2,609 research outputs found

    Joint Comprehensive Plan of Action Opportunity for HIF in Iran

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    Cooperation in fusion energy research and high-energy accelerators has been a “bridge over troubled waters” for most of a century. Physics research has traditionally been an international endeavor, involving the earliest accelerator developments, and hitting a hiatus only during World War II. Fusion energy research using magnetic confinement was internationalized by the Geneva meeting in 1958. Iran is and has been a participant in fusion research, even during the troubles of the past couple decades..

    Readiness of HIF Using the Single Pass RF Driver

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    Readiness for a concerted push to power production was the underlying theme from the inaugural HIF Workshop in 1976 through the review of ICF programs by DOE’s Energy Research and Advisory Board in 1979. Using John Lawson’s 1987 paper “Whither Heavy Ion Fusion?” [1] as a foil, this paper discusses the continuing vitality of the argument for HIF’s readiness against the backdrop that this vision is not in evidence today, having been occluded by political policies causing diversion of the HIF community into peripheral science that, although excellent, is in fact not required to complete the development of a HIF energy source..

    Joint Comprehensive Plan of Action Opportunity for HIF in Iran

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    Cooperation in fusion energy research and high-energy accelerators has been a “bridge over troubled waters” for most of a century. Physics research has traditionally been an international endeavor, involving the earliest accelerator developments, and hitting a hiatus only during World War II. Fusion energy research using magnetic confinement was internationalized by the Geneva meeting in 1958. Iran is and has been a participant in fusion research, even during the troubles of the past couple decades..

    Review of Current Literature for Prostatic Artery Embolization

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    Prostatic artery embolization (PAE) is an emerging, novel interventional technique in the management of patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). BPH is a common clinical condition in middle-aged and elderly men resulting in LUTS, including nocturia, urinary frequency, urgency, decreased urinary flow rates, hesitancy, and incomplete bladder emptying. Traditionally, LUTSs have been managed by medical or surgical therapies. Since the initial incidental discovery that selective PAE performed for uncontrolled bleeding secondary to BPH resulted in improved LUTS, the technique has continually evolved with a growing body of evidence supporting its safety and efficacy. However, despite the available data, PAE has yet to be established as a standard-of-care treatment option for patients with LUTS/BPH. In this article, the authors review the history and current state of PAE, including published data from case reports, animal studies, retrospective/prospective cohort studies, and prospective randomized controlled trials

    Comparison of Type II Endoleak Embolizations: Embolization of Endoleak Nidus Only versus Embolization of Endoleak Nidus and Branch Vessels

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    AbstractPurposeTo compare outcomes of type II endoleak embolization involving embolization of the endoleak nidus only vs embolization of the endoleak nidus and branch vessels in patients treated with endovascular repair of abdominal aortic aneurysms.Materials and MethodsTwenty-nine consecutive patients (mean age, 77.9 y; range, 63–88 y) with type II endoleak who underwent embolization from 2004 to 2015 were retrospectively reviewed. Patients were divided into 2 groups: embolization of endoleak nidus only (group A) and embolization of endoleak nidus and branch vessels (group B). Mean follow-up intervals were 20.5 months ± 14.7 in group A and 24.3 months ± 18.5 in group B. Outcomes were compared between groups by Mann–Whitney U and Pearson χ2 tests.ResultsMean interval from endovascular aneurysm repair to embolization was 47.6 months ± 42.9, and mean presentation time of endoleak before embolization was 23.1 months ± 25.8. Coils (n = 28) and liquid embolic agents (n = 23) were used for embolization. There were no significant differences in rates of residual endoleak (50% vs 53.8%; P = .96) or sac decrease/stabilization (62.5% vs 61.5%; P = .64). Procedure time and radiation exposure in group B (132.3 min ± 78.1; 232.4 Gy·cm2 ± 130.7) were greater than in group A (63.4 min ± 11.9; 61.5 Gy·cm2 ± 35.5; P < .01). There were no procedure-related complications.ConclusionsEmbolization of the endoleak nidus and branch vessels is not superior to embolization of only the nidus in terms of occlusion of type II endoleak and change in sac size despite requiring longer procedure times and resulting in greater patient radiation exposure

    DHODH modulates transcriptional elongation in the neural crest and melanoma

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    Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

    Evidence of the Generation of Isosaccharinic Acids and Their Subsequent Degradation by Local Microbial Consortia within Hyper-Alkaline Contaminated Soils, with Relevance to Intermediate Level Radioactive Waste Disposal

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    The contamination of surface environments with hydroxide rich wastes leads to the formation of high pH (>11.0) soil profiles. One such site is a legacy lime works at Harpur Hill, Derbyshire where soil profile indicated in-situ pH values up to pH 12. Soil and porewater profiles around the site indicated clear evidence of the presence of the α and β stereoisomers of isosaccharinic acid (ISA) resulting from the anoxic, alkaline degradation of cellulosic material. ISAs are of particular interest with regards to the disposal of cellulosic materials contained within the intermediate level waste (ILW) inventory of the United Kingdom, where they may influence radionuclide mobility via complexation events occurring within a geological disposal facility (GDF) concept. The mixing of uncontaminated soils with the alkaline leachate of the site resulted in ISA generation, where the rate of generation in-situ is likely to be dependent upon the prevailing temperature of the soil. Microbial consortia present in the uncontaminated soil were capable of surviving conditions imposed by the alkaline leachate and demonstrated the ability to utilise ISAs as a carbon source. Leachate-contaminated soil was sub-cultured in a cellulose degradation product driven microcosm operating at pH 11, the consortia present were capable of the degradation of ISAs and the generation of methane from the resultant H2/CO2 produced from fermentation processes. Following microbial community analysis, fermentation processes appear to be predominated by Clostridia from the genus Alkaliphilus sp, with methanogenesis being attributed to Methanobacterium and Methanomassiliicoccus sp. The study is the first to identify the generation of ISA within an anthropogenic environment and advocates the notion that microbial activity within an ILW-GDF is likely to influence the impact of ISAs upon radionuclide migration

    Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer

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    Chemotherapy resistance is a major obstacle in cancer treatment, yet the mechanisms of response to specific therapies have been largely unexplored in vivo. Employing genetic, genomic, and imaging approaches, we examined the dynamics of response to a mainstay chemotherapeutic, cisplatin, in multiple mouse models of human non-small-cell lung cancer (NSCLC). We show that lung tumors initially respond to cisplatin by sensing DNA damage, undergoing cell cycle arrest, and inducing apoptosis—leading to a significant reduction in tumor burden. Importantly, we demonstrate that this response does not depend on the tumor suppressor p53 or its transcriptional target, p21. Prolonged cisplatin treatment promotes the emergence of resistant tumors with enhanced repair capacity that are cross-resistant to platinum analogs, exhibit advanced histopathology, and possess an increased frequency of genomic alterations. Cisplatin-resistant tumors express elevated levels of multiple DNA damage repair and cell cycle arrest-related genes, including p53-inducible protein with a death domain (Pidd). We demonstrate a novel role for PIDD as a regulator of chemotherapy response in human lung tumor cells.National Institutes of Health (U.S.) (grant 5-UO1-CA84306)National Cancer Institute (U.S.) (CA034992

    A Distant Fast Radio Burst Associated with Its Host Galaxy by the Very Large Array

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    We present the discovery and subarcsecond localization of a new fast radio burst (FRB) by the Karl G. Jansky Very Large Array (VLA) and realfast search system. The FRB was discovered on 2019 June 14 with a dispersion measure of 959 pc cm⁻³. This is the highest DM of any localized FRB and its measured burst fluence of 0.6 Jy ms is less than nearly all other FRBs. The source is not detected to repeat in 15 hr of VLA observing and 153 hr of CHIME/FRB observing. We describe a suite of statistical and data quality tests we used to verify the significance of the event and its localization precision. Follow-up optical/infrared photometry with Keck and Gemini associate the FRB with a pair of galaxies with r ∼ 23 mag. The false-alarm rate for radio transients of this significance that are associated with a host galaxy is roughly 3×10⁻⁴ hr⁻¹. The two putative host galaxies have similar photometric redshifts of z_(phot) ∼ 0.6, but different colors and stellar masses. Comparing the host distance to that implied by the dispersion measure suggests a modest (~ 50 pc/cm⁻³) electron column density associated with the FRB environment or host galaxy/galaxies
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