8,073 research outputs found
Survival probabilities in the double trapping reaction A +B -> B, B + C -> C
We consider the double trapping reaction A + B -> B, B + C -> C in one
dimension. The survival probability of a given A particle is calculated under
various conditions on the diffusion constants of the reactants, and on the
ratio of initial B and C particle densities. The results are of more general
form than those obtained in previous work on the problem.Comment: 5 page
Reconstitution of T cell receptor signaling in ZAP-70-deficient cells by retroviral transduction of the ZAP-70 gene.
A variant of severe combined immunodeficiency syndrome (SCID) with a selective inability to produce CD8 single positive T cells and a signal transduction defect in peripheral CD4+ cells has recently been shown to be the result of mutations in the ZAP-70 gene. T cell receptor (TCR) signaling requires the association of the ZAP-70 protein tyrosine kinase with the TCR complex. Human T cell leukemia virus type I-transformed CD4+ T cell lines were established from ZAP-70-deficient patients and normal controls. ZAP-70 was expressed and appropriately phosphorylated in normal T cell lines after TCR engagement, but was not detected in T cell lines from ZAP-70-deficient patients. To determine whether signaling could be reconstituted, wild-type ZAP-70 was introduced into deficient cells with a ZAP-70 retroviral vector. High titer producer clones expressing ZAP-70 were generated in the Gibbon ape leukemia virus packaging line PG13. After transduction, ZAP-70 was detected at levels equivalent to those observed in normal cells, and was appropriately phosphorylated on tyrosine after receptor engagement. The kinase activity of ZAP-70 in the reconstituted cells was also appropriately upregulated by receptor aggregation. Moreover, normal and transduced cells, but not ZAP-70-deficient cells, were able to mobilize calcium after receptor ligation, indicating that proximal TCR signaling was reconstituted. These results indicate that this form of SCID may be corrected by gene therapy
Improved prediction accuracy for disease risk mapping using Gaussian process stacked generalization.
Maps of infectious disease-charting spatial variations in the force of infection, degree of endemicity and the burden on human health-provide an essential evidence base to support planning towards global health targets. Contemporary disease mapping efforts have embraced statistical modelling approaches to properly acknowledge uncertainties in both the available measurements and their spatial interpolation. The most common such approach is Gaussian process regression, a mathematical framework composed of two components: a mean function harnessing the predictive power of multiple independent variables, and a covariance function yielding spatio-temporal shrinkage against residual variation from the mean. Though many techniques have been developed to improve the flexibility and fitting of the covariance function, models for the mean function have typically been restricted to simple linear terms. For infectious diseases, known to be driven by complex interactions between environmental and socio-economic factors, improved modelling of the mean function can greatly boost predictive power. Here, we present an ensemble approach based on stacked generalization that allows for multiple nonlinear algorithmic mean functions to be jointly embedded within the Gaussian process framework. We apply this method to mapping Plasmodium falciparum prevalence data in sub-Saharan Africa and show that the generalized ensemble approach markedly outperforms any individual method
Empty spaces and the value of symbols: Estonia's 'war of monuments' from another angle
Taking as its point of departure the recent heightened discussion surrounding publicly sited monuments in Estonia, this article investigates the issue from the perspective of the country's eastern border city of Narva, focusing especially upon the restoration in 2000 of a 'Swedish Lion' monument to mark the 300th anniversary of Sweden's victory over Russia at the first Battle of Narva. This commemoration is characterised here as a successful local negotiation of a potentially divisive past, as are subsequent commemorations of the Russian conquest of Narva in 1704. A recent proposal to erect a statue of Peter the Great in the city, however, briefly threatened to open a new front in Estonia's ongoing 'war of monuments'. Through a discussion of these episodes, the article seeks to link the Narva case to broader conceptual issues of identity politics, nationalism and post-communist transition
Evaluation of C-reactive protein and haptoglobin as malaria episode markers in an area of high transmission in Africa
Field studies of malaria in endemic areas frequently use the presence or levels of parasitaemia, together with the measurement of fever, as the primary criteria with which to identify cases. However, since malaria cases do not always present with measurable fever, and since asymptomatic parasitaemia occurs, additional episode markers might be useful epidemiological tools. We have measured the C-reactive protein and haptoglobin levels in paediatric patients presenting to a village health post in the Kilombero District in Tanzania and in convalescent sera from the same patients, in order to evaluate these acute-phase reactants as alternative markers of Plasmodium falciparum episodes. Among afebrile patients, C-reactive protein levels were highly correlated with parasite density. High C-reactive protein levels are therefore probably indicative of recent clinical malaria episodes in currently afebrile individuals with high parasite densities. An appropriate case definition for malaria in epidemiological studies in endemic areas might therefore be hyperparasitaemia accompanied by either, or both, measurable fever and raised C-reactive protein levels. This would give less biased estimates of the overall burden of malaria morbidity than does a definition which requires measurable fever. Levels of haptoglobin were highly negatively correlated with parasitaemia, but did not appear to be useful episode markers because this correlation was probably not related to acute morbidity. However, haptoglobin can be useful to assess at community level the impact of interventions on parasitaemi
The role of metaphor in shaping the identity and agenda of the United Nations: the imagining of an international community and international threat
This article examines the representation of the United Nations in speeches delivered by its Secretary General. It focuses on the role of metaphor in constructing a common ‘imagining’ of international diplomacy and legitimising an international organisational identity. The SG legitimises the organisation, in part, through the delegitimisation of agents/actions/events constructed as threatening to the international community and to the well-being of mankind. It is a desire to combat the forces of menace or evil which are argued to motivate and determine the organisational agenda. This is predicated upon an international ideology of humanity in which difference is silenced and ‘working towards the common good’ is emphasised. This is exploited to rouse emotions and legitimise institutional power. Polarisation and antithesis are achieved through the employment of metaphors designed to enhance positive and negative evaluations. The article further points to the constitutive, persuasive and edifying power of topic and situationally-motivated metaphors in speech-making
Mapping the ρ1 GABAC Receptor Agonist Binding Pocket
γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain. The GABA receptor type C (GABAC) is a ligand-gated ion channel with pharmacological properties distinct from the GABAA receptor. To date, only three binding domains in the recombinant ρ1 GABAC receptor have been recognized among six potential regions. In this report, using the substituted cysteine accessibility method, we scanned three potential regions previously unexplored in the ρ1 GABAC receptor, corresponding to the binding loops A, E, and F in the structural model for ligand-gated ion channels. The cysteine accessibility scanning and agonist/antagonist protection tests have resulted in the identification of residues in loops A and E, but not F, involved in forming the GABAC receptor agonist binding pocket. Three of these newly identified residues are in a novel region corresponding to the extended stretch of loop E. In addition, the cysteine accessibility pattern suggests that part of loop A and part of loop E have a β-strand structure, whereas loop F is a random coil. Finally, when all of the identified ligand binding residues are mapped onto a three-dimensional homology model of the amino-terminal domain of the ρ1 GABAC receptor, they are facing toward the putative binding pocket. Combined with previous findings, a complete model of the GABAC receptor binding pocket was proposed and discussed in comparison with the GABAA receptor binding pocket
Analysis of Multiple Plasmodium falciparum Infections in Tanzanian Children during the Phase III Trial of the Malaria Vaccine SPf66
In the first phase III efficacy trial of the malaria vaccine SPf66 in Africa, MOIs in SPf66- and placebo-vaccinated children were analyzed by polymerase chain reaction-restriction fragment length polymorphism of the Plasmodium falciparum merozoite surface antigen 2 (MSA2). MOIs were significantly reduced in asymptomatic vaccine recipients compared with those in asymptomatic placebo recipients; however, no differences were observed among symptomatic children in the vaccine and control groups. These results show that immunization with SPf66 modulates the course of naturally occurring infections, as reflected by reduced MOIs. In placebo recipients, however, there was a significant negative correlation between numbers of infecting genotypes, as identified by MSA2, and morbidity. Asymptomatic placebo recipients had an average of 5 concurrent infections, whereas children with clinical cases had an average of 3.4 infections. These data provide further evidence that premunition from concurrent infections is important in immunity against clinical malaria. No such effect of multiple infections was found in the vaccinated grou
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