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- Murari, A., et al.
(författare)
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A control oriented strategy of disruption prediction to avoid the configuration collapse of tokamak reactors
- 2024
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. In this work we report how, deploying innovative analysis methods on thousands of JET experiments covering the isotopic compositions from hydrogen to full tritium and including the major D-T campaign, the nature of the various forms of collapse is investigated in all phases of the discharges. An original approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
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- Labit, B., et al.
(författare)
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Dependence on plasma shape and plasma fueling for small edge-localized mode regimes in TCV and ASDEX Upgrade
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:8
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 Institute of Physics Publishing. All rights reserved. Within the EUROfusion MST1 work package, a series of experiments has been conducted on AUG and TCV devices to disentangle the role of plasma fueling and plasma shape for the onset of small ELM regimes. On both devices, small ELM regimes with high confinement are achieved if and only if two conditions are fulfilled at the same time. Firstly, the plasma density at the separatrix must be large enough (ne,sep/nG ∼ 0.3), leading to a pressure profile flattening at the separatrix, which stabilizes type-I ELMs. Secondly, the magnetic configuration has to be close to a double null (DN), leading to a reduction of the magnetic shear in the extreme vicinity of the separatrix. As a consequence, its stabilizing effect on ballooning modes is weakened.
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6. |
- Zohm, H., et al.
(författare)
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Overview of ASDEX upgrade results in view of ITER and DEMO
- 2024
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Ingår i: Nuclear Fusion. - 0029-5515 .- 1741-4326. ; 64:11
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Tidskriftsartikel (refereegranskat)abstract
- Experiments on ASDEX Upgrade (AUG) in 2021 and 2022 have addressed a number of critical issues for ITER and EU DEMO. A major objective of the AUG programme is to shed light on the underlying physics of confinement, stability, and plasma exhaust in order to allow reliable extrapolation of results obtained on present day machines to these reactor-grade devices. Concerning pedestal physics, the mitigation of edge localised modes (ELMs) using resonant magnetic perturbations (RMPs) was found to be consistent with a reduction of the linear peeling-ballooning stability threshold due to the helical deformation of the plasma. Conversely, ELM suppression by RMPs is ascribed to an increased pedestal transport that keeps the plasma away from this boundary. Candidates for this increased transport are locally enhanced turbulence and a locked magnetic island in the pedestal. The enhanced D-alpha (EDA) and quasi-continuous exhaust (QCE) regimes have been established as promising ELM-free scenarios. Here, the pressure gradient at the foot of the H-mode pedestal is reduced by a quasi-coherent mode, consistent with violation of the high-n ballooning mode stability limit there. This is suggestive that the EDA and QCE regimes have a common underlying physics origin. In the area of transport physics, full radius models for both L- and H-modes have been developed. These models predict energy confinement in AUG better than the commonly used global scaling laws, representing a large step towards the goal of predictive capability. A new momentum transport analysis framework has been developed that provides access to the intrinsic torque in the plasma core. In the field of exhaust, the X-Point Radiator (XPR), a cold and dense plasma region on closed flux surfaces close to the X-point, was described by an analytical model that provides an understanding of its formation as well as its stability, i.e., the conditions under which it transitions into a deleterious MARFE with the potential to result in a disruptive termination. With the XPR close to the divertor target, a new detached divertor concept, the compact radiative divertor, was developed. Here, the exhaust power is radiated before reaching the target, allowing close proximity of the X-point to the target. No limitations by the shallow field line angle due to the large flux expansion were observed, and sufficient compression of neutral density was demonstrated. With respect to the pumping of non-recycling impurities, the divertor enrichment was found to mainly depend on the ionisation energy of the impurity under consideration. In the area of MHD physics, analysis of the hot plasma core motion in sawtooth crashes showed good agreement with nonlinear 2-fluid simulations. This indicates that the fast reconnection observed in these events is adequately described including the pressure gradient and the electron inertia in the parallel Ohm’s law. Concerning disruption physics, a shattered pellet injection system was installed in collaboration with the ITER International Organisation. Thanks to the ability to vary the shard size distribution independently of the injection velocity, as well as its impurity admixture, it was possible to tailor the current quench rate, which is an important requirement for future large devices such as ITER. Progress was also made modelling the force reduction of VDEs induced by massive gas injection on AUG. The H-mode density limit was characterised in terms of safe operational space with a newly developed active feedback control method that allowed the stability boundary to be probed several times within a single discharge without inducing a disruptive termination. Regarding integrated operation scenarios, the role of density peaking in the confinement of the ITER baseline scenario (high plasma current) was clarified. The usual energy confinement scaling ITER98(p,y) does not capture this effect, but the more recent H20 scaling does, highlighting again the importance of developing adequate physics based models. Advanced tokamak scenarios, aiming at large non-inductive current fraction due to non-standard profiles of the safety factor in combination with high normalised plasma pressure were studied with a focus on their access conditions. A method to guide the approach of the targeted safety factor profiles was developed, and the conditions for achieving good confinement were clarified. Based on this, two types of advanced scenarios (‘hybrid’ and ‘elevated’ q-profile) were established on AUG and characterised concerning their plasma performance.
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7. |
- Stroth, U., et al.
(författare)
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Progress from ASDEX Upgrade experiments in preparing the physics basis of ITER operation and DEMO scenario development
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- An overview of recent results obtained at the tokamak ASDEX Upgrade (AUG) is given. A work flow for predictive profile modelling of AUG discharges was established which is able to reproduce experimental H-mode plasma profiles based on engineering parameters only. In the plasma center, theoretical predictions on plasma current redistribution by a dynamo effect were confirmed experimentally. For core transport, the stabilizing effect of fast ion distributions on turbulent transport is shown to be important to explain the core isotope effect and improves the description of hollow low-Z impurity profiles. The L-H power threshold of hydrogen plasmas is not affected by small helium admixtures and it increases continuously from the deuterium to the hydrogen level when the hydrogen concentration is raised from 0 to 100%. One focus of recent campaigns was the search for a fusion relevant integrated plasma scenario without large edge localised modes (ELMs). Results from six different ELM-free confinement regimes are compared with respect to reactor relevance: ELM suppression by magnetic perturbation coils could be attributed to toroidally asymmetric turbulent fluctuations in the vicinity of the separatrix. Stable improved confinement mode plasma phases with a detached inner divertor were obtained using a feedback control of the plasma β. The enhanced D α H-mode regime was extended to higher heating power by feedback controlled radiative cooling with argon. The quasi-coherent exhaust regime was developed into an integrated scenario at high heating power and energy confinement, with a detached divertor and without large ELMs. Small ELMs close to the separatrix lead to peeling-ballooning stability and quasi continuous power exhaust. Helium beam density fluctuation measurements confirm that transport close to the separatrix is important to achieve the different ELM-free regimes. Based on separatrix plasma parameters and interchange-drift-Alfvén turbulence, an analytic model was derived that reproduces the experimentally found important operational boundaries of the density limit and between L- and H-mode confinement. Feedback control for the X-point radiator (XPR) position was established as an important element for divertor detachment control. Stable and detached ELM-free phases with H-mode confinement quality were obtained when the XPR was moved 10 cm above the X-point. Investigations of the plasma in the future flexible snow-flake divertor of AUG by means of first SOLPS-ITER simulations with drifts activated predict beneficial detachment properties and the activation of an additional strike point by the drifts.
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8. |
- Meyer, H.F., et al.
(författare)
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Overview of physics studies on ASDEX Upgrade
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Forskningsöversikt (refereegranskat)abstract
- The ASDEX Upgrade (AUG) programme, jointly run with the EUROfusion MST1 task force, continues to significantly enhance the physics base of ITER and DEMO. Here, the full tungsten wall is a key asset for extrapolating to future devices. The high overall heating power, flexible heating mix and comprehensive diagnostic set allows studies ranging from mimicking the scrape-off-layer and divertor conditions of ITER and DEMO at high density to fully non-inductive operation (q 95 = 5.5, ) at low density. Higher installed electron cyclotron resonance heating power 6 MW, new diagnostics and improved analysis techniques have further enhanced the capabilities of AUG. Stable high-density H-modes with MW m-1 with fully detached strike-points have been demonstrated. The ballooning instability close to the separatrix has been identified as a potential cause leading to the H-mode density limit and is also found to play an important role for the access to small edge-localized modes (ELMs). Density limit disruptions have been successfully avoided using a path-oriented approach to disruption handling and progress has been made in understanding the dissipation and avoidance of runaway electron beams. ELM suppression with resonant magnetic perturbations is now routinely achieved reaching transiently . This gives new insight into the field penetration physics, in particular with respect to plasma flows. Modelling agrees well with plasma response measurements and a helically localised ballooning structure observed prior to the ELM is evidence for the changed edge stability due to the magnetic perturbations. The impact of 3D perturbations on heat load patterns and fast-ion losses have been further elaborated. Progress has also been made in understanding the ELM cycle itself. Here, new fast measurements of and E r allow for inter ELM transport analysis confirming that E r is dominated by the diamagnetic term even for fast timescales. New analysis techniques allow detailed comparison of the ELM crash and are in good agreement with nonlinear MHD modelling. The observation of accelerated ions during the ELM crash can be seen as evidence for the reconnection during the ELM. As type-I ELMs (even mitigated) are likely not a viable operational regime in DEMO studies of 'natural' no ELM regimes have been extended. Stable I-modes up to have been characterised using -feedback. Core physics has been advanced by more detailed characterisation of the turbulence with new measurements such as the eddy tilt angle - measured for the first time - or the cross-phase angle of and fluctuations. These new data put strong constraints on gyro-kinetic turbulence modelling. In addition, carefully executed studies in different main species (H, D and He) and with different heating mixes highlight the importance of the collisional energy exchange for interpreting energy confinement. A new regime with a hollow profile now gives access to regimes mimicking aspects of burning plasma conditions and lead to nonlinear interactions of energetic particle modes despite the sub-Alfvénic beam energy. This will help to validate the fast-ion codes for predicting ITER and DEMO.
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9. |
- Bull, Peter, et al.
(författare)
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Förstudie obemannade farkoster
- 2012
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Rapport (populärvet., debatt m.m.)abstract
- Obemannade farkoster används allt oftare, och i allt fler roller, i dagens kon- flikter. Denna rapport ger en bred överblick över området militära obemannade farkoster, samt rekommendationer för inriktningen av framtida FoU-satsningar inom området.Överblicken över området har fokus på både system, förmågor och verksam- heter som är relevanta för Försvarsmakten. Genom att låta de insatsförmågor som definieras i FMUP (Försvarsmaktens utvecklingsplan) gå som en röd tråd genom rapporten, både när specifika system diskuteras och när möjliga scena- rier där obemannade farkoster kan vara till nytta beskrivs, har vi försökt hålla både bredd och relevans i dokumentet.Rekommendationerna vilar på en genomgång av de inriktningsdokument som producerats i Försvarsmakten, t.ex. Perspektivplanneringen och FMUP, besök vid de enheter som dagligen använder obemannade farkoster, UAV-enheten i Karlsborg och Swedec i Eksjö, samt den områdesöverblick som nämns ovan. Slutsatserna är att den effektivaste kompetensuppbyggnaden och kunskapsöver- föringen fås om man skapar breda tvärvetenskapliga projekt inom respektive systemkategori (UAV, UGV, etc) med nära kontakter till materielförsörjnings- processen och perspektivplaneringen. Dessa kan samla kompetensen inom FHS och FOI, övervaka forskningsfronten genom att bevaka tävlingar, konferenser samt delta i internationella samarbeten, samt överföra det samlade resultaten till Försvarsmakten genom demonstrationer av verkliga eller simulerade delsy- stem och interaktiva simuleringar av hela system. Just systemsimuleringar kan göras särskilt realistiska, eftersom interaktionen med de riktiga obemannade systemen till stor del sker igenom kontrollstationernas datorer. På så sätt ska- pas en känsla för både hot och möjligheter med de nya systemen, vilket gagnar både taktikutveckling och materielprocesser.
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10. |
- Pamilo, P, et al.
(författare)
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Molecular population genetics of social insects
- 1997
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Ingår i: ANNUAL REVIEW OF ECOLOGY AND SYSTEMATICS. - : ANNUAL REVIEWS INC. ; 28, s. 1-25
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Recension (övrigt vetenskapligt/konstnärligt)abstract
- The life of social insects centers around sedentary colonies that can include individuals belonging to different patrilines or matrilines, with a turnover of reproductives. The colony is a scene for both cooperation and conflicts, and the conceptual frame
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11. |
- Mathieu, C., et al.
(författare)
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Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes (the DEPICT-2 Study): 24-Week Results From a Randomized Controlled Trial
- 2018
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 41:9, s. 1938-1946
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEThis 24-week, double-blinded, phase 3 clinical trial (DEPICT-2; ClinicalTrials.gov, NCT02460978) evaluated efficacy and safety of dapagliflozin as adjunct therapy to adjustable insulin in patients with inadequately controlled type 1 diabetes (HbA(1c) 7.5-10.5%).RESEARCH DESIGN AND METHODSPatients were randomized 1:1:1 to dapagliflozin 5 mg (n = 271), dapagliflozin 10 mg (n = 270), or placebo (n = 272) plus insulin. Insulin dose was adjusted by investigators according to self-monitored glucose readings, local guidance, and individual circumstances.RESULTSBaseline characteristics were balanced between treatment groups. At week 24, dapagliflozin significantly decreased HbA(1c) (primary outcome; difference vs. placebo: dapagliflozin 5 mg -0.37% [95% CI -0.49, -0.26], dapagliflozin 10 mg -0.42% [-0.53, -0.30]), total daily insulin dose (-10.78% [-13.73, -7.72] and -11.08% [-14.04, -8.02], respectively), and body weight (-3.21% [-3.96, -2.45] and -3.74% [-4.49, -2.99], respectively) (P < 0.0001 for all). Mean interstitial glucose, amplitude of glucose excursion, and percent of readings within target glycemic range (>70 to 180 mg/dL) versus placebo were significantly improved. More patients receiving dapagliflozin achieved a reduction in HbA(1c) 0.5% without severe hypoglycemia compared with placebo. Adverse events were reported for 72.7%, 67.0%, and 63.2% of patients receiving dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo, respectively. Hypoglycemia, including severe hypoglycemia, was balanced between groups. There were more adjudicated definite diabetic ketoacidosis (DKA) events with dapagliflozin: 2.6%, 2.2%, and 0% for dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo, respectively.CONCLUSIONSDapagliflozin as adjunct therapy to adjustable insulin in patients with type 1 diabetes was well tolerated and improved glycemic control with no increase in hypoglycemia versus placebo but with more DKA events.
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- Escudero-Martinez, I, et al.
(författare)
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Cerebral Edema in Patients with severe Hemispheric Syndrome: Incidence, Risk Factors, and Outcomes-Data from SITS-ISTR
- 2023
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Ingår i: Journal of stroke. - : Korean Stroke Society. - 2287-6391 .- 2287-6405. ; 25:1, s. 101-
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose Cerebral edema (CED) in ischemic stroke can worsen prognosis and about 70% of patients who develop severe CED die if treated conservatively. We aimed to describe incidence, risk factors and outcomes of CED in patients with extensive ischemia.Methods Oservational study based on Safe Implementation of Treatments in Stroke-International Stroke Treatment Registry (2003–2019). Severe hemispheric syndrome (SHS) at baseline and persistent SHS (pSHS) at 24 hours were defined as National Institutes of Health Stroke Score (NIHSS) >15. Outcomes were moderate/severe CED detected by neuroimaging, functional independence (modified Rankin Scale 0–2) and death at 90 days.Results Patients (n=8,560) presented with SHS and developed pSHS at 24 hours; 82.2% received intravenous thrombolysis (IVT), 10.5% IVT+thrombectomy, and 7.3% thrombectomy alone. Median age was 77 and NIHSS 21. Of 7,949 patients with CED data, 3,780 (47.6%) had any CED and 2,297 (28.9%) moderate/severe CED. In the multivariable analysis, age <50 years (relative risk [RR], 1.56), signs of acute infarct (RR, 1.29), hyperdense artery sign (RR, 1.39), blood glucose >128.5 mg/dL (RR, 1.21), and decreased level of consciousness (RR, 1.14) were associated with moderate/severe CED (for all P<0.05). Patients with moderate/severe CED had lower odds to achieve functional Independence (adjusted odds ratio [aOR], 0.35; 95% confidence interval [CI], 0.23 to 0.55) and higher odds of death at 90 days (aOR, 2.54; 95% CI, 2.14 to 3.02).Conclusions In patients with extensive ischemia, the most important predictors for moderate/ severe CED were age <50, high blood glucose, signs of acute infarct, hyperdense artery on baseline scans, and decreased level of consciousness. CED was associated with worse functional outcome and a higher risk of death at 3 months.
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16. |
- Fredholm, BB, et al.
(författare)
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Consequences of eliminating adenosine A(1) receptors in mice
- 2003
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Ingår i: Drug Development Research (Proceedings of the Seventh International Symposium on Adenosine and Adenine Nucleotides - Part 1). - : Wiley. - 1098-2299 .- 0272-4391. ; 58, s. 350-
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Konferensbidrag (refereegranskat)abstract
- The second coding exon of the adenosine A, receptor gene was eliminated by homologous recombination. The phenotype of mice (mixed C57B6/129OlaHsd background) was studied, using siblings from matings of heterozygous mice. Among the offspring the ratio between+/+, +/-and -/-animals was 1:2:1. Over the first half-year-at least-growth and viability were the same in all genotypes. Binding of A(1) ligands was eliminated in-/-mice and halved in+/-mice. Blood pressure was increased in-/-mice and this was paralleled by an increase in plasma renin. Heart rate was unaffected, as was contractility. Furthermore, the response of the perfused heart to ischemia was similar in+/+and -/-hearts. However, remote preconditioning was eliminated in-/-mouse hearts. Tubuloglomerular feedback in the kidney was also lost in-/-mice. The analgesic response to a non-selective adenosing receptor agonist was lost in-/-mice, which also showed hyperalgesia in the tail-flick test. There was a slight hypoactivity in-/-mice, but responses to caffeine were essentially normal. The inhibition of excitatory neurotransmission in hippocampus by adenosine was lost in-/-mice and reduced in+/-mice. Responses to ATP were affected similarly. Hypoxic depression of synaptic transmission was essentially eliminated in hippocampus and hypoxic decrease in spinal respiratory neuron firing was markedly reduced. These results show that adenosine A, receptors play a physiologically important role in the kidney, spinal cord, and hippocampus and that they are critically important in the adaptive responses to hypoxia. (C) 2003 Wiley-Liss, Inc.
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- Jonsdottir, Ingibjörg H, 1966, et al.
(författare)
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Duration and mechanisms of the increased natural cytotoxicity seen after chronic voluntary exercise in rats.
- 1997
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Ingår i: Acta physiologica Scandinavica. - 0001-6772. ; 160:4, s. 333-9
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Tidskriftsartikel (refereegranskat)abstract
- We have recently shown that in vivo natural cytotoxicity is enhanced after chronic exercise in spontaneously hypertensive rats (SHRs). In the present report, we have studied the duration of this augmentation and some possible mechanisms involved. Exercise consisted of voluntary running for 4-5 weeks, with the running distance ranging from 2.7-15.6 km day(-1) during the last week of running. In vivo cytotoxicity was measured as clearance of injected 51Cr-labelled YAC-1 lymphoma cells from the lungs. The in vivo natural cytotoxicity was increased in running SHRs, and also in SHRs that had their running wheel locked for 24 and 48 h prior to the experiment, and was still present after 96 h. The enhancement of in vivo cytotoxicity after 5 weeks of exercise was abolished after an acute injection of the beta-adrenergic receptor antagonist timolol (0.5 mg kg(-1) i.v.), indicating that catecholamines are involved in this augmentation. Interestingly, 24 h after the last exercise bout, the increased natural cytotoxicity could be blocked by timolol. The opioid receptor antagonist naloxone given subcutaneously for 7 days by osmotic pumps (6 mg kg(-1) h(-1)) could not reverse the increased in vivo cytotoxicity seen in the running SHRs, suggesting that opioid receptor mechanisms are not involved, or at least not the naloxone-sensitive mu-receptor. Natural immunity was not influenced by the histamine H2 receptor antagonist ranitidine, either in controls or in runners, indicating that the natural killer cell-regulatory effect of histamine is not present in SHRs and does not seem to be involved in the exercise-induced changes in natural immune function. We conclude that the augmentation of in vivo natural cytotoxicity after voluntary chronic exercise in rats is long-lasting and that the augmentation is partly mediated by beta-adrenergic receptors.
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20. |
- Jonsdottir, Ingibjörg H, 1966, et al.
(författare)
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Physical exercise, endogenous opioids and immune function.
- 1997
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Ingår i: Acta physiologica Scandinavica. Supplementum. - 0302-2994. ; 640, s. 47-50
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Forskningsöversikt (refereegranskat)abstract
- The experimental data available today strongly indicate that various types of physiological stressors, including physical exercise and emotional stress, can influence immune function. Natural immunity represents a first line of defence in viral infections and cytotoxicity to a variety of tumour cells. Natural immunity is strongly influenced by chronic exercise and this regulation includes interaction between the nervous, endocrine and immune systems. Central mechanisms including the endogenous opioids are of great interest. Chronic activation of endogenous opioid systems augments natural cytotoxicity and the possible involvement the opioids in the exercise-induced enhancement of natural immunity is discussed. Also, catecholamines seem to play an important role in the regulation of immune function, both after chronic exercise and emotional stress. The physiological significance of the reported changes in natural cytotoxicity after exercise-training is as yet unclear.
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22. |
- Krieger, K., et al.
(författare)
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Investigation of transient melting of tungsten by ELMs in ASDEX Upgrade
- 2017
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Ingår i: Physica Scripta. - : IOP PUBLISHING LTD. - 0031-8949 .- 1402-4896. ; T170
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Tidskriftsartikel (refereegranskat)abstract
- Repetitive melting of tungsten by power transients originating from edge localized modes (ELMs) has been studied in the tokamak experiment ASDEX Upgrade. Tungsten samples were exposed to H-mode discharges at the outer divertor target plate using the Divertor Manipulator II system. The exposed sample was designed with an elevated sloped surface inclined against the incident magnetic field to increase the projected parallel power flux to a level were transient melting by ELMs would occur. Sample exposure was controlled by moving the outer strike point to the sample location. As extension to previous melt studies in the new experiment both the current flow from the sample to vessel potential and the local surface temperature were measured with sufficient time resolution to resolve individual ELMs. The experiment provided for the first time a direct link of current flow and surface temperature during transient ELM events. This allows to further constrain the MEMOS melt motion code predictions and to improve the validation of its underlying model assumptions. Post exposure ex situ analysis of the retrieved samples confirms the decreased melt motion observed at shallower magnetic field line to surface angles compared to that at leading edges exposed to the parallel power flux.
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- Phillip, M., et al.
(författare)
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Long-term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: pooled 52-week outcomes from the DEPICT-1 and-2 studies
- 2021
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Ingår i: Diabetes Obesity & Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 23:2, s. 549-560
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Tidskriftsartikel (refereegranskat)abstract
- Aim To evaluate the efficacy and safety of adjunct dapagliflozin therapy in patients with type 1 diabetes (T1D). Materials and Methods DEPICT-1 and -2 were randomized, double-blind, parallel-group, 24-week studies, with 28-week extension periods. Adults with T1D and HbA1c 7.5%-10.5% were randomized (1:1:1) to receive dapagliflozin 5 mg, 10 mg or placebo. The short- and long-term efficacy and safety of dapagliflozin were examined in an exploratory pooled analysis of both studies. Results Efficacy analyses included 530, 529 and 532 and safety analysis included 548, 566 and 532 patients in the dapagliflozin 5 mg, 10 mg and placebo groups, respectively. Baseline characteristics were similar between treatment groups. At week 24, reductions were seen with dapagliflozin 5 and 10 mg compared with placebo in HbA1c (-0.40%, -0.43% vs. 0.00%) and body weight (-2.45, -2.91 vs. 0.11 kg). HbA1c and body weight reductions versus placebo were also seen after 52 weeks of treatment. There was no imbalance in occurrence of severe hypoglycaemic events between groups. The proportion of patients experiencing definite diabetic ketoacidosis (DKA) was higher with dapagliflozin 5 mg (4.0%) and 10 mg (3.5%) compared with placebo (1.1%) over 52 weeks; most events were of mild or moderate severity, and all resolved with treatment. Conclusions Over 52 weeks, dapagliflozin provided glycaemic and weight benefits, with no increased frequency of severe hypoglycaemia compared with placebo. More DKA events were reported with dapagliflozin than placebo, highlighting the importance of appropriate patient selection, education and risk-mitigation strategies.
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26. |
- Thoren, S, et al.
(författare)
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Human microsomal prostaglandin E synthase-1: purification, functional characterization, and projection structure determination.
- 2003
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Ingår i: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 278:25, s. 209-22199
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Tidskriftsartikel (refereegranskat)abstract
- Human, microsomal, and glutathione-dependent prostaglandin (PG) E synthase-1 (mPGES-1) was expressed with a histidine tag in Escherichia coli. mPGES-1 was purified to apparent homogeneity from Triton X-100-solubilized bacterial extracts by a combination of hydroxyapatite and immobilized metal affinity chromatography. The purified enzyme displayed rapid glutathione-dependent conversion of PGH2 to PGE2 (Vmax; 170 µmol min–1 mg–1) and high kcat/Km (310 mM–1 s–1). Purified mPGES-1 also catalyzed glutathione-dependent conversion of PGG2 to 15-hydroperoxy-PGE2 (Vmax; 250 µmol min–1 mg–1). The formation of 15-hydroperoxy-PGE2 represents an alternative pathway for the synthesis of PGE2, which requires further investigation. Purified mPGES-1 also catalyzed glutathione-dependent peroxidase activity toward cumene hydroperoxide (0.17 µmol min–1 mg–1), 5-hydroperoxyeicosatetraenoic acid (0.043 µmol min–1 mg–1), and 15-hydroperoxy-PGE2 (0.04 µmol min–1 mg–1). In addition, purified mPGES-1 catalyzed slow but significant conjugation of 1-chloro-2,4-dinitrobenzene to glutathione (0.8 µmol min–1 mg–1). These activities likely represent the evolutionary relationship to microsomal glutathione transferases. Two-dimensional crystals of purified mPGES-1 were prepared, and the projection map determined by electron crystallography demonstrated that microsomal PGES-1 constitutes a trimer in the crystal, i.e. an organization similar to the microsomal glutathione transferase 1. Hydrodynamic studies of the mPGES-1-Triton X-100 complex demonstrated a sedimentation coefficient of 4.1 S, a partial specific volume of 0.891 cm3/g, and a Stokes radius of 5.09 nm corresponding to a calculated molecular weight of 215,000. This molecular weight, including bound Triton X-100 (2.8 g/g protein), is fully consistent with a trimeric organization of mPGES-1.
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- Zhu, Y, et al.
(författare)
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Abnormal vascular function and hypertension in mice deficient in estrogen receptor beta
- 2002
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 295:5554, s. 505-508
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Tidskriftsartikel (refereegranskat)abstract
- Blood vessels express estrogen receptors, but their role in cardiovascular physiology is not well understood. We show that vascular smooth muscle cells and blood vessels from estrogen receptor β (ERβ)–deficient mice exhibit multiple functional abnormalities. In wild-type mouse blood vessels, estrogen attenuates vasoconstriction by an ERβ-mediated increase in inducible nitric oxide synthase expression. In contrast, estrogen augments vasoconstriction in blood vessels from ERβ-deficient mice. Vascular smooth muscle cells isolated from ERβ-deficient mice show multiple abnormalities of ion channel function. Furthermore, ERβ-deficient mice develop sustained systolic and diastolic hypertension as they age. These data support an essential role for ERβ in the regulation of vascular function and blood pressure.
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29. |
- Zohari, Siamak, et al.
(författare)
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Phylogenetic analysis of the non-structural (NS) gene of influenza A viruses isolated from mallards in Northern Europe in 2005
- 2008
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Ingår i: Virology Journal. - 1743-422X. ; 5:Article ID: 147
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although the important role of the non-structural 1 (NS) gene of influenza A in virulence of the virus is well established, our knowledge about the extent of variation in the NS gene pool of influenza A viruses in their natural reservoirs in Europe is incomplete. In this study we determined the subtypes and prevalence of influenza A viruses present in mallards in Northern Europe and further analysed the NS gene of these isolates in order to obtain a more detailed knowledge about the genetic variation of NS gene of influenza A virus in their natural hosts. Results: A total number of 45 influenza A viruses of different subtypes were studied. Eleven haemagglutinin-and nine neuraminidase subtypes in twelve combinations were found among the isolated viruses. Each NS gene reported here consisted of 890 nucleotides; there were no deletions or insertions. Phylogenetic analysis clearly shows that two distinct gene pools, corresponding to both NS allele A and B, were present at the same time in the same geographic location in the mallard populations in Northern Europe. A comparison of nucleotide sequences of isolated viruses revealed a substantial number of silent mutations, which results in high degree of homology in amino acid sequences. The degree of variation within the alleles is very low. In our study allele A viruses displays a maximum of 5% amino acid divergence while allele B viruses display only 2% amino acid divergence. All the viruses isolated from mallards in Northern Europe possessed the typical avian ESEV amino acid sequence at the C-terminal end of the NSI protein. Conclusion: Our finding indicates the existence of a large reservoir of different influenza A viruses in mallards population in Northern Europe. Although our phylogenetic analysis clearly shows that two distinct gene pools, corresponding to both NS allele A and B, were present in the mallards populations in Northern Europe, allele B viruses appear to be less common in natural host species than allele A, comprising only about 13% of the isolates sequenced in this study.
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30. |
- Ablikim, M., et al.
(författare)
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Determination of spin and parity of D*(s) mesons
- 2023
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Ingår i: Physics Letters B. - : Elsevier. - 0370-2693 .- 1873-2445. ; 846
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Tidskriftsartikel (refereegranskat)abstract
- The spin and parity of the charmed mesons D*s+, D*0 and D*+ are determined for the first time to be JP = 1- with significances greater than 10σ over other hypotheses of 2+ and 3-, using an e+e- collision data sample with an integrated luminosity of 3.19 fb-1 collected by the BESIII detector at a center-of-mass energy of 4.178 GeV. Different spin-parity hypotheses are tested via a helicity amplitude analysis of the processes e+e--→ D*s+ D-s, D*0D0 and D*+D-, with D∗+s → D*+s γ, D∗0 → D0π0 , and D∗+ → D+π0. The results confirm the quark model predictions
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31. |
- Ablikim, M., et al.
(författare)
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Measurement of the CP-even fraction of D0 → K+K−π+π−
- 2023
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Ingår i: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 107:3
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Tidskriftsartikel (refereegranskat)abstract
- A determination of the CP-even fraction F+ in the decay D0→K+K−π+π− is presented. Using 2.93 fb−1 of e+e−→ψ(3770)→D¯D data collected by the BESIII detector, one charm meson is reconstructed in the signal mode and the other in a CP eigenstate or the decay D→K0S,Lπ+π−. Analysis of the relative rates of these double-tagged events yields the result F+=0.730±0.037±0.021, where the first uncertainty is statistical and the second is systematic. This is the first model-independent measurement of F+ in D0→K+K−π+π− decays.
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32. |
- Ablikim, M., et al.
(författare)
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Observation of the Y(4220) and Y(4390) in the process e(+)e(-) -> eta J/psi
- 2020
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 1550-7998 .- 1550-2368. ; 102:3
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Tidskriftsartikel (refereegranskat)abstract
- The cross sections of the process e(+)e(-) -> eta J/psi lip at center-of-mass energies (root s) between 3.81 and 4.60 GeV are measured with high precision by using data samples collected with the BESIII detector operating at the BEPCII storage ring. Three structures are observed by analyzing the line shape of the measured cross sections, and a maximum-likelihood fit including three resonances is performed by assuming the lowest lying structure is the psi(4040). For the other resonances, we obtain masses of (4218.6 +/- 3.8 +/- 2.5) and (4382.0 +/- 13.3 +/- 1.7) MeV/c(2) with corresponding widths of (82.0 +/- 5.7 +/- 0.4) and (135.8 +/- 60.8 +/- 22.5) MeV, respectively, where the first uncertainties are statistical and the second ones systematic. The measured resonant parameters are consistent with those of the Y(4220) and Y(4390) from previous measurements of different final states. For the first time, we observe the decays of the Y(4220) and Y(4390) into eta J/psi final states.
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33. |
- Ablikim, M., et al.
(författare)
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Study of e(+)e(-) -> D+D-pi(+)pi(-) at center-of-mass energies from 4.36 to 4.60 GeV
- 2020
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Ingår i: Physics Letters B. - : ELSEVIER. - 0370-2693 .- 1873-2445. ; 804
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Tidskriftsartikel (refereegranskat)abstract
- We report a study of the e(+)e(-) -> D+D-pi(+)pi(-) process using e(+)e(-) collision data samples with an integrated luminosity of 2.5 fb(-1) at center-of-mass energies from 4.36 to 4.60 GeV, collected with the BESIII detector at the BEPCII storage ring. The D1(2420)+ is observed in the D+pi(+)pi(-) mass spectrum. The mass and width of the D-1(2420)+ are measured to be (2427.2 +/- 1.0(stat).+/- 1.2(syst).) MeV/c(2) and (23.2 +/- 2.3(stat). +/- 2.3(syst).) MeV, respectively. In addition, the Born cross sections of the e(+)e(-) -> D-1(2420)D-+(-) + c.c. -> D+D-pi(+)pi(-) and e(+)e(-) -> psi(3770)pi(+)pi(-) -> D+D-pi(+)pi(-) processes are measured as a function of the center-of-mass energy. (c) 2020 The Author. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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34. |
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35. |
- Benrick, Anna, 1979, et al.
(författare)
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Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture
- 2017
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Ingår i: Faseb Journal. - : Federation of American Societies for Experimental Biology. - 0892-6638 .- 1530-6860. ; 31:8, s. 3288-3297
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Tidskriftsartikel (refereegranskat)abstract
- A single bout of low-frequency electroacupuncture (EA) causing muscle contractions increases whole-body glucose uptake in insulin-resistant rats. We explored the underlying mechanism of this finding and whether it can be translated into clinical settings. Changes in glucose infusion rate (GIR) were measured by euglycemic-hyperinsulinemic clamp during and after 45 min of low-frequency EA in 21 overweight/obese women with polycystic ovary syndrome (PCOS) and 21 controls matched for age, weight, and body mass index (experiment 1) and in rats receiving autonomic receptor blockers (experiment 2). GIR was higher after EA in controls and women with PCOS. Plasma serotonin levels and homovanillic acid, markers of vagal activity, decreased in both controls and patients with PCOS. Adipose tissue expression of pro-nerve growth factor (proNGF) decreased, and the mature NGF/proNGF ratio increased after EA in PCOS, but not in controls, suggesting increased sympathetic-driven adipose tissue metabolism. Administration of alpha-/beta-adrenergic receptor blockers in rats blocked the increase in GIR in response to EA. Muscarinic and dopamine receptor antagonist also blocked the response but with slower onset. In conclusion, a single bout of EA increases whole-body glucose uptake by activation of the sympathetic and partly the parasympathetic nervous systems, which could have important clinical implications for the treatment of insulin resistance.
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36. |
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37. |
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40. |
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41. |
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43. |
- Eriksson, EE, et al.
(författare)
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Importance of primary capture and L-selectin-dependent secondary capture in leukocyte accumulation in inflammation and atherosclerosis in vivo
- 2001
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 194:2, s. 205-217
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Tidskriftsartikel (refereegranskat)abstract
- In the multistep process of leukocyte extravasation, the mechanisms by which leukocytes establish the initial contact with the endothelium are unclear. In parallel, there is a controversy regarding the role for L-selectin in leukocyte recruitment. Here, using intravital microscopy in the mouse, we investigated leukocyte capture from the free flow directly to the endothelium (primary capture), and capture mediated through interactions with rolling leukocytes (secondary capture) in venules, in cytokine-stimulated arterial vessels, and on atherosclerotic lesions in the aorta. Capture was more prominent in arterial vessels compared with venules. In venules, the incidence of capture increased with increasing vessel diameter and wall shear rate. Secondary capture required a minimum rolling leukocyte flux and contributed by ∼20–50% of total capture in all studied vessel types. In arteries, secondary capture induced formation of clusters and strings of rolling leukocytes. Function inhibition of L-selectin blocked secondary capture and thereby decreased the flux of rolling leukocytes in arterial vessels and in large (>45 μm in diameter), but not small (<45 μm), venules. These findings demonstrate the importance of leukocyte capture from the free flow in vivo. The different impact of blockage of secondary capture in venules of distinct diameter range, rolling flux, and wall shear rate provides explanations for the controversy regarding the role of L-selectin in various situations of leukocyte recruitment. What is more, secondary capture occurs on atherosclerotic lesions, a fact that provides the first evidence for roles of L-selectin in leukocyte accumulation in atherogenesis.
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44. |
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45. |
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47. |
- Escutenaire, Sophie, et al.
(författare)
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SYBR Green real-time reverse transcription-polymerase chain reaction assay for the generic detection of coronaviruses
- 2007
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Ingår i: Archives of Virology. - : Springer Science and Business Media LLC. - 0304-8608 .- 1432-8798. ; 152:1, s. 41-58
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Tidskriftsartikel (refereegranskat)abstract
- Coronaviruses are etiologic agents of respiratory and enteric diseases in humans and in animals. In this study, a one-step real-time reverse transcription-polymerase chain reaction (RT-PCR) assay based on SYBR Green chemistry and degenerate primers was developed for the generic detection of coronaviruses. The primers, designed in the open reading frame 1b, enabled the detection of 32 animal coronaviruses including strains of canine coronavirus, feline coronavirus, transmissible gastroenteritis virus (TGEV), bovine coronavirus (BCoV), murine hepatitis virus (MHV) and infectious bronchitis virus (IBV). A specific amplification was also observed with the human coronaviruses (HCoV) HCoV-NL63, HCoV-OC43, HCoV-229E and severe acute respiratory syndrome coronavirus (SARS-CoV). The real-time RT-PCR detected down to 10 cRNA copies from TGEV, BCoV, SARS-CoV and IBV. In addition, the assay exhibited a high sensitivity and specificity on clinical samples from different animal species. The developed assay represents a potential tool for laboratory diagnostics and for detecting still uncharacterized coronaviruses.
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48. |
- Fjerdingstad, EJ, et al.
(författare)
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Multiple paternity in the leafcutter ant Atta colombica - a microsatellite DNA study
- 1998
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Ingår i: HEREDITY. - : BLACKWELL SCIENCE LTD. - 0018-067X. ; 80, s. 118-126
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- An evolutionary understanding of the causes, correlates and consequences of multiple paternity in eusocial Hymenoptera (all ants, some bees and some wasps) relies on accurate estimation of this parameter at the species, population and colony level. We dev
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49. |
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50. |
- Gillberg, P, et al.
(författare)
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Commencing growth hormone replacement in adults with a fixed low dose. Effects on serum lipoproteins, glucose metabolism, body composition, and cardiovascular function.
- 2001
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1096-6374. ; 11:5, s. 273-81
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Tidskriftsartikel (refereegranskat)abstract
- The safety and effects of a fixed low dose of growth hormone (GH), 0.17 mg/day was evaluated for 3 months, on glucose metabolism, serum lipids, body composition and cardiac function in 53 GH deficient adults aged 18-78 years. Body composition was determined by dual energy X-ray absorptiometry and total body water was determined by bioelectrical impedance. Echocardiography was used to assess cardiac function and bicycle ergonometry was used to determine exercise capacity. All investigations were performed at baseline and after 3 months. At 3 months, serum levels of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and lipoprotein (a) and lean body mass were increased (P<0.05). Total and low density lipoprotein cholesterol levels and fat mass were reduced (P<0.05). There was an increase in the serum glucose value at 120 min after an oral glucose tolerance test performed at 3 months (P<0.05), no other changes in glucose metabolism or in cardiac function were noted. Side-effects were few and mild. This fixed low-dose regime resulted in improvements in body composition and lipid profile, without causing serious side effects. This is therefore a valid method to institute GH replacement in adults.
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