249 research outputs found
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Wildfireâs Impact On Water Quality: Disinfection Byproduct Formation and Heavy Metal Leachability
Wildfire is a spatially and temporally complex phenomenon that has served a vital role in ecosystem function for millennia. However, drinking water providers have become increasingly aware of wildfire’s impacts on the quality of surface water. Increased loads of organic and inorganic constituents, transported by stormflow, are common in streams within burned catchments. As changes in climatic conditions and increased development in wildfire prone areas continues, drinking water providers will need a better understanding of these changes in order to adapt.
Dissolved organic matter (DOM) has the propensity to react with chemical disinfectants to form toxic disinfection byproducts (DBPs). However, wildfire induced chemical changes to DOM can potentially encourage the formation of haloacetonitriles; unregulated DBPs with a lower threshold of toxicity. The goal of the first section in this thesis was to isolate wildfire heating temperature, to better understand how it changes the solubility and reactivity of DOM originating from mineral soil. This was achieved by collecting mineral soil samples from fire prone locations and artificially heating them in a muffle furnace. DOM solubility was heightened at moderate (250°C-350°C) heating temperatures. Additionally, dichloroacetonitrile (DCAN) and dichloroacetic acid (DCAA) formation were stimulated at moderate (250°C) and high (450°C) heating temperatures. To further explore this phenomenon, optical properties were employed to better understand the intrinsic qualities of DOM. Although we identified some surprising correlations between these optical properties and DBP yield, there is still much work to be done to understand the underlying mechanisms.
Heavy metal contamination can be highly detrimental to the utilitarian and aesthetic qualities of surface water. In several cases, heavy metals have been detected at problematic levels in surface waters as a result of wildfire. However, the concentration and species of these heavy metals is controlled by several complex, spatially heterogenous interactions. Therefore, there exists a need to perform more catchment level studies to contribute knowledge to this complicated issue, as well as inform local water utilities. In the second part of this thesis, the leachability of several heavy metals was assessed from mineral soil and ash samples collected from the Colorado Ryan Fire.</p
Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer
Introduction
Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach.
Methods
Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, nâ=â84), gene expression profiling (nâ=â47), matched pre- and post-AI aCGH (nâ=â19 pairs) and Ki67-based AI-response analysis (nâ=â39).
Results
Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1).
Conclusions
These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response
Sun protection behaviors of state park workers in the southeastern USA
© The Author(s) 2019. Published by Oxford University Press on behalf of the British Occupational Hygiene Society. Background: Due to the nature of their work, state park workers receive substantial exposure to sunlight, putting them at an increased risk of developing skin cancer. Increased use of sun protection behaviors can reduce this risk. Objectives: Using the health belief model (HBM) as a theoretical framework, the purpose of this study was to assess factors associated with sun protection behaviors among state-park workers. Methods: In this cross-sectional study, a convenience sample of participants were recruited from 23 state parks in the Southeastern USA to complete a self-administered questionnaire based on the constructs of the HBM. Results: The sample comprised 310 state park workers. The majority of participants were non-Hispanic White (61.6%), male (63.5%), and were aged 39.56 (±13.97) years on average.The average duration of sun exposure during the workday was reported as 3.51 h (±1.88). Nearly 12% of the participants reported that their workplace had a sun-safety policy and ~10% reported receiving sun-safety training at their workplace.The majority of participants reported that they did not sufficiently use sun protection methods. Factors associated with sun protection behaviors included the HBM constructs of perceived benefits outweighing perceived barriers (standardized coefficient = 0.210, P = 0.001), self-efficacy (standardized coefficient = 0.333, P \u3c 0.001), and cues to action (standardized coefficient = 0.179, P = 0.004). Conclusion: Future research should explore the barriers to adopting and enforcing sun-safety policies in the workplace. HBM appears to be efficacious in explaining sun protection behaviors among state park workers. HBM constructs should be considered in future interventions aimed at increasing sun protection behaviors in this population
Retrieval of Physical Properties of Particulate Emission from Animal Feeding Operations Using Three-Wavelength Elastic Lidar Measurements
Agricultural operations produce a variety of particulates and gases that influence ambient air quality. Lidar (LIght Detection And Ranging) technology provides a means to derive quantitative information of particulate spatial distribution and optical/physical properties over remote distances. A three-wavelength scanning lidar system built at the Space Dynamic Laboratory (SDL) is used to extract optical parameters of particulate matter and to convert these optical properties to physical parameters of particles. This particulate emission includes background aerosols, emissions from the agricultural feeding operations, and fugitive dust from the road. Aerosol optical parameters are retrieved using the widely accepted solution proposed by Klett. The inversion algorithm takes advantage of measurements taken simultaneously at three lidar wavelengths (355, 532, and 1064 nm) and allows us to estimate the particle size distribution. A bimodal lognormal particle size distribution is assumed and mode radius, width of the distribution, and total number density are estimated, minimizing the difference between calculated and measured extinction coefficients at the three lidar wavelengths. The results of these retrievals are then compared with simultaneous point measurements at the feeding operation site, taken with standard equipment including optical particle counters, portable PM10 and PM2.5 ambient air samplers, multistage impactors, and an aerosol mass spectrometer
No effect of glutamine ingestion on indices of oxidative metabolism in stable COPD
COPD patients have reduced muscle glutamate which may contribute to an impaired response of oxidative metabolism to exercise. We hypothesised that prior glutamine supplementation would enhance View the MathML source peak, View the MathML source at lactate threshold and speed pulmonary oxygen uptake kinetics in COPD. 13 patients (9 males, age 66 ± 5 years, mean ± SD) with severe COPD (mean FEV1 0.88 ± 0.23 l, 33 ± 7% predicted) performed on separate days ramp cycle-ergometry (5â10 W minâ1) to volitional exhaustion and subsequently square-wave transitions to 80% estimated lactate threshold (LT) following consumption of either placebo (CON) or 0.125 g kg bmâ1 of glutamine (GLN) in 5 ml kg bmâ1 placebo. Oral glutamine had no effect on peak or View the MathML source at LT, {View the MathML source peak: CON = 0.70 ± 0.1 l minâ1 vs. GLN = 0.73 ± 0.2 l minâ1; LT: CON = 0.57 ± 0.1 l minâ1 vs. GLN = 0.54 ± 0.1 l minâ1} or View the MathML source kinetics {tau: CON = 68 ± 22 s vs. GLN = 68 ± 16 s}. Ingestion of glutamine before exercise did not improve indices of oxidative metabolism in this patient group
Intra-tumor genetic heterogeneity and alternative driver genetic alterations in breast cancers with heterogeneous HER2 gene amplification
Background HER2 is overexpressed and amplified in approximately 15% of invasive breast cancers, and is the molecular target and predictive marker of response to anti-HER2 agents. In a subset of these cases, heterogeneous distribution of HER2 gene amplification can be found, which creates clinically challenging scenarios. Currently, breast cancers with HER2 amplification/overexpression in just over 10% of cancer cells are considered HER2-positive for clinical purposes; however, it is unclear as to whether the HER2-negative components of such tumors would be driven by distinct genetic alterations. Here we sought to characterize the pathologic and genetic features of the HER2-positive and HER2-negative components of breast cancers with heterogeneous HER2 gene amplification and to define the repertoire of potential driver genetic alterations in the HER2-negative components of these cases.Results We separately analyzed the HER2-negative and HER2-positive components of 12 HER2 heterogeneous breast cancers using gene copy number profiling and massively parallel sequencing, and identified potential driver genetic alterations restricted to the HER2-negative cells in each case. In vitro experiments provided functional evidence to suggest that BRF2 and DSN1 overexpression/amplification, and the HER2 I767M mutation may be alterations that compensate for the lack of HER2 amplification in the HER2-negative components of HER2 heterogeneous breast cancers.Conclusions Our results indicate that even driver genetic alterations, such as HER2 gene amplification, can be heterogeneously distributed within a cancer, and that the HER2-negative components are likely driven by genetic alterations not present in the HER2-positive components, including BRF2 and DSN1 amplification and HER2 somatic mutations
Targeted proteomic quantitation of NRF2 signaling and predictive biomarkers in HNSCC
The NFE2L2 (NRF2) oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion, and chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry-based targeted proteomics assay based on internal standard-triggered parallel reaction monitoring to quantify 69 NRF2 pathway components and targets, as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC). We improved an existing internal standard-triggered parallel reaction monitoring acquisition algorithm, called SureQuant, to increase throughput, sensitivity, and precision. Testing the optimized platform on 27 lung and upper aerodigestive cancer cell models revealed 35 NRF2 responsive proteins. In formalin-fixed paraffin-embedded HNSCCs, NRF2 signaling intensity positively correlated with NRF2-activating mutations and with SOX2 protein expression. Protein markers of T-cell infiltration correlated positively with one another and with human papilloma virus infection status. CDKN2A (p16) protein expression positively correlated with the human papilloma virus oncogenic E7 protein and confirmed the presence of translationally active virus. This work establishes a clinically actionable HNSCC protein biomarker assay capable of quantifying over 600 peptides from frozen or formalin-fixed paraffin-embedded archived tissues in under 90 min
Effects of dietary nitrate, caffeine, and their combination on 20-km cycling time trial performance.
This is the accepted manuscript version of the following article: M. Glaister, J. R. Pattison, D. Muniz-Pumares, S. D. Patterson, and P. Foley, âEffects of Dietary Nitrate, Caffeine, and Their Combination on 20-km Cycling Time Trial Performanceâ, The Journal of Strength and Conditioning Research,Vol. 29(1): 165-174, January 2015. The final published version is available at: http://journals.lww.com/nsca-jscr/Pages/aboutthejournal.aspx ©2015 by the National Strength & Conditioning Association.The aim of this study was to examine the acute supplementation effects of dietary nitrate, caffeine, and their combination on 20-km cycling time trial performance. Using a randomized, counterbalanced, double-blind Latin-square design, 14 competitive female cyclists (age: 31 ± 7 years; height: 1.69 ± 0.07 m; body mass: 61.6 ± 6.0 kg) completed four 20-km time trials on a racing bicycle fitted to a turbo trainer. Approximately 2.5 hours before each trial, subjects consumed a 70-ml dose of concentrated beetroot juice containing either 0.45 g of dietary nitrate or with the nitrate content removed (placebo). One hour before each trial, subjects consumed a capsule containing either 5 mg·kg of caffeine or maltodextrin (placebo). There was a significant effect of supplementation on power output (p = 0.001), with post hoc tests revealing higher power outputs in caffeine (205 ± 21 W) vs. nitrate (194 ± 22 W) and placebo (194 ± 25 W) trials only. Caffeine-induced improvements in power output corresponded with significantly higher measures of heart rate (caffeine: 166 ± 12 b·min vs. placebo: 159 ± 15 b·min; p = 0.02), blood lactate (caffeine: 6.54 ± 2.40 mmol·L vs. placebo: 4.50 ± 2.11 mmol·L; p < 0.001), and respiratory exchange ratio (caffeine: 0.95 ± 0.04 vs. placebo: 0.91 ± 0.05; p = 0.03). There were no effects (p â„ 0.05) of supplementation on cycling cadence, rating of perceived exertion, (Equation is included in full-text article.), or integrated electromyographic activity. The results of this study support the well-established beneficial effects of caffeine supplementation on endurance performance. In contrast, acute supplementation with dietary nitrate seems to have no effect on endurance performance and adds nothing to the benefits afforded by caffeine supplementation.Peer reviewedFinal Accepted Versio
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Low-Multiplicity Burst Search At The Sudbury Neutrino Observatory
Results are reported from a search for low-multiplicity neutrino bursts in the Sudbury Neutrino Observatory. Such bursts could indicate the detection of a nearby core-collapse supernova explosion. The data were taken from Phase I (1999 November-2001 May), when the detector was filled with heavy water, and Phase II (2001 July-2003 August), when NaCl was added to the target. The search was a blind analysis in which the potential backgrounds were estimated and analysis cuts were developed to eliminate such backgrounds with 90% confidence before the data were examined. The search maintained a greater than 50% detection probability for standard supernovae occurring at a distance of up to 60 kpc for Phase I and up to 70 kpc for Phase II. No low-multiplicity bursts were observed during the data-taking period.Natural Sciences and Engineering Research Council, CanadaIndustry Canada, CanadaNational Research Council, CanadaNorthern Ontario Heritage Fund, CanadaAtomic Energy of Canada, Ltd., CanadaOntario Power Generation, CanadaHigh Performance Computing Virtual Laboratory, CanadaCanada Foundation for Innovation, CanadaCanada Research Chairs, CanadaDepartment of Energy, USNational Energy Research Scientific Computing Center, USAlfred P. Sloan Foundation, USScience and Technology Facilities Council, UKFundacao para a Ciencia e a Technologia, PortugalAstronom
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