Characterization and epitope mapping of human monoclonal antibodies to PDC-E2, the immunodominant autoantigen of primary biliary cirrhosis

Further to define the epitopes of PDC-E2, the major autoantigen in primary biliary cirrhosis (PBC), we have developed and characterized five human monoclonal antibodies. These antibodies were derived by fusing a regional hepatic lymph node from a patient with PBC with the mouse human heterohybrid cell line F3B6. Previous studies of epitope mapping of PDC-E2 have relied on whole sera and have suggested that the immunodominant epitope lies within the inner lipoyl domain of the molecule. However, selective absorption studies using whole sera and a series of overlapping recombinant peptides of PDC-E2 have suggested that the epitope may also include a large conformational component. Moreover, several laboratories have suggested that autoantibodies against the 2-oxo acids dehydrogenase autoantigens are cross-reactive. The five monoclonal antibodies generated included three IgG2a and two IgM antibodies and were studied for antigen specificity using recombinant PDC-E2, recombinant BCKD-E2, histone, dsDNA, IgG (Fc), collagen and a recombinant irrelevant liver specific control, the F alloantigen. The antibodies were also used to probe blots of human, bovine, mouse and rat mitochondria. Finally, fine specificity was studied by selective ELISA and absorption against overlapping expressing fragments of PDC-E2. All five monoclonals, but none of the other mitochondrial autoantigens were specific for PDC-E2. In fact, although affinity purified antibodies to PDC-E2 from patients with PBC cross-reacted with protein X, the human monoclonals did not, suggesting that protein X contains an epitope distinct from that found on PDC-E2. Additionally, all three IgG2 monoclonals recognized distinct epitopes within the inner lipoyl domain of PDC-E2. © 1992

Blocking TLR7- and TLR9-mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection

Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-α that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-α, albeit at low levels. pDC mediate a marked but transient IFN-α response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-α response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-α production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-α production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-α production may not reduce HIV-associated immunopathology. © 2013 Kader et al

Assessing Ageing Condition of Mineral Oil-Paper Insulation by Polarization/Depolarization Current

Accurately assessing the ageing status of oil-paper insulation in transformer is essential and important. Polarization and Depolarization Current (PDC) technique is effective in assessing the condition of oil-paper insulation system. Though the PDC behaviour of mineral oil-paper insulation has been widely investigated, there is no report about how to make the quantitative analysis of mineral oil-paper insulation ageing condition by PDC. The PDC characteristics of mineral oil-paper insulation samples were investigated over the ageing period at 110°C. A new method for assessing the ageing condition of mineral oil-paper insulation by calculating the depolarization charge quantity was proposed. Results show that the depolarization charge quantity of mineral oil-paper insulation sample is very sensitive to its ageing condition. The stable depolarization charge quantity could be used to predict the ageing condition of mineral oil-paper insulation

Limits on the deterministic creation of pure single-photon states using parametric down-conversion

Parametric down-conversion (PDC) is one of the most widely used methods to create pure single-photon states for quantum information applications. However little attention has been paid to higher-order photon components in the PDC process, yet these ultimately limit the prospects of generating single-photons of high quality. In this paper we investigate the impacts of higher-order photon components and multiple frequency modes on the heralding rates and single-photon fidelities. This enables us to determine the limits of PDC sources for single-photon generation. Our results show that a perfectly single-mode PDC source in conjunction with a photon-number resolving detector is ultimately capable of creating single-photon Fock states with unit fidelity and a maximal state creation probability of 25%. Hence an array of 17 switched sources is required to build a deterministic (>99% emission probability) pure single-photon source.Comment: 7 pages, 6 figure

Theory of filtered type-II PDC in the continuous-variable domain: Quantifying the impacts of filtering

Parametric down-conversion (PDC) forms one of the basic building blocks for quantum optical experiments. However, the intrinsic multimode spectral-temporal structure of pulsed PDC often poses a severe hindrance for the direct implementation of the heralding of pure single-photon states or, for example, continuous-variable entanglement distillation experiments. To get rid of multimode effects narrowband frequency filtering is frequently applied to achieve a single-mode behavior. A rigorous theoretical description to accurately describe the effects of filtering on PDC, however, is still missing. To date, the theoretical models of filtered PDC are rooted in the discrete-variable domain and only account for filtering in the low gain regime, where only a few photon pairs are emitted at any single point in time. In this paper we extend these theoretical descriptions and put forward a simple model, which is able to accurately describe the effects of filtering on PDC in the continuous-variable domain. This developed straightforward theoretical framework enables us to accurately quantify the trade-off between suppression of higher-order modes, reduced purity and lowered Einstein-Podolsky-Rosen (EPR) entanglement, when narrowband filters are applied to multimode type-II PDC.Comment: 15 pages, 13 figure

Parabolic Dish Concentrator (PDC-2) Development

The design of the Parabolic Dish Concentrator (PDC-2) is described. The following five subsystems of the concentrator are discussed: (1) reflective surface subsystem, (2) support structure subsystem, (3) foundation, (4) drive subsystem, and (5) electrical and control subsystem. The status of the PDC-2 development project is assessed

Measurement of Coupling PDC photon sources with single-mode and multimode optical fibers

We investigate the coupling efficiency of parametric downconversion light (PDC) into single and multi-mode optical fibers as a function of the pump beam diameter, crystal length and walk-off. We outline two different theoretical models for the preparation and collection of either single-mode or multi-mode PDC light (defined by, for instance, multi-mode fibers or apertures, corresponding to bucket detection). Moreover, we define the mode-matching collection efficiency, important for realizing a single-photon source based on PDC output into a well-defined single spatial mode. We also define a multimode collection efficiency that is useful for single-photon detector calibration applications.Comment: 13 pages, 12 figure