Strategies against nonsense: oxadiazoles as translational readthrough-inducing drugs (TRIDs)

This review focuses on the use of oxadiazoles as translational readthrough-inducing drugs (TRIDs) to rescue the functional full-length protein expression in mendelian genetic diseases caused by nonsense mutations. These mutations in specific genes generate premature termination codons (PTCs) responsible for the translation of truncated proteins. After a brief introduction on nonsense mutations and their pathological effects, the features of various classes of TRIDs will be described discussing differences or similarities in their mechanisms of action. Strategies to correct the PTCs will be presented, particularly focusing on a new class of Ataluren-like oxadiazole derivatives in comparison to aminoglycosides. Additionally, recent results on the efficiency of new candidate TRIDs in restoring the production of the cystic fibrosis transmembrane regulator (CFTR) protein will be presented. Finally, a prospectus on complementary strategies to enhance the effect of TRIDs will be illustrated together with a conclusive paragraph about perspectives, opportunities, and caveats in developing small molecules as TRIDs

Application of pactiter V3.3 code to the ACPS assessment of ITER neutral beam injectors primary heat transfer system

Activated Corrosion Products (ACPs) will be present in the various coolant loops of ITER: in-vessel and vacuum vessel, test blanket modules, auxiliary heating or diagnostic equipments. ACPs impact occupational exposure, routine effluents to the environment, and potential releases during accidents. Hence, the ACP inventory evaluation is an important task for ITER public and occupational safety. PACTITER v3.3 code is a computational tool derived from PACTOLE series of codes, modified in some modeling and computing capabilities. ITER Organization has included it as reference computer code for the ACP assessment. In the framework of its verification and validation activity, PACTITER v3.3 was used to assess the ACP inventory of the ITER Neutral Beam Injectors (NBIs) Primary Heat Transfer System (PHTS). This paper will document the preliminary results of this assessment, focusing on the impact of operation scenarios parameters (i.e. water chemistry, materials corrosion properties, etc.) and piping architecture

Holocene slip rate variability along the Pernicana fault system (Mt. Etna, Italy): Evidence from offset lava flows

The eastern flank of the Mount Etna stratovolcano is affected by extension and is slowly sliding eastward into the Ionian Sea. The Pernicana fault system forms the border of the northern part of this sliding area. It consists of three E-W−oriented fault sectors that are seismically active and characterized by earthquakes up to 4.7 in magnitude (M) capable of producing ground rupture and damage located mainly along the western and central sectors, and by continuous creep on the eastern sector. A new topographic study of the central sector of the Pernicana fault system shows an overall bell-shaped profile, with maximum scarp height of 35 m in the center of the sector, and two local minima that are probably due to the complex morphological relation between fault scarp and lava flows. We determined the ages of lava flows cut by the Pernicana fault system at 12 sites using cosmogenic 3He and 40Ar/39Ar techniques in order to determine the recent slip history of the fault. From the displacement-age relations, we estimate an average throw rate of ∼2.5 mm/yr over the last 15 k.y. The slip rate appears to have accelerated during the last 3.5 k.y., with displacement rates of up to ∼15 mm/yr, whereas between 3.5 and 15 ka, the throw rate averaged ∼1 mm/yr. This increase in slip rate resulted in significant changes in seismicity rates, for instance, decreasing the mean recurrence time of M ≥ 4.7 earthquakes from ∼200 to ∼20 yr. Based on empirical relationships, we attribute the variation in seismic activity on the Pernicana fault system to factors intrinsic to the system that are likely related to changes in the volcanic system. These internal factors could be fault interdependencies (such as those across the Taupo Rift, New Zealand) or they could represent interactions among magmatic, tectonic, and gravitational processes (e.g., Kīlauea volcano, Hawaii). Given their effect on earthquake recurrence intervals, these interactions need to be fully assessed in seismic hazard evaluations

Radioactive Waste Management of Fusion Power Plants

This chapter outlines the attractive environmental features of nuclear fusion, presents an integral scheme to manage fusion activated materials during operation and after decommissioning, compares the volume of fusion and fission waste, covers the recycling, clearance, and disposal concepts and their official radiological limits, and concludes with a section summarizing the newly developed strategy for fusion power plant

EChO Payload electronics architecture and SW design

EChO is a three-modules (VNIR, SWIR, MWIR), highly integrated spectrometer, covering the wavelength range from 0.55 $\mu$m, to 11.0 $\mu$m. The baseline design includes the goal wavelength extension to 0.4 $\mu$m while an optional LWIR module extends the range to the goal wavelength of 16.0 $\mu$m. An Instrument Control Unit (ICU) is foreseen as the main electronic subsystem interfacing the spacecraft and collecting data from all the payload spectrometers modules. ICU is in charge of two main tasks: the overall payload control (Instrument Control Function) and the housekeepings and scientific data digital processing (Data Processing Function), including the lossless compression prior to store the science data to the Solid State Mass Memory of the Spacecraft. These two main tasks are accomplished thanks to the Payload On Board Software (P-OBSW) running on the ICU CPUs.Comment: Experimental Astronomy - EChO Special Issue 201

Effects of parietal lesions in humans on color and location priming

To determine whether the parietal lobes contribute to the selection of nonspatial features known to be processed in the ventral stream, the current study examined the effect of chronic unilateral parietal lobe lesions in humans on color and location priming. Patients and normal controls performed a go/no-go color discrimination task in which either the same color and different color pairs of stimuli (prime and probe) were projected sequentially either in the same hemifield or in opposite hemifields. Control subjects and patients both showed independent effects of color and location priming. In the patients, primes in either field produced color priming for target probes in the ipsilesional field but not for probes in the contralesional field. This observation implicates the parietal cortex in processing activated codes of stimulus attributes not only for spatial information but also for visual features processed in the ventral visual pathways