No abstract

Key Points• MPO, via its catalytic activity, inhibits the generation of adaptive immunity by suppressing DC function.• MPO-mediated inhibition of adaptive immunity attenuates T cell-driven tissue inflammation.Myeloperoxidase (MPO) is important in intracellular microbial killing by neutrophils but extracellularly causes tissue damage. Its role in adaptive immunity and T-cell2mediated diseases is poorly understood. Here, T-cell responses in lymph nodes (LNs) were enhanced by MPO deletion or in vivo inhibition, causing enhanced skin delayed-type hypersensitivity and antigen (Ag)-induced arthritis. Responses of adoptively transferred OT-II T cells were greater in MPO-deficient than wild-type (WT) recipients. MPO, deposited by neutrophils in LNs after Ag injection, interacted with dendritic cells (DCs) in vivo. Culture of murine or human DCs with purified MPO or neutrophil supernatant showed that enzymatically dependent MPO-mediated inhibition of DC activation occurs via MPOgenerated reactive intermediates and involves DC Mac-1. Transfer of DCs cultured with WT, but not MPO-deficient, neutrophil supernatant attenuated Ag-specific immunity in vivo. MPO deficiency or in vivo inhibition increased DC activation in LNs after immunization. Studies with DQ-ovalbumin showed that MPO inhibits Ag uptake/processing by DCs. In vivo DC transfer and in vitro studies showed that MPO inhibits DC migration to LNs by reducing their expression of CCR7. Therefore, MPO, via its catalytic activity, inhibits the generation of adaptive immunity by suppressing DC activation, Ag uptake/processing, and migration to LNs to limit pathological tissue inflammation. (Blood. 2013;121(20):4195-4204)

Atomically smooth hexagonal boron nitride (h-BN) films are considered as a nearly ideal dielectric interface for two-dimensional (2D) heterostructure devices. Reported mono- to few-layer 2D h-BN films, however, are mostly small grain-sized, polycrystalline and randomly oriented. Here we report the growth of centimetre-sized atomically thin h-BN films composed of aligned domains on resolidified Cu. The films consist of monolayer single crystalline triangular and hexagonal domains with size of up to ∼10 μm. The domains converge to symmetrical multifaceted shapes such as "butterfly" and "6-apex-star" and exhibit ∼75% grain alignment for over millimetre distances as verified through transmission electron microscopy. Scanning electron microscopy images reveal that these domains are aligned for over centimetre distances. Defect lines are generated along the grain boundaries of mirroring h-BN domains due to the two different polarities (BN and NB) and edges with the same termination. The observed triangular domains with truncated edges and alternatively hexagonal domains are in accordance with Wulff shapes that have minimum edge energy. This work provides an extensive study on the aligned growth of h-BN single crystals over large distances and highlights the obstacles that are needed to be overcome for a 2D material with a binary configuration.

Mast cells contribute to the modulation of the immune response, but their role in autoimmune renal disease is not well understood. Here, we induced autoimmunity resulting in focal necrotizing GN by immunizing wild-type or mast cell-deficient (Kit W-sh/W-sh ) mice with myeloperoxidase. Mast cell-deficient mice exhibited more antimyeloperoxidase CD4+ T cells, enhanced dermal delayed-type hypersensitivity responses to myeloperoxidase, and more severe focal necrotizing GN. Furthermore, the lymph nodes draining the sites of immunization had fewer Tregs and reduced production of IL-10 in mice lacking mast cells. Reconstituting these mice with mast cells significantly increased the numbers of Tregs in the lymph nodes and attenuated both autoimmunity and severity of disease. After immunization with myeloperoxidase, mast cells migrated from the skin to the lymph nodes to contact Tregs. In an ex vivo assay, mast cells enhanced Treg suppression through IL-10. Reconstitution of mast cell-deficient mice with IL-10-deficient mast cells led to enhanced autoimmunity to myeloperoxidase and greater disease severity compared with reconstitution with IL-10-intact mast cells. Taken together, these studies establish a role for mast cells in mediating peripheral tolerance to myeloperoxidase, protecting them from the development of focal necrotizing GN in ANCA-associated vasculitis.

There is an increasing amount of research interest in synthesizing boron nitride nanotubes (BNNTs) as well as BN coatings to be used for various applications due to its outstanding mechanical, electrical and thermal properties. However, vertically aligned (VA) BNNTs are difficult to synthesize and the longest VA-BNNTs achieved to date are up to several tens of microns. Here, we report the synthesis of over millimeters long multi-walled BN coated carbon nanotubes (BN/CNT) and BNNT forests via a facile and effective two-step route involving template-assisted chemical vapor deposition at a relatively low temperature of 900 °C and subsequent annealing process. The as-prepared BN/CNTs and BNNTs retain the highly ordered vertically aligned structures of the CNT templates as identified by scanning electron microscopy.The structure and composition of the resulting products were studied using transmission electron microscopy, electron energy-loss spectroscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, Fourier transform infrared spectroscopy and thermogravimetric analysis. This versatile BN coating technique and the synthesis of millimeter-scale BN/CNTs and BNNTs pave a way for new applications especially where the aligned geometry of the NTs is essential such as for field-emission, interconnects and thermal management.

Loss of tolerance to neutrophil myeloperoxidase (MPO) underlies the development of ANCA-associated vasculitis and GN, but the mechanisms underlying this loss of tolerance are poorly understood. Here, we assessed the role of the thymus in deletion of autoreactive anti-MPO T cells and the importance of peripheral regulatory T cells in maintaining tolerance to MPO and protecting from GN. Thymic expression of MPO mRNA predominantly localized to medullary thymic epithelial cells. To assess the role of MPO in forming the T cell repertoire and the role of the autoimmune regulator Aire in thymic MPO expression, we compared the effects of immunizing Mpo 2/2 mice, Aire 2/2 mice, and control littermates with MPO.Immunized Mpo 2/2 and Aire 2/2 mice developed significantly more proinflammatory cytokine-producing anti-MPO T cells and higher ANCA titers than control mice. When we triggered GN with a subnephritogenic dose of anti-glomerular basement membrane antibody, Aire 2/2 mice had more severe renal disease than Aire +/+ mice, consistent with a role for Aire-dependent central deletion in establishing tolerance to MPO. Furthermore, depleting peripheral regulatory T cells in wild-type mice also led to more anti-MPO T cells, higher ANCA titers, and more severe GN after immunization with MPO. Taken together, these results suggest that Aire-dependent central deletion and regulatory T cell-mediated peripheral tolerance both play major roles in establishing and maintaining tolerance to MPO, thereby protecting against the development of anti-MPO GN.

Vertically aligned carbon nanotube (CNT) arrays have aroused considerable interest because of their remarkable mechanical properties. However, the mechanical behaviour of as-synthesized CNT arrays could vary drastically at a macro-scale depending on their morphologies, dimensions and array density, which are determined by the synthesis method. Here, we demonstrate a coaxial carbon@boron nitride nanotube (C@BNNT) array with enhanced compressive strength and shape recoverability. CNT arrays are grown using a commercially available thermal chemical vapor deposition (TCVD) technique and an outer BNNT with a wall thickness up to 1.37 nm is introduced by a post-growth TCVD treatment. Importantly, compared to the as-grown CNT arrays which deform almost plastically upon compression, the coaxial C@BNNT arrays exhibit an impressive ∼4-fold increase in compressive strength with nearly full recovery after the first compression cycle at a 50% strain (76% recovery maintained after 10 cycles), as well as a significantly high and persistent energy dissipation ratio (∼60% at a 50% strain after 100 cycles), attributed to the synergistic effect between the CNT and outer BNNT. Additionally, the as-prepared C@BNNT arrays show an improved structural stability in air at elevated temperatures, attributing to the outstanding thermal stability of the outer BNNT. This work provides new insights into tailoring the mechanical and thermal behaviours of arbitrary CNT arrays which enables a broader range of applications.

Abstract-A novel perceptually lossless coder is presented for the compression of medical images. Built on the JPEG 2000 coding framework, the heart of the proposed coder is a visual pruning function, embedded with an advanced human vision model to identify and to remove visually insignificant/irrelevant information. The proposed coder offers the advantages of simplicity and modularity with bit-stream compliance. Current results have shown superior compression ratio gains over that of its information lossless counterparts without any visible distortion. In addition, a case study consisting of 31 medical experts has shown that no perceivable difference of statistical significance exists between the original images and the images compressed by the proposed coder.Index Terms-Biomedical imaging, double blind testing, image coding, just-not-noticeable-difference, medical image coding, perceptually lossless image coding, 2-staged forced choice, vision model.