To identify the dose-volume parameters that predict the risk of chest wall (CW) pain and/or rib fracture after lung stereotactic body radiotherapy.
From a combined, larger multi-institution ...experience, 60 consecutive patients treated with three to five fractions of stereotactic body radiotherapy for primary or metastatic peripheral lung lesions were reviewed. CW pain was assessed using the Common Toxicity Criteria for pain. Peripheral lung lesions were defined as those located within 2.5 cm of the CW. A minimal point dose of 20 Gy to the CW was required. The CW volume receiving >or=20, >or=30, >or=40, >or=50, and >or=60 Gy was determined and related to the risk of CW toxicity.
Of the 60 patients, 17 experienced Grade 3 CW pain and five rib fractures. The median interval to the onset of severe pain and/or fracture was 7.1 months. The risk of CW toxicity was fitted to the median effective concentration dose-response model. The CW volume receiving 30 Gy best predicted the risk of severe CW pain and/or rib fracture (R(2) = 0.9552). A volume threshold of 30 cm(3) was observed before severe pain and/or rib fracture was reported. A 30% risk of developing severe CW toxicity correlated with a CW volume of 35 cm(3) receiving 30 Gy.
The development of CW toxicity is clinically relevant, and the CW should be considered an organ at risk in treatment planning. The CW volume receiving 30 Gy in three to five fractions should be limited to <30 cm(3), if possible, to reduce the risk of toxicity without compromising tumor coverage.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here, we investigated whether condensates ...concentrate small-molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target. This behavior was also observed in tumor cells, where drug partitioning influenced drug activity. Altering the properties of the condensate was found to affect the concentration and activity of drugs. These results suggest that selective partitioning and concentration of small molecules within condensates contributes to drug pharmacodynamics and that further understanding of this phenomenon may facilitate advances in disease therapy.
As studies of DNA methylation increase in scope, it has become evident that methylation has a complex relationship with gene expression, plays an important role in defining cell types, and is ...disrupted in many diseases. We describe large-scale single-base resolution DNA methylation profiling on a diverse collection of 82 human cell lines and tissues using reduced representation bisulfite sequencing (RRBS). Analysis integrating RNA-seq and ChIP-seq data illuminates the functional role of this dynamic mark. Loci that are hypermethylated across cancer types are enriched for sites bound by NANOG in embryonic stem cells, which supports and expands the model of a stem/progenitor cell signature in cancer. CpGs that are hypomethylated across cancer types are concentrated in megabase-scale domains that occur near the telomeres and centromeres of chromosomes, are depleted of genes, and are enriched for cancer-specific EZH2 binding and H3K27me3 (repressive chromatin). In noncancer samples, there are cell-type specific methylation signatures preserved in primary cell lines and tissues as well as methylation differences induced by cell culture. The relationship between methylation and expression is context-dependent, and we find that CpG-rich enhancers bound by EP300 in the bodies of expressed genes are unmethylated despite the dense gene-body methylation surrounding them. Non-CpG cytosine methylation occurs in human somatic tissue, is particularly prevalent in brain tissue, and is reproducible across many individuals. This study provides an atlas of DNA methylation across diverse and well-characterized samples and enables new discoveries about DNA methylation and its role in gene regulation and disease.
•We examine the area fraction covered by precipitates on grain boundaries by TEM.•Increasing of over-ageing time increases the grain boundary precipitates coverage.•Moderate over-ageing increases the ...SCC resistance of an Al–Zn–Mg alloy.•Excessive over-ageing decreases the SCC resistance of an Al–Zn–Mg alloy.
The correlations between grain boundary precipitates (GBPs) area fraction and stress corrosion cracking (SCC) susceptibility for an Al–Zn–Mg alloy have been studied using TEM statistical investigations and image analysis. The results reveal that SCC susceptibility of the Al–Zn–Mg alloy first decreases and then increases with the increase of GBPs area fraction, which does not agree with Dix’s anodic dissolution theory, suggesting that SCC of the Al–Zn–Mg alloy is dominated by hydrogen induced cracking when GBPs area fraction is relatively low and is dominated by anodic dissolution when GBPs area fraction is relatively high.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Diabet. Med. 30, 46–55 (2013)
Aims Whether long‐term cardiovascular risk is reduced by the Diabetes Prevention Program interventions is unknown. The aim of this study was to determine the long‐term ...differences in cardiovascular disease risk factors and the use of lipid and blood pressure medications by the original Diabetes Prevention Program intervention group.
Methods This long‐term follow‐up (median 10 years, interquartile range 9.0–10.5) of the three‐arm Diabetes Prevention Program randomized controlled clinical trial (metformin, intensive lifestyle and placebo), performed on 2766 (88%) of the Diabetes Prevention Program participants (who originally had impaired glucose tolerance), comprised a mean of 3.2 years of randomized treatment, approximately 1‐year transition (during which all participants were offered intensive lifestyle intervention) and 5 years follow‐up (Diabetes Prevention Program Outcomes Study). During the study, participants were followed in their original groups with their clinical care being provided by practitioners outside the research setting. The study determined lipoprotein profiles and blood pressure and medication use annually.
Results After 10 years’ follow‐up from Diabetes Prevention Program baseline, major reductions were seen for systolic (−2 to −3) and diastolic (−6 to −6.5 mmHg) blood pressure, and for LDL cholesterol (−0.51 to −0.6 mmol/l) and triglycerides (−0.23 to −0.25 mmol/l) in all groups, with no between‐group differences. HDL cholesterol also rose significantly (0.14 to 0.15 mmol/l) in all groups. Lipid (P = 0.01) and blood pressure (P = 0.09) medication use, however, were lower for the lifestyle group during the Diabetes Prevention Program Outcomes Study.
Conclusion Overall, intensive lifestyle intervention achieved, with less medication, a comparable long‐term effect on cardiovascular disease risk factors, to that seen in the metformin and placebo groups.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In 2012, NASA's Curiosity rover landed on Mars to assess its potential as a habitat for past life and investigate the paleoclimate record preserved by sedimentary rocks inside the ...~150-kilometer-diameter Gale impact crater. Geological reconstructions from Curiosity rover data have revealed an ancient, habitable lake environment fed by rivers draining into the crater. We synthesize geochemical and mineralogical data from lake-bed mudstones collected during the first 1300 martian solar days of rover operations in Gale. We present evidence for lake redox stratification, established by depth-dependent variations in atmospheric oxidant and dissolved-solute concentrations. Paleoclimate proxy data indicate that a transition from colder to warmer climate conditions is preserved in the stratigraphy. Finally, a late phase of geochemical modification by saline fluids is recognized.
Mycorrhizal fungi with different nutrient acquisition strategies influence plant species performance and physiology, thereby defining their trophic niche. This might drive resource competition ...dynamics that cumulatively impact tree species coexistence, but few manipulative experiments have directly tested this.
Combining surveys and experiments in a modern coexistence theory framework, we tested how variation in mycorrhizal strategies and nutrient conditions affects plant competitive outcomes. We focused on two genera of co‐occurring tree species with different mycorrhizal states: Acer (arbuscular mycorrhizal, AM) and Populus (dual mycorrhizal, but often considered predominantly ectomycorrhizal, EM).
The EM and AM fungal responsiveness in Populus species varied with latitude and nitrogen (N) limitation. Host‐specific soil microbiome conditioning and inorganic N fertilization combined to qualitatively affect coexistence outcomes. Lower N conditions favoured Populus over Acer trees, and N fertilization reversed this outcome for southern species, aligning with regional‐scale forest mycorrhizal transitions.
Results from the coexistence experiment also predict competitive exclusion between the tree species pairs, which could arise, in part, from their mycorrhizal differences and is consistent with alternative stable states in dominant forest mycorrhizal strategies. Such bistability appears in natural systems as a bimodal distribution of Populus vs. Acer tree species dominance using long‐term forest inventory data.
Synthesis: The magnitude and outcome of microbially mediated competition between Populus and Acer depends on soil nutrient availability, which likely relates to their mycorrhizal differentiation. These findings support the importance of mycorrhizal symbioses for contributing to large‐scale biogeographical patterns of tree species trophic niche separation across soil resource gradients and bistability in forest mycorrhizal structure.
Mycorrhizal fungi with different nutrient acquisition strategies influence plant species performance and physiology, which ultimately might determine competition and coexistence dynamics. We find that microbially mediated competition between Populus and Acer tree species depends on soil nutrient availability, likely related to their different mycorrhizal associations. These findings support the importance of mycorrhizal symbioses for contributing to large‐scale patterns of tree species distributions and forest mycorrhizal structure.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A rapidly spinning magnetar in a young supernova (SN) can produce a superluminous transient by converting a fraction of its rotational energy into radiation. Here, we present the first ...three-dimensional hydrodynamical simulations ever performed of a magnetar-powered SN in the circumstellar medium formed by the ejection of the outer layers of the star prior to the blast. We find that hydrodynamical instabilities form on two scales in the ejecta, not just one as in ordinary core-collapse SNe: in the hot bubble energized by the magnetar and in the forward shock of the SN as it plows up ambient gas. Pressure from the bubble also makes the instabilities behind the forward shock more violent and causes more mixing in the explosion than in normal SNe, with important consequences for the light curves and spectra of the event that cannot be captured by one-dimensional models. We also find that the magnetar can accelerate Ca and Si to velocities of ∼12,000 and account for their broadened emission lines in observations. Our simulations also reveal that energy from even weak magnetars can accelerate iron-group elements deep in the ejecta to 5000-7000 and explain the high-velocity Fe observed at early times in some core-collapse SNe such as SN 1987A.
In this paper, we present a steady-state experiment, energy balance and exergy analysis of exhaust gas in order to improve the recovery of the waste heat of an internal combustion engine (ICE). ...Considering the different characteristics of the waste heat of exhaust gas, cooling water, and lubricant, a combined thermodynamic cycle for waste heat recovery of ICE is proposed. This combined thermodynamic cycle consists of two cycles: the organic Rankine cycle (ORC), for recovering the waste heat of lubricant and high-temperature exhaust gas, and the Kalina cycle, for recovering the waste heat of low-temperature cooling water. Based on Peng–Robinson (PR) equation of state (EOS), the thermodynamic parameters in the high-temperature ORC were calculated and determined via an in-house computer program. Suitable working fluids used in high-temperature ORC are proposed and the performance of this combined thermodynamic cycle is analyzed. Compared with the traditional cycle configuration, more waste heat can be recovered by the combined cycle introduced in this paper.
► We study the energy balance of fuel in internal combustion engine. ► Heat recovery effect of exhaust gas is good when ICE is at a high-load condition. ► We propose a new combined thermodynamic cycle for waste heat of ICE. ► The combined cycle has a higher recovery efficiency than previous configurations.
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