Enhancement of myeloma development mediated though myeloma cell-Th2 cell interactions after microbial antigen presentation by myeloma cells and DCs

Microbial agents are regarded as a potential cause of tumors, but their direct effects on tumors, such as myeloma, are not well studied. Our studies demonstrated that expression of HLA-DR and CD40 on the myeloma cell membrane surface is upregulated by interferon-γ and/or microbial antigens (Ags). Unlike prior studies, our study showed that Th2 cells cannot promote myeloma growth directly. However, Bacillus Calmette–Guerin Vaccine (BCGV)-specific Th2 cells stimulated by BCGV-loaded dendritic cells (DCs) promoted myeloma clonogenicity directly when the myeloma cells expressed major histocompatibility complex Class-II molecules (MHC-II) and took up BCGV Ag. B-cell lymphoma 6 (Bcl-6) protein expression and the proportion of HLA-DR+ or CD40+ cells were higher in colonies of Th2 cell-stimulated myeloma cells. Furthermore, anti-HLA-DR or neutralizing CD40 antibody could prevent this increase in Bcl-6 expression and colony number. These results indicate that microbes and microbial Ag-specific Th2 cells may directly impact the biology of myeloma and contribute to tumor progression. Activation may be limited to MHC-II+ myeloma cells that retain B cell and stem cell characteristics. Taken together, our data suggest that factors involved in microbial Ag presentation, such as DCs, Th2 cells and so on, are potential targets for myeloma therapeutic intervention

Decreased production of TNF-alpha by lymph node cells indicates experimental autoimmune encephalomyelitis remission in Lewis rats

Experimental autoimmune encephalomyelitis (EAE) is mediated by CD4+ Th1 cells that mainly secrete IFN-γ and TNF-α, important cytokines in the pathophysiology of the disease. Spontaneous remission is, in part, attributed to the down regulation of IFN-γ and TNF-α by TGF-β. In the current paper, we compared weight, histopathology and immunological parameters during the acute and recovery phases of EAE to establish the best biomarker for clinical remission. Female Lewis rats were immunised with myelin basic protein (MBP) emulsified with complete Freund's adjuvant. Animals were evaluated daily for clinical score and weight prior to euthanisation. All immunised animals developed the expected characteristics of EAE during the acute phase, including significant weight loss and high clinical scores. Disease remission was associated with a significant reduction in clinical scores, although immunised rats did not regain their initial weight values. Brain inflammatory infiltrates were higher during the acute phase. During the remission phase, anti-myelin antibody levels increased, whereas TNF-α and IFN-γ production by lymph node cells cultured with MBP or concanavalin A, respectively, decreased. The most significant difference observed between the acute and recovery phases was in the induction of TNF-α levels in MBP-stimulated cultures. Therefore, the in vitro production of this cytokine could be used as a biomarker for EAE remission

European Strategy for Particle Physics -- Accelerator R&D Roadmap

The 2020 update of the European Strategy for Particle Physics emphasised the importance of an intensified and well-coordinated programme of accelerator R&D, supporting the design and delivery of future particle accelerators in a timely, affordable and sustainable way. This report sets out a roadmap for European accelerator R&D for the next five to ten years, covering five topical areas identified in the Strategy update. The R&D objectives include: improvement of the performance and cost-performance of magnet and radio-frequency acceleration systems; investigations of the potential of laser / plasma acceleration and energy-recovery linac techniques; and development of new concepts for muon beams and muon colliders. The goal of the roadmap is to document the collective view of the field on the next steps for the R&D programme, and to provide the evidence base to support subsequent decisions on prioritisation, resourcing and implementation.Comment: 270 pages, 58 figures. Editor: N. Mounet. LDG chair: D. Newbold. Panel chairs: P. V\'edrine (HFM), S. Bousson (RF), R. Assmann (plasma), D. Schulte (muon), M. Klein (ERL). Panel editors: B. Baudouy (HFM), L. Bottura (HFM), S. Bousson (RF), G. Burt (RF), R. Assmann (plasma), E. Gschwendtner (plasma), R. Ischebeck (plasma), C. Rogers (muon), D. Schulte (muon), M. Klein (ERL

First Cold Powering Test of REBCO Roebel Wound Coil for the EuCARD2 Future Magnet Development Project

EuCARD-2 is a project partly supported by FP7-European Commission aiming at exploring accelerator magnet technology for 20 T dipole operating field. The EuCARD-2 collaboration is liaising with similar programs for high field magnets in the USA and Japan. EuCARD-2 focuses, through the work-package 10 'Future magnets,' on the development of a 10 kA-class superconducting, high current density cable suitable for accelerator magnets, for a 5 T stand-alone dipole of 40 mm bore and about 1 m length. After standalone testing, the magnet will possibly be inserted in a large bore background dipole, to be tested at a peak field up to 18 T. This paper starts by reporting on a few of the highlight simulations that demonstrate the progress made in predicting: dynamic current distribution and influence on field quality, complex quench propagation between tapes, and minimum quench energy in the multitape cable. The multiphysics output importantly helps predicting quench signals and guides the development of the novel early detection systems. Knowing current position within individual tapes of each cable we present stress distribution throughout the coils. We report on the development of the mechanical component and assembly processes selected for Feather-M2 the 5 T EuCARD2 magnet. We describe the CERN variable temperature flowing helium cold gas test system. We describe the parallel integration of the FPGA early quench detection system, using pickup coils and temperature sensors, alongside the standard CERN magnet quench detection system using voltage taps. Finally we report on the first cold tests of the REBCO 10 kA class Roebel subscale coil named Feather-M0

MicroRNAs:New players in IBD

MicroRNAs (miRNAs) are small non-coding RNAs, 18–23 nucleotides long, which act as post-transcriptional regulators of gene expression. miRNAs are strongly implicated in the pathogenesis of many common diseases, including IBDs. This review aims to outline the history, biogenesis and regulation of miRNAs. The role of miRNAs in the development and regulation of the innate and adaptive immune system is discussed, with a particular focus on mechanisms pertinent to IBD and the potential translational applications