Data mining of plasma peptide chromatograms for biomarkers of air contaminant exposures

<p>Abstract</p> <p>Background</p> <p>Interrogation of chromatographic data for biomarker discovery becomes a tedious task due to stochastic variability in retention times arising from solvent and column performance. The difficulty is further compounded when the effects of exposure (e.g. to environmental contaminants) and biological variability result in varying numbers and intensities of peaks among chromatograms.</p> <p>Results</p> <p>We developed a software tool to correct the stochastic time shifts in chromatographic data through iterative selection of landmark peaks and isometric interpolation to improve alignment of all chromatographic peaks. To illustrate application of the tool, plasma peptides from Fischer rats exposed for 4 h to clean air or Ottawa urban particles (EHC-93) were separated by HPLC with autofluorescence detection, and the retention time shifts between chromatograms were corrected (dewarped). Both dewarped and non-dewarped datasets were then mined for models containing peptide peaks that best discriminate among the treatment groups using ClinproTools™. In general, models generated by dewarped datasets were able to better classify test sample chromatograms into either clean air or EHC-93 exposure groups, and 0 or 24 h post-recovery time groups. Peak areas of peptides in a model that produced the best discrimination of treatment groups were analyzed by two-way ANOVA with exposure (clean air, EHC-93) and recovery time (0 h, 24 h) as factors. Statistically significant (p < 0.05) time-dependent and exposure-dependent increases and decreases were noted establishing these as biomarker candidates for further validation.</p> <p>Conclusion</p> <p>Our software tool provides a simple and portable approach for alignment of chromatograms with complex, bi-directional retention time shifts prior to data mining. Reliable biomarker discovery can be achieved through chromatographic dewarping using our software followed by pattern recognition by commercial data mining applications.</p

Mjerenje raspodjele m-ksilena u tkivima štakora plinskokromatografskom analizom para iznad uzorka (head space gas chromatography)

An automated head space-gas chromatography (HS-GC) method was developed and evaluated for reliability in measurement of m-xylene in rat tissues. For tissue samples spiked with m-xylene (n=2), the analytical precision was better than 12% relative standard deviation (RSD) over the concentration range of 0.1 to cca 100 µg/g for liver and kidney, 0.1 to 170 µg/g for brain, 1.2 to 250 µg/g for fat, and 0.006 to 50 µg/mL for blood. For rats sacrificed immediately after an acute exposure to 1100 ppm of m-xylene, the relative tissue m-xylene concentrations were in the ascending order as follows: brain ≤ blood ≤kidney ≤ liver « fat. A precision of < 13% RSD was generally obtained for duplicale tissue samples from exposed animals, with m-xylene concentrations of about 10 µg/g of tissue.Razvijena je automatizirana metoda plinska head space kromatografije (izvorno: KS-GC), pouzdanost koje je provjerena mjerenjem m-ksilena u tkivima štakora. Analitička preciznost za uzorke tkiva (n-2) kojima je dodan m-ksilensneii u raspunu koncentracija od 0,1 do gotovo 100 µg/g za jetru i bubreg, uu 0,1 do 170 µg/g za mozak, od 1,2 do 250 µg/g za masno tkivo te od 0,006 do 50 µg/g za krv, pokazala se boljom od 12-postotne relativne standardne devijacije (RS0). Relativne koncentracije m-ksilena u tkivu štakora žrtvovanih odmah nakon akutne izloženosti m-ksilenu od 1100 ppm kretale su se ovim uzlaznim slijedom: mozak ≤ krv ≤ bubrcg < jetra « masno tkivo. Sveukupna preciznost iznosila je < 13% USD u paralelnim uzorcima izloženih životinja kod koncentracije m-ksilena u tkivu od oko 10 µg/g

Strategic Foresight & Sacred Practises: Exploring how sacred practises may create pathways towards equitable futures

In this paper, I explore whether and how strategic foresight could play a more significant role in shaping equitable, just, and sustainable futures. I critique and challenge the mainstream approach to strategic foresight by highlighting its limitations towards exploring and envisioning futures centering equity, justice, and shared well-being. Secondly, I delve into how sacred practices may help to create pathways toward these futures. I am looking to explore how individual and collective efforts for building our desired futures be strengthened by honouring the sacred and reclaiming different ways of knowing and being through practises we individually and collectively deem sacred. Data for this study was collected via a literature review and expert interviews. Expert interviews were analyzed via a thematic analysis. My findings suggest that due to various limitations embedded the field of strategic foresight, there is both an urgency and need for its ability to centre equity and diversity in many ways. As such honouring the sacred and sacred practises could have a role to play within this. Sacred practises also offer a different way for strategic foresight to contend with how it can play a larger role in building equitable, just, and sustainable futures. In conclusion, I argue that radical imagination needs to continue to exist unobstructed in the hands of people and communities. I strongly believe that one of the gateways to harness the power of radical imagination is through sacred practices

Acellular oxidative potential assay for screening of amorphous silica nanoparticles.

Rapid acellular screening of amorphous silica nanoforms of different sizes and surface modifications for their oxidative potential

Contrasting biological potency of particulate matter collected at sites impacted by distinct industrial sources

Association of biological effects in A549 cells with metal content in size-fractionated particles. Cytotoxic potencies according to lactate dehydrogenase (LDH) release and resazurin reduction were regressed against total, water-soluble, and non-water-soluble metals. Pearson product–moment correlation coefficient r-values are presented. LDH release. A) Total metals. UFP, r = 0.77, p = 0.13; PM0.1–2.5, r = −0.55, p = 0.34; PM2.5–10, r = 0.32, p = 0.60; PM>10, r = −0.68, p = 0.21. B) Water-soluble metals. UFP, r = 0.51, p = 0.38; PM0.1–2.5, r = −0.64, p = 0.25; PM2.5–10, r = −0.35, p = 0.57; PM>10, r = −0.68, p = 0.20. C) Non-water-soluble metals. UFP, r = 0.75, p = 0.14; PM0.1–2.5, r = −0.46, p = 0.43; PM2.5–10, r = 0.36, p = 0.55; PM>10, r = −0.68, p = 0.21. Resazurin reduction. D) UFP, r = −0.19, p = 0.76; PM0.1–2.5, r = −0.63, p = 0.26; PM2.5–10, r = −0.60, p = 0.28; PM>10,r = 0.18, p = 0.78. Water-soluble metals. UFP, r = −0.20, p = 0.74; PM0.1–2.5, r = −0.41, p = 0.49; PM2.5–10, r = −0.09, p = 0.88; PM>10, r = 0.04, p = 0.95. Non-water-soluble metals. UFP, r = −0.12, p = 0.84; PM0.1–2.5, r = −0.65, p = 0.24; PM2.5–10, r = −0.62, p = 0.26; PM>10, r = 0.18, p = 0.77. (PDF 43 kb

Synthesis and Physicochemical Characterization of Mesoporous S

There exists a knowledge gap in understanding potential toxicity of mesoporous silica nanoparticles. A critical step in assessing toxicity of these particles is to have a wide size range with different chemistries and physicochemical properties. There are several challenges when synthesizing mesoporous silica nanoparticles over a wide range of sizes including (1) nonuniform synthesis protocols using the same starting materials, (2) the low material yield in a single batch synthesis (especially for particles below 60–70 nm), and (3) morphological instability during surfactant removal process and surface modifications. In this study, we synthesized a library of mesoporous silica nanoparticles with approximate particle sizes of 25, 70, 100, 170, and 600 nm. Surfaces of the silica nanoparticles were modified with hydrophilic-CH2–(CH2)2–COOH and relatively hydrophobic-CH2–(CH2)10–COOH functional groups. All silica nanoparticles were analysed for morphology, surface functionality, surface area/pore volume, surface organic content, and dispersion characteristics in liquid media. Our analysis revealed the synthesis of a spectrum of monodisperse bare and surface modified mesoporous silica nanoparticles with a narrow particle size distribution and devoid of cocontaminants critical for toxicity studies. Complete physicochemical characterization of these synthetic mesoporous silica nanoparticles will permit systematic toxicology studies for investigation of structure-activity relationships