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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)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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- Yi, Chuixiang, et al.
(author)
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Climate control of terrestrial carbon exchange across biomes and continents
- 2010
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In: Environmental Research Letters. - : IOP Publishing. - 1748-9326. ; 5:3
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Journal article (peer-reviewed)abstract
- Understanding the relationships between climate and carbon exchange by terrestrial ecosystems is critical to predict future levels of atmospheric carbon dioxide because of the potential accelerating effects of positive climate-carbon cycle feedbacks. However, directly observed relationships between climate and terrestrial CO2 exchange with the atmosphere across biomes and continents are lacking. Here we present data describing the relationships between net ecosystem exchange of carbon (NEE) and climate factors as measured using the eddy covariance method at 125 unique sites in various ecosystems over six continents with a total of 559 site-years. We find that NEE observed at eddy covariance sites is (1) a strong function of mean annual temperature at mid-and high-latitudes, (2) a strong function of dryness at mid-and low-latitudes, and (3) a function of both temperature and dryness around the mid-latitudinal belt (45 degrees N). The sensitivity of NEE to mean annual temperature breaks down at similar to 16 degrees C (a threshold value of mean annual temperature), above which no further increase of CO2 uptake with temperature was observed and dryness influence overrules temperature influence.
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- Fredriksson, Albin, 1984-
(author)
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Robust optimization of radiation therapy accounting for geometric uncertainty
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Geometric errors may compromise the quality of radiation therapy treatments. Optimization methods that account for errors can reduce their effects.The first paper of this thesis introduces minimax optimization to account for systematic range and setup errors in intensity-modulated proton therapy. The minimax method optimizes the worst case outcome of the errors within a given set. It is applied to three patient cases and shown to yield improved target coverage robustness and healthy structure sparing compared to conventional methods using margins, uniform beam doses, and density override. Information about the uncertainties enables the optimization to counterbalance the effects of errors.In the second paper, random setup errors of uncertain distribution---in addition to the systematic range and setup errors---are considered in a framework that enables scaling between expected value and minimax optimization. Experiments on a phantom show that the best and mean case tradeoffs between target coverage and critical structure sparing are similar between the methods of the framework, but that the worst case tradeoff improves with conservativeness.Minimax optimization only considers the worst case errors. When the planning criteria cannot be fulfilled for all errors, this may have an adverse effect on the plan quality. The third paper introduces a method for such cases that modifies the set of considered errors to maximize the probability of satisfying the planning criteria. For two cases treated with intensity-modulated photon and proton therapy, the method increased the number of satisfied criteria substantially. Grasping for a little less sometimes yields better plans.In the fourth paper, the theory for multicriteria optimization is extended to incorporate minimax optimization. Minimax optimization is shown to better exploit spatial information than objective-wise worst case optimization, which has previously been used for robust multicriteria optimization.The fifth and sixth papers introduce methods for improving treatment plans: one for deliverable Pareto surface navigation, which improves upon the Pareto set representations of previous methods; and one that minimizes healthy structure doses while constraining the doses of all structures not to deteriorate compared to a reference plan, thereby improving upon plans that have been reached with too weak planning goals.
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- Lu, S. S., et al.
(author)
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Are urinary PAHs biomarkers of controlled exposure to diesel exhaust?
- 2014
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In: Biomarkers. - : Informa UK Limited. - 1354-750X .- 1366-5804. ; 19:4, s. 332-339
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Journal article (peer-reviewed)abstract
- Urinary polycyclic aromatic hydrocarbons (PAHs) were evaluated as possible biomarkers of exposure to diesel exhaust (DE) in two controlled-chamber studies. We report levels of 14 PAHs from 28 subjects in urine that were collected before, immediately after and the morning after exposure. Using linear mixed-effects models, we tested for effects of DE exposure and several covariates (time, age, gender and urinary creatinine) on urinary PAH levels. DE exposures did not significantly alter urinary PAH levels. We conclude that urinary PAHs are not promising biomarkers of short-term exposures to DE in the range of 106-276 mu g/m(3).
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