent regions of env are separated by more conserved segments. The 3' end of env is highly conserved, with only a single amino acid coding difference in p15env. The proviral long terminal repeats are also highly conserved, differing by only eight base substitutions and one base insertion. Specific probes constructed from the FeLV-A or FeLV-B env genes were used to compare the env genes of various exogenous FeLV isolates and the endogenous FeLV-related proviruses of normal cat DNA. An FeLV-A-derived env probe showed no hybridization to normal cat DNA but detected all FeLV-A and FeLV-C isolates tested. In contrast, an FeLV-B env probe detected independent FeLV-B isolates and a family of endogenous FeLV-related proviruses. Our observations provide strong evidence to support the hypothesis that FeLV-B viruses have arisen by recombination between FeLV-A and endogenous proviral elements in cat DNA.

Characterization of the IE110 gene of herpes simplex virus type 1.

Abstract: We have determined the DNA sequence of the herpes simplex virus type 1 (HSV-1) gene encoding the immediate early protein IE110, which is involved in transcriptional activation of later virus genes. The locations of the 5' and 3' termini of IE110 mRNA together with the positions of two introns, were identified. Examination of the DNA sequence suggested that translation starts at the first ATG after the 5' terminus of the mRNA, and that both introns occur in protein-coding sequence. The predicted IE110 polypeptide contains 775 amino acids, and has a molecular weight of 78452. It contains a cysteine-rich region resembling regions found in several proteins which interact functionally with DNA. An antiserum was raised to the predicted C terminal amino acid sequence of the IE110 polypeptide and was shown to immunoprecipitate the native protein from HSV-1-infected cell extracts. The functional importance of regions of the protein was evaluated by construction of frameshift and deletion mutants of a plasmid-borne IE110 gene. The mutants were tested for IE110 function by short-term transfection assays, and the results were correlated with the DNA sequence and RNA mapping studies.

Pharmacokinetics of albendazole in man

Abstract: The pharmacokinetics of albendazole were investigated in healthy volunteers and in patients receiving albendazole for treatment of hydatid disease. Unchanged albendazole was below detectable limits in plasma, urine, bile and cyst fluid. The major metabolite present in all fluids was the sulfoxide. Maximum concentrations of albendazole sulfoxide in plasma were very variable, probably due to variable absorption of albendazole.

Arousal and sensation-seeking components in the general explanation of gambling and gambling addictions.

Abstract: Following upon the first clear experimental evidence that states of high arousal accompany gambling in real-life situations, an attempt is made to clarify the implications of this new finding for the development of two possible forms of a neo-Pavlovian or classical conditioning addition to the traditional emphasis on operant conditioning in behavioral explanations of gambling. The explanatory scope and power of one (biological hedonist) version of the model is then demonstrated as applied to both normal regular and pathological gambling. The role of arousal and sensation-seeking factors is considered alongside the roles of other likely components in any possible general explanation of both regular and pathological gambling.

Population Pharmacokinetics Theory and Clinical Application

Abstract: Good therapeutic practice should always be based on an understanding of pharmacokinetic variability. This ensures that dosage adjustments can be made to accommodate differences in pharmacokinetics due to genetic, environmental, physiological or pathological factors. The identification of the circumstances in which these factors play a significant role depends on the conduct of pharmacokinetic studies throughout all stages of drug development. Advances in pharmacokinetic data analysis in the last 10 years have opened up a more comprehensive approach to this subject: early traditional small group studies may now be complemented by later population-based studies. This change in emphasis has been largely brought about by the development of appropriate computer software (NONMEM: Nonlinear Mixed Effects Model) and its successful application to the retrospective analysis of clinical data of a number of commonly used drugs, e.g. digoxin, phenytoin, gentamicin, procainamide, mexiletine and lignocaine (lidocaine). Success has been measured in terms of the provision of information which leads to increased efficiency in dosage adjustment, usually based on a subsequent Bayesian feedback procedure. The application of NONMEM to new drugs, however, raises a number of interesting questions, e.g. ‘what experimental design strategies should be employed?’ and ‘can kinetic parameter distributions other than those which are unimodal and normal be identified?’ An answer to the latter question may be provided by an alternative non-parametric maximum likelihood (NPML) approach.

A new theoretical framework for information retrieval

Abstract: A new framework based on a non-classical logic is proposed for investigating IR. The paper motivates the use of a particular conditional logic as the 'right' logic for IR. A new principle, the logical uncertainty principle, is proposed, to deal with the inherent uncertainty associated with applicable inferences.

Recent Advances in the Phenomenological Theory of Rubber Elasticity

Abstract: We have shown that representations for the strain-energy function in terms of the stretches λ1, λ1, λ1, with particular reference to the Valanis-Landel hypothesis, provide a very good corr...

Basal linear deposit in the human macula.

Abstract: We used electron microscopy and immunohistochemistry to study the macular regions of nine enucleated elderly human eyes and to document the various abnormalities present in the so-called basal linear deposit. These changes include bush-like strands of electron-dense material, which project from the basement membrane of the retinal pigment epithelium, deposition of wide-banded collagen, vesiculoid elements, membrane-bound structures and occasional melanin granules. Fibronectin was also identified in the basal linear deposit and in Bruch's membrane, but mucopolysaccharides could not be demonstrated. The presence of electron-empty spaces suggests a disturbance in water permeability. Our studies also showed neovascularisation beneath the retinal pigment epithelium in locations where the basal linear deposit was abundant, as well as erosion of Bruch's membrane by macrophages and endothelial cell processes. Our findings suggest that the basal linear deposit is an important precursor of neovascularisation. Possible pathogenetic mechanisms are discussed.

Scavenging Efficiency of Turkey Vultures in Tropical Forest

Abstract: L'efficacite depend du temps mis par l'oiseau pour detecter les carcasses en milieu couvert

The effect of verapamil on the pharmacokinetics of adriamycin.

Abstract: The concurrent administration of adriamycin (intravenous) and verpamil (oral) is of considerable interest because of experimental data suggesting that resistance to adriamycin may be overcome by this means. The potential for a pharmacokinetic interaction between the two drugs has therefore been investigated in five patients with small cell lung cancer treated with combination chemotherapy comprising adriamycin, VP16, vincristine and cyclophosphamide. The data indicate that a significant interaction takes place. Adriamycin peak levels, terminal halflife and the volume of distribution at steady state are higher, whereas plasma drug clearance and the volume of the central compartment are lower with co-administration of verapamil. There was no evidence of enhanced drug toxicity in this study; however, the data should be considered in the interpretation of clinical trials in which adriamycin and verapamil are used together, both in terms of toxicity and tumour response.

Increased exposure of parasite antigens at the surface of adult male Schistosoma mansoni exposed to praziquantel in vitro.

Abstract: Praziquantel is a broad-spectrum anthelmintic active against schistosome species which are major parasites of man. Two major effects on Schistosoma mansoni have been demonstrated; (i) spastic paralysis of the parasite musculature, possibly arising as a consequence of an influx of Ca2+ into the worm (Pax, Bennett & Fetterer, 1978; Coles, 1979) and (ii) vacuolation and degeneration of the worm tegument (Becker, Mehlhorn, Andrews, Thomas & Eckert, 1980). These events may contribute to the elimination of schistosomes in vivo, but this elimination may partly be dependent on the host immune response as infected T-cell-deprived mice are less able than immunologically intact animals to reduce their worm burdens following drug treatment (Doenhoff, Harrison, Sabah, Murare, Dunne & Hassounah, 1982). This latter observation raises the possibility that praziquantel may lower the ability of the parasite to evade host immunity by increasing the exposure of parasite antigens capable of acting as targets for host antibody, or antibody-armed cells at the worm surface. Consistent with this idea is the observation that adult schistosomes in praziquantel-treated mice are invaded a few hours after treatment by host granulocytes (Mehlhorn, Becker, Andrews, Thomas & Frenkel, 1981).

Substrate Hydroxylation and Cell Adhesion

Abstract: Adhesion of BHK cells to a variety of polymer surfaces carrying measured densities of hydroxyl and carboxyl groups was studied. The effects on cell adhesion of blocking hydroxyl groups by acetylation and carboxyl groups with diazomethane were measured. Hydroxyl groups were required for cell adhesion, though the very high surface densities of these groups diminished cell adhesion. The optimal surface density of OH groups for BHK adhesion was 2000 per 1 × 10−11cm2. Carboxyl groups slightly inhibit cell adhesion, since blocking of these groups by methylation increased adhesion. The role of oxidizing systems of cellular origin in conditioning of the substrate, in serum-free conditions, was demonstrated for leucocytes and BHK cells, in particular by the result that oxidizable substrates such as phytane and poly(1,2-butadiene) could be made suitable for cell adhesion by contact with cells.

Actions of α, β‐methylene ATP and 6‐hydroxydopamine on sympathetic neurotransmission in the vas deferens of the guinea‐pig, rat and mouse: support for co‐transmission

Abstract: alpha-Adrenoceptor antagonists (prazosin or phentolamine) reduced the contractile response to field stimulation of the isolated vasa deferentia of guinea-pig, rat and mouse. alpha, beta-Methylene ATP (alpha, beta-MeATP) reduced that portion of the contraction which was resistant to alpha-adrenoceptor blockade. alpha, beta-MeATP (1-800 microM) did not affect action potential conduction in the guinea-pig vas deferens nerves, and (up to 10 microM) did not reduce the stimulation-evoked overflow of [3H]-noradrenaline from this tissue. Spontaneous excitatory junction potentials (s.e.j.ps) in the majority of cells of guinea-pig, rat, and mouse vasa were abolished by alpha, beta-MeATP (0.1-10 microM). In a small number of cells s.e.j.ps were resistant to the actions of alpha, beta-MeATP (10 microM). Excitatory junction potentials (e.j.ps) in the majority of cells in vasa of all species studied were abolished by alpha, beta-MeATP (1-10 microM). E.j.ps elicited in some 'resistant' cells demonstrated marked facilitation characteristics. It is concluded that alpha, beta-MeATP inhibits s.e.j.ps and e.j.ps by a postjunctional action. In all species pretreatment of animals with 6-hydroxydopamine produced a marked reduction in noradrenaline (NA) content (as determined by fluorescence histochemistry) and abolished e.j.ps, findings which suggest that e.j.ps originated from sympathetic nerves. The results support the hypothesis that NA and ATP are co-transmitters in the sympathetic nerves of rodent vasa.

Variable transfer of Y-specific sequences in XX males

Abstract: A series of twelve XX males and their relatives have been examined by Southern blot analysis with fourteen different Y recombinants. The pattern of Y sequences present shows considerable variation between XX males. Furthermore, on the basis of the terminal transfer model, anomalous patterns of Y sequences are evident in certain XX males in that sequences located as proximal Yp by means of a Y deletion panel are found to be present in the absence of distal sequences. These anomalies can be resolved by proposing that the order of Yp sequences varies in the population in the form of inversion polymorphisms in the Y chromosomes of normal males. Alternatively, it is necessary to invoke multiple recombination events between the X and Y chromosomes to explain the patterns of Y sequences in these XX males. Southern analysis on DNA prepared from flow sorted X chromosomes of XX males indicates that the Y sequences in these patients are linked to X chromosomes.