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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
11

Effects of Perfluoroalkyl Compounds (PFCs) on the mRNA Expression Levels of Thyroid Hormone-responsive Genes in Primary Cultures of Avian Neuronal Cells

Vongphachan, Viengtha January 2011 (has links)
There is a growing interest in assessing the neurotoxic potential and endocrine disrupting properties of perfluoroalkyl compounds (PFCs). Several studies have reported in vitro and in vivo effects related to neuronal development, neural cell differentiation, pre- and post- natal development and behaviour. PFC exposure altered hormone levels (e.g. thyroid hormone, estrogen, and testosterone) and the expression of hormone-responsive genes in mammalian and aquatic species. Hormone-mediated events are critical in central nervous system development and function, especially those controlled by thyroid hormones (THs). The studies presented in this thesis are the first to assess the effects of PFCs on primary cultures of neuronal cells in two avian species; the domestic chicken (Gallus domesticus) and herring gull (Larus argentatus). The following TH-responsive genes were examined using real-time RT-PCR: type II iodothyronine 5’-deiodinase (D2), D3, transthyretin (TTR), neurogranin (RC3), octamer motif binding factor (Oct-1), and myelin basic protein (MBP). Several PFCs were shown to alter mRNA expression levels of genes associated with the TH pathway in avian neuronal cells. It was determined that short-chained PFCs (<8 carbons) altered the expression of TH-responsive genes to a greater extent than long-chained PFCs (≥8 carbons). Although several significant changes in mRNA expression were observed in TH-responsive genes following PFC exposure in chicken embryonic neuronal (CEN) cells (Chapter 2), there were fewer changes in herring gull embryonic neuronal (HGEN) cells (Chapter 3). The mRNA levels of D2, D3, TTR, and RC3 were altered following treatment with several short-chained PFCs in CEN cells. Oct-1 and RC3 expression were induced following treatment with several short-chained PFCs in HGEN cells. These studies are the first to report that PFC exposure alters mRNA expression in primary cultures of avian neuronal cells and provide insight into the possible mechanisms of action of PFCs in the avian brain.
12

Effects of Perfluoroalkyl Acids on In Ovo Toxicity and Gene Expression in the Domestic Chicken (Gallus gallus domesticus)

Cassone, Cristina January 2012 (has links)
Perfluoroalkyl acids (PFAAs) are a family of synthetic substances used in a wide variety of consumer and industrial applications, including non-stick and stain-resistant products. PFAAs, specifically perfluorinated sulfonates and carboxylates, are chemically stable and virtually non-biodegradable in the environment. In recent years, PFAAs have been detected in tissues and blood of humans and wildlife. Furthermore, PFAAs have a tendency to bioaccumulate and biomagnify in biota. Perfluorooctane sulfonate and perfluorooctanoate are known to be toxic when animals are exposed to environmentally-relevant levels, but scientists and regulators are challenged with determining and predicting their modes of action. There is some evidence to suggest that PFAAs can impact the thyroid hormone (TH) pathway and neurodevelopment. The studies presented in this thesis investigated the developmental effects and potential modes of action of newer PFAAs that are being introduced into the global market place. Egg injection experiments were performed in domestic chicken (Gallus gallus domesticus) embryos to assess the in ovo toxicity of perfluorohexane sulfonate (PFHxS) and perfluorohexanoate (PFHxA) during development. Real-time RT-PCR was used to measure the transcription of candidate genes in the liver and cerebral hemisphere of day 21-22 embryos. Candidate genes were selected based on their responsiveness to PFAA exposure in an in vitro screening assay conducted previously. In ovo exposure to PFHxS decreased embryo pipping success and overall growth at 38,000 ng/g; several orders of magnitude higher than concentrations reported in wild bird eggs. The expression of TH-responsive genes, including type II and III 5'-deiodinase, neurogranin, and octamer motif binding factor 1, were induced. In addition, PFHxS diminished free thyroxine (T4) levels in plasma. PFHxA had no affect on pipping success, gene expression or T4 levels in chicken embryos at the doses assessed. The transcriptional profiles in the cerebral hemisphere of chicken embryos exposed to 890 and 38,000 ng/g PFHxS were compared to a solvent control using microarray technology. The expression of 78 different genes were significantly altered (fold change > 1.5, p < 0.001) by PFHxS. Functional analysis showed that PFHxS affected genes involved in tissue development and morphology and cellular assembly and organization. Pathway and interactome analysis suggested that gene expression may be affected through integrin receptors and signaling pathways via TH–dependent and –independent modes of action. It is expected that the findings presented in this thesis will be of general relevance and importance to regulatory agencies and of interest to research scientists and risk assessors.
13

Využití N-fluoralkyl-1,2,3-triazolů v organické syntéze / Utilization of N-fluoroalkyl-1,2,3-triazoles in organic synthesis

Markos, Athanasios January 2021 (has links)
Athanasios Markos Abstract This Thesis deals with denitrogenative transformations of N-fluoroalkyl-1,2,3-triazoles, easily available heterocycles via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) of safe and stable N-fluoroalkyl azides and alkynes. The introductory chapter describes general approaches towards N1-substituted 1,2,3- triazoles, methods of N1-,-difluoroalkyl-1,2,3-triazoles preparation and both, transition metal-catalyzed and transition metal-free transformations of N1-substituted 1,2,3- triazoles. In the first part of the Thesis, rhodium-catalyzed reactions of N-fluoroalkyl-1,2,3-triazoles are described. Rhodium-catalyzed reactions of N-fluoroalkyl-1,2,3-triazoles in presence of suitable reagents provide access to five-membered N-fluoroalkyl heterocycles, 2- fluoroalkyl oxazoles and ketamides. In the second part of the Thesis, both Brønsted and Lewis acid-mediated transformations of N-fluoroalkyl-1,2,3-triazoles leading to stereodefined N-alkenyl compounds, such as enamides, enimines, amidines and other are discussed. The robustness of the method is showcased on gram scale syntheses and preparation of a drug analogue. At last, thermally-induced rearrangement of N-fluoroalkyl-1,2,3-triazoles to 3-fluoroalkyl-2H- azirines and the proposed mechanism of the reaction are described.
14

Analysis of Perfluoroalkyl Carboxylic Acids in Composite Dietary Samples by Gas Chromatography/Mass Spectrometry with Electron Capture Negative Ionization / ガスクロマトグラフィー負化学イオン化質量分析による食事中のフッ素化カルボン酸の分析

Fujii, Yukiko 24 March 2014 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第18193号 / 社医博第54号 / 新制||社医||8(附属図書館) / 31051 / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 中山 健夫, 教授 玉木 敬二, 教授 川上 浩司 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM
15

Method development of total oxidizable precursor assay for perfluoroalkyl acid precursors in domestic sludge

Söderlund, Lydia January 2018 (has links)
Per- and polyfluoroalkyl substances (PFASs) are persistent organic pollutants used in industrial applications and are globally distributed in the environment. A group of PFASs that are difficult to measure with today’s method are perfluoroalkyl acid precursors (PFAA precursors) that, when degraded, serves as indirect sources of PFAAs. This study has optimized a previously developed method for quantification of PFAA precursors in soil; through total oxidizable precursor assay (TOP assay) under alkaline conditions, to be applicable on sewage sludge. To achieve and maintain an alkaline environment during the entire oxidative treatment, several parameters were tested: concentrations of NaOH, persulfate and sample; additional clean-up with graphitized non-porous carbon and reaction time. Solid phase extraction-weak anion exchange (SPE-WAX) was used for clean-up and separation of analytes, and LC-MS/MS was used for quantification. The optimal conditions with the highest levels of PFAAs detected was obtained with 1.33 M NaOH, 60 mM persulfate, 3.57 g/L sludge with a reaction time of 6 hours. The use of graphitized non-porous carbon reduced matrix effects on oxidative conversion resulting in a higher pH as well as a higher degree of oxidation, but with some analyte loss.
16

The Effects of Perfluoroalkyl Compounds on In Ovo Toxicity and Hepatic mRNA Expression in the Domestic Chicken (Gallus gallus domesticus)

O'Brien, Jason 03 May 2011 (has links)
Perfluoroalkyl compounds (PFCs) are a group of chemical surfactants most notably used in non-stick and stain-resistance applications. Due to their wide-spread use and inherent resistance to degradation, several PFCs have become persistent environmental contaminants. Despite the high concentrations of PFCs reported in wild birds and their eggs, very little is known about the toxicological effects they have on avian species. This thesis investigates the developmental toxicity of PFCs in an avian model species: the domestic chicken (Gallus gallus domesticus). Egg injection experiments were performed to assess the in ovo toxicity of perfluorooctane sulfonate (technical grade, T-PFOS), perfluorooctanoic acid (PFOA), perfluorodecane sulfonate (PFDS) and perfluoroundecanoic acid (PFUdA). Real-time RT-PCR was then used to measure the transcription of candidate biomarker genes in the liver tissue of day 20 embryos. Candidate genes were selected based on their responsiveness to PFC exposure in previously conducted in vitro screening assays. In ovo exposure to PFOS resulted in a dose-dependent decrease in embryo pipping success (a measure of hatching success) with an LD50 of 93 μg/g (3.54 μg/g-672,910 μg/g, 95% confidence interval), however the expression of peroxisome proliferator-activated receptor alpha (PPARα)-regulated genes was not affected in liver tissue as hypothesized. PFOA, PFDS and PFUdA had no effect on the pipping success of chicken embryos. The expression of cytochrome P450 1A4 (CYP1A4) and liver fatty acid binding protein (L-FABP) mRNA increased in embryo liver tissue following in ovo exposure to PFUdA but was only statistically significant at 10 μg/g, which is several orders of magnitude higher than concentrations reported in wild bird eggs. The isomer-specific accumulation of PFOS in chicken embryo livers was also investigated using an in-port derivatization gas-chromatography/mass spectrometry (GC-MS) method. Prior to incubation, chicken eggs were injected with T-PFOS, composed of 63% linear isomer (L-PFOS) and 37.3% branched isomers. The isomer profiles in day-20 embryo liver tissue showed up to 20% enrichment in the proportion of L-PFOS, compared to T-PFOS, with a corresponding decrease in the proportion of branched isomers. This enrichment was inversely proportional to dose. Finally, the transcriptional profiles of cultured chicken embryonic hepatocytes (CEH) exposed to either T-PFOS or L-PFOS were compared using Agilent 4x44k Chicken (V2) Gene Expression microarrays. At equal concentrations (10 μM), T-PFOS altered the expression of significantly more genes (340 genes, >1.5 fold change, false discovery rate adjusted p<0.05) compared to L-PFOS (130 genes). Functional analysis showed that L-PFOS and T-PFOS affected genes involved in lipid metabolism, cellular growth and proliferation, and cell-cell signaling. Pathway and interactome analysis suggested that gene expression may be affected through RXR, oxidative stress response, TP53 signaling, MYC signaling, Wnt/β-catenin signaling and PPARγ and SREBP receptors. In all functional categories and pathways examined, T-PFOS had a more pronounced disruptive effect on transctional regulation than L-PFOS. In summary, egg injection experiments showed that T-PFOS (but not linear PFOA, PFDS or PFUdA) may affect the hatching success of the chicken at environmentally relevant concentrations. It was also demonstrated that the accumulation of PFOS in embryonic liver is isomer specific, and leads to an enrichment of L-PFOS. The increased transcriptional disruption caused by T-PFOS in cultured hepatocytes over L-PFOS suggests that the branched isomers may be largely responsible for the toxicological effects of PFOS. Combined, the results from this thesis demonstrate the importance of considering PFOS isomer burdens during risk assessment. In addition, gene expression analysis identified several candidate mechanisms for PFOS toxicity.
17

The Effects of Perfluoroalkyl Compounds on In Ovo Toxicity and Hepatic mRNA Expression in the Domestic Chicken (Gallus gallus domesticus)

O'Brien, Jason 03 May 2011 (has links)
Perfluoroalkyl compounds (PFCs) are a group of chemical surfactants most notably used in non-stick and stain-resistance applications. Due to their wide-spread use and inherent resistance to degradation, several PFCs have become persistent environmental contaminants. Despite the high concentrations of PFCs reported in wild birds and their eggs, very little is known about the toxicological effects they have on avian species. This thesis investigates the developmental toxicity of PFCs in an avian model species: the domestic chicken (Gallus gallus domesticus). Egg injection experiments were performed to assess the in ovo toxicity of perfluorooctane sulfonate (technical grade, T-PFOS), perfluorooctanoic acid (PFOA), perfluorodecane sulfonate (PFDS) and perfluoroundecanoic acid (PFUdA). Real-time RT-PCR was then used to measure the transcription of candidate biomarker genes in the liver tissue of day 20 embryos. Candidate genes were selected based on their responsiveness to PFC exposure in previously conducted in vitro screening assays. In ovo exposure to PFOS resulted in a dose-dependent decrease in embryo pipping success (a measure of hatching success) with an LD50 of 93 μg/g (3.54 μg/g-672,910 μg/g, 95% confidence interval), however the expression of peroxisome proliferator-activated receptor alpha (PPARα)-regulated genes was not affected in liver tissue as hypothesized. PFOA, PFDS and PFUdA had no effect on the pipping success of chicken embryos. The expression of cytochrome P450 1A4 (CYP1A4) and liver fatty acid binding protein (L-FABP) mRNA increased in embryo liver tissue following in ovo exposure to PFUdA but was only statistically significant at 10 μg/g, which is several orders of magnitude higher than concentrations reported in wild bird eggs. The isomer-specific accumulation of PFOS in chicken embryo livers was also investigated using an in-port derivatization gas-chromatography/mass spectrometry (GC-MS) method. Prior to incubation, chicken eggs were injected with T-PFOS, composed of 63% linear isomer (L-PFOS) and 37.3% branched isomers. The isomer profiles in day-20 embryo liver tissue showed up to 20% enrichment in the proportion of L-PFOS, compared to T-PFOS, with a corresponding decrease in the proportion of branched isomers. This enrichment was inversely proportional to dose. Finally, the transcriptional profiles of cultured chicken embryonic hepatocytes (CEH) exposed to either T-PFOS or L-PFOS were compared using Agilent 4x44k Chicken (V2) Gene Expression microarrays. At equal concentrations (10 μM), T-PFOS altered the expression of significantly more genes (340 genes, >1.5 fold change, false discovery rate adjusted p<0.05) compared to L-PFOS (130 genes). Functional analysis showed that L-PFOS and T-PFOS affected genes involved in lipid metabolism, cellular growth and proliferation, and cell-cell signaling. Pathway and interactome analysis suggested that gene expression may be affected through RXR, oxidative stress response, TP53 signaling, MYC signaling, Wnt/β-catenin signaling and PPARγ and SREBP receptors. In all functional categories and pathways examined, T-PFOS had a more pronounced disruptive effect on transctional regulation than L-PFOS. In summary, egg injection experiments showed that T-PFOS (but not linear PFOA, PFDS or PFUdA) may affect the hatching success of the chicken at environmentally relevant concentrations. It was also demonstrated that the accumulation of PFOS in embryonic liver is isomer specific, and leads to an enrichment of L-PFOS. The increased transcriptional disruption caused by T-PFOS in cultured hepatocytes over L-PFOS suggests that the branched isomers may be largely responsible for the toxicological effects of PFOS. Combined, the results from this thesis demonstrate the importance of considering PFOS isomer burdens during risk assessment. In addition, gene expression analysis identified several candidate mechanisms for PFOS toxicity.
18

The Effects of Perfluoroalkyl Compounds on In Ovo Toxicity and Hepatic mRNA Expression in the Domestic Chicken (Gallus gallus domesticus)

O'Brien, Jason 03 May 2011 (has links)
Perfluoroalkyl compounds (PFCs) are a group of chemical surfactants most notably used in non-stick and stain-resistance applications. Due to their wide-spread use and inherent resistance to degradation, several PFCs have become persistent environmental contaminants. Despite the high concentrations of PFCs reported in wild birds and their eggs, very little is known about the toxicological effects they have on avian species. This thesis investigates the developmental toxicity of PFCs in an avian model species: the domestic chicken (Gallus gallus domesticus). Egg injection experiments were performed to assess the in ovo toxicity of perfluorooctane sulfonate (technical grade, T-PFOS), perfluorooctanoic acid (PFOA), perfluorodecane sulfonate (PFDS) and perfluoroundecanoic acid (PFUdA). Real-time RT-PCR was then used to measure the transcription of candidate biomarker genes in the liver tissue of day 20 embryos. Candidate genes were selected based on their responsiveness to PFC exposure in previously conducted in vitro screening assays. In ovo exposure to PFOS resulted in a dose-dependent decrease in embryo pipping success (a measure of hatching success) with an LD50 of 93 μg/g (3.54 μg/g-672,910 μg/g, 95% confidence interval), however the expression of peroxisome proliferator-activated receptor alpha (PPARα)-regulated genes was not affected in liver tissue as hypothesized. PFOA, PFDS and PFUdA had no effect on the pipping success of chicken embryos. The expression of cytochrome P450 1A4 (CYP1A4) and liver fatty acid binding protein (L-FABP) mRNA increased in embryo liver tissue following in ovo exposure to PFUdA but was only statistically significant at 10 μg/g, which is several orders of magnitude higher than concentrations reported in wild bird eggs. The isomer-specific accumulation of PFOS in chicken embryo livers was also investigated using an in-port derivatization gas-chromatography/mass spectrometry (GC-MS) method. Prior to incubation, chicken eggs were injected with T-PFOS, composed of 63% linear isomer (L-PFOS) and 37.3% branched isomers. The isomer profiles in day-20 embryo liver tissue showed up to 20% enrichment in the proportion of L-PFOS, compared to T-PFOS, with a corresponding decrease in the proportion of branched isomers. This enrichment was inversely proportional to dose. Finally, the transcriptional profiles of cultured chicken embryonic hepatocytes (CEH) exposed to either T-PFOS or L-PFOS were compared using Agilent 4x44k Chicken (V2) Gene Expression microarrays. At equal concentrations (10 μM), T-PFOS altered the expression of significantly more genes (340 genes, >1.5 fold change, false discovery rate adjusted p<0.05) compared to L-PFOS (130 genes). Functional analysis showed that L-PFOS and T-PFOS affected genes involved in lipid metabolism, cellular growth and proliferation, and cell-cell signaling. Pathway and interactome analysis suggested that gene expression may be affected through RXR, oxidative stress response, TP53 signaling, MYC signaling, Wnt/β-catenin signaling and PPARγ and SREBP receptors. In all functional categories and pathways examined, T-PFOS had a more pronounced disruptive effect on transctional regulation than L-PFOS. In summary, egg injection experiments showed that T-PFOS (but not linear PFOA, PFDS or PFUdA) may affect the hatching success of the chicken at environmentally relevant concentrations. It was also demonstrated that the accumulation of PFOS in embryonic liver is isomer specific, and leads to an enrichment of L-PFOS. The increased transcriptional disruption caused by T-PFOS in cultured hepatocytes over L-PFOS suggests that the branched isomers may be largely responsible for the toxicological effects of PFOS. Combined, the results from this thesis demonstrate the importance of considering PFOS isomer burdens during risk assessment. In addition, gene expression analysis identified several candidate mechanisms for PFOS toxicity.
19

The Effects of Perfluoroalkyl Compounds on In Ovo Toxicity and Hepatic mRNA Expression in the Domestic Chicken (Gallus gallus domesticus)

O'Brien, Jason January 2011 (has links)
Perfluoroalkyl compounds (PFCs) are a group of chemical surfactants most notably used in non-stick and stain-resistance applications. Due to their wide-spread use and inherent resistance to degradation, several PFCs have become persistent environmental contaminants. Despite the high concentrations of PFCs reported in wild birds and their eggs, very little is known about the toxicological effects they have on avian species. This thesis investigates the developmental toxicity of PFCs in an avian model species: the domestic chicken (Gallus gallus domesticus). Egg injection experiments were performed to assess the in ovo toxicity of perfluorooctane sulfonate (technical grade, T-PFOS), perfluorooctanoic acid (PFOA), perfluorodecane sulfonate (PFDS) and perfluoroundecanoic acid (PFUdA). Real-time RT-PCR was then used to measure the transcription of candidate biomarker genes in the liver tissue of day 20 embryos. Candidate genes were selected based on their responsiveness to PFC exposure in previously conducted in vitro screening assays. In ovo exposure to PFOS resulted in a dose-dependent decrease in embryo pipping success (a measure of hatching success) with an LD50 of 93 μg/g (3.54 μg/g-672,910 μg/g, 95% confidence interval), however the expression of peroxisome proliferator-activated receptor alpha (PPARα)-regulated genes was not affected in liver tissue as hypothesized. PFOA, PFDS and PFUdA had no effect on the pipping success of chicken embryos. The expression of cytochrome P450 1A4 (CYP1A4) and liver fatty acid binding protein (L-FABP) mRNA increased in embryo liver tissue following in ovo exposure to PFUdA but was only statistically significant at 10 μg/g, which is several orders of magnitude higher than concentrations reported in wild bird eggs. The isomer-specific accumulation of PFOS in chicken embryo livers was also investigated using an in-port derivatization gas-chromatography/mass spectrometry (GC-MS) method. Prior to incubation, chicken eggs were injected with T-PFOS, composed of 63% linear isomer (L-PFOS) and 37.3% branched isomers. The isomer profiles in day-20 embryo liver tissue showed up to 20% enrichment in the proportion of L-PFOS, compared to T-PFOS, with a corresponding decrease in the proportion of branched isomers. This enrichment was inversely proportional to dose. Finally, the transcriptional profiles of cultured chicken embryonic hepatocytes (CEH) exposed to either T-PFOS or L-PFOS were compared using Agilent 4x44k Chicken (V2) Gene Expression microarrays. At equal concentrations (10 μM), T-PFOS altered the expression of significantly more genes (340 genes, >1.5 fold change, false discovery rate adjusted p<0.05) compared to L-PFOS (130 genes). Functional analysis showed that L-PFOS and T-PFOS affected genes involved in lipid metabolism, cellular growth and proliferation, and cell-cell signaling. Pathway and interactome analysis suggested that gene expression may be affected through RXR, oxidative stress response, TP53 signaling, MYC signaling, Wnt/β-catenin signaling and PPARγ and SREBP receptors. In all functional categories and pathways examined, T-PFOS had a more pronounced disruptive effect on transctional regulation than L-PFOS. In summary, egg injection experiments showed that T-PFOS (but not linear PFOA, PFDS or PFUdA) may affect the hatching success of the chicken at environmentally relevant concentrations. It was also demonstrated that the accumulation of PFOS in embryonic liver is isomer specific, and leads to an enrichment of L-PFOS. The increased transcriptional disruption caused by T-PFOS in cultured hepatocytes over L-PFOS suggests that the branched isomers may be largely responsible for the toxicological effects of PFOS. Combined, the results from this thesis demonstrate the importance of considering PFOS isomer burdens during risk assessment. In addition, gene expression analysis identified several candidate mechanisms for PFOS toxicity.
20

Catalytic and Photocatalytic Removal of Contaminants of Emerging Concerns (CECs) and Per-/Polyfluoroalkyl Substances (PFAS) from Wastewater Effluents for Water Reuse Applications

Abdelraheem, Wael H.M. January 2020 (has links)
No description available.

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