Tokamak cooling systems and power conversion system options

DEMO will be a fusion power plant demonstrating the integration into the grid architecture of an electric utility grid. The design of the power conversion chain is of particular importance, as it must adequately account for the specifics of nuclear fusion on the generation side and ensure compatibility with the electric utility grid at all times. One of the special challenges the foreseen pulsed operation, which affects the operation of the entire heat transport chain. This requires a time-dependant analysis of different concept design approaches to ensure proof of reliable operation and efficiency to obtain nuclear licensing. Several architectures of Balance of Plant were conceived and developed during the DEMO Pre-Concept Design Phase in order to suit needs and constraints of the in-vessel systems, with particular regard to the different blanket concepts. At this early design stage, emphasis was given to the achievement of robust solutions for all essential Balance of Plant systems, which have chiefly to ensure feasible and flexible operation modes during the main DEMO operating phases – Pulse, Dwell and ramp-up/down – and to adsorb and compensate for potential fusion power fluctuations during plasma flat-top. Although some criticalities, requiring further design improvements were identified, these preliminary assessments showed that the investigated cooling system architectures have the capability to restore nominal conditions after any of the abovementioned cases and that the overall availability could meet the DEMO top-level requirements. This paper describes the results of the studies on the tokamak coolant and Power Conversion System (PCS) options and critically highlights the aspects that require further work

Effect of the ethinylestradiol/norelgestromin contraceptive patch on body composition. Results of bioelectrical impedance analysis in a population of Italian women

<p>Abstract</p> <p>Background</p> <p>As weight gain is one of the most frequently cited reasons for not using and for discontinuing hormonal contraceptives, in an open-label, single-arm, multicentre clinical study we evaluated the effect of the ethinylestradiol/norelgestromin contraceptive patch (EVRA, Janssen-Cilag International, Belgium) on body composition using bioelectrical impedance analysis (BIA).</p> <p>Methods</p> <p>Body weight and impedance vector components (resistance (R) and reactance (Xc), at 50 kHz frequency, Akern-RJL Systems analyzer) were recorded before entry, after 1, 3 and 6 months in 182 Italian healthy women aged 29 yr (18 to 45), and with BMI 21.8 kg/m²(16 to 31). Total body water (TBW) was estimated with a BIA regression equation. Vector BIA was performed with the RXc mean graph method and the Hotelling's T²test for paired and unpaired data.</p> <p>Results</p> <p>After 6 months body weight increased by 0.64 kg (1.1%) and TBW increased by 0.51 L (1.7%). The pattern of impedance vector displacement indicated a small increase in soft tissue hydration (interstitial gel fluid). Body composition changes did not significantly differ among groups of previous contraceptive methods. Arterial blood pressure did not significantly change over time.</p> <p>Conclusion</p> <p>After 6 months of treatment with the ethinylestradiol/norelgestromin contraceptive patch we found a minimal, clinically not relevant, increase in body weight less than 1 kg that could be attributed to an adaptive interstitial gel hydration. This fluctuation is physiological as confirmed by the lack of any effect on blood pressure. This could be useful in increasing women's choice, acceptability and compliance of the ethinylestradiol/norelgestromin contraceptive patch.</p

Divertor of the European DEMO: Engineering and technologies for power exhaust

In a power plant scale fusion reactor, a huge amount of thermal power produced by the fusion reaction and external heating must be exhausted through the narrow area of the divertor targets. The targets must withstand the intense bombardment of the diverted particles where high heat fluxes are generated and erosion takes place on the surface. A considerable amount of volumetric nuclear heating power must also be exhausted. To cope with such an unprecedented power exhaust challenge, a highly efficient cooling capacity is required. Furthermore, the divertor must fulfill other critical functions such as nuclear shielding and channeling (and compression) of exhaust gas for pumping. Assuring the structural integrity of the neutron-irradiated (thus embrittled) components is a crucial prerequisite for a reliable operation over the lifetime. Safety, maintainability, availability, waste and costs are another points of consideration. In late 2020, the Pre-Conceptual Design activities to develop the divertor of the European demonstration fusion reactor were officially concluded. On this occasion, the baseline design and the key technology options were identified and verified by the project team (EUROfusion Work Package Divertor) based on seven years of R&D efforts and endorsed by Gate Review Panel. In this paper, an overview of the load specifications, brief descriptions of the design and the highlights of the technology R&D work are presented together with the further work still needed

A novel homozygous YARS2 mutation in two italian siblings and a review of literature

YARS2 encodes the mitochondrial tyrosyl-tRNA synthetase that catalyzes the covalent binding of tyrosine to its cognate mt-tRNA. Mutations in YARS2 have been identified in patients with myopathy, lactic acidosis, and sideroblastic anemia type 2 (MLASA2). We report here on two siblings with a novel mutation and a review of literature. The older patient presented at 2 months with marked anemia and lactic acidemia. He required periodic blood transfusions until 14 months of age. Cognitive and motor development was normal. His younger sister was diagnosed at birth, presenting with anemia and lactic acidosis at 1 month of age requiring periodical transfusions. She is now 14 months old and doing well. For both our patients, there was no clinical evidence of muscle involvement. We found a new homozygous mutation in YARS2, located in the α-anticodon-binding (αACB) domain, involved in the interaction with the anticodon of the cognate mt-tRNATyr. Our study confirms that MLASA must be considered in patients with congenital sideroblastic anemia and underlines the importance of early diagnosis and supportive therapy in order to prevent severe complications. Clinical severity is variable among YARS2-reported patients: our review of the literature suggests a possible phenotype-genotype correlation, although this should be confirmed in a larger population

High-Throughput Screening of Patient-Derived Cultures Reveals Potential for Precision Medicine in Glioblastoma

Identifying drugs for the treatment of glioblastoma (GBM), a rapidly fatal disease, has been challenging. Most screening efforts have been conducted with immortalized cell lines grown with fetal bovine serum, which have little relevance to the genomic features found in GBM patients. Patient-derived neurosphere cultures, while being more physiologically relevant, are difficult to screen and therefore are only used to test a few drug candidates after initial screening efforts. Laminin has been used to generate two-dimensional cell lines from patient tumors, preserving the genomic signature and alleviating some screening hurdles. We present here the first side-by-side comparison of inhibitor sensitivity of laminin and neurosphere-grown patient-derived GBM cell lines and show that both of these culture methods result in the same pattern of inhibitor sensitivity. We used these screening methods to evaluate the dependencies of seven patient-derived cell models: three grown on laminin and four grown as neurospheres, against 56 agents in 17-point dose–response curves in 384-well format in triplicate. This allowed us to establish differential sensitivity of chemotherapeutic agents across the seven patient-derived models. We found that MEK inhibition caused patient-sample-specific growth inhibition and that bortezomib, an FDA-approved proteasome inhibitor, was potently lethal in all patient-derived models. Furthermore, the screening results led us to test the combination of the Bcl-2 inhibitor ABT-263, and the mTOR inhibitor AZD-8055, which we found to be synergistic in a subset of patient-derived GBM models. Thus, we have identified new candidate therapeutics and developed a high-throughput screening system using patient-derived GBM samples

Copper-Binding Small Molecule Induces Oxidative Stress and Cell-Cycle Arrest in Glioblastoma-Patient-Derived Cells

Transition metals are essential, but deregulation of their metabolism causes toxicity. Here, we report that the compound NSC319726 binds copper to induce oxidative stress and arrest glioblastoma-patient-derived cells at picomolar concentrations. Pharmacogenomic analysis suggested that NSC319726 and 65 other structural analogs exhibit lethality through metal binding. Although NSC319726 has been reported to function as a zinc ionophore, we report here that this compound binds to copper to arrest cell growth. We generated and validated pharmacogenomic predictions: copper toxicity was substantially inhibited by hypoxia, through an hypoxia-inducible-factor-1α-dependent pathway; copper-bound NSC319726 induced the generation of reactive oxygen species and depletion of deoxyribosyl purines, resulting in cell-cycle arrest. These results suggest that metal-induced DNA damage may be a consequence of exposure to some xenobiotics, therapeutic agents, as well as other causes of copper dysregulation, and reveal a potent mechanism for targeting glioblastomas