ABSTRACT: Three 1 MV/40A accelerators in heating neutral beams (HNB) are on track to be implemented in the International Thermonuclear Experimental Reactor (ITER). ITER may produce 500 MWt of power by 2026 and may serve as a green energy roadmap for the world. They will generate -1 MV 1 h long-pulse ion beams to be neutralised for plasma heating. Due to frequently occurring vacuum sparking in the accelerators, the snubbers are used to limit the fault arc current to improve ITER safety. However, recent analyses of its reference design have raised concerns. General nonlinear transformer theory is developed for the snubber to unify the former snubbers' different design models with a clear mechanism. Satisfactory agreement between theory and tests indicates that scaling up to a 1 MV voltage may be possible. These results confirm the nonlinear process behind transformer theory and map out a reliable snubber design for a safer ITER.
Project description:Current standards for safe delivery of electrical stimulation to the central nervous system are based on foundational studies which examined post-mortem tissue for histological signs of damage. This set of observations and the subsequently proposed limits to safe stimulation, termed the “Shannon limits,” allow for a simple calculation (using charge per phase and charge density) to determine the intensity of electrical stimulation that can be delivered safely to brain tissue. In the three decades since the Shannon limits were reported, advances in molecular biology have allowed for more nuanced and detailed approaches to be used to expand current understanding of the physiological effects of stimulation. Here, we investigated spatial transcriptomics as a new approach to assess the safety and efficacy of electrical stimulation in the brain. Electrical stimulation was delivered to the rat visual cortex with either acute or chronic electrode implantation procedures (acute: tissue collection 3 hours post-stimulation on the day of surgery; chronic: stimulation delivered 1-month post-implantation, and tissue collection 24 hours later). To explore the influence of device type and stimulation parameters, we used carbon fiber ultramicroelectrode arrays (7 µm diameter) and microwire electrode arrays (50 µm diameter) delivering charge and charge density levels selected above and below reported tissue damage thresholds (range: 2-20 nC, 0.1-1 mC/cm2). Spatial transcriptomics was performed using Visium Spatial Gene Expression Slides (10x Genomics), which enabled simultaneous immunohistochemistry and spatial transcriptomics to directly compare traditional histological metrics to transcriptional profiles within each tissue sample. Our data revealed unique spatial patterns of differentially expressed genes that are related to cellular processes including inflammation, cell cycle progression, and plasticity. Effects were dependent on stimulation parameters and were localized to both traditional and ultra-small device locations. The abundance of data gathered using this approach allows for sophisticated analysis that can be used to generate new hypotheses while also revealing novel potential biomarkers of neurostimulation.
Project description:Cardiotoxicity remains a major cause of drug withdrawal, partially due to lacking predictability of animal models. Additionally, risk of cardiotoxicity following treatment of cancer patients is treatment limiting. It is unclear which patients will develop heart failure following therapy. Human pluripotent stem cell (hPSC)-derived cardiomyocytes present an unlimited cell source and may offer individualized solutions to this problem. We developed a platform to predict molecular and functional aspects of cardiotoxicity. Our platform can discriminate between the different cardiotoxic mechanisms of existing and novel anthracyclines Doxorubicin (DOXO), Aclarubicin (ACLA) and Amrubicin (AMR). DOXO and ACLA unlike AMR substantially affected the transcriptome, mitochondrial membrane integrity, contractile force and transcription factor availability. Cardiomyocytes recovered fully within two or three weeks, corresponding to the intermittent clinical treatment regimen. Our system permits the study of hPSC-cardiomyocyte recovery and the effects of accumulated dose after multiple dosing, allowing individualized cardiotoxicity evaluation, which effects millions of cancer patients treated with anthracyclines annually.
Project description:Assessing the groundwater quality at a Saudi Arabian agricultural site and the occurrence of antibiotic-resistant opportunistic pathogens on irrigated food produce
Project description:To explore the effect of butyrate on intestinal epithelial cells in collagen-induced arthritis (CIA) mouse model, we conducted Single-Cell RNA Sequencing profiling of intestinal tissue in response to butyrate treatment.
Project description:17 patients with myelofibrosis contributed paired research samples; the time points were pre-study and 12 weeks after commencing study treatment with CYT387.Gene expression analysis was investigated to study the effects of drug treatment. Additional analysis invesitigated differences in expression patterns in groups of anemia responders and non-responders following drug treatment. 34 samples representing 17 patients. Each patient submitted 1 pre-treatment sample and 1 post 12 weeks of treatment.
Project description:safety versus fear conditioning. Mice were trained with 4 unpaired (Safety) or paired (Fear) CS-US presentations over 3 days. Mice were killed by decapitation 4hrs after the last training session.
Project description:In this study we used non-targeted molecular profiling to provide insight into the extent of variation in the maize transcriptome, proteome and metabolome by analyzing replicas of two genetically modified and one isogenic maize genotype. Three white maize lines, the transgenic commercial Bt hybrid line DKC78-15 Bt (event MON810 from Monsanto), the transgenic commercial Roundup Ready (RR) line DKC78-35R (event NK603 from Monsanto) and its respective control line CRN 3505 (conventional from Monsanto) were grown in three consecutive years, and in two or three different locations in South Africa.
Project description:In this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery During drug discovery and development, the early identification of adverse effects is expected to reduce costly late stage failures of candidate drugs. As risk/safety assessment takes place rather late during the development process and due to the limited predictivity of animal models to the human situation, modern unbiased high-dimensional biology read-outs are sought, such as molecular signatures of in vivo response using high-throughput cell-based assays. In this theoretical proof-of-concept we provide findings of an in-depth exploration of a single chemical core structure. Via transcriptional profiling we identified a subset of close analogs which commonly down-regulate tubulin genes across cellular contexts, suggesting possible spindle poison effects. Confirmation via a qualified toxicity assay (in vitro micronucleus test) and the identification of a characteristic aggregate-formation phenotype via exploratory high content imaging validated the inititial findings. SAR analysis triggered the synthesis of a new set of compounds and allowed us to extend the series showing the genotoxic effect. We demonstrate the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery. We share our thoughts on how this approach may be incorporated into drug development strategies. Cells were cultured using standard protocols, seeded in 96 well plate, cultured for 8 hours before treatment with a number of inhouse synthesized compounds. The treatments represent different chemical structures/small molecules that have been synthesized in the context of developing a new drug targeting PDE10A.