327 research outputs found
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
YBaCuO and YBa(CuAg)O (at
0.02) crystals. The so-called fishtail-effect (FE) or second
magnetization peak has been observed in a wide temperature range
0.4~~0.8 for . 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 . The value
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
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 False Start in the Race Against Doping in Sport: Concerns With Cycling’s Biological Passport
Professional cycling has suffered from a number of doping scandals. The sport’s governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling’s biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist’s system. Instead, the biological passport tracks biological variables in a cyclist’s blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports
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
The Large Enriched Germanium Experiment for Neutrinoless Double Beta Decay (LEGEND)
The observation of neutrinoless double-beta decay (0)
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
0.1 count /(FWHMtyr) in the region of the signal. The
current generation 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 signal region of all 0
experiments. Building on this success, the LEGEND collaboration has been formed
to pursue a tonne-scale Ge experiment. The collaboration aims to develop
a phased 0 experimental program with discovery potential
at a half-life approaching or at years, using existing resources as
appropriate to expedite physics results.Comment: Proceedings of the MEDEX'17 meeting (Prague, May 29 - June 2, 2017
Flux Modulations seen by the Muon Veto of the GERDA Experiment
The GERDA experiment at LNGS of INFN is equipped with an active muon veto.
The main part of the system is a water Cherenkov veto with 66~PMTs in the water
tank surrounding the GERDA cryostat. The muon flux recorded by this veto shows
a seasonal modulation. Two effects have been identified which are caused by
secondary muons from the CNGS neutrino beam (2.2 %) and a temperature
modulation of the atmosphere (1.4 %). A mean cosmic muon rate of /(sm) was found in good agreement with other experiments at
LNGS at a depth of 3500~meter water equivalent.Comment: 7 pages, 6 figure
Hyperfine spectroscopy of hydrogen and antihydrogen in ASACUSA
The ASACUSA collaboration at the Antiproton Decelerator of CERN aims at a
precise measurement of the antihydrogen ground-state hyperfine structure as a
test of the fundamental CPT symmetry. A beam of antihydrogen atoms is formed in
a CUSP trap, undergoes Rabi-type spectroscopy and is detected downstream in a
dedicated antihydrogen detector. In parallel measurements using a polarized
hydrogen beam are being performed to commission the spectroscopy apparatus and
to perform measurements of parameters of the Standard Model Extension (SME).
The current status of antihydrogen spectroscopy is reviewed and progress of
ASACUSA is presented.Comment: Proceedings of the 7th International Syposium on Symmetries in
Subatomic Physics SSP2018, Aachen (Germany), 10 - 15 Jun 2018. Corrected
error in Fig. 1, updated caption, add titles to reference
Limit on the Radiative Neutrinoless Double Electron Capture of Ar from GERDA Phase I
Neutrinoless double electron capture is a process that, if detected, would
give evidence of lepton number violation and the Majorana nature of neutrinos.
A search for neutrinoless double electron capture of Ar has been
performed with germanium detectors installed in liquid argon using data from
Phase I of the GERmanium Detector Array (GERDA) experiment at the Gran Sasso
Laboratory of INFN, Italy. No signal was observed and an experimental lower
limit on the half-life of the radiative neutrinoless double electron capture of
Ar was established: 3.6 10 yr at 90 % C.I.Comment: 7 pages, 3 figure
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