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- Abe, K., et al.
(författare)
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J-PARC Neutrino Beamline Upgrade Technical Design Report
- 2019
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Rapport (refereegranskat)abstract
- In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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| 2. |
- 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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| 3. |
- Babst, F., et al.
(författare)
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When tree rings go global: Challenges and opportunities for retro- and prospective insight
- 2018
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 197, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- The demand for large-scale and long-term information on tree growth is increasing rapidly as environmental change research strives to quantify and forecast the impacts of continued warming on forest ecosystems. This demand, combined with the now quasi-global availability of tree-ring observations, has inspired researchers to compile large tree-ring networks to address continental or even global-scale research questions. However, these emergent spatial objectives contrast with paleo-oriented research ideas that have guided the development of many existing records. A series of challenges related to how, where, and when samples have been collected is complicating the transition of tree rings from a local to a global resource on the question of tree growth. Herein, we review possibilities to scale tree-ring data (A) from the sample to the whole tree, (B) from the tree to the site, and (C) from the site to larger spatial domains. Representative tree-ring sampling supported by creative statistical approaches is thereby key to robustly capture the heterogeneity of climate-growth responses across forested landscapes. We highlight the benefits of combining the temporal information embedded in tree rings with the spatial information offered by forest inventories and earth observations to quantify tree growth and its drivers. In addition, we show how the continued development of mechanistic tree-ring models can help address some of the non-linearities and feedbacks that complicate making inference from tree-ring data. By embracing scaling issues, the discipline of dendrochronology will greatly increase its contributions to assessing climate impacts on forests and support the development of adaptation strategies. © 2018 Elsevier Ltd
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| 4. |
- Axelsson, Annika S., et al.
(författare)
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Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes
- 2017
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 9:394
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Tidskriftsartikel (refereegranskat)abstract
- A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. By interrogating a library of 3800 drug signatures, we identified sulforaphane as a compound that may reverse the disease signature. Sulforaphane suppressed glucose production from hepatic cells by nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and decreased expression of key enzymes in gluconeogenesis. Moreover, sulforaphane reversed the disease signature in the livers from diabetic animals and attenuated exaggerated glucose production and glucose intolerance by a magnitude similar to that of metformin. Finally, sulforaphane, provided as concentrated broccoli sprout extract, reduced fasting blood glucose and glycated hemoglobin (HbA1c) in obese patients with dysregulated type 2 diabetes.
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| 8. |
- Zhao, Baodan, et al.
(författare)
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High Open-Circuit Voltages in Tin-Rich Low-Bandgap Perovskite-Based Planar Heterojunction Photovoltaics
- 2017
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Ingår i: Advanced Materials. - : Wiley-VCH Verlagsgesellschaft. - 0935-9648 .- 1521-4095. ; 29
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Tidskriftsartikel (refereegranskat)abstract
- Low-bandgap CH3NH3(PbxSn1–x)I3 (0 ≤ x ≤ 1) hybrid perovskites (e.g., ≈1.5–1.1 eV) demonstrating high surface coverage and superior optoelectronic properties are fabricated. State-of-the-art photovoltaic (PV) performance is reported with power conversion efficiencies approaching 10% in planar heterojunction architecture with small (<450 meV) energy loss compared to the bandgap and high (>100 cm2 V−1s−1) intrinsic carrier mobilities.
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