Advanced glycation end-products (AGEs) induce concerted changes in the osteoblastic expression of their receptor RAGE and in the activation of extracellular signal-regulated kinases (ERK)

An increase in the interaction between advanced glycation end-products (AGEs) and their receptor RAGE is believed to contribute to the pathogenesis of chronic complications of Diabetes mellitus, which can include bone alterations such as osteopenia. We have recently found that extracellular AGEs can directly regulate the growth and development of rat osteosarcoma UMR106 cells, and of mouse calvaria-derived MC3T3E1 osteoblasts throughout their successive developmental stages (proliferation, differentiation and mineralisation), possibly by the recognition of AGEs moieties by specific osteoblastic receptors which are present in both cell lines. In the present study we examined the possible expression of RAGE by UMR106 and MC3T3E1 osteoblastic cells, by immunoblot analysis. We also investigated whether short-, medium- or long-term exposure of osteoblasts to extracellular AGEs, could modify their affinity constant and maximal binding for AGEs (by 125I-AGE-BSA binding experiments), their expression of RAGE (by immunoblot analysis) and the activation status of the osteoblastic ERK 1/2 signal transduction mechanism (by immunoblot analysis for ERK and P-ERK). Our results show that both osteoblastic cell lines express readily detectable levels of RAGE. Short-term exposure of phenotypically mature osteoblastic UMR106 cells to AGEs decrease the cellular density of AGE-binding sites while increasing the affinity of these sites for AGEs. This culture condition also dose-dependently increased the expression of RAGE and the activation of ERK. In proliferating MC3T3E1 pre-osteoblasts, 24-72 h exposure to AGEs did not modify expression of RAGE, ERK activation or the cellular density of AGE-binding sites. However, it did change the affinity of these binding sites forAGEs, with both higher- and lower-affinity sites now being apparent. Medium-term ( 1 week) incubation of differentiated MC3T3E1 osteoblasts with AGEs, induced a simultaneous increase in RAGE expression and in the relative amount of P-ERK. Mineralising MC3T3E1 cultures grown for 3 weeks in the presence of extracellular AGEs showed a decrease both in RAGE and P-ERK expression. These results indicate that, in phenotypically mature osteoblastic cells, changes in ERK activation closely follow the AGEs-induced regulation of RAGE expression. Thus, the AGEs-induced biological effects that we have observed previously in osteoblasts, could be mediated by RAGE in the later stages of development, and mediated by other AGE receptors in the earlier pre-osteoblastic stage

The Canary Basin contribution to the seasonal cycle of the Atlantic Meridional Overturning Circulation at 26°N

This study examines the seasonal cycle of the Atlantic Meridional Overturning Circulation (AMOC) and its eastern boundary contributions. The cycle has a magnitude of 6 Sv, as measured by the RAPID/MOCHA/WBTS project array at 26°N, which is driven largely by the eastern boundary. The eastern boundary variations are explored in the context of the regional circulation around the Canary Islands. There is a 3 month lag between maximum wind forcing and the largest eastern boundary transports, which is explained in terms of a model for Rossby wave generated at the eastern boundary. Two dynamic processes take place through the Lanzarote Passage (LP) in fall: the recirculation of the Canary Current and the northward flow of the Intermediate Poleward Undercurrent. In contrast, during the remaining seasons the transport through the LP is southward due to the Canary Upwelling Current. These processes are linked to the seasonal cycle of the AMOC

Compensation between meridional flow components of the Atlantic MOC at 26°N

From ten years of observations of the Atlantic meridional overturning circulation (MOC) at 26° N (2004–2014), we revisit the question of flow compensation between components of the circulation. Contrasting with early results from the observations, transport variations of the Florida Current (FC) and upper mid-ocean (UMO) transports (top 1000 m east of the Bahamas) are now found to compensate on sub-annual timescales. The observed compensation between the FC and UMO transports is associated with horizontal circulation and means that this part of the correlated variability does not project onto the MOC. A deep baroclinic response to wind-forcing (Ekman transport) is also found in the lower North Atlantic Deep Water (LNADW; 3000–5000 m) transport. In contrast, co-variability between Ekman and the LNADW transports does contribute to overturning. On longer timescales, the southward UMO transport has continued to strengthen, resulting in a continued decline of the MOC. Most of this interannual variability of the MOC can be traced to changes in isopycnal displacements on the western boundary, within the top 1000 m and below 2000 m. Substantial trends are observed in isopycnal displacements in the deep ocean, underscoring the importance of deep boundary measurements to capture the variability of the Atlantic MOC

Quenching 2D Quantum Gravity

We simulate the Ising model on a set of fixed random $\phi^3$ graphs, which corresponds to a {\it quenched} coupling to 2D gravity rather than the annealed coupling that is usually considered. We investigate the critical exponents in such a quenched ensemble and compare them with measurements on dynamical $\phi^3$ graphs, flat lattices and a single fixed $\phi^3$ graph.Comment: 8 page

Major variations in subtropical North Atlantic heat transport at short (5 day) timescales and their causes

Variability in the North Atlantic ocean heat transport at 26.5°N on short (5-day) timescales is identified and contrasted with different behaviour at monthly intervals using a combination of RAPID/MOCHA/WBTS measurements and the NEMO-LIM2 1/12° ocean circulation/sea ice model. Wind forcing plays the leading role in establishing the heat transport variability through the Ekman transport response of the ocean and the associated driving atmospheric conditions vary significantly with timescale. We find that at 5-day timescales the largest changes in the heat transport across 26.5°N coincide with north-westerly airflows originating over the American land mass that drive strong southward anomalies in the Ekman flow. During these events the northward heat transport reduces by 0.5-1.4 PW. In contrast, the Ekman transport response at longer monthly timescales is smaller in magnitude (up to 0.5 PW) and consistent with expected variations in the leading mode of North Atlantic atmospheric variability, the North Atlantic Oscillation. The north-westerly airflow mechanism can have a prolonged influence beyond the central 5-day timescale and on occasion can reduce the accumulated winter ocean heat transport into the North Atlantic by ∼40%

Stellar populations of classical and pseudo-bulges for a sample of isolated spiral galaxies

In this paper we present the stellar population synthesis results for a sample of 75 bulges in isolated spiral Sb-Sc galaxies, using the spectroscopic data from the Sloan Digital Sky Survey and the STARLIGHT code. We find that both pseudo-bulges and classical bulges in our sample are predominantly composed of old stellar populations, with mean mass-weighted stellar age around 10 Gyr. While the stellar population of pseudo-bulges is, in general, younger than that of classical bulges, the difference is not significant, which indicates that it is hard to distinguish pseudo-bulges from classical bulges, at least for these isolated galaxies, only based on their stellar populations. Pseudo-bulges have star formation activities with relatively longer timescale than classical bulges, indicating that secular evolution is more important in this kind of systems. Our results also show that pseudo-bulges have a lower stellar velocity dispersion than their classical counterparts, which suggests that classical bulges are more dispersion-supported than pseudo-bulges.Comment: 10 pages, 8 figures. Accepted for publication in Astrophysics & Space Scienc

Elastic Scattering of Pions From the Three-nucleon System

We examine the scattering of charged pions from the trinucleon system at a pion energy of 180 MeV. The motivation for this study is the structure seen in the experimental angular distribution of back-angle scattering for pi+ 3He and pi- 3H but for neither pi- 3He nor pi+ 3H. We consider the addition of a double spin flip term to an optical model treatment and find that, though the contribution of this term is non-negligible at large angles for pi+ 3He and pi- 3H, it does not reproduce the structure seen in the experiment.Comment: 15 pages + 5 figure

Controls on Ice Cliff Distribution and Characteristics on Debris-Covered Glaciers

Ice cliff distribution plays a major role in determining the melt of debris-covered glaciers but its controls are largely unknown. We assembled a data set of 37,537 ice cliffs and determined their characteristics across 86 debris-covered glaciers within High Mountain Asia (HMA). We find that 38.9% of the cliffs are stream-influenced, 19.5% pond-influenced and 19.7% are crevasse-originated. Surface velocity is the main predictor of cliff distribution at both local and glacier scale, indicating its dependence on the dynamic state and hence evolution stage of debris-covered glacier tongues. Supraglacial ponds contribute to maintaining cliffs in areas of thicker debris, but this is only possible if water accumulates at the surface. Overall, total cliff density decreases exponentially with debris thickness as soon as the debris layer reaches a thickness of over 10 cm

Some History of Functional Programming Languages

We study a series of milestones leading to the emergence of lazy, higher order, polymorphically typed, purely functional programming languages. An invited lecture given at TFP12, St Andrews University, 12 June 2012