| 1. |
- 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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| 2. |
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| 3. |
- Joffrin, E., et al.
(författare)
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Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Forskningsöversikt (refereegranskat)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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| 4. |
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| 5. |
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| 6. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 7. |
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| 8. |
- Kovacs, Gabor G., et al.
(författare)
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Aging-related tau astrogliopathy (ARTAG) : harmonized evaluation strategy
- 2016
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 131:1, s. 87-102
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Tidskriftsartikel (refereegranskat)abstract
- Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of astroglial tau pathology in the aged brain, facilitating communication among neuropathologists and researchers, and informing interpretation of clinical biomarkers and imaging studies that focus on tau-related indicators.
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| 9. |
- Kovacs, Gabor G., et al.
(författare)
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Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG)
- 2017
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Ingår i: Journal of Neuropathology and Experimental Neurology. - : Oxford University Press (OUP). - 0022-3069 .- 1554-6578. ; 76:7, s. 605-619
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Tidskriftsartikel (refereegranskat)abstract
- Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was > 60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (> 90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity.
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| 10. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 11. |
- Alafuzoff, Irina, et al.
(författare)
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Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions : an inter-laboratory study by the BrainNet Europe consortium
- 2015
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Ingår i: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 122:7, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- The BrainNet Europe consortium assessed the reproducibility in the assignment of the type of frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein (TDP) 43 following current recommendations. The agreement rates were influenced by the immunohistochemical (IHC) method and by the classification strategy followed. p62-IHC staining yielded good uniform quality of stains, but the most reliable results were obtained implementing specific Abs directed against the hallmark protein TDP43. Both assessment of the type and the extent of lesions were influenced by the Abs and by the quality of stain. Assessment of the extent of the lesions yielded poor results repeatedly; thus, the extent of pathology should not be used in diagnostic consensus criteria. Whilst 31 neuropathologists typed 30 FTLD-TDP cases, inter-rater agreement ranged from 19 to 100 per cent, being highest when applying phosphorylated TDP43/IHC. The agreement was highest when designating Type C or Type A/B. In contrast, there was a poor agreement when attempting to separate Type A or Type B FTLD-TDP. In conclusion, we can expect that neuropathologist, independent of his/her familiarity with FTLD-TDP pathology, can identify a TDP43-positive FTLD case. The goal should be to state a Type (A, B, C, D) or a mixture of Types (A/B, A/C or B/C). Neuropathologists, other clinicians and researchers should be aware of the pitfalls whilst doing so. Agreement can be reached in an inter-laboratory setting regarding Type C cases with thick and long neurites, whereas the differentiation between Types A and B may be more troublesome.
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| 12. |
- Alafuzoff, Irina, et al.
(författare)
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Staging of neurofibrillary pathology in Alzheimer's disease : a study of the BrainNet Europe Consortium.
- 2008
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Ingår i: Brain Pathology. - : Wiley. - 1015-6305 .- 1750-3639. ; 18:4, s. 484-96
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Tidskriftsartikel (refereegranskat)abstract
- It has been recognized that molecular classifications will form the basis for neuropathological diagnostic work in the future. Consequently, in order to reach a diagnosis of Alzheimer's disease (AD), the presence of hyperphosphorylated tau (HP-tau) and beta-amyloid protein in brain tissue must be unequivocal. In addition, the stepwise progression of pathology needs to be assessed. This paper deals exclusively with the regional assessment of AD-related HP-tau pathology. The objective was to provide straightforward instructions to aid in the assessment of AD-related immunohistochemically (IHC) detected HP-tau pathology and to test the concordance of assessments made by 25 independent evaluators. The assessment of progression in 7-microm-thick sections was based on assessment of IHC labeled HP-tau immunoreactive neuropil threads (NTs). Our results indicate that good agreement can be reached when the lesions are substantial, i.e., the lesions have reached isocortical structures (stage V-VI absolute agreement 91%), whereas when only mild subtle lesions were present the agreement was poorer (I-II absolute agreement 50%). Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers.
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| 13. |
- Alder-Rangel, Alene, et al.
(författare)
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The Third International Symposium on Fungal Stress – ISFUS
- 2020
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Ingår i: Fungal Biology. - : Elsevier BV. - 1878-6146. ; 124:5, s. 235-252
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Tidskriftsartikel (refereegranskat)abstract
- Stress is a normal part of life for fungi, which can survive in environments considered inhospitable or hostile for other organisms. Due to the ability of fungi to respond to, survive in, and transform the environment, even under severe stresses, many researchers are exploring the mechanisms that enable fungi to adapt to stress. The International Symposium on Fungal Stress (ISFUS) brings together leading scientists from around the world who research fungal stress. This article discusses presentations given at the third ISFUS, held in São José dos Campos, São Paulo, Brazil in 2019, thereby summarizing the state-of-the-art knowledge on fungal stress, a field that includes microbiology, agriculture, ecology, biotechnology, medicine, and astrobiology.
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| 14. |
- Maróti, Zoltán, et al.
(författare)
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The genetic origin of Huns, Avars, and conquering Hungarians
- 2022
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 32:13, s. 2858-2870, 2858–2870.e1–e7
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Tidskriftsartikel (refereegranskat)abstract
- Huns, Avars, and conquering Hungarians were migration-period nomadic tribal confederations that arrived in three successive waves in the Carpathian Basin between the 5th and 9th centuries. Based on the historical data, each of these groups are thought to have arrived from Asia, although their exact origin and relation to other ancient and modern populations have been debated. Recently, hundreds of ancient genomes were analyzed from Central Asia, Mongolia, and China, from which we aimed to identify putative source populations for the above-mentioned groups. In this study, we have sequenced 9 Hun, 143 Avar, and 113 Hungarian conquest period samples and identified three core populations, representing immigrants from each period with no recent European ancestry. Our results reveal that this “immigrant core” of both Huns and Avars likely originated in present day Mongolia, and their origin can be traced back to Xiongnus (Asian Huns), as suggested by several historians. On the other hand, the “immigrant core” of the conquering Hungarians derived from an earlier admixture of Mansis, early Sarmatians, and descendants of late Xiongnus. We have also shown that a common “proto-Ugric” gene pool appeared in the Bronze Age from the admixture of Mezhovskaya and Nganasan people, supporting genetic and linguistic data. In addition, we detected shared Hun-related ancestry in numerous Avar and Hungarian conquest period genetic outliers, indicating a genetic link between these successive nomadic groups. Aside from the immigrant core groups, we identified that the majority of the individuals from each period were local residents harboring “native European” ancestry.
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| 15. |
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| 16. |
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| 17. |
- Alafuzoff, Irina, et al.
(författare)
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Assessment of beta-amyloid deposits in human brain : a study of the BrainNet Europe Consortium
- 2009
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 117:3, s. 309-320
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Tidskriftsartikel (refereegranskat)abstract
- beta-Amyloid (A-beta) related pathology shows a range of lesions which differ both qualitatively and quantitatively. Pathologists, to date, mainly focused on the assessment of both of these aspects but attempts to correlate the findings with clinical phenotypes are not convincing. It has been recently proposed in the same way as iota and alpha synuclein related lesions, also A-beta related pathology may follow a temporal evolution, i.e. distinct phases, characterized by a step-wise involvement of different brain-regions. Twenty-six independent observers reached an 81% absolute agreement while assessing the phase of A-beta, i.e. phase 1 = deposition of A-beta exclusively in neocortex, phase 2 = additionally in allocortex, phase 3 = additionally in diencephalon, phase 4 = additionally in brainstem, and phase 5 = additionally in cerebellum. These high agreement rates were reached when at least six brain regions were evaluated. Likewise, a high agreement (93%) was reached while assessing the absence/presence of cerebral amyloid angiopathy (CAA) and the type of CAA (74%) while examining the six brain regions. Of note, most of observers failed to detect capillary CAA when it was only mild and focal and thus instead of type 1, type 2 CAA was diagnosed. In conclusion, a reliable assessment of A-beta phase and presence/absence of CAA was achieved by a total of 26 observers who examined a standardized set of blocks taken from only six anatomical regions, applying commercially available reagents and by assessing them as instructed. Thus, one may consider rating of A-beta-phases as a diagnostic tool while analyzing subjects with suspected Alzheimer's disease (AD). Because most of these blocks are currently routinely sampled by the majority of laboratories, assessment of the A-beta phase in AD is feasible even in large scale retrospective studies.
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| 18. |
- Betancourt, Lazaro Hiram, et al.
(författare)
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The human melanoma proteome atlas-Defining the molecular pathology
- 2021
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Ingår i: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 11:7, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in-depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.
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| 19. |
- Biswas, Dhruva, et al.
(författare)
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A clonal expression biomarker associates with lung cancer mortality
- 2019
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:10, s. 1540-1548
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Tidskriftsartikel (refereegranskat)abstract
- An aim of molecular biomarkers is to stratify patients with cancer into disease subtypes predictive of outcome, improving diagnostic precision beyond clinical descriptors such as tumor stage(1). Transcriptomic intratumor heterogeneity (RNA-ITH) has been shown to confound existing expression-based biomarkers across multiple cancer types(2-6). Here, we analyze multi-region whole-exome and RNA sequencing data for 156 tumor regions from 48 patients enrolled in the TRACERx study to explore and control for RNA-ITH in non-small cell lung cancer. We find that chromosomal instability is a major driver of RNA-ITH, and existing prognostic gene expression signatures are vulnerable to tumor sampling bias. To address this, we identify genes expressed homogeneously within individual tumors that encode expression modules of cancer cell proliferation and are often driven by DNA copy-number gains selected early in tumor evolution. Clonal transcriptomic biomarkers overcome tumor sampling bias, associate with survival independent of clinicopathological risk factors, and may provide a general strategy to refine biomarker design across cancer types.
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| 20. |
- Catto, P. J., et al.
(författare)
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Kinetic effects on a tokamak pedestal ion flow, ion heat transport and bootstrap current
- 2013
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 55:4
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Tidskriftsartikel (refereegranskat)abstract
- We consider the effects of a finite radial electric field on ion orbits in a subsonic pedestal. Using a procedure that makes a clear distinction between a transit average and a flux surface average we are able to solve the kinetic equation to retain the modifications due to finite E X B drift orbit departures from flux surfaces. Our approach properly determines the velocity space localized, as well as the nonlocal, portion of the ion distribution function in the banana and plateau regimes in the small aspect ratio limit. The rapid variation of the poloidal ion flow coefficient and the electrostatic potential in the total energy modify previous banana regime evaluations of the ion flow, the bootstrap current, and the radial ion heat flux in a subsonic pedestal. In the plateau regime, the rapid variation of the poloidal flow coefficient alters earlier results for the ion flow and bootstrap current, while leaving the ion heat flux unchanged since the rapid poloidal variation of the total energy was properly retained.
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| 21. |
- Cinege, Gyöngyi, et al.
(författare)
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Broad Ultrastructural and Transcriptomic Changes Underlie the Multinucleated Giant Hemocyte Mediated Innate Immune Response against Parasitoids
- 2022
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Ingår i: Journal of Innate Immunity. - : S. Karger. - 1662-811X .- 1662-8128. ; 14:4, s. 335-354
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Tidskriftsartikel (refereegranskat)abstract
- Multinucleated giant hemocytes (MGHs) represent a novel type of blood cell in insects that participate in a highly efficient immune response against parasitoid wasps involving isolation and killing of the parasite. Previously, we showed that circulating MGHs have high motility and the interaction with the parasitoid rapidly triggers encapsulation. However, structural and molecular mechanisms behind these processes remained elusive. Here, we used detailed ultrastructural analysis and live cell imaging of MGHs to study encapsulation in Drosophila ananassae after parasitoid wasp infection. We found dynamic structural changes, mainly driven by the formation of diverse vesicular systems and newly developed complex intracytoplasmic membrane structures, and abundant generation of giant cell exosomes in MGHs. In addition, we used RNA sequencing to study the transcriptomic profile of MGHs and activated plasmatocytes 72 h after infection, as well as the uninduced blood cells. This revealed that differentiation of MGHs was accompanied by broad changes in gene expression. Consistent with the observed structural changes, transcripts related to vesicular function, cytoskeletal organization, and adhesion were enriched in MGHs. In addition, several orphan genes encoding for hemolysin-like proteins, pore-forming toxins of prokaryotic origin, were expressed at high level, which may be important for parasitoid elimination. Our results reveal coordinated molecular and structural changes in the course of MGH differentiation and parasitoid encapsulation, providing a mechanistic model for a powerful innate immune response.
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| 22. |
- Cinege, Gyöngyi, et al.
(författare)
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Cellular immunity of Drosophila willistoni reveals novel complexity in insect anti-parasitoid defense
- 2024
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Ingår i: Cells. - : MDPI. - 2073-4409. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- Coevolution of hosts and their parasites has shaped heterogeneity of effector hemocyte types, providing immune defense reactions with variable effectiveness. In this work, we characterize hemocytes of Drosophila willistoni, a species that has evolved a cellular immune system with extensive variation and a high degree of plasticity. Monoclonal antibodies were raised and used in indirect immunofluorescence experiments to characterize hemocyte subpopulations, follow their functional features and differentiation. Pagocytosis and parasitization assays were used to determine the functional characteristics of hemocyte types. Samples were visualized using confocal and epifluorescence microscopy. We identified a new multinucleated giant hemocyte (MGH) type, which differentiates in the course of the cellular immune response to parasitoids. These cells differentiate in the circulation through nuclear division and cell fusion, and can also be derived from the central hematopoietic organ, the lymph gland. They have a binary function as they take up bacteria by phagocytosis and are involved in the encapsulation and elimination of the parasitoid. Here, we show that, in response to large foreign particles, such as parasitoids, MGHs differentiate, have a binary function and contribute to a highly effective cellular immune response, similar to the foreign body giant cells of vertebrates.
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| 23. |
- Cinege, Gyöngyi, et al.
(författare)
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Distinctive features of Zaprionus indianus hemocyte differentiation and function revealed by transcriptomic analysis
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insects have specialized cell types that participate in the elimination of parasites, for instance, the lamellocytes of the broadly studied species Drosophila melanogaster. Other drosophilids, such as Drosophila ananassae and the invasive Zaprionus indianus, have multinucleated giant hemocytes, a syncytium of blood cells that participate in the encapsulation of the eggs or larvae of parasitoid wasps. These cells can be formed by the fusion of hemocytes in circulation or originate from the lymph gland. Their ultrastructure highly resembles that of the mammalian megakaryocytes.Methods: Morphological, protein expressional, and functional features of blood cells were revealed using epifluorescence and confocal microscopy. The respective hemocyte subpopulations were identified using monoclonal antibodies in indirect immunofluorescence assays. Fluorescein isothiocyanate (FITC)-labeled Escherichia coli bacteria were used in phagocytosis tests. Gene expression analysis was performed following mRNA sequencing of blood cells.Results: D. ananassae and Z. indianus encapsulate foreign particles with the involvement of multinucleated giant hemocytes and mount a highly efficient immune response against parasitoid wasps. Morphological, protein expressional, and functional assays of Z. indianus blood cells suggested that these cells could be derived from large plasmatocytes, a unique cell type developing specifically after parasitoid wasp infection. Transcriptomic analysis of blood cells, isolated from naïve and wasp-infected Z. indianus larvae, revealed several differentially expressed genes involved in signal transduction, cell movements, encapsulation of foreign targets, energy production, and melanization, suggesting their role in the anti-parasitoid response. A large number of genes that encode proteins associated with coagulation and wound healing, such as phenoloxidase activity factor-like proteins, fibrinogen-related proteins, lectins, and proteins involved in the differentiation and function of platelets, were constitutively expressed. The remarkable ultrastructural similarities between giant hemocytes and mammalian megakaryocytes, and presence of platelets, and giant cell-derived anucleated fragments at wound sites hint at the involvement of this cell subpopulation in wound healing processes, in addition to participation in the encapsulation reaction.Conclusion: Our observations provide insights into the broad repertoire of blood cell functions required for efficient defense reactions to maintain the homeostasis of the organism. The analysis of the differentiation and function of multinucleated giant hemocytes gives an insight into the diversification of the immune mechanisms.
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| 24. |
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| 25. |
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| 26. |
- Deans, Andrew R, et al.
(författare)
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Finding Our Way through Phenotypes.
- 2015
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite a large and multifaceted effort to understand the vast landscape of phenotypic data, their current form inhibits productive data analysis. The lack of a community-wide, consensus-based, human- and machine-interpretable language for describing phenotypes and their genomic and environmental contexts is perhaps the most pressing scientific bottleneck to integration across many key fields in biology, including genomics, systems biology, development, medicine, evolution, ecology, and systematics. Here we survey the current phenomics landscape, including data resources and handling, and the progress that has been made to accurately capture relevant data descriptions for phenotypes. We present an example of the kind of integration across domains that computable phenotypes would enable, and we call upon the broader biology community, publishers, and relevant funding agencies to support efforts to surmount today's data barriers and facilitate analytical reproducibility.
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| 27. |
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| 28. |
- Gordeeva, Alisa, et al.
(författare)
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Layered Zinc Hydroxide Dihydrate, Zn-5(OH)(10)center dot 2H(2)O, from Hydrothermal Conversion of epsilon-Zn(OH)(2) at Gigapascal Pressures and its Transformation to Nanocrystalline ZnO
- 2020
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Ingår i: ACS Omega. - : AMER CHEMICAL SOC. - 2470-1343. ; 5:28, s. 17617-17627
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Tidskriftsartikel (refereegranskat)abstract
- Layered zinc hydroxides (LZHs) with the general formula (Zn2+)(x)(OH-)(2x-my ),(A(m-))(y)center dot nH(2)O (A(m-) = Cl- , NO3- , ac(-) , SO42-, etc) are considered as useful precursors for the fabrication of functional ZnO nanostructures. Here, we report the synthesis and structure characterization of the hitherto unknown "binary" representative of the LZH compound family, Zn-5(OH)(10)center dot 2H(2)O, with A(m-) = OH- , x = 5, y = 2, and n = 2. Zn-5(OH)(10)center dot 2H(2)O was afforded quantitatively by pressurizing mixtures of epsilon-Zn(OH)(2) (wulfingite) and water to 1-2 GPa and applying slightly elevated temperatures, 100-200 degrees C. The monoclinic crystal structure was characterized from powder X-ray diffraction data (space group C2/c, a = 15.342(7) angstrom, b = 6.244(6) angstrom, c = 10.989(7) angstrom, beta = 100.86(1)degrees). It features neutral zinc hydroxide layers, composed of octahedrally and tetrahedrally coordinated Zn ions with a 3:2 ratio, in which H2O is intercalated. The interlayer d(200) distance is 7.53 angstrom. The H-bond structure of Zn-5(OH)(10)center dot 2H(2)O was analyzed by a combination of infrared/Raman spectroscopy, computational modeling, and neutron powder diffraction. Interlayer H2O molecules are strongly H-bonded to five surrounding OH groups and appear orientationally disordered. The decomposition of Zn-5(OH)(10)center dot 2H(2)O, which occurs thermally between 70 and 100 degrees C, was followed in an in situ transmission electron microscopy study and ex situ annealing experiments. It yields initially 5-15 nm sized hexagonal w-ZnO crystals, which, depending on the conditions, may intergrow to several hundred nm-large two-dimensional, flakelike crystals within the boundary of original Zn-5(OH)(10)center dot 2H(2)O particles.
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| 29. |
- Gordeeva, Alisa, et al.
(författare)
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Layered Zinc Hydroxide Dihydrate, Zn5(OH)10·2H2O, from Hydrothermal Conversion of ε-Zn(OH)2 at Gigapascal Pressures and its Transformation to Nanocrystalline ZnO
- 2020
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 5:28, s. 17617-17627
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Tidskriftsartikel (refereegranskat)abstract
- Layered zinc hydroxides (LZHs) with the general formula (Zn2+)x(OH–)2x−my(Am–)y·nH2O (Am– = Cl–, NO3–, ac–, SO42–, etc) are considered as useful precursors for the fabrication of functional ZnO nanostructures. Here, we report the synthesis and structure characterization of the hitherto unknown “binary” representative of the LZH compound family, Zn5(OH)10·2H2O, with Am– = OH–, x = 5, y = 2, and n = 2. Zn5(OH)10·2H2O was afforded quantitatively by pressurizing mixtures of ε-Zn(OH)2 (wulfingite) and water to 1–2 GPa and applying slightly elevated temperatures, 100–200 °C. The monoclinic crystal structure was characterized from powder X-ray diffraction data (space group C2/c, a = 15.342(7) Å, b = 6.244(6) Å, c = 10.989(7) Å, β = 100.86(1)°). It features neutral zinc hydroxide layers, composed of octahedrally and tetrahedrally coordinated Zn ions with a 3:2 ratio, in which H2O is intercalated. The interlayer d(200) distance is 7.53 Å. The H-bond structure of Zn5(OH)10·2H2O was analyzed by a combination of infrared/Raman spectroscopy, computational modeling, and neutron powder diffraction. Interlayer H2O molecules are strongly H-bonded to five surrounding OH groups and appear orientationally disordered. The decomposition of Zn5(OH)10·2H2O, which occurs thermally between 70 and 100 °C, was followed in an in situ transmission electron microscopy study and ex situ annealing experiments. It yields initially 5–15 nm sized hexagonal w-ZnO crystals, which, depending on the conditions, may intergrow to several hundred nm-large two-dimensional, flakelike crystals within the boundary of original Zn5(OH)10·2H2O particles.
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| 30. |
- Gram, Dorte X., et al.
(författare)
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Capsaicin-sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetes
- 2007
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Ingår i: European Journal of Neuroscience. - : Wiley. - 1460-9568 .- 0953-816X. ; 25:1, s. 213-223
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Tidskriftsartikel (refereegranskat)abstract
- The system that regulates insulin secretion from beta-cells in the islet of Langerhans has a capsaicin-sensitive inhibitory component. As calcitonin gene-related peptide (CGRP)-expressing primary sensory fibers innervate the islets, and a major proportion of the CGRP-containing primary sensory neurons is sensitive to capsaicin, the islet-innervating sensory fibers may represent the capsaicin-sensitive inhibitory component. Here, we examined the expression of the capsaicin receptor, vanilloid type 1 transient receptor potential receptor (TRPV1) in CGRP-expressing fibers in the pancreatic islets, and the effect of selective elimination of capsaicin-sensitive primary afferents on the decline of glucose homeostasis and insulin secretion in Zucker diabetic fatty (ZDF) rats, which are used to study various aspects of human type 2 diabetes mellitus. We found that CGRP-expressing fibers in the pancreatic islets also express TRPV1. Furthermore, we also found that systemic capsaicin application before the development of hyperglycemia prevents the increase of fasting, non-fasting, and mean 24-h plasma glucose levels, and the deterioration of glucose tolerance assessed on the fifth week following the injection. These effects were accompanied by enhanced insulin secretion and a virtually complete loss of CGRP- and TRPV1-coexpressing islet-innervating fibers. These data indicate that CGRP-containing fibers in the islets are capsaicin sensitive, and that elimination of these fibers contributes to the prevention of the deterioration of glucose homeostasis through increased insulin secretion in ZDF rats. Based on these data we propose that the activity of islet-innervating capsaicin-sensitive fibers may have a role in the development of reduced insulin secretion in human type 2 diabetes mellitus.
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| 31. |
- Hanson, C, et al.
(författare)
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Sensitivity to extrinsically supplied interferon and the endogenous expression of interferon in melanoma cell lines.
- 1999
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Ingår i: Melanoma research. - 0960-8931. ; 9:5, s. 451-6
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Tidskriftsartikel (refereegranskat)abstract
- Interferons (IFNs) have been shown to Induce loss of growth potential in melanoma cell lines. However, human melanomas have shown limited responsiveness to clinical therapy with IFN. In a previous study on melanoma cell lines we found that greatest sensitivity to IFN was found in cell lines with the greatest number of copies of chromosome 9p, where the IFN gene family is located. In the present study the expression In melanoma cell lines of IFN genes, IFN receptor genes and standard control genes (beta-actin, glyceraldehyde-3-phosphate dehydrogenase, 18S rRNA and cyclophilin) was investigated using the reverse transcription-polymerase chain reaction, together with an exogenous standard (cyclophllin armoured RNA). We found that the sensitivity to extrinsically supplied IFN seems to correlate with the expression of endogenous IFN genes. The two melanoma cell lines producing the highest relative amount of IFN mRNA transcripts also demonstrated the most marked response to extrinsically supplied IFN. We hypothesize that tumours with enhanced endogenous IFN production may respond more positively to IFN treatment.
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| 32. |
- Jenei, István Zoltán, et al.
(författare)
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Structural phase transition in vanadium at high pressure and high temperature : Influence of nonhydrostatic conditions
- 2011
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 83:5
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Tidskriftsartikel (refereegranskat)abstract
- Vanadium has been reported to undergo phase transition upon compression from body-centered cubic (bcc) to rhombohedral structure around 62 GPa. In this paper we confirm the bcc to rhombohedral phase transition at 61.5 GPa under quasihydrostatic compression in the Ne pressure medium. Under the nonhydrostatic condition we find the phase transition occurring at 30 GPa at ambient temperature and 37 GPa at 425 K. We find the transition under the hydrostatic condition is hindered and it can occur at much lower pressure under the nonhydrostatic condition.
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| 33. |
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| 34. |
- Kagan, G., et al.
(författare)
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Neoclassical Theory of Pedestal Flows and Comparison with Alcator C-Mod Measurements
- 2012
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Ingår i: Contributions to Plasma Physics. - : Wiley. - 0863-1042 .- 1521-3986. ; 52:5-6, s. 365 - 371
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Tidskriftsartikel (refereegranskat)abstract
- Neoclassical implications of the strong radial electric field, inherently present in an H-mode tokamak pedestal, are considered. The main ion poloidal flow in the pedestal is predicted to be reduced in magnitude, or even reversed, compared with its core counterpart. The resulting change in the neoclassical formula for the impurity flow is shown to result in improved agreement with boron measurements in the Alcator C-Mod pedestal. In addition, due to the ion flow being modified, the bootstrap current is expected to be enhanced in the pedestal over conventional predictions.
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| 35. |
- Kormin, Dmitrii, et al.
(författare)
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Spectral interferometry with waveform-dependent relativistic high-order harmonics from plasma surfaces
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The interaction of ultra-intense laser pulses with matter opened the way to generate the shortest light pulses available nowadays in the attosecond regime. Ionized solid surfaces, also called plasma mirrors, are promising tools to enhance the potential of attosecond sources in terms of photon energy, photon number and duration especially at relativistic laser intensities. Although the production of isolated attosecond pulses and the understanding of the underlying interactions represent a fundamental step towards the realization of such sources, these are challenging and have not yet been demonstrated. Here, we present laser-waveform-dependent high-order harmonic radiation in the extreme ultraviolet spectral range supporting well-isolated attosecond pulses, and utilize spectral interferometry to understand its relativistic generation mechanism. This unique interpretation of the measured spectra provides access to unrevealed temporal and spatial properties such as spectral phase difference between attosecond pulses and field-driven plasma surface motion during the process.
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| 36. |
- Ma, Guangjin, et al.
(författare)
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Waveform-dependent relativistic high-order harmonics and field-driven plasma surface dynamics
- 2019
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Ingår i: Ultrafast Optics 2019. - : SPIE. - 9781510635128 ; , s. 106-110
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Konferensbidrag (refereegranskat)abstract
- Attosecond XUV-pump XUV-probe experiments demand high brightness attosecond light source benefitting from state-of-the-art ultrashort ultraintense laser technology. Current most promising route towards high energy attosecond light source is through relativistic high-order harmonic generation from plasma surfaces. In this paper, we investigate waveform-dependent relativistic high-order harmonic generation from plasma surfaces, and use spectral interferometry to understand its generation process. The unique interpretation has allowed access to unrevealed temporal structure of the generated few-pulse attotrain with evidence supporting a well-isolated attosecond pulse. It also provides a way to measure field-driven plasma surface motion in its generation process.
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| 37. |
- Macsari, Istvan, et al.
(författare)
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3-Oxoisoindoline-1-carboxamides : Potent, State-Dependent Blockers of Voltage-Gated Sodium Channel Na(V)1.7 with Efficacy in Rat Pain Models
- 2012
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:15, s. 6866-6880
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Tidskriftsartikel (refereegranskat)abstract
- The voltage-gated sodium channel Na(V)1.7 is believed to be a critical mediator of pain sensation based on clinical genetic studies and pharmacological results. Clinical utility of nonselective sodium channel blockers is limited due to serious adverse drug effects. Here, we present the optimization, structure activity relationships, and in vitro and in vivo characterization of a novel series of Na(V)1.7 inhibitors based on the oxoisoindoline core. Extensive studies with focus on optimization of Na(V)1.7 potency, selectivity over Na(V)1.5, and metabolic stability properties produced several interesting oxoisoindoline carboxamides (16A, 26B, 28, 51, 60, and 62) that were further characterized. The oxoisoindoline carboxamides interacted with the local anesthetics binding site. In spite of this, several compounds showed functional selectivity versus Na(V)1.5 of more than 100-fold. This appeared to be a combination of subtype and state-dependent selectivity. Compound 28 showed concentration-dependent inhibition of nerve injury-induced ectopic in an ex vivo DRG preparation from SNL rats. Compounds 16A and 26B demonstrated concentration-dependent efficacy in preclinical behavioral pain models. The oxoisoindoline carboxamides series described here may be valuable for further investigations for pain therapeutics.
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| 38. |
- Macsari, Istvan, et al.
(författare)
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Phenyl isoxazole voltage-gated sodium channel blockers : structure and activity relationship
- 2011
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 21:13, s. 3871-3876
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Tidskriftsartikel (refereegranskat)abstract
- Blocking of certain sodium channels is considered to be an attractive mechanism to treat chronic pain conditions. Phenyl isoxazole carbamate 1 was identified as a potent and selective Na(V)1.7 blocker. Structural analogues of 1, both carbamates, ureas and amides, were proven to be useful in establishing the structure-activity relationship and improving ADME related properties. Amide 24 showed a good overall in vitro profile, that translated well to rat in vivo PK.
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| 39. |
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| 40. |
- Thompson, Robin N., et al.
(författare)
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Key questions for modelling COVID-19 exit strategies
- 2020
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 287:1932
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Tidskriftsartikel (refereegranskat)abstract
- Combinations of intense non-pharmaceutical interventions (lockdowns) were introduced worldwide to reduce SARS-CoV-2 transmission. Many governments have begun to implement exit strategies that relax restrictions while attempting to control the risk of a surge in cases. Mathematical modelling has played a central role in guiding interventions, but the challenge of designing optimal exit strategies in the face of ongoing transmission is unprecedented. Here, we report discussions from the Isaac Newton Institute 'Models for an exit strategy' workshop (11-15 May 2020). A diverse community of modellers who are providing evidence to governments worldwide were asked to identify the main questions that, if answered, would allow for more accurate predictions of the effects of different exit strategies. Based on these questions, we propose a roadmap to facilitate the development of reliable models to guide exit strategies. This roadmap requires a global collaborative effort from the scientific community and policymakers, and has three parts: (i) improve estimation of key epidemiological parameters; (ii) understand sources of heterogeneity in populations; and (iii) focus on requirements for data collection, particularly in low-to-middle-income countries. This will provide important information for planning exit strategies that balance socio-economic benefits with public health.
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| 41. |
- Thorn, D. B., et al.
(författare)
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Polarization and anisotropic emission of K-shell radiation from heavy few electron ions
- 2011
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Ingår i: Canadian journal of physics (Print). - 0008-4204 .- 1208-6045. ; 89:5, s. 513-519
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Tidskriftsartikel (refereegranskat)abstract
- The population of magnetic sublevels in hydrogen-like uranium ions has been investigated in relativistic ion-atom collisions by observing the subsequent X-ray emission. Using the gas target at the experimental storage ring facility we observed the angular emission of Lyman-alpha radiation from hydrogen-like uranium ions. The alignment parameter for three different interaction energies was measured and found to agree well with theory. In addition, the use of different gas targets allowed for the electron-impact excitation process to be observed.
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| 42. |
- Visnes, Torkild, et al.
(författare)
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Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation
- 2018
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 362:6416, s. 834-
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Tidskriftsartikel (refereegranskat)abstract
- The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor-alpha-induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor kappa B and proinflammatory gene expression, resulting in decreased immune cell recruitment to mouse lungs. Thus, we present a proof of concept that targeting oxidative DNA repair can alleviate inflammatory conditions in vivo.
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| 43. |
- Wan, Guihong, et al.
(författare)
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Development and validation of time-to-event models to predict metastatic recurrence of localized cutaneous melanoma
- 2024
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Ingår i: Journal of the American Academy of Dermatology. - 0190-9622. ; 90:2, s. 288-298
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Tidskriftsartikel (refereegranskat)abstract
- Background: The recent expansion of immunotherapy for stage IIB/IIC melanoma highlights a growing clinical need to identify patients at high risk of metastatic recurrence and, therefore, most likely to benefit from this therapeutic modality. Objective: To develop time-to-event risk prediction models for melanoma metastatic recurrence. Methods: Patients diagnosed with stage I/II primary cutaneous melanoma between 2000 and 2020 at Mass General Brigham and Dana-Farber Cancer Institute were included. Melanoma recurrence date and type were determined by chart review. Thirty clinicopathologic factors were extracted from electronic health records. Three types of time-to-event machine-learning models were evaluated internally and externally in the distant versus locoregional/nonrecurrence prediction. Results: This study included 954 melanomas (155 distant, 163 locoregional, and 636 1:2 matched nonrecurrences). Distant recurrences were associated with worse survival compared to locoregional/nonrecurrences (HR: 6.21, P < .001) and to locoregional recurrences only (HR: 5.79, P < .001). The Gradient Boosting Survival model achieved the best performance (concordance index: 0.816; time-dependent AUC: 0.842; Brier score: 0.103) in the external validation. Limitations: Retrospective nature and cohort from one geography. Conclusions: These results suggest that time-to-event machine-learning models can reliably predict the metastatic recurrence from localized melanoma and help identify high-risk patients who are most likely to benefit from immunotherapy.
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| 44. |
- Wheeler, David C., et al.
(författare)
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The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial : baseline characteristics
- 2020
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Ingår i: Nephrology, Dialysis and Transplantation. - OXFORD ENGLAND : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 35:10, s. 1700-1711
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Tidskriftsartikel (refereegranskat)abstract
- Background. The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium-glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials. Methods. In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) <= 200mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75mL/min/1.73m(2) were randomized to dapagliflozin 10mg once daily or placebo. Mean eGFR was 43.1mL/min/1.73m(2) and median UACR was 949 mg/g (108mg/mmol). Results. Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensinconverting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1mL/min/1.73m(2) lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR). Conclusions. Participants with a wide range of underlying kidney diseases receiving renin-angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2-4 and increased albuminuria, with and without T2D.
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| 45. |
- Wotzlaw, Jörn-Frederik, et al.
(författare)
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In-situ garnet 238U-230Th geochronology of Holocene silica-undersaturated volcanic tuffs at millennial-scale precision
- 2019
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Ingår i: Quaternary Geochronology. - : Elsevier BV. - 1871-1014 .- 1878-0350. ; 50, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Radioisotopic dates for Late Pleistocene to Holocene silica-undersaturated volcanic rocks are often imprecise, limiting our ability to assess the frequency of eruptions in alkaline volcanic provinces, evaluate related volcanic risk and date associated archaeological sites. Here, we present a new approach to dating alkaline volcanic rocks employing 238U-230Th disequilibrium dating of Ca-rich garnet phenocrysts by laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS). We document analytical protocols and apply this technique to date magmatic garnets from the 472 AD Pollena eruption of Vesuvius (Southern Italy) and from the Engare Sero Footprint Tuff, a volcaniclastic unit attributed to Oldoinyo Lengai (Northern Tanzania). Garnet phenocrysts from the Pollena phonolite yield a well-defined U-Th isochron with a date of 2.28 ± 0.71 ka (1σ) that is indistinguishable from the historical date and suggests that garnet crystallized close to eruption with a pre-eruption residence time of less than 1.6 kyr. Garnets from the Engare Sero Footprint Tuff yield a U-Th isochron date of4.91 ± 0.58 ka (1σ). This date is compatible with 14C and 40Ar/39Ar dates that bracket tuff deposition to between ∼5 and ∼19 ka but confidently constrains the age of the Engare Sero Footprint Tuff to the mid-Holocene. These examples demonstrate the potential of this new approach for dating Late Pleistocene to Holocene silica-undersaturated volcanic rocks at millennial-scale precision and for investigating magma chamber processes beneath active alkaline volcanoes.
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| 46. |
- Yi, Longqing, 1988, et al.
(författare)
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Proton acceleration in a laser-induced relativistic electron vortex
- 2019
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Ingår i: Journal of Plasma Physics. - 0022-3778 .- 1469-7807. ; 85:4
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Tidskriftsartikel (refereegranskat)abstract
- We show that when a solid plasma foil with a density gradient on the front surface is irradiated by an intense laser pulse at a grazing angle, similar to 80 degrees, a relativistic electron vortex is excited in the near-critical-density layer after the laser pulse depletion. The vortex structure and dynamics are studied using particle-in-cell simulations. Due to the asymmetry introduced by non-uniform background density, the vortex drifts at a constant velocity, typically 0.2-0.3 times the speed of light. The strong magnetic field inside the vortex leads to significant charge separation; in the corresponding electric field initially stationary protons can be captured and accelerated to twice the velocity of the vortex (100-200 MeV). A representative scenario - with laser intensity of 10(21) W cm(-2) - is discussed: two-dimensional simulations suggest that a quasi-monoenergetic proton beam can be obtained with a mean energy 140 MeV and an energy spread of similar to 10% We derive an analytical estimate for the vortex velocity in terms of laser and plasma parameters, demonstrating that the maximum proton energy can be controlled by the incidence angle of the laser and the plasma density gradient.
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| 47. |
- Yilmaz, Mehmet B., et al.
(författare)
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Renal Effects of Levosimendan : A Consensus Report
- 2013
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Ingår i: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 27:6, s. 581-590
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Forskningsöversikt (refereegranskat)abstract
- Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure. This review describes the effects of the inodilator levosimendan on renal function. A panel of 25 scientists and clinicians from 15 European countries (Austria, Finland, France, Hungary, Germany, Greece, Italy, Portugal, the Netherlands, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and Ukraine) convened and reached a consensus on the current interpretation of the renal effects of levosimendan described both in non-clinical research and in clinical study reports. Most reports on the effect of levosimendan indicate an improvement of renal function in heart failure, sepsis and cardiac surgery settings. However, caution should be applied as study designs differed from randomized, controlled studies to uncontrolled ones. Importantly, in the largest HF study (REVIVE I and II) no significant changes in the renal function were detected. As it regards the mechanism of action, the opening of mitochondrial K-ATP channels by levosimendan is involved through a preconditioning effect. There is a strong rationale for randomized controlled trials seeking beneficial renal effects of levosimendan. As an example, a study is shortly to commence to assess the role of levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARDS).
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