Inhibitor of DNA binding 1 as a secreted angiogenic transcription factor in rheumatoid arthritis

Abstract Introduction Rheumatoid arthritis (RA) is characterized by enhanced blood vessel development in joint synovium. This involves the recruitment of endothelial progenitor cells (EPCs), allowing for de novo vessel formation and pro-inflammatory cell infiltration. Inhibitor of DNA Binding 1 (Id1) is a transcription factor characteristic of EPCs that influences cell maturation. Method Enzyme-linked immunosorbant assay (ELISA) and polymerase chain reaction (PCR) were used to examine Id1 levels in synovial fluid (SF) and endothelial cells (ECs), respectively. Immunohistology was used to determine the expression of Id1 in synovial tissue (ST). Human dermal microvascular EC (HMVEC) migration and tube forming assays were used to determine if recombinant human Id1 (rhuId1) and/or RA SF immunodepleted Id1 showed angiogenic activity. We also utilized the RA ST severe combined immunodeficient (SCID) mouse chimera to examine if Id1 recruits EPCs to RA synovium. Results ST samples immunostained for Id1 showed heightened expression in RA compared to osteoarthritis (OA) and normal (NL) ST. By immunofluorescence staining, we found significantly more Id1 in RA compared to OA and NL vasculature, showing that Id1 expressing cells, and therefore EPCs, are most active in vascular remodeling in the RA synovium. We also detected significantly more Id1 in RA compared to OA and other arthritis SFs by ELISA, which correlates highly with Chemokine (C-X-C motif) ligand 16 (CXCL16) levels. In vitro chemotaxis assays showed that Id1 is highly chemotactic for HMVECs and can be attenuated by inhibition of Nuclear Factor κB and phosphoinositide 3-kinase. Using in vitro Matrigel assays, we found that HMVECs form tubes in response to rhuId1 and that Id1 immunodepleted from RA SF profoundly decreases tube formation in Matrigel in vitro. PCR showed that Id1 mRNA could be up-regulated in EPCs compared to HMVECs in response to CXCL16. Finally, using the K/BxN serum induced arthritis model, we found that EC CXCR6 correlated with Id1 expression by immunohistochemistry. Conclusions We conclude that Id1 correlates highly with CXCL16 expression, EPC recruitment, and blood vessel formation in the RA joint, and that Id1 is potently angiogenic and can be up-regulated in EPCs by CXCL16.http://deepblue.lib.umich.edu/bitstream/2027.42/110805/1/13075_2013_Article_4258.pd

Evaluating Leniency with Missing Information on Undetected Cartels: Exploring Time-Varying Policy Impacts on Cartel Duration

This paper examines the effects of European Commission’s (EC) new leniency program on the EC’s capabilities in detecting and deterring cartels. As a supplementary analysis, the US leniency is studied. I discuss a dynamic model of cartel formation and dissolution to illustrate how changes in antitrust policies and economic conditions might affect cartel duration. Comparative statics results are then corroborated with empirical estimates of hazard functions adjusted to account for both the heterogeneity of cartels and the time-varying policy impacts suggested by theory. Contrary to earlier studies, my statistical tests are consistent with the theoretic predictions that following an efficacious leniency program, the average duration of discovered cartels rises in the short run and falls in the long run. The results shed light on the design of enforcement programs against cartels and other forms of conspiracy

Nitrile-assistant eutectic electrolytes for cryogenic operation of lithium ion batteries at fast charges and discharges

The charge/discharge characteristics of lithium ion batteries at low temperature (LT = -20 ??C) are enhanced by using ethylene carbonate (EC)-based electrolytes with the help of assistant solvents of nitriles. Conventional liquid electrolytes (e.g. a mixture of EC and dimethyl carbonate (DMC), abbreviated as LED) cannot support a satisfactory capacity at low temperature as well as at high rates even if electric vehicles require low-temperature operation. Introducing propionitrile or butyronitrile (Pn or Bn) into LED (resulting in LEDPn or LEDBn) as a co-solvent increases significantly the high-rate capacities at -20??C. For example, LEDPn delivers 62% of the available capacity at 1 C and 46% at 3 C with a 2.7 V cut-off while the control LED provides just 6% and 4% at the same rates. Successful operation at -20??C with nitrile-assistant electrolytes results from high ionic conductivity, low viscosity and freezing point depression caused by the eutectic behavior of the carbonates (EC/DMC) and Pn. Based on the phase diagram of Pn with EC/DMC, we expect a meaningful battery operation up to -110??C, probably lower, at the eutectic composition.close0

Graphene-Based Nanostructures in Electrocatalytic Oxygen Reduction

Application of graphene-type materials in electrocatalysis is a topic of growing scientific and technological interest. A tremendous amount of research has been carried out in the field of oxygen electroreduction, particularly with respect to potential applications in the fuel cell research also with use of graphene-type catalytic components. This work addresses fundamental aspects and potential applications of graphene structures in the oxygen reduction electrocatalysis. Special attention will be paid to creation of catalytically active sites by using non-metallic heteroatoms as dopants, formation of hierarchical nanostructured electrocatalysts, their long-term stability, and application as supports for dispersed metals (activating interactions)

"Subsidiarity, Federalism and Regulatory Competition: A Political Economy Perspective"

This paper shows different effects implied by the subsidiarity principle as viewed from a rational choice perspective. It is conceived as a survey of ideas and of relevant literature. The article gives an overview of theoretical approaches relevant to the issues which bridge the dichotomy of economics and of political science. A main focus is on the link between institutional features and policy outcomes. In this contribution, three main aspects of subsidiarity are looked at. Firstly, the allocation of decision-making power to lower political levels will have repercussions on the behavior of member states and on actors on the sub-national levels (such as national interest groups). In the absence of decisions by institutions of the Union, many policy areas will basically constitute collective action problems: mutually beneficial outcomes (or public goods) can only be secured if member states have no incentives to free ride and if special interest groups are prevented from obtaining benefits to the detriment of the "public interest". Such aspects are considered in Section II. Secondly, subsidiarity may lead to a redistribution of policy competences between the Union institutions and the member states. This has implications on the degree of centralization within the Union (and on political legitimacy). Very prominently, it may to a certain degree introduce competition between national bureaucracies. These issues are addressed in Section 111. Finally, enhanced legislative power for the member states will by necessity lead to the maintenance of a divergence in the laws and the regulations of member states with respect to several policy areas. From an economic perspective, within a common market framework, this implies that national rules and regulations will be in competition with each other -- an effect also provoked by the introduction of the "new approach" in the framework of the internal market program. Section IV provides an overview of theoretical approaches cornected to regulatory competition and illustrates selected evidence from EU practice