Direct-drive laser fusion: status, plans and future Campbell, E M; Sangster, T C; Goncharov, V N ...
Philosophical transactions of the Royal Society of London. Series A: Mathematical, physical, and engineering sciences,
01/2021, Volume:
379, Issue:
2189
Journal Article
Peer reviewed
Open access
Laser-direct drive (LDD), along with laser indirect (X-ray) drive (LID) and magnetic drive with pulsed power, is one of the three viable inertial confinement fusion approaches to achieving fusion ...ignition and gain in the laboratory. The LDD programme is primarily being executed at both the Omega Laser Facility at the Laboratory for Laser Energetics and at the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory. LDD research at Omega includes cryogenic implosions, fundamental physics including material properties, hydrodynamics and laser-plasma interaction physics. LDD research on the NIF is focused on energy coupling and laser-plasma interactions physics at ignition-scale plasmas. Limited implosions on the NIF in the 'polar-drive' configuration, where the irradiation geometry is configured for LID, are also a feature of LDD research. The ability to conduct research over a large range of energy, power and scale size using both Omega and the NIF is a major positive aspect of LDD research that reduces the risk in scaling from OMEGA to megajoule-class lasers. The paper will summarize the present status of LDD research and plans for the future with the goal of ultimately achieving a burning plasma in the laboratory. This article is part of a discussion meeting issue 'Prospects for high gain inertial fusion energy (part 2)'.
Acute and chronic exposures to organophosphates (OPs), including agricultural pesticides, industrial chemicals, and chemical warfare agents, remain a significant worldwide health risk. The mechanisms ...by which OPs alter development and cognition in exposed individuals remain poorly understood, in part due to the large number of structurally diverse OPs and the wide range of affected proteins and signaling pathways. To investigate the influence of structure on OP targets in mammalian systems, we have developed a series of probes for activity-based protein profiling (ABPP) featuring two distinct reactive groups that mimic OP chemical reactivity. FOP features a fluorophosphonate moiety, and PODA and CODA utilize a dialkynyl phosphate ester; both reactive group types target serine hydrolase activity. As the oxon represents the highly reactive and toxic functional group of many OPs, the new probes described herein enhance our understanding of tissue-specific reactivity of OPs. Chemoproteomic analysis of mouse tissues treated with the probes revealed divergent protein profiles, demonstrating the influence of probe structure on protein targeting. These targets also vary in sensitivity toward different OPs. The simultaneous use of multiple probes in ABPP experiments may therefore offer more comprehensive coverage of OP targets; FOP consistently labeled more targets in both brain and liver than PODA or CODA, suggesting the dialkyne warhead is more selective for enzymes in major signaling pathways than the more reactive fluorophosphonate warhead. Additionally, the probes can be used to assess reactivation of OP-inhibited enzymes by N-oximes and may serve as diagnostic tools for screening of therapeutic candidates in a panel of protein targets. These applications will help clarify the short- and long-term effects of OP toxicity beyond acetylcholinesterase inhibition, investigate potential points of convergence for broad spectrum therapeutic development, and support future efforts to screen candidate molecules for efficacy in various model systems.
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IJS, KILJ, NUK, PNG, UL, UM
Topotecan is cytotoxic to glioma cells but is clinically ineffective because of drug delivery limitations. Systemic delivery is limited by toxicity and insufficient brain penetrance, and, to date, ...convection-enhanced delivery (CED) has been restricted to a single treatment of restricted duration. To address this problem, we engineered a subcutaneously implanted catheter-pump system capable of repeated, chronic (prolonged, pulsatile) CED of topotecan into the brain and tested its safety and biological effects in patients with recurrent glioblastoma.
We did a single-centre, open-label, single-arm, phase 1b clinical trial at Columbia University Irving Medical Center (New York, NY, USA). Eligible patients were at least 18 years of age with solitary, histologically confirmed recurrent glioblastoma showing radiographic progression after surgery, radiotherapy, and chemotherapy, and a Karnofsky Performance Status of at least 70. Five patients had catheters stereotactically implanted into the glioma-infiltrated peritumoural brain and connected to subcutaneously implanted pumps that infused 146 μM topotecan 200 μL/h for 48 h, followed by a 5–7-day washout period before the next infusion, with four total infusions. After the fourth infusion, the pump was removed and the tumour was resected. The primary endpoint of the study was safety of the treatment regimen as defined by presence of serious adverse events. Analyses were done in all treated patients. The trial is closed, and is registered with ClinicalTrials.gov, NCT03154996.
Between Jan 22, 2018, and July 8, 2019, chronic CED of topotecan was successfully completed safely in all five patients, and was well tolerated without substantial complications. The only grade 3 adverse event related to treatment was intraoperative supplemental motor area syndrome (one 20% of five patients in the treatment group), and there were no grade 4 adverse events. Other serious adverse events were related to surgical resection and not the study treatment. Median follow-up was 12 months (IQR 10–17) from pump explant. Post-treatment tissue analysis showed that topotecan significantly reduced proliferating tumour cells in all five patients.
In this small patient cohort, we showed that chronic CED of topotecan is a potentially safe and active therapy for recurrent glioblastoma. Our analysis provided a unique tissue-based assessment of treatment response without the need for large patient numbers. This novel delivery of topotecan overcomes limitations in delivery and treatment response assessment for patients with glioblastoma and could be applicable for other anti-glioma drugs or other CNS diseases. Further studies are warranted to determine the effect of this drug delivery approach on clinical outcomes.
US National Institutes of Health, The William Rhodes and Louise Tilzer Rhodes Center for Glioblastoma, the Michael Weiner Glioblastoma Research Into Treatment Fund, the Gary and Yael Fegel Foundation, and The Khatib Foundation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
A high-granularity mixed spectrometer consisting of high-resolution Ge and very fast LaBr3(Ce)-scintillator detectors has been installed around a fission target at the cold-neutron guide PF1B of the ...high-flux reactor of the Institut Laue–Langevin. Lifetimes of excited states in the range of 10ps to 10ns can be measured in around 100 exotic neutron-rich fission fragments using Ge-gated LaBr3(Ce)–LaBr3(Ce) or Ge–Ge–LaBr3(Ce)–LaBr3(Ce) coincidences. We report on various characteristics of the EXILL&FATIMA spectrometer for the energy range of 40keV up to 6.8MeV and present results of ps-lifetime test measurements in a fission fragment. The results are discussed with respect to possible systematic errors induced by background contributions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
FATIMA — FAst TIMing Array for DESPEC at FAIR Rudigier, M.; Podolyák, Zs; Regan, P.H. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
07/2020, Volume:
969
Journal Article
Peer reviewed
Open access
The components, working principle and characteristics of FATIMA (FAst TIMing Array), a fast-timing detector system for DESPEC at FAIR, are described. The core system includes 36 LaBr3(Ce) ...scintillator detectors, a mounting frame for the DESPEC station and a VME-based fast-timing data acquisition system. The current electronic timing circuit is based on V812 constant fraction discriminators and V1290 time-to-digital converters. Gamma-ray energies are measured using V1751 digitisers. Characteristics of the core FATIMA system including efficiency, energy, and coincidence resolving time, as well as limitations, are discussed on the basis of test measurements performed in the S4 cave at GSI, Germany. The coincidence γ-γ time resolution for the prompt 60Co cascade is determined to be ∼320 ps full width at half maximum. The total full energy peak efficiency at 1 MeV for the 36 detector array in the DESPEC setup is 2.9%. The energy-dependent prompt response centroid curve with the current CFD/TDC combination is shown to be smooth; the centroid shift method can be applied for the measurement of half-lives below 200 ps. An overview of applications of the FATIMA detectors as an ancilliary system in combination with other detector arrays during recent years is given. Data on the operation of the detectors in the presence of magnetic fields are presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
A simple 3D dynamic model for inertial confinement fusion (ICF) implosions has been developed and used to assess the impacts of low-mode asymmetry, aneurysms and mix-induced radiative loss on capsule ...performance across ICF platforms. The model, while benchmarked against radiation hydrodynamics simulations, benefits from simplicity and speed to allow rapid assessment of possible sources of degradation as well as to help build intuition about the relative importance of different effects. Degradations in the model result from 3D areal density perturbations that grow under deceleration from a radial stagnation flow, resulting in reduced convergence, stagnation pressure and temperature. When available, experimental data are used as input to seed 3D perturbations in the model so that the actual observed hotspot and shell areal density asymmetry at stagnation, as well as the radiation loss increase from mix impurities, are accurately reproduced. This model is applied to a broad set of implosion data from the NIF and Omega, including examples from both indirect drive and direct drive. The model matches most experimental observables and explains major performance degradation mechanisms which can result in 30-100-fold reductions in yield. We examine a modified ignition criterion that accounts for the increase in expansion work, due to the presence of 3D perturbations and loss-of-confinement in thin regions of the shell.
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