Driven by the CMB temperature-redshift (T -z) relation as demanded by deconfining SU(2) Yang-Mills thermodynamics, an according cosmological model is proposed and analysed. This model -SU(2) cmb -exhibits a dark sector, representing ΛCDM with a certain late-time dark-matter density which transitions to a reduced (present-day) density parameter at high z. We statistically analyse constraints on cosmological parameters directly imposed by the values of the standard co-moving ruler r d and the angular size of the sound horizon θ * . Compared to the ΛCDM best fit to 2015 Planck data, we require an increased (present-day) dark matter density when r d · H 0 = const and a value H 0 ∼ 73.5 km s −1 Mpc −1 -typical for local extractions -are used. The ratio between the density parameters of primordial and late-time dark matter ranges between 0.5 and 0.7. We confirm this trend by fitting the predictions of SU(2) cmb , obtained from a modified CLASS code, to the angular power spectra TT, TE, and EE. We consider adiabatic, scalar primordial curvature perturbations and distinguish two treatments of thermal quasi-particles in the perturbation equations. Best fits predict a red-tilted primordial power spectrum. Moreover, a low baryon density is obtained compared with the coincidence value of BBN, the ΛCDM best fit of the 2015 Planck data, and the observed deuterium abundance. Our derived values of H 0 support the results of local cosmological observations. Also, there is a tendency for late reionisation. Pdflatex could not properly compile abstracts with less than

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Mitochondrial dysfunction is increasingly recognized as a contributor to age-related muscle loss and functional impairment. Therefore, we developed a high throughput screening strategy that enabled the identification of compounds boosting mitochondrial energy production in a human skeletal muscle cell model. Screening of 7949 pure natural products revealed 22 molecules that significantly increased oxygen consumption and ATP levels in myotubes. One of the most potent compounds was the flavanone hesperetin. Hesperetin (10 µM) increased intracellular ATP by 33% and mitochondrial spare capacity by 25%. Furthermore, the compound reduced oxidative stress in primary myotubes as well as muscle tissue in vivo. In aged mice administration of hesperetin (50 mg/kg/d) completely reverted the age-related decrease of muscle fiber size and improved running performance of treated animals. These results provide a novel screening platform for the discovery of drugs that can improve skeletal muscle function in patients suffering from sarcopenia or other disorders associated with mitochondrial dysfunction.

We present a hybrid single-molecule technique combining magnetic tweezers and Förster resonance energy transfer (FRET) measurements. Through applying external forces to a paramagnetic sphere, we induce conformational changes in DNA nanostructures, which are detected in two output channels simultaneously. First, by tracking a magnetic bead with high spatial and temporal resolution, we observe overall DNA length changes along the force axis. Second, the measured FRET efficiency between two fluorescent probes monitors local conformational changes. The synchronized orthogonal readout in different observation channels will facilitate deciphering the complex mechanisms of biomolecular machines.

Dual-target inhibitors gained increased attention in the past years. A novel in silico approach was employed for the discovery of dual 5-lipoxygenase/soluble epoxide hydrolase inhibitors. The ligand-based approach uses excessive pharmacophore elucidation and pharmacophore alignment in conjunction with shape-based scoring. The virtual screening results were verified in vitro, leading to nine novel inhibitors including a dual-target compound.

More than half a century after the discovery of ultra-high energy cosmic rays (UHECRs), their origin is still an open question. The study of anisotropies in the arrival directions of such particles is an essential ingredient to solve this puzzle. We update our previous analysis of large-scale anisotropies observed by the Pierre Auger Observatory using the latest data collected before the AugerPrime upgrade. We select events with zenith angles up to 80 degrees, implying a sky coverage of 85%, and energies above 4 EeV, for which the surface detector of the Observatory is fully efficient. Dipolar and quadrupolar amplitudes are evaluated through a combined Fourier analysis of the event count rate in right ascension and azimuth. The analysis is performed in three energy bins with boundaries at 4, 8, 16 and 32 EeV and two additional cumulative bins with energies above 8 and 32 EeV. The most significant signal is a dipolar modulation in right ascension for energies above 8 EeV, as previously reported, with statistical significance of 6.6 . Additionally, we report the measurements of the angular power spectrum for the same energy bins with the same dataset.

Current research leads to the assumption that drugs affecting more than one target could result in a more efficient treatment of diseases and fewer safety concerns. Administration of drugs inhibiting only one branch of the arachidonic acid cascade is usually accompanied by side effects. We therefore designed and synthesized a library of hybrid molecules incorporating an imidazo[1,2-a]pyridine and an urea moiety as novel soluble epoxide hydrolase (sEH)/5-lipoxygenase (5-LO) dual inhibitors. Evaluation of the compounds was accomplished by in vitro testing using recombinant enzyme assays.

In this work we present the interpretation of the energy spectrum and mass composition data as measured by the Pierre Auger Collaboration above 6 × 1017 eV. We use an astrophysical model with two extragalactic source populations to model the hardening of the cosmic-ray flux at around 5 × 1018 eV (the so-called “ankle” feature) as a transition between these two components. We find our data to be well reproduced if sources above the ankle emit a mixed composition with a hard spectrum and a low rigidity cutoff. The component below the ankle is required to have a very soft spectrum and a mix of protons and intermediate-mass nuclei. The origin of this intermediate-mass component is not well constrained and it could originate from either Galactic or extragalactic sources. To the aim of evaluating our capability to constrain astrophysical models, we discuss the impact on the fit results of the main experimental systematic uncertainties and of the assumptions about quantities affecting the air shower development as well as the propagation and redshift distribution of injected ultra-high-energy cosmic rays (UHECRs).