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Background In the patients with primary Sjogren’s syndrome (pSS), overexpression of CD40 was reported. The increased CD40 expression contributes to enhance CD40-CD40L interaction and promotes the inflammatory response in various ways. Objectives To investigate whether CD40 DNA vaccine could inhibit the immune response and slow the disease progression of SS in non-obese diabetic (NOD) mice. Methods Female 8-week-old NOD mice were randomly divided into 3 groups. CD40 DNA vaccine group received pTaget CD40 DNA vaccine at a weekly dose of 50 ug for 4 weeks. Vector and NS group were administered an equivalent amount of empty vector or NS. Serum anti-CD40 antibody was measured by ELISA. Lymphocytes infiltration in the salivary glands was monitored by focus score (FS) calculation. Salivary CD40 was stained by immunohistochemistry. Splenic lymphocyte phenotypes were analysed by flow cytometry. CD40, TNF-α and IL-6 levels in the salivary glands were detected by PCR. Serum ANA was monitored by immunoflurescene. Results 1) CD40 DNA vaccination induced anti-CD40 antibody response We found the positive rate on anti-CD40 antibody in vaccine group was 80% at week 6% and 100% at week 10, which was significantly increased compared with that in nonvaccinated ones.(p 2) Expression of CD40 decreased in salivary glands in vaccine group At week 10, CD40 expression on ductal epithelial and endothelial cells in NOD mice of vaccine group was significantly decreased positive staining. CD40 mRNA expression level showed a significantly reduction compared to vector group (0.51±0.31 vs. 1.56±0.53, p 3) Down-regulation of lymphocytes infiltration in the salivary glands of mice in vaccine group At week 10, infiltration of lymphocytes was inhibited in treated group while increased in control group (F=5.275, P 4) CD40 DNA vaccine reduced the expression of TNF-α and IL-6 in the salivary glands In vaccine group, the expression level of TNF-α mRNA in salivary glands were declined significantly as compared to baseline (0.41±0.25 vs. 0.98±0.16, p 5) Disturbances in spleen DC and plasma cell subpopulations At week 6, the total numbers of CD11c+DC decreased as compared with two control groups (p 6) Level of ANA reduced in the vaccine group At week 10, the expression of ANA in HEp-2 cells is strong positive (++++) in both control groups, but only positive (+) in vaccine group. Conclusions These findings indicate that CD40 DNA vaccine can downregulate the expression of proinflammatory cytokines of TNF-α and IL-6, decrease the percentage of DCs and plasma cells, ameliorate the pathologic change in NOD mice with SS, and thus inhibit the autoimmune inflammation. Disclosure of Interest None declared

Association of P2RY1 and P2RY12 polymorphisms with on-aspirin platelet reactivity was investigated.Platelet reactivity was assessed by the light transmission aggregometry and TxB(2) assay in 423 patients with coronary artery disease (CAD) on aspirin. High residual platelet reactivity (RPR) was defined by ≥20% and ≥70% maximal aggregation stimulated with 0.5 mg/mL arachidonic acid (AA) and 10 μm ADP, respectively. Moderate RPR was considered aggregation ≥20% with AA, ≥70% with ADP, or ≥1 ng/mL stimulated TxB(2) . Fourteen P2RY1 and 35 P2RY12 single nucleotide polymorphisms (SNPs) were genotyped.High RPR was detected in 24% of the patients. Moderate RPR was observed in 31% with AA, 57% with 5 μm ADP, and 82% with 10 μm ADP. Stimulated TxB(2) was ≥1 ng/mL in 23% of patients. P2RY12 SNP rs9859538 was associated with high RPR (OR = 2.16, 95% CI = 1.24-3.75, P-value = 0.004). Four P2RY12 SNPs, rs1491974, rs10513398, rs3732765, and rs10935841, showed association with moderate RPR (OR = 1.79-2.94, P-value = 0.04-0.028), while five, rs7615865, rs1388623, rs1388622, rs7634096, and rs7637803, were associated with low RPR (OR = 0.50-0.55, P-value = 0.008-0.026), following ADP stimulation. TxB(2) level1 ng/mL was linked to five P2RY1 SNPs, rs1439010, rs1371097, rs701265, rs12497578, and rs2312265 (OR = 0.36-0.54, P-value = 0.003-0.039).Polymorphisms in P2RY1 and P2RY12 are associated with on-aspirin platelet reactivity in patients with CAD.

A new high-performance undoped In/sub 0.53/Ga/sub 0.47/As metal-semiconductor-metal photodetector (MSM-PD) with an undoped InP barrier-enhancement layer is reported. The layers were grown by the low-pressure metalorganic vapor-phase epitaxy (LP-MOVPE) technique. The main features of this device include: a very low dark current of less than 60 nA, (100*100) mu m/sup 2/, at 1.5 V; a short risetime of 30 ps at 6 V; and a high responsivity of 0.42 A/W for lambda =1.3 mu m. >

Chromosomal abnormalities are associated with a variety of diseases. We have developed a new technique for detecting chromosomal abnormalities, and the technique combines conventional 4',6-diamidino-2-phenyl-indole staining (DAPI) with image analysis. The image analysis consists of two simple steps: deconvolution and three-dimensional reconstruction. The technique has been reported for analyzing plant chromosomes but has not been applied to analyze human chromosomes yet. To test the technique, we analyzed five translocations: 46,XX,t(3;21)(12;18), 46,XX,t(11;22), 46,XY,t(7;22), 46,XY,t(11;18), and 46,XY,t(3;7). The results showed that the karyotype of the 46,XX,t(3;21)(12;18) was 46,XX,t(3;21)(q11.1;p13),t(12;18) (q21.2;q23), and the karyotypes of the 46,XX,t(11;22), 46,XY,t(7;22), 46,XY,t(11;18), and 46,XY,t(3;7) were 46,XX,t(11;22)(q23;q12.1); 46,XY,t(7;22)(q32;q13.2); 46,XY,t(11;18)(q13.3;q23), and 46,XY,t(3;7)(q22.1;p13), respectively. The identity of derivative chromosomes involved in the translocations was verified by chromosome painting as well as FISH analyses with centromere probes. The new technique has two advantages: the procedure is simple and convenient, and the results are accurate. The technique has the potential to be used in cytogenetic studies and clinical diagnosis of human diseases in the future.

A pipeline project normally not only covers a large geographic range, but also deals with a variety of data sources, such as geological, geographical, environmental, engineering and socioeconomic data. GIS has proven to be the effective approach to integrating, managing and analyzing these heterogeneous data sources. Due to the nature of pipeline applications, the third dimension of geospatial data is of considerable importance for pipeline planning, construction and maintenance. There is an increasing demand for the development of a 3-D GIS for pipeline applications. With the advent of Internet, distributed computing and computer graphics technologies, development of web-based 3-D GIS becomes technologically possible. The combination of 3-D GIS and web-based computing technologies opens a whole new avenue to the pipeline industry. In this paper, we will address the development of a web-based 3D GIS in terms of benefits and technical challenges. The detailed system architecture as well as the algorithms developed is also discussed. Finally, potential applications for the pipeline industry are introduced and a prototype system, GeoEye 3D, developed by the Department of Geomatics Engineering at the University of Calgary is described.Copyright © 2000 by ASME

Background Chromosome 9p21 variants have been strongly associated with coronary heart disease in genome-wide association studies, but questions remain on the mechanism of risk, specifically whether the locus contributes to coronary atheroma burden or plaque instability. We investigated the relationship of 9p21 locus with (1) angiographic coronary artery disease (CAD) burden and (2) myocardial infarction (MI) in individuals with underlying CAD. Methods:We established a collaboration of 21 studies consisting of 33,673 subjects with information on both CAD (clinical or angiographic) and MI status along with 9p21 genotype. Tabular data were provided for each cohort on the presence and burden of angiographic CAD; MI cases with underlying CAD; and the diabetic status of all subjects. Results We first confirmed an association between 9p21 and CAD using angiographically defined cases and controls (pooled OR=1.31 (95% CI 1.20 to 1.43)). Among subjects with angiographic CAD (n=20,987), random-effects model identified an association with multi-vessel CAD, compared to those with single-vessel disease (OR=1.10 (95% CI 1.04 to 1.17) per copy of risk allele). Genotypic models showed an OR of 1.15 (95% CI 1.04 to 1.26) for heterozygous carrier and 1.23 (95% CI 1.08 to 1.39) for homozygous carrier. Finally, there was no significant association between 9p21 and prevalent MI when both cases (n=17 791) and controls (n=15 882) had underlying CAD (OR=0.99 (95% CI 0.95 to 1.03) per risk allele). Conclusions The 9p21 locus shows convincing association with greater burden of CAD, but not with MI in the presence of underlying CAD. This adds further weight to the hypothesis that 9p21 locus primarily mediates an atherosclerotic phenotype.

In this work, the process of mist deposition is explored as a method used to deposit organic semiconductors for applications in organic light emitting diodes (OLEDs). The deposition kinetics of a specially formulated hole transport agent is studied. The results indicate that the mist-deposited organic film thickness varies linearly with precursor concentration, deposition time and substrate potential. Depending upon process parameters, a deposition rate in the range of 50 nm min−1 is readily achievable. Evolution of surface roughness revealed distinct stages in the film formation process. The growth of secondary layers was observed before the formation of a complete initial film layer. A working OLED with the hole transport layer deposited by mist deposition was demonstrated. The luminance of the device was measured to be a maximum of 3000 cd m−2 and the efficiency was 6.7 cd A−1.