Showing papers by "University of Oxford published in 1998"
TL;DR: In this article, the authors present a model that incorporates this overall argument in the form of a series of hypothesized relationships between different dimensions of social capital and the main mechanisms and proces.
Abstract: Scholars of the theory of the firm have begun to emphasize the sources and conditions of what has been described as “the organizational advantage,” rather than focus on the causes and consequences of market failure. Typically, researchers see such organizational advantage as accruing from the particular capabilities organizations have for creating and sharing knowledge. In this article we seek to contribute to this body of work by developing the following arguments: (1) social capital facilitates the creation of new intellectual capital; (2) organizations, as institutional settings, are conducive to the development of high levels of social capital; and (3) it is because of their more dense social capital that firms, within certain limits, have an advantage over markets in creating and sharing intellectual capital. We present a model that incorporates this overall argument in the form of a series of hypothesized relationships between different dimensions of social capital and the main mechanisms and proces...
15,365 citations
TL;DR: In this article, the authors improved the description of both electron energy loss spectra and parameters characterizing the structural stability of the material compared with local spin density functional theory by taking better account of electron correlations in the $3d$ shell of metal ions in nickel oxide.
Abstract: We demonstrate how by taking better account of electron correlations in the $3d$ shell of metal ions in nickel oxide it is possible to improve the description of both electron energy loss spectra and parameters characterizing the structural stability of the material compared with local spin density functional theory.
10,045 citations
TL;DR: The Condensation algorithm uses “factored sampling”, previously applied to the interpretation of static images, in which the probability distribution of possible interpretations is represented by a randomly generated set.
Abstract: The problem of tracking curves in dense visual clutter is challenging. Kalman filtering is inadequate because it is based on Gaussian densities which, being unimo dal, cannot represent simultaneous alternative hypotheses. The Condensation algorithm uses “factored sampling”, previously applied to the interpretation of static images, in which the probability distribution of possible interpretations is represented by a randomly generated set. Condensation uses learned dynamical models, together with visual observations, to propagate the random set over time. The result is highly robust tracking of agile motion. Notwithstanding the use of stochastic methods, the algorithm runs in near real-time.
5,804 citations
TL;DR: The absolute improvement in recurrence was greater during the first 5 years, whereas the improvement in survival grew steadily larger throughout the first 10 years, and these benefits appeared to be largely irrespective of age, menopausal status, daily tamoxifen dose, and of whether chemotherapy had been given to both groups.
3,701 citations
TL;DR: Multilocus sequence typing (MLST), which exploits the unambiguous nature and electronic portability of nucleotide sequence data for the characterization of microorganisms, can be applied to almost all bacterial species and other haploid organisms, including those that are difficult to cultivate.
Abstract: Traditional and molecular typing schemes for the characterization of pathogenic microorganisms are poorly portable because they index variation that is difficult to compare among laboratories. To overcome these problems, we propose multilocus sequence typing (MLST), which exploits the unambiguous nature and electronic portability of nucleotide sequence data for the characterization of microorganisms. To evaluate MLST, we determined the sequences of ≈470-bp fragments from 11 housekeeping genes in a reference set of 107 isolates of Neisseria meningitidis from invasive disease and healthy carriers. For each locus, alleles were assigned arbitrary numbers and dendrograms were constructed from the pairwise differences in multilocus allelic profiles by cluster analysis. The strain associations obtained were consistent with clonal groupings previously determined by multilocus enzyme electrophoresis. A subset of six gene fragments was chosen that retained the resolution and congruence achieved by using all 11 loci. Most isolates from hyper-virulent lineages of serogroups A, B, and C meningococci were identical for all loci or differed from the majority type at only a single locus. MLST using six loci therefore reliably identified the major meningococcal lineages associated with invasive disease. MLST can be applied to almost all bacterial species and other haploid organisms, including those that are difficult to cultivate. The overwhelming advantage of MLST over other molecular typing methods is that sequence data are truly portable between laboratories, permitting one expanding global database per species to be placed on a World-Wide Web site, thus enabling exchange of molecular typing data for global epidemiology via the Internet.
3,695 citations
TL;DR: It is proposed that the emergence of indirect reciprocity was a decisive step for the evolution of human societies and the probability of knowing the ‘image’ of the recipient must exceed the cost-to-benefit ratio of the altruistic act.
Abstract: Darwinian evolution has to provide an explanation for cooperative behaviour. Theories of cooperation are based on kin selection (dependent on genetic relatedness)1,2, group selection3,4,5 and reciprocal altruism6,7,8. The idea of reciprocal altruism usually involves direct reciprocity: repeated encounters between the same individuals allow for the return of an altruistic act by the recipient10,11,12,13,14,15,16. Here we present a new theoretical framework, which is based on indirect reciprocity17 and does not require the same two individuals ever to meet again. Individual selection can nevertheless favour cooperative strategies directed towards recipients that have helped others in the past. Cooperation pays because it confers the image of a valuable community member to the cooperating individual. We present computer simulations and analytic models that specify the conditions required for evolutionary stability18 of indirect reciprocity. We show that the probability of knowing the ‘image’ of the recipient must exceed the cost-to-benefit ratio of the altruistic act. We propose that the emergence of indirect reciprocity was a decisive step for the evolution of human societies.
2,417 citations
TL;DR: In this article, a 12-item questionnaire for patients having a total knee replacement (TKR) was developed and a prospective study of 117 patients before operation and at follow-up six months later, asking them to complete the new questionnaire and the form SF36.
Abstract: We have developed a 12-item questionnaire for patients having a total knee replacement (TKR). We made a prospective study of 117 patients before operation and at follow-up six months later, asking them to complete the new questionnaire and the form SF36. Some also filled in the Stanford Health Assessment Questionnaire (HAQ). An orthopaedic surgeon completed the American Knee Society (AKS) clinical score. The single score derived from the new questionnaire had high internal consistency, and its reproducibility, examined by test-retest reliability, was found to be satisfactory. Its validity was established by obtaining significant correlations in the expected direction with the AKS scores and the relevant parts of the SF36 and HAQ. Sensitivity to change was assessed by analysing the differences between the preoperative scores and those at follow-up. We also compared change in scores with the patients' retrospective judgement of change in their condition. The effect size for the new questionnaire compared favourably with those for the relevant parts of the SF36. The change scores for the new knee questionnaire were significantly greater (p < 0.0001) for patients who reported the most improvement in their condition. The new questionnaire provides a measure of outcome for TKR that is short, practical, reliable, valid and sensitive to clinically important changes over time.
2,177 citations
TL;DR: This review will focus on the possibility that the cerebellum contains an internal model or models of the motor apparatus, and the necessity of such a model and the evidence, based on the ocular following response, that inverse models are found within the Cerebellar circuitry.
2,147 citations
TL;DR: A quintet of potentially modifiable risk factors for coronary artery disease exists in patients with type 2 diabetes mellitus, which are increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density cholesterol, raised blood pressure, hyperglycaemia, and smoking.
Abstract: Objective: To evaluate baseline risk factors for coronary artery disease in patients with type 2 diabetes mellitus. Design: A stepwise selection procedure, adjusting for age and sex, was used in 2693 subjects with complete data to determine which risk factors for coronary artery disease should be included in a Cox proportional hazards model. Subjects: 3055 white patients (mean age 52) with recently diagnosed type 2 diabetes mellitus and without evidence of disease related to atheroma. Median duration of follow up was 7.9 years. 335 patients developed coronary artery disease within 10 years. Outcome measures: Angina with confirmatory abnormal electrocardiogram; non-fatal and fatal myocardial infarction. Results: Coronary artery disease was significantly associated with increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, and increased triglyceride concentration, haemoglobin A1c, systolic blood pressure, fasting plasma glucose concentration, and a history of smoking. The estimated hazard ratios for the upper third relative to the lower third were 2.26 (95% confidence interval 1.70 to 3.00) for low density lipoprotein cholesterol, 0.55 (0.41 to 0.73) for high density lipoprotein cholesterol, 1.52 (1.15 to 2.01) for haemoglobin A1c, and 1.82 (1.34 to 2.47) for systolic blood pressure. The estimated hazard ratio for smokers was 1.41(1.06 to 1.88). Conclusion: A quintet of potentially modifiable risk factors for coronary artery disease exists in patients with type 2 diabetes mellitus. These risk factors are increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, raised blood pressure, hyperglycaemia, and smoking. Key messages Coronary artery disease is the major cause of mortality in patients with type 2 diabetes mellitus Patients without evidence of disease related to atheroma at diagnosis of type 2 diabetes mellitus had an increased standardised mortality ratio compared with the population of the United Kingdom 11% of patients in this study had a myocardial infarction or developed angina over a median of 8 years9 follow up The potentially modifiable risk factors for coronary artery disease were increased concentrations of low density lipoprotein cholesterol, decreased concentrations of high density lipoprotein cholesterol, hypertension, hyperglycaemia, and smoking; these are also risk factors for coronary artery disease in the general population Evidence is needed on whether modifying these risk factors will reduce coronary artery disease in patients with type 2 diabetes mellitus
2,003 citations
TL;DR: In this article, an error-correction mechanism (ECM) test is proposed for cointegration in a single-equation framework where the regressors are weakly exogenous for the parameters of interest.
Abstract: A new test is proposed for cointegration in a single-equation framework where the regressors are weakly exogenous for the parameters of interest. The test is denoted as an error-correction mechanism (ECM) test and is based upon the ordinary least squares coefficient of the lagged dependent variable in an autoregressive distributed lag model augmented with leads of the regressors. The limit distributions of the standardized coeffi cient and t-ratio versions of the ECM tests are obtained and critical values are provided. These limit distributions do not depend upon nuisance parameters but they depend on the number of regressors. Finally, we compare their power properties with those of other cointegration tests available in the literature and find the circumstances under which the ECM tests have a better performance.
1,952 citations
Journal Article•
TL;DR: This research highlights the need to understand more fully the rationale behind the continued use of these devices, as well as the barriers to their adoption.
Abstract: s. Outcome research 249 Questionnaire 63,152 Would pick up refer-
TL;DR: JAM is a new component of endothelial and epithelial junctions that play a role in regulating monocyte transmigration and is identified as a novel immunoglobulin gene superfamily member that consists of two V-type Ig domains.
Abstract: Tight junctions are the most apical components of endothelial and epithelial intercellular cleft. In the endothelium these structures play an important role in the control of paracellular permeability to circulating cells and solutes. The only known integral membrane protein localized at sites of membrane–membrane interaction of tight junctions is occludin, which is linked inside the cells to a complex network of cytoskeletal and signaling proteins. We report here the identification of a novel protein (junctional adhesion molecule [JAM]) that is selectively concentrated at intercellular junctions of endothelial and epithelial cells of different origins. Confocal and immunoelectron microscopy shows that JAM codistributes with tight junction components at the apical region of the intercellular cleft. A cDNA clone encoding JAM defines a novel immunoglobulin gene superfamily member that consists of two V-type Ig domains. An mAb directed to JAM (BV11) was found to inhibit spontaneous and chemokine-induced monocyte transmigration through an endothelial cell monolayer in vitro. Systemic treatment of mice with BV11 mAb blocked monocyte infiltration upon chemokine administration in subcutaneous air pouches. Thus, JAM is a new component of endothelial and epithelial junctions that play a role in regulating monocyte transmigration.
TL;DR: In this paper, it was shown that γ-ray bursts are sensitive to an energy dispersion predicted by some approaches to quantum gravity, which is sufficient to test theories of quantum gravity.
Abstract: The recent confirmation that at least some γ-ray bursts originate at cosmological distances1,2,3,4 suggests that the radiation from them could be used to probe some of the fundamental laws of physics. Here we show that γ-ray bursts will be sensitive to an energy dispersion predicted by some approaches to quantum gravity. Many of the bursts have structure on relatively rapid timescales5, which means that in principle it is possible to look for energy-dependent dispersion of the radiation, manifested in the arrival times of the photons, if several different energy bands are observed simultaneously. A simple estimate indicates that, because of their high energies and distant origin, observations of these bursts should be sensitive to a dispersion scale that is comparable to the Planck energy scale (∼1019 GeV), which is sufficient to test theories of quantum gravity. Such observations are already possible using existing γ-ray burst detectors.
TL;DR: In this article, a quantum optical experimental implementation of teleportation of unknown pure quantum states was reported, which realizes all of the nonlocal aspects of the original scheme proposed by Bennett et al. and is equivalent to it up to a local operation.
Abstract: We report on a quantum optical experimental implementation of teleportation of unknown pure quantum states. This realizes all of the nonlocal aspects of the original scheme proposed by Bennett et al. and is equivalent to it up to a local operation. We exhibit results for the teleportation of a linearly polarized state and of an elliptically polarized state. We show that the experimental results cannot be explained in terms of a classical channel alone. The Bell measurement in our experiment can distinguish between all four Bell states simultaneously allowing, in the ideal case, a 100% success rate of teleportation. [S0031-9007(97)05275-7]
TL;DR: It is demonstrated that the elementary processes of mutation and selection alone are suifficient to promote rapid proliferation of new designs and support the theory that trade-offs in competitive ability drive adaptive radiation.
Abstract: Successive adaptive radiations have played a pivotal role in the evolution of biological diversity1,2,3. The effects of adaptive radiation are often seen4,5,6, but the underlying causes are difficult to disentangle and remain unclear7,8,9. Here we examine directly therole of ecological opportunity and competition in driving genetic diversification. We use the common aerobic bacterium Pseudomonas fluorescens10, which evolves rapidly under novel environmental conditions to generate a large repertoire of mutants11,12,13. When provided with ecological opportunity (afforded by spatial structure), identical populations diversify morphologically, but when ecological opportunity is restricted there is no such divergence. In spatially structured environments, the evolution of variant morphs follows a predictable sequence and we show that competition among the newly evolved niche-specialists maintains this variation. These results demonstrate that the elementary processes of mutation and selection alone are suifficient to promote rapid proliferation of new designs and support the theory that trade-offs in competitive ability drive adaptive radiation14,15.
TL;DR: Brain-imaging data revealed a partial overlap between neural systems involved in the performance of spatial versus temporal orientation of attention tasks, and hemispheric asymmetries revealed preferential right and left parietal activation for spatial and temporal attention, respectively.
Abstract: Although attention is distributed across time as well as space, the temporal allocation of attention has been less well researched than its spatial counterpart. A temporal analog of the covert spatial orientation task [Posner MI, Snyder CRR, Davidson BJ (1980) Attention and the detection of signals. J Exp Psychol Gen 109:160-174] was developed to compare the neural systems involved in directing attention to spatial locations versus time intervals. We asked whether there exists a general system for allocating attentional resources, independent of stimulus dimension, or whether functionally specialized brain regions are recruited for directing attention toward spatial versus temporal aspects of the environment. We measured brain activity in seven healthy volunteers by using positron emission tomography (PET) and in eight healthy volunteers by using functional magnetic resonance imaging (fMRI). The task manipulated cued attention to spatial locations (S) and temporal intervals (T) in a factorial design. Symbolic central cues oriented subjects toward S only (left or right), toward T only (300 msec or 1500 msec), toward both S and T simultaneously, or provided no information regarding S or T. Subjects also were scanned during a resting baseline condition. Behavioral data showed benefits and costs for performance during temporal attention similar to those established for spatial attention. Brain-imaging data revealed a partial overlap between neural systems involved in the performance of spatial versus temporal orientation of attention tasks. Additionally, hemispheric asymmetries revealed preferential right and left parietal activation for spatial and temporal attention, respectively. Parietal cortex was activated bilaterally by attending to both dimensions simultaneously. This is the first direct comparison of the neural correlates of attending to spatial versus temporal cues.
TL;DR: In this article, a common pattern underpinning quantum algorithms can be identified when quantum computation is viewed as multiparticle interference, and an explicit algorithm for generating any prescribed interference pattern with an arbitrary precision is provided.
Abstract: Quantum computers use the quantum interference of different computational paths to enhance correct outcomes and suppress erroneous outcomes of computations. A common pattern underpinning quantum algorithms can be identified when quantum computation is viewed as multiparticle interference. We use this approach to review (and improve) some of the existing quantum algorithms and to show how they are related to different instances of quantum phase estimation. We provide an explicit algorithm for generating any prescribed interference pattern with an arbitrary precision.
TL;DR: A pneumococcal multilocus sequence typing scheme and database is developed by sequencing approximately 450 bp fragments of seven housekeeping loci from 295 isolates to provide an allelic profile, or sequence type (ST), and the relatedness between isolates was obtained by constructing a dendrogram from the matrix of pairwise differences between STs.
Abstract: SUMMARY: The population biology of Streptococcus pneumoniae is poorly understood. Most of the important issues could be addressed by the molecular characterization of large, well sampled populations from carriage and from the different manifestations of pneumococcal disease. The authors have therefore developed a pneumococcal multilocus sequence typing scheme and database by sequencing - 450 bp fragments of seven housekeeping loci from 295 isolates. The combination of alleles at the seven loci provided an allelic profile, or sequence type (ST), and the relatedness between isolates was obtained by constructing a dendrogram from the matrix of paiwvise differences between STs. The typing scheme was validated using pneumococci of known genetic relatedness and could resolve 6 billion STs. Among 274 isolates from recent cases of invasive pneumococcal disease in eight countries,143 STs were resolved, but 12 STs contained at least five isolates (range 5-21 isolates). The repeated recovery of indistinguishable isolates from invasive disease in different countries implies that these STs define strains with an increased capacity to cause invasive disease. The relationship between STs and serotypes suggested that, in the longer term, capsular genes have been distributed horizontally within the pneumococcal population, but in the short term, expansion of clones occurs with only occasional changes of serotype. The multilocus sequence typing scheme provides a powerful new approach to the characterization of pneumococci, since it provides molecular typing datathat are electronically portable between laboratories, and which can be used to probe aspects of the population and evolutionary biology of these organisms. A Web sitefor themolecular characterization of pneumococci by MLST is available (http://mlst.zoo.ox.ac.uk).
TL;DR: To use evidence regarding both costs and outcomes of primary THR to model how much more effective newer prostheses must be to justify higher costs.
Abstract: Objectives- T identify the literature on primary total hip replacement(THR) surgery that is relevant to the question of whether prostheses differ in their medium to longer term outcomes, and to synthesise this evidence. To use evidence regarding both costs and outcomes of primary THR to model how much more effective newer prostheses must be to justify higher costs
TL;DR: An interactive protein secondary structure prediction Internet server is presented that simplifies the use of current prediction algorithms and allows conservation patterns important to structure and function to be identified.
Abstract: UNLABELLED An interactive protein secondary structure prediction Internet server is presented. The server allows a single sequence or multiple alignment to be submitted, and returns predictions from six secondary structure prediction algorithms that exploit evolutionary information from multiple sequences. A consensus prediction is also returned which improves the average Q3 accuracy of prediction by 1% to 72.9%. The server simplifies the use of current prediction algorithms and allows conservation patterns important to structure and function to be identified. AVAILABILITY http://barton.ebi.ac.uk/servers/jpred.h tml CONTACT geoff@ebi.ac.uk
TL;DR: The broad selectivity of the monosaccharide‐binding site and the geometrical arrangement of multiple CRDs in the intact lectins explains the ability of the proteins to mediate discrimination between self and non‐self.
Abstract: Protein-carbohydrate interactions serve multiple functions in the immune system. Many animal lectins (sugar-binding proteins) mediate both pathogen recognition and cell-cell interactions using structurally related Ca(2+)-dependent carbohydrate-recognition domains (C-type CRDs). Pathogen recognition by soluble collections such as serum mannose-binding protein and pulmonary surfactant proteins, and also the macrophage cell-surface mannose receptor, is effected by binding of terminal monosaccharide residues characteristic of bacterial and fungal cell surfaces. The broad selectivity of the monosaccharide-binding site and the geometrical arrangement of multiple CRDs in the intact lectins explains the ability of the proteins to mediate discrimination between self and non-self. In contrast, the much narrower binding specificity of selectin cell adhesion molecules results from an extended binding site within a single CRD. Other proteins, particularly receptors on the surface of natural killer cells, contain C-type lectin-like domains (CTLDs) that are evolutionarily divergent from the C-type lectins and which would be predicted to function through different mechanisms.
TL;DR: In this paper, the effective action for low x physics based on a Wilson renormalization group approach was studied, where the average value and the average fluctuation of extra color charge density generated by integrating out gluons with intermediate values of $x were analyzed.
Abstract: We continue the study of the effective action for low x physics based on a Wilson renormalization group approach. We express the full nonlinear renormalization group equation in terms of the average value and the average fluctuation of extra color charge density generated by integrating out gluons with intermediate values of $x$. This form clearly exhibits the nature of the phenomena driving the evolution and should serve as the basis of the analysis of saturation effects at high gluon density at small $x$.
TL;DR: In this paper, it was shown that cholinergic activation is sufficient to induce 40-Hz network oscillations in the hippocampus in vitro, which can persist for hours in the CA3 subfield.
Abstract: Acetylcholine is vital for cognitive functions of the brain. Although its actions in the individual cell are known in some detail, its effects at the network level are poorly understood. The hippocampus, which receives a major cholinergic input from the medial septum/diagonal band, is important in memory and exhibits network activity at 40 Hz during relevant behaviours. Here we show that cholinergic activation is sufficient to induce 40-Hz network oscillations in the hippocampus in vitro. Oscillatory activity is generated spontaneously in the CA3 subfield and can persist for hours. During the oscillatory state, principal neurons fire action potentials that are phase-related to the extracellular oscillation, but each neuron fires in only a small proportion of the cycles. Both excitatory and inhibitory synaptic events participate during the network oscillation in a precise temporal pattern. These results indicate that subcortical cholinergic input can control hippocampal memory processing by inducing fast network oscillations.
TL;DR: The cerebral cortex consists of a large population of principal neurons reciprocally connected to the thalamus and to each other via axon collaterals releasing excitatory amino acids, and a smaller population of mainly local circuit GABAergic neurones.
TL;DR: Evidence for inhibitory effects of fatty acids on whole body glucose utilization ad oxidation (predominantly muscles) is decisive and enzyme mechanisms mediating these effects are well established, and a permissive role for fatty acids in the insulin secretory response of islet beta-cells has now been firmly established.
Abstract: Competition for respiration between substrates in animal tissues has been known for at least 80 years. The most important interaction, quantitatively is between glucose and fatty acids. The starting point in 1963 for the so called Glucose Fatty Acid Cycle was the realisation that the metabolic relationship between glucose and fatty acids is reciprocal and not dependent. Glucose provision promotes glucose oxidation and glucose and lipid storage, and inhibits fatty acid oxidation. Provision of free fatty acids promotes fatty acid oxidation and storage, inhibits glucose oxidation and may promote glucose storage if glycogen reserves are incomplete. This review is concerned predominantly with evidence in man in vivo. In the authors opinion the evidence for inhibitory effects of fatty acids on whole body glucose utilization ad oxidation (predominantly muscles) is decisive and enzyme mechanisms mediating these effects are well established. There is also much evidence that fatty acid oxidation inhibits glucose oxidation and stimulates glucose formation in liver and again enzyme mechanism are known. A permissive role for fatty acids in the insulin secretory response of islet beta-cells has now been firmly established and can be visualised as a mechanism to protect continuing provision of respiratory substrate. Longer term exposure of islet beta-cells to fatty acids impairs the insulin secretory response to glucose and mechanisms are known. There is compelling evidence that fatty acid oxidation may impair glucose oxidation in uncontrolled Type 1 and Type 2 diabetes, but no convincing evidence that fatty acids have a role in diminished glucose storage (glycogen deposition) in Type 2 diabetes. The inhibition of glucose storage which may follow prolonged elevation of plasma FFA in man and experimental animals is associated with glycogen repletion whereas the inhibition of glucose storage in Type 2 diabetes is associated with glycogen depletion. The precise role of fatty acids in disturbed carbohydrate metabolism in Type 2 diabetes is an area where future progress is confidently predicted.
TL;DR: The exclusive extrasynaptic presence of the δ subunit-containing receptors, together with their kinetic properties, suggests that tonic inhibition could be mediated mainly by Extrasynaptic α6β2/3δ receptors, whereas phasic inhibition is attributable to the activation of synaptic receptors.
Abstract: Two types of GABA A receptor-mediated inhibition (phasic and tonic) have been described in cerebellar granule cells, although these cells receive GABAergic input only from a single cell type, the Golgi cell In adult rats, granule cells express six GABA A receptor subunits abundantly (α1, α6, β2, β3, γ2, and δ), which are coassembled into at least four to six distinct GABA A receptor subtypes We tested whether a differential distribution of GABA A receptors on the surface of granule cells could play a role in the different forms of inhibition, assuming that phasic inhibition originates from the activation of synaptic receptors, whereas tonic inhibition is provided mainly by extrasynaptic receptors The α1, α6, β2/3, and γ2 subunits have been found by immunogold localizations to be concentrated in GABAergic Golgi synapses and also are present in the extrasynaptic membrane at a lower concentration In contrast, immunoparticles for the δ subunit could not be detected in synaptic junctions, although they were abundantly present in the extrasynaptic dendritic and somatic membranes Gold particles for the α6, γ2, and β2/3, but not the α1 and δ, subunits also were concentrated in some glutamatergic mossy fiber synapses, where their colocalization with AMPA-type glutamate receptors was demonstrated The exclusive extrasynaptic presence of the δ subunit-containing receptors, together with their kinetic properties, suggests that tonic inhibition could be mediated mainly by extrasynaptic α 6 β 2/3 δ receptors, whereas phasic inhibition is attributable to the activation of synaptic α 1 β 2/3 γ 2 , α 6 β 2/3 γ 2 , and α 1 α 6 β 2/3 γ 2 receptors
TL;DR: In this paper, the authors proposed a multivariate test whose null hypothesis is violated only when all of the processes in question are stationary, and applied the tests to real exchange rates among the G5 over the recent float.
TL;DR: This paper gives a comprehensive description of Markov modelling for economic evaluation, including a discussion of the assumptions on which the type of model is based, most notably the memoryless quality ofMarkov models often termed the ‘Markovian assumption’.
Abstract: Markov models are often employed to represent stochastic processes, that is, random processes that evolve over time. In a healthcare context, Markov models are particularly suited to modelling chronic disease. In this article, we describe the use of Markov models for economic evaluation of healthcare interventions. The intuitive way in which Markov models can handle both costs and outcomes make them a powerful tool for economic evaluation modelling. The time component of Markov models can offer advantages of standard decision tree models, particularly with respect to discounting. This paper gives a comprehensive description of Markov modelling for economic evaluation, including a discussion of the assumptions on which the type of model is based, most notably the memoryless quality of Markov models often termed the ‘Markovian assumption’. A hypothetical example of a drug intervention to slow the progression of a chronic disease is employed to demonstrate the modelling technique and the possible methods of analysing Markov models are explored. Analysts should be aware of the limitations of Markov models, particularly the Markovian assumption, although the adept modeller will often find ways around this problem.
TL;DR: This review presents the progess made recently in understanding key elements of this reaction and describes a solution to the often quoted Levinthal Paradox.
Abstract: The mechanism of protein folding (represented schematically below) is one of the most fascinating problems in the field of chemical reactions. This review presents the progess made recently in understanding key elements of this reaction and describes a solution to the often quoted Levinthal Paradox.
TL;DR: The number and variability of synaptic AMPA receptors in the rat hippocampus are determined using quantitative immunogold localization and it is estimated that the AMPA receptor content of C/A synapses on CA3 pyramidal spines ranges from <3 to 140.