Cytokines and Soluble Receptors in Breast Milk as Enhancers of Oral Tolerance Development

The postpartum period is an important window during which environmental factors can shape the life-long health of the infant. This time period often coincides with substantial milk consumption either in the form of breast milk or from cow's milk sources, such as infant formulas. Although breast milk is the most beneficial source of nutrients for infants during the first 6 months after birth, its role in regulating food allergy development, through regulation of oral tolerance, is still controversial. Breast milk contains several factors that can impact mucosal immune function, including immune cells, antibodies, microbiota, oligosaccharides, cytokines, and soluble receptors. However, there is considerable variation in the assessed levels of cytokines and soluble receptors between studies and across the lactation period. Most of these cytokines and soluble receptors are absent, or only found in limited quantities, in commercial baby formulas. Differences in content of these pluripotent factors, which impact on both the mother and the neonate, could contribute to the controversy surrounding the role of breast milk regulating oral tolerance. This review highlights current knowledge about the importance of cytokines and soluble receptors in breast milk on the development of oral tolerance and tolerance-relateddisorders. Understanding the mechanisms by which such milk components might promote oral tolerance could aid in the development of improved strategies for allergy prevention

Mast Cells in Cardiac Fibrosis: New Insights Suggest Opportunities for Intervention

Mast cells (MC) are innate immune cells present in virtually all body tissues with key roles in allergic disease and host defense. MCs recognize damage-associated molecular patterns (DAMPs) through expression of multiple receptors including Toll-like receptors and the IL-33 receptor ST2. MCs can be activated to degranulate and release pre-formed mediators, to synthesize and secrete cytokines and chemokines without degranulation, and/or to produce lipid mediators. MC numbers are generally increased at sites of fibrosis. They are potent, resident, effector cells producing mediators that regulate the fibrotic process. The nature of the secretory products produced by MCs depend on micro-environmental signals and can be both pro- and anti-fibrotic. MCs have been repeatedly implicated in the pathogenesis of cardiac fibrosis and in angiogenic responses in hypoxic tissues, but these findings are controversial. Several rodent studies have indicated a protective role for MCs. MC-deficient mice have been reported to have poorer outcomes after coronary artery ligation and increased cardiac function upon MC reconstitution. In contrast, MCs have also been implicated as key drivers of fibrosis. MC stabilization during a hypertensive rat model and an atrial fibrillation mouse model rescued associated fibrosis. Discrepancies in the literature could be related to problems with mouse models of MC deficiency. To further complicate the issue, mice generally have a much lower density of MCs in their cardiac tissue than humans, and as such comparing MC deficient and MC containing mouse models is not necessarily reflective of the role of MCs in human disease. In this review, we will evaluate the literature regarding the role of MCs in cardiac fibrosis with an emphasis on what is known about MC biology, in this context. MCs have been well-studied in allergic disease and multiple pharmacological tools are available to regulate their function. We will identify potential opportunities to manipulate human MC function and the impact of their mediators with a view to preventing or reducing harmful fibrosis. Important therapeutic opportunities could arise from increased understanding of the impact of such potent, resident immune cells, with the ability to profoundly alter long term fibrotic processes

Tunnel magnetoresistance in scandium nitride magnetic tunnel junctions using first principles

The magnetic tunnel junction is a cornerstone of spintronic devices and circuits, providing the main way to convert between magnetic and electrical information. In state-of-the-art magnetic tunnel junctions, magnesium oxide is used as the tunnel barrier between magnetic electrodes, providing a uniquely large tunnel magnetoresistance at room temperature. However, the wide bandgap and band alignment of magnesium oxide-iron systems increases the resistance-area product and causes challenges of device-to-device variability and tunnel barrier degradation under high current. Here, we study using first principles narrower-bandgap scandium nitride tunneling properties and transport in magnetic tunnel junctions in comparison to magnesium oxide. These simulations demonstrate a high tunnel magnetoresistance in Fe/ScN/Fe MTJs via {\Delta}_1 and {\Delta}_2' symmetry filtering with low wavefunction decay rates, allowing a low resistance-area product. The results show that scandium nitride could be a new tunnel barrier material for magnetic tunnel junction devices to overcome variability and current-injection challenges

Mast cells selectively produce inflammatory mediators and impact the early response to Chlamydia reproductive tract infection

IntroductionChlamydia trachomatis (C. trachomatis) is a Gram-negative obligate intracellular bacterium that causes reproductive tract complications in women, including ectopic pregnancies and tubal factor infertility. We hypothesized that mast cells, which are common at mucosal barriers, may contribute to responses to Chlamydia infection and aimed to define human mast cell responses to C. trachomatis.MethodsHuman cord blood-derived mast cells (CBMCs) were exposed to C. trachomatis to assess bacterial uptake, mast cell degranulation, gene expression, and production of inflammatory mediators. The role of formyl peptide receptors and Toll-like receptor 2 (TLR2) were investigated using pharmacological inhibitors and soluble TLR2. Mast cell-deficient mice and littermate controls were used to examine the in vivo role of mast cells in influencing the immune response to Chlamydia infection in the female reproductive tract.ResultsC. trachomatis bacteria were taken up by human mast cells but did not replicate efficiently inside CBMCs. C. trachomatis-activated mast cells did not degranulate but maintained viability and exhibited cellular activation with homotypic aggregation and upregulation of ICAM-1. However, they significantly enhanced the gene expression of IL1B, CCL3, NFKB1, CXCL8, and IL6. Inflammatory mediators were produced, including TNF, IL-1β, IL-1RA, IL-6, GM-CSF, IL-23, CCL3, CCL5, and CXCL8. Endocytic blockade resulted in reduced gene expression of IL6, IL1B, and CCL3, suggesting C. trachomatis induced mast cell activation in both extracellular and intracellular locations. The IL-6 response to C. trachomatis was reduced when CBMCs were treated with C. trachomatis coated with soluble TLR2. Mast cells derived from TLR2-deficient mice also demonstrated a reduced IL-6 response to C. muridarum. Five days following C. muridarum infection, mast cell-deficient mice showed attenuated CXCL2 production and significantly reduced numbers of neutrophils, eosinophils, and B cells in the reproductive tract when compared with mast cell-containing littermates.DiscussionTaken together, these data demonstrate that mast cells are reactive to Chlamydia spp. through multiple mechanisms that include TLR2-dependent pathways. Mast cells also play an important role in shaping in vivo immune responses in Chlamydia reproductive tract infection through both effector cell recruitment and modification of the chemokine microenvironment

Physics performances for Scalar Electron, Scalar Muon and Scalar Neutrino searches at 3 TeV and 1.4 TeV at CLIC

The determination of scalar lepton and gaugino masses is an important part of the programme of spectroscopic studies of Supersymmetry at a high energy e+e- linear collider. In this article we present results of a study of the processes: e+e- -> eR eR -> e+e- chi0 chi, e+e- -> muR muR -> mu mu- chi0 chi0, e+e- -> eL eL -> e e chi0 chi0 and e+e- -> snu_e snu_e -> e e chi+ chi-in two Supersymmetric benchmark scenarios at 3 TeV and 1.4 TeV at CLIC. We characterize the detector performance, lepton energy resolution and boson mass resolution. We report the accuracy of the production cross section measurements and the eR muR, snu_e, chi+ and chi0 mass determination, estimate the systematic errors affecting the mass measurement and discuss the requirements on the detector time stamping capability and beam polarization. The analysis accounts for the CLIC beam energy spectrum and the dominant beam-induced background. The detector performances are incorporated by full simulation and reconstruction of the events within the framework of the CLIC_ILD_CDR detector concept

Dark Matter and Baryons in the Most X-ray Luminous and Merging Galaxy Cluster RX J1347.5-1145

The galaxy cluster RX J1347-1145 is one of the most X-ray luminous and most massive clusters known. Its extreme mass makes it a prime target for studying issues addressing cluster formation and cosmology. In this paper we present new high-resolution HST/ACS and Chandra X-ray data. The high resolution and sensitivity of ACS enabled us to detect and quantify several new multiply imaged sources, we now use a total of eight for the strong lensing analysis. Combining this information with shape measurements of weak lensing sources in the central regions of the cluster, we derive a high-resolution, absolutely-calibrated mass map. This map provides the best available quantification of the total mass of the central part of the cluster to date. We compare the reconstructed mass with that inferred from the new Chandra X-ray data, and conclude that both mass estimates agree extremely well in the observed region, namely within 400 / h_70 kpc of the cluster center. In addition we study the major baryonic components (gas and stars) and hence derive the dark matter distribution in the center of the cluster. We find that the dark matter and baryons are both centered on the BCG within the uncertainties (alignment is better than <10 kpc). We measure the corresponding 1-D profiles and find that dark matter distribution is consistent with both NFW and cored profiles, indicating that a more extended radial analysis is needed to pinpoint the concentration parameter, and hence the inner slope of the dark matter profile.Comment: 12 pages, Accepted for publication in ApJ, full-res version http://www.physics.ucsb.edu/~marusa/RXJ1347.pd

Causality in relativistic many body theory

The stability of the nuclear matter system with respect to density fluctuations is examined exploring in detail the pole structure of the electro-nuclear response functions. Making extensive use of the method of dispersion integrals we calculate the full polarization propagator not only for real energies in the spacelike and timelike regime but also in the whole complex energy plane. The latter proved to be necessary in order to identify unphysical causality violating poles which are the consequence of a neglection of vacuum polarization. On the contrary it is shown that Dirac sea effects stabilize the nuclear matter system shifting the unphysical pole from the upper energy plane back to the real axis. The exchange of strength between these real timelike collective excitations and the spacelike energy regime is shown to lead to a reduction of the quasielastic peak as it is seen in electron scattering experiments. Neglecting vacuum polarization one also obtains a reduction of the quasielastic peak but in this case the strength is partly shifted to the causality violating pole mentioned above which consequently cannot be considered as a physical reliable result. Our investigation of the response function in the energy region above the threshold of nucleon anti-nucleon production leads to another remarkable result. Treating the nucleons as point-like Dirac particles we show that for any isospin independent NN-interaction RPA-correlations provide a reduction of the production amplitude for $p\bar p$-pairs by a factor 2.Comment: 19 pages Latex including 12 postscript figure

Tunnel magnetoresistance in scandium nitride magnetic tunnel junctions using first principles

The magnetic tunnel junction is a cornerstone of spintronic devices and circuits, providing the main way to convert between magnetic and electrical information. In state-of-the-art magnetic tunnel junctions, magnesium oxide is used as the tunnel barrier between magnetic electrodes, providing a uniquely large tunnel magnetoresistance at room temperature. However, the wide bandgap and band alignment of magnesium oxide-iron systems increases the resistance-area product and causes challenges of device-to-device variability and tunnel barrier degradation under high current. Here, we study using first principles narrower-bandgap scandium nitride tunneling properties and transport in magnetic tunnel junctions in comparison to magnesium oxide. These simulations demonstrate a high tunnel magnetoresistance in Fe/ScN/Fe MTJs via Δ1 and Δ2′ symmetry filtering with low wavefunction decay rates, allowing a low resistance-area product. The results show that scandium nitride could be a new tunnel barrier material for magnetic tunnel junction devices to overcome variability and current-injection challenges.The authors acknowledge computing resources from the Texas Advanced Computing Center (TACC) at the University of Texas at Austin (http://www.tacc.utexas.edu), funding and discussions from Sandia National Laboratories, and funding from the Center for Dynamics and Control of Materials (CDCM) supported by the National Science Foundation under NSF Award Number DMR-1720595.Center for Dynamics and Control of Material