The heating neutral beam injectors (HNBs) of ITER are designed to deliver 16.7 MW of 1 MeV D0 or 0.87 MeV H0 to the ITER plasma for up to 3600 s. They will be the most powerful neutral beam (NB) ...injectors ever, delivering higher energy NBs to the plasma in a tokamak for longer than any previous systems have done. The design of the HNBs is based on the acceleration and neutralisation of negative ions as the efficiency of conversion of accelerated positive ions is so low at the required energy that a realistic design is not possible, whereas the neutralisation of H− and D− remains acceptable ( 56%). The design of a long pulse negative ion based injector is inherently more complicated than that of short pulse positive ion based injectors because: negative ions are harder to create so that they can be extracted and accelerated from the ion source; electrons can be co-extracted from the ion source along with the negative ions, and their acceleration must be minimised to maintain an acceptable overall accelerator efficiency; negative ions are easily lost by collisions with the background gas in the accelerator; electrons created in the extractor and accelerator can impinge on the extraction and acceleration grids, leading to high power loads on the grids; positive ions are created in the accelerator by ionisation of the background gas by the accelerated negative ions and the positive ions are back-accelerated into the ion source creating a massive power load to the ion source; electrons that are co-accelerated with the negative ions can exit the accelerator and deposit power on various downstream beamline components. The design of the ITER HNBs is further complicated because ITER is a nuclear installation which will generate very large fluxes of neutrons and gamma rays. Consequently all the injector components have to survive in that harsh environment. Additionally the beamline components and the NB cell, where the beams are housed, will be activated and all maintenance will have to be performed remotely. This paper describes the design of the HNB injectors, but not the associated power supplies, cooling system, cryogenic system etc, or the high voltage bushing which separates the vacuum of the beamline from the high pressure SF6 of the high voltage (1 MV) transmission line, through which the power, gas and cooling water are supplied to the beam source. Also the magnetic field reduction system is not described.
•Understanding the factors that can sustainably enhance soybean yield is critical.•Higher microbial diversity promoted less soybean damage by insect herbivores.•Soybean exhibits high tolerance to ...herbivory regardless of microbial diversity.•Promoting microbial diversity may promote a sustainable agricultural economy.
Biodiversity within ecological communities has been shown to influence plant resistance and tolerance to herbivory, and may strongly interact with climate change. However, the effects of diversity within microbial symbionts on their plant hosts’ responses to herbivores is less well documented, particularly within the context of agricultural systems. Here we examine the interactive effects of rhizobial diversity and drought in promoting soybean resistance and tolerance to insect and mammalian herbivores in an outdoor pot experiment. We demonstrate that soybean plants provided with a diverse mixture of rhizobial strains experience 30% less damage by chewing insect herbivores under both drought (reduced watering and increased temperature) and ambient weather conditions, as well as half as much colonization by aphids under drought conditions. This effect was not due to the presence of any particularly beneficial rhizobial strain (i.e., not a selection effect), but rather due to an enhanced benefit provided by the rhizobial strains in combination (i.e., a complementarity effect). No effects of rhizobial diversity were observed on the rate of defoliation by rabbits. While rhizobial diversity did affect soybean resistance to insect herbivores, these differences in insect damage did not carry through to affect soybean growth or final yield. Thus, soybean plants exhibited high tolerance to herbivory regardless of our experimentally imposed rhizobial diversity or drought treatments. With future projections for increased pest outbreaks and drought, understanding the factors that can sustainably enhance agricultural yield is critical. Our results suggest that promoting rhizobial diversity within soybean agriculture may be one nature-based solution to promote the resistance of this critical crop to insect pests.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose
Monoclonal antibody (mAb)-based PET (immunoPET) imaging can characterise tumour lesions non-invasively. It may be a valuable tool to determine which patients may benefit from treatment with a ...specific monoclonal antibody (mAb) and evaluate treatment response. For
89
Zr immunoPET imaging, higher sensitivity of state-of-the art PET/CT systems equipped with silicon photomultiplier (SiPM)-based detector elements may be beneficial as the low positron abundance of
89
Zr causes a low signal-to-noise level. Moreover, the long physical half-life limits the amount of activity that can be administered to the patients leading to poor image quality even when using long scan durations. Here, we investigated the difference in semiquantitative performance between the PMT-based Biograph mCT, our clinical reference system, and the SiPM-based Biograph Vision PET/CT in
89
Zr immunoPET imaging. Furthermore, the effects of scan duration reduction using the Vision on semiquantitative imaging parameters and its influence on image quality assessment were evaluated.
Methods
Data were acquired on day 4 post 37 MBq
89
Zr-labelled mAb injection. Five patients underwent a double scan protocol on both systems. Ten patients were scanned only on the Vision. For PET image reconstruction, three protocols were used, i.e. one camera-dependent protocol and European Association of Nuclear Medicine Research Limited (EARL) standards 1 and 2 compliant protocols. Vision data were acquired in listmode and were reprocessed to obtain images at shorter scan durations. Semiquantitative PET image parameters were derived from tumour lesions and healthy tissues to assess differences between systems and scan durations. Differently reconstructed images obtained using the Vision were visually scored regarding image quality by two nuclear medicine physicians.
Results
When images were reconstructed using 100% acquisition time on both systems following EARL standard 1 compliant reconstruction protocols, results regarding semiquantification were comparable. For Vision data, reconstructed images that conform to EARL1 standards still resulted in comparable semiquantification at shorter scan durations (75% and 50%) regarding 100% acquisition time.
Conclusion
Scan duration of
89
Zr immunoPET imaging using the Vision can be decreased up to 50% compared with using the mCT while maintaining image quality using the EARL1 compliant reconstruction protocol.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
The ITER neutral beam (NB) injectors are the first injectors that will have to operate under conditions and constraints similar to those that will be encountered in a fusion reactor. These injectors ...will have to operate in a hostile radiation environment and they will become highly radioactive due to the neutron flux from ITER. The injectors will use a single large ion source and accelerator that will produce 40 A 1 MeV D − beams for pulse lengths of up to 3600 s. Significant design changes have been made to the ITER heating NB (HNB) injector over the past 4 years. The main changes are: Modifications to allow installation and maintenance of the beamline components with an overhead crane. The beam source vessel shape has been changed and the beam source moved to allow more space for the connections between the 1 MV bushing and the beam source. The RF driven negative ion source has replaced the filamented ion source as the reference design. The ion source and extractor power supplies will be located in an air insulated high voltage (−1 MV) deck located outside the tokamak building instead of inside an SF 6 insulated HV deck located above the injector. Introduction of an all metal absolute valve to prevent any tritium in the machine to escape into the NB cell during maintenance. This paper describes the status of the design as of December 2008 including the above mentioned changes. The very important power supply system of the neutral beam injectors is not described in any detail as that merits a paper beyond the competence of the present authors. The R&D required to realize the injectors described in this paper must be carried out on a dedicated neutral beam test facility, which is not described here.
A recent intervention study demonstrated the occurrence of irilone as second most abundant isoflavone next to daidzein in human plasma after consumption of a red clover-based dietary supplement ...(RCDS) containing predominately formononetin ≫ biochanin A > irilone (12 % of these isoflavones). To elucidate the relevance of this finding, in the present study (1) the representativeness of the isoflavone composition of the RCDS and (2) the estrogenic activity of irilone were investigated. Thus, major isoflavones were quantified in eight commercially available RCDS. Furthermore, the estrogenic activities of irilone and other isoflavones were determined by marker gene expression in Ishikawa and cell proliferation in MCF-7 cells. Irilone amounted to 1.8–10.9 mg/g capsule content and 5–18 % of the three major isoflavones, respectively, demonstrating the general occurrence of irilone in RCDS. Moreover, irilone significantly induced the activity of alkaline phosphatase (AlP) as well as AlP, progesterone receptor, and androgen receptor mRNA levels in Ishikawa cells. Furthermore, irilone significantly induced MCF-7 cell proliferation. Neither 17β-estradiol (E2)-induced AlP activity nor E2-induced MCF-7 cell proliferation was affected by irilone. ICI182,780 antagonized IRI-induced effects on both AlP activity and cell proliferation, suggesting an estrogen receptor agonistic mode of action. Taking into account the estrogenic activity of red clover isoflavones (formononetin, biochanin A, prunetin, glycitein) and their biotransformation products (daidzein, genistein, ethylphenol) as well as published plasma levels of isoflavones after consumption of RCDS, irilone could contribute approximately 50 % of the E2 equivalents estimated for daidzein.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Despite being widely used to investigate 17β-estradiol (E2)-induced mammary gland (MG) carcinogenesis and prevention thereof, estrogen homeostasis and its significance in the female August Copenhagen ...Irish (ACI) rat model is unknown. Thus, levels of 12 estrogens including metabolites and conjugates were determined mass spectrometrically in 38 plasmas and 52 tissues exhibiting phenotypes ranging from normal to palpable tumor derived from a representative ACI study using two different diets. In tissues, 40 transcripts encoding proteins involved in estrogen (biotrans)formation, ESR1-mediated signaling, proliferation and oxidative stress were analyzed (TaqMan PCR). Influence of histo(patho)logic phenotypes and diet on estrogen and transcript levels was analyzed by 2-way ANOVA and explanatory variables influencing levels and bioactivity of estrogens in tissues were identified by multiple linear regression models. Estrogen profiles in tissue and plasma and the influence of
Hsd17b1
levels on intra-tissue levels of E2 and E1 conclusively indicated intra-mammary formation of E2 in ACI tumors by HSD17B1-mediated conversion of E1. Proliferation in ACI tumors was influenced by
Egfr, Igf1r, Hgf
and
Met
levels. 2-MeO-E1, the only oxidative estrogen metabolite detected above 28–42 fmol/g, was predominately observed in hyperplastic tissues and intra-tissue conversion of E1 seemed to contribute to its levels. The association of the occurrence of 2-MeO-E1 with higher levels of oxidative stress observed in hyperplastic and tumor tissues remained equivocal. Thus, the present study provides mechanistic explanation for previous and future results observed in the ACI model.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In parallel to the developments dedicated to the ITER neutral beam (NB) system, CEA-IRFM with laboratories in France and Switzerland are studying the feasibility of a new generation of NB system able ...to provide heating and current drive for the future DEMOnstration fusion reactor. For the steady-state scenario, the NB system will have to provide a high NB power level with a high wall-plug efficiency ( ∼ 60%). Neutralization of the energetic negative ions by photodetachment (so called photoneutralization), if feasible, appears to be the ideal solution to meet these performances, in the sense that it could offer a high beam neutralization rate (>80%) and a wall-plug efficiency higher than 60%. The main challenge of this new injector concept is the achievement of a very high power photon flux which could be provided by 3 MW Fabry-Perot optical cavities implanted along the 1 MeV D− beam in the neutralizer stage. The beamline topology is tall and narrow to provide laminar ion beam sheets, which will be entirely illuminated by the intra-cavity photon beams propagating along the vertical axis. The paper describes the present R&D (experiments and modelling) addressing the development of a new ion source concept (Cybele source) which is based on a magnetized plasma column. Parametric studies of the source are performed using Langmuir probes in order to characterize and compare the plasma parameters in the source column with different plasma generators, such as filamented cathodes, radio-frequency driver and a helicon antenna specifically developed at SPC-EPFL satisfying the requirements for the Cybele (axial magnetic field of 10 mT, source operating pressure: 0.3 Pa in hydrogen or deuterium). The paper compares the performances of the three plasma generators. It is shown that the helicon plasma generator is a very promising candidate to provide an intense and uniform negative ion beam sheet.
The soy isoflavone daidzein (DAI) is known to undergo metabolism to equol (EQO) and to 3′-hydroxy-DAI (3′-HO-DAI) and 6-hydroxy-DAI (6-HO-DAI) in humans. In order to better understand the ...implications of soy diets for human health, the hormonal and genotoxic activities of these DAI metabolites were studied in cultured human endometrial carcinoma cells. When the estrogenicity was tested by cell-free binding to recombinant human estrogen receptor (ER) α and β as well as by the induction of enzyme activity and gene expression of alkaline phosphatase (ALP) in Ishikawa cells, the ranking order was EQO
>
DAI
>
3′-HO-DAI
>
6-HO-DAI. All compounds had a higher affinity to ERβ than to ERα. No significant anti-estrogenic effects of the DAI metabolites were observed in the cells at non-cytotoxic concentrations. The in vitro genotoxicity was assessed by analyzing effects on cell cycle distribution and cell morphology as well as the induction of micronuclei (MN). EQO caused a slight increase in G1 and decrease in S phase of the cell cycle, and slightly but significantly induced kinetochore-positive as well as kinetochore-negative MN and an elevated proportion of abnormal mitotic spindles. 3′-HO-DAI, but not 6-HO-DAI, induced kinetochore-negative MN. The observation that major human metabolites of DAI exhibit estrogenic and genotoxic potential may be of relevance for the safety evaluation of diets containing soy isoflavones.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Antipsychotic-induced weight gain is a major health concern in children and adolescents. The aim of this study was to identify risk factors for weight gain during short-, middle- and long-term ...treatment with antipsychotic drugs in this young population. We analysed a combined prospective and a retrospective observational cohort of Dutch children and adolescents, starting with risperidone, aripiprazole or pipamperone treatment. Linear mixed models were used to test whether sex, age, baseline body-mass-index (BMI)
z
score, type of antipsychotic, dose equivalent/kg, duration of use, previous antipsychotic use, ethnicity, physical exercise, IQ, concomitant medication, and psychiatric classification predicted the BMI
z
score for a follow-up of < 15 weeks, 15–52 weeks or > 52 weeks. A total of 144 patients were included with a median interquartile range (IQR) age of 9 (4) years and median follow-up of 30 (73) weeks. During the complete follow-up, the median (IQR) weight gain was 0.37 (0.95) BMI
z
score points. Antipsychotic-induced weight gain was found to be most pronounced during the first 15 weeks of use (BMI
z
score increase per week
β
= 0.02, 95% CI 0.01–0.03,
p
= 0.002). A higher baseline BMI
z
score and the absence of stimulant use were associated with a higher BMI
z
score during the entire follow-up and after 15 weeks, respectively. Previous treatment with an antipsychotic drug was associated with less weight gain during the first 15 weeks of treatment. Our findings underscore the importance of close patient monitoring during the first weeks of antipsychotic treatment with a focus on patients with a high baseline BMI
z
score.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
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