The synthesis of complex organic compounds is largely a manual process that is often incompletely documented. To address these shortcomings, we developed an abstraction that maps commonly reported ...methodological instructions into discrete steps amenable to automation. These unit operations were implemented in a modular robotic platform by using a chemical programming language that formalizes and controls the assembly of the molecules. We validated the concept by directing the automated system to synthesize three pharmaceutical compounds, diphenhydramine hydrochloride, rufinamide, and sildenafil, without any human intervention. Yields and purities of products and intermediates were comparable to or better than those achieved manually. The syntheses are captured as digital code that can be published, versioned, and transferred flexibly between platforms with no modification, thereby greatly enhancing reproducibility and reliable access to complex molecules.
Lithium metal anodes offer high theoretical capacities (3,860 milliampere-hours per gram)
, but rechargeable batteries built with such anodes suffer from dendrite growth and low Coulombic efficiency ...(the ratio of charge output to charge input), preventing their commercial adoption
. The formation of inactive ('dead') lithium- which consists of both (electro)chemically formed Li
compounds in the solid electrolyte interphase and electrically isolated unreacted metallic Li
(refs
)-causes capacity loss and safety hazards. Quantitatively distinguishing between Li
in components of the solid electrolyte interphase and unreacted metallic Li
has not been possible, owing to the lack of effective diagnostic tools. Optical microscopy
, in situ environmental transmission electron microscopy
, X-ray microtomography
and magnetic resonance imaging
provide a morphological perspective with little chemical information. Nuclear magnetic resonance
, X-ray photoelectron spectroscopy
and cryogenic transmission electron microscopy
can distinguish between Li
in the solid electrolyte interphase and metallic Li
, but their detection ranges are limited to surfaces or local regions. Here we establish the analytical method of titration gas chromatography to quantify the contribution of unreacted metallic Li
to the total amount of inactive lithium. We identify the unreacted metallic Li
, not the (electro)chemically formed Li
in the solid electrolyte interphase, as the dominant source of inactive lithium and capacity loss. By coupling the unreacted metallic Li
content to observations of its local microstructure and nanostructure by cryogenic electron microscopy (both scanning and transmission), we also establish the formation mechanism of inactive lithium in different types of electrolytes and determine the underlying cause of low Coulombic efficiency in plating and stripping (the charge and discharge processes, respectively, in a full cell) of lithium metal anodes. We propose strategies for making lithium plating and stripping more efficient so that lithium metal anodes can be used for next-generation high-energy batteries.
Abstract Against the background of the rapid development of nuclear energy and nuclear technology, the number of places with radioactivity has gradually risen, which poses a significant safety hazard ...to human beings. Aiming at indoor radioactive places, this paper designs a detector that can be mounted on a robot, and experiments prove that this detector can accurately detect α-surface contamination and β-surface contamination. The surface contamination is measured using a combination of a remote-controlled robot and a detector.
The thermal and electromagnetic loads related to disruptions in ITER are substantial and require careful design of tokamak components to ensure they reach the projected lifetime and to ensure that ...safety relevant components fulfil their function for the worst foreseen scenarios. The disruption load specifications are the basis for the design process of components like the full-W divertor, the blanket modules and the vacuum vessel and will set the boundary conditions for ITER operations. This paper will give a brief overview on the disruption loads and mitigation strategies for ITER and will discuss the physics basis which is continuously refined through the current disruption R&D programs.
Lutetium-177 177LuLu-PSMA-617 is a radiolabelled small molecule that delivers β radiation to cells expressing prostate-specific membrane antigen (PSMA), with activity and safety in patients with ...metastatic castration-resistant prostate cancer. We aimed to compare 177LuLu-PSMA-617 with cabazitaxel in patients with metastatic castration-resistant prostate cancer.
We did this multicentre, unblinded, randomised phase 2 trial at 11 centres in Australia. We recruited men with metastatic castration-resistant prostate cancer for whom cabazitaxel was considered the next appropriate standard treatment. Participants were required to have adequate renal, haematological, and liver function, and an Eastern Cooperative Oncology Group performance status of 0–2. Previous treatment with androgen receptor-directed therapy was allowed. Men underwent gallium-68 68GaGa-PSMA-11 and 2-flourine-1818Ffluoro-2-deoxy-D-glucose (FDG) PET-CT scans. PET eligibility criteria for the trial were PSMA-positive disease, and no sites of metastatic disease with discordant FDG-positive and PSMA-negative findings. Men were randomly assigned (1:1) to 177LuLu-PSMA-617 (6·0–8·5 GBq intravenously every 6 weeks for up to six cycles) or cabazitaxel (20 mg/m2 intravenously every 3 weeks for up to ten cycles). The primary endpoint was prostate-specific antigen (PSA) response defined by a reduction of at least 50% from baseline. This trial is registered with ClinicalTrials.gov, NCT03392428.
Between Feb 6, 2018, and Sept 3, 2019, we screened 291 men, of whom 200 were eligible on PET imaging. Study treatment was received by 98 (99%) of 99 men randomly assigned to 177LuLu-PSMA-617 versus 85 (84%) of 101 randomly assigned to cabazitaxel. PSA responses were more frequent among men in the 177LuLu-PSMA-617 group than in the cabazitaxel group (65 vs 37 PSA responses; 66% vs 37% by intention to treat; difference 29% (95% CI 16–42; p<0·0001; and 66% vs 44% by treatment received; difference 23% 9–37; p=0·0016). Grade 3–4 adverse events occurred in 32 (33%) of 98 men in the 177LuLu-PSMA-617 group versus 45 (53%) of 85 men in the cabazitaxel group. No deaths were attributed to 177LuLu-PSMA-617.
177LuLu-PSMA-617 compared with cabazitaxel in men with metastatic castration-resistant prostate cancer led to a higher PSA response and fewer grade 3 or 4 adverse events. 177LuLu-PSMA-617 is a new effective class of therapy and a potential alternative to cabazitaxel.
Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, The Distinguished Gentleman's Ride, It's a Bloke Thing, and CAN4CANCER.
The Fukushima-Daiichi accident revealed that the zirconium fuel claddings have the significant safety risk of hydrogen detonation due to the strong oxidation and hydrogen release during the design ...basis accidents (DBA) and beyond design basis accidents (BDBA). Therefore, research and development of accident tolerant fuel (ATF) concepts that aim to improve nuclear fuel safety during normal operation, operational transients and possible accident scenarios have been boosted in the last decade. Deposition of protective coatings on Zircaloy cladding tubes has been considered as a near-term solution of enhanced ATF cladding. Among the candidate coating materials, there is no doubt that the research progress of Cr coating is the fastest around the world because of the advantages of such type of coating: excellent good chemical stability (including oxidation resistance and hydrothermal corrosion resistance), low thermal neutrons absorption cross-section, and excellent adherent. In this paper, the oxidation, diffusion, and mechanical properties of Cr-coated Zr alloys in normal operation conditions and accident conditions of nuclear reactors are reviewed. The factors that cause the failure of the coating are analyzed, and some questions that need to be clarified and further studied are proposed.
•Focus on Cr-coated Zr alloy ATF cladding.•Oxidation and diffusion behavior reviewed.•Mechanical property of the coating discussed.•Failure mechanism analyzed.•Questions to be solved in the future proposed.
Objectives
N‐acetylcysteine (NAC) is a clinically approved thiol‐containing redox modulatory compound currently in trials for many neurological and psychiatric disorders. Although generically labeled ...as an “antioxidant,” poor understanding of its site(s) of action is a barrier to its use in neurological practice. Here, we examined the efficacy and mechanism of action of NAC in rodent models of hemorrhagic stroke.
Methods
Hemin was used to model ferroptosis and hemorrhagic stroke in cultured neurons. Striatal infusion of collagenase was used to model intracerebral hemorrhage (ICH) in mice and rats. Chemical biology, targeted lipidomics, arachidonate 5‐lipoxygenase (ALOX5) knockout mice, and viral‐gene transfer were used to gain insight into the pharmacological targets and mechanism of action of NAC.
Results
NAC prevented hemin‐induced ferroptosis by neutralizing toxic lipids generated by arachidonate‐dependent ALOX5 activity. NAC efficacy required increases in glutathione and is correlated with suppression of reactive lipids by glutathione‐dependent enzymes such as glutathione S‐transferase. Accordingly, its protective effects were mimicked by chemical or molecular lipid peroxidation inhibitors. NAC delivered postinjury reduced neuronal death and improved functional recovery at least 7 days following ICH in mice and can synergize with clinically approved prostaglandin E2 (PGE2).
Interpretation
NAC is a promising, protective therapy for ICH, which acted to inhibit toxic arachidonic acid products of nuclear ALOX5 that synergized with exogenously delivered protective PGE2 in vitro and in vivo. The findings provide novel insight into a target for NAC, beyond the generic characterization as an antioxidant, resulting in neuroprotection and offer a feasible combinatorial strategy to optimize efficacy and safety in dosing of NAC for treatment of neurological disorders involving ferroptosis such as ICH. Ann Neurol 2018;84:854–872
•This article is focusing on improvement of metal-steam oxidation model.•Existing metal-steam oxidation models are only function of temperature.•It is predicted that steam velocity can considerably ...affect on oxidation phenomenon.•Convective cooling effect of steam on metal-steam oxidation was identified.•Existing oxidation models should be improved by considering steam velocity effect.
An experiment for high temperature steam convection effect on Zircaloy cladding oxidation phenomenon is designed and carried out in this study. Many studies for high temperature steam oxidation of Zircaloy cladding had performed for nuclear safety under the LOCA condition. And almost experiments were carried out using TGA to measure mass gain accurately caused by oxidation. And steam oxidation models of Zircaloy cladding had developed based on TGA experimental data. However, high steam velocity as much as LOCA condition can’t be applied to the TGA because this steam flow results in uncertainty of measured mass gain values. For this reason, steam oxidation experiments had been performed in relatively low steam velocity region which is not corresponding to the LOCA condition. So, existing oxidation models were function of only temperature and never included steam convection effect. Experimental methodology and apparatus for identifying high temperature isothermal steam convection effect on the Zircaloy cladding were developed in this study. As a results of this experiment, it is confirmed that high temperature steam convection considerably affects to behavior of Zircaloy cladding oxidation phenomenon. The experimental results definitely show that steam velocity can be affect Cladding temperature, mass gain, and oxidation coefficient. And it is shown that a new steam oxidation model reflecting steam convection effect is required through comparison between current experimental data and existing oxidation models. It is expected that accuracy of safety analysis can be improve and operational margin might be increased if a new steam oxidation model including steam convection effect is developed. In conclusion, high temperature steam convection effect on Zircaloy cladding oxidation phenomenon was identified, and a first step was well established for developing a new steam oxidation model including steam convection effect through this experimental study.
The nuclear sector, as a pivotal provider of clean energy, plays a crucial role in advancing green economies. This sector is currently experiencing a resurgence, particularly with the recent emphasis ...on small modular reactors (SMRs), signaling a significant momentum toward nuclear energy expansion. However, ensuring the safety of nuclear facilities remains critical for the responsible deployment of this technology. Radiation Shielding Ultra-High-Performance Concrete (RS-UHPC)—an advanced type of concrete engineered for optimal packing density to enhance mechanical properties and durability while effectively attenuating radiation—emerges as a promising solution for reinforcing the Defense in Depth (DiD) strategy in nuclear infrastructure. Nevertheless, the existing understanding of RS-UHPC is limited and dispersed. By the time of writing this review, the authors are unaware of any comprehensive review on the subject. This study aims to fill this gap by providing a thorough review of RS-UHPC formulations, critically analyzing existing literature, and identifying key RS-UHPC ingredients and mixture design techniques that influence RS-UHPC properties. Research priorities were identified to further advance RS-UHPC formulation, focusing on specific enhancements in mechanical, durability, and radiation shielding performance. The findings summarized herein contribute to a deeper understanding of the RS-UHPC compositional domain and mix design approaches, ultimately facilitating the achievement of desirable RS-UHPC performance and enhancing the DiD of nuclear facilities.
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•Radiation-shielding UHPC (RS-UHPC) is promising for enhancing nuclear safety.•This review provides insights on raw materials and their influence on RS-UHPC performance.•Some heavyweight aggregates decrease fluidity, requiring HRWRA adjustment.•RS-UHPC compressive strength is influenced by heavyweight aggregates and nanofillers.•Heavyweight aggregates significantly increase gamma radiation shielding efficiency.
Magnesium batteries appear a viable alternative to overcome the safety and energy density limitations faced by current lithium-ion technology. The development of a competitive magnesium battery is ...plagued by the existing notion of poor magnesium mobility in solids. Here we demonstrate by using ab initio calculations, nuclear magnetic resonance, and impedance spectroscopy measurements that substantial magnesium ion mobility can indeed be achieved in close-packed frameworks (~ 0.01-0.1 mS cm
at 298 K), specifically in the magnesium scandium selenide spinel. Our theoretical predictions also indicate that high magnesium ion mobility is possible in other chalcogenide spinels, opening the door for the realization of other magnesium solid ionic conductors and the eventual development of an all-solid-state magnesium battery.
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