A translational research experience in Argentina.

Background: The Argentinean programwas initiatedmore than a decade ago as the first experience of systematic translational research focused on NCL in Latin America. The aim was to overcome misdiagnoses and underdiagnoses in the region. Subjects: 216 NCL suspected individuals from 8 different countries and their direct family members. Methods: Clinical assessment, enzyme testing, electron microscopy, and DNA screening. Results and discussion: 1) The study confirmed NCL disease in 122 subjects. Phenotypic studies comprised epileptic seizures and movement disorders, ophthalmology, neurophysiology, image analysis, rating scales, enzyme testing, and electron microscopy, carried out under a consensus algorithm; 2) DNA screening and validation of mutations in genes PPT1 (CLN1), TPP1 (CLN2), CLN3, CLN5, CLN6, MFSD8 (CLN7), and CLN8: characterization of variant types, novel/knownmutations and polymorphisms; 3) Progress of the epidemiological picture in Latin America; and 4) NCL-like pathology studies in progress. The Translational Research Program was highly efficient in addressing the misdiagnosis/underdiagnosis in the NCL disorders. The study of “orphan diseases” in a public administrated hospital should be adopted by the health systems, as it positively impacts upon the family's quality of life, the collection of epidemiological data, and triggers research advances. This article is part of a Special Issue entitled: “Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease)”publishedVersio

Deliverable Raport D4.6 Tools for generating QMRF and QPRF reports

Scientific reports carry significant importance for the straightforward and effective transfer of knowledge, results and ideas. Good practice dictates that reports should be well-structured and concise. This deliverable describes the reporting services for models, predictions and validation tasks that have been integrated within the eNanoMapper (eNM) modelling infrastructure. Validation services have been added to the Jaqpot Quattro (JQ) modelling platform and the nano-lazar read-across framework developed within WP4 to support eNM modelling activities. Moreover, we have proceeded with the development of reporting services for predictions and models, respectively QPRF and QMRF reports. Therefore, in this deliverable, we first describe the three validation schemes created, namely training set split, cross- and external validation in detail and demonstrate their functionality both on API and UI levels. We then proceed with the description of the read across functionalities and finally, we present and describe the QPRF and QMRF reporting services

The wavefront of the radio signal emitted by cosmic ray air showers

Analyzing measurements of the LOPES antenna array together with corresponding CoREAS simulations for more than 300 measured events with energy above $10^{17}\,$eV and zenith angles smaller than $45^\circ$, we find that the radio wavefront of cosmic-ray air showers is of approximately hyperbolic shape. The simulations predict a slightly steeper wavefront towards East than towards West, but this asymmetry is negligible against the measurement uncertainties of LOPES. At axis distances $\gtrsim 50\,$m, the wavefront can be approximated by a simple cone. According to the simulations, the cone angle is clearly correlated with the shower maximum. Thus, we confirm earlier predictions that arrival time measurements can be used to study the longitudinal shower development, but now using a realistic wavefront. Moreover, we show that the hyperbolic wavefront is compatible with our measurement, and we present several experimental indications that the cone angle is indeed sensitive to the shower development. Consequently, the wavefront can be used to statistically study the primary composition of ultra-high energy cosmic rays. At LOPES, the experimentally achieved precision for the shower maximum is limited by measurement uncertainties to approximately $140\,$g/cm$^2$. But the simulations indicate that under better conditions this method might yield an accuracy for the atmospheric depth of the shower maximum, $X_\mathrm{max}$, better than $30\,$g/cm$^2$. This would be competitive with the established air-fluorescence and air-Cherenkov techniques, where the radio technique offers the advantage of a significantly higher duty-cycle. Finally, the hyperbolic wavefront can be used to reconstruct the shower geometry more accurately, which potentially allows a better reconstruction of all other shower parameters, too.Comment: accepted by JCA

Experimental evidence for the sensitivity of the air-shower radio signal to the longitudinal shower development

We observe a correlation between the slope of radio lateral distributions, and the mean muon pseudorapidity of 59 individual cosmic-ray-air-shower events. The radio lateral distributions are measured with LOPES, a digital radio interferometer co-located with the multi-detector-air-shower array KASCADE-Grande, which includes a muon-tracking detector. The result proves experimentally that radio measurements are sensitive to the longitudinal development of cosmic-ray air-showers. This is one of the main prerequisites for using radio arrays for ultra-high-energy particle physics and astrophysics.Comment: 6 pages, 5 figures, accepted for publication by Physical Review