A captured room temperature stable Wheland intermediate as a key structure for the orthogonal decoration of 4-amino-pyrido[2,3-d]pyrimidin-7 (8H)-ones

Wheland intermediates are usually unstable compounds and only a few have been isolated at very low temperatures. During our work on tyrosine kinase inhibitors, we studied the bromination of 7 in order to obtain a dibromo substituted pyrido[2,3-d]pyrimidin-7(8H)-one which could be orthogonally decorated. Surprisingly, treatment of 7 with 3 equiv. of Br2 in acetic acid (AcOH) afforded 12, a captured room temperature stable Wheland bromination intermediate stabilized by the bromination of the imino tautomer of the amino group at C4 of the pyridopyrimidine skeleton. The structure was confirmed by crystal structure determination from powder X-ray diffraction data. Treatment of 12 with DMSO afforded the dibromo substituted compound 13 presenting a bromine atom at C6 and C5-C6 unsaturation. 13 was directly accessed by treating 7 with N-bromosuccinimide (NBS), a protocol extended to other compounds using NBS or N-iodosuccinimide (NIS) to afford 6-halo substituted systems. 26, bearing an iodine at C6 and a p-bromophenylamino at C2, allows the orthogonal decoration of pyridopyrimidines

Status of a European Standard for the protection of helium cryostats against excessive pressure

The overpressure protection of various types of cryogenic vessels is covered by a number of International Standards. Helium cryostats, however, include additional components such as superconducting magnets and cavities, electrical heaters and control valves with associated piping, which significantly influence the potential risk. At the European Committee for Standardization CEN, a new working group was hence founded as CEN/TC 268/WG6, dealing with ‘Specific helium technology applications’. Its aim is to develop a European Standard for the protection of helium cryostats against excessive pressure that is harmonized with the European Pressure Equipment Directive. It will cover the typical conditions in accidental scenarios in order to harmonize the risk assessment as well as design practices for the pressure relieving systems. We report about the general concept of this new Standard, its structure and content, and the actual status of the project

Spin Structures of Textured and Isotropic Nd-Fe-B-Based Nanocomposites: Evidence for Correlated Crystallographic and Spin Textures

peer reviewedR-AGR-0134 - IRP12 - Interface 2012 (20120701-20150630) - MICHELS Andrea

The DEMO magnet system – Status and future challenges

We present the pre-concept design of the European DEMO Magnet System, which has successfully passed the DEMO plant-level gate review in 2020. The main design input parameters originate from the so-called DEMO 2018 baseline, which was produced using the PROCESS systems code. It defines a major and minor radius of 9.1 m and 2.9 m, respectively, an on-axis magnetic field of 5.3 T resulting in a peak field on the toroidal field (TF) conductor of 12.0 T. Four variants, all based on low-temperature superconductors (LTS), have been designed for the 16 TF coils. Two of these concepts were selected to be further pursued during the Concept Design Phase (CDP): the first having many similarities to the ITER TF coil concept and the second being the most innovative one, based on react-and-wind (RW) Nb3Sn technology and winding the coils in layers. Two variants for the five Central Solenoid (CS) modules have been investigated: an LTS-only concept resembling to the ITER CS and a hybrid configuration, in which the innermost layers are made of high-temperature superconductors (HTS), which allows either to increase the magnetic flux or to reduce the outer radius of the CS coil. Issues related to fatigue lifetime which emerged in mechanical analyses will be addressed further in the CDP. Both variants proposed for the six poloidal field coils present a lower level of risk for future development. All magnet and conductor design studies included thermal-hydraulic and mechanical analyses, and were accompanied by experimental tests on both LTS and HTS prototype samples (i.e. DC and AC measurements, stability tests, quench evolution etc.). In addition, magnet structures and auxiliary systems, e.g. cryogenics and feeders, were designed at pre-concept level. Important lessons learnt during this first phase of the project were fed into the planning of the CDP. Key aspects to be addressed concern the demonstration and validation of critical technologies (e.g. industrial manufacturing of RW Nb3Sn and HTS long conductors, insulation of penetrations and joints), as well as the detailed design of the overall Magnet System and mechanical structures

The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models

Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. This virus has proven to be safe and effective in adult gliomas. Here we report that the administration of Delta-24-RGD is safe in mice and results in a significant increase in survival in immunodeficient and immunocompetent models of pHGG and DIPGs. Our results show that the Delta-24-RGD antiglioma effect is mediated by the oncolytic effect and the immune response elicited against the tumor. Altogether, our data highlight the potential of this virus as treatment for patients with these tumors. Of clinical significance, these data have led to the start of a phase I/II clinical trial at our institution for newly diagnosed DIPG (NCT03178032)

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Thin-section petrography and SR-\ub5XRD for the identification of micro-crystallites in the brown decorations of ceramic lead glazes

The Mn-and Fe-rich micro-crystalline precipitates formed in the decorations of lead glazes during ceramic firing are responsible for colour, shine and opacity, among other visual characteristics, besides being the most important relics of the technology. Due to their small size and growth habits, the micro-crystalline precipitates may remain unidentified on polished cross sections of the glazes. Thin-section petrography, combined with synchrotron-radiation X-ray micro-diffraction, appears to be a very powerful tool to reveal the presence, growth habits, distribution and nature of the micro-crystallites. This is illustrated here by two case studies directly related to the brown decorations technology: the 19th century French imitations of the Ligurian Taches Noires pottery from the Joques workshop and the 17th century Catalan-decorated tablewares. Melanotekite, cristobalite and hematite micro-crystallites were found in the glazes of the French imitations. Hematite acted as nucleating agent effective in promoting both the crystallization of melanotekite and cristobalite. The presence of cristobalite is not related to alkali ions, which are normally responsible for its formation far from equilibrium conditions. Melanotekite and cristobalite can be considered as technological markers associated to the Joques production and then be used to identify imitations of this workshop. Braunite and kentrolite were identified in the brown decoration of the Catalan tablewares. The manganese pigment was probably mixed with a lead oxide compound and applied directly over the raw glaze. The presence of braunite and kentrolite indicates a firing temperature of about 950 \ub0C. Thin-section petrography reveals that the crystallite growth has taken place under two different conditions. Euhedral braunite crystallites were produced during the heating. A drop in temperature during the firing process gave rise to the crystallization of dendritic braunite and kentrolite