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- Block, Keith I., et al.
(författare)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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Ingår i: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
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Forskningsöversikt (refereegranskat)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 2. |
- Olefeldt, David, et al.
(författare)
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The Boreal-Arctic Wetland and Lake Dataset (BAWLD)
- 2021
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Ingår i: Earth System Science Data. - : Copernicus Gesellschaft MBH. - 1866-3508 .- 1866-3516. ; 13:11, s. 5127-5149
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Tidskriftsartikel (refereegranskat)abstract
- Methane emissions from boreal and arctic wetlands, lakes, and rivers are expected to increase in response to warming and associated permafrost thaw. However, the lack of appropriate land cover datasets for scaling field-measured methane emissions to circumpolar scales has contributed to a large uncertainty for our understanding of present-day and future methane emissions. Here we present the BorealArctic Wetland and Lake Dataset (BAWLD), a land cover dataset based on an expert assessment, extrapolated using random forest modelling from available spatial datasets of climate, topography, soils, permafrost conditions, vegetation, wetlands, and surface water extents and dynamics. In BAWLD, we estimate the fractional coverage of five wetland, seven lake, and three river classes within 0.5 x 0.5 degrees grid cells that cover the northern boreal and tundra biomes (17 % of the global land surface). Land cover classes were defined using criteria that ensured distinct methane emissions among classes, as indicated by a co-developed comprehensive dataset of methane flux observations. In BAWLD, wetlands occupied 3.2 x 10(6) km(2) (14 % of domain) with a 95 % confidence interval between 2.8 and 3.8 x 10(6) km(2). Bog, fen, and permafrost bog were the most abundant wetland classes, covering similar to 28 % each of the total wetland area, while the highest-methane-emitting marsh and tundra wetland classes occupied 5 % and 12 %, respectively. Lakes, defined to include all lentic open-water ecosystems regardless of size, covered 1.4 x 10(6) km(2) (6 % of domain). Low-methane-emitting large lakes (>10 km(2)) and glacial lakes jointly represented 78 % of the total lake area, while high-emitting peatland and yedoma lakes covered 18 % and 4 %, respectively. Small (<0.1 km(2)) glacial, peatland, and yedoma lakes combined covered 17 % of the total lake area but contributed disproportionally to the overall spatial uncertainty in lake area with a 95 % confidence interval between 0.15 and 0.38 x 10(6) km(2). Rivers and streams were estimated to cover 0.12 x 10(6) km(2) (0.5 % of domain), of which 8 % was associated with high-methane-emitting headwaters that drain organic-rich landscapes. Distinct combinations of spatially co-occurring wetland and lake classes were identified across the BAWLD domain, allowing for the mapping of "wetscapes" that have characteristic methane emission magnitudes and sensitivities to climate change at regional scales. With BAWLD, we provide a dataset which avoids double-accounting of wetland, lake, and river extents and which includes confidence intervals for each land cover class. As such, BAWLD will be suitable for many hydrological and biogeochemical modelling and upscaling efforts for the northern boreal and arctic region, in particular those aimed at improving assessments of current and future methane emissions.
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