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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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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.
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- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 5. |
- Menden, MP, et al.
(författare)
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Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
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Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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| 6. |
- Doornenbal, P., et al.
(författare)
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RISING: Gamma‐ray Spectroscopy with Radioactive Beams at GSI
- 2007
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Ingår i: AIP Conference Proceedings. - : AIP. - 0094-243X. - 9780735413283 ; 891, s. 99-107
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Konferensbidrag (refereegranskat)abstract
- The Rare Isotope Spectroscopic INvestigation at GSI (RISING) project is a major pan‐European collaboration. Its physics aims are the studies of exotic nuclear matter with abnormal proton‐to‐neutron ratios compared with naturally occurring isotopes. RISING combines the FRagment Separator (FRS) which allows relativistic energies and projectile fragmentation reactions with EUROBALL Ge Cluster detectors for γ spectroscopic research. The RISING setup can be used in two different configurations. Either the nuclei of interest are investigated after being stopped or the heavy ions hit a secondary target at relativistic energies and the thereby occurring excitations are studied. For the latter case, MINIBALL Ge detectors and the HECTOR array are used in addition. Example achievements of the Fast Beam setup are presented and compared to various shell model calculations, while for the Stopped Beam setup initial results are shown.
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| 7. |
- Park, Joochun, et al.
(författare)
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Toward the limit of nuclear binding on the N = Z line : Spectroscopy of Cd-96
- 2019
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Ingår i: Physical Review C. - : AMER PHYSICAL SOC. - 2469-9985 .- 2469-9993. ; 99:2
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Tidskriftsartikel (refereegranskat)abstract
- A gamma -decaying isomeric state (tau(1/2) = 197(-17)(+19) ns) has been identified in Cd-96, which is one alpha particle away from the last known bound N = Z nucleus, Sn-100. Comparison of the results with shell-model calculations has allowed a tentative experimental level scheme to be deduced and the isomer to be interpreted as a medium-spin negative-parity spin trap based on the coupling of isoscalar (T = 0) and isovector (T = 1) neutron-proton pairs. The data also suggest evidence for the population of a 9(+) T = 1 state, which is predicted by shell-model calculations to be yrast. Such a low-lying T = 1 state, which is unknown in lighter mass even-even self-conjugate nuclei, can also be interpreted in terms of the coupling of T = 0 and T = 1 neutron-proton pairs.
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| 8. |
- Saito, T. R., et al.
(författare)
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The WASA-FRS project at GSI and its perspective
- 2023
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Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier. - 0168-583X .- 1872-9584. ; 542, s. 22-25
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Tidskriftsartikel (refereegranskat)abstract
- A novel technique to study bound states of exotic hadrons in subatomic nuclei, such as hypernuclei and mesic nuclei, has been developed by employing the Fragment Separator FRS and the WASA central detector at GSI. Two experiments, S447 for studying light hypernuclei, especially hypertriton and a Ann bound state, and S490 for searching for ri' mesic-nuclei, were recently performed. Data analyses are currently in progress, and light charged particles such as protons and x & PLUSMN; are clearly observed and identified in the both experiments. For S447, light nuclear fragments that can also be residual nuclei from decays of hypernuclei of interests have been analysed by the FRS, and a momentum resolution, Ap/p, of 5 x 10-4 has been achieved. Further data analyses are to be completed. The WASA-FRS project will be continued and extended with the FRS at FAIR Phase 0, and upgrading of the WASA magnet and detectors is currently in progress. Furthermore, construction of a larger detector system with the Super-FRS at FAIR Phase 1 is also under consideration.
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| 9. |
- Tanaka, Y. K., et al.
(författare)
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WASA-FRS EXPERIMENTS IN FAIR PHASE-0 AT GSI
- 2023
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Ingår i: ACTA PHYSICA POLONICA B PROCEEDINGS SUPPLEMENT. - : Jagiellonian University.
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Konferensbidrag (refereegranskat)abstract
- We have developed a new and unique experimental setup integrating the central part of the Wide Angle Shower Apparatus (WASA) into the Fragment Separator (FRS) at GSI. This combination opens up possibilities of new experiments with high-resolution spectroscopy at forward 0 and measurements of light decay particles with nearly full solid-angle acceptance in coincidence. The first series of the WASA-FRS experiments have been successfully carried out in 2022. The developed experimental setup and two physics experiments performed in 2022 including the status of the preliminary data analysis are introduced.
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| 10. |
- Lehr, C., et al.
(författare)
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Unveiling the two-proton halo character of 17 Ne: Exclusive measurement of quasi-free proton-knockout reactions
- 2022
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 827
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Tidskriftsartikel (refereegranskat)abstract
- The proton drip-line nucleus 17Ne is investigated experimentally in order to determine its two-proton halo character. A fully exclusive measurement of the 17Ne(p,2p)16F→15⁎O+p quasi-free one-proton knockout reaction has been performed at GSI at around 500 MeV/nucleon beam energy. All particles resulting from the scattering process have been detected. The relevant reconstructed quantities are the angles of the two protons scattered in quasi-elastic kinematics, the decay of 16F into 15O (including γ decays from excited states) and a proton, as well as the 15O+p relative-energy spectrum and the 16F momentum distributions. The latter two quantities allow an independent and consistent determination of the fractions of l=0 and l=2 motion of the valence protons in 17Ne. With a resulting relatively small l=0 component of only around 35(3)%, it is concluded that 17Ne exhibits a rather modest halo character only. The quantitative agreement of the two values deduced from the energy spectrum and the momentum distributions supports the theoretical treatment of the calculation of momentum distributions after quasi-free knockout reactions at high energies by taking into account distortions based on the Glauber theory. Moreover, the experimental data allow the separation of valence-proton knockout and knockout from the 15O core. The latter process contributes with 11.8(3.1) mb around 40% to the total proton-knockout cross section of 30.3(2.3) mb, which explains previously reported contradicting conclusions derived from inclusive cross sections.
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