| 1. |
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| 2. |
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| 3. |
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| 4. |
- Abel, I, et al.
(författare)
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Overview of the JET results with the ITER-like wall
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
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Tidskriftsartikel (refereegranskat)abstract
- Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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| 5. |
- Romanelli, F, et al.
(författare)
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Overview of the JET results
- 2011
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
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Tidskriftsartikel (refereegranskat)abstract
- Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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| 6. |
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| 7. |
- Sekiguchi, M, et al.
(författare)
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Integrated multiomics analysis of hepatoblastoma unravels its heterogeneity and provides novel druggable targets
- 2020
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Ingår i: NPJ precision oncology. - : Springer Science and Business Media LLC. - 2397-768X. ; 4:1, s. 20-
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Tidskriftsartikel (refereegranskat)abstract
- Although hepatoblastoma is the most common pediatric liver cancer, its genetic heterogeneity and therapeutic targets are not well elucidated. Therefore, we conducted a multiomics analysis, including mutatome, DNA methylome, and transcriptome analyses, of 59 hepatoblastoma samples. Based on DNA methylation patterns, hepatoblastoma was classified into three clusters exhibiting remarkable correlation with clinical, histological, and genetic features. Cluster F was largely composed of cases with fetal histology and good outcomes, whereas clusters E1 and E2 corresponded primarily to embryonal/combined histology and poor outcomes. E1 and E2, albeit distinguishable by different patient age distributions, were genetically characterized by hypermethylation of the HNF4A/CEBPA-binding regions, fetal liver-like expression patterns, upregulation of the cell cycle pathway, and overexpression of NQO1 and ODC1. Inhibition of NQO1 and ODC1 in hepatoblastoma cells induced chemosensitization and growth suppression, respectively. Our results provide a comprehensive description of the molecular basis of hepatoblastoma and rational therapeutic strategies for high-risk cases.
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| 8. |
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| 9. |
- Isobe, T, et al.
(författare)
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Multi-omics analysis defines highly refractory RAS burdened immature subgroup of infant acute lymphoblastic leukemia
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4501-
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Tidskriftsartikel (refereegranskat)abstract
- KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) represents the most refractory type of childhood leukemia. To uncover the molecular heterogeneity of this disease, we perform RNA sequencing, methylation array analysis, whole exome and targeted deep sequencing on 84 infants with KMT2A-rearranged leukemia. Our multi-omics clustering followed by single-sample and single-cell inference of hematopoietic differentiation establishes five robust integrative clusters (ICs) with different master transcription factors, fusion partners and corresponding stages of B-lymphopoietic and early hemato-endothelial development: IRX-type differentiated (IC1), IRX-type undifferentiated (IC2), HOXA-type MLLT1 (IC3), HOXA-type MLLT3 (IC4), and HOXA-type AFF1 (IC5). Importantly, our deep mutational analysis reveals that the number of RAS pathway mutations predicts prognosis and that the most refractory subgroup of IC2 possesses 100% frequency and the heaviest burden of RAS pathway mutations. Our findings highlight the previously under-appreciated intra- and inter-patient heterogeneity of KMT2A-rearranged infant ALL and provide a rationale for the future development of genomics-guided risk stratification and individualized therapy.
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| 10. |
- Kubota, Y, et al.
(författare)
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Comprehensive genetic analysis of pediatric germ cell tumors identifies potential drug targets
- 2020
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 544-
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the molecular pathogenesis of pediatric germ cell tumors (GCTs), we performed DNA methylation array analysis, whole transcriptome sequencing, targeted capture sequencing, and single-nucleotide polymorphism array analysis using 51 GCT samples (25 female, 26 male), including 6 germinomas, 2 embryonal carcinomas, 4 immature teratomas, 3 mature teratomas, 30 yolk sac tumors, and 6 mixed germ cell tumors. Among the 51 samples, 11 were from infants, 23 were from young children, and 17 were from those aged ≥10 years. Sixteen of the 51 samples developed in the extragonadal regions. Germinomas showed upregulation of pluripotent genes and global hypomethylation. Pluripotent genes were also highly expressed in embryonal carcinomas. These genes may play essential roles in embryonal carcinomas given that their binding sites are hypomethylated. Yolk sac tumors exhibited overexpression of endodermal genes, such as GATA6 and FOXA2, the binding sites of which were hypomethylated. Interestingly, infant yolk sac tumors had different DNA methylation patterns from those observed in older children. Teratomas had higher expression of ectodermal genes, suggesting a tridermal nature. Based on our results, we suggest that KIT, TNFRSF8, and ERBB4 may be suitable targets for the treatment of germinoma, embryonal carcinomas, and yolk sac tumors, respectively.
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| 11. |
- Orsini, S., et al.
(författare)
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Inner southern magnetosphere observation of Mercury via SERENA ion sensors in BepiColombo mission
- 2022
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Mercury’s southern inner magnetosphere is an unexplored region as it was not observed by earlier space missions. In October 2021, BepiColombo mission has passed through this region during its first Mercury flyby. Here, we describe the observations of SERENA ion sensors nearby and inside Mercury’s magnetosphere. An intermittent high-energy signal, possibly due to an interplanetary magnetic flux rope, has been observed downstream Mercury, together with low energy solar wind. Low energy ions, possibly due to satellite outgassing, were detected outside the magnetosphere. The dayside magnetopause and bow-shock crossing were much closer to the planet than expected, signature of a highly eroded magnetosphere. Different ion populations have been observed inside the magnetosphere, like low latitude boundary layer at magnetopause inbound and partial ring current at dawn close to the planet. These observations are important for understanding the weak magnetosphere behavior so close to the Sun, revealing details never reached before.
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| 12. |
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| 13. |
- Jakosky, B. M., et al.
(författare)
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MAVEN observations of the response of Mars to an interplanetary coronal mass ejection
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 350:6261
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Tidskriftsartikel (refereegranskat)abstract
- Coupling between the lower and upper atmosphere, combined with loss of gas from the upper atmosphere to space, likely contributed to the thin, cold, dry atmosphere of modern Mars. To help understand ongoing ion loss to space, the Mars Atmosphere and Volatile Evolution (MAVEN) spacecraft made comprehensive measurements of the Mars upper atmosphere, ionosphere, and interactions with the Sun and solar wind during an interplanetary coronal mass ejection impact in March 2015. Responses include changes in the bow shock and magnetosheath, formation of widespread diffuse aurora, and enhancement of pick-up ions. Observations and models both show an enhancement in escape rate of ions to space during the event. Ion loss during solar events early in Mars history may have been a major contributor to the long-term evolution of the Mars atmosphere.
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| 14. |
- Miyoshi, Y., et al.
(författare)
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The energization and radiation in geospace (ERG) project
- 2012
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Ingår i: Dynamics of The Earth's Radiation Belts and Inner Magnetosphere. - : American Geophysical Union (AGU). - 9780875904894 ; , s. 103-116
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Konferensbidrag (refereegranskat)abstract
- The Energization and Radiation in Geospace (ERG) project for solar cycle 24 will explore how relativistic electrons in the radiation belts are generated during space storms. This geospace exploration project consists of three research teams: the ERG satellite observation team, the ground-based network observation team, and the integrated data analysis/simulation team. Satellite observation will provide in situ measurements of features such as the plasma distribution function, electric and magnetic fields, and plasma waves, whereas remote sensing by ground-based observations using, for example, HF radars, magnetometers, optical instruments, and radio wave receivers will provide the global state of the geospace. Various kinds of data will be integrated and compared with numerical simulations for quantitative understanding. Such a synergetic approach is essential for comprehensive understanding of relativistic electron generation/loss processes through crossenergy and cross-regional coupling in which different plasma populations and regions are dynamically coupled with each other. In addition, the ERG satellite will utilize a new and innovative measurement technique for wave-particle interactions that can directly measure the energy exchange process between particles and plasma waves. In this paper, we briefly review some of the profound problems regarding relativistic electron accelerations and losses that will be solved by the ERG project, and we provide an overview of the project.
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| 15. |
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| 16. |
- Milillo, A., et al.
(författare)
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Investigating Mercury's Environment with the Two-Spacecraft BepiColombo Mission
- 2020
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Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 216:5
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Forskningsöversikt (refereegranskat)abstract
- The ESA-JAXA BepiColombo mission will provide simultaneous measurements from two spacecraft, offering an unprecedented opportunity to investigate magnetospheric and exospheric dynamics at Mercury as well as their interactions with the solar wind, radiation, and interplanetary dust. Many scientific instruments onboard the two spacecraft will be completely, or partially devoted to study the near-space environment of Mercury as well as the complex processes that govern it. Many issues remain unsolved even after the MESSENGER mission that ended in 2015. The specific orbits of the two spacecraft, MPO and Mio, and the comprehensive scientific payload allow a wider range of scientific questions to be addressed than those that could be achieved by the individual instruments acting alone, or by previous missions. These joint observations are of key importance because many phenomena in Mercury's environment are highly temporally and spatially variable. Examples of possible coordinated observations are described in this article, analysing the required geometrical conditions, pointing, resolutions and operation timing of different BepiColombo instruments sensors.
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| 17. |
- Sasaki, S, et al.
(författare)
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Dexterous finger movements in primate without monosynaptic corticomotoneuronal excitation
- 2004
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Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 92:5, s. 3142-3147
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Tidskriftsartikel (refereegranskat)abstract
- It is generally accepted that the precision grip and independent finger movements (IFMs) in monkey and man are controlled by the direct (monosynaptic) corticomotoneuronal (CM) pathway. This view is based on previous observations that pyramidotomy causes near permanent deficits of IFMs. However, in addition to the direct CM pathway, pyramidotomy interrupts several corticofugal connections to the brain stem and upper cervical segments. Indirect (oligosynaptic) CM pathways, which are phylogenetically older, have been considered to be of little or no importance in prehension. In three adult macaque monkeys, complete transection of the direct CM pathway was made in C4/C5, which is rostral to the forelimb segments (C6–Th1). Electrophysiological recordings revealed lack of the direct lateral corticospinal tract (LCST) volley, monosynaptic extracellular field potentials in the motor nuclei, and monosynaptic CM excitation. However, a disynaptic volley, disynaptic field potentials and disynaptic CM excitation mediated via C3–C4 propriospinal neurons remained after the lesion. Thus the lesion interrupted the monosynaptic CM pathway and oligosynaptic LCST pathways mediated by interneurons in the forelimb segments. Precision grip and IFMs were observed already after 1–28 days postoperatively. Weakness in force and deficits in preshaping remained for an observation period of 3 mo. Indirect CM pathways may be important for neuro-rehabilitation.
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| 18. |
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| 20. |
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| 21. |
- Hallermalm, K, et al.
(författare)
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Tumor necrosis factor-alpha induces coordinated changes in major histocompatibility class I presentation pathway, resulting in increased stability of class I complexes at the cell surface
- 2001
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 98:4, s. 1108-1115
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Tidskriftsartikel (refereegranskat)abstract
- It is demonstrated that similar to interferon γ (IFN-γ), tumor necrosis factor-α (TNF-α) induces coordinated changes at different steps of the major histocompatibility complex (MHC) class I processing and presentation pathway in nonprofessional antigen-presenting cells (APCs). TNF-α up-regulates the expression of 3 catalytic immunoproteasome subunits—LMP2, LMP7, and MECL-1—the immunomodulatory proteasome activator PA28α, the TAP1/TAP2 heterodimer, and the total pool of MHC class I heavy chain. It was also found that in TNF-α–treated cells, MHC class I molecules reconstitute more rapidly and have an increased average half-life at the cell surface. Biochemical changes induced by TNF-α in the MHC class I pathway were translated into increased sensitivity of TNF-α–treated targets to lysis by CD8+ cytotoxic T cells, demonstrating improved presentation of at least certain endogenously processed MHC class I–restricted peptide epitopes. Significantly, it was demonstrated that the effects of TNF-α observed in this experimental system were not mediated through the induction of IFN-γ. It appears to be likely that TNF-α–mediated effects on MHC class I processing and presentation do not involve any intermediate messengers. Collectively, these data demonstrate the existence of yet another biologic activity exerted by TNF-α, namely its capacity to act as a coordinated multi-step modulator of the MHC class I pathway of antigen processing and presentation. These results suggest that TNF-α may be useful when a concerted up-regulation of the MHC class I presentation machinery is required but cannot be achieved by IFN-γ.
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| 22. |
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| 23. |
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Kamio, S., et al.
(författare)
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First experiments on plasma production using field-aligned ICRF fast wave antennas in the large helical device
- 2021
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Ingår i: Nuclear Fusion. - : Institute of Physics (IOP). - 0029-5515 .- 1741-4326. ; 61:11
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Tidskriftsartikel (refereegranskat)abstract
- The results of the first experimental series to produce a plasma using the ion cyclotron range of frequency (ICRF) in the large helical device (LHD) within the minority scenario developed at Uragan-2M (U-2M) are presented. The motivation of this study is to provide plasma creation in conditions when an electron cyclotron resonance heating start-up is not possible, and in this way widen the operational frame of helical machines. The major constraint of the experiments is the low RF power to reduce the possibility of arcing. No dangerous voltage increase at the radio-frequency (RF) system elements and no arcing has been detected. As a result, a low plasma density is obtained and the antenna-plasma coupling is not optimal. However, such plasmas are sufficient to be used as targets for further neutral beam injection (NBI) heating. This will open possibilities to explore new regimes of operation at LHD and Wendelstein 7-X (W7-X) stellarator. The successful RF plasma production in LHD in this experimental series stimulates the planning of further studies of ICRF plasma production aimed at increasing plasma density and temperature within the ICRF minority scenario as well as investigating the plasma prolongation by NBI heating.
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| 28. |
- Kimura, S, et al.
(författare)
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Association of high-risk neuroblastoma classification based on expression profiles with differentiation and metabolism
- 2021
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:1, s. e0245526-
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma, the most common extracranial solid malignancy among children, originates from undifferentiated neural crest cells (NCC). Despite recent intensified treatment, high-risk patients still have a high mortality rate. To explore a new therapeutic strategy, we performed an integrated genomic and transcriptomic analysis of 30 high-risk neuroblastoma cases. Based on the expression profiling of RNA sequencing, neuroblastoma was classified into Mesenchymal (MES; n = 5) and Noradrenergic (ADRN; n = 25) clusters, as previously reported in the super-enhancer landscape. The expression patterns in MES-cluster cases were similar to normal adrenal glands, with enrichment in secretion-related pathways, suggesting chromaffin cell-like features built from NCC-derived Schwann cell precursors (SCPs). In contrast, neuron-related pathways were enriched in the ADRN-cluster, indicating sympathoblast features reported to originate from NCC but not via SCPs. Thus, MES- and ADRN-clusters were assumed to be corresponding to differentiation pathways through SCP and sympathoblast, respectively. ADRN-cluster cases were further classified into MYCN- and ATRX-clusters, characterized by genetic alterations, MYCN amplifications and ATRX alterations, respectively. MYCN-cluster cases showed high expression of ALDH18A1, encoding P5CS related to proline production. As reported in other cancers, this might cause reprogramming of proline metabolism leading to tumor specific proline vulnerability candidate for a target therapy of metabolic pathway. In ATRX-cluster, SLC18A2 (VMAT2), an enzyme known to prevent cell toxicity due to the oxidation of dopamine, was highly expressed and VMAT2 inhibitor (GZ-793A) represented significant attenuation of cell growth in NB-69 cell line (high SLC18A2 expression, no MYCN amplification) but not in IMR-32 cell line (MYCN amplification). In addition, the correlation of VMAT2 expression with metaiodobenzylguanidine (MIBG) avidity suggested a combination of VMAT2 inhibitor and MIBG radiation for a novel potential therapeutic strategy in ATRX-cluster cases. Thus, targeting the characteristics of unique neuroblastomas may prospectively improve prognosis.
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| 29. |
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| 30. |
- Lunde, J., et al.
(författare)
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Ion-dispersion and rapid electron fluctuations in the cusp : a case study
- 2008
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Ingår i: Annales Geophysicae. - 0992-7689 .- 1432-0576. ; 26:8, s. 2485-2502
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Tidskriftsartikel (refereegranskat)abstract
- We present results from co-ordinated measurements with the low altitude REIMEI satellite and the ESR (EISCAT Svalbard Radar), together with other ground-based instruments carried out in February 2006. The results mainly relate to the dayside cusp where clear signatures of so-called ion-dispersion are seen in the satellite data. The cusp ion-dispersion is important for helping to understand the temporal and spatial structure of magnetopause reconnection. Whenever a satellite crosses boundaries of flux tubes or convection cells, cusp structures such as ion-dispersion will always be encountered. In our case we observed 3 distinct steps in the ion energy, but it includes at least 2 more steps as well, which we interpret as temporal features in relation to pulsed reconnection at the magnetopause. In addition, fast variations of the electron flux and energy occurring during these events have been studied in detail. The variations of the electron population, if interpreted as structures crossed by the REIMEI satellite, would map near the magnetopause to similar features as observed previously with the Cluster satellites. These were explained as Alfven waves originating from an X-line of magnetic reconnection.
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| 31. |
- Ogawa, Y., et al.
(författare)
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Coordinated EISCAT Svalbard radar and Reimei satellite observations of ion upflows and suprathermal ions
- 2008
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 113:A5, s. A05306-
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Tidskriftsartikel (refereegranskat)abstract
- The relationship between bulk ion upflows and suprathermal ions was investigated using data simultaneously obtained from the European Incoherent Scatter (EISCAT) Svalbard radar (ESR) and the Reimei satellite. Simultaneous observations were conducted in November 2005 and August 2006, and 14 conjunction data sets have been obtained at approximately 630 km in the dayside ionosphere. Suprathermal ions with energies of a few eV were present in the dayside cusp region, and the ion velocity distribution changed from an isotropic Maxwellian near the cusp region to tail heating at energies above a few eV in the cusp region. The velocity distribution of the suprathermal ions has a peak perpendicular or oblique to the geomagnetic field, and the temperature of the suprathermal ions was 0.9-1.4 eV. An increase in the phase space density (PSD) of the suprathermal ions, measured with the Reimei, was correlated with bulk ion upflow observed at the same altitude using EISCAT, and with the energy flux of precipitating electrons with energies of 50-500 eV. The PSD also has a good correlation with the electron temperature, which was increased by precipitation, but not with the ion temperature (0.1-0.3 eV) at the same altitude measured with EISCAT. These results suggest that plasma waves such as broadband extremely low frequency (BBELF) wavefields associated with precipitation are connected to the bulk ion upflows in the cusp and effectively cause the heating of suprathermal ions. The heating of suprathermal ions disagrees with anisotropic heating due to O+-O resonant charge exchange.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Du, QQ, et al.
(författare)
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Generation of mega brown adipose tissue in adults by controlling brown adipocyte differentiation in vivo
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:40, s. e2203307119-
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Tidskriftsartikel (refereegranskat)abstract
- Brown adipose tissue (BAT) is a highly specialized adipose tissue in its immobile location and size during the entire adulthood. In response to cold exposure and other β3-adrenoreceptor stimuli, BAT commits energy consumption by nonshivering thermogenesis (NST). However, the molecular machinery in controlling the BAT mass in adults is unknown. Here, we show our surprising findings that the BAT mass and functions can be manipulated in adult animals by controlling BAT adipocyte differentiation in vivo. Platelet-derived growth factor receptor α (PDGFα) expressed in BAT progenitor cells served a signaling function to avert adipose progenitor differentiation. Genetic and pharmacological loss-of-function of PDGFRα eliminated the differentiation barrier and permitted progenitor cell differentiation to mature and functional BAT adipocytes. Consequently, an enlarged BAT mass (megaBAT) was created by PDGFRα inhibition owing to increases of brown adipocyte numbers. Under cold exposure, a microRNA-485 (miR-485) was identified as a master suppressor of the PDGFRα signaling, and delivery of miR-485 also produced megaBAT in adult animals. Noticeably, megaBAT markedly improved global metabolism, insulin sensitivity, high-fat-diet (HFD)-induced obesity, and diabetes by enhancing NST. Together, our findings demonstrate that the adult BAT mass can be increased by blocking the previously unprecedented inhibitory signaling for BAT progenitor cell differentiation. Thus, blocking the PDGFRα for the generation of megaBAT provides an attractive strategy for treating obesity and type 2 diabetes mellitus (T2DM).
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| 38. |
- Ebrahim, Shimaa A M, et al.
(författare)
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Drosophila Avoids Parasitoids by Sensing Their Semiochemicals via a Dedicated Olfactory Circuit.
- 2015
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- Detecting danger is one of the foremost tasks for a neural system. Larval parasitoids constitute clear danger to Drosophila, as up to 80% of fly larvae become parasitized in nature. We show that Drosophila melanogaster larvae and adults avoid sites smelling of the main parasitoid enemies, Leptopilina wasps. This avoidance is mediated via a highly specific olfactory sensory neuron (OSN) type. While the larval OSN expresses the olfactory receptor Or49a and is tuned to the Leptopilina odor iridomyrmecin, the adult expresses both Or49a and Or85f and in addition detects the wasp odors actinidine and nepetalactol. The information is transferred via projection neurons to a specific part of the lateral horn known to be involved in mediating avoidance. Drosophila has thus developed a dedicated circuit to detect a life-threatening enemy based on the smell of its semiochemicals. Such an enemy-detecting olfactory circuit has earlier only been characterized in mice and nematodes.
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| 39. |
- Hasegawa, H., et al.
(författare)
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Kelvin-Helmholtz waves at the Earth's magnetopause : Multiscale development and associated reconnection
- 2009
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 114:12, s. A12207-
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Tidskriftsartikel (refereegranskat)abstract
- We examine traversals on 20 November 2001 of the equatorial magnetopause boundary layer simultaneously at similar to 1500 magnetic local time (MLT) by the Geotail spacecraft and at similar to 1900 MLT by the Cluster spacecraft, which detected rolled-up MHD-scale vortices generated by the Kelvin-Helmholtz instability (KHI) under prolonged northward interplanetary magnetic field conditions. Our purpose is to address the excitation process of the KHI, MHD-scale and ion-scale structures of the vortices, and the formation mechanism of the low-latitude boundary layer (LLBL). The observed KH wavelength (>4 x 10(4) km) is considerably longer than predicted by the linear theory from the thickness (similar to 1000 km) of the dayside velocity shear layer. Our analyses suggest that the KHI excitation is facilitated by combined effects of the formation of the LLBL presumably through high-latitude magnetopause reconnection and compressional magnetosheath fluctuations on the dayside, and that breakup and/or coalescence of the vortices are beginning around 1900 MLT. Current layers of thickness a few times ion inertia length similar to 100 km and of magnetic shear similar to 60 degrees existed at the trailing edges of the vortices. Identified in one such current sheet were signatures of local reconnection: Alfvenic outflow jet within a bifurcated current sheet, nonzero magnetic field component normal to the sheet, and field-aligned beam of accelerated electrons. Because of its incipient nature, however, this reconnection process is unlikely to lead to the observed dusk-flank LLBL. It is thus inferred that the flank LLBL resulted from other mechanisms, namely, diffusion and/or remote reconnection unidentified by Cluster.
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| 40. |
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| 41. |
- Hosaka, K, et al.
(författare)
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Dual roles of endothelial FGF-2-FGFR1-PDGF-BB and perivascular FGF-2-FGFR2-PDGFRβ signaling pathways in tumor vascular remodeling
- 2018
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Ingår i: Cell discovery. - : Springer Science and Business Media LLC. - 2056-5968. ; 4, s. 3-
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Tidskriftsartikel (refereegranskat)abstract
- Perivascular cells are important cellular components in the tumor microenvironment (TME) and they modulate vascular integrity, remodeling, stability, and functions. Here we show using mice models that FGF-2 is a potent pericyte-stimulating factor in tumors. Mechanistically, FGF-2 binds to FGFR2 to stimulate pericyte proliferation and orchestrates the PDGFRβ signaling for vascular recruitment. FGF-2 sensitizes the PDGFRβ signaling through increasing PDGFRβ levels in pericytes. To ensure activation of PDGFRβ, the FGF-2–FGFR1-siganling induces PDGF-BB and PDGF-DD, two ligands for PDGFRβ, in angiogenic endothelial cells. Thus, FGF-2 directly and indirectly stimulates pericyte proliferation and recruitment by modulating the PDGF–PDGFRβ signaling. Our study identifies a novel mechanism by which the FGF-2 and PDGF-BB collaboratively modulate perivascular cell coverage in tumor vessels, thus providing mechanistic insights of pericyte–endothelial cell interactions in TME and conceptual implications for treatment of cancers and other diseases by targeting the FGF-2–FGFR-pericyte axis.
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Hosaka, K, et al.
(författare)
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Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3704-
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Tidskriftsartikel (refereegranskat)abstract
- FGF-2 displays multifarious functions in regulation of angiogenesis and vascular remodeling. However, effective drugs for treating FGF-2+ tumors are unavailable. Here we show that FGF-2 modulates tumor vessels by recruiting NG2+ pricytes onto tumor microvessels through a PDGFRβ-dependent mechanism. FGF-2+ tumors are intrinsically resistant to clinically available drugs targeting VEGF and PDGF. Surprisingly, dual targeting the VEGF and PDGF signaling produces a superior antitumor effect in FGF-2+ breast cancer and fibrosarcoma models. Mechanistically, inhibition of PDGFRβ ablates FGF-2-recruited perivascular coverage, exposing anti-VEGF agents to inhibit vascular sprouting. These findings show that the off-target FGF-2 is a resistant biomarker for anti-VEGF and anti-PDGF monotherapy, but a highly beneficial marker for combination therapy. Our data shed light on mechanistic interactions between various angiogenic and remodeling factors in tumor neovascularization. Optimization of antiangiogenic drugs with different principles could produce therapeutic benefits for treating their resistant off-target cancers.
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| 46. |
- Hunt, L, et al.
(författare)
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Gene-specific expression and calcium activation of Arabidopsis thaliana phospholipase C isoforms
- 2004
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Ingår i: New Phytologist. - : Wiley. - 1469-8137 .- 0028-646X. ; 162:3, s. 643-654
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Tidskriftsartikel (refereegranskat)abstract
- PI-PLCs synthesise the calcium releasing second messenger IP3. We investigated the expression patterns of the Arabidopsis PI-PLC gene family and measured in vitro activity of encoded enzymes. Gene specific RT-PCR and promoter-GUS fusions were used to analyse AtPLC gene expression patterns. The five available AtPLC cDNAs were expressed as fusion proteins in Escherichia coli. All members of the AtPLC gene family were expressed in multiple organs of the plant. AtPLC1, and AtPLC5 expression was localized to the vascular cells of roots and leaves with AtPLC5::GUS also detected in the guard cells. AtPLC4::GUS was detected in pollen and cells of the stigma surface. In seedlings, AtPLC2 and AtPLC3 were constitutively expressed, while AtPLCs 1, 4 and 5 were induced by abiotic stresses. AtPLC1-5 were all shown to have phospholipase C activity in the presence of calcium ions. AtPLCs showed limited tissue specific expression and expression of at least three genes was increased by abiotic stress. The differing calcium sensitivities of recombinant AtPLC protein activities may provide a mechanism for generating calcium signatures.
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| 47. |
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| 48. |
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| 49. |
- Jing, X, et al.
(författare)
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COVID-19 instigates adipose browning and atrophy through VEGF in small mammals
- 2022
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:12, s. 1674-
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Tidskriftsartikel (refereegranskat)abstract
- Patients with COVID-19 frequently manifest adipose atrophy, weight loss and cachexia, which significantly contribute to poor quality of life and mortality1,2. Browning of white adipose tissue and activation of brown adipose tissue are effective processes for energy expenditure3–7; however, mechanistic and functional links between SARS-CoV-2 infection and adipose thermogenesis have not been studied. In this study, we provide experimental evidence that SARS-CoV-2 infection augments adipose browning and non-shivering thermogenesis (NST), which contributes to adipose atrophy and body weight loss. In mouse and hamster models, SARS-CoV-2 infection activates brown adipose tissue and instigates a browning or beige phenotype of white adipose tissues, including augmented NST. This browning phenotype was also observed in post-mortem adipose tissue of four patients who died of COVID-19. Mechanistically, high levels of vascular endothelial growth factor (VEGF) in the adipose tissue induces adipose browning through vasculature–adipocyte interaction. Inhibition of VEGF blocks COVID-19-induced adipose tissue browning and NST and partially prevents infection-induced body weight loss. Our data suggest that the browning of adipose tissues induced by COVID-19 can contribute to adipose tissue atrophy and weight loss observed during infection. Inhibition of VEGF signaling may represent an effective approach for preventing and treating COVID-19-associated weight loss.
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| 50. |
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