Alternating and Modified Alternating Least Squares Applied to Raman Spectra of Finished Gasolines.

Extraction of components from individual refinery streams (e.g., reformates and alkylates) in finished gasoline was undertaken using Raman spectroscopy to characterize the chemical content of the finished product.

Comparison of Step-Based Metrics Under Laboratory and Free-Living Conditions in Femoroacetabular Impingement Syndrome.

Context: Femoroacetabular impingement syndrome (FAIS) causes pain and functional limitations. Little is known regarding walking characteristics, volume, and intensity evaluated in laboratory and free-living conditions and whether these measures differ between those with FAIS and uninjured individuals.

Objective: To examine the differences in laboratory gait measures and free-living step-based metrics between individuals with FAIS and uninjured control participants.

Positive blood phosphatidylethanol concentration is associated with unfavorable waitlist-related outcomes for patients medically appropriate for liver transplantation.

Background: Excessive alcohol use is a leading etiology of liver disease and indication for liver transplantation. Accurate measurement of alcohol use remains a challenge in the management of patients in the pre-, peri-, and post-liver transplant settings. Blood 16:0-18:1 phosphatidylethanol (PEth) concentration is a sensitive and specific biomarker of binge and moderate, chronic alcohol use.

Persistence of improved glucose homeostasis in Gclm null mice with age and cadmium treatment.

Antioxidant signaling/communication is among the most important cellular defense and survival pathways, and the importance of redox signaling and homeostasis in aging has been well-documented. Intracellular levels of glutathione (GSH), a very important endogenous antioxidant, both govern and are governed by the Nrf2 pathway through expression of genes involved in its biosynthesis, including the subunits of the rate-limiting enzyme (glutamate cysteine ligase, GCL) in GSH production, GCLC and GCLM. Mice homozygous null for the Gclm gene are severely deficient in GSH compared to wild-type controls, expressing approximately 10% of normal GSH levels.

Elamipretide (SS-31) treatment attenuates age-associated post-translational modifications of heart proteins.

It has been demonstrated that elamipretide (SS-31) rescues age-related functional deficits in the heart but the full set of mechanisms behind this have yet to be determined. We investigated the hypothesis that elamipretide influences post-translational modifications to heart proteins. The S-glutathionylation and phosphorylation proteomes of mouse hearts were analyzed using shotgun proteomics to assess the effects of aging on these post-translational modifications and the ability of the mitochondria-targeted drug elamipretide to reverse age-related changes.

Benzalkonium Chloride Disinfectants Induce Apoptosis, Inhibit Proliferation, and Activate the Integrated Stress Response in a 3-D Model of Neurodevelopment.

We previously found that the widely used disinfectants, benzalkonium chlorides (BACs), alter cholesterol and lipid homeostasis in neuronal cell lines and in neonatal mouse brains. Here, we investigate the effects of BACs on neurospheres, an three-dimensional model of neurodevelopment. Neurospheres cultured from mouse embryonic neural progenitor cells (NPCs) were exposed to increasing concentrations (from 1 to 100 nM) of a short-chain BAC (BAC C12), a long-chain BAC (BAC C16), and AY9944 (a known DHCR7 inhibitor).

Carbonyl Reductase 1 Plays a Significant Role in Converting Doxorubicin to Cardiotoxic Doxorubicinol in Mouse Liver, but the Majority of the Doxorubicinol-Forming Activity Remains Unidentified.

Doxorubicin is a widely used cancer therapeutic, but its effectiveness is limited by cardiotoxic side effects. Evidence suggests cardiotoxicity is due not to doxorubicin, but rather its metabolite, doxorubicinol. Identification of the enzymes responsible for doxorubicinol formation is important in developing strategies to prevent cardiotoxicity.

Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice.

Sarcopenia and exercise intolerance are major contributors to reduced quality of life in the elderly for which there are few effective treatments. We tested whether enhancing mitochondrial function and reducing mitochondrial oxidant production with SS-31 (elamipretide) could restore redox balance and improve skeletal muscle function in aged mice. Young (5 mo) and aged (26 mo) female C57BL/6Nia mice were treated for 8-weeks with 3 mg/kg/day SS-31.

Kinetics of Glutathione Depletion and Antioxidant Gene Expression as Indicators of Chemical Modes of Action Assessed in Vitro in Mouse Hepatocytes with Enhanced Glutathione Synthesis.

Here we report a vertically integrated in vitro - in silico study that aims to elucidate the molecular initiating events involved in the induction of oxidative stress (OS) by seven diverse chemicals (cumene hydroperoxide, t-butyl hydroperoxide, hydroquinone, t-butyl hydroquinone, bisphenol A, Dinoseb, and perfluorooctanoic acid). To that end, we probe the relationship between chemical properties, cell viability, glutathione (GSH) depletion, and antioxidant gene expression. Concentration-dependent effects on cell viability were assessed by MTT assay in two Hepa-1 derived mouse liver cell lines: a control plasmid vector transfected cell line (Hepa-V), and a cell line with increased glutamate-cysteine ligase (GCL) activity and GSH content (CR17).

Quantum dot induced acute changes in lung mechanics are mouse strain dependent.

Introduction: Concerns have been raised regarding occupational exposure to engineered nanomaterials (ENMs). Potential impacts on lung function from inhalation exposures are of concern as the lung is a sensitive ENM target in animals. Epidemiological data suggest that occupational exposure to ENMs may impact respiratory and cardiovascular health.

Prostacyclin and EMT Pathway Markers for Monitoring Response to Lung Cancer Chemoprevention.

Lung cancer is the leading cause of cancer death worldwide and global burden could be reduced through targeted application of chemoprevention. The development of squamous lung carcinoma has been linked with persistent, high-grade bronchial dysplasia. Bronchial histology improved in former smokers in a chemoprevention trial with the prostacyclin analogue iloprost.

Chemometric Methods for Estimating the Strain Hardening Modulus in Polyethylene Resins.

The feasibility of using multiway or N-way partial least square (NPLS) methods to estimate physical properties of 1-butene and 1-hexene polyethylene (PE) copolymers directly from multidimensional data obtained from size exclusion chromatography coupled to a Fourier transform infrared detector (SEC FT-IR) was explored. Digital sample sets of horizontal slices (slabs) of two-dimensional data simulating the molecular weight distribution and the corresponding orthogonal FT-IR spectra were correlated to a particular Y-block response using NPLS. The NPLS results were compared to those obtained through separate estimations using various algorithms and exploratory response surface methods.

Library Search Prefilters for Vehicle Manufacturers to Assist in the Forensic Examination of Automotive Paints.

Pattern recognition techniques have been applied to the infrared (IR) spectral libraries of the Paint Data Query (PDQ) database to differentiate between nonidentical but similar IR spectra of automotive paints. To tackle the problem of library searching, search prefilters were developed to identify the vehicle make from IR spectra of the clear coat, surfacer-primer, and e-coat layers. To develop these search prefilters with the appropriate degree of accuracy, IR spectra from the PDQ database were preprocessed using the discrete wavelet transform to enhance subtle but significant features in the IR spectral data.

Genetic determinants of susceptibility to silver nanoparticle-induced acute lung inflammation in mice.

Silver nanoparticles (AgNPs) are employed in a variety of consumer products; however, rodent studies indicate that AgNPs can cause lung inflammation and toxicity in a strain- and particle type-dependent manner, but mechanisms of susceptibility remain unclear. The aim of this study was to assess the variation in AgNP-induced lung inflammation and toxicity across multiple inbred mouse strains and to use genome-wide association (GWA) mapping to identify potential candidate susceptibility genes. Mice received doses of 0.

Boosting the Performance of Genetic Algorithms for Variable Selection in Partial Least Squares Spectral Calibrations.

A genetic algorithm (GA) for variable selection in partial least squares (PLS) regression that incorporates adaptive boosting to identify informative wavelengths in near-infrared (NIR) spectra has been developed. Three studies demonstrating the advantages of incorporating an adaptive boosting routine into a GA that employs the root mean square error of calibration as its fitness function are highlighted: (1) prediction of hydroxyl number of terpolymers from NIR diffuse reflectance spectra; (2) calibration of acetone from NIR transmission spectra of mixtures of water, acetone, t-butyl alcohol and isopropyl alcohol; and (3) determination of the active pharmaceutical ingredients in drug tablets from NIR diffuse reflectance spectra. The performance of the GA with adaptive boosting to select wavelengths was compared with one without adaptive boosting.

Characterization of rat or human hepatocytes cultured in microphysiological systems (MPS) to identify hepatotoxicity.

The liver is the main site for drug and xenobiotics metabolism, including inactivation or bioactivation. In order to improve the predictability of drug safety and efficacy in clinical development, and to facilitate the evaluation of the potential human health effects from exposure to environmental contaminants, there is a critical need to accurately model human organ systems such as the liver in vitro. We are developing a microphysiological system (MPS) based on a new commercial microfluidic platform (Nortis, Inc.

Glutathione as a Biomarker in Parkinson's Disease: Associations with Aging and Disease Severity.

. Oxidative stress contributes to Parkinson's disease (PD) pathophysiology and progression. The objective was to describe central and peripheral metabolites of redox metabolism and to describe correlations between glutathione (Glu) status, age, and disease severity.

Pattern Recognition-Assisted Infrared Library Searching of the Paint Data Query Database to Enhance Lead Information from Automotive Paint Trace Evidence.

Multilayered automotive paint fragments, which are one of the most complex materials encountered in the forensic science laboratory, provide crucial links in criminal investigations and prosecutions. To determine the origin of these paint fragments, forensic automotive paint examiners have turned to the paint data query (PDQ) database, which allows the forensic examiner to compare the layer sequence and color, texture, and composition of the sample to paint systems of the original equipment manufacturer (OEM). However, modern automotive paints have a thin color coat and this layer on a microscopic fragment is often too thin to obtain accurate chemical and topcoat color information.

Evidential significance of automotive paint trace evidence using a pattern recognition based infrared library search engine for the Paint Data Query Forensic Database.

A prototype library search engine has been further developed to search the infrared spectral libraries of the paint data query database to identify the line and model of a vehicle from the clear coat, surfacer-primer, and e-coat layers of an intact paint chip. For this study, search prefilters were developed from 1181 automotive paint systems spanning 3 manufacturers: General Motors, Chrysler, and Ford. The best match between each unknown and the spectra in the hit list generated by the search prefilters was identified using a cross-correlation library search algorithm that performed both a forward and backward search.

Central nervous system uptake of intranasal glutathione in Parkinson's disease.

Glutathione (GSH) is depleted early in the course of Parkinson's disease (PD), and deficiency has been shown to perpetuate oxidative stress, mitochondrial dysfunction, impaired autophagy, and cell death. GSH repletion has been proposed as a therapeutic intervention. The objective of this study was to evaluate whether intranasally administered reduced GSH, (in)GSH, is capable of augmenting central nervous system GSH concentrations, as determined by magnetic resonance spectroscopy in 15 participants with mid-stage PD.

Susceptibility to quantum dot induced lung inflammation differs widely among the Collaborative Cross founder mouse strains.

Quantum dots (QDs) are engineered semiconductor nanoparticles with unique physicochemical properties that make them potentially useful in clinical, research and industrial settings. However, a growing body of evidence indicates that like other engineered nanomaterials, QDs have the potential to be respiratory hazards, especially in the context of the manufacture of QDs and products containing them, as well as exposures to consumers using these products. The overall goal of this study was to investigate the role of mouse strain in determining susceptibility to QD-induced pulmonary inflammation and toxicity.

Toxicity and oxidative stress induced by semiconducting polymer dots in RAW264.7 mouse macrophages.

The rapid development and acceptance of PDots for biological applications depends on an in depth understanding of their cytotoxicity. In this paper, we performed a comprehensive study of PDot cytotoxicity at both the gross cell effect level (such as cell viability, proliferation and necrosis) and more subtle effects (such as redox stress) on RAW264.7 cells, a murine macrophage cell line with high relevance to in vivo nanoparticle disposition.

Pattern recognition-assisted infrared library searching of automotive clear coats.

Pattern recognition techniques have been developed to search the infrared (IR) spectral libraries of the paint data query (PDQ) database to differentiate between similar but nonidentical IR clear coat paint spectra. The library search system consists of two separate but interrelated components: search prefilters to reduce the size of the IR library to a specific assembly plant or plants corresponding to the unknown paint sample and a cross-correlation searching algorithm to identify IR spectra most similar to the unknown in the subset of spectra identified by the prefilters. To develop search prefilters with the necessary degree of accuracy, IR spectra from the PDQ database were preprocessed using wavelets to enhance subtle but significant features in the data.

Search prefilters to assist in library searching of infrared spectra of automotive clear coats.

Clear coat searches of the infrared (IR) spectral library of the paint data query (PDQ) forensic database often generate an unusable number of hits that span multiple manufacturers, assembly plants, and years. To improve the accuracy of the hit list, pattern recognition methods have been used to develop search prefilters (i.e.