| 1. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 2. |
- Davies, Neil, et al.
(författare)
-
The founding charter of the Genomic Observatories Network
- 2014
-
Ingår i: GigaScience. - 2047-217X. ; 3:2
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract The co-authors of this paper hereby state their intention to work together to launch the Genomic Observatories Network (GOs Network) for which this document will serve as its Founding Charter. We define a Genomic Observatory as an ecosystem and/or site subject to long-term scientific research, including (but not limited to) the sustained study of genomic biodiversity from single-celled microbes to multicellular organisms.An international group of 64 scientists first published the call for a global network of Genomic Observatories in January 2012. The vision for such a network was expanded in a subsequent paper and developed over a series of meetings in Bremen (Germany), Shenzhen (China), Moorea (French Polynesia), Oxford (UK), Pacific Grove (California, USA), Washington (DC, USA), and London (UK). While this community-building process continues, here we express our mutual intent to establish the GOs Network formally, and to describe our shared vision for its future. The views expressed here are ours alone as individual scientists, and do not necessarily represent those of the institutions with which we are affiliated.
|
|
| 3. |
- Kehoe, Laura, et al.
(författare)
-
Make EU trade with Brazil sustainable
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Satizabal, Claudia L., et al.
(författare)
-
Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
-
Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
|
|
| 7. |
|
|
| 8. |
- Bach, Lennart T, et al.
(författare)
-
Influence of Ocean Acidification on a Natural Winter-to-Summer Plankton Succession: First Insights from a Long-Term Mesocosm Study Draw Attention to Periods of Low Nutrient Concentrations
- 2016
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8
-
Tidskriftsartikel (refereegranskat)abstract
- Every year, the oceans absorb about 30% of anthropogenic carbon dioxide (CO2) leading to a re-equilibration of the marine carbonate system and decreasing seawater pH. Today, there is increasing awareness that these changes-summarized by the term ocean acidification (OA)-could differentially affect the competitive ability of marine organisms, thereby provoking a restructuring of marine ecosystems and biogeochemical element cycles. In winter 2013, we deployed ten pelagic mesocosms in the Gullmar Fjord at the Swedish west coast in order to study the effect of OA on plankton ecology and biogeochemistry under close to natural conditions. Five of the ten mesocosms were left unperturbed and served as controls (similar to 380 mu atm pCO(2)), whereas the others were enriched with CO2-saturated water to simulate realistic end-of-the-century carbonate chemistry conditions (mu 760 mu atm pCO(2)). We ran the experiment for 113 days which allowed us to study the influence of high CO2 on an entire winter-to-summer plankton succession and to investigate the potential of some plankton organisms for evolutionary adaptation to OA in their natural environment. This paper is the first in a PLOS collection and provides a detailed overview on the experimental design, important events, and the key complexities of such a "long-term mesocosm" approach. Furthermore, we analyzed whether simulated end-of-the-century carbonate chemistry conditions could lead to a significant restructuring of the plankton community in the course of the succession. At the level of detail analyzed in this overview paper we found that CO2-induced differences in plankton community composition were non-detectable during most of the succession except for a period where a phytoplankton bloom was fueled by remineralized nutrients. These results indicate: (1) Long-term studies with pelagic ecosystems are necessary to uncover OA-sensitive stages of succession. (2) Plankton communities fueled by regenerated nutrients may be more responsive to changing carbonate chemistry than those having access to high inorganic nutrient concentrations and may deserve particular attention in future studies.
|
|
| 9. |
- Bausch, Birke, et al.
(författare)
-
Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention
- 2017
-
Ingår i: JAMA Oncology. - : AMER MEDICAL ASSOC. - 2374-2437 .- 2374-2445. ; 3:9, s. 1204-1212
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Effective cancer prevention is based on accurate molecular diagnosis and results of genetic family screening, genotype-informed risk assessment, and tailored strategies for early diagnosis. The expanding etiology for hereditary pheochromocytomas and paragangliomas has recently included SDHA, TMEM127, MAX, and SDHAF2 as susceptibility genes. Clinical management guidelines for patients with germline mutations in these 4 newly included genes are lacking. OBJECTIVE To study the clinical spectra and age-related penetrance of individuals with mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes. DESIGN, SETTING, AND PATIENTS This study analyzed the prospective, longitudinally followed up European-American-Asian Pheochromocytoma-Paraganglioma Registry for prevalence of SDHA, TMEM127, MAX, and SDHAF2 germline mutation carriers from 1993 to 2016. Genetic predictive testing and clinical investigation by imaging from neck to pelvis was offered to mutation-positive registrants and their relatives to clinically characterize the pheochromocytoma/paraganglioma diseases associated with mutations of the 4 new genes. MAIN OUTCOMES AND MEASURES Prevalence and spectra of germline mutations in the SDHA, TMEM127, MAX, and SDHAF2 genes were assessed. The clinical features of SDHA, TMEM127, MAX, and SDHAF2 disease were characterized. RESULTS Of 972 unrelated registrants without mutations in the classic pheochromocytoma- and paraganglioma-associated genes (632 female [65.0%] and 340 male [35.0%]; age range, 8-80; mean [SD] age, 41.0 [13.3] years), 58 (6.0%) carried germline mutations of interest, including 29 SDHA, 20 TMEM127, 8 MAX, and 1 SDHAF2. Fifty-three of 58 patients (91%) had familial, multiple, extra-adrenal, and/or malignant tumors and/or were younger than 40 years. Newly uncovered are 7 of 63 (11%) malignant pheochromocytomas and paragangliomas in SDHA and TMEM127 disease. SDHA disease occurred as early as 8 years of age. Extra-adrenal tumors occurred in 28 mutation carriers (48%) and in 23 of 29 SDHA mutation carriers (79%), particularly with head and neck paraganglioma. MAX disease occurred almost exclusively in the adrenal glands with frequently bilateral tumors. Penetrance in the largest subset, SDHA carriers, was 39% at 40 years of age and is statistically different in index patients (45%) vs mutation-carrying relatives (13%; P amp;lt; .001). CONCLUSIONS AND RELEVANCE The SDHA, TMEM127, MAX, and SDHAF2 genes may contribute to hereditary pheochromocytoma and paraganglioma. Genetic testing is recommended in patients at clinically high risk if the classic genes are mutation negative. Gene-specific prevention and/or early detection requires regular, systematic whole-body investigation.
|
|
| 10. |
- Beal, Jacob, et al.
(författare)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 11. |
- Berger, Uta, et al.
(författare)
-
Towards reusable building blocks for agent-based modelling and theory development
- 2024
-
Ingår i: Environmental Modelling & Software. - 1364-8152 .- 1873-6726. ; 175
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the increasing use of standards for documenting and testing agent -based models (ABMs) and sharing of open access code, most ABMs are still developed from scratch. This is not only inefficient, but also leads to ad hoc and often inconsistent implementations of the same theories in computational code and delays progress in the exploration of the functioning of complex social -ecological systems (SES). We argue that reusable building blocks (RBBs) known from professional software development can mitigate these issues. An RBB is a submodel that represents a particular mechanism or process that is relevant across many ABMs in an application domain, such as plant competition in vegetation models, or reinforcement learning in a behavioural model. RBBs need to be distinguished from modules, which represent entire subsystems and include more than one mechanism and process. While linking modules faces the same challenges as integrating different models in general, RBBs are atomic enough to be more easily re -used in different contexts. We describe and provide examples from different domains for how and why building blocks are used in software development, and the benefits of doing so for the ABM community and to individual modellers. We propose a template to guide the development and publication of RBBs and provide example RBBs that use this template. Most importantly, we propose and initiate a strategy for community -based development, sharing and use of RBBs. Individual modellers can have a much greater impact in their field with an RBB than with a single paper, while the community will benefit from increased coherence, facilitating the development of theory for both the behaviour of agents and the systems they form. We invite peers to upload and share their RBBs via our website - preferably referenced by a DOI (digital object
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Bonavita, M., et al.
(författare)
-
New binaries from the SHINE survey
- 2022
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 663
-
Tidskriftsartikel (refereegranskat)abstract
- We present the multiple stellar systems observed within the SpHere INfrared survey for Exoplanet (SHINE). SHINE searched for sub-stellar companions to young stars using high contrast imaging. Although stars with known stellar companions within the SPHERE field of view (< 5.5 arcsec) were removed from the original target list, we detected additional stellar companions to 78 of the 463 SHINE targets observed so far. Twenty-seven per cent of the systems have three or more components. Given the heterogeneity of the sample in terms of observing conditions and strategy, tailored routines were used for data reduction and analysis, some of which were specifically designed for these datasets. We then combined SPHERE data with literature and archival data, TESS light curves, and Gaia parallaxes and proper motions for an accurate characterisation of the systems. Combining all data, we were able to constrain the orbits of 25 systems. We carefully assessed the completeness of our sample for separations between 50–500 mas (corresponding to periods of a few years to a few decades), taking into account the initial selection biases and recovering part of the systems excluded from the original list due to their multiplicity. This allowed us to compare the binary frequency for our sample with previous studies and highlight interesting trends in the mass ratio and period distribution. We also found that, when such an estimate was possible, the values of the masses derived from dynamical arguments were in good agreement with the model predictions. Stellar and orbital spins appear fairly well aligned for the 12 stars that have enough data, which favours a disk fragmentation origin. Our results highlight the importance of combining different techniques when tackling complex problems such as the formation of binaries and show how large samples can be useful for more than one purpose.
|
|
| 15. |
- Breznau, Nate, et al.
(författare)
-
Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
- 2022
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
-
Tidskriftsartikel (refereegranskat)abstract
- This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
|
|
| 16. |
- Camacho Dejay, Rafael, et al.
(författare)
-
Polarization Imaging of Emissive Charge Transfer States in Polymer/Fullerene Blends
- 2014
-
Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 26:23, s. 6695-6704
-
Tidskriftsartikel (refereegranskat)abstract
- Photoexcitation of conjugated polymerfullerene blends results in population of a local charge transfer (CT) state at the interface between the two materials. The competition between recombination and dissociation of this interfacial state limits the generation of fully separated free charges. Therefore, a detailed understanding of the CT states is critical for building a comprehensive picture of the organic solar cells operation. We applied a new fluorescence microscopy method called two-dimensional polarization imaging to gain insight into the orientation of the transition dipole moments of the CT states, and the associated excitation energy transfer processes in TQ1:PCBM blend films. The polymer phase was oriented mechanically to relate the polymer dipole moment orientation to that of the CT states. CT state formation was observed to be much faster than energy transfer in the polymer phase. However, after being formed an emissive CT state does not exchange excitation energy with other CT states, suggesting that they are spatially and/or energetically isolated. We found that the quantum yield of the CT emission is smaller for CT states spatially located in the highly oriented polymer domains, which is interpreted as the result of enhanced CT state dissociation in highly ordered structures.
|
|
| 17. |
- Carde, Patrice, et al.
(författare)
-
Eight Cycles of ABVD Versus Four Cycles of BEACOPP(escalated) Plus Four Cycles of BEACOPP(baseline) in Stage III to IV, International Prognostic Score >= 3, High-Risk Hodgkin Lymphoma : First Results of the Phase III EORTC 20012 Intergroup Trial
- 2016
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 34:17, s. 2028-
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose To compare patients with high-risk stage III to IV Hodgkin lymphoma (HL) in the phase III European Organisation for Research and Treatment of Cancer 20012 Intergroup trial (Comparison of Two Combination Chemotherapy Regimens in Treating Patients With Stage III or Stage IV Hodgkin's Lymphoma) who were randomly assigned to either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP). Patients and Methods Patients with clinical stage III or IV HL, International Prognostic Score of 3 or higher, and age 60 years or younger received ABVD for eight cycles (ABVD(8)) or escalated-dose BEACOPP (BEACOPP(escalated)) for four cycles followed by baseline BEACOPP (BEACOPP(baseline)) for four cycles (BEACOPP(4+4)) without radiotherapy. Primary end points were event-free survival (EFS), treatment discontinuation, no complete response (CR) or unconfirmed complete response (CRu) after eight cycles, progression, relapse, or death. Secondary end points were CR rate, overall survival (OS), quality of life, secondary malignancies, and disease-free survival in CR/CRu patients. Results Between 2002 and 2010, 549 patients were randomly assigned to ABVD(8) (n = 275) or BEACOPP(4+4) (n = 274). Other characteristics included median age, 35 years; male, 75%; stage IV, 74%; "B" symptoms, 81%; and International Prognostic Score >= 4, 59%. WHO performance status was 0 (34%), 1 (48%), or 2 (17%). Median follow-upwas 3.6 years. CR/CRu was 82.5% in both arms. At 4 years, EFS was 63.7% for ABVD(8) versus 69.3% for BEACOPP(4+4) (hazard ratio [HR], 0.86; 95% CI, 0.64 to 1.15; P = .312); disease-free survival was 85.8% versus 91.0% (HR, 0.59; 95% CI, 0.33 to 1.06; P = .076), and OS was 86.7% versus 90.3% (HR, 0.71; 95% CI, 0.42 to 1.21; P = .208). Death as a result of toxicity occurred in six and five patients, early discontinuation (before cycle 5) in 12 and 26 patients, treatment crossovers in five and 10 patients, and secondary malignancies in eight and 10 patients in the ABVD(8) and BEACOPP(4+4) arms, respectively. Conclusion ABVD(8) and BEACOPP(4+4) resulted in similar EFS and OS in patients with high-risk advanced-stage HL. Because BEACOPP(4+4) did not demonstrate a favorable effectiveness or toxicity ratio compared with ABVD(8), treatment burden, immediate and late toxicities, and associated costs must be considered before selecting one of these regimens on which to build future treatment strategies.
|
|
| 18. |
- Conze, Lei Liu, et al.
(författare)
-
Construction and deep sequencing of cDNA libraries representing medium-sized RNA
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Transcriptome analysis has recently become feasible with the application of RNA-seq, the high-throughput sequencing analysis of RNAs through cDNA synthesis. Current transcriptome analysis approaches are limited to analysis of long (>200 nts) or short (~20 nts) RNAs. Here we describe an approach that can be used for the analysis of the medium-sized (~200 nts) RNA transcriptome, which reveals the full-length sequence of RNAs at the single molecule level. Our approach can easily be adapted to generate libraries that are suitable for sequencing by several of the currently used next-generation platforms.
|
|
| 19. |
- Conze, Lei Liu, et al.
(författare)
-
The primate spliceosomal snRNA transcriptome as revealed by deep sequencing
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Small nuclear RNAs (snRNAs) in combination with protein factors form the spliceosomes and are essential for pre-mRNA splicing. In this study we have characterized the spliceosomal snRNA (U snRNA) transcriptome in human, chimpanzee and rhesus using a recently developed high-throughput sequencing approach. Our study has revealed that the U snRNA transcriptomes of all three primates have a similar composition and that the vast majority of the U snRNAs originate from a few well-defined loci. We have detected some heterogeneity in the U snRNA transcriptomes that is primarily caused by the presence of SNPs in the few expressed loci that we have identified.
|
|
| 20. |
- Davies, N., et al.
(författare)
-
Report of the 14th Genomic Standards Consortium Meeting, Oxford, UK, September 17-21, 2012
- 2014
-
Ingår i: Standards in Genomic Sciences. - : Springer Science and Business Media LLC. - 1944-3277. ; 9:3, s. 1236-1250
-
Tidskriftsartikel (refereegranskat)abstract
- This report summarizes the proceedings of the 14th workshop of the Genomic Standards Consortium (GSC) held at the University of Oxford in September 2012. The primary goal of the workshop was to work towards the launch of the Genomic Observatories (GOs) Network under the GSC. For the first time, it brought together potential GOs sites, GSC members, and a range of interested partner organizations. It thus represented the first meeting of the GOs Network (GOs1). Key outcomes include the formation of a core group of “champions” ready to take the GOs Network forward, as well as the formation of working groups. The workshop also served as the first meeting of a wide range of participants in the Ocean Sampling Day (OSD) initiative, a first GOs action. Three projects with complementary interests – COST Action ES1103, MG4U and Micro B3 – organized joint sessions at the workshop. A two-day GSC Hackathon followed the main three days of meetings.
|
|
| 21. |
|
|
| 22. |
- Fomalont, E. B., et al.
(författare)
-
THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW
- 2015
-
Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 808:1
-
Tidskriftsartikel (refereegranskat)abstract
- A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to similar to 15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at similar to 350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.
|
|
| 23. |
- Frassinetti, Lorenzo, et al.
(författare)
-
Role of the pedestal position on the pedestal performance in AUG, JET-ILW and TCV and implications for ITER
- 2019
-
Ingår i: Nuclear Fusion. - : Institute of Physics Publishing. - 0029-5515 .- 1741-4326. ; 59:7
-
Tidskriftsartikel (refereegranskat)abstract
- The role of the pedestal position on the pedestal performance has been investigated in AUG, JET-ILW and TCV. When the pedestal is peeling-ballooning (PB) limited, the three machines show a similar behaviour. The outward shift of the pedestal density relative to the pedestal temperature can lead to the outward shift of the pedestal pressure which, in turns, reduces the PB stability, degrades the pedestal confinement and reduces the pedestal width. Once the experimental density position is considered, the EPED model is able to correctly predict the pedestal height. An estimate of the impact of the density position on a ITER baseline scenario shows that the maximum reduction in the pedestal height is 10% while the reduction in the fusion power is between 10% and 40% depending on the assumptions for the core transport model used. In other plasmas, where the pedestal density is shifted even more outwards relative to the pedestal temperature, the pedestal does not seem PB limited and a different behaviour is observed. The outward shift of the density is still empirically correlated with the pedestal degradation but no change in the pressure position is observed and the PB model is not able to correctly predict the pedestal height. On the other hand, the outward shift of the density leads to a significant increase of η e and η i (where η e,i is the ratio of density to temperature scale lengths, ) which leads to the increase of the growth rate of microinstabilities (mainly ETG and ITG) by 50%. This suggests that, in these plasmas, the increase in the turbulent transport due to the outward shift of the density might play an important role in the decrease of the pedestal performance.
|
|
| 24. |
|
|
| 25. |
- Gaulton, Kyle J, et al.
(författare)
-
Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
-
Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
|
|
