ATP induces Ca2+signaling in human chondrons cultured in three-dimensional agarose films

OBJECTIVE: In vivo, chondrocytes are surrounded by an extracellular matrix, preventing direct cell-to-cell contact. Consequently, intercellular communication through gap junctions is unlikely. However, signaling at a distance is possible through extracellular messengers such as nitric oxide (NO) and nucleotides and nucleosides, adenosine triphosphate (ATP), uridine triphosphate (UTP), or adenosine diphosphate (ADP). We hypothesized that chondrons, chondrocytes surrounded by their native pericellular matrix, increase their intracellular calcium concentration ([Ca(2+)]ic) in response to ATP and other signaling molecules and that the source of Ca(2+) is from intracellular stores. The objectives of this study were to determine if chondrons in a 3-D gel respond to ATP by increasing [Ca(2+)]ic through a purinoceptor mechanism and to test whether chondrons in whole tissue samples would respond to ATP in a similar fashion. DESIGN: Human chondrons, cultured in a three-dimensional agarose gel or in whole cartilage loaded with Fura-2AM, a calcium sensitive dye, were stimulated with 1, 5 and 10 microM ATP. A ratio-imaging fluorescence technique was used to quantitate the [Ca(2+)]ic. RESULTS: ATP-stimulated chondrons increased their [Ca(2+)]ic from a basal level of 60 nM to over 1000 nM. Chondrons incubated in calcium-free medium also increased their [Ca(2+)]ic in response to ATP, indicating the source of Ca(2+) was not extracellular. ATP-induced calcium signaling was inhibited in chondrons pre-treated with suramin, a generic purinoceptor blocker. In addition, UTP and adenosine 5'-O-(3-thiotriphosphate) (ATPgammas) induced a calcium response, but 2-methylthio-ATP (2-MeSATP), ADP, and adenosine did not induce a significant increase in [Ca(2+)]ic, substantiating that the P2Y2 purinoceptor was dominant. Chondrons in whole cartilage increased [Ca(2+)]ic in response to ATP. CONCLUSIONS: We conclude that chondrons in 3-D culture respond to ATP by increasing [Ca(2+)]ic via P2Y2 receptor activation. Thus, ATP can pass through the agarose gel and the pericellular matrix, bind purinoceptors and increase intracellular Ca(2+) in a signaling response

Orally administered extract from \u3ci\u3ePrunella vulgaris\u3c/i\u3e attenuates spontaneous colitis in mdr1a\u3csup\u3e-/-\u3c/sup\u3e mice

AIM: To investigate the ability of a Prunella vulgaris (P. vulgaris) ethanolic extract to attenuate spontaneous typhlocolitis in mdr1a-/- mice. METHODS: Vehicle (5% ethanol) or P. vulgaris ethanolic extract (2.4 mg/d) were administered daily by oral gavage to mdr1a-/- or wild type FVBWT mice from 6 wk of age up to 20 wk of age. Clinical signs of disease were noted by monitoring weight loss. Mice experiencing weight loss in excess of 15% were removed from the study. At the time mice were removed from the study, blood and colon tissue were collected for analyses that included histological evaluation of lesions, inflammatory cytokine levels, and myeloperoxidase activity. RESULTS: Administration of P. vulgaris extracts to mdr1a-/- mice delayed onset of colitis and reduced severity of mucosal inflammation when compared to vehicle-treated mdr1a-/- mice. Oral administration of the P. vulgaris extract resulted in reduced (P \u3c 0.05) serum levels of IL-10 (4.6 ± 2 vs 19.4 ± 4), CXCL9 (1319.0 ± 277 vs 3901.0 ± 858), and TNFα (9.9 ± 3 vs 14.8 ± 1) as well as reduced gene expression by more than two-fold for Ccl2, Ccl20, Cxcl1, Cxcl9, IL-1 α, Mmp10, VCAM-1, ICAM, IL-2, and TNFα in the colonic mucosa of mdr1a-/- mice compared to vehicle-treated mdr1a-/- mice. Histologically, several microscopic parameters were reduced (P \u3c 0.05) in P. vulgaris -treated mdr1a-/- mice, as was myeloperoxidase activity in the colon (2.49 ± 0.16 vs 3.36 ± 0.06, P \u3c 0.05). The numbers of CD4+ T cells (2031.9 ± 412.1 vs 5054.5 ± 809.5) and germinal center B cells (2749.6 ± 473.7 vs 4934.0 ± 645.9) observed in the cecal tonsils of P. vulgaris - treated mdr1a-/- were significantly reduced (P \u3c 0.05) from vehicle-treated mdr1a-/- mice. Vehicle-treated mdr1a-/- mice were found to produce serum antibodies to antigens derived from members of the intestinal microbiota, indicative of severe colitis and a loss of adaptive tolerance to the members of the microbiota. These serum antibodies were greatly reduced or absent in P. vulgaris -treated mdr1a-/- mice. CONCLUSION: The anti-inflammatory activity of P. vulgaris ethanolic extract effectively attenuated the severity of intestinal inflammation in mdr1a-/- mice

A Centre-Stable Manifold for the Focussing Cubic NLS in R1+3R^{1+3}

Consider the focussing cubic nonlinear Schr\"odinger equation in $R^3$: $$i\psi_t+\Delta\psi = -|\psi|^2 \psi.$$ It admits special solutions of the form $e^{it\alpha}\phi$, where $\phi$ is a Schwartz function and a positive ($\phi>0$) solution of $$-\Delta \phi + \alpha\phi = \phi^3.$$ The space of all such solutions, together with those obtained from them by rescaling and applying phase and Galilean coordinate changes, called standing waves, is the eight-dimensional manifold that consists of functions of the form $e^{i(v \cdot + \Gamma)} \phi(\cdot - y, \alpha)$. We prove that any solution starting sufficiently close to a standing wave in the $\Sigma = W^{1, 2}(R^3) \cap |x|^{-1}L^2(R^3)$ norm and situated on a certain codimension-one local Lipschitz manifold exists globally in time and converges to a point on the manifold of standing waves. Furthermore, we show that \mc N is invariant under the Hamiltonian flow, locally in time, and is a centre-stable manifold in the sense of Bates, Jones. The proof is based on the modulation method introduced by Soffer and Weinstein for the $L^2$-subcritical case and adapted by Schlag to the $L^2$-supercritical case. An important part of the proof is the Keel-Tao endpoint Strichartz estimate in $R^3$ for the nonselfadjoint Schr\"odinger operator obtained by linearizing around a standing wave solution.Comment: 56 page

Hypogene Calcitization: Evaporite Diagenesis in the Western Delaware Basin

Evaporite calcitization within the Castile Formation of the Delaware Basin is more widespread and diverse than originally recognized. Coupled field and GIS studies have identified more than 1000 individual occurrences of calcitization within the Castile Formation outcrop area, which includes both calcitized masses (limestone buttes) and laterally extensive calcitized horizons (limestone sheets). Both limestone buttes and sheets commonly contain a central brecciated zone that we attribute to hypogene dissolution. Lithologic fabric of calcitized zones ranges from little alteration of original varved laminae to fabrics showing extensive laminae distortion as well as extensive vuggy and open cavernous porosity. Calcitization is most abundant in the western portion of the Castile outcrop region where surface denudation has been greatest. Calcitization often forms linear trends, indicating fluid migration along fractures, but also occurs as dense clusters indicating focused, ascending, hydrocarbon-rich fluids. Native sulfur, secondary tabular gypsum (i.e. selenite) and hypogene caves are commonly associated with clusters of calcitization. This assemblage suggests that calcium sulfate diagenesis within the Castile Formation is dominated by hypogene speleogemesis

Customer emotions in service failure and recovery encounters

Emotions play a significant role in the workplace, and considerable attention has been given to the study of employee emotions. Customers also play a central function in organizations, but much less is known about customer emotions. This chapter reviews the growing literature on customer emotions in employee–customer interfaces with a focus on service failure and recovery encounters, where emotions are heightened. It highlights emerging themes and key findings, addresses the measurement, modeling, and management of customer emotions, and identifies future research streams. Attention is given to emotional contagion, relationships between affective and cognitive processes, customer anger, customer rage, and individual differences

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

All-sky search for long-duration gravitational wave transients with initial LIGO

We present the results of a search for long-duration gravitational wave transients in two sets of data collected by the LIGO Hanford and LIGO Livingston detectors between November 5, 2005 and September 30, 2007, and July 7, 2009 and October 20, 2010, with a total observational time of 283.0 days and 132.9 days, respectively. The search targets gravitational wave transients of duration 10-500 s in a frequency band of 40-1000 Hz, with minimal assumptions about the signal waveform, polarization, source direction, or time of occurrence. All candidate triggers were consistent with the expected background; as a result we set 90% confidence upper limits on the rate of long-duration gravitational wave transients for different types of gravitational wave signals. For signals from black hole accretion disk instabilities, we set upper limits on the source rate density between 3.4×10-5 and 9.4×10-4 Mpc-3 yr-1 at 90% confidence. These are the first results from an all-sky search for unmodeled long-duration transient gravitational waves. © 2016 American Physical Society

Search for neutral resonances decaying into a Z boson and a pair of b jets or τ leptons

A search is performed for a new resonance decaying into a lighter resonance and a Z boson. Two channels are studied, targeting the decay of the lighter resonance into either a pair of oppositely charged τ leptons or a bb‾ pair. The Z boson is identified via its decays to electrons or muons. The search exploits data collected by the CMS experiment at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.8 fb −1 . No significant deviations are observed from the standard model expectation and limits are set on production cross sections and parameters of two-Higgs-doublet models

Search for a low-mass pseudoscalar Higgs boson produced in association with a bb⁻ pair in pp collisions at √s=8 TeV

A search is reported for a light pseudoscalar Higgs boson decaying to a pair of tau leptons, produced in association with a b (b) over bar pair, in the context of two-Higgs-doublet models. The results are based on pp collision data at a centre-of-mass energy of 8 TeV collected by the CMS experiment at the LHC and corresponding to an integrated luminosity of 19.7 fb(-1). Pseudoscalar boson masses between 25 and 80 GeV are probed. No evidence for a pseudoscalar boson is found and upper limits are set on the product of cross section and branching fraction to tau pairs between 7 and 39 pb at the 95% confidence level. This excludes pseudoscalar A bosons with masses between 25 and 80 GeV, with SM-like Higgs boson negative couplings to down-type fermions, produced in association with bb pairs, in Type II, two-Higgs-doublet models. (C) 2016 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommonnorg/licensesiby/4.01)

Phenomenological MSSM interpretation of CMS searches in pp collisions at √s=7 and 8 TeV

Searches for new physics by the CMS collaboration are interpreted in the framework of the phenomenological minimal supersymmetric standard model (pMSSM). The data samples used in this study were collected at root s = 7 and 8 TeV and have integrated luminosities of 5.0 fb(-1) and 19.5 fb(-1), respectively. A global Bayesian analysis is performed, incorporating results from a broad range of CMS supersymmetry searches, as well as constraints from other experiments. Because the pMSSM incorporates several well-motivated assumptions that reduce the 120 parameters of the MSSM to just 19 parameters defined at the electroweak scale, it is possible to assess the results of the study in a relatively straightforward way. Approximately half of the model points in a potentially accessible subspace of the pMSSM are excluded, including all pMSSM model points with a gluino mass below 500 GeV, as well as models with a squark mass less than 300 GeV. Models with chargino and neutralino masses below 200 GeV are disfavored, but no mass range of model points can be ruled out based on the analyses considered. The nonexcluded regions in the pMSSM parameter space are characterized in terms of physical processes and key observables, and implications for future searches are discussed