Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression

Maturation of high-affinity B lymphocytes is precisely controlled during the germinal center reaction. This is dependent on CD4(+)CXCR5(+) follicular helper T cells (TFH) and inhibited by CD4(+)CXCR5(+)Foxp3(+) follicular regulatory T cells (TFR). Because NFAT2 was found to be highly expressed and activated in follicular T cells, we addressed its function herein. Unexpectedly, ablation of NFAT2 in T cells caused an augmented GC reaction upon immunization. Consistently, however, TFR cells were clearly reduced in the follicular T cell population due to impaired homing to B cell follicles. This was TFR-intrinsic because only in these cells NFAT2 was essential to up-regulate CXCR5. The physiological relevance for humoral (auto-)immunity was corroborated by exacerbated lupuslike disease in the presence of NFAT2-deficient TFR cells

A Linear Parameter-Varying Approach to Data Predictive Control

By means of the linear parameter-varying (LPV) Fundamental Lemma, we derive novel data-driven predictive control (DPC) methods for LPV systems. In particular, we present output-feedback and state-feedback-based LPV-DPC methods with terminal ingredients, which guarantee exponential stability and recursive feasibility. We provide methods for the data-based computation of these terminal ingredients. Furthermore, an in-depth analysis of the properties and implementation aspects of the LPV-DPC schemes is given, including alternative recursive formulations, application for nonlinear systems and handling noise-disturbed data. We demonstrate the performance of the proposed methods on a simulation example involving a nonlinear unbalanced disc system.Comment: Submitted to IEEE-TAC. Extended version. 17 page

Theory for the coupling between longitudinal phonons and intrinsic Josephson oscillations in layered superconductors

In this publication a microscopic theory for the coupling of intrinsic Josephson oscillations in layered superconductors with longitudinal c-axis-phonons is developed. It is shown that the influence of lattice vibrations on the c-axis transport can be fully described by introducing an effective longitudinal dielectric function. Resonances in the I-V-characteristic appear at van Hove singularities of both acoustical and optical longitudinal phonon branches. This provides a natural explanation of the recently discovered subgap structures in the I-V-characteristic of highly anisotropic cuprate superconductors. The effect of the phonon dispersion on the damping of these resonances and the coupling of Josephson oscillations in different resistive junctions due to phonons are discussed in detail.Comment: submitted to Phys. Rev. B, corrections following referee repor

Answering Twitter Questions: a Model for Recommending Answerers through Social Collaboration

International audienceIn this paper, we specifically consider the challenging task of solving a question posted on Twitter. The latter generally remains unanswered and most of the replies, if any, are only from members of the questioner's neighborhood. As outlined in previous work related to community Q&A, we believe that question-answering is a collaborative process and that the relevant answer to a question post is an aggregation of answer nuggets posted by a group of relevant users. Thus, the problem of identifying the relevant answer turns into the problem of identifying the right group of users who would provide useful answers and would possibly be willing to collaborate together in the long-term. Accordingly, we present a novel method, called CRAQ, that is built on the collaboration paradigm and formulated as a group entropy optimization problem. To optimize the quality of the group, an information gain measure is used to select the most likely " informative " users according to topical and collaboration likelihood predictive features. Crowd-based experiments performed on two crisis-related Twitter datasets demonstrate the effectiveness of our collaborative-based answering approach

Long-Term Potentiation in the CA1 Hippocampus Induced by NR2A Subunit-Containing NMDA Glutamate Receptors Is Mediated by Ras-GRF2/Erk Map Kinase Signaling

BACKGROUND: NMDA-type glutamate receptors (NMDARs) are major contributors to long-term potentiation (LTP), a form of synaptic plasticity implicated in the process of learning and memory. These receptors consist of calcium-permeating NR1 and multiple regulatory NR2 subunits. A majority of studies show that both NR2A and NR2B-containing NMDARs can contribute to LTP, but their unique contributions to this form of synaptic plasticity remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we show that NR2A and NR2B-containing receptors promote LTP differently in the CA1 hippocampus of 1-month old mice, with the NR2A receptors functioning through Ras-GRF2 and its downstream effector, Erk Map kinase, and NR2B receptors functioning independently of these signaling molecules. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that NR2A-, but not NR2B, containing NMDA receptors induce LTP in pyramidal neurons of the CA1 hippocampus from 1 month old mice through Ras-GRF2 and Erk. This difference add new significance to the observation that the relative levels of these NMDAR subtypes is regulated in neurons, such that NR2A-containing receptors become more prominent late in postnatal development, after sensory experience and synaptic activity

Multiple roles of GluN2B-containing NMDA receptors in synaptic plasticity in juvenile hippocampus

AbstractIn the CA1 area of the hippocampus N-methyl-d-aspartate receptors (NMDARs) mediate the induction of long-term depression (LTD), short-term potentiation (STP) and long-term potentiation (LTP). All of these forms of synaptic plasticity can be readily studied in juvenile hippocampal slices but the involvement of particular NMDAR subunits in the induction of these different forms of synaptic plasticity is currently unclear. Here, using NVP-AAM077, Ro 25-6981 and UBP145 to target GluN2A-, 2B- and 2D-containing NMDARs respectively, we show that GluN2B-containing NMDARs (GluN2B) are involved in the induction of LTD, STP and LTP in slices prepared from P14 rat hippocampus. A concentration of Ro (1 μM) that selectively blocks GluN2B-containing diheteromers is able to block LTD. It also inhibits a component of STP without affecting LTP. A higher concentration of Ro (10 μM), that also inhibits GluN2A/B triheteromers, blocks LTP. UBP145 selectively inhibits the Ro-sensitive component of STP whereas NVP inhibits LTP. These data are consistent with a role of GluN2B diheretomers in LTD, a role of both GluN2B- and GluN2D- containing NMDARs in STP and a role of GluN2A/B triheteromers in LTP.This article is part of the Special Issue entitled ‘Ionotropic glutamate receptors’

Motion Planning via Manifold Samples

We present a general and modular algorithmic framework for path planning of robots. Our framework combines geometric methods for exact and complete analysis of low-dimensional configuration spaces, together with practical, considerably simpler sampling-based approaches that are appropriate for higher dimensions. In order to facilitate the transfer of advanced geometric algorithms into practical use, we suggest taking samples that are entire low-dimensional manifolds of the configuration space that capture the connectivity of the configuration space much better than isolated point samples. Geometric algorithms for analysis of low-dimensional manifolds then provide powerful primitive operations. The modular design of the framework enables independent optimization of each modular component. Indeed, we have developed, implemented and optimized a primitive operation for complete and exact combinatorial analysis of a certain set of manifolds, using arrangements of curves of rational functions and concepts of generic programming. This in turn enabled us to implement our framework for the concrete case of a polygonal robot translating and rotating amidst polygonal obstacles. We demonstrate that the integration of several carefully engineered components leads to significant speedup over the popular PRM sampling-based algorithm, which represents the more simplistic approach that is prevalent in practice. We foresee possible extensions of our framework to solving high-dimensional problems beyond motion planning.Comment: 18 page

Surface modification of Ti-4Al-2V alloy by nitrogen implantation

Ti-4Al-2V is a new type of alpha titanium alloy that suitable for the application in high-temperature and high-pressure water/steam environment. Ti-4Al-2V can be used in marine engineering, nuclear power industry. In this paper the surface characterization of the Ti-4Al-2V implanted with 75 keV nitrogen with fluences of 3 × 10 17 and 8 × 10 17  N + /cm 2 is investigated by glancing-incidence XRD, XPS and microhardness. The results show that new phase TiN are formed after N implantation in the surface region. The nitrogen implantation increases the surface hardness up to 340 and 260% for fluence of 8 × 10 17 and 3 × 10 17  N + /cm 2 , respectively. The enhancement of hardness is related to the formation of TiN and irradiation induced hardness.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43177/1/10853_2005_Article_5365.pd