TY - CONF TI - Characterization of atmospheric pressure rf discharges with aqueous plasma facing surfaces AU - Lindsay, A. AU - Byrns, B. AU - Knappe, D. AU - Shannon, S. AB - Summary form only given. Plasma modification of liquids has opened a broad range of new applications ranging from wound treatment to water purification to agricultural fertigation and herbicide. Two of the primary challenges facing systems designed to modify liquid chemistry through plasma treatment have been throughput and efficient introduction of liquid species in the active plasma region. In this presentation, we present novel pathways for both source scale up and liquid incorporation that can make plasma treatment of liquids more economically viable. C2 - 2015/// C3 - ICOPS/BEAMS 2014 - 41st IEEE International Conference on Plasma Science and the 20th International Conference on High-Power Particle Beams DA - 2015/// DO - 10.1109/PLASMA.2014.7012279 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84923050875&partnerID=MN8TOARS ER - TY - RPRT TI - Removal of perfluoroalkyl substances by PAC adsorption and anion exchange AU - Dudley, L.A. AU - Arevalo, E.C. AU - Knappe, D.R.U. A3 - Water Research Foundation DA - 2015/// PY - 2015/// M1 - 4344 M3 - Executive summary PB - Water Research Foundation SN - 4344 ER - TY - RPRT TI - Removal of volatile organic contaminants (VOCs) from drinking water via granular activated carbon treatment AU - Summers, R.S. AU - Kempisty, D. AU - Daugherty, T. AU - Knappe, D. A3 - Water Research Foundation DA - 2015/// PY - 2015/// M1 - 4440 M3 - Final report PB - Water Research Foundation SN - 4440 ER - TY - CONF TI - Developing Energy and Greenhouse Gas Emission Factors for Anaerobic Digestion in U.S. EPA's Waste Reduction Model AU - Renz, B. AU - Evans, C. AU - Barlaz, M.A. AU - Levis, J.W. AU - Kollar, T. AU - Boland, C. T2 - LCA XV C2 - 2015/// CY - Vancouver, BC DA - 2015/// PY - 2015/10// ER - TY - CONF TI - Methods to measure the hydrogen sulfide production potential of sulfate-containing wastes disposed in landfills AU - Sun, W.J. AU - Sun, M. AU - Barlaz, M.A. T2 - 15th International Waste Management and Landfill Symposium C2 - 2015/// CY - S. Margherita di Pula (CA), Italy DA - 2015/// PY - 2015/10/5/ ER - TY - CONF TI - A systematic evaluation of the costs and environmental impacts associated with future municipal solid waste management AU - Levis, J. AU - Barlaz, M. AU - DeCarolis, J. AU - Ranjithan, R. T2 - 5th International Waste Management and Landfill Symposium C2 - 2015/// CY - S. Margherita di Pula (CA), Italy DA - 2015/// PY - 2015/10/5/ ER - TY - JOUR TI - Response to the letter by Gallo D., et al AU - Belcher, S.M. T2 - Endocrinology DA - 2015/// PY - 2015/// DO - 10.1210/en.2015-1484 VL - 156 IS - 8 SP - L8-L9 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84938684568&partnerID=MN8TOARS ER - TY - JOUR TI - Non-monotonic dose-response relationships and endocrine disruptors: A qualitative method of assessment -No section- AU - Lagarde, F. AU - Beausoleil, C. AU - Belcher, S.M. AU - Belzunces, L.P. AU - Emond, C. AU - Guerbet, M. AU - Rousselle, C. T2 - Environmental Health: A Global Access Science Source AB - Experimental studies investigating the effects of endocrine disruptors frequently identify potential unconventional dose-response relationships called non-monotonic dose-response (NMDR) relationships. Standardized approaches for investigating NMDR relationships in a risk assessment context are missing. The aim of this work was to develop criteria for assessing the strength of NMDR relationships. A literature search was conducted to identify published studies that report NMDR relationships with endocrine disruptors. Fifty-one experimental studies that investigated various effects associated with endocrine disruption elicited by many substances were selected. Scoring criteria were applied by adaptation of an approach previously used for identification of hormesis-type dose-response relationships. Out of the 148 NMDR relationships analyzed, 82 were categorized with this method as having a “moderate” to “high” level of plausibility for various effects. Numerous modes of action described in the literature can explain such phenomena. NMDR can arise from numerous molecular mechanisms such as opposing effects induced by multiple receptors differing by their affinity, receptor desensitization, negative feedback with increasing dose, or dose-dependent metabolism modulation. A stepwise decision tree was developed as a tool to standardize the analysis of NMDR relationships observed in the literature with the final aim to use these results in a Risk Assessment purpose. This decision tree was finally applied to studies focused on the effects of bisphenol A. DA - 2015/// PY - 2015/// DO - 10.1186/1476-069X-14-13 VL - 14 IS - 1 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84929008164&partnerID=MN8TOARS KW - Endocrine disruptors KW - NMDR KW - Non-monotonic KW - Dose-response KW - Risk assessment KW - Bisphenol A ER - TY - JOUR TI - Estrogen receptor-β up-regulates IGF1R expression and activity to inhibit apoptosis and increase growth of medulloblastoma AU - Cookman, C.J. AU - Belcher, S.M. T2 - Endocrinology AB - Medulloblastoma (Med) is the most common malignant brain tumor in children. The role of ESR2 [estrogen receptor (ER)-β] in promoting Med growth was comprehensively examined in three in vivo models and human cell lines. In a novel Med ERβ-null knockout model developed by crossing Esr2(-/-) mice with cerebellar granule cell precursor specific Ptch1 conditional knockout mice, the tumor growth rate was significantly decreased in males and females. The absence of Esr2 resulted in increased apoptosis, decreased B-cell lymphoma 2 (BCL2), and IGF-1 receptor (IGF1R) expression, and decreased levels of active MAPKs (ERK1/2) and protein kinase B (AKT). Treatment of Med in Ptch1(+/-) Trp53(-/-) mice with the antiestrogen chemotherapeutic drug Faslodex significantly increased symptom-free survival, which was associated with increased apoptosis and decreased BCL2 and IGF1R expression and signaling. Similar effects were also observed in nude mice bearing D283Med xenografts. In vitro studies in human D283Med cells metabolically stressed by glutamine withdrawal found that 17β-estradiol and the ERβ selective agonist 2,3-bis(4-hydroxyphenyl)-propionitrile dose dependently protected Med cells from caspase-3-dependent cell death. Those effects were associated with increased phosphorylation of IGF1R, long-term increases in ERK1/2 and AKT signaling, and increased expression of IGF-1, IGF1R, and BCL2. Results of pharmacological experiments revealed that the cytoprotective actions of estradiol were dependent on ERβ and IGF1R receptor tyrosine kinase activity and independent of ERα and G protein-coupled estrogen receptor 1 (G protein coupled receptor 30). The presented results demonstrate that estrogen promotes Med growth through ERβ-mediated increases in IGF1R expression and activity, which induce cytoprotective mechanisms that decrease apoptosis. DA - 2015/// PY - 2015/// DO - 10.1210/en.2015-1141 VL - 156 IS - 7 SP - 2395-2408 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84937605783&partnerID=MN8TOARS ER - TY - JOUR TI - Bisphenol a alters autonomic tone and extracellular matrix structure and induces sex-specific effects on cardiovascular function in male and female CD-1 mice AU - Belcher, S.M. AU - Gear, R.B. AU - Kendig, E.L. T2 - Endocrinology AB - The aim of this study was to determine whether bisphenol A (BPA) has adverse effects on cardiovascular functions in CD-1 mice and define sex-specific modes of BPA action in the heart. Dams and analyzed progeny were maintained on a defined diet containing BPA (0.03, 0.3, 3, 30, or 300 ppm) that resulted in BPA exposures from 4-5 to approximately 5000 μg/kg · d or a diet containing 17α-ethinyl estradiol (EE; ∼0.02, 0.2, and 0.15 μg/kg · d) as an oral bioavailable estrogen control. Assessment of electrocardiogram parameters using noninvasive methods found that ventricular functions in both male and female mice were not altered by either BPA or EE. However, exposure-related changes in the rates of ventricular contraction, suggestive of a shift in sympathovagal balance of heart rate control toward increased parasympathetic activity, were detected in males. Decreased systolic blood pressure was observed in males exposed to BPA above 5 μg/kg · d and in females from the highest BPA exposure group. Morphometric histological measures revealed sexually dimorphic changes in the composition of the cardiac collagen extracellular matrix, increases in fibrosis, and evidence of modest exposure-related remodeling. Experiments using the α-selective adrenergic agonist phenylephrine found that BPA enhanced reflex bradycardia in females, but not males, revealed that BPA and EE exposure sex specifically altered the sympathetic regulation of the baroreflex circuits. Increased sensitivity to the cardiotoxic effects of the β-adrenergic agonist isoproterenol was observed in BPA- and EE-exposed females. This effect was not observed in males, in which BPA or EE exposures were protective of isoproterenol-induced ischemic damage and hypertrophy. The results of RNA sequence analysis identified significant sex-specific changes in gene expression in response to BPA that were consistent with the observed exposure-related phenotypic changes in the collagenous and noncollagenous extracellular matrix, cardiac remodeling, altered autonomic responses, changes in ion channel and transporter functions, and altered glycolytic and lipid metabolism. DA - 2015/// PY - 2015/// DO - 10.1210/en.2014-1847 VL - 156 IS - 3 SP - 882-895 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84923884313&partnerID=MN8TOARS ER - TY - JOUR TI - Comprehensive characterization of the Published Kinase Inhibitor Set AU - Elkins, Jonathan M AU - Fedele, Vita AU - Szklarz, Marta AU - Abdul Azeez, Kamal R AU - Salah, Eidarus AU - Mikolajczyk, Jowita AU - Romanov, Sergei AU - Sepetov, Nikolai AU - Huang, Xi-Ping AU - Roth, Bryan L AU - Al Haj Zen, Ayman AU - Fourches, Denis AU - Muratov, Eugene AU - Tropsha, Alex AU - Morris, Joel AU - Teicher, Beverly A AU - Kunkel, Mark AU - Polley, Eric AU - Lackey, Karen E AU - Atkinson, Francis L AU - Overington, John P AU - Bamborough, Paul AU - Müller, Susanne AU - Price, Daniel J AU - Willson, Timothy M AU - Drewry, David H AU - Knapp, Stefan AU - Zuercher, William J T2 - Nature Biotechnology AB - Despite the success of protein kinase inhibitors as approved therapeutics, drug discovery has focused on a small subset of kinase targets. Here we provide a thorough characterization of the Published Kinase Inhibitor Set (PKIS), a set of 367 small-molecule ATP-competitive kinase inhibitors that was recently made freely available with the aim of expanding research in this field and as an experiment in open-source target validation. We screen the set in activity assays with 224 recombinant kinases and 24 G protein-coupled receptors and in cellular assays of cancer cell proliferation and angiogenesis. We identify chemical starting points for designing new chemical probes of orphan kinases and illustrate the utility of these leads by developing a selective inhibitor for the previously untargeted kinases LOK and SLK. Our cellular screens reveal compounds that modulate cancer cell growth and angiogenesis in vitro. These reagents and associated data illustrate an efficient way forward to increasing understanding of the historically untargeted kinome. DA - 2015/10/26/ PY - 2015/10/26/ DO - 10.1038/NBT.3374 VL - 34 IS - 1 SP - 95-103 J2 - Nat Biotechnol LA - en OP - SN - 1087-0156 1546-1696 UR - http://dx.doi.org/10.1038/NBT.3374 DB - Crossref ER - TY - JOUR TI - In Response : Conservation versus functional diversification of nuclear receptors: An academic perspective AU - Kullman, Seth W. T2 - Environmental Toxicology and Chemistry AB - Environmental Toxicology and ChemistryVolume 34, Issue 3 p. 463-465 ET&C Perspectives In Response: Conservation versus functional diversification of nuclear receptors: An academic perspective Seth W. Kullman, Seth W. Kullman North Carolina State University Raleigh, North Carolina, USASearch for more papers by this author Seth W. Kullman, Seth W. Kullman North Carolina State University Raleigh, North Carolina, USASearch for more papers by this author First published: 24 February 2015 https://doi.org/10.1002/etc.2832Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume34, Issue3March 2015Pages 463-465 RelatedInformation DA - 2015/2/24/ PY - 2015/2/24/ DO - 10.1002/ETC.2832 VL - 34 IS - 3 SP - 463-465 J2 - Environ Toxicol Chem LA - en OP - SN - 0730-7268 UR - http://dx.doi.org/10.1002/ETC.2832 DB - Crossref ER - TY - CHAP TI - Mass Spectrometry for Biomarker Development AU - Wu, C. AU - Liu, T. AU - Baker, E.S. AU - Rodland, K.D. AU - Smith, R.D. T2 - General Methods in Biomarker Research and their Applications A2 - Preedy, V.R. A2 - Patel, V.B. PY - 2015/// SP - 17–48 PB - Springer ER - TY - JOUR TI - New Master of Science program emphasizing Safety Pharmacology—Results to date AU - Matlib, Abdul AU - Belcher, Scott AU - Rapoport, Robert AU - Millard, Ron AU - Wang, Hong-Sheng AU - Maggio, John T2 - Journal of Pharmacological and Toxicological Methods DA - 2015/9// PY - 2015/9// DO - 10.1016/J.VASCN.2015.08.114 VL - 75 SP - 191-192 J2 - Journal of Pharmacological and Toxicological Methods LA - en OP - SN - 1056-8719 UR - http://dx.doi.org/10.1016/J.VASCN.2015.08.114 DB - Crossref ER - TY - JOUR TI - Effects of whole life exposure to Bisphenol A or 17α-ethinyl estradiol in uterus of nulligravida CD1 mice AU - Kendziorski, Jessica A. AU - Belcher, Scott M. T2 - Data in Brief AB - Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) with known estrogenic activity. Exposure to BPA in adult mice was shown previously to increase uterine pathology with associated alterations in the immune response and fibrosis. Reported here are uterine histopathology findings from CD1 mice exposed to BPA or 17α-ethinyl estradiol at multiple doses from conception through postnatal day 90. Along with uterine pathology, impacts of exposure on collagen accumulation and F4/80 positive macrophage numbers, as an indicator of immune response in the endometrium and myometrium, are presented. These companion data are from offspring (F1) of the dams analyzed for effects of adult exposures published in the Reproductive Toxicology manuscript titled “Strain-Specific Induction of Endometrial Periglandular Fibrosis in Mice Exposed during Adulthood to the Endocrine Disrupting Chemical Bisphenol A” (doi: 10.1016/j.reprotox.2015.08.001). DA - 2015/12// PY - 2015/12// DO - 10.1016/J.DIB.2015.10.034 VL - 5 SP - 948-953 J2 - Data in Brief LA - en OP - SN - 2352-3409 UR - http://dx.doi.org/10.1016/J.DIB.2015.10.034 DB - Crossref KW - BPA KW - Estrogen KW - EDC KW - endocrine disruption KW - Collagen KW - Fibrosis KW - Immune KW - Macrophage ER - TY - JOUR TI - Phosphorylation is an on/off switch for 5-hydroxyconiferaldehyde O-methyltransferase activity in poplar monolignol biosynthesis AU - Wang, Jack P. AU - Chuang, Ling AU - Loziuk, Philip L. AU - Chen, Hao AU - Lin, Ying-Chung AU - Shi, Rui AU - Qu, Guan-Zheng AU - Muddiman, David C. AU - Sederoff, Ronald R. AU - Chiang, Vincent L. T2 - Proceedings of the National Academy of Sciences AB - Although phosphorylation has long been known to be an important regulatory modification of proteins, no unequivocal evidence has been presented to show functional control by phosphorylation for the plant monolignol biosynthetic pathway. Here, we present the discovery of phosphorylation-mediated on/off regulation of enzyme activity for 5-hydroxyconiferaldehyde O-methyltransferase 2 (PtrAldOMT2), an enzyme central to monolignol biosynthesis for lignification in stem-differentiating xylem (SDX) of Populus trichocarpa. Phosphorylation turned off the PtrAldOMT2 activity, as demonstrated in vitro by using purified phosphorylated and unphosphorylated recombinant PtrAldOMT2. Protein extracts of P. trichocarpa SDX, which contains endogenous kinases, also phosphorylated recombinant PtrAldOMT2 and turned off the recombinant protein activity. Similarly, ATP/Mn(2+)-activated phosphorylation of SDX protein extracts reduced the endogenous SDX PtrAldOMT2 activity by ∼ 60%, and dephosphorylation fully restored the activity. Global shotgun proteomic analysis of phosphopeptide-enriched P. trichocarpa SDX protein fractions identified PtrAldOMT2 monophosphorylation at Ser(123) or Ser(125) in vivo. Phosphorylation-site mutagenesis verified the PtrAldOMT2 phosphorylation at Ser(123) or Ser(125) and confirmed the functional importance of these phosphorylation sites for O-methyltransferase activity. The PtrAldOMT2 Ser(123) phosphorylation site is conserved across 93% of AldOMTs from 46 diverse plant species, and 98% of the AldOMTs have either Ser(123) or Ser(125). PtrAldOMT2 is a homodimeric cytosolic enzyme expressed more abundantly in syringyl lignin-rich fiber cells than in guaiacyl lignin-rich vessel cells. The reversible phosphorylation of PtrAldOMT2 is likely to have an important role in regulating syringyl monolignol biosynthesis of P. trichocarpa. DA - 2015/6/24/ PY - 2015/6/24/ DO - 10.1073/PNAS.1510473112 VL - 112 IS - 27 SP - 8481-8486 J2 - Proc Natl Acad Sci USA LA - en OP - SN - 0027-8424 1091-6490 UR - http://dx.doi.org/10.1073/PNAS.1510473112 DB - Crossref KW - AldOMT KW - COMT KW - lignin KW - phosphoproteomics KW - phosphoregulation ER - TY - JOUR TI - Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds AU - Alves, Vinicius M. AU - Muratov, Eugene AU - Fourches, Denis AU - Strickland, Judy AU - Kleinstreuer, Nicole AU - Andrade, Carolina H. AU - Tropsha, Alexander T2 - Toxicology and Applied Pharmacology AB - Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using Random Forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers was 71-88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. DA - 2015/4// PY - 2015/4// DO - 10.1016/J.TAAP.2014.12.014 VL - 284 IS - 2 SP - 262-272 J2 - Toxicology and Applied Pharmacology LA - en OP - SN - 0041-008X UR - http://dx.doi.org/10.1016/J.TAAP.2014.12.014 DB - Crossref KW - Skin sensitization KW - QSAR KW - Virtual screening KW - Skin toxicants ER - TY - JOUR TI - Materials Cartography: Representing and Mining Materials Space Using Structural and Electronic Fingerprints AU - Isayev, Olexandr AU - Fourches, Denis AU - Muratov, Eugene N. AU - Oses, Corey AU - Rasch, Kevin AU - Tropsha, Alexander AU - Curtarolo, Stefano T2 - Chemistry of Materials AB - As the proliferation of high-throughput approaches in materials science is increasing the wealth of data in the field, the gap between accumulated-information and derived-knowledge widens. We address the issue of scientific discovery in materials databases by introducing novel analytical approaches based on structural and electronic materials fingerprints. The framework is employed to (i) query large databases of materials using similarity concepts, (ii) map the connectivity of the materials space (i.e., as a materials cartogram) for rapidly identifying regions with unique organizations/properties, and (iii) develop predictive Quantitative Materials Structure-Property Relation- ships (QMSPR) models for guiding materials design. In this study, we test these fingerprints by seeking target material properties. As a quantitative example, we model the critical temperatures of known superconductors. Our novel materials fingerprinting and materials cartography approaches contribute to the emerging field of materials informatics by enabling effective computational tools to analyze, visualize, model, and design new materials. DA - 2015/1/17/ PY - 2015/1/17/ DO - 10.1021/CM503507H VL - 27 IS - 3 SP - 735-743 J2 - Chem. Mater. LA - en OP - SN - 0897-4756 1520-5002 UR - http://dx.doi.org/10.1021/CM503507H DB - Crossref ER - TY - JOUR TI - Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization AU - Alves, Vinicius M. AU - Muratov, Eugene AU - Fourches, Denis AU - Strickland, Judy AU - Kleinstreuer, Nicole AU - Andrade, Carolina H. AU - Tropsha, Alexander T2 - Toxicology and Applied Pharmacology AB - Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R(2)=0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q(2)ext=0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. DA - 2015/4// PY - 2015/4// DO - 10.1016/J.TAAP.2014.12.013 VL - 284 IS - 2 SP - 273-280 J2 - Toxicology and Applied Pharmacology LA - en OP - SN - 0041-008X UR - http://dx.doi.org/10.1016/J.TAAP.2014.12.013 DB - Crossref KW - Skin sensitization KW - Skin permeability KW - QSAR KW - Virtual screening KW - Skin toxicants ER - TY - JOUR TI - Drug Side Effect Profiles as Molecular Descriptors for Predictive Modeling of Target Bioactivity AU - Baker, Nancy C. AU - Fourches, Denis AU - Tropsha, Alexander T2 - Molecular Informatics AB - We have explored the potential of using side effect profiles of drugs to predict their bioactivities at the receptor level. Serotonin 5-HT6 binding and dopamine antagonism were investigated in separate studies. A set of 5-HT6 binders and non-binders was retrieved from the PDSP Ki database, whereas dopamine antagonists were retrieved from the MeSH Pharmaceutical Action file. The side effect data was extracted from ChemoText, a data repository containing MeSH annotations pulled from MEDLINE records. These side effects profiles were treated as molecular descriptors enabling a QSAR-like approach to build models that could reliably discriminate different classes of molecules, e.g., binders versus non-binders, and dopamine antagonists versus non-antagonists. Selected models with the best external prediction performances were applied to a library of ca. 1000 chemicals with known side effects profiles in order to predict their potential 5-HT6 binding and/or dopamine antagonism. In each case the virtual screening process was able to identify putatively active compounds that through subsequent literature-based validation were found to be likely or known 5-HT6 binders or dopamine antagonists. These results demonstrate that side effect profiles can be utilized to predict a drug's unknown molecular activity, thus representing a valuable opportunity in repositioning the drug for a new indications. DA - 2015/2// PY - 2015/2// DO - 10.1002/MINF.201400134 VL - 34 IS - 2-3 SP - 160-170 J2 - Mol. Inf. LA - en OP - SN - 1868-1743 UR - http://dx.doi.org/10.1002/MINF.201400134 DB - Crossref KW - Side effects KW - Machine learning KW - QSAR KW - Drug repurposing ER - TY - JOUR TI - Strain-specific induction of endometrial periglandular fibrosis in mice exposed during adulthood to the endocrine disrupting chemical bisphenol A AU - Kendziorski, Jessica A. AU - Belcher, Scott M. T2 - Reproductive Toxicology AB - The aim of this study was to compare effects of bisphenol A (BPA) on collagen accumulation in uteri of two mouse strains. Adult C57Bl/6N and CD-1 mice were exposed to dietary BPA (0.004-40mg/kg/day) or 17α-ethinyl estradiol (0.00002-0.001mg/kg/day) as effect control. An equine endometrosis-like phenotype with increased gland nesting and periglandular collagen accumulation was characteristic of unexposed C57Bl/6N, but not CD-1, endometrium. BPA non-monotonically increased gland nest density and periglandular collagen accumulation in both strains. Increased collagen I and III expression, decreased matrix metalloproteinase 2 (MMP2) and MMP14 expression, and increased immune response were associated with the endometrosis phenotype in the C57Bl/6N strain and the 30ppm BPA CD-1 group. The association between the pro-collagen shift in increased collagen expression and decreased MMP2 expression and activity implies that strain differences and BPA exposure alter regulation of endometrial remodeling and contribute to increased fibrosis, a component of several human uterine diseases. DA - 2015/12// PY - 2015/12// DO - 10.1016/J.REPROTOX.2015.08.001 VL - 58 SP - 119-130 J2 - Reproductive Toxicology LA - en OP - SN - 0890-6238 UR - http://dx.doi.org/10.1016/J.REPROTOX.2015.08.001 DB - Crossref KW - BPA KW - Endocrine disruptor KW - Uterus KW - Mouse KW - Collagen KW - Dose response KW - Endometrial periglandular fibrosis KW - Equine endometrosis KW - Matrix metalloproteinase KW - Non-monotonic ER - TY - JOUR TI - Phosphoproteome Analysis Links Protein Phosphorylation to Cellular Remodeling and Metabolic Adaptation during Magnaporthe oryzae Appressorium Development AU - Franck, William L. AU - Gokce, Emine AU - Randall, Shan M. AU - Oh, Yeonyee AU - Eyre, Alex AU - Muddiman, David C. AU - Dean, Ralph A. T2 - Journal of Proteome Research AB - The rice pathogen, Magnaporthe oryzae, undergoes a complex developmental process leading to formation of an appressorium prior to plant infection. In an effort to better understand phosphoregulation during appressorium development, a mass spectrometry based phosphoproteomics study was undertaken. A total of 2924 class I phosphosites were identified from 1514 phosphoproteins from mycelia, conidia, germlings, and appressoria of the wild type and a protein kinase A (PKA) mutant. Phosphoregulation during appressorium development was observed for 448 phosphosites on 320 phosphoproteins. In addition, a set of candidate PKA targets was identified encompassing 253 phosphosites on 227 phosphoproteins. Network analysis incorporating regulation from transcriptomic, proteomic, and phosphoproteomic data revealed new insights into the regulation of the metabolism of conidial storage reserves and phospholipids, autophagy, actin dynamics, and cell wall metabolism during appressorium formation. In particular, protein phosphorylation appears to play a central role in the regulation of autophagic recycling and actin dynamics during appressorium formation. Changes in phosphorylation were observed in multiple components of the cell wall integrity pathway providing evidence that this pathway is highly active during appressorium development. Several transcription factors were phosphoregulated during appressorium formation including the bHLH domain transcription factor MGG_05709. Functional analysis of MGG_05709 provided further evidence for the role of protein phosphorylation in regulation of glycerol metabolism and the metabolic reprogramming characteristic of appressorium formation. The data presented here represent a comprehensive investigation of the M. oryzae phosphoproteome and provide key insights on the role of protein phosphorylation during infection-related development. DA - 2015/5/15/ PY - 2015/5/15/ DO - 10.1021/PR501064Q VL - 14 IS - 6 SP - 2408-2424 J2 - J. Proteome Res. LA - en OP - SN - 1535-3893 1535-3907 UR - http://dx.doi.org/10.1021/PR501064Q DB - Crossref KW - Magnaporthe oryzae KW - quantitative phosphoproteomics KW - appressorium formation KW - network analysis KW - transcription factors ER - TY - JOUR TI - Leachate Quality Monitoring from Conventional, Retrofit, and Bio-Reactor Landfill Cells AU - Abichou, Tarek AU - Barlaz, Morton A. AU - Goldsmith, Doug AU - Green, Roger AU - Hater, Gary T2 - Journal of Hazardous, Toxic, and Radioactive Waste AB - The recirculation of leachate is a common strategy to accelerate the decomposition of municipal solid waste in landfills. In this study, leachates from a conventional landfill cell without supplemental liquid addition (Control cell), a new landfill area that had a piping network installed as waste was being placed (As-Built cell), and a conventional landfill that was modified to allow for the recirculation of liquids (Retrofit cell) were monitored at the outer loop landfill bioreactor (OLLB) in Louisville, Kentucky. In general, leachates from the Retrofit cells were statistically different from leachates from the As-Built and Control cells. This is likely because the waste in Retrofit cells was about 6 years old when liquids were first introduced and the waste had already reached a more mature state prior to supplemental liquids addition. Based on time series data, the Retrofit cells, which received nitrified leachate, did not show signs of accelerated waste decomposition based on the leachate chemistry. In contrast, there were significant differences in parameters affected by waste biodegradation [temperature, pH, biological oxygen demand (BOD), chemical oxygen demand (COD), volatile organic acid (VOA), total organic carbon (TOC)] between the As-Built and Control cells, suggesting that the introduction of liquids accelerated waste decomposition in the As-Built cells. Trends were generally similar in the As-Built cells compared to the Control cells, even though concentrations of some parameters were higher in the As-Built cells. The elevated temperature in the As-Built cells suggests more active decomposition. DA - 2015/10// PY - 2015/10// DO - 10.1061/(asce)hz.2153-5515.0000288 VL - 19 IS - 4 SP - 04015009 J2 - J. Hazard. Toxic Radioact. Waste LA - en OP - SN - 2153-5493 2153-5515 UR - http://dx.doi.org/10.1061/(asce)hz.2153-5515.0000288 DB - Crossref ER - TY - JOUR TI - A framework for incorporating ecological releases in single reservoir operation AU - Wang, Hui AU - Brill, Earl D. AU - Ranjithan, Ranji S. AU - Sankarasubramanian, A. T2 - Advances in Water Resources AB - Most reservoir operation practices consider downstream environmental flow as a constraint to meet a minimum release. The resulting flow regime may not necessarily provide downstream aquatic conditions to support healthy ecosystems. These effects can be quantified in terms of changes in values of parameters that represent the flow regimes. Numerous studies have focused on determining the ecological response to hydrological alteration caused by reservoir operation. To mitigate hydrological alteration and restore the natural flow regime as much as possible, a reservoir operation framework is proposed to explicitly incorporate ecological flow requirements. A general optimization-based decision model is presented to consider simultaneously the multiple anthropogenic uses of the reservoir and desirable ecological releases represented by parameters that capture the flow regime. Multiple uses of the reservoir, including water supply, hydropower generation, etc., are modeled as a mixed integer programming problem. Hydropower generation, which is represented by a nonlinear function that usually depends on head and water flow, is linearized using a two-dimensional function. Investigations using a reservoir in Virginia, located in the southeastern United States, demonstrate that compared to standard releases based on current operation practice, releases simulated using this framework perform better in mimicking pre-development flows. The tradeoff between anthropogenic use and ecological releases is investigated. The framework is first demonstrated for instances with perfect stream flow information. To examine the flexibility of this framework in reservoir release management, monthly flow forecasts and disaggregated daily flow conditions are incorporated. Retrospective monthly flow forecasts are obtained through regression models that use gridded precipitation forecasts and gridded soil moisture estimates as predictors. A nonparametric method is chosen to disaggregate monthly flow forecasts to daily flow conditions. Compared with daily flow climatology, forecasted monthly and daily flow better preserves flow variability and result in lower changes of flow parameters under the proposed framework. DA - 2015/4// PY - 2015/4// DO - 10.1016/j.advwatres.2015.01.006 VL - 78 SP - 9-21 J2 - Advances in Water Resources LA - en OP - SN - 0309-1708 UR - http://dx.doi.org/10.1016/j.advwatres.2015.01.006 DB - Crossref KW - Ecological flow requirements KW - Natural flow regime KW - Sustainable reservoir operation KW - Mixed integer linear programming ER - TY - JOUR TI - Role of multimodel combination and data assimilation in improving streamflow prediction over multiple time scales AU - Li, Weihua AU - Sankarasubramanian, A. AU - Ranjithan, R. S. AU - Sinha, Tushar T2 - Stochastic Environmental Research and Risk Assessment DA - 2015/9/24/ PY - 2015/9/24/ DO - 10.1007/s00477-015-1158-6 VL - 30 IS - 8 SP - 2255-2269 J2 - Stoch Environ Res Risk Assess LA - en OP - SN - 1436-3240 1436-3259 UR - http://dx.doi.org/10.1007/s00477-015-1158-6 DB - Crossref ER - TY - JOUR TI - Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma AU - Igartua, Catherine AU - Myers, Rachel A. AU - Mathias, Rasika A. AU - Pino-Yanes, Maria AU - Eng, Celeste AU - Graves, Penelope E. AU - Levin, Albert M. AU - Del-Rio-Navarro, Blanca E. AU - Jackson, Daniel J. AU - Livne, Oren E. AU - Rafaels, Nicholas AU - Edlund, Christopher K. AU - Yang, James J. AU - Huntsman, Scott AU - Salam, Muhammad T. AU - Romieu, Isabelle AU - Mourad, Raphael AU - Gern, James E. AU - Lemanske, Robert F. AU - Wyss, Annah AU - Hoppin, Jane A. AU - Barnes, Kathleen C. AU - Burchard, Esteban G. AU - Gauderman, W. James AU - Martinez, Fernando D. AU - Raby, Benjamin A. AU - Weiss, Scott T. AU - Williams, L. Keoki AU - London, Stephanie J. AU - Gilliland, Frank D. AU - Nicolae, Dan L. AU - Ober, Carole T2 - Nature Communications AB - Abstract Common variants at many loci have been robustly associated with asthma but explain little of the overall genetic risk. Here we investigate the role of rare (<1%) and low-frequency (1–5%) variants using the Illumina HumanExome BeadChip array in 4,794 asthma cases, 4,707 non-asthmatic controls and 590 case–parent trios representing European Americans, African Americans/African Caribbeans and Latinos. Our study reveals one low-frequency missense mutation in the GRASP gene that is associated with asthma in the Latino sample ( P =4.31 × 10 −6 ; OR=1.25; MAF=1.21%) and two genes harbouring functional variants that are associated with asthma in a gene-based analysis: GSDMB at the 17q12–21 asthma locus in the Latino and combined samples ( P =7.81 × 10 −8 and 4.09 × 10 −8 , respectively) and MTHFR in the African ancestry sample ( P =1.72 × 10 −6 ). Our results suggest that associations with rare and low-frequency variants are ethnic specific and not likely to explain a significant proportion of the ‘missing heritability’ of asthma. DA - 2015/1/16/ PY - 2015/1/16/ DO - 10.1038/ncomms6965 VL - 6 IS - 1 J2 - Nat Commun LA - en OP - SN - 2041-1723 UR - http://dx.doi.org/10.1038/ncomms6965 DB - Crossref ER - TY - JOUR TI - Associations of Ozone and PM2.5 Concentrations With Parkinsonʼs Disease Among Participants in the Agricultural Health Study AU - Kirrane, Ellen F. AU - Bowman, Christal AU - Davis, J. Allen AU - Hoppin, Jane A. AU - Blair, Aaron AU - Chen, Honglei AU - Patel, Molini M. AU - Sandler, Dale P. AU - Tanner, Caroline M. AU - Vinikoor-Imler, Lisa AU - Ward, Mary H. AU - Luben, Thomas J. AU - Kamel, Freya T2 - Journal of Occupational and Environmental Medicine AB - Objective: This study describes associations of ozone and fine particulate matter with Parkinson's disease observed among farmers in North Carolina and Iowa. Methods: We used logistic regression to determine the associations of these pollutants with self-reported, doctor-diagnosed Parkinson's disease. Daily predicted pollutant concentrations were used to derive surrogates of long-term exposure and link them to study participants' geocoded addresses. Results: We observed positive associations of Parkinson's disease with ozone (odds ratio = 1.39; 95% CI: 0.98 to 1.98) and fine particulate matter (odds ratio = 1.34; 95% CI: 0.93 to 1.93) in North Carolina but not in Iowa. Conclusions: The plausibility of an effect of ambient concentrations of these pollutants on Parkinson's disease risk is supported by experimental data demonstrating damage to dopaminergic neurons at relevant concentrations. Additional studies are needed to address uncertainties related to confounding and to examine temporal aspects of the associations we observed. DA - 2015/5// PY - 2015/5// DO - 10.1097/JOM.0000000000000451 VL - 57 IS - 5 SP - 509-517 J2 - Journal of Occupational and Environmental Medicine LA - en OP - SN - 1076-2752 UR - http://dx.doi.org/10.1097/JOM.0000000000000451 DB - Crossref ER - TY - JOUR TI - IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans AU - Pearce, Neil AU - Blair, Aaron AU - Vineis, Paolo AU - Ahrens, Wolfgang AU - Andersen, Aage AU - Anto, Josep M. AU - Armstrong, Bruce K. AU - Baccarelli, Andrea A. AU - Beland, Frederick A. AU - Berrington, Amy AU - Bertazzi, Pier Alberto AU - Birnbaum, Linda S. AU - Brownson, Ross C. AU - Bucher, John R. AU - Cantor, Kenneth P. AU - Cardis, Elisabeth AU - Cherrie, John W. AU - Christiani, David C. AU - Cocco, Pierluigi AU - Coggon, David AU - Comba, Pietro AU - Demers, Paul A. AU - Dement, John M. AU - Douwes, Jeroen AU - Eisen, Ellen A. AU - Engel, Lawrence S. AU - Fenske, Richard A. AU - Fleming, Lora E. AU - Fletcher, Tony AU - Fontham, Elizabeth AU - Forastiere, Francesco AU - Frentzel-Beyme, Rainer AU - Fritschi, Lin AU - Gerin, Michel AU - Goldberg, Marcel AU - Grandjean, Philippe AU - Grimsrud, Tom K. AU - Gustavsson, Per AU - Haines, Andy AU - Hartge, Patricia AU - Hansen, Johnni AU - Hauptmann, Michael AU - Heederik, Dick AU - Hemminki, Kari AU - Hemon, Denis AU - Hertz-Picciotto, Irva AU - Hoppin, Jane A. AU - Huff, James AU - Jarvholm, Bengt AU - Kang, Daehee AU - Karagas, Margaret R. AU - Kjaerheim, Kristina AU - Kjuus, Helge AU - Kogevinas, Manolis AU - Kriebel, David AU - Kristensen, Petter AU - Kromhout, Hans AU - Laden, Francine AU - Lebailly, Pierre AU - LeMasters, Grace AU - Lubin, Jay H. AU - Lynch, Charles F. AU - Lynge, Elsebeth AU - ‘t Mannetje, Andrea AU - McMichael, Anthony J. AU - McLaughlin, John R. AU - Marrett, Loraine AU - Martuzzi, Marco AU - Merchant, James A. AU - Merler, Enzo AU - Merletti, Franco AU - Miller, Anthony AU - Mirer, Franklin E. AU - Monson, Richard AU - Nordby, Karl-Cristian AU - Olshan, Andrew F. AU - Parent, Marie-Elise AU - Perera, Frederica P. AU - Perry, Melissa J. AU - Pesatori, Angela Cecilia AU - Pirastu, Roberta AU - Porta, Miquel AU - Pukkala, Eero AU - Rice, Carol AU - Richardson, David B. AU - Ritter, Leonard AU - Ritz, Beate AU - Ronckers, Cecile M. AU - Rushton, Lesley AU - Rusiecki, Jennifer A. AU - Rusyn, Ivan AU - Samet, Jonathan M. AU - Sandler, Dale P. AU - de Sanjose, Silvia AU - Schernhammer, Eva AU - Costantini, Adele Seniori AU - Seixas, Noah AU - Shy, Carl AU - Siemiatycki, Jack AU - Silverman, Debra T. AU - Simonato, Lorenzo AU - Smith, Allan H. AU - Smith, Martyn T. AU - Spinelli, John J. AU - Spitz, Margaret R. AU - Stallones, Lorann AU - Stayner, Leslie T. AU - Steenland, Kyle AU - Stenzel, Mark AU - Stewart, Bernard W. AU - Stewart, Patricia A. AU - Symanski, Elaine AU - Terracini, Benedetto AU - Tolbert, Paige E. AU - Vainio, Harri AU - Vena, John AU - Vermeulen, Roel AU - Victora, Cesar G. AU - Ward, Elizabeth M. AU - Weinberg, Clarice R. AU - Weisenburger, Dennis AU - Wesseling, Catharina AU - Weiderpass, Elisabete AU - Zahm, Shelia Hoar T2 - Environmental Health Perspectives AB - Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed.We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health. DA - 2015/6// PY - 2015/6// DO - 10.1289/ehp.1409149 VL - 123 IS - 6 SP - 507-514 J2 - Environmental Health Perspectives LA - en OP - SN - 0091-6765 1552-9924 UR - http://dx.doi.org/10.1289/ehp.1409149 DB - Crossref ER - TY - JOUR TI - Enhancing bottom-up and top-down proteomic measurements with ion mobility separations AU - Baker, E.S. AU - Burnum-Johnson, K.E. AU - Ibrahim, Y.M. AU - Orton, D.J. AU - Monroe, M.E. AU - Kelly, R.T. AU - Moore, R.J. AU - Zhang, X. AU - Théberge, R. AU - Costello, C.E. AU - Smith, R.D. T2 - Proteomics AB - Proteomic measurements with greater throughput, sensitivity, and structural information are essential for improving both in-depth characterization of complex mixtures and targeted studies. While LC separation coupled with MS (LC-MS) measurements have provided information on thousands of proteins in different sample types, the introduction of a separation stage that provides further component resolution and rapid structural information has many benefits in proteomic analyses. Technical advances in ion transmission and data acquisition have made ion mobility separations an opportune technology to be easily and effectively incorporated into LC-MS proteomic measurements for enhancing their information content. Herein, we report on applications illustrating increased sensitivity, throughput, and structural information by utilizing IMS-MS and LC-IMS-MS measurements for both bottom-up and top-down proteomics measurements. DA - 2015/// PY - 2015/// DO - 10.1002/pmic.201500048 VL - 15 IS - 16 SP - 2766-2776 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84938738882&partnerID=MN8TOARS KW - Ion mobility separations KW - Ion mobility spectrometry KW - Mass spectrometry KW - Proteomics ER - TY - JOUR TI - Enhancing biological analyses with three dimensional field asymmetric ion mobility, low field drift tube ion mobility and mass spectrometry (μFAIMS/IMS-MS) separations AU - Zhang, X. AU - Ibrahim, Y.M. AU - Chen, T.-C. AU - Kyle, J.E. AU - Norheim, R.V. AU - Monroe, M.E. AU - Smith, R.D. AU - Baker, E.S. T2 - Analyst AB - Novel μFAIMS/IMS-MS three dimensional separations were optimized to enhance separation power and selectivity in biological analyses. DA - 2015/// PY - 2015/// DO - 10.1039/c5an00897b VL - 140 IS - 20 SP - 6955-6963 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84942612537&partnerID=MN8TOARS ER - TY - JOUR TI - Development of a new ion mobility (quadrupole) time-of-flight mass spectrometer AU - Ibrahim, Y.M. AU - Baker, E.S. AU - Danielson, W.F. AU - Norheim, R.V. AU - Prior, D.C. AU - Anderson, G.A. AU - Belov, M.E. AU - Smith, R.D. T2 - International Journal of Mass Spectrometry AB - A new ion mobility spectrometer (IMS) platform was developed to improve upon the sensitivity and reproducibility of our previous platforms, and further enhance IMS-MS utility for broad 'pan-omics' measurements. The new platform incorporated an improved electrospray ionization source and interface for enhanced sensitivity, and providing the basis for further benefits based upon implementation of multiplexed IMS. The ion optics included electrodynamic ion funnels at both the entrance and exit of the IMS, an ion funnel trap for ion injection, and a design in which nearly all ion optics (e.g. drift rings, ion funnels) were fabricated using printed circuit board technology. The IMS resolving power achieved was ~73 for singly-charged ions, very close to the predicted diffusion-limited resolving power (~75). The platform's performance evaluation (e.g. for proteomics measurements) include LC-IMS-TOF MS datasets for 30 technical replicates for a trypsin digested human serum, and included platform performance in each dimension (LC, IMS and MS) separately. DA - 2015/// PY - 2015/// DO - 10.1016/j.ijms.2014.07.034 VL - 377 IS - 1 SP - 655-662 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85027921067&partnerID=MN8TOARS ER - TY - JOUR TI - Muscle Segment Homeobox Genes Direct Embryonic Diapause by Limiting Inflammation in the Uterus AU - Cha, Jeeyeon AU - Burnum-Johnson, Kristin E. AU - Bartos, Amanda AU - Li, Yingju AU - Baker, Erin S. AU - Tilton, Susan C. AU - Webb-Robertson, Bobbie-Jo M. AU - Piehowski, Paul D. AU - Monroe, Matthew E. AU - Jegga, Anil G. AU - Murata, Shigeo AU - Hirota, Yasushi AU - Dey, Sudhansu K. T2 - Journal of Biological Chemistry AB - Embryonic diapause is a reproductive strategy widespread in the animal kingdom. This phenomenon is defined by a temporary arrest in blastocyst growth and metabolic activity within a quiescent uterus without implantation until the environmental and maternal milieu become favorable for pregnancy to progress. We found that uterine Msx expression persists during diapause across species; their inactivation in the mouse uterus results in termination of diapause with the development of implantation-like responses (“pseudoimplantation”) that ultimately succumbed to resorption. To understand the cause of this failure, we compared proteome profiles between floxed and Msx-deleted uteri. In deleted uteri, several functional networks, including transcription/translation, ubiquitin-proteasome, inflammation, and endoplasmic reticulum stress, were dysregulated. Computational modeling predicted intersection of these pathways on an enhanced inflammatory signature. Further studies showed that this signature was reflected in increased phosphorylated IκB levels and nuclear NFκB in deleted uteri. This was associated with enhanced proteasome activity and endoplasmic reticulum stress. Interestingly, treatment with anti-inflammatory glucocorticoid (dexamethasone) reduced the inflammatory signature with improvement of the diapause phenotype. These findings highlight an unexpected role of uterine Msx in limiting aberrant inflammatory responses to maintain embryonic diapause. Embryonic diapause is a reproductive strategy widespread in the animal kingdom. This phenomenon is defined by a temporary arrest in blastocyst growth and metabolic activity within a quiescent uterus without implantation until the environmental and maternal milieu become favorable for pregnancy to progress. We found that uterine Msx expression persists during diapause across species; their inactivation in the mouse uterus results in termination of diapause with the development of implantation-like responses (“pseudoimplantation”) that ultimately succumbed to resorption. To understand the cause of this failure, we compared proteome profiles between floxed and Msx-deleted uteri. In deleted uteri, several functional networks, including transcription/translation, ubiquitin-proteasome, inflammation, and endoplasmic reticulum stress, were dysregulated. Computational modeling predicted intersection of these pathways on an enhanced inflammatory signature. Further studies showed that this signature was reflected in increased phosphorylated IκB levels and nuclear NFκB in deleted uteri. This was associated with enhanced proteasome activity and endoplasmic reticulum stress. Interestingly, treatment with anti-inflammatory glucocorticoid (dexamethasone) reduced the inflammatory signature with improvement of the diapause phenotype. These findings highlight an unexpected role of uterine Msx in limiting aberrant inflammatory responses to maintain embryonic diapause. DA - 2015/// PY - 2015/// DO - 10.1074/jbc.M115.655001 VL - 290 IS - 24 SP - 15337-15349 UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000356177300044&KeyUID=WOS:000356177300044 ER - TY - BOOK TI - Mass spectrometry for biomarker development AU - Wu, C. AU - Liu, T. AU - Baker, E.S. AU - Rodland, K.D. AU - Smith, R.D. AB - Biomarkers potentially play a crucial role in early disease diagnosis, prognosis, and targeted therapy. In the past decade, mass spectrometry-based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g., shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy across the different stages of biomarker development, with a particular emphasis on blood-based biomarker development. DA - 2015/// PY - 2015/// DO - 10.1007/978-94-007-7696-8_21 VL - 1-2 SE - 17-48 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84958696691&partnerID=MN8TOARS ER - TY - JOUR TI - Ion manipulations in structures for lossless ion manipulations (SLIM): computational evaluation of a 90° turn and a switch. AU - Garimella, Sandilya V B AU - Ibrahim, Yehia M AU - Webb, Ian K AU - Ipsen, Andreas B AU - Chen, Tsung-Chi AU - Tolmachev, Aleksey V AU - Baker, Erin S AU - Anderson, Gordon A AU - Smith, Richard D T2 - The Analyst AB - The process of redirecting ions through 90° turns and 'tee' switches utilizing Structures for Lossless Ion Manipulations (SLIM) was evaluated at 4 Torr pressure using SIMION simulations and theoretical methods. The nature of pseudo-potential in SLIM-tee structures has also been explored. Simulations show that 100% transmission efficiency in SLIM devices can be achieved with guard electrode voltages lower than ∼10 V. The ion plume width in these conditions is ∼1.6 mm while at lower guard voltages lead to greater plume widths. Theoretical calculations show marginal loss of ion mobility resolving power (<5%) during ion turn due to the finite plume widths (i.e. race track effect). More robust SLIM designs that reduce the race track effect while maximizing ion transmission are also reported. In addition to static turns, the dynamic switching of ions into orthogonal channels was also evaluated both using SIMION ion trajectory simulations and experimentally. Simulations and theoretical calculations were in close agreement with experimental results and were used to develop more refined SLIM designs. DA - 2015/// PY - 2015/// DO - 10.1039/c5an00844a VL - 140 IS - 20 SP - 6845-52 UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=MEDLINE&KeyUT=MEDLINE:26289106&KeyUID=MEDLINE:26289106 ER - TY - JOUR TI - Ion Trapping, Storage, and Ejection in Structures for Lossless Ion Manipulations AU - Zhang, X. AU - Garimella, S.V.B. AU - Prost, S.A. AU - Webb, I.K. AU - Chen, T.-C. AU - Tang, K. AU - Tolmachev, A.V. AU - Norheim, R.V. AU - Baker, E.S. AU - Anderson, G.A. AU - Ibrahim, Y.M. AU - Smith, R.D. T2 - Analytical Chemistry AB - A new Structures for Lossless Ion Manipulations (SLIM) module, having electrode arrays patterned on a pair of parallel printed circuit boards (PCB), was constructed and utilized to investigate capabilities for ion trapping at a pressure of 4 Torr. Positive ions were confined by application of RF voltages to a series of inner rung electrodes with alternating phase on adjacent electrodes, in conjunction with positive DC potentials on surrounding guard electrodes on each PCB. An axial DC field was also introduced by stepwise varying the DC potentials applied to the inner rung electrodes to control the ion transport and accumulation inside the ion trapping region. We show that ions can be trapped and accumulated with up to 100% efficiency, stored for at least 5 h with no significant losses, and then could be rapidly ejected from the SLIM trap. The present results provide a foundation for the development of much more complex SLIM devices that facilitate extended ion manipulations. DA - 2015/// PY - 2015/// DO - 10.1021/acs.analchem.5b00214 VL - 87 IS - 12 SP - 6010-6016 UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000356755100023&KeyUID=WOS:000356755100023 ER - TY - JOUR TI - Pesticide use and risk of end-stage renal disease among licensed pesticide applicators in the Agricultural Health Study AU - Lebov, Jill F AU - Engel, Lawrence S AU - Richardson, David AU - Hogan, Susan L AU - Hoppin, Jane A AU - Sandler, Dale P T2 - Occupational and Environmental Medicine AB - Experimental studies suggest a relationship between pesticide exposure and renal impairment, but epidemiological evidence is limited. We evaluated the association between exposure to 39 specific pesticides and end-stage renal disease (ESRD) incidence in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina.Via linkage to the US Renal Data System, we identified 320 ESRD cases diagnosed between enrolment (1993-1997) and December 2011 among 55 580 male licensed pesticide applicators. Participants provided information on use of pesticides via self-administered questionnaires. Lifetime pesticide use was defined as the product of duration and frequency of use and then modified by an intensity factor to account for differences in pesticide application practices. Cox proportional hazards models, adjusted for age and state, were used to estimate associations between ESRD and: (1) ordinal categories of intensity-weighted lifetime use of 39 pesticides, (2) poisoning and high-level pesticide exposures and (3) pesticide exposure resulting in a medical visit or hospitalisation.Positive exposure-response trends were observed for the herbicides alachlor, atrazine, metolachlor, paraquat, and pendimethalin, and the insecticide permethrin. More than one medical visit due to pesticide use (HR=2.13; 95% CI 1.17 to 3.89) and hospitalisation due to pesticide use (HR=3.05; 95% CI 1.67 to 5.58) were significantly associated with ESRD.Our findings support an association between ESRD and chronic exposure to specific pesticides, and suggest pesticide exposures resulting in medical visits may increase the risk of ESRD.Clinicaltrials.gov NCT00352924. DA - 2015/7/15/ PY - 2015/7/15/ DO - 10.1136/oemed-2014-102615 VL - 73 IS - 1 SP - 3-12 J2 - Occup Environ Med LA - en OP - SN - 1351-0711 1470-7926 UR - http://dx.doi.org/10.1136/oemed-2014-102615 DB - Crossref ER - TY - CONF TI - Integrating literature-based curated data to predict mechanisms of toxicity AU - Mattingly, C.J. T2 - OpenTox USA 2015 C2 - 2015/// CY - Baltimore, MD DA - 2015/// PY - 2015/2/10/ ER - TY - JOUR TI - Impact of low-dose oral exposure to bisphenol A (BPA) on Juvenile and adult rat exploratory and anxiety behavior: A CLARITY-BPA Consortium Study AU - Rebuli, M.E. AU - Camacho, L. AU - Adonay, M.E. AU - Reif, D.M. AU - Aylor, D.L. AU - Patisaul, H.B. T2 - Toxicological Sciences AB - Bisphenol A (BPA) is a high volume production chemical and has been identified as an endocrine disruptor, prompting concern that developmental exposure could impact brain development and behavior. Rodent and human studies suggest that early life BPA exposure may result in an anxious, hyperactive phenotype but results are conflicting and data from studies using multiple doses below the no-observed-adverse-effect level are limited. To address this, the present studies were conducted as part of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) program. The impact of perinatal BPA exposure (2.5, 25, or 2500 µg/kg body weight (bw)/day) on behaviors related to anxiety and exploratory activity was assessed in juvenile (prepubertal) and adult NCTR Sprague-Dawley rats of both sexes. Ethinyl estradiol (0.5 µg/kg bw/day) was used as a reference estrogen. Exposure spanned gestation and lactation with dams gavaged from gestational day 6 until birth and then the offspring gavaged directly through weaning (n = 12/sex/group). Behavioral assessments included open field, elevated plus maze, and zero maze. Anticipated sex differences in behavior were statistically identified or suggested in most cases. No consistent effects of BPA were observed for any endpoint, in either sex, at either age compared to vehicle controls; however, significant differences between BPA-exposed and ethinyl estradiol-exposed groups were identified for some endpoints. Limitations of this study are discussed and include suboptimal statistical power and low concordance across behavioral tasks. These data do not indicate BPA-related effects on anxiety or exploratory activity in these developmentally exposed rats. DA - 2015/// PY - 2015/// DO - 10.1093/toxsci/kfv163 VL - 148 IS - 2 SP - 341-354 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84952932385&partnerID=MN8TOARS KW - bisphenol A KW - CLARITY KW - behavior KW - anxiety KW - exploratory activity KW - endocrine disruption KW - EDC KW - sexually dimorphic KW - brain KW - BPA KW - plastic ER - TY - JOUR TI - Food for Thought...: Toxicity testing in the 21st century beyond environmental chemicals AU - Rovida, C. AU - Asakura, S. AU - Daneshian, M. AU - Hofman-Huether, H. AU - Leist, M. AU - Meunier, L. AU - Reif, D. AU - Rossi, A. AU - Schmutz, M. AU - Valentin, J.-P. AU - Zurlo, J. AU - Hartung, T. T2 - Altex AB - After the publication of the report titled Toxicity Testing in the 21st Century – A Vision and a Strategy, many initiatives started to foster a major paradigm shift for toxicity testing – from apical endpoints in animal-based tests to mechanistic endpoints through delineation of pathways of toxicity (PoT) in human cell based systems. The US EPA has funded an important project to develop new high throughput technologies based on human cell based in vitro technologies. These methods are currently being incorporated into the chemical risk assessment process. In the pharmaceutical industry, the efficacy and toxicity of new drugs are evaluated during preclinical investigations that include drug metabolism, pharmacokinetics, pharmacodynamics and safety toxicology studies. The results of these studies are analyzed and extrapolated to predict efficacy and potential adverse effects in humans. However, due to the high failure rate of drugs during the clinical phases, a new approach for a more predictive assessment of drugs both in terms of efficacy and adverse effects is getting urgent. The food industry faces the challenge of assessing novel foods and food ingredients for the general population, while using animal safety testing for extrapolation purposes is often of limited relevance. The question is whether the latest paradigm shift proposed by the Tox21c report for chemicals may provide a useful tool to improve the risk assessment approach also for drugs and food ingredients. DA - 2015/// PY - 2015/// DO - 10.14573/altex.1506201 VL - 32 IS - 3 SP - 171-181 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84938603406&partnerID=MN8TOARS KW - food ingredients KW - drugs KW - Tox21c KW - safety assessment ER - TY - BOOK TI - Embracing complexity: Searching for gene-gene and gene environment interactions in genetic epidemiology AU - Motsinger, A.A. AU - Reif, D.M. DA - 2015/// PY - 2015/// DO - 10.1201/b18597 SE - 19-58 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85053966420&partnerID=MN8TOARS ER - TY - JOUR TI - Data-driven asthma endotypes defined from blood biomarker and gene expression data AU - George, B.J. AU - Reif, D.M. AU - Gallagher, J.E. AU - Williams-DeVane, C.R. AU - Heidenfelder, B.L. AU - Hudgens, E.E. AU - Jones, W. AU - Neas, L. AU - Cohen Hubal, E.A. AU - Edwards, S.W. T2 - PLoS ONE AB - The diagnosis and treatment of childhood asthma is complicated by its mechanistically distinct subtypes (endotypes) driven by genetic susceptibility and modulating environmental factors. Clinical biomarkers and blood gene expression were collected from a stratified, cross-sectional study of asthmatic and non-asthmatic children from Detroit, MI. This study describes four distinct asthma endotypes identified via a purely data-driven method. Our method was specifically designed to integrate blood gene expression and clinical biomarkers in a way that provides new mechanistic insights regarding the different asthma endotypes. For example, we describe metabolic syndrome-induced systemic inflammation as an associated factor in three of the four asthma endotypes. Context provided by the clinical biomarker data was essential in interpreting gene expression patterns and identifying putative endotypes, which emphasizes the importance of integrated approaches when studying complex disease etiologies. These synthesized patterns of gene expression and clinical markers from our research may lead to development of novel serum-based biomarker panels. DA - 2015/// PY - 2015/// DO - 10.1371/journal.pone.0117445 VL - 10 IS - 2 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84922569392&partnerID=MN8TOARS ER - TY - BOOK TI - Computational Methods Used in Systems Biology AU - Meisner, M. AU - Reif, D.M. AB - The overarching theme of systems biology is that of complex interactions between multiscale systems, so it follows that computational methods used in systems biology aim to integrate data and originate from an interdisciplinary slate of scientific fields. To deal with “omic” data generation discussed in previous chapters, suitable analysis methods for systems biology must account for measurements made across scales of time, space, and biological organization. Importantly, analysis methods must first account for the specifics (and peculiarities) of individual technology platforms. For the more established platforms, such as chip hybridization and sequencing techniques, progress in computational methods research has resulted in a trend toward standardization, where coalescence of statistical methods into powerful software packages handle early stages of analysis in a generally accepted manner. For emerging platforms, computational methods remain diffuse, although popular approaches share many statistical similarities with more mature methods. Once individual data components have been analyzed, integration into a systems framework can begin. DA - 2015/// PY - 2015/// DO - 10.1016/B978-0-12-801564-3.00005-5 SE - 85-115 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84940026164&partnerID=MN8TOARS ER - TY - JOUR TI - Comparison of toxicity values across zebrafish early life stages and mammalian studies: Implications for chemical testing AU - Ducharme, N.A. AU - Reif, D.M. AU - Gustafsson, J.-A. AU - Bondesson, M. T2 - Reproductive Toxicology AB - With the high cost and slow pace of toxicity testing in mammals, the vertebrate zebrafish has become a tractable model organism for high throughput toxicity testing. We present here a meta-analysis of 600 chemicals tested for toxicity in zebrafish embryos and larvae. Nineteen aggregated and 57 individual toxicity endpoints were recorded from published studies yielding 2695 unique data points. These data points were compared to lethality and reproductive toxicology endpoints analyzed in rodents and rabbits and to exposure values for humans. We show that although many zebrafish endpoints did not correlate to rodent or rabbit acute toxicity data, zebrafish could be used to accurately predict relative acute toxicity through the rat inhalation, rabbit dermal, and rat oral exposure routes. Ranking of the chemicals based on toxicity and teratogenicity in zebrafish, as well as human exposure levels, revealed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene, and chlorpyrifos ranked in the top nine of all chemicals for these three categories, and as such should be considered high priority chemicals for testing in higher vertebrates. DA - 2015/// PY - 2015/// DO - 10.1016/j.reprotox.2014.09.005 VL - 55 SP - 3-10 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84939415843&partnerID=MN8TOARS KW - Meta-analysis KW - Toxicity KW - Teratogen KW - Zebrafish KW - Human exposure ER - TY - JOUR TI - Carcinogenicity of lindane, DDT, and 2,4-dichlorophenoxyacetic acid. AU - Loomis, D AU - Guyton, K AU - Grosse, Y AU - El, Ghissasi F AU - Bouvard, V AU - Benbrahim-Tallaa, L AU - Guha, N AU - Mattock, H AU - Straif, K AU - France T2 - The Lancet. Oncology AB - Lancet Oncology, The - In Press.Proof corrected by the author Available online since mercredi 24 juin 2015 DA - 2015/8// PY - 2015/8// DO - 10.1016/s1470-2045(15)00081-9 VL - 8 UR - http://europepmc.org/abstract/med/26111929 ER - TY - JOUR TI - Part 2: Sensitivity comparisons of the mayfly Centroptilum triangulifer to Ceriodaphnia dubia and Daphnia magna using standard reference toxicants; NaCl, KCl and CuSO4 AU - Struewing, Katherine A. AU - Lazorchak, James M. AU - Weaver, Paul C. AU - Johnson, Brent R. AU - Funk, David H. AU - Buchwalter, David B. T2 - CHEMOSPHERE AB - Criteria for establishing water quality standards that are protective for 95% of the native species are generally based upon laboratory toxicity tests. These tests utilize common model organisms that have established test methods. However, for invertebrates these species represent mostly the zooplankton community and are not inclusive of all taxa. In order to examine a potential under-representation in emerging aquatic invertebrates the US Environmental Protection Agency has cultured a parthenogenetic mayfly, Centroptilum triangulifer (Ephemeroptera: Baetidae). This study established a 48 h acute and a 14-day short-term chronic testing procedure for C. triangulifer and compared its sensitivity to two model invertebrates, Ceriodaphnia dubia and Daphnia magna. Toxicity tests were conducted to determine mortality and growth effects using standard reference toxicants: NaCl, KCl and CuSO4. In 48-h acute tests, the average LC50 for the mayfly was 659 mg L−1 NaCl, 1957 mg L−1 KCl, and 11 μg L−1 CuSO4. IC25 values, using dry weight as the endpoint, were 228 mg L−1 NaCl, 356 mg L−1 KCl and 5 μg L−1 CuSO4. C. triangulifer was the most sensitive species in NaCl acute and chronic growth tests. At KCl concentrations tested, C. triangulifer was less sensitive for acute tests but was equally or more sensitive than C. dubia and D. magna for growth measurements. This study determined C. triangulifer has great potential and benefits for use in ecotoxicological studies. DA - 2015/11// PY - 2015/11// DO - 10.1016/j.chemosphere.2014.04.096 VL - 139 SP - 597-603 SN - 1879-1298 KW - Mayfly KW - Comparative toxicity KW - NaCl KW - KCl KW - CuSO4 ER - TY - JOUR TI - Part 1: Laboratory culture of Centroptilum triangulifer (Ephemeroptera: Baetidae) using a defined diet of three diatoms AU - Weaver, Paul C. AU - Lazorchak, James M. AU - Struewing, Katherine A. AU - DeCelles, Susanna J. AU - Funk, David H. AU - Buchwalter, David B. AU - Johnson, Brent R. T2 - CHEMOSPHERE AB - Development of methods for assessing exposure and effects of waterborne toxicants on stream invertebrate species is important to elucidate environmentally relevant information. Current protocols for freshwater invertebrate toxicity testing almost exclusively utilize cladocerans, amphipods or chironomids rather than the more typical aquatic insect taxa found in lotic systems. Centroptilum triangulifer is a parthenogenetic mayfly occurring in depositional habitats of streams and rivers of the Eastern U.S. and Canada. C. triangulifer is an ideal stream insect for toxicity testing under field and laboratory conditions because of its short life cycle, parthenogenetic mode of reproduction, and it represents a group considered sensitive to environmental stressors. In this study, a colony of C. triangulifer was reared using a defined diet of three diatoms, Mayamaea atomus var. permitis, Nitzschia cf. pusilla, and Achnanthidium minutissimum. Percent survival (⩾80%), fecundity measurements (⩾1000 eggs) and pre-egg laying weights were used as indicators of overall colony health and fitness in our laboratory water (Lab-line) and in Moderately Hard Reconstituted Water (MHRW). Lab-line reared C. triangulifer had average survival rate of 92.69% for eleven generations and 82.99% over thirteen generations. MHRW reared C. triangulifer had an average survival rate of 80.65% for four generations and three generations of fecundities greater than 1000 eggs per individual. Pre-egg laying weight and fecundity were highly correlated and a best-fit model equation was derived to estimate egg counts for future generations. Establishment of this culturing protocol provides a more ecologically relevant species for toxicity testing and aids in further stressor identification for stream bioassessments. DA - 2015/11// PY - 2015/11// DO - 10.1016/j.chemosphere.2014.04.092 VL - 139 SP - 589-596 SN - 1879-1298 KW - Benthic macroinvertebrates KW - Water quality criteria KW - Ecotoxicology KW - Parthenogenetic mayfly KW - Culture method KW - Diatoms ER - TY - JOUR TI - Opinions of clinical veterinarians at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections AU - Jacob, Megan E. AU - Hoppin, Jane A. AU - Steers, Nicola AU - Davis, Jennifer L. AU - Davidson, Gigi AU - Hansen, Bernie AU - Lunn, Katharine F. AU - Murphy, K. Marcia AU - Papich, Mark G. T2 - Journal of the American Veterinary Medical Association AB - Abstract Objective —To determine opinions of faculty members with clinical appointments, clinical veterinarians, residents, and interns at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections. Design —Cross-sectional survey. Sample —71 veterinarians. Procedures —An online questionnaire was sent to all veterinarians with clinical service responsibilities at the North Carolina State University veterinary teaching hospital (n = 167). The survey included 23 questions regarding demographic information, educational experiences, current prescribing practices, and personal opinions related to antimicrobial selection, antimicrobial use, restrictions on antimicrobial use, and antimicrobial resistance. Results —Of the 167 veterinarians eligible to participate, 71 (43%) responded. When respondents were asked to rate their level of concern (very concerned = 1; not concerned = 5) about antimicrobial-resistant infections, most (41/70 [59%]) assigned a score of 1, with mean score for all respondents being 1.5. Most survey participants rated their immediate colleagues (mean score, 1.9) as more concerned than other veterinary medical professionals (mean score, 2.3) and their clients (mean score, 3.4). Fifty-nine of 67 (88%) respondents felt that antimicrobials were overprescribed at the hospital, and 32 of 69 (46%) respondents felt uncomfortable prescribing at least one class of antimicrobials (eg, carbapenems or glycopeptides) because of public health concerns. Conclusions and Clinical Relevance —Findings indicated that veterinarians at this teaching hospital were concerned about antimicrobial resistance, thought antimicrobials were overprescribed, and supported restricting use of certain antimicrobial classes in companion animals. Findings may be useful in educating future veterinarians and altering prescribing habits and antimicrobial distribution systems in veterinary hospitals. DA - 2015/10/15/ PY - 2015/10/15/ DO - 10.2460/javma.247.8.938 VL - 247 IS - 8 SP - 938-944 J2 - Journal of the American Veterinary Medical Association LA - en OP - SN - 0003-1488 UR - http://dx.doi.org/10.2460/javma.247.8.938 DB - Crossref ER - TY - JOUR TI - Meeting multiple water quality objectives through treatment using locally generated char: improving organoleptic properties and removing synthetic organic contaminants and disinfection by-products AU - Kearns, Joshua P. AU - Shimabuku, Kyle K. AU - Mahoney, Ryan B. AU - Knappe, Detlef R. U. AU - Summers, R. Scott T2 - JOURNAL OF WATER SANITATION AND HYGIENE FOR DEVELOPMENT AB - A variety of natural and anthropogenic contaminants can compromise the safety and esthetics of surface water collected for drinking and disinfected using chlorine by households in developing communities. While household chlorination is effective against most microbial pathogens, many users find the taste and odor of chlorine unacceptable and revert to drinking untreated water. Moreover, reactions between chlorine and the dissolved organic matter form harmful disinfection by-products (DBPs) such as trihalomethanes (THMs). Char adsorbers have been used to treat drinking water for thousands of years and are still widely used today. Results obtained here demonstrate that locally produced biomass chars (biochars) exhibit removal capacities comparable to those of activated carbon for removal of THMs, synthetic organic chemicals (SOCs) such as warfarin (WFN) (anticoagulant pharmaceutical, rodenticide), and naturally occurring trace organics such as the taste-and-odor compound 2-methylisoborneol (cyanobacterial metabolite). Results show chars can be used effectively to remove objectionable tastes and odors related to chlorine and cyanobacteria, DBPs, and SOCs. The use of char may lead to microbial risk reduction through greater acceptance of chlorine-based disinfection due to improved water esthetics, as well as chemical risk reduction associated with DBP and SOC exposure. DA - 2015/// PY - 2015/// DO - 10.2166/washdev.2015.172 VL - 5 IS - 3 SP - 359-372 SN - 2043-9083 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84940023189&partnerID=MN8TOARS KW - adsorption KW - biochar KW - charcoal KW - chemical water contaminants KW - point-of-use water treatment ER - TY - JOUR TI - Influence of C-Trap Ion Accumulation Time on the Detectability of Analytes in IR-MALDESI MSI AU - Rosen, Elias P. AU - Bokhart, Mark T. AU - Nazari, Milad AU - Muddiman, David C. T2 - ANALYTICAL CHEMISTRY AB - Laser desorption followed by post electrospray ionization requires synchronized timing of the key events (sample desorption/ionization, mass spectrometry analysis, and sample translation) necessary to conduct mass spectrometry imaging (MSI) with adequate analyte sensitivity. In infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MSI analyses, two laser pulses are used for analysis at each volumetric element, or voxel, of a biological sample and ion accumulation in the C-trap exceeding 100 ms is necessary to capture all sample-associated ions using an infrared laser with a 20 Hz repetition rate. When coupled to an Orbitrap-based mass spectrometer like the Q Exactive Plus, this time window for ion accumulation exceeds dynamically controlled trapping of samples with comparable ion flux by Automatic Gain Control (AGC), which cannot be used during MSI analysis. In this work, a next-generation IR-MALDESI source has been designed and constructed that incorporates a mid-infrared OPO laser capable of operating at 100 Hz and allows requisite C-trap inject time during MSI to be reduced to 30 ms. Analyte detectability of the next-generation IR-MALDESI integrated source has been evaluated as a function of laser repetition rate (100-20 Hz) with corresponding C-trap ion accumulation times (30-110 ms) in both untargeted and targeted analysis of biological samples. Reducing the C-trap ion accumulation time resulted in increased ion abundance by up to 3 orders of magnitude for analytes ranging from xenobiotics to endogenous lipids, and facilitated the reduction of voxel-to-voxel variability by more than 3-fold. DA - 2015/10/20/ PY - 2015/10/20/ DO - 10.1021/acs.analchem.5b02641 VL - 87 IS - 20 SP - 10483-10490 SN - 1520-6882 ER - TY - JOUR TI - Feasibility of Using Traditional Kiln Charcoals in Low-Cost Water Treatment: Role of Pyrolysis Conditions on 2,4-D Herbicide Adsorption AU - Kearns, Joshua P. AU - Knappe, Detlef R. U. AU - Summers, R. Scott T2 - ENVIRONMENTAL ENGINEERING SCIENCE AB - Prior research has established that pyrolysis temperature during charcoal production is the primary variable influencing adsorption capacity. The first objective of this work was to monitor thermal conditions during charcoal production within three common traditional kiln models. Then, a programmable laboratory furnace pyrolyzer was used to generate chars from eucalyptus, pine, and longan woods and bamboo under a similar range of thermal conditions as identified in the field study. Using chars produced from the furnace, the second objective of this study was to investigate the influence of biomass feedstock and grain size, peak pyrolysis temperature, and duration of thermal treatment on 2,4-D herbicide sorption capacity. A third objective was to determine if chars produced in the laboratory furnace using thermal profiles similar to those observed in the horizontal drum kiln would exhibit similar adsorbent characteristics to kiln charcoals. Field observations revealed significant variability in temperature profiles during pyrolysis in traditional charcoal kilns, and laboratory experiments indicated corresponding variability in equilibrium 2,4-D uptake from surface water ranging from virtually no adsorption to around 10% of the adsorption capacity of commercial activated carbon. Increasing pyrolysis temperature or duration increased 2,4-D adsorption capacity, whereas feedstock did not affect adsorption capacity for the materials studied. Similar herbicide adsorption capacity was observed for furnace chars and kiln charcoals generated using similar thermal profiles. The difficulty of achieving precise temperature control with traditional charcoal production systems contributes to wide thermal variability within and between batches, which translates to wide variability in adsorption of organic compounds. DA - 2015/11/1/ PY - 2015/11/1/ DO - 10.1089/ees.2015.0243 VL - 32 IS - 11 SP - 912-921 SN - 1557-9018 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84946830926&partnerID=MN8TOARS KW - 2,4-D KW - adsorption KW - biochar KW - charcoal KW - decentralized water treatment KW - engineering for developing communities KW - low cost adsorbents ER - TY - JOUR TI - Cancer incidence and metolachlor use in the Agricultural Health Study: An update AU - Silver, Sharon R. AU - Bertke, Steven J. AU - Hines, Cynthia J. AU - Alavanja, Michael C.R. AU - Hoppin, Jane A. AU - Lubin, Jay H. AU - Rusiecki, Jennifer A. AU - Sandler, Dale P. AU - Beane Freeman, Laura E. T2 - International Journal of Cancer AB - Metolachlor, a widely used herbicide, is classified as a Group C carcinogen by the U.S. Environmental Protection Agency based on increased liver neoplasms in female rats. Epidemiologic studies of the health effects of metolachlor have been limited. The Agricultural Health Study (AHS) is a prospective cohort study including licensed private and commercial pesticide applicators in Iowa and North Carolina enrolled 1993-1997. We evaluated cancer incidence through 2010/2011 (NC/IA) for 49,616 applicators, 53% of whom reported ever using metolachlor. We used Poisson regression to evaluate relations between two metrics of metolachlor use (lifetime days, intensity-weighted lifetime days) and cancer incidence. We saw no association between metolachlor use and incidence of all cancers combined (n = 5,701 with a 5-year lag) or most site-specific cancers. For liver cancer, in analyses restricted to exposed workers, elevations observed at higher categories of use were not statistically significant. However, trends for both lifetime and intensity-weighted lifetime days of metolachor use were positive and statistically significant with an unexposed reference group. A similar pattern was observed for follicular cell lymphoma, but no other lymphoma subtypes. An earlier suggestion of increased lung cancer risk at high levels of metolachlor use in this cohort was not confirmed in this update. This suggestion of an association between metolachlor and liver cancer among pesticide applicators is a novel finding and echoes observation of increased liver neoplasms in some animal studies. However, our findings for both liver cancer and follicular cell lymphoma warrant follow-up to better differentiate effects of metolachlor use from other factors. DA - 2015/6/25/ PY - 2015/6/25/ DO - 10.1002/ijc.29621 VL - 137 IS - 11 SP - 2630-2643 J2 - Int. J. Cancer LA - en OP - SN - 0020-7136 UR - http://dx.doi.org/10.1002/ijc.29621 DB - Crossref KW - cancer KW - epidemiology KW - pesticide KW - occupation ER - TY - JOUR TI - Predicting characteristics of rainfall driven estrogen runoff and transport from swine AFO spray fields AU - Lee, Boknam AU - Kullman, Sethw. AU - Yost, Erin E. AU - Meyer, Michael T. AU - Worley-Davis, Lynn AU - Williams, C. Michael AU - Reckhow, Kenneth H. T2 - SCIENCE OF THE TOTAL ENVIRONMENT AB - Animal feeding operations (AFOs) have been implicated as potentially major sources of estrogenic contaminants into the aquatic environment due to the relatively minimal treatment of waste and potential mobilization and transport of waste components from spray fields. In this study a Bayesian network (BN) model was developed to inform management decisions and better predict the transport and fate of natural steroidal estrogens from these sites. The developed BN model integrates processes of surface runoff and sediment loss with the modified universal soil loss equation (MUSLE) and the soil conservation service curve number (SCS-CN) runoff model. What-if scenario simulations of lagoon slurry wastes to the spray fields were conducted for the most abundant natural estrogen estrone (E1) observed in the system. It was found that E1 attenuated significantly after 2 months following waste slurry application in both spring and summer seasons, with the overall attenuation rate predicted to be higher in the summer compared to the spring. Using simulations of rainfall events in conjunction with waste slurry application rates, it was predicted that the magnitude of E1 runoff loss is significantly higher in the spring as compared to the summer months, primarily due to spray field crop management plans. Our what-if scenario analyses suggest that planting Bermuda grass in the spray fields is likely to reduce runoff losses of natural estrogens near the water bodies and ecosystems, as compared to planting of soybeans. DA - 2015/11/1/ PY - 2015/11/1/ DO - 10.1016/j.scitotenv.2015.06.051 VL - 532 SP - 571-580 SN - 1879-1026 KW - Estrogen runoff and transport KW - Bayesian network model KW - Swine animal feeding operation KW - Spray fields ER - TY - JOUR TI - Pesticide exposure and end-stage renal disease risk among wives of pesticide applicators in the Agricultural Health Study AU - Lebov, Jill F. AU - Engel, Lawrence S. AU - Richardson, David AU - Hogan, Susan L. AU - Sandler, Dale P. AU - Hoppin, Jane A. T2 - Environmental Research AB - Pesticide exposure has been found to cause renal damage and dysfunction in experimental studies, but epidemiological research on the renal effects of chronic low-level pesticide exposure is limited. We investigated the relationships between end-stage renal disease (ESRD) among wives of licensed pesticide applicators (N=31,142) in the Agricultural Health Study (AHS) and (1) personal pesticide use, (2) exposure to the husband's pesticide use, and (3) other pesticide-associated farming and household activities. AHS participants reported pesticide exposure via self-administered questionnaires at enrollment (1993–1997). ESRD cases were identified via linkage to the United States Renal Data System. Associations between ESRD and pesticide exposures were estimated with Cox proportional hazard regression models controlling for age at enrollment. Models of associations with farming and household factors were additionally adjusted for personal use of pesticides. We identified 98 ESRD cases diagnosed between enrollment and 31 December 2011. Although women who ever applied pesticides (56% of cohort) were less likely than those who did not apply to develop ESRD (Hazard Ratio (HR): 0.42; 95% CI: 0.28, 0.64), among women who did apply pesticides, the rate of ESRD was significantly elevated among those who reported the highest (vs. lowest) cumulative general pesticide use (HR: 4.22; 95% CI: 1.26, 14.20). Among wives who never applied pesticides, ESRD was associated with husbands' ever use of paraquat (HR=1.99; 95% CI: 1.14, 3.47) and butylate (HR=1.71; 95% CI: 1.00, 2.95), with a positive exposure–response pattern for husband’s cumulative use of these pesticides. ESRD may be associated with direct and/or indirect exposure to pesticides among farm women. Future studies should evaluate indirect exposure risk among other rural populations. DA - 2015/11// PY - 2015/11// DO - 10.1016/j.envres.2015.10.002 VL - 143 SP - 198-210 J2 - Environmental Research LA - en OP - SN - 0013-9351 UR - http://dx.doi.org/10.1016/j.envres.2015.10.002 DB - Crossref KW - Pesticide exposure KW - End-stage renal disease KW - Farm women KW - Agricultural exposures ER - TY - JOUR TI - Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study AU - Lerro, Catherine C AU - Koutros, Stella AU - Andreotti, Gabriella AU - Friesen, Melissa C AU - Alavanja, Michael C AU - Blair, Aaron AU - Hoppin, Jane A AU - Sandler, Dale P AU - Lubin, Jay H AU - Ma, Xiaomei AU - Zhang, Yawei AU - Beane Freeman, Laura E T2 - Occupational and Environmental Medicine AB -