Fine-tuning of substrate architecture and surface chemistry promotes muscle tissue development

Tissue engineering has been increasingly brought to the scientific spotlight in response to the tremendous demand for regeneration, restoration or substitution of skeletal or cardiac muscle after traumatic injury, tumour ablation or myocardial infarction. In vitro generation of a highly organized and contractile muscle tissue, however, crucially depends on an appropriate design of the cell culture substrate. The present work evaluated the impact of substrate properties, in particular morphology, chemical surface composition and mechanical properties, on muscle cell fate. To this end, aligned and randomly oriented micron (3.3±0.8 μm) or nano (237±98 nm) scaled fibrous poly(ε-caprolactone) non-wovens were processed by electrospinning. A nanometer-thick oxygen functional hydrocarbon coating was deposited by a radio frequency plasma process. C2C12 muscle cells were grown on pure and as-functionalized substrates and analysed for viability, proliferation, spatial orientation, differentiation and contractility. Cell orientation has been shown to depend strongly on substrate architecture, being most pronounced on micron-scaled parallel-oriented fibres. Oxygen functional hydrocarbons, representing stable, non-immunogenic surface groups, were identified as strong triggers for myotube differentiation. Accordingly, the highest myotube density (28±15% of total substrate area), sarcomeric striation and contractility were found on plasma-coated substrates. The current study highlights the manifold material characteristics to be addressed during the substrate design process and provides insight into processes to improve bio-interfaces.

Measurement of the W+ W- cross section in sqrt(s) = 7 TeV pp collisions with ATLAS

This Letter presents a measurement of the W+ W- production cross section in sqrt(s) = 7  TeV pp collisions by the ATLAS experiment, using 34  pb(-1) of integrated luminosity produced by the Large Hadron Collider at CERN. Selecting events with two isolated leptons, each either an electron or a muon, 8 candidate events are observed with an expected background of 1.7 ± 0.6 events. The measured cross section is 41(-16)(+20)(stat) ± 5(syst)±1(lumi)  pb, which is consistent with the standard model prediction of 44 ± 3  pb calculated at next-to-leading order in QCD.

Search for a heavy particle decaying into an electron and a muon with the ATLAS detector in sqrt[s] = 7 TeV pp collisions at the LHC

This Letter presents the first search for a heavy particle decaying into an e ± μ(-/+) final state in sqrt[s] = 7 TeV pp collisions at the LHC. The data were recorded by the ATLAS detector during 2010 and correspond to a total integrated luminosity of 35 pb(-1). No excess above the standard model background expectation is observed. Exclusions at 95% confidence level are placed on two representative models. In an R-parity violating supersymmetric model, tau sneutrinos with a mass below 0.75 TeV are excluded, assuming all R-parity violating couplings are zero except λ(311)' = 0.11 and λ312 = 0.07. In a lepton flavor violating model, a Z'-like vector boson with masses of 0.70-1.00 TeV and corresponding cross sections times branching ratios of 0.175-0.183 pb is excluded. These results extend to higher mass R-parity violating sneutrinos and lepton flavor violating Z's than previous constraints from the Tevatron.

Measurement of dijet azimuthal decorrelations in pp collisions at sqrt(s)=7 TeV

Azimuthal decorrelations between the two central jets with the largest transverse momenta are sensitive to the dynamics of events with multiple jets. We present a measurement of the normalized differential cross section based on the full data set (∫Ldt=36  pb(-1)) acquired by the ATLAS detector during the 2010 sqrt(s)=7  TeV proton-proton run of the LHC. The measured distributions include jets with transverse momenta up to 1.3 TeV, probing perturbative QCD in a high-energy regime.

Search for supersymmetry using final states with one lepton, jets, and missing transverse momentum with the ATLAS detector in √s=7 TeV pp collisions

This Letter presents the first search for supersymmetry in final states containing one isolated electron or muon, jets, and missing transverse momentum from √s=7  TeV proton-proton collisions at the LHC. The data were recorded by the ATLAS experiment during 2010 and correspond to a total integrated luminosity of 35  pb(-1). No excess above the standard model background expectation is observed. Limits are set on the parameters of the minimal supergravity framework, extending previous limits. Within this framework, for A(0)=0 GeV, tanβ=3, and μ>0 and for equal squark and gluino masses, gluino masses below 700 GeV are excluded at 95% confidence level.

Search for diphoton events with large missing transverse energy in 7 TeV proton-proton collisions with the ATLAS detector

A search for diphoton events with large missing transverse energy is presented. The data were collected with the ATLAS detector in proton-proton collisions at √s=7 TeV at the CERN Large Hadron Collider and correspond to an integrated luminosity of 3.1 pb⁻¹. No excess of such events is observed above the standard model background prediction. In the context of a specific model with one universal extra dimension with compactification radius R and gravity-induced decays, values of 1/R<729 GeV are excluded at 95% C. L., providing the most sensitive limit on this model to date.

Search for a standard model Higgs boson in the H→ZZ→ℓ(+)ℓ(-)νν decay channel with the ATLAS detector

A search for a heavy standard model Higgs boson decaying via H→ZZ→→ℓ(+)ℓ(-)νν, where ℓ=e, μ, is presented. It is based on proton-proton collision data at √s=7 TeV, collected by the ATLAS experiment at the LHC in the first half of 2011 and corresponding to an integrated luminosity of 1.04 fb(-1). The data are compared to the expected standard model backgrounds. The data and the background expectations are found to be in agreement and upper limits are placed on the Higgs boson production cross section over the entire mass window considered; in particular, the production of a standard model Higgs boson is excluded in the region 340

Fingerprints of changes in the terrestrial carbon cycle in response to large reorganizations in ocean circulation

CO2 and carbon cycle changes in the land, ocean and atmosphere are investigated using the comprehensive carbon cycle-climate model NCAR CSM1.4-carbon. Ensemble simulations are forced with freshwater perturbations applied at the North Atlantic and Southern Ocean deep water formation sites under pre-industrial climate conditions. As a result, the Atlantic Meridional Overturning Circulation reduces in each experiment to varying degrees. The physical climate fields show changes qualitatively in agreement with results documented in the literature, but there is a clear distinction between northern and southern perturbations. Changes in the physical variables, in turn, affect the land and ocean biogeochemical cycles and cause a reduction, or an increase, in the atmospheric CO2 concentration by up to 20 ppmv, depending on the location of the perturbation. In the case of a North Atlantic perturbation, the land biosphere reacts with a strong reduction in carbon stocks in some tropical locations and in high northern latitudes. In contrast, land carbon stocks tend to increase in response to a southern perturbation. The ocean is generally a sink of carbon although large reorganizations occur throughout various basins. The response of the land biosphere is strongest in the tropical regions due to a shift of the Intertropical Convergence Zone. The carbon fingerprints of this shift, either to the south or to the north depending on where the freshwater is applied, can be found most clearly in South America. For this reason, a compilation of various paleoclimate proxy records of Younger Dryas precipitation changes are compared with our model results. The proxy records, in general, show good agreement with the model's response to a North Atlantic freshwater perturbation.

General Protocol for the Culture of Cells on Plasma-Coated Electrospun Scaffolds

As opposed to culture on standard tissue-treated plastic, cell culture on three-dimensional scaffolds impedes additional challenges with respect to substrate preparation, cell seeding, culture maintenance, and analysis. We herewith present a general route for the culture of primary cells, differentiated cells, or stem cells on plasma-coated, electrospun scaffolds. We describe a method to prepare and fix the scaffolds in culture wells and discuss a convenient method for cell seeding and subsequent analysis by scanning electron microscopy or immunohistology.

Anisotropically oriented electrospun matrices with an imprinted periodic micropattern: a new scaffold for engineered muscle constructs

Engineered muscle constructs provide a promising perspective on the regeneration or substitution of irreversibly damaged skeletal muscle. However, the highly ordered structure of native muscle tissue necessitates special consideration during scaffold development. Multiple approaches to the design of anisotropically structured substrates with grooved micropatterns or parallel-aligned fibres have previously been undertaken. In this study we report the guidance effect of a scaffold that combines both approaches, oriented fibres and a grooved topography. By electrospinning onto a topographically structured collector, matrices of parallel-oriented poly(ε-caprolactone) fibres with an imprinted wavy topography of 90 µm periodicity were produced. Matrices of randomly oriented fibres or parallel-oriented fibres without micropatterns served as controls. As previously shown, un-patterned, parallel-oriented substrates induced myotube orientation that is parallel to fibre direction. Interestingly, pattern addition induced an orientation of myotubes at an angle of 24° (statistical median) relative to fibre orientation. Myotube length was significantly increased on aligned micropatterned substrates in comparison to that on aligned substrates without pattern (436 ± 245 µm versus 365 ± 212 µm; p < 0.05). We report an innovative, yet simple, design to produce micropatterned electrospun scaffolds that induce an unexpected myotube orientation and an increase in myotube length.

The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study

During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses.

Urinary metabolites and antioxidant products of exogenous melatonin in the mouse

Exogenous melatonin is widely used for sleep disorders and has potential value in neuroprotection, cardioprotection and as an antioxidant. Here, a novel method is described for the determination of melatonin and six metabolites in mouse urine by use of LC-MS/MS and GC-MS. LC-MS/MS is used for the measurement of melatonin, N1-acetyl-5-methoxykynuramine (AMK), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and 6-hydroxymelatonin (6-HMEL), while GC/MS is used for the determination of N-[2-(5-methoxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide (2-OMEL) and cyclic 3-hydroxymelatonin (3-HMEL) with detection limits on column of 0.02-0.5 pmol, depending on the metabolite. Following oral administration of melatonin to mice, a 0-24 hr urine collection revealed the presence of melatonin (0.2% dose), 6-HMEL (37.1%) and NAS (3.1%) comprising >90% of the total metabolites; AMK and AFMK were also detected at 0.01% each; 2-OMEL was found at 2.2% of the dose, which is >100 times more than the AMK/AFMK pathway, and comprises >5% of the melatonin-related material detected in mouse urine. 3-HMEL was largely found as a sulfate conjugate. These studies establish sensitive assays for determination of six melatonin metabolites in mouse urine and confirm the potential for antioxidant activity of melatonin through the identification in vivo of AMK and AFMK, ring-opened metabolites with a high capacity for scavenging reactive oxygen species.