| 1. |
- Martin, P., et al.
(författare)
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Overview of the RFX-mod fusion science programme
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 53:10, s. 104018-
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Forskningsöversikt (refereegranskat)abstract
- This paper reports the highlights of the RFX-mod fusion science programme since the last 2010 IAEA Fusion Energy Conference. The RFX-mod fusion science programme focused on two main goals: exploring the fusion potential of the reversed field pinch (RFP) magnetic configuration and contributing to the solution of key science and technology problems in the roadmap to ITER. Active control of several plasma parameters has been a key tool in this endeavour. New upgrades on the system for active control of magnetohydrodynamic (MHD) stability are underway and will be presented in this paper. Unique among the existing fusion devices, RFX-mod has been operated both as an RFP and as a tokamak. The latter operation has allowed the exploration of edge safety factor q edge < 2 with active control of MHD stability and studies concerning basic energy and flow transport mechanisms. Strong interaction has continued with the stellarator community in particular on the physics of helical states and on three-dimensional codes.
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| 2. |
- Martin, P., et al.
(författare)
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Overview of the RFX fusion science program
- 2011
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 51:9, s. 094023-
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Tidskriftsartikel (refereegranskat)abstract
- This paper summarizes the main achievements of the RFX fusion science program in the period between the 2008 and 2010 IAEA Fusion Energy Conferences. RFX-mod is the largest reversed field pinch in the world, equipped with a system of 192 coils for active control of MHD stability. The discovery and understanding of helical states with electron internal transport barriers and core electron temperature >1.5 keV significantly advances the perspectives of the configuration. Optimized experiments with plasma current up to 1.8 MA have been realized, confirming positive scaling. The first evidence of edge transport barriers is presented. Progress has been made also in the control of first-wall properties and of density profiles, with initial first-wall lithization experiments. Micro-turbulence mechanisms such as ion temperature gradient and micro-tearing are discussed in the framework of understanding gradient-driven transport in low magnetic chaos helical regimes. Both tearing mode and resistive wall mode active control have been optimized and experimental data have been used to benchmark numerical codes. The RFX programme also provides important results for the fusion community and in particular for tokamaks and stellarators on feedback control of MHD stability and on three-dimensional physics. On the latter topic, the result of the application of stellarator codes to describe three-dimensional reversed field pinch physics will be presented.
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| 3. |
- Zuin, M., et al.
(författare)
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Overview of the RFX-mod fusion science activity
- 2017
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Ingår i: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 57:10
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports the main recent results of the RFX-mod fusion science activity. The RFX-mod device is characterized by a unique flexibility in terms of accessible magnetic configurations. Axisymmetric and helically shaped reversed-field pinch equilibria have been studied, along with tokamak plasmas in a wide range of q(a) regimes (spanning from 4 down to 1.2 values). The full range of magnetic configurations in between the two, the so-called ultra-low q ones, has been explored, with the aim of studying specific physical issues common to all equilibria, such as, for example, the density limit phenomenon. The powerful RFX-mod feedback control system has been exploited for MHD control, which allowed us to extend the range of experimental parameters, as well as to induce specific magnetic perturbations for the study of 3D effects. In particular, transport, edge and isotope effects in 3D equilibria have been investigated, along with runaway mitigations through induced magnetic perturbations. The first transitions to an improved confinement scenario in circular and D-shaped tokamak plasmas have been obtained thanks to an active modification of the edge electric field through a polarized electrode. The experiments are supported by intense modeling with 3D MHD, gyrokinetic, guiding center and transport codes. Proposed modifications to the RFX-mod device, which will enable further contributions to the solution of key issues in the roadmap to ITER and DEMO, are also briefly presented.
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| 4. |
- Lorenzini, R., et al.
(författare)
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Self-organized helical equilibria as a new paradigm for ohmically heated fusion plasmas
- 2009
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Ingår i: Nature Physics. - : Springer Science and Business Media LLC. - 1745-2473 .- 1745-2481. ; 5:8, s. 570-574
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Tidskriftsartikel (refereegranskat)abstract
- In the quest for new energy sources, the research on controlled thermonuclear fusion has been boosted by the start of the construction phase of the International Thermonuclear Experimental Reactor (ITER). ITER is based on the tokamak magnetic configuration, which is the best performing one in terms of energy confinement. Alternative concepts are however actively researched, which in the long term could be considered for a second generation of reactors. Here, we show results concerning one of these configurations, the reversed-field pinch (RFP). By increasing the plasma current, a spontaneous transition to a helical equilibrium occurs, with a change of magnetic topology. Partially conserved magnetic flux surfaces emerge within residual magnetic chaos, resulting in the onset of a transport barrier. This is a structural change and sheds new light on the potential of the RFP as the basis for a low-magnetic-field ohmic fusion reactor.
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| 5. |
- Martin, P., et al.
(författare)
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Overview of RFX-mod results
- 2009
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 49:10, s. 104019-
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Tidskriftsartikel (refereegranskat)abstract
- With the exploration of the MA plasma current regime in up to 0.5 s long discharges, RFX-mod has opened new and very promising perspectives for the reversed field pinch (RFP) magnetic configuration, and has made significant progress in understanding and improving confinement and in controlling plasma stability. A big leap with respect to previous knowledge and expectations on RFP physics and performance has been made by RFX-mod since the last 2006 IAEA Fusion Energy Conference. A new self-organized helical equilibrium has been experimentally achieved ( the Single Helical Axis-SHAx-state), which is the preferred state at high current. Strong core electron transport barriers characterize this regime, with electron temperature gradients comparable to those achieved in tokamaks, and by a factor of 4 improvement in confinement time with respect to the standard RFP. RFX-mod is also providing leading edge results on real-time feedback control of MHD instabilities, of general interest for the fusion community.
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| 6. |
- Romano, K. A., et al.
(författare)
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Gut Microbiota-Generated Phenylacetylglutamine and Heart Failure
- 2023
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Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The gut microbiota-dependent metabolite phenylacetylgutamine (PAGln) is both associated with atherothrombotic heart disease in humans, and mechanistically linked to cardiovascular disease pathogenesis in animal models via modulation of adrenergic receptor signaling.Methods: Here we examined both clinical and mechanistic relationships between PAGln and heart failure (HF). First, we examined associations among plasma levels of PAGln and HF, left ventricular ejection fraction, and N-terminal pro-B-type natriuretic peptide in 2 independent clinical cohorts of subjects undergoing coronary angiography in tertiary referral centers (an initial discovery US Cohort, n=3256; and a validation European Cohort, n=829). Then, the impact of PAGln on cardiovascular phenotypes relevant to HF in cultured cardiomyoblasts, and in vivo were also examined.Results: Circulating PAGln levels were dose-dependently associated with HF presence and indices of severity (reduced ventricular ejection fraction, elevated N-terminal pro-B-type natriuretic peptide) independent of traditional risk factors and renal function in both cohorts. Beyond these clinical associations, mechanistic studies showed both PAGln and its murine counterpart, phenylacetylglycine, directly fostered HF-relevant phenotypes, including decreased cardiomyocyte sarcomere contraction, and B-type natriuretic peptide gene expression in both cultured cardiomyoblasts and murine atrial tissue.Conclusions: The present study reveals the gut microbial metabolite PAGln is clinically and mechanistically linked to HF presence and severity. Modulating the gut microbiome, in general, and PAGln production, in particular, may represent a potential therapeutic target for modulating HF.Registration: URL: ; Unique identifier: NCT00590200 and URL: ; Unique identifier: DRKS00020915.
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| 7. |
- Nemet, I., et al.
(författare)
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Atlas of gut microbe-derived products from aromatic amino acids and risk of cardiovascular morbidity and mortality
- 2023
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Ingår i: European Heart Journal. - 0195-668X. ; 44:32
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Tidskriftsartikel (refereegranskat)abstract
- Aims Precision microbiome modulation as a novel treatment strategy is a rapidly evolving and sought goal. The aim of this study is to determine relationships among systemic gut microbial metabolite levels and incident cardiovascular disease risks to identify gut microbial pathways as possible targets for personalized therapeutic interventions.Methods and results Stable isotope dilution mass spectrometry methods to quantitatively measure aromatic amino acids and their metabolites were used to examine sequential subjects undergoing elective diagnostic cardiac evaluation in two independent cohorts with longitudinal outcome data [US (n = 4000) and EU (n = 833) cohorts]. It was also used in plasma from humans and mice before vs. after a cocktail of poorly absorbed antibiotics to suppress gut microbiota. Multiple aromatic amino acid-derived metabolites that originate, at least in part, from gut bacteria are associated with incident (3-year) major adverse cardiovascular event (MACE) risks (myocardial infarction, stroke, or death) and all-cause mortality independent of traditional risk factors. Key gut microbiota-derived metabolites associated with incident MACE and poorer survival risks include: (i) phenylacetyl glutamine and phenylacetyl glycine (from phenylalanine); (ii) p-cresol (from tyrosine) yielding p-cresol sulfate and p-cresol glucuronide; (iii) 4-OH-phenyllactic acid (from tyrosine) yielding 4-OH-benzoic acid and 4-OH-hippuric acid; (iv) indole (from tryptophan) yielding indole glucuronide and indoxyl sulfate; (v) indole-3-pyruvic acid (from tryptophan) yielding indole-3-lactic acid and indole-3-acetyl-glutamine, and (vi) 5-OH-indole-3-acetic acid (from tryptophan).Conclusion Key gut microbiota-generated metabolites derived from aromatic amino acids independently associated with incident adverse cardiovascular outcomes are identified, and thus will help focus future studies on gut-microbial metabolic outputs relevant to host cardiovascular health.
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| 8. |
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| 9. |
- Benson, Tyler W., et al.
(författare)
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Gut Microbiota-Derived Trimethylamine N-Oxide Contributes to Abdominal Aortic Aneurysm Through Inflammatory and Apoptotic Mechanisms
- 2023
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 147:14, s. 1079-1096
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Tidskriftsartikel (refereegranskat)abstract
- Background:Large-scale human and mechanistic mouse studies indicate a strong relationship between the microbiome-dependent metabolite trimethylamine N-oxide (TMAO) and several cardiometabolic diseases. This study aims to investigate the role of TMAO in the pathogenesis of abdominal aortic aneurysm (AAA) and target its parent microbes as a potential pharmacological intervention.Methods:TMAO and choline metabolites were examined in plasma samples, with associated clinical data, from 2 independent patient cohorts (N=2129 total). Mice were fed a high-choline diet and underwent 2 murine AAA models, angiotensin II infusion in low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice or topical porcine pancreatic elastase in C57BL/6J mice. Gut microbial production of TMAO was inhibited through broad-spectrum antibiotics, targeted inhibition of the gut microbial choline TMA lyase (CutC/D) with fluoromethylcholine, or the use of mice genetically deficient in flavin monooxygenase 3 (Fmo3(-/-)). Finally, RNA sequencing of in vitro human vascular smooth muscle cells and in vivo mouse aortas was used to investigate how TMAO affects AAA.Results:Elevated TMAO was associated with increased AAA incidence and growth in both patient cohorts studied. Dietary choline supplementation augmented plasma TMAO and aortic diameter in both mouse models of AAA, which was suppressed with poorly absorbed oral broad-spectrum antibiotics. Treatment with fluoromethylcholine ablated TMAO production, attenuated choline-augmented aneurysm initiation, and halted progression of an established aneurysm model. In addition, Fmo3(-/-) mice had reduced plasma TMAO and aortic diameters and were protected from AAA rupture compared with wild-type mice. RNA sequencing and functional analyses revealed choline supplementation in mice or TMAO treatment of human vascular smooth muscle cells-augmented gene pathways associated with the endoplasmic reticulum stress response, specifically the endoplasmic reticulum stress kinase PERK.Conclusions:These results define a role for gut microbiota-generated TMAO in AAA formation through upregulation of endoplasmic reticulum stress-related pathways in the aortic wall. In addition, inhibition of microbiome-derived TMAO may serve as a novel therapeutic approach for AAA treatment where none currently exist.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Therrien, AS, et al.
(författare)
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Relationships between Prenatal Distress and Infant Body Mass Index in the First Year of Life in a Lower-Middle Income Country
- 2020
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Ingår i: International journal of environmental research and public health. - : MDPI AG. - 1660-4601. ; 17:19
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Tidskriftsartikel (refereegranskat)abstract
- Prenatal stress affects body composition in childhood and later in life. However, few studies assess body composition in infancy. Furthermore, most are in high-income countries and do not consider interactive or curvilinear relationships. We assessed distress and diet during pregnancy via questionnaires among 310 women in Vanuatu, a lower-middle income country. We measured body mass index (BMI) among 54 infants at 4–12 months of age. We analyzed interactive relationships between prenatal distress and diet with BMI Z-scores, and curvilinear relationships between distress and BMI Z-scores. There were no direct linear or interactive relationships between prenatal distress or diet with BMI Z-scores. We observed curvilinear relationships between prenatal distress and BMI Z-scores (p = 0.008), explaining 13.3 percent of unique variance. Results highlight that relationships between prenatal stress and body composition are evident in infancy but might not be detected if only linear relationships are assessed. Analyses in more diverse samples might help to explain inconsistencies in past studies.
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| 17. |
- Bonini, M., et al.
(författare)
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Adsorption of Amino Acids and Glutamic Acid-Based Surfactants on Imogolite Clays
- 2017
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 33:9, s. 2411-2419
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Tidskriftsartikel (refereegranskat)abstract
- Aluminum oxide surfaces are of utmost interest in different biotech applications, in particular for their use as adjuvants (i.e., booster of the immune response against infectious agents in vaccines production). In this framework, imogolite clays combine the chemical flexibility of an exposed alumina surface with 1D nanostructure. This work reports on the interaction between amino acids and imogolite, using turbidimetry, zeta-potential measurements, and Fourier transform infrared spectroscopy as main characterization tools. Amino acids with different side chain functional groups were investigated, showing that glutamic acid (Glu) has the strongest affinity for the imogolite surface. This was exploited to prepare a composite material made of a synthetic surfactant bearing a Glu polar head and a hydrophobic C-12 alkyl tail, adsorbed onto the surface of imogolite. The adsorption of a model drug (rhodamine B isothiocyanate) by the hybrid was evaluated both in water and in physiological saline conditions. The findings of this paper suggest that the combination between the glutamate headgroup and imogolite represents a promising platform for the fabrication of hybrid nanostructures with tailored functionalities.
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| 19. |
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| 20. |
- Walsh, Claire, 1983, et al.
(författare)
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The mevalonate precursor enzyme HMGCS1 is a novel marker and key mediator of cancer stem cell enrichment in luminal and basal models of breast cancer
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:7
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Tidskriftsartikel (refereegranskat)abstract
- The definitive characterization of common cancer stem cell (CSCs) subpopulations in breast cancer subtypes with distinct genotypic and phenotypic features remains an ongoing challenge. In this study, we have used a non-biased genome wide screening approach to identify transcriptional networks that may be specific to the CSC subpopulations in both luminal and basal breast cancer subtypes. In depth studies of three CSC-enriched breast cancer cell lines representing various subtypes of breast cancer revealed a striking hyperactivation of the mevalonate metabolic pathway in comparison to control cells. The upregulation of metabolic networks is a key feature of tumour cells securing growth and proliferative capabilities and dysregulated mevalonate metabolism has been associated with tumour malignancy and cellular transformation in breast cancer. Furthermore, accumulating evidence suggests that Simvastatin therapy, a mevalonate pathway inhibitor, could affect breast cancer progression and reduce breast cancer recurrence. When detailing the mevalonate pathway in breast cancer using a single-cell qPCR, we identified the mevalonate precursor enzyme, HMGCS1, as a specific marker of CSC-enriched subpopulations within both luminal and basal tumour subtypes. Down-regulation of HMGCS1 also decreased the CSC fraction and function in various model systems, suggesting that HMGCS1 is essential for CSC-activities in breast cancer in general. These data was supported by strong associations between HMGCS1 expression and aggressive features, such as high tumour grade, p53 mutations as well as ER-negativity in lymph node positive breast cancer. Importantly, loss of HMGCS1 also had a much more pronounced effect on CSC-activities compared to treatment with standard doses of Simvastatin. Taken together, this study highlights HMGCS1 as a potential gatekeeper for dysregulated mevalonate metabolism important for CSC-features in both luminal and basal breast cancer subtypes. Pharmacological inhibition of HMGCS1 could therefore be a superior novel treatment approach for breast cancer patients via additional CSC blocking functions.
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