Nanomechanics of the endothelial glycocalyx in experimental sepsis

The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the luminal side of the endothelium, regulates vascular adhesiveness and permeability. Although central to the pathophysiology of vascular barrier dysfunction in sepsis, glycocalyx damage has been generally understudied, in part because of the aberrancy of in vitro preparations and its degradation during tissue handling. The aim of this study was to analyze inflammation-induced damage of the eGC on living endothelial cells by atomic-force microscopy (AFM) nanoindentation technique. AFM revealed the existence of a mature eGC on the luminal endothelial surface of freshly isolated rodent aorta preparations ex vivo, as well as on cultured human pulmonary microvascular endothelial cells (HPMEC) in vitro. AFM detected a marked reduction in glycocalyx thickness (266 ± 12 vs. 137 ± 17 nm, P<0.0001) and stiffness (0.34 ± 0.03 vs. 0.21 ± 0.01 pN/mn, P<0.0001) in septic mice (1 mg E. coli lipopolysaccharides (LPS)/kg BW i.p.) compared to controls. Corresponding in vitro experiments revealed that sepsis-associated mediators, such as thrombin, LPS or Tumor Necrosis Factor-α alone were sufficient to rapidly decrease eGC thickness (-50%, all P<0.0001) and stiffness (-20% P<0.0001) on HPMEC. In summary, AFM nanoindentation is a promising novel approach to uncover mechanisms involved in deterioration and refurbishment of the eGC in sepsis

Evolution of the fishtail-effect in pure and Ag-doped MG-YBCO

We report on magnetic measurements carried out in a textured YBa$_2$Cu$_3$O$_{7-\delta}$ and YBa$_2$(Cu$_{1-x}$Ag$_x$)$_3$O$_{7-\delta}$ (at $x \approx$ 0.02) crystals. The so-called fishtail-effect (FE) or second magnetization peak has been observed in a wide temperature range 0.4~$<T/T_c<$~0.8 for $\textbf{H}\parallel c$. The origin of the FE arises for the competition between surface barrier and bulk pinning. This is confirmed in a non-monotonically behavior of the relaxation rate $R$. The value $H_{max}$ for Ag-doped crystals is larger than for the pure one due to the presence of additional pinning centers, above all on silver atoms.Comment: 6 pages, 6 figure

Whole-body vibration training induces hypertrophy of the human patellar tendon

I Brage finner du siste tekst-versjon av artikkelen, og den kan inneholde ubetydelige forskjeller fra forlagets pdf-versjon. Forlagets pdf-versjon finner du på onlinelibrary.wiley.com / In Brage you'll find the final text version of the article, and it may contain insignificant differences from the journal's pdf version. The definitive version is available at onlinelibrary.wiley.comAnimal studies suggest that regular exposure to whole-body vibration (WBV) induces an anabolic response in bone and tendon. However, the effects of this type of intervention on human tendon properties and its influence on the muscle-tendon unit function have never been investigated. The aim of this study was to investigate the effect of WBV training on the patellar tendon mechanical, material and morphological properties, the quadriceps muscle architecture and the knee extension torque–angle relationship. Fifty-five subjects were randomized into either a vibration, an active control, or an inactive control group. The active control subjects performed isometric squats on a vibration platform without vibration. Muscle and tendon properties were measured using ultrasonography and dynamometry. Vibration training induced an increase in proximal (6.3%) and mean (3.8%) tendon cross-sectional area, without any appreciable change in tendon stiffness and modulus or in muscle architectural parameters. Isometric torque at a knee angle of 90° increased in active controls (6.7%) only and the torque–angle relation remained globally unchanged in all groups. The present protocol did not appreciably alter knee extension torque production or the musculo-tendinous parameters underpinning this function. Nonetheless, this study shows for the first time that WBV elicits tendon hypertrophy in humans.Seksjon for fysisk prestasjonsevne / Department of Physical Performanc

Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group

Background: Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood-brain barrier has demonstrated preclinical activity in glioma models. Patients and methods: Patients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m2 over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points. Results: Thirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3-18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3-12.3), with a 1-year survival rate of 31.6% (95% CI 17.7-46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination. Conclusions: No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administratio

A Study of the PDGF Signaling Pathway with PRISM

In this paper, we apply the probabilistic model checker PRISM to the analysis of a biological system -- the Platelet-Derived Growth Factor (PDGF) signaling pathway, demonstrating in detail how this pathway can be analyzed in PRISM. We show that quantitative verification can yield a better understanding of the PDGF signaling pathway.Comment: In Proceedings CompMod 2011, arXiv:1109.104

Ultra thin polymer foil cryogenic window for antiproton deceleration and storage

We present the design and characterisation of a cryogenic window based on an ultra-thin aluminised PET foil at T < 10K, which can withstand a pressure difference larger than 1bar at a leak rate < $1\times 10^{-9}$ mbar$\cdot$ l/s. Its thickness of approximately 1.7 $\mu$m makes it transparent to various types of particles over a broad energy range. To optimise the transfer of 100keV antiprotons through the window, we tested the degrading properties of different aluminium coated PET foils of thicknesses between 900nm and 2160nm, concluding that 1760nm foil decelerates antiprotons to an average energy of 5 keV. We have also explicitly studied the permeation as a function of coating thickness and temperature, and have performed extensive thermal and mechanical endurance and stress tests. Our final design integrated into the experiment has an effective open surface consisting of 7 holes with 1 mm diameter and will transmit up to 2.5% of the injected 100keV antiproton beam delivered by the AD/ELENA-facility of CERN

Ultra-thin polymer foil cryogenic window for antiproton deceleration and storage

We present the design and characterization of a cryogenic window based on an ultra-thin aluminized biaxially oriented polyethylene terephthalate foil at T < 10 K, which can withstand a pressure difference larger than 1 bar at a leak rate < 1 × 1 0 − 9 mbar l/s. Its thickness of ∼1.7 μm makes it transparent to various types of particles over a broad energy range. To optimize the transfer of 100 keV antiprotons through the window, we tested the degrading properties of different aluminum coated polymer foils of thicknesses between 900 and 2160 nm, concluding that 1760 nm foil decelerates antiprotons to an average energy of 5 keV. We have also explicitly studied the permeation as a function of coating thickness and temperature and have performed extensive thermal and mechanical endurance and stress tests. Our final design integrated into the experiment has an effective open surface consisting of seven holes with a diameter of 1 mm and will transmit up to 2.5% of the injected 100 keV antiproton beam delivered by the Antiproton Decelerator and Extra Low ENergy Antiproton ring facility of CERN

The Large Enriched Germanium Experiment for Neutrinoless Double Beta Decay (LEGEND)

The observation of neutrinoless double-beta decay (0${\nu}{\beta}{\beta}$) would show that lepton number is violated, reveal that neutrinos are Majorana particles, and provide information on neutrino mass. A discovery-capable experiment covering the inverted ordering region, with effective Majorana neutrino masses of 15 - 50 meV, will require a tonne-scale experiment with excellent energy resolution and extremely low backgrounds, at the level of $\sim$0.1 count /(FWHM$\cdot$t$\cdot$yr) in the region of the signal. The current generation $^{76}$Ge experiments GERDA and the MAJORANA DEMONSTRATOR utilizing high purity Germanium detectors with an intrinsic energy resolution of 0.12%, have achieved the lowest backgrounds by over an order of magnitude in the 0${\nu}{\beta}{\beta}$ signal region of all 0${\nu}{\beta}{\beta}$ experiments. Building on this success, the LEGEND collaboration has been formed to pursue a tonne-scale $^{76}$Ge experiment. The collaboration aims to develop a phased 0${\nu}{\beta}{\beta}$ experimental program with discovery potential at a half-life approaching or at $10^{28}$ years, using existing resources as appropriate to expedite physics results.Comment: Proceedings of the MEDEX'17 meeting (Prague, May 29 - June 2, 2017

The first search for bosonic super-WIMPs with masses up to 1 MeV/c2^2 with GERDA

We present the first search for bosonic super-WIMPs as keV-scale dark matter candidates performed with the GERDA experiment. GERDA is a neutrinoless double-beta decay experiment which operates high-purity germanium detectors enriched in $^{76}$Ge in an ultra-low background environment at the Laboratori Nazionali del Gran Sasso (LNGS) of INFN in Italy. Searches were performed for pseudoscalar and vector particles in the mass region from 60 keV/c$^2$ to 1 MeV/c$^2$. No evidence for a dark matter signal was observed, and the most stringent constraints on the couplings of super-WIMPs with masses above 120 keV/c$^2$ have been set. As an example, at a mass of 150 keV/c$^2$ the most stringent direct limits on the dimensionless couplings of axion-like particles and dark photons to electrons of $g_{ae} < 3 \cdot 10^{-12}$ and ${\alpha'}/{\alpha} < 6.5 \cdot 10^{-24}$ at 90% credible interval, respectively, were obtained.Comment: 6 pages, 3 figures, submitted to Physical Review Letters, added list of authors, updated ref. [21