The effect of advanced glycation endproduct accumulation on bone

Diabetes is associated with increased fracture risk, which leads to increased morbidity and eventual mortality with a substantial financial burden. Type 2 Diabetics also have increased fracture risk, despite having the same or higher BMD as non-diabetics with a low fracture risk. One hypothesis for this is increased modifications made to the extra-cellular matrix via non-enzymatic glycation (NEG) that can occur in a hyperglycemic environment, such as with diabetes. The accumulation of NEG products, known as advanced glycation endproducts (AGEs) can possibly lead to microdamage and eventual weakening of the bone itself. We developed a time-response model in order to induce a wide range of AGEs in a manner that would sustain the mineral integrity of the bone and could be applied to a variety of bone sample types. This was performed on 65 rat tibias, distributed amongst 8 groups (3,7,10, & 14 days) for both ribose and control. Secondly, the protocol was performed on human cortical beam samples cut from 10 donor tibias with 3,5 and 7 day time points for ribose and control groups. All samples were incubated in a 0.6 M ribose solution or 0.0 M ribose control solution. There was a 7, 4, and 5-fold increase in AGEs at the 7, 10, and 14 day time points respectively over controls in the rat tibia study. There was no significant variation in cortical porosity, however TTMD was significantly less dense in the 14-day ribose treated groups. There was a trend toward higher AGEs with time in the human cortical beam specimens, but no significant increase. The AGEs values in the human cortical beam specimens were much lower than expected based on previous trials and reports in the literature. We were able to establish a time-response model for AGE accumulation in bone. However, the effects of AGEs on bone material properties remains inconclusive

The effect of advanced glycation endproduct accumulation on bone

Diabetes is associated with increased fracture risk, which leads to increased morbidity and eventual mortality with a substantial financial burden. Type 2 Diabetics also have increased fracture risk, despite having the same or higher BMD as non-diabetics with a low fracture risk. One hypothesis for this is increased modifications made to the extra-cellular matrix via non-enzymatic glycation (NEG) that can occur in a hyperglycemic environment, such as with diabetes. The accumulation of NEG products, known as advanced glycation endproducts (AGEs) can possibly lead to microdamage and eventual weakening of the bone itself. We developed a time-response model in order to induce a wide range of AGEs in a manner that would sustain the mineral integrity of the bone and could be applied to a variety of bone sample types. This was performed on 65 rat tibias, distributed amongst 8 groups (3,7,10, & 14 days) for both ribose and control. Secondly, the protocol was performed on human cortical beam samples cut from 10 donor tibias with 3,5 and 7 day time points for ribose and control groups. All samples were incubated in a 0.6 M ribose solution or 0.0 M ribose control solution. There was a 7, 4, and 5-fold increase in AGEs at the 7, 10, and 14 day time points respectively over controls in the rat tibia study. There was no significant variation in cortical porosity, however TTMD was significantly less dense in the 14-day ribose treated groups. There was a trend toward higher AGEs with time in the human cortical beam specimens, but no significant increase. The AGEs values in the human cortical beam specimens were much lower than expected based on previous trials and reports in the literature. We were able to establish a time-response model for AGE accumulation in bone. However, the effects of AGEs on bone material properties remains inconclusive

Kinetics of Topological Stone-Wales Defect Formation in Single Walled Carbon

Topological Stone-Wales defect in carbon nanotubes plays a central role in plastic deformation, chemical functionalization, and superstructure formation. Here, we systematically investigate the formation kinetics of such defects within density functional approach coupled with the transition state theory. We find that both the formation and activation energies depend critically on the nanotube chairality, diameter, and defect orientation. The microscopic origin of the observed dependence is explained with curvature induced rehybridization in nanotube. Surprisingly, the kinetic barrier follows an empirical Br{\o}nsted-Evans-Polanyi type correlation with the corresponding formation energy, and can be understood in terms of overlap between energy-coordinate parabolas representing the structures with and without the defect. Further, we propose a possible route to substantially decrease the kinetic activation barrier. Such accelerated rates of defect formation are desirable in many novel electronic, mechanical and chemical applications, and also facilitate the formation of three-dimensional nanotube superstructures.Comment: 10 pages, Supporting information, The Journal of Physical Chemistry C (2015

Flexicurity in the European Union: flexibility for outsiders, security for insiders

Flexicurity is at the heart of European policy debates. Its aim is to overcome the tensions between labour market flexibility on the one hand, and the provision of social security for workers on the other hand. To date, there is little insight into whether flexicurity policies have been adopted across the European Union. Therefore, the aim of this paper is to analyse to what extent labour market policies have been reformed along the lines of the flexicurity concept across 18 European countries over the period 1985-2008. Focusing on the main axes of the flexicurity concept, new datasets are used to examine changes in employment protection legislation, unemployment benefits and active labour market policies. Data on the strictness of employment regulation indicate that reforms have been influenced by labour market insiders, since the level of flexibility has been increased more for temporary employment, the labour market outsiders, than for regular employment, the insiders. Although gross unemployment replacement rates suggest that unemployment benefits have become more generous, net replacement rates indicate that the level of income security from benefits actually has been decreased. Moreover, data illustrate that larger shares of European labour forces have temporary contracts. As such, the gap between insiders and outsiders on the labour market has been increased. This development is contrary to the goals of the European Commission.Flexicurity, insider-outsider theory, labour market policy, welfare state, political economy

Global Tactical Cross-Asset Allocation: Applying Value and Momentum Across Asset Classes

In this paper we examine global tactical asset allocation (GTAA) strategies across a broad range of asset classes. Contrary to market timing for single asset classes and tactical allocation across similar assets, this topic has received little attention in the existing literature. Our main finding is that momentum and value strategies applied to GTAA across twelve asset classes deliver statistically and economically significant abnormal returns. For a long top-quartile and short bottom-quartile portfolio based on a combination of momentum and value signals we find a return of 12% per annum over the 1986-2007 period. Performance is stable over time, also present in an out-of-sample period and sufficiently high to overcome transaction costs in practice. The return cannot be explained by potential structural biases towards asset classes with high risk premiums, nor the Fama French and Carhart hedge factors. We argue that financial markets may be macro inefficient due to insufficient ‘smart money’ being available to arbitrage mispricing effects away.momentum;GTAA;global asset allocation;value effect