The role of adenosine in chondrocyte death in murine osteoarthritis and in a murine chondrocyte cell line

SummaryObjectiveTo investigate the role of adenosine in chondrocyte death in murine osteoarthritis (OA).Methods5′-Nucleotidase (5′NT) generates adenosine. Enzyme activity was measured histochemically in normal murine and osteoarthritic STR/ort strain tibial cartilage. Adenosine-mediated cell death was investigated in MC615 chondrocyte cultures. Adenosine receptors (ARs) were assessed by reverse transcriptase polymerase chain reaction (RT-PCR). Cellular uptake of [3H] adenosine was measured with or without the inhibitor, nitrobenzylthioinosine (NBTI). Cell death was assessed by cell counting and DNA laddering following selective receptor stimulation, or after modulating adenosine metabolism with adenosine deaminase (ADA) or adenosine kinase (AK) inhibitors [erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and Iodotubericidin (Itub)], or with homocysteine (HC). Markers of apoptosis were assessed by Western blotting. Cell studies were validated by incubating normal murine knee joints in a medium containing adenosine and metabolic inhibitors. Apoptotic chondrocytes were identified with the TUNEL reaction.Results5′NT activity in STR/ort tibial cartilage increased with development of OA, especially close to OA lesions. Adenosine induced MC615 cell death in the presence of ADA inhibition (100μM EHNA), or 1mM HC, or both. Adenosine uptake, mediated by NBTI-sensitive adenosine transporters, was required for cell death. ARs were expressed (A2b>A2a>A1) but were not involved in mediating cell death. Cell death involved the activation of caspase-3 and DNA fragmentation and was prevented by inhibiting caspase activity. However, neither caspase-8 nor caspase-9 was detected. Adenosine+EHNA induced chondrocyte apoptosis in normal murine knee joints.ConclusionIncreased adenosine production may induce chondrocyte apoptosis and play a role in OA in STR/ort mice

Non-linear instability of Kerr-type Cauchy horizons

Using the general solution to the Einstein equations on intersecting null surfaces developed by Hayward, we investigate the non-linear instability of the Cauchy horizon inside a realistic black hole. Making a minimal assumption about the free gravitational data allows us to solve the field equations along a null surface crossing the Cauchy Horizon. As in the spherical case, the results indicate that a diverging influx of gravitational energy, in concert with an outflux across the CH, is responsible for the singularity. The spacetime is asymptotically Petrov type N, the same algebraic type as a gravitational shock wave. Implications for the continuation of spacetime through the singularity are briefly discussed.Comment: 11 pages RevTeX, two postscript figures included using epsf.st

Access to infertility consultations: what women tell us about it?

The main objective of the present paper is to evaluate the perception of women concerning the barriers and access to infertility consultations. Socio cultural and economic access to infertility consultations is detached and three municipalities of the northwest of Portugal were chosen as an example of a peripheral country. A quantitative/qualitative study was done with 60 women. Three dimensions were evaluated: geographic and structural and functional access; economic access; and sociocultural access. The main barriers were mainly identified in the last two dimensions. The economic access was the less well evaluated by women being the cost of treatment (medication, and concentration of costs in a short period) difficult to bear. This can justify a greater involvement of the Portuguese Government, by developing policies for the reimbursement of part of the costs. Also, some changes in structural and functional access must be done with special regard to the separation of the infertility consultations from the reproductive medicine section. The setting of the teams, with a follow-up by the same team of health professionals is also needed

Can induced gravity isotropize Bianchi I, V, or IX Universes?

We analyze if Bianchi I, V, and IX models in the Induced Gravity (IG) theory can evolve to a Friedmann--Roberson--Walker (FRW) expansion due to the non--minimal coupling of gravity and the scalar field. The analytical results that we found for the Brans-Dicke (BD) theory are now applied to the IG theory which has $\omega \ll 1$ ($\omega$ being the square ratio of the Higgs to Planck mass) in a cosmological era in which the IG--potential is not significant. We find that the isotropization mechanism crucially depends on the value of $\omega$. Its smallness also permits inflationary solutions. For the Bianch V model inflation due to the Higgs potential takes place afterwads, and subsequently the spontaneous symmetry breaking (SSB) ends with an effective FRW evolution. The ordinary tests of successful cosmology are well satisfied.Comment: 24 pages, 5 figures, to be published in Phys. Rev. D1

Origin and Evolution of Saturn's Ring System

The origin and long-term evolution of Saturn's rings is still an unsolved problem in modern planetary science. In this chapter we review the current state of our knowledge on this long-standing question for the main rings (A, Cassini Division, B, C), the F Ring, and the diffuse rings (E and G). During the Voyager era, models of evolutionary processes affecting the rings on long time scales (erosion, viscous spreading, accretion, ballistic transport, etc.) had suggested that Saturn's rings are not older than 100 My. In addition, Saturn's large system of diffuse rings has been thought to be the result of material loss from one or more of Saturn's satellites. In the Cassini era, high spatial and spectral resolution data have allowed progress to be made on some of these questions. Discoveries such as the ''propellers'' in the A ring, the shape of ring-embedded moonlets, the clumps in the F Ring, and Enceladus' plume provide new constraints on evolutionary processes in Saturn's rings. At the same time, advances in numerical simulations over the last 20 years have opened the way to realistic models of the rings's fine scale structure, and progress in our understanding of the formation of the Solar System provides a better-defined historical context in which to understand ring formation. All these elements have important implications for the origin and long-term evolution of Saturn's rings. They strengthen the idea that Saturn's rings are very dynamical and rapidly evolving, while new arguments suggest that the rings could be older than previously believed, provided that they are regularly renewed. Key evolutionary processes, timescales and possible scenarios for the rings's origin are reviewed in the light of tComment: Chapter 17 of the book ''Saturn After Cassini-Huygens'' Saturn from Cassini-Huygens, Dougherty, M.K.; Esposito, L.W.; Krimigis, S.M. (Ed.) (2009) 537-57

Stein's method on Wiener chaos

We combine Malliavin calculus with Stein's method, in order to derive explicit bounds in the Gaussian and Gamma approximations of random variables in a fixed Wiener chaos of a general Gaussian process. We also prove results concerning random variables admitting a possibly infinite Wiener chaotic decomposition. Our approach generalizes, refines and unifies the central and non-central limit theorems for multiple Wiener-It\^o integrals recently proved (in several papers, from 2005 to 2007) by Nourdin, Nualart, Ortiz-Latorre, Peccati and Tudor. We apply our techniques to prove Berry-Ess\'een bounds in the Breuer-Major CLT for subordinated functionals of fractional Brownian motion. By using the well-known Mehler's formula for Ornstein-Uhlenbeck semigroups, we also recover a technical result recently proved by Chatterjee, concerning the Gaussian approximation of functionals of finite-dimensional Gaussian vectors.Comment: 39 pages; Two sections added; To appear in PTR

The forms of repetition in social and environmental reports: insights from Hume's notion of ?impressions?

This paper focuses on the use of repetition, both in narrative and visual forms, in social and environmental reports. It investigates the forms of repetition as a rhetorical device adopted by the preparer of a social and environmental report in helping the process of knowledge acquisition, as outlined by Hume (1739). Drawing from Hume?s (1739) philosophical idea of an ?impression?, and the work of Davison (2014a) we classify repetitions into ?identical?, ?similar? and ?accumulated? forms. It is argued that the rationale for distinguishing between the different forms of repetition can be linked to their different potential or intensity in acting on different stimuli with a view to enhance learning. The empirical element of this study is based on the stand-alone social and environmental reports of a sample of 86 cooperative banks in Northern Italy; the analysis of these reports indicates that repetition is widespread and that cooperative banks use all forms of repetition, albeit to a varying extent within the different reported themes. The paper contributes to the literature by offering an alternative interpretation of repetition using an interdisciplinary perspective and by providing new insights on social and environmental reporting practices in the cooperative banking sector

Simplicity in Visual Representation: A Semiotic Approach

Simplicity, as an ideal in the design of visual representations, has not received systematic attention. High-level guidelines are too general, and low-level guidelines too ad hoc, too numerous, and too often incompatible, to serve in a particular design situation. This paper reviews notions of visual simplicity in the literature within the analytical framework provided by Charles Morris' communication model, specifically, his trichotomy of communication levels—the syntactic, the semantic, and the pragmatic. Simplicity is ultimate ly shown to entail the adjudication of incompatibilities both within, and between, levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68281/2/10.1177_105065198700100103.pd

Will a rising sea sink some estuarine wetland ecosystems?

Sea-level rise associatedwith climate change presents amajor challenge to plant diversity and ecosystemservice provision in coastal wetlands. In this study,we investigate the effect of sea-level rise on benthos, vegetation, and ecosystem diversity in a tidal wetland in westWales, the UK. Present relationships between plant communities and environmental variableswere investigated through 50 plots atwhich vegetation (species and coverage), hydrological (surface or groundwater depth, conductivity) and soil (matrix chroma, presence or absence ofmottles, organic content, particle size) data were collected. Benthic communities were sampled at intervals along a continuum from saline to freshwater. To ascertain future changes to the wetlands' hydrology, a GIS-based empirical model was developed. Using a LiDAR derived land surface, the relative effect of peat accumulation and rising sea levels were modelled over 200 years to determine how frequently portions of the wetland will be inundated by mean sea level, mean high water spring and mean high water neap conditions. The model takes into account changing extents of peat accumulation as hydrological conditions alter. Model results show that changes to the wetland hydrology will initially be slow. However, changes in frequency and extent of inundation reach a tipping point 125 to 175 years from2010 due to the extremely low slope of the wetland. From then onwards, large portions of the wetland become flooded at every flood tide and saltwater intrusion becomes more common. This will result in a reduction in marsh biodiversity with plant communities switching toward less diverse and occasionally monospecific communities that are more salt tolerant.IS