| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 2. |
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| 3. |
- 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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| 4. |
- Oishi, Yumiko, et al.
(författare)
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SREBP1 Contributes to Resolution of Pro-inflammatory TLR4 Signaling by Reprogramming Fatty Acid Metabolism
- 2017
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Ingår i: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 25:2, s. 412-427
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages play pivotal roles in both the induction and resolution phases of inflammatory processes. Macrophages have been shown to synthesize anti-inflammatory fatty acids in an LXR-dependent manner, but whether the production of these species contributes to the resolution phase of inflammatory responses has not been established. Here, we identify a biphasic program of gene expression that drives production of anti-inflammatory fatty acids 12-24 hr following TLR4 activation and contributes to downregulation of mRNAs encoding pro-inflammatory mediators. Unexpectedly, rather than requiring LXRs, this late program of anti-inflammatory fatty acid biosynthesis is dependent on SREBP1 and results in the uncoupling of NFκB binding from gene activation. In contrast to previously identified roles of SREBP1 in promoting production of IL1β during the induction phase of inflammation, these studies provide evidence that SREBP1 also contributes to the resolution phase of TLR4-induced gene activation by reprogramming macrophage lipid metabolism.
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| 5. |
- Henry, Barbara J., et al.
(författare)
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A critical review of the application of polymer of low concern and regulatory criteria to fluoropolymers
- 2018
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Ingår i: Integrated Environmental Assessment and Management. - : Society of Environmental Toxicology and Chemistry (SETAC). - 1551-3777 .- 1551-3793. ; 14:3, s. 316-334
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Forskningsöversikt (refereegranskat)abstract
- Per- and poly-fluoroalkyl substances (PFAS) are a group of fluorinated substances that are in the focus of researchers and regulators due to widespread presence in the environment and biota, including humans, of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Fluoropolymers, high molecular weight polymers within the PFAS group, have unique properties that constitute a distinct class within the PFAS group. Fluoropolymers have thermal, chemical, photochemical, hydrolytic, oxidative and biological stability. They have negligible residual monomer and oligomer content and low to no leachables. Fluoropolymers are practically insoluble in water and not subject to long-range transport. With a molecular weight well over 100,000 Da, fluoropolymers cannot cross the cell membrane. Fluoropolymers are not bioavailable or bioaccumulative, as evidenced by toxicology studies on PTFE: acute and subchronic systemic toxicity, irritation, sensitization, local toxicity on implantation, cytotoxicity, in vitro and in vivo genotoxicity, hemolysis, complement activation, and thrombogenicity. Clinical studies of patients receiving permanently implanted PTFE cardiovascular medical devices demonstrate no chronic toxicity or carcinogenicity, reproductive or developmental or endocrine toxicity. This paper brings together fluoropolymer toxicity data, human clinical data, and physical-chemical-thermal-biological data for review and assessment to show that fluoropolymers satisfy widely accepted assessment criteria to be considered as "Polymers of Low Concern". This review concludes that fluoropolymers are distinctly different from other polymeric and non-polymeric per- and poly-fluoroalkyl substances and should be separated from them for hazard assessment or regulatory purposes. Grouping fluoropolymers with all classes of PFAS for "read across" or structure activity relationship assessment is not scientifically appropriate.
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| 6. |
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| 7. |
- Knight, S., et al.
(författare)
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Cavity-enhanced optical Hall effect in two-dimensional free charge carrier gases detected at terahertz frequencies
- 2015
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Ingår i: Optics Letters. - : Optical Society of America. - 0146-9592 .- 1539-4794. ; 40:12, s. 2688-2691
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Tidskriftsartikel (refereegranskat)abstract
- The effect of a tunable, externally coupled Fabry-Perot cavity to resonantly enhance the optical Hall effect signatures at terahertz frequencies produced by a traditional Drude-like two-dimensional electron gas is shown and discussed in this Letter. As a result, the detection of optical Hall effect signatures at conveniently obtainable magnetic fields, for example, by neodymium permanent magnets, is demonstrated. An AlInN/GaN-based high-electron mobility transistor structure grown on a sapphire substrate is used for the experiment. The optical Hall effect signatures and their dispersions, which are governed by the frequency and the reflectance minima and maxima of the externally coupled Fabry-Perot cavity, are presented and discussed. Tuning the externally coupled Fabry-Perot cavity strongly modifies the optical Hall effect signatures, which provides a new degree of freedom for optical Hall effect experiments in addition to frequency, angle of incidence, and magnetic field direction and strength. (C) 2015 Optical Society of America
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| 8. |
- Mölstad, Sigvard, et al.
(författare)
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Lessons learnt during 20 years of the swedish strategic programme against antibiotic resistance
- 2017
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Ingår i: Bulletin of the World Health Organization. - : WORLD HEALTH ORGANIZATION. - 0042-9686 .- 1564-0604. ; 95:11, s. 764-773
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Increasing use of antibiotics and rising levels of bacterial resistance to antibiotics are a challenge to global health and development. Successful initiatives for containing the problem need to be communicated and disseminated. In Sweden, a rapid spread of resistant pneumococci in the southern part of the country triggered the formation of the Swedish strategic programme against antibiotic resistance, also known as Strama, in 1995. The creation of the programme was an important starting point for long-term coordinated efforts to tackle antibiotic resistance in the country. This paper describes the main strategies of the programme: committed work at the local and national levels; monitoring of antibiotic use for informed decision-making; a national target for antibiotic prescriptions; surveillance of antibiotic resistance for local, national and global action; tracking resistance trends; infection control to limit spread of resistance; and communication to raise awareness for action and behavioural change. A key element for achieving long-term changes has been the bottom-up approach, including working closely with prescribers at the local level. The work described here and the lessons learnt could inform countries implementing their own national action plans against antibiotic resistance.
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| 9. |
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| 10. |
- Weidemann, Eva, et al.
(författare)
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14th congress of combustion by-products and their health effects-origin, fate, and health effects of combustion-related air pollutants in the coming era of bio-based energy sources
- 2016
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Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 23:8, s. 8141-8159
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Tidskriftsartikel (refereegranskat)abstract
- The 14th International Congress on Combustion By-Products and Their Health Effects was held in UmeAyen, Sweden from June 14th to 17th, 2015. The Congress, mainly sponsored by the National Institute of Environmental Health Sciences Superfund Research Program and the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, focused on the Origin, fate and health effects of combustion-related air pollutants in the coming era of bio-based energy sources. The international delegates included academic and government researchers, engineers, scientists, policymakers and representatives of industrial partners. The Congress provided a unique forum for the discussion of scientific advances in this research area since it addressed in combination the health-related issues and the environmental implications of combustion by-products. The scientific outcomes of the Congress included the consensus opinions that: (a) there is a correlation between human exposure to particulate matter and increased cardiac and respiratory morbidity and mortality; (b) because currently available data does not support the assessment of differences in health outcomes between biomass smoke and other particulates in outdoor air, the potential human health and environmental impacts of emerging air-pollution sources must be addressed. Assessment will require the development of new approaches to characterize combustion emissions through advanced sampling and analytical methods. The Congress also concluded the need for better and more sustainable e-waste management and improved policies, usage and disposal methods for materials containing flame retardants.
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