Interleukin-1 receptor accessory protein blockade limits the development of atherosclerosis and reduces plaque inflammation

The interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor required for signalling through the IL-1, IL-33, and IL-36 receptors. Using a novel anti-IL1RAP-blocking antibody, we investigated the role of IL1RAP in atherosclerosis.Single-cell RNA sequencing data from human atherosclerotic plaques revealed the expression of IL1RAP and several IL1RAP-related cytokines and receptors, including IL1B and IL33. Histological analysis showed the presence of IL1RAP in both the plaque and adventitia, and flow cytometry of murine atherosclerotic aortas revealed IL1RAP expression on plaque leucocytes, including neutrophils and macrophages. High-cholesterol diet fed apolipoprotein E-deficient (Apoe-/-) mice were treated with a novel non-depleting IL1RAP-blocking antibody or isotype control for the last 6 weeks of diet. IL1RAP blockade in mice resulted in a 20% reduction in subvalvular plaque size and limited the accumulation of neutrophils and monocytes/macrophages in plaques and of T cells in adventitia, compared with control mice. Indicative of reduced plaque inflammation, the expression of several genes related to leucocyte recruitment, including Cxcl1 and Cxcl2, was reduced in brachiocephalic arteries of anti-IL1RAP-treated mice, and the expression of these chemokines in human plaques was mainly restricted to CD68+ myeloid cells. Furthermore, in vitro studies demonstrated that IL-1, IL-33, and IL-36 induced CXCL1 release from both macrophages and fibroblasts, which could be mitigated by IL1RAP blockade.Limiting IL1RAP-dependent cytokine signalling pathways in atherosclerotic mice reduces plaque burden and plaque inflammation, potentially by limiting plaque chemokine production.Biopharmaceutic

Guiding the deposition flux in an ionized magnetron discharge

A study of the ability to control the deposition flux in a high power impulse magnetron sputtering discharge using an external magnetic field is presented in this article. Pulses with peak power of 1.4 kWcm-2 were applied to a conventional planar magnetron equipped with an Al target. The high power creates a high degree of ionization of the sputtered material, which opens for an opportunity to control of the energy and direction of the deposition species. An external magnetic field was created with a current carrying coil placed in front of the target. To measure the distribution of deposition material samples were placed in an array surrounding the target and the depositions were made with and without the external magnetic field. The distribution is significantly changed when the magnetic field is present. An increase of 80 % in deposition rate is observed for the sample placed in the central position (right in front of the target center) and the deposition rate is strongly decreased on samples placed to the side of the target. The measurements were also performed on a conventional direct current magnetron discharge, but no major effect of the magnetic field was observed in that case.Original publication: J. Bohlmark, M. Östbye, M. Lattemann, H. Ljungcrantz, T. Rosell, and U. Helmersson, Guiding the deposition flux in an ionized magnetron discharge, 2006, Thin Solid Films, (515), 4, 1928-1931. http://dx.doi.org/10.1016/j.tsf.2006.07.183. Copyright: Elsevier B.V., http://www.elsevier.com/</p

Conductive nanocomposite ceramics as tribological and electrical contact materials

Conductive ceramics have widespread use in many industrial applications. One important application for such materials is electrical contact technology. Over the last few years, a new class of nanocomposite ceramic thin film materials has been developed with contact coatings as one key objective. This family of materials has proven to combine the favorable contact properties of metals, such as low electrical and thermal resistivity, and high ductility, with those of ceramics such as low friction and wear rate, high chemical integrity and good high-temperature properties. Furthermore, it is also found that the tribological properties of such materials can be tailored by alloying thus creating a triboactive system. The technology is now industrialized, and a practical example of a contact system utilizing a nanocomposite coating for improved performance is given

Microstructure evolution of Ti-Si-C-Ag nanocomposite coatings deposited by DC magnetron sputtering

Nanocomposite coatings consisting of Ag and TiCx (x andlt; 1) crystallites in a matrix of amorphous SiC were deposited by high-rate magnetron sputtering from Ti-Si-C-Ag compound targets. Different target compositions were used to achieve coatings with a Si content of similar to 13 at.%, while varying the C/Ti ratio and Ag content. Electron microscopy, helium ion microscopy, X-ray photoelectron spectroscopy and X-ray diffraction were employed to trace Ag segregation during deposition and possible decomposition of amorphous SiC. Eutectic interaction between Ag and Si is observed, and the Ag forms threading grains which coarsen with increased coating thickness. The coatings can be tailored for conductivity horizontally or vertically by controlling the shape and distribution of the Ag precipitates. Coatings were fabricated with hardness in the range 10-18 GPa and resistivity in the range 77-142 mu Omega cm.Original Publication:Jonas Lauridsen, Per Eklund, Jens Jensen, H Ljungcrantz, A Oberg, E Lewin, U Jansson, A Flink, H Hogberg and Lars Hultman, Microstructure evolution of Ti-Si-C-Ag nanocomposite coatings deposited by DC magnetron sputtering, 2010, ACTA MATERIALIA, (58), 20, 6592-6599.http://dx.doi.org/10.1016/j.actamat.2010.08.018Copyright: Elsevier Science B.V., Amsterdam.http://www.elsevier.com

Structural basis for substrate specificities of cellular deoxyribonucleoside kinases

Deoxyribonucleoside kinases phosphorylate deoxyribonucleosides and activate a number of medically important nucleoside analogs. Here we report the structure of the Drosophila deoxyribonucleoside kinase with deoxycytidine bound at the nucleoside binding site and that of the human deoxyguanosine kinase with ATP at the nucleoside substrate binding site. Compared to the human kinase, the Drosophila kinase has a wider substrate cleft, which may be responsible for the broad substrate specificity of this enzyme. The human deoxyguanosine kinase is highly specific for purine substrates; this is apparently due to the presence of Arg 118, which provides favorable hydrogen bonding interactions with the substrate. The two new structures provide an explanation for the substrate specificity of cellular deoxyribonucleoside kinases

Transforming U.S. Healthcare: Integrating Health Law, Medicine, and Business Solutions

Deborah German, Dean, College of Medicine, University of Central Florida • Jeanette Schreiber, Associate Dean, College of Medicine, University of Central Florida • Ashley Bacot, Risk Manager, Rosen Hotel