Edge effects in electrostatic calibrations for the measurement of the Casimir force

We have performed numerical simulations to evaluate the effect on the capacitance of finite size boundaries realistically present in the parallel plane, sphere-plane, and cylinder-plane geometries. The potential impact of edge effects in assessing the accuracy of the parameters obtained in the electrostatic calibrations of Casimir force experiments is then discussed

The influence of temporal coherence on the dynamical Casimir effect

We study the dynamical Casimir effect in the presence of a finite coherence time, which is associated with a finite quality factor of the optical cavity. We use the time refraction model, where a fixed cavity with a modulated optical medium, replaces the empty cavity with a vibrating mirror. Temporal coherence is described with the help of cavity quasi-mode operators. Asymptotic expressions for the number of photon pairs generated from vacuum are derived.Comment: 8 pages, 1 figur

Imaging regulatory T cell dynamics and CTLA4-mediated suppression of T cell priming

Foxp3(+) regulatory T cells (Tregs) maintain immune homoeostasis through mechanisms that remain incompletely defined. Here by two-photon (2P) imaging, we examine the cellular dynamics of endogenous Tregs. Tregs are identified as two non-overlapping populations in the T-zone and follicular regions of the lymph node (LN). In the T-zone, Tregs migrate more rapidly than conventional T cells (Tconv), extend longer processes and interact with resident dendritic cells (DC) and Tconv. Tregs intercept immigrant DCs and interact with antigen-induced DC: Tconv clusters, while continuing to form contacts with activated Tconv. During antigen-specific responses, blocking CTLA4-B7 interactions reduces Treg-Tconv interaction times, increases the volume of DC: Tconv clusters and enhances subsequent Tconv proliferation in vivo. Our results demonstrate a role for altered cellular choreography of Tregs through CTLA4-based interactions to limit T-cell priming

Thermal and dissipative effects in Casimir physics

We report on current efforts to detect the thermal and dissipative contributions to the Casimir force. For the thermal component, two experiments are in progress at Dartmouth and at the Institute Laue Langevin in Grenoble. The first experiment will seek to detect the Casimir force at the largest explorable distance using a cylinder-plane geometry which offers various advantages with respect to both sphere-plane and parallel-plane geometries. In the second experiment, the Casimir force in the parallel-plane configuration is measured with a dedicated torsional balance, up to 10 micrometers. Parallelism of large surfaces, critical in this configuration, is maintained through the use of inclinometer technology already implemented at Grenoble for the study of gravitationally bound states of ultracold neutrons, For the dissipative component of the Casimir force, we discuss detection techniques based upon the use of hyperfine spectroscopy of ultracold atoms and Rydberg atoms. Although quite challenging, this triad of experimental efforts, if successful, will give us a better knowledge of the interplay between quantum and thermal fluctuations of the electromagnetic field and of the nature of dissipation induced by the motion of objects in a quantum vacuum.Comment: Contribution to QFEXT'06, appeared in special issue of Journal of Physics

Second harmonic generation in SiC polytypes

LMTO calculations are presented for the frequency dependent second harmonic generation (SHG) in the polytypes 2H, 4H, 6H, 15R and 3C of SiC. All independent tensor components are calculated. The spectral features and the ratios of the 333 to 311 tensorial components are studied as a function of the degree of hexagonality. The relationship to the linear optical response and the underlying band structure are investigated. SHG is suggested to be a sensitive tool for investigating the near band edge interband excitations.Comment: 12 pages, 10 figure

Prophylactic allergen immunotherapy with Der p 2 prevents murine asthma by regulating lung GM-CSF

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Tariff-Mediated Network Effects versus Strategic Discounting: Evidence from German Mobile Telecommunications

Mobile telecommunication operators routinely charge subscribers lower prices for calls on their own network than for calls to other networks (on-net discounts). Studies on tariff-mediated network effects suggest this is due to large operators using on-net discounts to damage smaller rivals. Alternatively, research on strategic discounting suggests small operators use on-net discounts to advertise with low on-net prices. We test the relative strength of these effects using data on tariff setting in German mobile telecommunications between 2001 and 2009. We find that large operators are more likely to offer tariffs with on-net discounts but there is no consistently significant difference in the magnitude of discounts. Our results suggest that tariff-mediated network effects are the main cause of on-net discounts

Early IL-1 signaling promotes iBALT induction after influenza virus infection

Inducible bronchus-associated lymphoid tissue (iBALT) is a long lasting tertiary lymphoid tissue that can be induced following influenza A virus (IAV) infection. Previous studies have shown that iBALT structures containing germinal center (GC) B cells protect against repeated infection by contributing locally to the cellular and humoral immune response. If we are to exploit this in vaccination strategies, we need a better understanding on how iBALT structures are induced. One hypothesis is that the strength of the initial innate response dictates induction of iBALT. In the present study, we investigated the role of interleukin (IL)-1 and IL-1R signaling on iBALT formation. Mice lacking the IL-1R had a delayed viral clearance and, thus, a prolonged exposure to viral replication, leading to increased disease severity, compared to wild-type mice. Contradictorily, iBALT formation following clearance of the virus was heavily compromised in Il1r1-/- mice. Quantification of gene induction after IAV infection demonstrated induction of IL-1α and to a much lesser extent of IL-1β. Administration of recombinant IL-1α to the lungs of wild-type mice, early but not late, after IAV infection led to more pronounced iBALT formation and an increased amount of GC B cells in the lungs. Bone marrow chimeric mice identified the stromal compartment as the crucial IL-1 responsive cell for iBALT induction. Mechanistically, Q-PCR analysis of lung homogenates revealed a strongly diminished production of CXCL13, a B cell-attracting chemokine, in Il1r-/- mice during the early innate phase of IAV infection. These experiments demonstrate that appropriate innate IL-1α-IL-1R signaling is necessary for IAV clearance and at the same time instructs the formation of organized tertiary lymphoid tissues through induction of CXCL13 early after infection. These findings are discussed in the light of recent insights on the pathogenesis of tertiary lymphoid organ formation in the lung in various diseases where the IL-1 axis is hyperactive, such as rheumatoid arthritis and COPD

A bispecific antibody strategy to target multiple type 2 cytokines in asthma

Background: Asthma is a chronic inflammatory airway disease in which innate and adaptive immune cells act together to cause eosinophilic inflammation, goblet cell metaplasia (GCM), and bronchial hyperreactivity (BHR). In clinical trials using biologicals against IL-4 receptor (IL-4R) alpha or IL-5, only a subset of patients with moderate-to-severe asthma responded favorably, suggesting that distinct pathophysiologic mechanisms are at play in subgroups of patients called endotypes. However, the effect of multiple cytokine blockade using bispecific antibodies has not been tested. Objective: We sought to target simultaneously the IL-4, IL-13, and IL-5 signaling pathways with a novel IL-4R alpha/IL-5-bispecific antibody in a murine house dust mite (HDM) model of asthma. Methods: Two mAbs neutralizing IL-4R alpha and IL-5 were generated by using a llama-based antibody platform. Their heavy and light chains were then cotransfected in mammalian cells, resulting in a heterogeneous antibody mixture from which the bispecific antibody was isolated by using a dual anti-idiotypic purification process. C57BL/6J mice were finally sensitized and challenged to HDM extracts and treated during challenge with the antibodies. Results: We successfully generated and characterized the monospecific and bispecific antibodies targeting IL-4R alpha and IL-5. The monospecific antibodies could suppress eosinophilia, IgE synthesis, or both, whereas only the IL-4R alpha/IL-5-bispecific antibody and the combination of monospecific antibodies additionally inhibited GCM and BHR. Conclusion: Type 2 cytokines act synergistically to cause GCM and BHR in HDM-exposed mice. These preclinical results show the feasibility of generating bispecific antibodies that target multiple cytokine signaling pathways as superior inhibitors of asthma features, including the difficult-to-treat GCM

The ubiquitin-editing enzyme A20 controls NK cell homeostasis through regulation of mTOR activity and TNF

The ubiquitin-editing enzyme A20 is a well-known regulator of immune cell function and homeostasis. In addition, A20 protects cells from death in an ill-defined manner. While most studies focus on its role in the TNF-receptor complex, we here identify a novel component in the A20-mediated decision between life and death. Loss of A20 in NK cells led to spontaneous NK cell death and severe NK cell lymphopenia. The few remaining NK cells showed an immature, hyperactivated phenotype, hallmarked by the basal release of cytokines and cytotoxic molecules. NK-A20(-/-) cells were hypersensitive to TNF-induced cell death and could be rescued, at least partially, by a combined deficiency with TNF. Unexpectedly, rapamycin, a well-established inhibitor of mTOR, also strongly protected NK-A20(-/-) cells from death, and further studies revealed that A20 restricts mTOR activation in NK cells. This study therefore maps A20 as a crucial regulator of mTOR signaling and underscores the need for a tightly balanced mTOR pathway in NK cell homeostasis