1,218 research outputs found
CCR7 is required for the in vivo function of CD4+ CD25+ regulatory T cells
CCR7-mediated migration of naive T cells into the secondary lymphoid organs is a prerequisite for their encounter with mature dendritic cells, the productive presentation of cognate antigen, and consequent T cell proliferation and effector differentiation. Therefore, CCR7 was suggested to play an important role in the initiation of adaptive immune responses. In this study, we show that primary immunity can also develop in the absence of CCR7. Moreover, CCR7-deficient knockout (KO) mice display augmented immune responses. Our data cumulatively suggest that enhanced immunity in CCR7 KO mice is caused by the defective lymph node (LN) positioning of FoxP3(+) CD4(+) CD25(+) regulatory T cells (T reg cells) and the consequent impediment of their function. The FoxP3(+) T reg cells express CCR7 and, after their adoptive transfer, migrate into the LNs of wild-type mice. Here, they proliferate in situ upon antigen stimulation and inhibit the generation of antigen-specific T cells. Conversely, transferred CCR7-deficient T reg cells fail to migrate into the LNs and suppress antigen-induced T cell responses. The transfer of combinations of naive and T reg cells from wild-type and CCR7 KO mice into syngeneic severe combined immunodeficient mice directly demonstrates that CCR7-deficient T reg cells are less effective than their wild-type counterparts in preventing the development of inflammatory bowel diseas
Power, norms and institutional change in the European Union: the protection of the free movement of goods
How do institutions of the European Union change? Using an institutionalist approach, this article highlights the interplay between power, cognitive limits, and the normative order that underpins institutional settings and assesses their impact upon the process of institutional change. Empirical evidence from recent attempts to reinforce the protection of the free movement of goods in the EU suggests that, under conditions of uncertainty, actors with ambiguous preferences assess attempts at institutional change on the basis of the historically defined normative order which holds a given institutional structure together. Hence, path dependent and incremental change occurs even when more ambitious and functionally superior proposals are on offer
TrustedPals: Secure Multiparty Computation Implemented with Smart Cards
We study the problem of Secure Multi-party Computation (SMC) in a model where individual processes contain a tamper-proof security module, and introduce the TrustedPals framework, an efficient smart card based implementation of SMC for any number of participating entities in such a model. Security modules can be trusted by other processes and can establish secure channels between each other. However, their availability is restricted by their host, that is, a corrupted party can stop the computation of its own security module as well as drop any message sent by or to its security module. We show that in this model SMC can be implemented by reducing it to a fault-tolerance problem at the level of security modules. Since the critical part of the computation can be executed locally on the smart card, we can compute any function securely with a protocol complexity which is polynomial only in the number of processes (that is, the complexity does not depend on the function which is computed), in contrast to previous approaches
The ÎČ3-integrin endothelial adhesome regulates microtubule-dependent cell migration
Integrin ÎČ3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely ÎČ3's role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the ÎČ3-dependent adhesome. We show that depletion of ÎČ3-integrin in this cell type leads to changes in microtubule behaviour that control cell migration. ÎČ3-integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2-driven control of active Rac1 localisation. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when ÎČ3-integrin levels are reduced
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Basic theory behind parameterizing atmospheric convection
Last fall, a network of the European Cooperation in Science and Technology (COST), called âBasic Concepts for Convection Parameterization in Weather Forecast and Climate Modelsâ (COST Action ES0905; see http://w3.cost.esf.org/index.php?id=205&action_number=ES0905), organized a 10-day training course on atmospheric convection and its parameterization. The aim of the workshop, held on the island of Brac, Croatia, was to help young scientists develop an in-depth understanding of the core theory underpinning convection parameterizations. The speakers also sought to impart an appreciation of the various approximations, compromises, and ansatz necessary to translate theory into operational practice for numerical models
Mitochondrial diversity analysis of Glossina palpalis gambiensis from Mali and Senegal
West African riverine tsetse populations of Glossina palpalis gambiensis Vanderplank (Diptera: Glossinidae) were investigated for gene flow, inferred from mitochondrial diversity in samples of 69 flies from Senegal and 303 flies from three river drainages in Mali. Four polymorphic mitochondrial loci were scored. Mean haplotype diversities were 0.30 in Mali and 0.18 over both Mali and Senegal. These diversities estimate the probabilities that two randomly chosen tsetse have different haplotypes. Substantial rates of gene flow were detected among flies sampled along tributaries belonging to the river basins of the Senegal, Niger, and Bani in Mali. There was virtually no gene flow between tsetse in Senegal and Mali. No seasonal effects on gene flow were detected. The implications of these preliminary findings for the implementation of area-wide integrated pest management (AW-IPM) programmes against riverine tsetse in West Africa are discussed
Evaluation of the performance variation of porous air pads on discontinuous surfaces
A new high accuracy position measurement system has been developed. It measures the position of a 0.1âŻmm diameter copper-beryllium wire that informs alignment of energy beams in advanced particle accelerators. This new measurement system employs air pads to provide precision and friction free rotation of a sensor. To enable the measuring system to be positioned over the wire, a slot is required in the measuring device rotor. To optimise the design of this measuring system it was necessary to understand the performance of the air pads as they pass over the gaps (slots) in the rotor. This paper describes modelling and experiments that were performed to gain understanding of air pad performance when encountering such a surface gap. Particularly, an analytical model of the variation of load of a 20âŻmmâŻĂâŻ40âŻmm porous air pad during the passing of a 1.5âŻmm wide slotted surface. Subsequent experimentation revealed that the general behaviour of the load variation had been captured effectively. The results of this analysis reveal that air pads of this size can reliably pass above an opening of this size with about 14% reduction in force. The results and the methodology presented in this paper can be used as an effective basis for future designs and studie
Critical structure factor in Ising systems
We perform a large-scale Monte Carlo simulation of the three-dimensional
Ising model on simple cubic lattices of size L^3 with L=128 and 256. We
determine the corresponding structure factor (Fourier transform of the
two-point function) and compare it with several approximations and with
experimental results. We also compute the turbidity as a function of the
momentum of the incoming radiation, focusing in particular on the deviations
from the Ornstein-Zernicke expression of Puglielli and Ford.Comment: 16 page
Correlations of structural, magnetic, and dielectric properties of undoped and doped CaCu3Ti4O12
The present work reports synthesis, as well as a detailed and careful
characterization of structural, magnetic, and dielectric properties of
differently tempered undoped and doped CaCu3Ti4O12 (CCTO) ceramics. For this
purpose, neutron and x-ray powder diffraction, SQUID measurements, and
dielectric spectroscopy have been performed. Mn-, Fe-, and Ni-doped CCTO
ceramics were investigated in great detail to document the influence of
low-level doping with 3d metals on the antiferromagnetic structure and
dielectric properties. In the light of possible magnetoelectric coupling in
these doped ceramics, the dielectric measurements were also carried out in
external magnetic fields up to 7 T, showing a minor but significant dependence
of the dielectric constant on the applied magnetic field. Undoped CCTO is
well-known for its colossal dielectric constant in a broad frequency and
temperature range. With the present extended characterization of doped as well
as undoped CCTO, we want to address the question why doping with only 1% Mn or
0.5% Fe decreases the room-temperature dielectric constant of CCTO by a factor
of ~100 with a concomitant reduction of the conductivity, whereas 0.5% Ni
doping changes the dielectric properties only slightly. In addition,
diffraction experiments and magnetic investigations were undertaken to check
for possible correlations of the magnitude of the colossal dielectric constants
with structural details or with magnetic properties like the magnetic ordering,
the Curie-Weiss temperatures, or the paramagnetic moment. It is revealed, that
while the magnetic ordering temperature and the effective moment of all
investigated CCTO ceramics are rather similar, there is a dramatic influence of
doping and tempering time on the Curie-Weiss constant.Comment: 10 pages, 11 figure
Matter power spectrum and the challenge of percent accuracy
Future galaxy surveys require one percent precision in the theoretical knowledge of the power spectrum over a large range including very nonlinear scales. While this level of accuracy is easily obtained in the linear regime with perturbation theory, it represents a serious challenge for small scales where numerical simulations are required. In this paper we quantify the precision of present-day N -body methods, identifying main potential error sources from the set-up of initial conditions to the measurement of the final power spectrum. We directly compare three widely used N -body codes, Ramses, Pkdgrav3, and Gadget3 which represent three main discretisation techniques: the particle-mesh method, the tree method, and a hybrid combination of the two. For standard run parameters, the codes agree to within one percent at kâ€1 hMpc â1 and to within three percent at kâ€10 hMpc â1. We also consider the bispectrum and show that the reduced bispectra agree at the sub-percent level for kâ€2 hMpc â1 . In a second step, we quantify potential errors due to initial conditions, box size, and resolution using an extended suite of simulations performed with our fastest code Pkdgrav3. We demonstrate that the simulation box size should not be smaller than L=0.5 h â1 Gpc to avoid systematic finite-volume effects (while much larger boxes are required to beat down the statistical sample variance). Furthermore, a maximum particle mass of M p =10 9 h â1 M â is required to conservatively obtain one percent precision of the matter power spectrum. As a consequence, numerical simulations covering large survey volumes of upcoming missions such as DES, LSST, and Euclid will need more than a trillion particles to reproduce clustering properties at the targeted accuracy
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