| 1. |
- 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. |
- Blösch, Günter, et al.
(författare)
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Twenty-three unsolved problems in hydrology (UPH) - a community perspective
- 2019
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Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158
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Tidskriftsartikel (refereegranskat)abstract
- This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
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| 3. |
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| 4. |
- Seibert, J., et al.
(författare)
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Effects of wildfire on catchment runoff response : a modelling approach to detect changes in snow-dominated forested catchments
- 2010
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Ingår i: Hydrology research. - : IWA Publishing. - 0029-1277 .- 2224-7955. ; 41:5, s. 378-390
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Tidskriftsartikel (refereegranskat)abstract
- Wildfire is an important disturbance affecting hydrological processes through alteration of vegetation cover and soil characteristics. The effects of fire on hydrological systems at the catchment scale are not well known, largely because site specific data from both before and after wildfire are rare. In this study a modelling approach was employed for change detection analyses of one such dataset to quantify effects of wildfire on catchment hydrology. Data from the Entiat Experimental Forest (Washington State, US) were used, a conceptual runoff model was applied for pre- and post-fire periods and changes were analyzed in three different ways: reconstruction of runoff series, comparison of model parameters and comparison of simulations using parameter sets calibrated to the two different periods. On average, observed post-fire peak flows were 120% higher than those modelled based on pre-fire conditions. For the post-fire period, parameter values for the snow routine indicated deeper snow packs and earlier and more rapid snowmelt. The net effect of the changes in all parameters was largely increased post-fire peak flows. Overall, the analyses show that change detection modelling provides a viable alternative to the paired-watershed approach for analyzing wildfire disturbance effects on runoff dynamics and supports discussions on changes in hydrological processes.
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| 5. |
- Ali, Genevieve, et al.
(författare)
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Comparison of threshold hydrologic response across northern catchments
- 2015
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Ingår i: Hydrological Processes. - : Wiley. - 0885-6087 .- 1099-1085. ; 29:16, s. 3575-3591
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Tidskriftsartikel (refereegranskat)abstract
- Nine mid-latitude to high-latitude headwater catchments - part of the Northern Watershed Ecosystem Response to Climate Change (North-Watch) programme - were used to analyze threshold response to rainfall and snowmelt-driven events and link the different responses to the catchment characteristics of the nine sites. The North-Watch data include daily time-series of various lengths of multiple variables such as air temperature, precipitation and discharge. Rainfall and meltwater inputs were differentiated using a degree-day snowmelt approach. Distinct hydrological events were identified, and precipitation-runoff response curves were visually assessed. Results showed that eight of nine catchments showed runoff initiation thresholds and effective precipitation input thresholds. For rainfall-triggered events, catchment hydroclimatic and physical characteristics (e.g. mean annual air temperature, median flow path distance to the stream, median sub-catchment area) were strong predictors of threshold strength. For snowmelt-driven events, however, thresholds and the factors controlling precipitation-runoff response were difficult to identify. The variability in catchments responses to snowmelt was not fully explained by runoff initiation thresholds and input magnitude thresholds. The quantification of input intensity thresholds (e.g. snow melting and permafrost thawing rates) is likely required for an adequate characterization of nonlinear spring runoff generation in such northern environments.
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| 6. |
- Ameli, Ali A., et al.
(författare)
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Primary weathering rates, water transit times, and concentration-discharge relations : A theoretical analysis for the critical zone
- 2017
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Ingår i: Water resources research. - : AMER GEOPHYSICAL UNION. - 0043-1397 .- 1944-7973. ; 53:1, s. 942-960
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Tidskriftsartikel (refereegranskat)abstract
- The permeability architecture of the critical zone exerts a major influence on the hydrogeochemistry of the critical zone. Water flow path dynamics drive the spatiotemporal pattern of geochemical evolution and resulting streamflow concentration-discharge (C-Q) relation, but these flow paths are complex and difficult to map quantitatively. Here we couple a new integrated flow and particle tracking transport model with a general reversible Transition State Theory style dissolution rate law to explore theoretically how C-Q relations and concentration in the critical zone respond to decline in saturated hydraulic conductivity (K-s) with soil depth. We do this for a range of flow rates and mineral reaction kinetics. Our results show that for minerals with a high ratio of equilibrium concentration ( Ceq) to intrinsic weathering rate ( Rmax), vertical heterogeneity in K-s enhances the gradient of weathering-derived solute concentration in the critical zone and strengthens the inverse stream C-Q relation. As CeqRmax decreases, the spatial distribution of concentration in the critical zone becomes more uniform for a wide range of flow rates, and stream C-Q relation approaches chemostatic behavior, regardless of the degree of vertical heterogeneity in K-s. These findings suggest that the transport-controlled mechanisms in the hillslope can lead to chemostatic C-Q relations in the stream while the hillslope surface reaction-controlled mechanisms are associated with an inverse stream C-Q relation. In addition, as CeqRmax decreases, the concentration in the critical zone and stream become less dependent on groundwater age (or transit time).
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| 7. |
- Harris, David M., et al.
(författare)
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Hydrograph Separation Using Continuous Open System Isotope Mixing
- 1995
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Ingår i: Water resources research. - 0043-1397 .- 1944-7973. ; 31:1, s. 157-171
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Tidskriftsartikel (refereegranskat)abstract
- We propose a new hydrograph separation method for runoff source modeling based on continuous open system isotope mixing using a variable source area and three isotopic reservoirs. The three reservoirs are (1) direct precipitation on saturated areas, (2) a near-stream saturated zone, and (3) subsurface water in upslope areas. The reservoir sizes and isotopic compositions evolve due to continuous, open system mixing. Streamflow is composed of rainfall on saturated areas and water exfiltrated from the near-stream Saturated zone. The contributing source fractions are determined using the observed isotopic compositions of the stream and the modeled isotopic compositions of the contributing reservoirs, which are functions of time. The near-stream saturated zone receives inflow from upslope areas which are not Surface saturated. The surface-saturated area changes dynamically based on the difference between lateral inflow and contributions to streamflow from the near-stream saturated zone. The upslope zone (reservoir 3) evolves by mixing with rainfall. This hydrograph separation method requires (1) a function which relates the amount of water stored in the near-stream saturated zone to saturated area, (2) a function which relates saturated area fraction to total streamflow, and (3) knowledge of the water storage capacity in reservoirs 2 and 3. The hydrograph separation method was applied to oxygen isotope data for rainfall and runoff during a 36-hour storm at the Gardsjon Fl catchment in southwestern Sweden, The hydrograph separation method was used to estimate time-dependent streamflow contributions due to overland flow of storm rainfall and. subsurface flow of mainly preevent water. We also used the separation method to estimate parameters for relations between saturated area fraction and streamflow, and saturated area and subsurface water storage. We show that streamflow contributions from overland flow may be described by a simple analytic function of antecedent conditions and catchment parameters.
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| 8. |
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| 9. |
- Seibert, Jan, et al.
(författare)
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Gauging the ungauged basin: What is the value of limited streamflow measurements? (solicited)
- 2007
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The long-standing issue of hydrological predictions for ungauged basins has received increased attention thanks to the PUB imitative. Given all the problems on making predictions in totally ungauged catchments one might argue that the best thing to do in an ungauged basin is to actually take a few runoff measurements. In this study we explored how implementing such a procedure might support predictions in an ungauged basin. We used the well-studied Maimai watershed as a hypothetical ungauged basin where we pretend to start with no runoff data and add different sub-sets of the available data to constrain a simple catchment model. These sub-sets were single runoff events or a limited number of point values; in other words these data represent what could be measured with limited efforts in an ungauged basin. Besides these runoff data we used different types of soft data to constrain the model. We recently presented ‘soft data’ as a general framework to facilitate communication between experimentalist and modeler for new ways to test models and quantify uncertainty, parameter identifiabilty and parameter uncertainty. The model simulations were then validated using the available runoff data from different years. We found that surprisingly little runoff data was necessary to derive model parameterizations which provided good results for the validation periods, especially when these runoff data were combined with soft data. We argue that the improved dialog between experimentalist and modeler may be a necessary next step within the PUB movement for moving from calibration-reliant models to ones grounded in understanding and applicability to ungauged basins.
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| 10. |
- Seibert, Jan, et al.
(författare)
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Groundwater dynamics along a hillslope : A test of the steady state hypothesis
- 2003
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Ingår i: Water resources research. - 0043-1397 .- 1944-7973. ; 39:1, s. 1014-
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Tidskriftsartikel (refereegranskat)abstract
- [1] Appropriate conceptual simplifications and assumptions are a central issue for hydrological modeling, especially when those models serve as the foundation for more complex hydrochemical or ecological models. A common and often unexamined assumption in conceptual modeling is that the relation between groundwater levels and runoff can be described as a succession of steady state conditions. This results in a single-valued, monotonic function between the groundwater levels and runoff. Consequently, the simulated rise and fall in groundwater levels always follow the dynamics of runoff. We tested this assumption with an analysis of detailed groundwater level data along two opposing hillslopes along a stream reach in a Swedish till catchment at Svartberget. Groundwater levels in areas close to the stream followed the dynamics of the runoff. The correlation between groundwater level and runoff decreased markedly for wells farther than approximately 40 m from the stream. The levels were often independent of streamflow: Upslope area groundwater could be rising when riparian groundwater and runoff were falling, and vice versa. There was a high degree of correlation between groundwater levels at similar distances from the stream. The median Spearman rank correlation between wells within 35 m from the stream was 0.86 and for wells located more than 60 m from the stream was 0.96. This indicated that there is a common hydrological pattern even in the upslope area that can be identified and modeled. Despite the widespread acceptance of the steady state assumption previously in this and other study catchments, our study shows that it is not valid for the investigated hillslope site. If the divergence from steady state, with potential ramifications for other processes such as runoff chemistry, is common, then it will be worthwhile to reconsider the appropriate range of applicability for the steady state hypothesis, and the alternatives to that hypothesis.
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