Evaluation of presumably disease causing SCN1A variants in a cohort of common epilepsy syndromes

Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation: We identified 8 known missense mutations, previously reported as path

Recovering nanotechnologies from the past: the production of Renaissance luster ceramics

Luster was one of the most sophisticated technique for the decoration of majolicas during the Renaissance period. Luster consists of a thin metallic film containing silver, copper and other substances, like iron oxide and cinnabar, applied in a reducing atmosphere on a previously glazed ceramic. In this way, beautiful iridescent reflections of different colours (in particular gold and ruby-red) are obtained. The characterisation and the study of luster decorated majolicas is of great interest for archaeologists and today also offers possibilities to produce pottery with outstanding decoration, following ancient examples, since nowadays Italian artisans are interested in the reproduction of the ancient recipes and procedures. Luster technique developed in Iraq, then spread to Egypt, Persia and Spain, following the expansion of the Arabian culture during the Medieval time. From Spain (Valencia, Manises and Malaga), luster was introduced in the Italian peninsula, mostly in Central Italy where it was used to decorate the most beautiful majolicas. Gubbio and Deruta, located in the Umbria region were important centres for this activity. It has to be pointed out that the Italian artisans developed their own style, for the decorative motifs, as well as for what concerns the metallic colours obtained. For this reason, the local artisans became keepers of refined and secret recipes and techniques for decorating ceramic objects. Mastro Giorgio Andreoli da Gubbio was the most important artist in this field, whose works can be found in the most important Museums of the world and are very well known in the antique trade market as well. His fame is due to the fact that optimising the luster technique, he obtained outstanding results, that were not possible to replicate at his time and at present. He was specialised mainly in two kinds of reflects: an intense golden-yellow and a ruby-red colour, but the original recipes and technological procedures used at that time, were and remained a secret after his death and until today. In the specific case of the Renaissance period, information on the majolica production technology were passed on by the Knight Cipriano Piccolpasso from Casteldurante, who wrote a treatise entitled \u201cThe three books on the art of the Potter\u201d (1558). Anyway, the information reported by Piccolpasso could not be entirely correct, due to the aforementioned reasons regarding the secrecy. Referring to his information, the objects were obtained in the desired form and fired in a first step at 1000 \ub0C. Once cooked and cooled down, the object was immersed in the glaze constituted by sand, potassium carbonate, salts and oxides, such as lead and tin oxides, finely grinded and mixed with water. After drying in air, it was possible to decorate the glaze surface by using very soft brushes, made by bristle of goat, and, sometimes, for very fine details, whiskers of cats and mice, too. After that, sprayed with a transparent paint, the object underwent a second firing at 900 \ub0C. At the end of this process, the object was complete. But, if we refer to luster, another step was required to achieve the result of producing reflections and iridescences on majolica. Ancient documentation indicates that the luster was obtained using a mixture of copper and silver salts, clays, ochre and other optional substances, dissolved or dispersed in vinegar, firing it in a reducing atmosphere at about 600 \ub0C in special kilns made for this purpose where probably it was easier to control both the temperature and atmosphere. Luster films resulted to be formed by copper and silver cluster of nanometric dimension. The colour and the properties of the luster films depend on the elemental composition of the impasto applied on the ceramic surface, as well as on other factors like the metallic nanoclusters dimension, the firing conditions, the underlying glaze composition and the procedure used. A very interesting aspect is represented by the difference between the Italian and the Hispano-Moresque recipes: Italian artisans added to the impasto for luster preparation also bismuth, probably in order to keep down the cost. In fact the cosalite phase (Pb2Bi2S5) has been disclosed in the Italian lustres and it can be considered a marker which allows to attribute an object of uncertain provenance to the Italian production. For luster characterization the following analytical techniques can be usefully employed: X-ray Diffraction (XRD), Atomic Absorption Spectrometry with Electrothermal Atomization (ETAAS), Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES), Scanning Electron Microscopy/Energy Dispersive X-ray Spectroscopy (SEM-EDX), Scanning Electron Microscopy equipped with a back scattered electrons detector (SEM-BSE), Transmission Electron Microscopy/Energy Dispersive X-ray Spectroscopy/Selected Area Electron Diffraction (TEM-EDX-SAED), Small Angle X-ray Scattering (SAXS) and UV-Vis diffuse reflectance spectroscopy

Combined use of SEM-EDS, OM and XRD for the characterization of corrosion products grown on silver roman coins

In the framework of the PROMET project (European Commission contract No. 509126) aimed to develop new analytical techniques and materials for monitoring and protecting metal artefacts and monuments from the Mediterranean region, the corrosion products grown on silver Roman coins during archaeological burial is studied by means of scanning electron microscopy combined with energy dispersive spectrometry (SEM-EDS), X-ray diffraction (XRD) and optical microscopy (OM) technique