BCP crystals increase prostacyclin production and upregulate the prostacyclin receptor in OA synovial fibroblasts: potential effects on mPGES1 and MMP-13

SummaryObjectiveTo investigate the potential involvement of prostacyclin in basic calcium phosphate (BCP) crystal-induced responses in osteoarthritic synovial fibroblasts (OASF).MethodsOASF grown in culture were stimulated with BCP crystals. Prostacyclin production was measured by enzyme immunoassay. Expression of messenger RNA (mRNA) transcripts was assessed by real-time polymerase chain reaction (PCR). Expression of prostacyclin synthase (PGIS) and the prostacyclin (IP) receptor was measured. The effects of iloprost, a prostacyclin analogue, on expression of genes implicated in osteoarthritis such as microsomal prostaglandin E2 synthase 1 (mPGES1) and matrix metalloproteinases (MMPs) were also studied. FPT inhibitor II, a farnesyl transferase inhibitor, was used to antagonize iloprost-induced responses.ResultsBCP crystal stimulation led to a five-fold increase in prostacyclin production in OASF compared to untreated cells. This induction was attenuated by cyclooxygenase (COX)-2 and COX-1 inhibition at 4 and 32h, respectively. PGIS and IP receptor transcripts were constitutively expressed in OASF. BCP crystals upregulated IP receptor expression two-fold. While iloprost diminished BCP crystal-stimulated IP receptor upregulation, the inhibitory effect of iloprost was blocked by the farnesyl transferase inhibitor. In addition, iloprost upregulated mPGES1 and downregulated MMP-13 expression in BCP crystal-stimulated OASF, effects that were not influenced by the farnesyl transferase inhibitor.ConclusionsThese data showed for the first time that BCP crystals can increase prostacyclin production and upregulate expression of the IP receptor in OASF. The potential of prostacyclin to influence BCP crystal-stimulated responses was supported by the effects of iloprost on the expression of the IP receptor, mPGES1 and MMP-13. These data demonstrate the potential involvement of prostacyclin in BCP crystal-associated osteoarthritis (OA) and suggest that inhibition of PG synthesis with non-steroidal anti-inflammatory drugs may have both deleterious and beneficial effects in BCP crystal-associated OA

Views from the coalface: chemo-sensors, sensor networks and the semantic sensor web

Currently millions of sensors are being deployed in sensor networks across the world. These networks generate vast quantities of heterogeneous data across various levels of spatial and temporal granularity. Sensors range from single-point in situ sensors to remote satellite sensors which can cover the globe. The semantic sensor web in principle should allow for the unification of the web with the real-word. In this position paper, we discuss the major challenges to this unification from the perspective of sensor developers (especially chemo-sensors) and integrating sensors data in real-world deployments. These challenges include: (1) identifying the quality of the data; (2) heterogeneity of data sources and data transport methods; (3) integrating data streams from different sources and modalities (esp. contextual information), and (4) pushing intelligence to the sensor level

Achieving Health Equity in Embedded Pragmatic Trials for People Living with Dementia and Their Family Caregivers

Embedded pragmatic clinical trials (ePCTs) advance research on Alzheimer's disease/Alzheimer's disease and related dementias (AD/ADRD) in real-world contexts; however, health equity issues have not yet been fully considered, assessed, or integrated into ePCT designs. Health disparity populations may not be well represented in ePCTs without special efforts to identify and successfully recruit sites of care that serve larger numbers of these populations. The National Institute on Aging (NIA) Imbedded Pragmatic Alzheimer's disease (AD) and AD-Related Dementias (AD/ADRD) Clinical Trials (IMPACT) Collaboratory's Health Equity Team will contribute to the overall mission of the collaboratory by developing and implementing strategies to address health equity in the conduct of ePCTs and ensure the collaboratory is a national resource for all Americans with dementia. As a first step toward meeting these goals, this article reviews what is currently known about the inclusion of health disparities populations of people living with dementia (PLWD) and their caregivers in ePCTs, highlights unique challenges related to health equity in the conduct of ePCTs, and suggests priority areas in the design and implementation of ePCTs to increase the awareness and avoidance of pitfalls that may perpetuate and magnify healthcare disparities

Ontological representation and governance of business semantics in compliant service networks

The Internet would enable new ways for service innovation and trading, as well as for analysing the resulting value networks, with an unprecedented level of scale and dynamics. Yet most related economic activities remain of a largely brittle and manual nature. Service-oriented business implementations focus on operational aspects at the cost of value creation aspects such as quality and regulatory compliance. Indeed they enforce how to carry out a certain business in a prefixed non-adaptive manner rather than capturing the semantics of a business domain in a way that would enable service systems to adapt their role in changing value propositions. In this paper we set requirements for SDL-compliant business service semantics, and propose a method for their ontological representation and governance. We demonstrate an implementation of our approach in the context of service-oriented Information Governance

Extragalactic neutrino background from very young pulsars surrounded by supernova envelopes

We estimate the extragalactic muon neutrino background which is produced by hadrons injected by very young pulsars at an early phase after supernova explosion. It is assumed that hadrons are accelerated in the pulsar wind zone which is filled with thermal photons captured below the expanding supernova envelope. In collisions with those thermal photons hadrons produce pions which decay into muon neutrinos. At a later time, muon neutrinos are also produced by the hadrons in collisions with matter of the expanding envelope. We show that extragalactic neutrino background predicted by such a model should be detectable by the planned 1 km$^2$ neutrino detector if a significant part of pulsars is born with periods shorter than $\sim 10$ ms. Since such population of pulsars is postulated by the recent models of production of extremely high energy cosmic rays, detection of neutrinos with predicted fluxes can be used as their observational test.Comment: 4 pages, 2 figures, A&A style, accepted to A&A Let

Search for Higgs bosons decaying to tautau pairs in ppbar collisions at sqrt(s) = 1.96 TeV

We present a search for the production of neutral Higgs bosons decaying into tautau pairs in ppbar collisions at a center-of-mass energy of 1.96 TeV. The data, corresponding to an integrated luminosity of 5.4 fb-1, were collected by the D0 experiment at the Fermilab Tevatron Collider. We set upper limits at the 95% C.L. on the product of production cross section and branching ratio for a scalar resonance decaying into tautau pairs, and we then interpret these limits as limits on the production of Higgs bosons in the minimal supersymmetric standard model (MSSM) and as constraints in the MSSM parameter space.Comment: 7 pages, 5 figures, submitted to PL

Measurement of the photon+b+b-jet production differential cross section in ppˉp\bar{p} collisions at \sqrt{s}=1.96~\TeV

We present measurements of the differential cross section dsigma/dpT_gamma for the inclusive production of a photon in association with a b-quark jet for photons with rapidities |y_gamma|< 1.0 and 30<pT_gamma <300 GeV, as well as for photons with 1.5<|y_gamma|< 2.5 and 30< pT_gamma <200 GeV, where pT_gamma is the photon transverse momentum. The b-quark jets are required to have pT>15 GeV and rapidity |y_jet| < 1.5. The results are based on data corresponding to an integrated luminosity of 8.7 fb^-1, recorded with the D0 detector at the Fermilab Tevatron $p\bar{p}$ Collider at sqrt(s)=1.96 TeV. The measured cross sections are compared with next-to-leading order perturbative QCD calculations using different sets of parton distribution functions as well as to predictions based on the kT-factorization QCD approach, and those from the Sherpa and Pythia Monte Carlo event generators.Comment: 10 pages, 9 figures, submitted to Phys. Lett.

Limits on anomalous trilinear gauge boson couplings from WW, WZ and Wgamma production in pp-bar collisions at sqrt{s}=1.96 TeV

We present final searches of the anomalous gammaWW and ZWW trilinear gauge boson couplings from WW and WZ production using lepton plus dijet final states and a combination with results from Wgamma, WW, and WZ production with leptonic final states. The analyzed data correspond to up to 8.6/fb of integrated luminosity collected by the D0 detector in pp-bar collisions at sqrt{s}=1.96 TeV. We set the most stringent limits at a hadron collider to date assuming two different relations between the anomalous coupling parameters Delta\kappa_\gamma, lambda, and Delta g_1^Z for a cutoff energy scale Lambda=2 TeV. The combined 68% C.L. limits are -0.057<Delta\kappa_\gamma<0.154, -0.015<lambda<0.028, and -0.008<Delta g_1^Z<0.054 for the LEP parameterization, and -0.007<Delta\kappa<0.081 and -0.017<lambda<0.028 for the equal couplings parameterization. We also present the most stringent limits of the W boson magnetic dipole and electric quadrupole moments.Comment: 10 pages, 5 figures, submitted to PL