Molecular mechanism of basic calcium phosphate crystal-induced activation of human fibroblasts: Role of nuclear factor κB, activator protein 1, and protein kinase C

Synovial fluid basic calcium phosphate (BCP) crystals are markers of severe joint degeneration in osteoarthritis. BCP crystals cause mitogenesis of articular cells and stimulate matrix metalloprotease production, thus promoting degradation of articular tissues. Previous work suggested that BCP crystal-induced cell activation required intracellular crystal dissolution, induction of proto-oncogene expression, and activation of signal transduction pathways involving protein kinase C and mitogen-activated protein kinases. Here we further elucidate the mechanisms of BCP crystal-induced cell activation as BCP crystals activate transcription factors nuclear factor κB and activator protein I in human fibroblasts. We confirm the role of protein kinase C in BCP crystal-induced mitogenesis in human fibroblasts. In contrast, we demonstrate that BCP crystals do not activate signal transduction pathways involving protein tyrosine kinases or phosphatidylinositol 3-kinase. These data further define the mechanism of cell activation by BCP crystals and confirm its selectivity, an observation that may have therapeutic implications

Approximating multi-dimensional Hamiltonian flows by billiards

Consider a family of smooth potentials $V_{\epsilon}$, which, in the limit $\epsilon\to0$, become a singular hard-wall potential of a multi-dimensional billiard. We define auxiliary billiard domains that asymptote, as $\epsilon\to0$ to the original billiard, and provide asymptotic expansion of the smooth Hamiltonian solution in terms of these billiard approximations. The asymptotic expansion includes error estimates in the $C^{r}$ norm and an iteration scheme for improving this approximation. Applying this theory to smooth potentials which limit to the multi-dimensional close to ellipsoidal billiards, we predict when the separatrix splitting persists for various types of potentials

Democracy, Globalization and Private Investment in Ghana

The article examines the effects of democracy and globalization on private investment in Ghana for the period 1980–2012, using the autoregressive distributed lag (ARDL) bounds test for cointegration and the error correction model (ECM). Two models are used. In Model 1, democracy is proxy by an index for institutional quality (Polity 2), while Model 2 uses an index for civil liberties as proxy for democracy. The results for Model 1 show globalization and public investment increase private investment, while exchange rate volatility and trade openness decrease private investment in both the long and short run. In addition, national income and interest rate reduce private investment in the short run. In the case of Model 2, credit to the private sector and public investment increase private investment, while exchange rate volatility and trade openness decrease private investment in both the long and short run. Finally, national income and interest rate reduce private investment in the short run. The findings and policy recommendations of the article provide vital information for policy implementation in Ghana

Physiological and biochemical adaptations to training in Rana pipiens

Fifteen Rana pipiens were trained on a treadmill thrice weekly for 6.5 weeks to assess the effects of training on an animal that supports activity primarily through anaerobiosis. Endurance for activity increased 35% in these frogs as a result of training ( P =0.006, Fig. 1). This increased performance was not due to enhanced anaerobiosis. Total lactate produced during exercise did not differ significantly for the trained or untrained animals in either gastrocnemius muscle (2.77±0.21 and 2.82±0.13 mg/g, respectively) or whole body (1.32±0.10 and 1.47±0.06 mg/g, respectively). Glycogen depletion also did not differ between the two groups (Fig. 2c). The primary response to training appeared to involve augmentation of aerobic metabolism, a response similar to that reported for mammals. Gastrocnemius muscles of trained frogs underwent a 38% increase over those of untrained individuals in the maximum activity of citrate synthase (14.5±1.0 and 10.5±0.9 μmoles/(g wet wt·min); P =0.008). This enzyme was also positively correlated with the level of maximum performance for all animals tested ( r =0.61, P <0.01) and with the degree of improvement in the trained animals ( r =0.72, P <0.05). In addition to an increased aerobic capacity, the trained animals demonstrated a greater removal of lactate from the muscle 15 min after fatigue (Fig. 2b).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47124/1/360_2004_Article_BF00710002.pd

The Classification of Linearly Polarized Transverse Electric Waves

AbstractRecently the author has undertaken the classification of continuous solutions to some common vector PDEs. These include the simplest of Beltrami solutions to hydrodynamic flows and electromagnetic wave equations (which are, in fact, closely related). In this paper, we consider linearly polarized transverse electric wave solutions to the electromagnetic wave equation:∇×E=iωH;∇×H=−iωE. Using Clebsch functions and differential geometric techniques the author is able to give a discussion of the most general possible forms of propagation of linearly polarized waves. A zero curvature condition (which asserts that the Clebsch functions necessary to represent the solutions are expressible in terms of Cartesian variables) reduces the study of vector PDEs to nonlinear PDEs, which may be solved in special cases. The benefit is that the Clebsch representation is the one that is the most useful for analyzing the structure of the flow. This method of analysis is now a feasible solution method due to the tremendous advances in mathematical software allowing one to compute curvatures, given metric functions. For the special case of linearly polarized transverse electric waves the analysis may be applied to a great extent

Monetary union and the economic geography of Europe

Monetary union is likely to change the spatial structure of economic activity in the EU. This article reviews what is known about these effects and discusses the implications for EMU. We argue that EMU is likely to promote a modest increase in specialization amongst EU countries, although industry-specific shocks are sufficiently small for this not to pose further difficulties for macroeconomic management. Improvements in market access are likely to raise income levels in insiders relative to outsiders. Taking a very long-term view, the urban structure of the EU might be expected to become more polarized, developing a steeper size distribution