Reduced CD40L expression on ex vivo activated CD4+T-lymphocytes from patients with excellent renal allograft function measured with a rapid whole blood flow cytometry procedure

Background: The CD40-CD40L (CD154) costimulatory pathway plays a critical role in the pathogenesis of kidney allograft rejection. In renal transplant biopsies, CD4+ CD40L+ graft-infiltrating cells were detected during chronic rejection in contrast to acute rejection episodes. Using a rapid noninvasive FACS procedure, we were able to demonstrate CD40L upregulation in peripheral blood of patients with chronic renal allograft dysfunction. Materials and Methods: Whole blood from recipients of renal allografts was stimulated with PMA and ion-omycin and measured by flow cytometry. Patients were assigned to three groups based on transplant function. Group 1: 26 patients with excellent renal transplant function; group 2: 28 patients with impaired transplant function; group 3: 14 patients with chronic allograft dysfunction and group 4: 8 healthy controls. Results: The median percentage +/-SEM of CD4+/ CD40L+ cells stimulated ex vivo at 10 ng/ml PMA was as follows: group 1: 28.3 +/- 4.1%; group 2: 18.4 +/- 2.4%; group 3: 50.1 +/- 5.0% and group 4: 40.4 +/- 3.4%. Subdivisions of groups 2 and 3 resulted in different CD40L expression patterns. Patients with increased serum creatinine since the initial phase after transplantation ( groups 2a and 3a) revealed a higher percentage of CD4+ CD40L+ cells than patients showing a gradual increase over time ( groups 2b and 3b). Consequently, patients of group 3a exhibited a significantly reduced transplant function compared with those of group 3b. Conclusion: After PMA + ionomycin stimulation, patients with excellent kidney graft function displayed significantly reduced expression of CD40L surface molecules on CD4+ cells early after transplantation. Those with a chronic dysfunction of the renal graft showed significantly more CD4+ cells expressing CD40L compared to the other transplanted groups. These results demonstrate that the percentage of CD4+ CD40L+ cells stimulated ex vivo in peripheral blood may be a valuable marker for chronic allograft nephropathy. Copyright (C) 2004 S. Karger AG, Basel

Remote Infrared Imaging of the Space Shuttle During Hypersonic Flight: HYTHIRM Mission Operations and Coordination

The Hypersonic Thermodynamic Infrared Measurements (HYTHIRM) project has been responsible for obtaining spatially resolved, scientifically calibrated in-flight thermal imagery of the Space Shuttle Orbiter during reentry. Starting with STS-119 in March of 2009 and continuing through to the majority of final flights of the Space Shuttle, the HYTHIRM team has to date deployed during seven Shuttle missions with a mix of airborne and ground based imaging platforms. Each deployment of the HYTHIRM team has resulted in obtaining imagery suitable for processing and comparison with computational models and wind tunnel data at Mach numbers ranging from over 18 to under Mach 5. This paper will discuss the detailed mission planning and coordination with the NASA Johnson Space Center Mission Control Center that the HYTHIRM team undergoes to prepare for and execute each mission

A dual process account of creative thinking

This article explicates the potential role played by type 1 thinking (automatic, fast) and type 2 thinking (effortful, logical) in creative thinking. The relevance of Evans's (2007) models of conflict of dual processes in thinking is discussed with regards to creative thinking. The role played by type 1 thinking and type 2 thinking during the different stages of creativity (problem finding and conceptualization, incubation, illumination, verification and dissemination) is discussed. It is proposed that although both types of thinking are active in creativity, the extent to which they are active and the nature of their contribution to creativity will vary between stages of the creative process. Directions for future research to test this proposal are outlined; differing methodologies and the investigation of different stages of creative thinking are discussed. © Taylor & Francis Group, LLC

Decision-Making Ontology for Information System Engineering

International audienceInformation Systems (IS) engineering (ISE) processes contain steps where decisions must be made. Moreover, the growing role of IS in organizations involves requirements for ISE such as quality, cost and time. Considering these aspects implies that the number of researches dealing with decision-making (DM) in ISE increasingly grows. As DM becomes widespread in the ISE field, it is necessary to build a representation, shared between researchers and practitioners, of DM concepts and their relations with DM problems in ISE. In this paper, we present a DM ontology which aims at formalizing DM knowledge. Its goal is to enhance DM and to support DM activities in ISE. This ontology is illustrated within the requirements engineering field

Use of SF6 to estimate anthropogenic CO2 in the upper ocean

The highest concentrations of anthropogenic carbon (C_ant) are found in the upper layers of the world ocean. However, this is where seasonal variability of inorganic carbon and related parameters due to thermal and biological effects complicates use of back-calculation approaches for C ant . Tracer based approaches to C_ant estimation are unaffected by biological variability and have found wide application. However, slow-down, even reversal, of the atmospheric growth of chlorofluorocarbons (CFCs) restricts use of these tracers for C ant estimation for waters ventilated since the mid 1990s. Here we apply SF6, a tracer that continues to increase in the atmosphere, as a basis for the C_ant estimation, using samples collected in the midlatitude North Atlantic in 2004. C ant estimates derived from water mass transit time distributions (TTDs) calculated with SF6 are compared to those based on CFC-12. For recently ventilated waters (pCFC-12 > ∼450 ppt), the uncertainty of SF6 based estimates of C_ant is ∼6 μmol kg−1 less than that of CFC-12 based estimates. CFC-12 based estimates remain more reliable for older (deeper) water masses, as a result of the longer input history and more readily detectable concentrations of CFC-12. Historical data suggest that the near-surface saturation of CFC-12 has increased over time, in inverse proportion to its atmospheric growth rate. Use of a time-dependent saturation of CFC-12 in TTD calculations appears to provide more reliable estimation of C_ant

A characteristics framework for Semantic Information Systems Standards

Semantic Information Systems (IS) Standards play a critical role in the development of the networked economy. While their importance is undoubted by all stakeholders—such as businesses, policy makers, researchers, developers—the current state of research leaves a number of questions unaddressed. Terminological confusion exists around the notions of “business semantics”, “business-to-business interoperability”, and “interoperability standards” amongst others. And, moreover, a comprehensive understanding about the characteristics of Semantic IS Standards is missing. The paper addresses this gap in literature by developing a characteristics framework for Semantic IS Standards. Two case studies are used to check the applicability of the framework in a “real-life” context. The framework lays the foundation for future research in an important field of the IS discipline and supports practitioners in their efforts to analyze, compare, and evaluate Semantic IS Standard

Detailed analysis of the variability of peptidylarginine deiminase type 4 in German patients with rheumatoid arthritis: a case control study

Peptidylarginine deiminase type 4 (PADI4) genotypes were shown to influence susceptibility to rheumatoid arthritis ( RA) in the Japanese population. Such an association could not previously be confirmed in different European populations. In the present study, we analysed exons 2 - 4 of PADI4 in 102 German RA patients and 102 healthy individuals to study the influence of PADI4 variability on RA susceptibility by means of haplotype-specific DNA sequencing. Analyses of the influence of PADI4 and HLA-DRB1 genotypes on disease activity and on levels of anti-cyclic citrullinated peptide antibodies were performed. Comparing the frequencies of PADI4 haplotype 4 (padi4\_89* G, padi4\_90* T, padi4\_92* G, padi4\_94* T, padi4\_104* C, padi4\_95* G, padi4\_96* T) ( patients, 14.7%; controls, 7.8%; odds ratio = 2.0, 95% confidence interval = 1.1 - 3.8) and carriers of this haplotype ( patients, 27.5%; controls, 13.7%; odds ratio = 2.4, 95% confidence interval = 1.2 - 4.8), a significant positive association of PADI4 haplotype 4 with RA could be demonstrated. Other PADI4 haplotypes did not differ significantly between patients and controls. Regarding the individual PADI4 variants, padi4\_89 ( A. G), padi4\_90 (C --> T), and padi4\_94 (C --> T) were significantly associated with RA ( patients, 49.5%; controls, 38.7%; odds ratio = 1.6, 95% confidence interval = 1.1 - 2.3). Considering novel PADI4 variants located in or near to exons 2, 3, and 4, no quantitative or qualitative differences between RA patients (8.8%) and healthy controls (10.8%) could be demonstrated. While the PADI4 genotype did not influence disease activity and the anticyclic citrullinated peptide antibody level, the presence of the HLA-DRB1 shared epitope was significantly associated with higher anti-cyclic citrullinated peptide antibody levels ( P = 0.033). The results of this small case - control study support the hypothesis that variability of the PADI4 gene may influence susceptibility to RA in the German population. Quantitative or qualitative differences in previously undefined PADI4 variants between patients and controls could not be demonstrated

Observation of an Excited Bc+ State

Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date

Acetate Kinase Isozymes Confer Robustness in Acetate Metabolism

Acetate kinase (ACK) (EC no: 2.7.2.1) interconverts acetyl-phosphate and acetate to either catabolize or synthesize acetyl-CoA dependent on the metabolic requirement. Among all ACK entries available in UniProt, we found that around 45% are multiple ACKs in some organisms including more than 300 species but surprisingly, little work has been done to clarify whether this has any significance. In an attempt to gain further insight we have studied the two ACKs (AckA1, AckA2) encoded by two neighboring genes conserved in Lactococcus lactis (L. lactis) by analyzing protein sequences, characterizing transcription structure, determining enzyme characteristics and effect on growth physiology. The results show that the two ACKs are most likely individually transcribed. AckA1 has a much higher turnover number and AckA2 has a much higher affinity for acetate in vitro. Consistently, growth experiments of mutant strains reveal that AckA1 has a higher capacity for acetate production which allows faster growth in an environment with high acetate concentration. Meanwhile, AckA2 is important for fast acetate-dependent growth at low concentration of acetate. The results demonstrate that the two ACKs have complementary physiological roles in L. lactis to maintain a robust acetate metabolism for fast growth at different extracellular acetate concentrations. The existence of ACK isozymes may reflect a common evolutionary strategy in bacteria in an environment with varying concentrations of acetate