Retinal S-antigen Th1 cell epitope mapping in patients with Behcet's disease

Background - Retinal S-antigen (S-Ag) is a most characterized autoantigen of autoimmune uveitis. The recognized immunodominant epitope of human S-Ag in patients with uveitis has not been identified. In this study, we selected certain patients with active uveitis to map the Th1 cell epitope spectrum of human S-Ag in Behcet's disease(BD). Methods - Blood samples were taken from eight active BD patients who showed an immune response to 40 mixed overlapping peptides spanning the entire sequence of human S-Ag. Peripheral blood mononuclear cells were isolated and stimulated with single S-Ag peptide at 5 mu g/ml or 20 mu g/ml. Single-cell immune responses were measured by IFN-gamma ELIspot assay. Results - BD patients heterogeneously responded to the S-Ag peptides at two concentrations. In general, the responses to 5 mu g/ml peptides were slightly stronger than those to 20 mu g/ml peptides, while the maximum SFC frequency to single peptide at the two concentrations was similar. Several peptides including P31, P35 and P40 induced a prominent response, with the frequency of S-Ag specific cells being about 0.007%. Significant reactivity pattern shift was noted in patients with different disease courses. Conclusions - Certain active BD patients have S-Ag specific Th1 cells with a low frequency. The S-Ag epitope specificity between patients is highly heterogeneous, and varies with the uveitis cours

Hamiltonian Formalism of the de-Sitter Invariant Special Relativity

Lagrangian of the Einstein's special relativity with universal parameter $c$ ($\mathcal{SR}_c$) is invariant under Poincar\'e transformation which preserves Lorentz metric $\eta_{\mu\nu}$. The $\mathcal{SR}_c$ has been extended to be one which is invariant under de Sitter transformation that preserves so called Beltrami metric $B_{\mu\nu}$. There are two universal parameters $c$ and $R$ in this Special Relativity (denote it as $\mathcal{SR}_{cR}$). The Lagrangian-Hamiltonian formulism of $\mathcal{SR}_{cR}$ is formulated in this paper. The canonic energy, canonic momenta, and 10 Noether charges corresponding to the space-time's de Sitter symmetry are derived. The canonical quantization of the mechanics for $\mathcal{SR}_{cR}$-free particle is performed. The physics related to it is discussed.Comment: 24 pages, no figur

Splenic CD8(+) T cells secrete TGF-beta 1 to exert suppression in mice with anterior chamber-associated immune deviation

Background CD8(+) regulatory T cells (Treg) have been considered to be involved in a model of ocular-induced tolerance, known as anterior chamber-associated immune deviation (ACAID). The mechanisms of suppression by CD8(+) T cells in ACAID remain only poorly understood. TGF-beta 1 is considered as an inhibitory cytokine for immunosuppression in some models. The production of TGF-beta 1 by CD8(+) T cells in ACAID, and whether CD8+ T cells exert suppression through TGF-beta 1, is unknown. Methods The suppressive effect of CD8(+) T cells in ACAID mice was determined by a local adoptive transfer (LAT) assay. The production of TGF-beta 1 by CD8(+) T cells was measured by enzyme-linked immunosorbent assay (ELISA). Anti-TGF-beta 1 antibodies were used in the LAT assay to test if they could block the inhibitory effect of CD8(+) T cells. Results CD8(+) T cells from ACAID mice were shown to block the delayed-type hypersensitivity (DTH) response in an antigen-specific manner in a LAT assay. These CD8+ T cells secreted TGF-beta 1, and their suppression could partially be blocked by anti-TGF-beta 1 antibodies. Conclusions Our study confirms that CD8+ T cells from ACAID mice possess inhibitory properties. This population exerts part of its suppressive function via the production of TGF-beta 1

Epitope recognition of peptide-imprinted polymers for Regenerating protein 1 (REG1)

Molecularly imprinted polymers (MIPs) were developed to replace natural antibodies with a cost-effective and durable synthetic material. Molecular imprinting of proteins conventionally utilizes the whole protein as the template, which is complex (as many different epitopes may be imprinted) and expensive. In this work, seven peptides (13–18 amino acids) were synthesized and used as templates for the imprinting and recognition of Regenerating Protein 1 (REG1). REG1 is involved in the proliferation and differentiation of diverse cell types, and was recently described as a urinary biomarker for pancreatic ductal adenocarcinoma (PDAC). Peptide-imprinted poly(ethylene-co-vinyl alcohol)s (PIPs), containing four different mole fractions of ethylene were cast on screen-printed electrodes to find the optimum composition for both the sensing and the extraction of REG1 in an E. coli culture medium. Peptides with fewer than 16 amino acids and two or three aromatic and hydrophobic groups have a higher affinity for MIPs of poly(ethylene-co-vinyl alcohol) (EVAL) with 27 mol% of ethylene, while those with four aromatic and hydrophobic groups have a higher affinity for MIPs with EVALs that contain 32 mol% of ethylene. The peptide / EVAL combination that maximized both imprinting effectiveness and response to REG1B was the sequence NEDRETWVDADLY imprinted into 32 mol% EVAL. This EVAL composition and template peptide were then modified by incorporation of magnetic nanoparticles, thus extending applications for PIPs to include extraction of REG1 protein from E. coli culture medium

Phosphoproteins and protein-kinase activity in isolated envelopes of pea (Pisum sativum L.) chloroplasts

A protein kinase was found in envelope membranes of purified pea (Pisum sativum L.) chloroplasts. Separation of the two envelope membranes showed that most of the enzyme activity was localized in the outer envelope. The kinase was activated by Mg2+ and inhibited by ADP and pyrophosphate. It showed no response to changes in pH in the physiological range (pH 7-8) or conventional protein substrates. Up to ten phosphorylated proteins could be detected in the envelope-membrane fraction. The molecular weights of these proteins, as determined by polyacrylamide-gel electrophoresis were: two proteins higher than 145 kDa, 97, 86, 62, 55, 46, 34 and 14 kDa. The 86-kDa band being the most pronounced. Experiments with separated inner and outer envelopes showed that most labeled proteins are also localized in the outer-envelope fraction. The results indicate a major function of the outer envelope in the communication between the chloroplast and the parent cell

Characterization study of GaN-based epitaxial layer and light-emitting diode on nature-patterned sapphire substrate

[[abstract]]Chemical wet etching on c-plane sapphire wafers by three etching solutions (H3PO4, H2SO4, and H3PO4/H2SO4 mixing solution) was studied. Among these etching agents, the mixing H3PO4/H2SO4 solution has the fastest etching rate (1.5 μm/min). Interestingly, we found that H2SO4 does not etch the c-plane sapphire wafer in thickness; instead, a facet pyramidal pattern is formed on the c-plane sapphire wafer. GaN light-emitting diode (LED) epitaxial structure was grown on the sapphire wafer with the pyramidal pattern and the standard flat sapphire wafer. X-ray diffraction and photoluminescence measurement show that the pyramidal pattern on the sapphire wafer improved crystalline quality but augmented the compressive stress level in the GaN LED epilayer. The horizontal LED chips fabricated on the pyramidal-patterned sapphire wafer have a larger light output than the horizontal LED chips fabricated on the standard flat sapphire wafer by 20%.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]紙本[[booktype]]電子

Mesoscale magnetism at the grain boundaries in colossal magnetoresistive films

We report the discovery of mesoscale regions with distinctive magnetic properties in epitaxial La$_{1-x}$Sr$_{x}$MnO$_{3}$ films which exhibit tunneling-like magnetoresistance across grain boundaries. By using temperature-dependent magnetic force microscopy we observe that the mesoscale regions are formed near the grain boundaries and have a different Curie temperature (up to 20 K {\it higher}) than the grain interiors. Our images provide direct evidence for previous speculations that the grain boundaries in thin films are not magnetically and electronically sharp interfaces. The size of the mesoscale regions varies with temperature and nature of the underlying defect.Comment: 4 pages of text, 4 figure

Measurement of the Intrinsic Radiopurity of Cs-137/U-235/U-238/Th-232 in CsI(Tl) Crystal Scintillators

The inorganic crystal scintillator CsI(Tl) has been used for low energy neutrino and Dark Matter experiments, where the intrinsic radiopurity is an issue of major importance. Low-background data were taken with a CsI(Tl) crystal array at the Kuo-Sheng Reactor Neutrino Laboratory. The pulse shape discrimination capabilities of the crystal, as well as the temporal and spatial correlations of the events, provide powerful means of measuring the intrinsic radiopurity of Cs-137 as well as the U-235, U-238 and Th-232 series. The event selection algorithms are described, with which the decay half-lives of Po-218, Po-214, Rn-220, Po-216 and Po-212 were derived. The measurements of the contamination levels, their concentration gradients with the crystal growth axis, and the uniformity among different crystal samples, are reported. The radiopurity in the U-238 and Th-232 series are comparable to those of the best reported in other crystal scintillators. Significant improvements in measurement sensitivities were achieved, similar to those from dedicated massive liquid scintillator detector. This analysis also provides in situ measurements of the detector performance parameters, such as spatial resolution, quenching factors, and data acquisition dead time.Comment: 28 pages, 12 figure

Regulation of TMPRSS6 by BMP6 and iron in human cells and mice.

Mutations in transmembrane protease, serine 6 (TMPRSS6), encoding matriptase-2, are responsible for the familial anemia disorder iron-refractory iron deficiency anemia (IRIDA). Patients with IRIDA have inappropriately elevated levels of the iron regulatory hormone hepcidin, suggesting that TMPRSS6 is involved in negatively regulating hepcidin expression. Hepcidin is positively regulated by iron via the bone morphogenetic protein (BMP)-SMAD signaling pathway. In this study, we investigated whether BMP6 and iron also regulate TMPRSS6 expression. Here we demonstrate that, in vitro, treatment with BMP6 stimulates TMPRSS6 expression at the mRNA and protein levels and leads to an increase in matriptase-2 activity. Moreover, we identify that inhibitor of DNA binding 1 is the key element of the BMP-SMAD pathway to regulate TMPRSS6 expression in response to BMP6 treatment. Finally, we show that, in mice, Tmprss6 mRNA expression is stimulated by chronic iron treatment or BMP6 injection and is blocked by injection of neutralizing antibody against BMP6. Our results indicate that BMP6 and iron not only induce hepcidin expression but also induce TMPRSS6, a negative regulator of hepcidin expression. Modulation of TMPRSS6 expression could serve as a negative feedback inhibitor to avoid excessive hepcidin increases by iron to help maintain tight homeostatic balance of systemic iron levels

Studies of Prototype CsI(Tl) Crystal Scintillators for Low-Energy Neutrino Experiments

Crystal scintillators provide potential merits for the pursuit of low-energy low-background experiments. A CsI(Tl) scintillating crystal detector is being constructed to study low-energy neutrino physics at a nuclear reactor, while projects are underway to adopt this technique for dark matter searches. The choice of the geometrical parameters of the crystal modules, as well as the optimization of the read-out scheme, are the results of an R&D program. Crystals with 40 cm in length were developed. The detector requirements and the achieved performance of the prototypes are presented. Future prospects for this technique are discussed.Comment: 32 pages, 14 figure