Showing papers by "University of Oxford published in 1993"

Merger rates in hierarchical models of galaxy formation

Abstract: We present an analytical description of the merging of virialized haloes which is applicable to any hierarchical model in which structure grows via gravitational instability. The formulae are an extension of the Press-Schechter model. The dependence of the merger rate on halo mass, epoch, the spectrum of initial density fluctuations and the density parameter Ω0 is explicitly quantified. We calculate the distribution of halo formation times and survival times. We also describe a Monte Carlo method for constructing representative histories of merger events leading to formation of haloes of a prescribed mass. Applying these results to the age distribution of rich clusters of galaxies, we infer that a high value of the density parameter (Ω0 ≳ 0.5) is required to reproduce the substantial fraction of rich clusters that exhibit significant substructure, if such substructure only persists for a time 0.2t0 after a merger, where t0 is the present age of the universe. We also investigate the rate of infall of satellite galaxies into galactic discs, by combining our Monte Carlo technique for halo mergers with an estimate of the time required for dynamical friction to erode the orbits of the baryonic cores of the accreted galaxies. We find that, even for Ω0 = 1, the infall rate is low (provided that the satellite orbits are not too eccentric), and that we would expect only a modest fraction of stellar discs to be thickened or disrupted by this process.

Multiple defects of immune cell function in mice with disrupted interferon-gamma genes

Abstract: Interferon-gamma (IFN-gamma) is a pleiotrophic cytokine with immunomodulatory effects on a variety of immune cells. Mice with a targeted disruption of the IFN-gamma gene were generated. These mice developed normally and were healthy in the absence of pathogens. However, mice deficient in IFN-gamma had impaired production of macrophage antimicrobial products and reduced expression of macrophage major histocompatibility complex class II antigens. IFN-gamma-deficient mice were killed by a sublethal dose of the intracellular pathogen Mycobacterium bovis. Splenocytes exhibited uncontrolled proliferation in response to mitogen and alloantigen. After a mixed lymphocyte reaction, T cell cytolytic activity was enhanced against allogeneic target cells. Resting splenic natural killer cell activity was reduced in IFN-gamma-deficient mice. Thus, IFN-gamma is essential for the function of several cell types of the murine immune system.

Thermoelasticity without energy dissipation

Abstract: This paper deals with thermoelastic material behavior without energy dissipation; it deals with both nonlinear and linear theories, although emphasis is placed on the latter. In particular, the linearized theory of thermoelasticity discussed possesses the following properties: (a) the heat flow, in contrast to that in classical thermoelasticity characterized by the Fourier law, does not involve energy dissipation; (b) a constitutive equation for an entropy flux vector is determined by the same potential function which also determines the stress; and (c) it permits the transmission of heat as thermal waves at finite speed. Also, a general uniqueness theorem is proved which is appropriate for linear thermoelasticity without energy dissipation.

‘‘Event-ready-detectors’’ Bell experiment via entanglement swapping

Abstract: Using independent sources one can realize an ``event-ready'' Bell--Einstein-Podolsky-Rosen experiment in which one can measure directly the probabilities of the various outcomes including nondetection of both particles. Our proposal involves two parametric down-converters. Subcoherence-time monitoring of the idlers provides a noninteractive quantum measurement entangling and preselecting the independent signals without touching them. We give the conditions for high fringe visibility and particle collection efficiency as required for a Bell test.

A strategy of win-stay, lose-shift that outperforms tit-for-tat in the Prisoner's Dilemma game.

Abstract: The Prisoner's Dilemma is the leading metaphor for the evolution of cooperative behaviour in populations of selfish agents, especially since the well-known computer tournaments of Axelrod and their application to biological communities. In Axelrod's simulations, the simple strategy tit-for-tat did outstandingly well and subsequently became the major paradigm for reciprocal altruism. Here we present extended evolutionary simulations of heterogeneous ensembles of probabilistic strategies including mutation and selection, and report the unexpected success of another protagonist: Pavlov. This strategy is as simple as tit-for-tat and embodies the fundamental behavioural mechanism win-stay, lose-shift, which seems to be a widespread rule. Pavlov's success is based on two important advantages over tit-for-tat: it can correct occasional mistakes and exploit unconditional cooperators. This second feature prevents Pavlov populations from being undermined by unconditional cooperators, which in turn invite defectors. Pavlov seems to be more robust than tit-for-tat, suggesting that cooperative behaviour in natural situations may often be based on win-stay, lose-shift.

Short form 36 (SF36) health survey questionnaire: normative data for adults of working age.

Abstract: OBJECTIVES--To gain population norms for the short form 36 health survey questionnaire (SF36) in a large community sample and to explore the questionnaire's internal consistency and validity. DESIGN--Postal survey by using a booklet containing the SF36 and several other items concerned with lifestyles and illness. SETTING--The sample was drawn from computerised registers of the family health services authorities for Berkshire, Buckinghamshire, Northamptonshire, and Oxfordshire. SAMPLE--13,042 randomly selected subjects aged 18-64 years. MAIN OUTCOME MEASURES--Scores for the eight health dimensions of the SF36. RESULTS--The survey achieved a response rate of 72% (n = 9332). Internal consistency of the different dimensions of the questionnaire was high. Normative data broken down by age, sex, and social class were consistent with those from previous studies. CONCLUSIONS--The SF36 is a potentially valuable tool in medical research. The normative data provided here may further facilitate its validation and use.

ALSCRIPT: a tool to format multiple sequence alignments.

Abstract: The ALSCRIPT program described in this article was developed specifically to allow the easy formatting and graphical display of large multiple alignments. Although written originally for the author's use, the interface is relatively friendly, and should be easy to learn by anyone familiar with plotting graphs

Is the cerebellum a smith predictor

Abstract: The motor system may use internal predictive models of the motor apparatus to achieve better control than would be possible by negative feedback. Several theories have proposed that the cerebellum may form these predictive representations. In this article, we review these theories and try to unify them by reference to an engineering control model known as a Smith Predictor. We suggest that the cerebellum forms two types of internal model. One model is a forward predictive model of the motor apparatus (e.g., limb and muscle), providing a rapid prediction of the sensory consequences of each movement. The second model is of the time delays in the control loop (due to receptor and effector delays, axonal conductances, and cognitive processing delays). This model delays a copy of the rapid prediction so that it can be compared in temporal register with actual sensory feedback from the movement. The result of this comparison is used both to correct for errors in performance and as a training signal to learn the first model. We discuss evidence that the cerebellum could form both of these models and suggest that the cerebellum may hold at least two separate Smith Predictors. One, in the lateral cerebellum, would predict the movement outcome in visual, egocentric, or peripersonal coordinates. Another, in the intermediate cerebellum, would predict the consequences in motor coordinates. Generalization of the Smith Predictor theory is discussed in light of cerebellar involvement in nonmotor control systems, including autonomic functions and cognition.

Human Development in Poor Countries: On the Role of Private Incomes and Public Services

Abstract: Development is often taken to mean rising incomes. Discussions of the "goals of development" now often emphasize the reduction of poverty, rather than raising average incomes per se. The role of social services—particularly basic health and education—has also received greater emphasis in the 1980s, viewed mainly as instruments for raising the incomes of the poor. But, in all these approaches, income growth of one sort or another is what development is all about. A rather different view of the meaning of development has recently found expression in the 1990 Human Development Report (HRD) produced by the United Nations Development Programme. A conceptual underpinning for this approach can be found in the work of Amartya Sen. The essence of this view is that human development—what people can actually do and be—is the overriding purpose of economic development. Underdevelopment is viewed as the lack of certain basic capabilities, rather than lack of income per se. We do not aim here to advocate one of these approaches over the other, but rather to explore their implications for development policy. For instance, what does the human development approach imply about the role of economic growth and, in particular, about reducing income poverty? Should development priorities shift toward the provision of public services in poor countries, even if such a shift is at the expense of income growth?

The Frontal Lobes and Voluntary Action

Abstract: 1. Voluntary action 2. Motor cortex (area 4) 3. Lateral premotor cortext (area 6) 4. Medial premotor cortex (area 6) 5. Premotor area 8 6. Dorsal prefrontal cortex (areas 4, 6 and 9) 7. Ventral prefrontal cortex (areas 11, 12, 13 and 14) 8. Basal ganglia 9. The organisation of the frontal lobe 10. Thought and voluntary action 11. Speech

The expression of the adhesion molecules ICAM‐1, VCAM‐1, PECAM, and E‐selectin in human atherosclerosis

Abstract: The expression of PECAM, ICAM-1, VCAM-1, and E-selectin was studied in 64 samples of human coronary arteries taken from 15 explanted hearts obtained within 5 min of transplantation. Normal artery (n = 12), predominantly fibrous plaques (n = 23), and plaques containing extracellular lipid (n = 26) and three segments showing recanalization channels were studied. All endothelial cells strongly and equally expressed PECAM; positive staining was used to check that artefactual denudation of the endothelial surface had not occurred. PECAM was also present in some lipid-filled macrophages. Normal arteries showed no VCAM-1 staining but focal segments of the endothelium were positive for ICAM-1 and E-selectin. ICAM-1 was strongly and constantly expressed by the endothelium over all types of plaques and in macrophages. E-selectin expression was confined to endothelial cells and occurred on the surface in 35 per cent of fibrous and 22 per cent of lipid-containing plaques. VCAM-1 staining of surface endothelium occurred in 39 per cent of fibrous and 20 per cent of lipid-containing plaques. A population of spindle-shaped cells of macrophage type (positive for EMB11 antigen) expressed VCAM-1 in lipid-containing plaques. Adventitial vessels adjacent to plaques showed endothelial expression of ICAM-1 and E-selectin. VCAM-1 staining of adventitial vessel endothelium was associated with local lymphoid aggregation. In conclusion, the expression of cell adhesion molecules is an important element in the inflammatory component of atherosclerosis and contributes to both monocyte and lymphocyte activation and recruitment from adventitial vessels and the arterial lumen.

Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat

Abstract: We have investigated the polymorphism in intron 2 of the interleukin-1 receptor antagonist gene and identified two new alleles of the system. We have shown that the polymorphism is caused by the variable copy number of an 86-bp sequence, by using the polymerase chain reaction and primers immediately flanking the repeat region, and by direct sequencing. The repeat region contains three potential protein-binding sites and therefore the variable copy number may have functional significance.

The spatial dilemmas of evolution

Abstract: Evolutionary game theory can be extended to include spatial dimensions. The individual players are placed in a two-dimensional spatial array. In each round every individual “plays the game” with its immediate neighbours. After this, each site is occupied by its original owner or by one of the neighbours, depending on who scored the highest payoff. These rules specify a deterministic cellular automaton. We find that spatial effects can change the outcome of frequency dependent selection. Strategies may coexist that would not coexist in homogeneous populations. Spatial games have interesting mathematical properties. There are static or chaotically changing patterns. For symmetrical starting conditions we find “dynamical fractals” and “evolutionary kaleidoscopes.” There is a new world to be explored.

Visualization of focal sites of transcription within human nuclei

Abstract: HeLa cells were encapsulated in agarose microbeads, permeabilized and incubated with Br-UTP in a 'physiological' buffer; then sites of RNA synthesis were immunolabelled using an antibody that reacts with Br-RNA. After extending nascent RNA chains by < 400 nucleotides in vitro, approximately 300-500 focal synthetic sites can be seen in each nucleus by fluorescence microscopy. Most foci also contain a component of the splicing apparatus detected by an anti-Sm antibody. alpha-amanitin, an inhibitor of RNA polymerase II, prevents incorporation into these foci; then, using a slightly higher salt concentration, approximately 25 nucleolar foci became clearly visible. Both nucleolar and extra-nucleolar foci remain after nucleolytic removal of approximately 90% chromatin. An underlying structure probably organizes groups of transcription units into 'factories' where transcripts are both synthesized and processed.

Protein sequence alignments: a strategy for the hierarchical analysis of residue conservation

Abstract: An algorithm is described for the systematic characterization of the physico-chemical properties seen at each position in a multiple protein sequence alignment. The new algorithm allows questions important in the design of mutagenesis experiments to be quickly answered since positions in the alignment that show unusual or interesting residue substitution patterns may be rapidly identified. The strategy is based on a flexible set-based description of amino acid properties, which is used to define the conservation between any group of amino acids. Sequences in the alignment are gathered into subgroups on the basis of sequence similarity, functional, evolutionary or other criteria. All pairs of subgroups are then compared to highlight positions that confer the unique features of each subgroup. The algorithm is encoded in the computer program AMAS (Analysis of Multiply Aligned Sequences) which provides a textual summary of the analysis and an annotated (boxed, shaded and/or coloured) multiple sequence alignment. The algorithm is illustrated by application to an alignment of 67 SH2 domains where patterns of conserved hydrophobic residues that constitute the protein core are highlighted. The analysis of charge conservation across annexin domains identifies the locations at which conserved charges change sign. The algorithm simplifies the analysis of multiple sequence data by condensing the mass of information present, and thus allows the rapid identification of substitutions of structural and functional importance.

Variability of deltaic processes in terms of sediment supply, with particular emphasis on grain size

Abstract: Short term variability in delta form and process can be partly explained by the relative strength of hydraulic parameters such as river discharge, discharge variability, wave energy flux and tidal range. However, the calibre or grain size is also important. The amount, mode of transport and grain size of the sediment load delivered to a delta front have a considerable effect on the facies, formative physical processes, related depositional environments and morphology of the deltaic depositional system. The available grain size influences (1) the gradient and channel pattern of the fluvial system on the delta plain; (2) the mixing behaviour of sediment as it discharges into the ambient basin waters at the river mouth; (3) the type of shoreline, whether reflective or dissipative, and its response to both wave energy and tidal regime; and (4) the deformation and resedimentation processes on the subaqueous delta front. Long term aspects of deltaic sedimentation, including a few generalized relationships between sediment supply and physiographic setting, are briefly introduced. The need for further detailed research on modern and ancient deltaic dispersal systems is emphasized, and specific suggestions are given for future research.

General results concerning the trade-off between gaining energy and avoiding predation

Abstract: When animals can choose from a range of feeding options, often those options with a higher energetic gain carry a higher risk of predation. This paper analyses the optimal trade-off between food and predation. We are primarily interested in how an animal’s decisions and its state change over time. Our models are very general. They can be applied to growth decisions, such as choice of habitat, in which case we might consider how the state variable size changes over an animal’s lifetime. Equally our models are applicable to short-term foraging decisions, such as vigilance level, in which case we might consider how energy reserves vary over a day. We concentrate on two cases: (i) the animal must reach a fixed state, its fitness depending on when this is attained; (ii) the animal must survive to a fixed time, its fitness depending on its final state. In case (i) minimization of m ortality per unit increase of state is optimal under certain baseline conditions. In case (ii) behaviour is constant over time under baseline conditions (the 9Risk-spreading Theorem’). We analyse how these patterns are modified by complicating factors, e.g. time penalties, premature termination of the food supply, stochasticity in food supply or in metabolic expenditure, and state-dependence in the ability to obtain food, in metabolic expenditure and in predation risk. From this analysis we obtain a variety of possible explanations for why an animal should reduce its intake rate over time (i.e. show satiation). We show how earlier work can be viewed as special cases of our results.

Human lysozyme gene mutations cause hereditary systemic amyloidosis

Abstract: HEREDITARY non-neuropathic systemic amyloidosis (Ostertag-type)1 is a rare autosomal dominant disease in which amyloid deposition in the viscera is usually fatal by the fifth decade. In some families it is caused by mutations in the apolipoprotein AI gene2,3 but in two unrelated English families under our care the amyloid deposits did not contain apoAI, despite a report that this may have been the case in one of them4. Lysozyme is a ubiquitous bacteriolytic enzyme present in external secretions5 and in polymorphs and macrophages, but its physiological role is not always clear6. Here we report that in these two families, lysozyme is the amyloid fibril protein. Affected individuals are heterozygous for point mutations in the lysozyme gene that cause substitution of highly conserved residues, namely threonine for isoleucine at position 56 in one family, and histidine for aspartic acid at residue 67 in the other. Amyloid fibrils from one individual were composed of the full-length Thr-56 variant lysozyme molecule. To our knowledge, this is the first report of naturally occurring variants of human lysozyme and of lysozyme-associated disease. As the structures of human7 and hen egg-white lysozyme8 are known to atomic resolution and their folding and structure-function relationships have been exhaustively analysed, our observations should provide a powerful model for understanding amyloidogenesis.

Integration, Specialization, and the Adjustment

Abstract: In the United States, many industries have a Silicon Valley-type geographic localization. In Europe, these same industries often have four or more major centers of production. This difference is presumably the result of the formal and informal trade barriers that have divided the European market. With the growing integration of that market, however, there is the possibility that Europe will develop an American-style economic geography. This paper uses a theoretical model of industrial localization to demonstrate this possibility, and to show the possible transition costs associated with this shift.

Staging of gastrulating mouse embryos by morphological landmarks in the dissecting microscope

Abstract: We describe and illustrate a set of morphological landmarks for classifying mouse embryos by gross morphology from before gastrulation to the beginning of organogenesis. These landmarks are visible at the resolution of the dissecting microscope in embryos that are intact except for reflexion of Reichert's membrane. Adoption of these criteria should facilitate interpretation of both the expression patterns of genes and the consequences of experimental manipulation of embryos during early postimplantation development.

The zootype and the phylotypic stage.

Abstract: What is it that defines an animal? The definition provided here, made on the basis of developmental biology, suggests methods for resolving phylogenetic problems.

Thinning and opening of carbon nanotubes by oxidation using carbon dioxide

Abstract: THE discovery1 and bulk synthesis2 of carbon nanotubes has stimulated great interest. It has been suggested that these structures may have useful electronic3–5 and mechanical6 properties, and these might be modified by introducing foreign materials into the nanotubes. But the tubes are invariably capped at the ends. Ajayan and lijima7 have succeeded in drawing molten material (lead or one of its compounds) into the tubes by heating them in the presence of lead and oxygen; less than 1% of the tubes in the sample studied could be filled in this way. Here we report that heating in carbon dioxide gas can result in the partial or complete destruction of the tube caps and stripping of the outer layers to produce thinner tubes. In some cases, we have thinned the extremity of tubes to a single layer. The opened tubes can be regarded as nanoscale test-tubes for adsorption of other molecules, and this controlled method of thinning may allow studies of the properties of single tubes.

Detection of transient protein folding populations by mass spectrometry.

Abstract: Hydrogen-deuterium exchange measurements are becoming increasingly important in studies of the dynamics of protein molecules and, particularly, of their folding behavior. Electrospray ionization mass spectrometry (ESI-MS) has been used to obtain the distribution of masses within a population of protein molecules that had undergone hydrogen exchange in solution. This information is complementary to that from nuclear magnetic resonance spectroscopy (NMR) experiments, which measure the average occupancy of individual sites over the distribution of protein molecules. In experiments with hen lysozyme, a combination of ESI-MS and NMR was used to distinguish between alternative mechanisms of hydrogen exchange, providing insight into the nature and populations of transient folding intermediates. These results have helped to detail the pathways available to a protein during refolding.

Techniques for requirements elicitation

Abstract: The authors survey and evaluate techniques for eliciting requirements of computer-based systems, paying particular attention to dealing with social issues. The methods surveyed include introspection, interviews, questionnaires, and protocol, conversation, interaction, and discourse analyses. The last three techniques grew out of ethnomethodology and sociolinguistics. They can elicit tacit knowledge by observing actual interactions in the workplace, and can also be applied to the system development process itself. >

Exhumation of high-pressure rocks: a review of concepts and processes

Abstract: The exhumation of high-pressure metamorphic rocks requires either the removal of the overburden that caused the high pressures, or the transport of the metamorphic rocks through the overburden Exhumation cannot be achieved simply by thrusting or strike-slip faulting It may be caused by erosion of shortened and thickened crust, but this is unlikely to be the only mechanism for exhuming rocks from depths greater than about 20 km One or more of the following additional mechanisms may be involved 1 Corner flow of low-viscosity material trapped between the upper and lower plates in a subduction zone can cause upward flow of deeply buried rock, and may explain some occurrences of high-pressure tectonic blocks in melange This process does not, however, appear to be adequate to explain the exhumation of regional high-pressure terrains 2 Buoyancy forces acting directly on metamorphic rock bodies may cause them to rise relative to more dense surroundings This is likely to be the most important mechanism of exhumation of crustal rocks subducted into the mantle, but cannot explain the emplacement of coherent tracts of high-density metamorphic rock into shallow crustal levels Some high-pressure blocks emplaced at shallow levels in accretionary terrains may have been entrained in diapiric intrusions of low-density mud or serpentinite 3 Extension driven by the forces associated with contrasts in surface elevation may explain the exhumation and structural setting of many high-pressure terrains Extension may occur in the upper part of an accretionary wedge thickened by underplating; or it may affect the whole lithosphere in a region of intracontinental convergence, if surface elevation has been increased by the removal of a lithospheric root In the second case extension may be accompanied by magmatism and an evolution towards higher temperature during decompression of the metamorphic terrain