Endoluminal beta-radiation therapy for the prevention of coronary restenosis after balloon angioplasty.

BACKGROUND: Beta radiation is effective in reducing vascular neointimal proliferation in animals after injury caused by balloon angioplasty. However, the lowest dose that can prevent restenosis after coronary angioplasty has yet to be determined. METHODS: After successful balloon angioplasty of a previously untreated coronary stenosis, 181 patients were randomly assigned to receive 9, 12, 15, or 18 Gy of radiation delivered by a centered yttrium-90 source. Adjunctive stenting was required in 28 percent of the patients. The primary end point was the minimal luminal diameter six months after treatment, as a function of the delivered dose of radiation. RESULTS: At the time of follow-up coronary angiography, the mean minimal luminal diameter was 1.67 mm in the 9-Gy group, 1.76 mm in the 12-Gy group, 1.83 mm in the 15-Gy group, and 1.97 mm in the 18-Gy group (P=0.06 for the comparison of 9 Gy with 18 Gy), resulting in restenosis rates of 29 percent, 21 percent, 16 percent, and 15 percent, respectively (P=0.14 for the comparison of 9 Gy with 18 Gy). At that time, 86 percent of the patients had had no serious cardiac events. In 130 patients treated with balloon angioplasty alone, restenosis rates were 28 percent, 17 percent, 16 percent, and 4 percent, respectively (P=0.02 for the comparison of 9 Gy with 18 Gy). Among these patients, there was a dose-dependent enlargement of the lumen in 28 percent, 50 percent, 45 percent, and 74 percent of patients, respectively (P<0.001 for the comparison of 9 Gy with 18 Gy). The rate of repeated revascularization was 18 percent with 9 Gy and 6 percent with 18 Gy (P=0.26). CONCLUSIONS: Intracoronary beta radiation therapy produces a significant dose-dependent decrease in the rate of restenosis after angioplasty. An 18-Gy dose not only prevents the renarrowing of the lumen typically observed after successful balloon angioplasty, but actually induces luminal enlargement

Chassis organism from Corynebacterium glutamicum – a top-down approach to identify and delete irrelevant gene clusters

Unthan S, Baumgart M, Radek A, et al. Chassis organism from Corynebacterium glutamicum – a top-down approach to identify and delete irrelevant gene clusters. Biotechnology Journal. 2015;10(2):290-301

Reduced proteasome activity in the aging brain results in ribosome stoichiometry loss and aggregation.

A progressive loss of protein homeostasis is characteristic of aging and a driver of neurodegeneration. To investigate this process quantitatively, we characterized proteome dynamics during brain aging in the short-lived vertebrate Nothobranchius furzeri combining transcriptomics and proteomics. We detected a progressive reduction in the correlation between protein and mRNA, mainly due to post-transcriptional mechanisms that account for over 40% of the age-regulated proteins. These changes cause a progressive loss of stoichiometry in several protein complexes, including ribosomes, which show impaired assembly/disassembly and are enriched in protein aggregates in old brains. Mechanistically, we show that reduction of proteasome activity is an early event during brain aging and is sufficient to induce proteomic signatures of aging and loss of stoichiometry in vivo. Using longitudinal transcriptomic data, we show that the magnitude of early life decline in proteasome levels is a major risk factor for mortality. Our work defines causative events in the aging process that can be targeted to prevent loss of protein homeostasis and delay the onset of age-related neurodegeneration

Hollow-core Optical Fiber Gas Lasers (HOFGLAS): a review [Invited]

International audienceThe development of hollow core photonic crystal fibers with low losses over a broad spectral region in the near IR enabled the demonstration of a novel laser type - Hollow-core Optical Fiber Gas Laser (HOFGLAS). The laser combines attractive features of fiber lasers such as compactness and long interaction length of pump and laser radiation with those of gas lasers such as the potential for high output power and narrow line width. This paper summarizes recent developments and describes the demonstration of C2H2 and HCN prototype lasers. Avenues to extend laser emission further into the IR are discussed

Simplified Models for LHC New Physics Searches

This document proposes a collection of simplified models relevant to the design of new-physics searches at the LHC and the characterization of their results. Both ATLAS and CMS have already presented some results in terms of simplified models, and we encourage them to continue and expand this effort, which supplements both signature-based results and benchmark model interpretations. A simplified model is defined by an effective Lagrangian describing the interactions of a small number of new particles. Simplified models can equally well be described by a small number of masses and cross-sections. These parameters are directly related to collider physics observables, making simplified models a particularly effective framework for evaluating searches and a useful starting point for characterizing positive signals of new physics. This document serves as an official summary of the results from the "Topologies for Early LHC Searches" workshop, held at SLAC in September of 2010, the purpose of which was to develop a set of representative models that can be used to cover all relevant phase space in experimental searches. Particular emphasis is placed on searches relevant for the first ~50-500 pb-1 of data and those motivated by supersymmetric models. This note largely summarizes material posted at http://lhcnewphysics.org/, which includes simplified model definitions, Monte Carlo material, and supporting contacts within the theory community. We also comment on future developments that may be useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results from "Topologies for Early LHC Searches" workshop (SLAC, September 2010). Supplementary material can be found at http://lhcnewphysics.or

Nanoclusters of the resting T cell antigen receptor (TCR) localize to non-raft domains

© 2014 Elsevier B.V. In the last decade an increasing number of plasma membrane (PM) proteins have been shown to be non-randomly distributed but instead forming submicron-sized oligomers called nanoclusters. Nanoclusters exist independently of the ligand-bound state of the receptors and their existence implies a high degree of lateral organisation of the PM and its proteins. The mechanisms that drive receptor nanoclustering are largely unknown. One well-defined example of a transmembrane receptor that forms nanoclusters is the T cell antigen receptor (TCR), a multisubunit protein complex whose nanoclustering influences its activity. Membrane lipids, namely cholesterol and sphingomyelin, have been shown to contribute to TCR nanoclustering. However, the identity of the membrane microdomain in which the TCR resides remains controversial. Using a GFP-labeled TCR we show here that the resting TCR localized in the disordered domain of giant PM vesicles (GPMVs) and PM spheres (PMSs) and that single and nanoclustered TCRs are found in the high-density fractions in sucrose gradients. Both findings are indicative of non-raft localization. We discuss possible mechanisms of TCR nanoclustering in T cells. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling.German Research Foundation (GSC-4, the Spemann Graduate School and EXC294, the BIOSS Center for Biological Signalling Studies, by the German Research Foundation grant SCH 976/2-1, and by the European Union through grant FP7/2007-2013 SYBILLAPeer Reviewe