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Here we study links between aminoglycoside-induced mistranslation, protein misfolding and neuropathy. We demonstrate that aminoglycosides induce misreading in mammalian cells and assess endoplasmic reticulum (ER) stress and unfolded protein response (UPR) pathways. Genome-wide transcriptome and proteome analyses revealed upregulation of genes related to protein folding and degradation. Quantitative PCR confirmed induction of UPR markers including C/EBP homologous protein, glucose-regulated protein 94, binding immunoglobulin protein and X-box binding protein-1 (XBP1) mRNA splicing, which is crucial for UPR activation. We studied the effect of a compromised UPR on aminoglycoside ototoxicity in haploinsufficient XBP1 (XBP1 +/− ) mice. Intra-tympanic aminoglycoside treatment caused high-frequency hearing loss in XBP1 +/− mice but not in wild-type littermates. Densities of spiral ganglion cells and synaptic ribbons were decreased in gentamicin-treated XBP1 +/− mice, while sensory cells were preserved. Co-injection of the chemical chaperone tauroursodeoxycholic acid attenuated hearing loss. These results suggest that aminoglycoside-induced ER stress and cell death in spiral ganglion neurons is mitigated by XBP1, masking aminoglycoside neurotoxicity at the organismal level.

The four persistent radio sources in the northern sky with the highest flux density at metre wavelengths are Cassiopeia A, Cygnus A, Taurus A, and Virgo A; collectively they are called the A-team. Their flux densities at ultra-low frequencies (<100 MHz) can reach several thousands of janskys, and they often contaminate observations of the low-frequency sky by interfering with image processing. Furthermore, these sources are foreground objects for all-sky observations hampering the study of faint signals, such as the cosmological 21 cm line from the epoch of reionisation. We aim to produce robust models for the surface brightness emission as a function of frequency for the A-team sources at ultra-low frequencies. These models are needed for the calibration and imaging of wide-area surveys of the sky with low-frequency interferometers. This requires obtaining images at an angular resolution better than 15 arcsec with a high dynamic range and good image fidelity. We observed the A-team with the Low Frequency Array (LOFAR) at frequencies between 30 MHz and 77 MHz using the Low Band Antenna (LBA) system. We reduced the datasets and obtained an image for each A-team source. The paper presents the best models to date for the sources Cassiopeia A, Cygnus A, Taurus A, and Virgo A between 30 MHz and 77 MHz. We were able to obtain the aimed resolution and dynamic range in all cases. Owing to its compactness and complexity, observations with the long baselines of the International LOFAR Telescope will be required to improve the source model for Cygnus A further.

Type II radio bursts are evidence of shocks in the solar atmosphere and inner heliosphere that emit radio waves ranging from sub-meter to kilometer lengths. These shocks may be associated with CMEs and reach speeds higher than the local magnetosonic speed. Radio imaging of decameter wavelengths (20-90 MHz) is now possible with LOFAR, opening a new radio window in which to study coronal shocks that leave the inner solar corona and enter the interplanetary medium and to understand their association with CMEs. To this end, we study a coronal shock associated with a CME and type II radio burst to determine the locations at which the radio emission is generated, and we investigate the origin of the band-splitting phenomenon.

Context. The Sun is an active star that produces large-scale energetic events such as solar flares and coronal mass ejections and numerous smaller-scale events such as solar jets. These events are often associated with accelerated particles that can cause emission at radio wavelengths. The reconfiguration of the solar magnetic field in the corona is believed to be the cause of the majority of solar energetic events and accelerated particles. Aims. Here, we investigate a bright J-burst that was associated with a solar jet and the possible emission mechanism causing these two phenomena. Methods. We used data from the Solar Dynamics Observatory (SDO) to observe a solar jet, and radio data from the Low Frequency Array (LOFAR) and the Nançay Radioheliograph (NRH) to observe a J-burst over a broad frequency range (33-173 MHz) on 9 July 2013 at ~11:06 UT. Results. The J-burst showed fundamental and harmonic components and it was associated with a solar jet observed at extreme ultraviolet wavelengths with SDO. The solar jet occurred at a time and location coincident with the radio burst, in the northern hemisphere, and not inside a group of complex active regions in the southern hemisphere. The jet occurred in the negative polarity region of an area of bipolar plage. Newly emerged positive flux in this region appeared to be the trigger of the jet. Conclusions. Magnetic reconnection between the overlying coronal field lines and the newly emerged positive field lines is most likely the cause of the solar jet. Radio imaging provides a clear association between the jet and the J-burst which shows the path of the accelerated electrons.

Context. Observing Jupiter's synchrotron emission from the Earth remains today the sole method to scrutinize the distribution and dynamical behavior of the ultra energetic electrons magnetically trapped around the planet (because in-situ particle data are limited in the inner magnetosphere). Aims. We perform the first resolved and low-frequency imaging of the synchrotron emission with LOFAR at 127 MHz. The radiation comes from low energy electrons (~1-30 MeV) which map a broad region of Jupiter's inner magnetosphere. Methods (see article for complete abstract) Results. The first resolved images of Jupiter's radiation belts at 127-172 MHz are obtained along with total integrated flux densities. They are compared with previous observations at higher frequencies and show a larger extent of the synchrotron emission source (>=4 \\(R_J\\)). The asymmetry and the dynamic of east-west emission peaks are measured and the presence of a hot spot at lambda_III=230 {\\deg} \\(\\pm\\) 25 {\\deg}. Spectral flux density measurements are on the low side of previous (unresolved) ones, suggesting a low-frequency turnover and/or time variations of the emission spectrum. Conclusions. LOFAR is a powerful and flexible planetary imager. The observations at 127 MHz depict an extended emission up to ~4-5 planetary radii. The similarities with high frequency results reinforce the conclusion that: i) the magnetic field morphology primarily shapes the brightness distribution of the emission and ii) the radiating electrons are likely radially and latitudinally distributed inside about 2 \\(R_J\\). Nonetheless, the larger extent of the brightness combined with the overall lower flux density, yields new information on Jupiter's electron distribution, that may shed light on the origin and mode of transport of these particles.

Measuring radio emission from air showers offers a novel way to determine properties of the primary cosmic rays such as their mass and energy. Theory predicts that relativistic time compression effects lead to a ring of amplified emission which starts to dominate the emission pattern for frequencies above ~100 MHz. In this article we present the first detailed measurements of this structure. Ring structures in the radio emission of air showers are measured with the LOFAR radio telescope in the frequency range of 110 - 190 MHz. These data are well described by CoREAS simulations. They clearly confirm the importance of including the index of refraction of air as a function of height. Furthermore, the presence of the Cherenkov ring offers the possibility for a geometrical measurement of the depth of shower maximum, which in turn depends on the mass of the primary particle.

Some radio pulsars show clear drifting subpulses, in which subpulses are seen to drift in pulse longitude in a systematic pattern. Here we examine how the drifting subpulses of PSR B0809+74 evolve with time and observing frequency. We show that the subpulse period (P3) is constant on timescales of days, months and years, and between 14-5100 MHz. Despite this, the shapes of the driftbands change radically with frequency. Previous studies have concluded that, while the subpulses appear to move through the pulse window approximately linearly at low frequencies (< 500 MHz), a discrete step of 180 degrees in subpulse phase is observed at higher frequencies (> 820 MHz) near to the peak of the average pulse profile. We use LOFAR, GMRT, GBT, WSRT and Effelsberg 100-m data to explore the frequency-dependence of this phase step. We show that the size of the subpulse phase step increases gradually, and is observable even at low frequencies. We attribute the subpulse phase step to the presence of two separate driftbands, whose relative arrival times vary with frequency - one driftband arriving 30 pulses earlier at 20 MHz than it does at 1380 MHz, whilst the other arrives simultaneously at all frequencies. The drifting pattern which is observed here cannot be explained by either the rotating carousel model or the surface oscillation model, and could provide new insight into the physical processes happening within the pulsar magnetosphere.

PSR B0823+26, a 0.53-s radio pulsar, displays a host of emission phenomena over timescales of seconds to (at least) hours, including nulling, subpulse drifting, and mode-changing. Studying pulsars like PSR B0823+26 provides further insight into the relationship between these various emission phenomena and what they might teach us about pulsar magnetospheres. Here we report on the LOFAR discovery that PSR B0823+26 has a weak and sporadically emitting 'quiet' (Q) emission mode that is over 100 times weaker (on average) and has a nulling fraction forty-times greater than that of the more regularly-emitting 'bright' (B) mode. Previously, the pulsar has been undetected in the Q-mode, and was assumed to be nulling continuously. PSR B0823+26 shows a further decrease in average flux just before the transition into the B-mode, and perhaps truly turns off completely at these times. Furthermore, simultaneous observations taken with the LOFAR, Westerbork, Lovell, and Effelsberg telescopes between 110 MHz and 2.7 GHz demonstrate that the transition between the Q-mode and B-mode occurs within one single rotation of the neutron star, and that it is concurrent across the range of frequencies observed.

The current study investigated how students’ private in-class use of technical devices is associated with teachers’ mental health. Data of 361 teachers from primary and secondary schools in Germany were assessed via online surveys. The present cross-sectional results show a positive association between burden caused by the students’ private in-class use of technical devices and teachers’ depression symptoms. Both were negatively linked to teachers’ positive mental health (PMH) and teachers’ competence in handling students’ private in-class use of technical devices. In a moderated mediation analysis, the association between burden and depression symptoms was mediated by PMH. Teachers’ competence moderated the link between PMH and depression symptoms. Specifically, the higher the competence, the weaker the relationship between both variables. Thus, the protective effect of teachers’ competence could be especially important in persons with low PMH. Competence training in handling students’ use of technical devices is discussed as a potential step that could protect teachers’ mental health.

Regular exercise has well-established health benefits, some of which are mediated through changes in plasma lipoproteins. This study investigated the relative importance of the amount and the intensity of regular exercise in producing changes in plasma lipoproteins. The amount of exercise per week proved to have a greater effect on lipoproteins than did the intensity of exercise. The amount of exercise had a greater effect on lipoproteins than the intensity of exercise. Increased physical activity and fitness are clearly associated with reductions in the risk of cardiovascular disease, 1 – 5 but the optimal intensity or amount of exercise necessary for reductions in risk or risk factors is unknown. Because of apparently conflicting information, 1 – 3 there is confusion about what recommendations to make for exercise that will confer specific health benefits. In spite of the importance of this issue, there have been no prospective studies investigating the effects of different amounts and intensities of exercise. Although regular exercise is known to decrease the risk of cardiovascular disease, comprehensive reviews 6 , 7 suggest that exercise has . . .