Showing papers by "Imperial College London published in 1985"

Sequence and structure of a human glucose transporter

Abstract: The amino acid sequence of the glucose transport protein from human HepG2 hepatoma cells was deduced from analysis of a complementary DNA clone. Structural analysis of the purified human erythrocyte glucose transporter by fast atom bombardment mapping and gas phase Edman degradation confirmed the identity of the clone and demonstrated that the HepG2 and erythrocyte transporters are highly homologous and may be identical. The protein lacks a cleavable amino-terminal signal sequence. Analysis of the primary structure suggests the presence of 12 membrane-spanning domains. Several of these may form amphipathic alpha helices and contain abundant hydroxyl and amide side chains that could participate in glucose binding or line a transmembrane pore through which the sugar moves. The amino terminus, carboxyl terminus, and a highly hydrophilic domain in the center of the protein are all predicted to lie on the cytoplasmic face. Messenger RNA species homologous to HepG2 glucose transporter messenger RNA were detected in K562 leukemic cells, HT29 colon adenocarcinoma cells, and human kidney tissue.

Hydrogen bonding and biological specificity analysed by protein engineering

Abstract: The role of complementary hydrogen bonding as a determinant of biological specificity has been examined by protein engineering of the tyrosyl-tRNA synthetase. Deletion of a side chain between enzyme and substrate to leave an unpaired, uncharged hydrogen-bond donor or acceptor weakens binding energy by only 0.5–1.5 kcal mol−1. But the presence of an unpaired and charged donor or acceptor weakens binding by a further ∼3 kcal mol−1.

Structure of large fragment of Escherichia coli DNA polymerase I complexed with dTMP

Abstract: The 33-A resolution crystal structure of the large proteolytic fragment of Escherichia coli DNA polymerase I complexed with deoxythymidine monophosphate consists of two domains, the smaller of which binds zinc-deoxythymidine monophosphate The most striking feature of the larger domain is a deep crevice of the appropriate size and shape for binding double-stranded B-DNA A flexible subdomain may allow the enzyme to surround completely the DNA substrate, thereby allowing processive nucleotide polymerization without enzyme dissociation

Maximum likelihood estimation in a class of nonregular cases

Abstract: SUMMARY We consider maximum likelihood estimation of the parameters of a probability density which is zero for x 2, the information matrix is finite and the classical asymptotic properties continue to hold. For cx = 2 the maximum likelihood estimators are asymptotically efficient and normally distributed, but with a different rate of convergence. For 1 < a < 2, the maximum likelihood estimators exist in general, but are not asymptotically normal, while the question of asymptotic efficiency is still unsolved. For cx < 1, the maximum likelihood estimators may not exist at all, but alternatives are proposed. All these results are already known for the case of a single unknown location parameter 0, but are here extended to the case in which there are additional unknown parameters. The paper concludes with a discussion of the applications in extreme value theory.

Accounting in its social context: Towards a history of value added in the United Kingdom

Abstract: Although the relationship between accounting and society has been posited frequently, it has been subjected to little systematic analysis. This paper reviews some existing theories of the social nature of accounting practice and, by so doing, identifies a number of significant conceptual problems. Using the case of the rise of interest in value added accounting in the United Kingdom in the 1970s, the paper conducts a social analysis of this particular event and then seeks to draw out the theoretical issues and problems which emerge from this exercise. Finally, the implications of these for the social analysis of accounting are discussed.

Vaccination and herd immunity to infectious diseases

Abstract: An understanding of the relationship between the transmission dynamics of infectious agents and herd immunity provides a template for the design of effective control programmes based on mass immunization. Mathematical models of the spread and persistence of infection provide important insights into the problem of how best to protect the community against disease.

Helminth infections of humans: mathematical models, population dynamics, and control.

Abstract: Publisher Summary This chapter reviews the role of mathematical models in the investigations of the population or transmission dynamics of human helminths. It focuses on the biological assumptions employed in model construction, the insights that emerge from model analysis, the comparison of predictions with observed trends, and the estimation of parameter values from epidemiological data. The chapter provides a brief description of observed epidemiological patterns, concentrating on age-prevalence and age-intensity trends and a historical review of the development of the mathematical models of helminth infections. The chapter also discusses mathematical models for schistosome flukes, for intestinal nematodes, and for the filarial infections and the essential features of the models for specific infections to provide a general framework for the description of helminth transmission dynamics. The general framework is presented to consider the design of control policies for helminth infections in human communities.

An Exact Two-Dimensional Non-Guillotine Cutting Tree Search Procedure

Abstract: We consider the two-dimensional cutting problem of cutting a number of rectangular pieces from a single large rectangle so as to maximize the value of the pieces cut. We develop a Lagrangean relaxation of a zero-one integer programming formulation of the problem and use it as a bound in a tree search procedure. Subgradient optimization is used to optimize the bound derived from the Lagrangean relaxation. Problem reduction tests derived from both the original problem and the Lagrangean relaxation are given. Incorporating the bound and the reduction tests into a tree search procedure enables moderately sized problems to be solved.

Localization of cystic fibrosis locus to human chromosome 7cen–q22

Abstract: Cystic fibrosis (CF) is the most common genetic disease in Caucasian populations, with an incidence of 1 in 2,000 live births in the United Kingdom, and a carrier frequency of approximately 1 in 20. The biochemical basis of the disease is not known, although membrane transport phenomena associated with CF have been described recently. Consanguinity studies have shown that the inheritance of CF is consistent with it being a recessive defect caused by a mutation at a single autosomal locus. Eiberg et al. have reported a genetic linkage between the CF locus and a polymorphic locus controlling activity of the serum aryl esterase paraoxonase (PON). The chromosomal location of PON, however, is not known. Linkage to a DNA probe, DOCR1-917, was also recently found at a genetic distance of approximately 15 centimorgans (L.-C. Tsui and H. Donnis-Keller, personal communication), but no chromosomal localization was given. Here we report tight linkage between the CF locus and an anonymous DNA probe, pJ3.11, which has been assigned to chromosome 7cen-q22.

Resonant ULF waves: A new interpretation

Abstract: Many important properties of ultra-low frequency (ULF) magnetic pulsations (∼1 to 10 minute periods) observed in the magnetosphere and by ground-based magnetometers have been interpreted successfully in terms of resonant field line models. These models describe the pulsations as transverse hydromagnetic waves standing on dipole flux tubes with fixed ends in the ionosphere. Signal structure and frequency are consistently explained, but the models fail to provide convincing explanations of the discrete spectra often observed. In this letter we propose that the spectrum of excitations is dominated by frequencies that correspond to eigenfrequencies of the fast (compressional) mode in the outer magnetosphere. In the presence of plasma inhomogeneities, the eigenmodes of the fast mode damp, even in the absence of dissipation, through coupling to transverse waves. We discuss the properties of a damped eigenmode, pointing out the analogy to the properties of damped surface eigenmodes. The coupled waves exhibit field line resonance behavior on the magnetic shell where the transverse mode dispersion relation is satisfied, but the spectrum is dominated by fast mode eigenfrequencies.

Dynamic Configuration for Distributed Systems

Abstract: Dynamic system configuration is the ability to modify and extend a system while it is running. The facility is a requirement in large distributed systems where it may not be possible or economic to stop the entire system to allow modification to part of its hardware or software. It is also useful during production of the system to aid incremental integration of component parts, and during operation to aid system evolution. The paper introduces a model of the configuration process which permits dynamic incremental modification and extension. Using this model we determine the properties required by languages and their execution environments to support dynamic configuration. CONIC, the distributed system which has been developed at Imperial College with the specific objective of supporting dynamic configuration, is described to illustrate the feasibility of the model.

Algorithms for Unconstrained Two-Dimensional Guillotine Cutting

Abstract: In this paper we consider the unconstrained, two-dimensional, guillotine cutting problem. This is the problem that occurs in the cutting of a number of rectangular pieces from a single large rectangle, so as to maximize the value of the pieces cut, where any cuts that are made are restricted to be guillotine cuts. We consider both the staged version of the problem (where the cutting is performed in a number of distinct stages) and the general (non-staged) version of the problem. A number of algorithms, both heuristic and optimal, based upon dynamic programming are presented. Computational results are given for large problems.

Age-related changes in the rate of disease transmission: implications for the design of vaccination programmes.

Abstract: Mathematical models are developed to aid in the investigation of the implications of heterogeneity in contact with infection within a community, on the design of mass vaccination programmes for the control of childhood viral and bacterial infections in developed countries. Analyses are focused on age-dependency in the rate at which individuals acquire infection, the question of 'who acquires infection from whom', and the implications of genetic variability in susceptibility to infection. Throughout, theoretical predictions are based on parameter estimates obtained from epidemiological studies and are compared with observed temporal trends in disease incidence and age-stratified serological profiles. Analysis of case notification records and serological data suggest that the rate at which individuals acquire many common infections changes from medium to high and then to low levels in the infant, child and teenage plus adult age groups respectively. Such apparent age-dependency in attack rate acts to reduce slightly the predicted levels of herd immunity required for the eradication of infections such as measles, when compared with the predictions of models based on age-independent transmission. The action of maternally derived immunity in prohibiting vaccination in infants, and the broad span of age classes over which vaccination currently takes place in the U.K., however, argue that levels of herd immunity of between 90 and 94% would be required to eliminate measles. Problems surrounding the interpretation of apparent age-related trends in the acquisition of infection and their relevance to the design of vaccination programmes, are discussed in relation to the possible role of genetically based variation in susceptibility to infection and observations on epidemics in 'virgin' populations. Heterogeneous mixing models provide predictions of changes in serology and disease incidence under the impact of mass vaccination which well mirror observed trends in England and Wales.

Recent star formation in interacting galaxies - II. Super starbursts in merging galaxies.

Abstract: Contrairement au cas des Seyfert, les proprietes radio, IR et optiques des objets resultant du fusionnement ne revelent pas de source centrale compacte non thermique, et peuvent etre interpretees grâce a un sursaut de formation stellaire d'intensite et d'etendue spatiale extraordinaires: ce sont les «super sursauts stellaires». On suggere qu'ils se produisent au cours de la plupart des fusionnements

A technical note on the inclusion of pressure dependent demand and leakage terms in water supply network models

Abstract: This note suggests a technique for including pressure dependent demand and leakage terms in simulation models for water distribution systems. Empirical functions are used to relate consumer outflows and leakage losses to the network pressures and the inclusion of these functions in the mathematical formulation of the network analysis problem is described. An application to an existing distribution system is presented where it is shown that the extended network model proposed leads to more realistic simulation results when the network pressures are too low to provide specified consumer demands, or high enough to cause significant leakage losses. It is also found that the computational requirements of network analysis and simulation are not significantly affected by the inclusion of the additional terms.

The Taupo eruption, New Zealand I. General aspects

Abstract: The ca . a.d. 186 Taupo eruption was the latest eruption at the Taupo Volcanic Centre, occurring from a vent, at Horomatangi Reefs, now submerged beneath Lake Taupo in the central North Island of New Zealand. Minor initial phreatomagmatic activity was followed by the dry vent 6 km 3 Hatepe plinian outburst. Large amounts of water then entered the vent during the 2.5 km 3 Hatepe phreatoplinian ash phase, eventually stopping the eruption, though large amounts of water continued to be ejected from the vent area, causing gullying of the ash deposits. After a break of several hours to weeks, phreatoplinian activity resumed, generating the 1.3 km 3 Rotongaio ash, notable for its fine grainsize and for containing significant quantities of non- or poorly-vesicular juvenile material. The vent area then became dry again, and eruption rates and power markedly increased into the 23 km 3 Taupo ‘ ultraplinian ’ phase, which is the most powerful plinian outburst yet documented. Synchronous with this ultraplinian activity, lesser volumes of non- to partially-welded ignimbrite were generated by diversion of ejecta from, or partial collapse of, the eruption column. The rapid rate of magma withdraw al during this phase removed support from the vent area, to trigger local vent collapse and initiate the catastrophic eruption of the ca. 30 km 3 Taupo ignimbrite. Finally, after some years, lava was extruded on to the floor of the reformed Lake Taupo, and floating fragments derived from the lava carapace were driven ashore. The known eruption volume is more than 65 km 3 , while additional volumes are represented by primary material now beneath Lake Taupo and layer 3 to the ignim brite phases; a total volume of more than 105 km 3 is likely, equivalent to more than 35 km 3 of magma plus more than 3 km 3 of lithic debris. Airfall deposits more than 10 cm thick blanketed 30000 km 2 of land east of the vent, while ignimbrite covers a near-circular area of 20000 km 2 . Widespread and locally severe ground shaking occurred during, but mostly after the eruption, associated with subsidence in the Lake Taupo basin. Secondary deposits are abundant above and extending beyond the Taupo ignimbrite, consisting of the products of surface water interacting with the still-hot ignimbrite and subsequent water reworking of the light, pumiceous materials. The complexity and size of this eruption preclude accurate forecasting of the size, nature and return period of the inevitable next eruption from the Taupo Volcanic Centre.

The Taupo eruption, New Zealand. II. The Taupo Ignimbrite

Abstract: The ca. 30 km 3 Taupo ignimbrite was erupted as a climax to the ca. AD 186 Taupo eruption in the central North Island of New Zealand. It was erupted as a single vent-generated flow unit over a time period of ca. 400 s and was emplaced very rapidly (locally at more than 250-300 m s -1 ) and violently. The parent flow reached 8 0 + 10 km from source in all directions, crossed all but one of the mountains within its range and only stopped when it ran out of material. The ignimbrite is divisible into layers 1 and 2, and a distant facies which combines features of both layers. Layer 1 was generated as a result of strong fluidization in the flow head, caused by air ingestion, and consists of two main facies. Layer 1(P) is a pumiceous, mildly to strongly fines-depleted unit, generated by the expulsion of material from the flow front, and termed the jetted deposits. The overlying layer 1 (H) is a thinner, crystal- and lithic-rich, fines-depleted unit, generated by the sedimentation of coarse/dense constituents segregated out by strong fluidization within the flow head and termed the ground layer. Layer 2 consists of two facies with similar compositions but contrasting morphologies; during emplacement, material left behind by the flow body partially drained into depressions to form the valley-ponded ignimbrite, leaving the veneer deposit as a thin, landscape mantling layer on interfluves. The distant facies occurs in some outermost hilly areas of the ignimbrite where the flow velocity remained high but its volume had shrunk through deposition so that air ingestion fluidization affected the whole flow. The ignimbrite shows great lateral variations. Each facies, or variants therein, exhibits systematic degrees of development with varying distances from vent. Near vent, the flow consisted of a series of batches of material which by ca. 25 km had coalesced into a single wavy flow and by ca. 40 km into a single wave. Out to ca. 13 km, the flow was rather dilute and highly turbulent as it deflated from the collapsing eruption column. Beyond this distance it was fairly concentrated, being less than 100% expanded over its non-fluidized compacted state, and had acquired a fluidization-induced stable density stratification, which strongly suppressed turbulence in the flow body. Deflation from the eruption column was largely complete by ca. 13 km but influenced the flow as far as 20-25 km from vent. Grainsize and compositional parameters measured in the ignimbrite show lateral variations which equal or exceed the entire spectrum of published ignimbrite data. The flow had deflated and coalesced from the eruption column by ca. 20 km from vent. Beyond this distance most lateral variations are modelled by considering the flow to be a giant fluidized bed. As the flow moved, material was deposited from its base, and hence predictable vertical variations in the model fluidized bed are comparable with lateral variations in the ignimbrite. The agreement is excellent, and, in particular, discontinuities in the nature of the ignimbrite at 55-60 km from vent suggest that the more distal ignimbrite represents a vast segregation layer generated above the moving flow. Differences between the model and variations of some parameters reflect the influence of kinetic processes, such as shearing and local fluidization, that operated regardless of the bulk flow composition. The strong fluidization in the flow is a result of the high flow velocities (promoting air ingestion), not vice versa as is often accepted. Contrasts in the natures of layers 1 and 2 imply that the first material erupted contained significantly coarser, and a higher content of, lithics than the bulk of the flow. During emplacement, this earlier material was depleted by deposition and diluted by material introduced from the flow body. Systematic regional variations also occur in the ignimbrite: for example, it contains lower crystal: lithic ratios and higher density pumice in a northeasterly sector, and vice versa to the southwest. Ignimbrite found in mountainous areas shows changes consistent with its derivation from the upper, more mobile and pumiceous top of the flow. Fluidization processes generated structures and facies in the ignimbrite on various scales. Individual segregation bodies found at any exposure show features mimicking those of the ground layer, i.e. fines depletion and crystal- and lithic-enrichment. Fluidization-induced grading visible at individual exposures accounts for the great range of grading styles seen in the valley-ponded ignimbrite, and strong fluidization has locally generated an upper fines- and pumice- rich segregation layer (here termed layer 2c). On the largest scale, fluidization was primarily responsible for the generation of the layer 1 deposits, and for the grainsize and compositional zonation within the flow that produced the lateral variations in the ignimbrite. Ingested and heated air is inferred to have been the most important gas source for fluidization within the flow, although several other gas sources were locally dominant. It is clear that the thickness, grainsize and composition of the ignimbrite at any point are not simply related to values of these parameters in either the originally erupted material or the parent flow, and that, except for its density, the dimensions and composition of the parent flow cannot be directly inferred from the ignimbrite.

Search for a transition in the three-dimensional J Ising spin-glass

Abstract: The three-dimensional Ising spin-glass in zero field with nearest-neighbor interactions having \ifmmode\pm\else\textpm\fi{}J distribution is studied by Monte Carlo simulations for samples of linear dimension L with 3\ensuremath{\le}L\ensuremath{\le}20. Results for the probability distribution, ${\mathrm{P}}_{\mathrm{L}}$(q), of the spin-glass order parameter are analyzed by finite-size scaling. Data for T\ensuremath{\ge}1.2 are consistent with a conventional phase transition at ${\mathrm{T}}_{\mathrm{c}}$${=1.2}_{\mathrm{\ensuremath{-}}0.2}^{+0.1}$, with exponents \ensuremath{ u}=1.3\ifmmode\pm\else\textpm\fi{}0.3 and \ensuremath{\eta}=-0.3\ifmmode\pm\else\textpm\fi{}0.2. However, results at lower temperature indicate marginal behavior and suggest that the lower critical dimensional is close to three.

Herd immunity to helminth infection and implications for parasite control

Abstract: Despite much research on immunological responses to helminth parasites, knowledge of the dynamic interplay between levels of herd immunity in humans and the rates of exposure, establishment and mortality of parasites remains limited. We describe here a simple mathematical model for the population dynamics of helminth infections which mirrors the development of a degree of acquired immunity within populations which are genetically heterogeneous with respect to immunological responsiveness. We interpret observed patterns in the age-specific intensity of infection and attempt to understand the possible effects of control measures based on chemotherapy and vaccination. Mass chemotherapy can, in some circumstances, reduce the level of herd immunity such that average worm burdens in the adult age classes rise above their precontrol levels. When certain individuals or groups are predisposed to heavy infection, selective or targeted drug treatment can have significantly greater impact than mass or random application. Conversely, model predictions suggest that effective parasite control by vaccination (if and when vaccines become available) is difficult to achieve in communities that are genetically heterogeneous in their ability to mount protective responses to infection.