Plasmonic-Solitonic coupling structure

The applications of optics, in particular non-linear optics, have joined the electrical ones in many contexts, often equaling or exceeding them thanks to the characteristics ensured by the physical nature of light such as high speed of propagation and low losses. In recent years, nanotechnologies combined with plasmon propagation are shaping a new development scenario that touches areas such as medicine, robotics or neurobiology. In fact, nano-devices are able to reproduce a very large number of functions ensuring very small dimensions. Among these, the applications of surface plasmon polariton waves are becoming more and more important, thanks to their peculiar behavior both as an electric wave and as a light wave. In this work we present an innovative structure consisting of a nano metallic waveguide on which it is possible to propagate a surface-plasmon- polariton signal at the interface with a photorefractive dielectric material. At the end of the guide, the diffracting light can generate, under suitable conditions, a self-confined light beam (bright-screening-photorefractive soliton). In this way the polariton plasmon waves propagating at the interface are automatically coupled within a soliton-based optical waveguide. By definition, soliton guides have very low propagation losses, opening the possibility of using this type of hybrid interconnection in extended complex circuits, for example as memories, thanks to the intrinsic plasticity of the photorefractive nonlinear refractive index

CD21-/low B cells: a snapshot of a unique B cell subset in health and disease

B cells represent one of the cellular components of the immune system thatprotects the individual from invading pathogens. In response to the invader,these cells differentiate into plasma cells and produce large amounts of antibodiesthat bind to and eliminate the pathogen. A hallmark of autoimmune diseases isthe production of autoantibodies i.e. antibodies that recognize self. Those that areconsidered pathogenic can damage tissues and organs, either by direct binding orwhen deposited as immune complexes. For decades, B cells have been consideredto play a major role in autoimmune diseases by antibody production. However, aspathogenic autoantibodies appear to derive mainly from T cell dependentresponses, T cells have been the focus for many years. The successful treatment ofpatients with autoimmune diseases with either B cell depletion therapy(rituximab) or inhibition of B cell survival (belimumab), suggested that notonly the autoantibodies but also other B cell features are important. This hascaused a surg e of interest in B cells and their biology resulting in theidentification of various subsets e.g. regulatory B cells, several memory B cellsubsets etc. Also, in other conditions such as chronic viral infect ions and primaryimmunodeficiency, several B cell subsets with unique characteristics have beenidentified. In this review, we will discuss one of these subsets, a subset that isexpanded in conditions characterized by chronic immune stimulation. This B cellsubset lacks, or expresses low, surface levels of the complement receptor 2(CD21) and has therefore been termed CD21-/lowB cell

Dual stimulation by autoantigen and CpG fosters the proliferation of exhausted rheumatoid factor-specific CD21low B cells in hepatitis C virus-cured mixed cryoglobulinemia

Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of B cells expressing B cell receptors (BCRs), often encoded by the VH1-69 variable gene, endowed with both rheumatoid factor (RF) and anti-HCV specificity. These cells display an atypical CD21low phenotype and functional exhaustion evidenced by unresponsiveness to BCR and Toll-like receptor 9 (TLR9) stimuli. Although antiviral therapy is effective on MC vasculitis, pathogenic B cell clones persist long thereafter and can cause virus-independent disease relapses. MethodsClonal B cells from patients with HCV-associated type 2 MC or healthy donors were stimulated with CpG or heath-aggregated IgG (as surrogate immune complexes) alone or in combination; proliferation and differentiation were then evaluated by flow cytometry. Phosphorylation of AKT and of the p65 NF-kB subunit were measured by flow cytometry. TLR9 was quantified by qPCR and by intracellular flow cytometry, and MyD88 isoforms were analyzed using RT-PCR. DiscussionWe found that dual triggering with autoantigen and CpG restored the capacity of exhausted VH1-69pos B cells to proliferate. The signaling mechanism for this BCR/TLR9 crosstalk remains elusive, since TLR9 mRNA and protein as well as MyD88 mRNA were normally expressed and CpG-induced phosphorylation of p65 NF-kB was intact in MC clonal B cells, whereas BCR-induced p65 NF-kB phosphorylation was impaired and PI3K/Akt signaling was intact. Our findings indicate that autoantigen and CpG of microbial or cellular origin may unite to foster persistence of pathogenic RF B cells in HCV-cured MC patients. BCR/TLR9 crosstalk might represent a more general mechanism enhancing systemic autoimmunity by the rescue of exhausted autoreactive CD21low B cells

Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding VH81X-expressing B cells

Random recombination of antibody heavy- and light-chain genes results in a diverse B-cell receptor (BCR) repertoire including self-reactive BCRs. However, tolerance mechanisms that prevent the development of self-reactive B cells remain incompletely understood. The absence of the surrogate light chain, which assembles with antibody heavy chain forming a pre-BCR, leads to production of antinuclear antibodies (ANAs). Here we show that the naive follicular B-cell pool is enriched for cells expressing prototypic ANA heavy chains in these mice in a non-autoimmune background with a broad antibody repertoire. This results in the spontaneous formation of T-cell-dependent germinal centres that are enriched with B cells expressing prototypic ANA heavy chains. However, peripheral tolerance appears maintained by selection thresholds on cells entering the memory B-cell and plasma cell pools, as exemplified by the exclusion of cells expressing the intrinsically self-reactive VH81X from both pool

Dissecting Integrin Expression and Function on Memory B Cells in Mice and Humans in Autoimmunity

Immunological memory ensures life-long protection against previously encountered pathogens, and in mice and humans the spleen is an important reservoir for long-lived memory B cells (MBCs). It is well-established that integrins play several crucial roles in lymphocyte survival and trafficking, but their involvement in the retention of MBCs in secondary lymphoid organs, and differences between B cell subsets in their adhesion capacity to ICAM-1 and/or VCAM-1 have not yet been confirmed. Here, we use an autoimmune mouse model, where MBCs are abundant, to show that the highest levels of LFA-1 and VLA-4 amongst B cells are found on MBCs. In vivo blockade of VLA-4 alone or in combination with LFA-1, but not LFA-1 alone, causes a release of MBCs from the spleen into the blood stream. In humans, we find that in peripheral blood, spleens, and tonsils from healthy donors the highest expression levels of the integrins LFA-1 and VLA-4 are also found on MBCs. Consistent with this, we found MBCs to have a higher capacity to adhere to ICAM-1 and VCAM-1 than naïve B cells. In patients with the autoimmune disease rheumatoid arthritis, it is the MBCs that have the highest levels of LFA-1 and VLA-4; moreover, compared with healthy donors, naïve B and MBCs of patients receiving anti-TNF medication have enhanced levels of the active form of LFA-1. Commensurate levels of the active αL subunit can be induced on B cells from healthy donors by exposure to the integrin ligands. Thus, our findings establish the selective use of the integrins LFA-1 and VLA-4 in the localization and adhesion of MBCs in both mice and humans

CD21–/low B cells in healthy individuals are antigen experienced cells

In several conditions such as chronic viral infections and primary immunodeficiency, a unique B cell subset has been found expanded. This B cell subset lacks, or expresses low, surface levels of the complement receptor 2 (CD21) and has therefore been termed CD21–/low B cells. However, little is known about the CD21–/low B cell subset in peripheral blood from healthy donors. We show that CD21–/low cells represent approximately 5% of B cells in peripheral blood from adults but are barely detectable in cord blood, after excluding transitional B cells. The CD21–/low subset can be divided into CD38– 24+ and CD38– 24low cells, where most of the CD38– 24+ are CD27+ IgM+ IgD+ and the CD38– 24low are switched CD27–. Expression levels of additional markers, e.g. CD95 and CD62L, are similar to those on classical memory B cells. The majority of CD21–/low cells lack expression of the ABCB1 transporter, which is a marker restricted to naïve B cells. We also investigated the CD21–/low B cells response to various single stimuli. In order to do that, we determined the change in CD69 expression, an activation marker, after 3 hours stimulation. Both CD21+ naïve and memory B cells responded to all single stimuli by up-regulation of CD69 and to a similar extent. The CD21–/low subsets did not respond to the same extent and the lowest response was observed for the CD24low subset. Stimulation with a combination of BCR, Toll-like receptor (TLR) 7/8 and interleukin (IL)2 induces proliferation and differentiation of the CD21–/low B cells comparable to CD21+CD27+ memory B cells. Their response excluding BCR agonist is not on par with that of classical memory B cells, although clearly above that of naïve B cells. In conclusion, as in disease and tonsils of healthy individuals, the CD21–/low B cell subset in peripheral blood from healthy adults is a functionally and phenotypically heterogeneous population composed mainly of memory B cells

Switched CD21–/low B cells with an antigen-presenting phenotype in the infant thymus

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Winter Thermal Multi-Objective Optimization: a Simulation Case Study

In this work we propose a new approach based on multi-objective optimization combined with simulation tools in order to improve the building thermal energy performance during winter by keeping into account gas consumption and user comfort. In particular different scenarios have been investigated and results showed that there is a nearly 20% potential of energy saving. Experimentation has been carried out by simulating a real building and comparisons refer to the real settings applied to it