| 1. |
- Reimerdes, H., et al.
(författare)
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Overview of the TCV tokamak experimental programme
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- The tokamak a configuration variable (TCV) continues to leverage its unique shaping capabilities, flexible heating systems and modern control system to address critical issues in preparation for ITER and a fusion power plant. For the 2019-20 campaign its configurational flexibility has been enhanced with the installation of removable divertor gas baffles, its diagnostic capabilities with an extensive set of upgrades and its heating systems with new dual frequency gyrotrons. The gas baffles reduce coupling between the divertor and the main chamber and allow for detailed investigations on the role of fuelling in general and, together with upgraded boundary diagnostics, test divertor and edge models in particular. The increased heating capabilities broaden the operational regime to include T (e)/T (i) similar to 1 and have stimulated refocussing studies from L-mode to H-mode across a range of research topics. ITER baseline parameters were reached in type-I ELMy H-modes and alternative regimes with 'small' (or no) ELMs explored. Most prominently, negative triangularity was investigated in detail and confirmed as an attractive scenario with H-mode level core confinement but an L-mode edge. Emphasis was also placed on control, where an increased number of observers, actuators and control solutions became available and are now integrated into a generic control framework as will be needed in future devices. The quantity and quality of results of the 2019-20 TCV campaign are a testament to its successful integration within the European research effort alongside a vibrant domestic programme and international collaborations.
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| 2. |
- Underwood, J, et al.
(författare)
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Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
- 2019
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Ingår i: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:6, s. ofz198-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.MethodsDifferences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.ResultsThe prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.ConclusionDifferent methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.
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| 3. |
- Biel, W., et al.
(författare)
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Diagnostics for plasma control - : From ITER to DEMO
- 2019
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Ingår i: Fusion engineering and design. - : ELSEVIER SCIENCE SA. - 0920-3796 .- 1873-7196. ; 146:A, s. 465-472
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Tidskriftsartikel (refereegranskat)abstract
- The plasma diagnostic and control (D&C) system for a future tokamak demonstration fusion reactor (DEMO) will have to provide reliable operation near technical and physics limits, while its front-end components will be subject to strong adverse effects within the nuclear and high temperature plasma environment. The ongoing developments for the ITER D&C system represent an important starting point for progressing towards DEMO. Requirements for detailed exploration of physics are however pushing the ITER diagnostic design towards using sophisticated methods and aiming for large spatial coverage and high signal intensities, so that many front-end components have to be mounted in forward positions. In many cases this results in a rapid aging of diagnostic components, so that additional measures like protection shutters, plasma based mirror cleaning or modular approaches for frequent maintenance and exchange are being developed. Under the even stronger fluences of plasma particles, neutron/gamma and radiation loads on DEMO, durable and reliable signals for plasma control can only be obtained by selecting diagnostic methods with regard to their robustness, and retracting vulnerable front-end components into protected locations. Based on this approach, an initial DEMO D&C concept is presented, which covers all major control issues by signals to be derived from at least two different diagnostic methods (risk mitigation).
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| 4. |
- de Wit, Meike, et al.
(författare)
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Colorectal cancer candidate biomarkers identified by tissue secretome proteome profiling
- 2014
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 99, s. 26-39
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a major health problem. Biomarkers associated with molecular changes in cancer cells can aid early detection, diagnosis, prognosis, therapy selection, and disease monitoring. Tumor tissue secretomes are a rich source of candidate biomarkers. To identify CRC protein biomarkers, secretomes of four pairs of human CRC tissue and patient-matched normal colon tissue samples, and secretomes of five CRC cell lines were analyzed by GeLC-MS/MS. Subsequent data analysis was based on label-free spectral counting, Ingenuity Pathway Analysis, Secretome/SignalP, STRING and Cytoscape, resulting in 2703 protein identifications in the tissue secretomes, of which 409 proteins were significantly more present in CRC samples than in controls. Biomarker selection of 76 candidates was based on consistent and abundant over-representation in cancer-compared to control-secretomes, and presumed neoplastic origin. Overlap analysis with previously obtained datasets revealed 21 biomarkers suited for early detection of CRC. Immunohistochemistry confirmed overexpression in CRC of one candidate marker (MCM5). In conclusion, a human reference dataset of 76 candidate biomarkers was identified for which we illustrate that combination with existing pre-clinical datasets allows pre-selection of biomarkers for blood- or stool-based assays to support clinical management of CRC. Further dedicated validation studies are required to demonstrate their clinical applicability. Biological significance Tissue secretome proteomes are a rich source of candidate biomarkers. Several secretome proteome datasets have been obtained from pre-clinical in vitro and in vivo colorectal cancer (CRC) model systems, yielding promising CRC biomarkers obtained under well-defined experimentally controlled conditions. However, which of these biomarker proteins are actually secreted by human CRC samples was not known. To our knowledge, this is the first study that directly compares secretome proteomes from clinically relevant human CRC tissues to patient-matched normal colon tissues. We identified 76 human CRC protein biomarkers that may facilitate blood-based or stool-based assay development to support clinical management of CRC. Overlap analysis with datasets from well-defined pre-clinical studies helps to determine what clinical application suits these human CRC biomarkers best, i.e. early detection, diagnosis, prognosis, therapy selection, and/or disease monitoring of CRC. This is demonstrated for a CRC mouse model dataset, revealing 21 human CRC biomarkers suited for early detection of CRC.
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| 5. |
- Edebo, Anders, 1968, et al.
(författare)
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Circumferential and axial distribution of esophageal mucosal damage in reflux disease.
- 2007
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Ingår i: Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus / I.S.D.E. - : Oxford University Press (OUP). - 1120-8694. ; 20:3, s. 232-8
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the axial and radial distribution of histological markers including hyperplasia of the basal cell layer, elongation of the papillae and dilatation of the intercellular spaces of the squamous epithelium in patients with nonerosive reflux disease compared to controls and to relate this to the macroscopic topography in erosive reflux disease. Two different study populations were included in this report. Endoscopic esophageal biopsies were taken from 21 healthy control subjects and 21 nonerosive reflux disease patients before and after 4 weeks of esomeprazole therapy. Endoscopic still images from 50 erosive reflux disease patients were reviewed for the radial orientation of LA grade A and/or B esophagitis (Los Angeles criteria for grading of reflux esophagitis). The 3 o'clock position of the squamocolumnar junction showed significantly thicker basal cell layer (P=0.011) and more intercellular space dilatation (P=0.01) in nonerosive reflux disease patients compared to the 9 o'clock position. Only a significant difference in dilatation of the intercellular spaces (P=0.018) between nonerosive reflux disease patients and controls were observed in the 3 o'clock region at the squamocolumnar junction, whereas 1-2 cm orally, all three histological criteria differed significantly (P
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| 6. |
- Edebo, Anders, 1968, et al.
(författare)
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Magnification endoscopy for diagnosis of nonerosive reflux disease: a proposal of diagnostic criteria and critical analysis of observer variability.
- 2007
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Ingår i: Endoscopy. - : Georg Thieme Verlag KG. - 1438-8812 .- 0013-726X. ; 39:3, s. 195-201
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND STUDY AIMS: This study tested the diagnostic value of high-resolution endoscopy for the recognition of subtle diagnostic esophageal mucosal changes in nonerosive reflux disease. PATIENTS AND METHODS: Ten control subjects and eleven patients with nonerosive reflux disease confirmed by a validated questionnaire, standard endoscopy, and 24-hour pH-metry participated in the study. Still images were collected by high-resolution endoscopes from the distal esophagus in a standardized manner, incorporating iodine staining. Assessments were repeated in the patients with reflux disease after 4 weeks of esomeprazole therapy. Interobserver variability in the recognition of the proposed criteria was initially evaluated by 27 endoscopists using an Internet-based process. After optimisation of image quality the evaluation was repeated face-to-face with six expert endoscopists. RESULTS: No criterion was identified in either assessment that was sufficiently sensitive and specific to patients with reflux disease to be clinically useful. The kappa value, used to assess interobserver variation, was acceptably high only for invisibility of palisade vessels (0.59). Triangular indentations, apical mucosal breaks, and pinpoint blood vessels at the squamocolumnar junction were identified more frequently in the patients with reflux disease ( P < 0.05). These changes and the invisibility of the palisade vessels were significantly less prevalent in reflux patients after therapy ( P < 0.01). CONCLUSIONS: Though some distal esophageal mucosal appearances observed with the high-resolution endoscope appeared to be related to nonerosive esophageal mucosal injury, none of these changes proved to be sufficiently sensitive and specific to justify their use as a diagnostic criterion for nonerosive reflux disease.
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| 7. |
- Hong, Cynthia, et al.
(författare)
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The E3 Ubiquitin Ligase IDOL Induces the Degradation of the Low Density Lipoprotein Receptor Family Members VLDLR and ApoER2
- 2010
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Ingår i: Journal of Biological Chemistry. - : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. - 0021-9258 .- 1083-351X. ; 285:26, s. 19720-19726
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Tidskriftsartikel (refereegranskat)abstract
- We have previously identified the E3 ubiquitin ligase-inducible degrader of the low density lipoprotein receptor ( LDLR) ( Idol) as a post-translational modulator of LDLR levels. Idol is a direct target for regulation by liver X receptors (LXRs), and its expression is responsive to cellular sterol status independent of the sterol-response element-binding proteins. Here we demonstrate that Idol also targets two closely related LDLR family members, VLDLR and ApoE receptor 2 (ApoER2), proteins implicated in both neuronal development and lipid metabolism. Idol triggers ubiquitination of the VLDLR and ApoER2 on their cytoplasmic tails, leading to their degradation. We further show that the level of endogenous VLDLR is sensitive to cellular sterol content, Idol expression, and activation of the LXR pathway. Pharmacological activation of the LXR pathway in mice leads to increased Idol expression and to decreased Vldlr levels in vivo. Finally, we establish an unexpected functional link between LXR and Reelin signaling. We demonstrate that LXR activation results in decreased Reelin binding to VLDLR and reduced Dab1 phosphorylation. The identification of VLDLR and ApoER2 as Idol targets suggests potential roles for this LXR-inducible E3 ligase in the central nervous system in addition to lipid metabolism.
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