A comparison of the cosmic-ray energy scales of Tunka-133 and KASCADE-Grande via their radio extensions Tunka-Rex and LOPES

The radio technique is a promising method for detection of cosmic-ray air showers of energies around $100\,$PeV and higher with an array of radio antennas. Since the amplitude of the radio signal can be measured absolutely and increases with the shower energy, radio measurements can be used to determine the air-shower energy on an absolute scale. We show that calibrated measurements of radio detectors operated in coincidence with host experiments measuring air showers based on other techniques can be used for comparing the energy scales of these host experiments. Using two approaches, first via direct amplitude measurements, and second via comparison of measurements with air shower simulations, we compare the energy scales of the air-shower experiments Tunka-133 and KASCADE-Grande, using their radio extensions, Tunka-Rex and LOPES, respectively. Due to the consistent amplitude calibration for Tunka-Rex and LOPES achieved by using the same reference source, this comparison reaches an accuracy of approximately $10\,\%$ - limited by some shortcomings of LOPES, which was a prototype experiment for the digital radio technique for air showers. In particular we show that the energy scales of cosmic-ray measurements by the independently calibrated experiments KASCADE-Grande and Tunka-133 are consistent with each other on this level

O -GlcNAc and Neurodegeneration: Biochemical Mechanisms and Potential Roles in Alzheimer\u27s Disease and Beyond

Alzheimer disease (AD) is a growing problem for aging populations worldwide. Despite significant efforts, no therapeutics are available that stop or slow progression of AD, which has driven interest in the basic causes of AD and the search for new therapeutic strategies. Longitudinal studies have clarified that defects in glucose metabolism occur in patients exhibiting Mild Cognitive Impairment (MCI) and glucose hypometabolism is an early pathological change within AD brain. Further, type 2 diabetes mellitus (T2DM) is a strong risk factor for the development of AD. These findings have stimulated interest in the possibility that disrupted glucose regulated signaling within the brain could contribute to the progression of AD. One such process of interest is the addition of O-linked N-acetylglucosamine (O-GlcNAc) residues onto nuclear and cytoplasmic proteins within mammals. O-GlcNAc is notably abundant within brain and is present on hundreds of proteins including several, such as tau and the amyloid precursor protein, which are involved in the pathophysiology AD. The cellular levels of O-GlcNAc are coupled to nutrient availability through the action of just two enzymes. O-GlcNAc transferase (OGT) is the glycosyltransferase that acts to install O-GlcNAc onto proteins and O-GlcNAcase (OGA) is the glycoside hydrolase that acts to remove O-GlcNAc from proteins. Uridine 5′-diphosphate-N-acetylglucosamine (UDP-GlcNAc) is the donor sugar substrate for OGT and its levels vary with cellular glucose availability because it is generated from glucose through the hexosamine biosynthetic pathway (HBSP). Within the brains of AD patients O-GlcNAc levels have been found to be decreased and aggregates of tau appear to lack O-GlcNAc entirely. Accordingly, glucose hypometabolism within the brain may result in disruption of the normal functions of O-GlcNAc within the brain and thereby contribute to downstream neurodegeneration. While this hypothesis remains largely speculative, recent studies using different mouse models of AD have demonstrated the protective benefit of pharmacologically increased brain O-GlcNAc levels. In this review we summarize the state of knowledge in the area of O-GlcNAc as it pertains to AD while also addressing some of the basic biochemical roles of O-GlcNAc and how these might contribute to protecting against AD and other neurodegenerative diseases