Dissertations / Theses: 'Chemical profiling'

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Ogunleye, Olatokumbo Olajumi Luca. "Chemical Inducers of Dimerization for Profiling Protein Kinases." Diss., The University of Arizona, 2015. http://hdl.handle.net/10150/579019.

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Chemical inducers of dimerization (CID) represent an important tool that has been implemented in numerous biological applications namely protein functions, protein stability, signal transduction, gene transcription, etc. Most generally CIDs are defined as bivalent molecules capable of inducing proximity between two targeted proteins. This proximity can in turn promote or disfavor a certain biological activity. Cell permeable small molecules in particular represent a very effective method to induce precise temporal and spatial control over a specific biological target. Our lab has devoted much effort in studying and elucidating the activity and functions of protein kinases, which represent a very attractive therapeutic target for the treatment of cancer and many other disorders. Towards this goal we have developed a general CID enabled three-hybrid split-luciferase methodology for the investigation of kinase-inhibitor interactions in vitro. We demonstrate that by modulating the kinase-ligand affinity of the CID we are able to successfully profile many structurally non-related protein kinases. We also investigate the use of weaker affinity kinase ligands to allow competitive displacement of CID by the selected inhibitor. In addition we report the design, synthesis and applications of novel CID's for the profiling of kinase inhibitors in mammalian cells and we demonstrate the feasibility of the assay to be used as a new platform for the discovery of cell permeable kinase inhibitors. Finally, we report a new ligand-gated split-kinase that can be selectively activated by photocleavable inducers of dimerization. We further prove how the activity of split-proteins can be deactivated with temporal control with use of non DNA damaging UV radiation.

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PUNZALAN, LOUVY LYNN CALVELO. "Chemoproteomic Profiling of a Pharmacophore-Focused Chemical Library." Kyoto University, 2020. http://hdl.handle.net/2433/259001.

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Peterson, Vanessa M. (Vanessa Marie). "Detecting and molecular profiling cancer cells in patients." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/86863.

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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2013.
"September 2013." Page 173 blank. Cataloged from PDF version of thesis.
Includes bibliographical references (pages 152-163).
Although tumor cells obtained from human patients by surgical biopsy, image-guided intervention, blood draws or fluid drainage (paracentesis, thoracentesis) are a valuable source for analyzing tumor cells, conventional means of proteomic analysis are limited. Highly sensitive and quantitative technologies for point-of-care and multiplexed analysis on small sample sizes are in great demand. To this end, we developed three technologies to improve our understanding of the molecular signatures of cancer in clinical samples. In the first section, we describe a diagnostic magnetic resonance (DMR) device that was developed for point-of-care analyses of human tumors. We optimized a magnetic nanoparticle assay to improve sensitivity and robustness of the DMR approach. The DMR device was tested by analyzing samples from 50 patients. The results were then validated in an independent cohort of 20 additional patients. DMR enabled quantification of multiple protein markers in all patients. Using a four-protein signature enabled us to achieve 96% accuracy for establishing cancer diagnosis, surpassing conventional clinical analysis by immunohistochemistry. Results also show that protein expression patterns decay with time, underscoring the temporal need for rapid sampling and diagnoses. Also, a surprising degree of heterogeneity in protein expression both across different patient samples and even within the same tumor was observed, which has important implications for molecular diagnostics and therapeutic drug targeting. In the second section we molecularly profiled tumor cells in ascites - peritoneal fluid frequently drained for symptomatic relief in advanced ovarian cancer (OvCA) patients. First, we profiled a comprehensive panel of 85 biomarkers in ovarian cancer and benign cell lines. From this data set, 31 markers were identified and profiled in a training set of human ascites samples (n=1 8). We identified an ascites-derived tumor signature termed ATCdx containing four markers which was then validated in a cohort of 47 patients (33 ovarian cancer and 14 control) and correctly identified all 33 ovarian cancer patients. Serial samples were obtained from a subset of patients' serial samples (n=7) and profiled, demonstrating that ATCs can be used to measure treatment response and differentiate responders from non-responders. Finally, we specifically designed a novel microfluidic enrichment chip that allows rapid visualization of cancer cells in heterogeneous ascites fluid. This chip requires small sample volumes (< 1 mL) and has single cell detection sensitivity. Furthermore, it is inexpensive to construct and can be easily fabricated using soft lithographic techniques, providing a point-of-care method that could potentially find widespread use for ATC analyses and diagnosis. In the final section, a multiplexed proteomic assay using a photocleavable DNA barcoding method was developed to multiplex protein detection in single cells. We tested 94 antibodies against common cancer markers to examine different treatment responses and heterogeneity at the single cell level. We then extended our analysis to human clinical samples to demonstrate the potential of protein-based measurements to assist in monitoring cancer therapy through differential changes before and after treatment. We show that protein based tumor profiles can provide sufficient information to predict treatment response. Finally, we examined interpatient variability and intratumoral heterogeneity of single cells with this highly sensitive assay. Together, these technologies can help overcome current clinical limitations and expedite advancements in cancer treatment.
by Vanessa M. Peterson.
Ph. D.

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Kabbani, Nazir. "Chemical-genetic profiling of platelet-activating factor in yeast." Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28189.

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The basic biological processes between the yeast Saccharomyces cerevisiae and mammals are highly conserved. Yeast posses many genes that are implicated in human diseases and have been successfully used as a model for the study of neurodegeneration. Platelet-Activating Factor (C16:0 PAF) causes neuronal cell death independent of its receptor and has been implicated in Alzheimer's disease. I hypothesized that yeast could be used as a model system for deciphering PAF receptor-independent signalling and have utilized genome-wide chemical genomic screening in yeast to further characterize the molecular mechanism of PAF toxicity. Two complementary screens implicate PAF in many cellular processes, some of which parallel results obtained in mammalian studies. I have found that PAF challenge is cytotoxic, delays cell cycle progression, and affects actin stability leading to spindle misorientation and bi-nucleate mother cells.

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Goudsmits, E. "Chemical profiling of ballistic materials : analysis of organic gunshot residue." Thesis, Liverpool John Moores University, 2018. http://researchonline.ljmu.ac.uk/8454/.

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Gunshot residue (GSR) is a complex chemical mixture that is created during the discharge of a firearm. Its detection and interpretation play a crucial role in the investigation of firearm incidents. Current GSR analysis is limited to inorganic GSR (IGSR), however, the evidential value could be strengthened by inclusion of organic GSR (OGSR). The present study aims to address this potential by proposing a categorisation system for relevant OGSR compounds and developing a methodology for the collection, extraction and analysis of both organic and inorganic GSR from a single sample. The organic composition of more than 50 propellant powders has been determined and compared against more than 200 propellant compositions reported in the literature. This work has resulted in a three-tier categorisation system for OGSR compounds, which together with the current IGSR classification will provide unequivocal identification of GSR materials with the possibility of discriminating between GSR from different ammunition types. Evaluation of MonoTrap extraction showed that this is an effective pre-concentration technique for the characterisation of propellants. Solid-phase microextraction (SPME), however, was the superior method for the extraction of OGSR compounds from various sampling media, including swabs and stubs. The optimised methodology involves GSR collection using carbon adhesive stubs followed by SPME gas chromatography – mass spectrometry (GC-MS) analysis of OGSR and subsequent scanning electron microscopy – energy-dispersive X-ray spectrometry (SEM-EDX) analysis for IGSR. This protocol has resulted in the detection of both characteristic IGSR and categorised organic compounds, demonstrating the ability to obtain a full chemical profile from a single sample. Detection of both first and second tier organic compounds provides complementary compositional information that could be used to discriminate between samples. Furthermore, this methodology requires no changes to the current sampling and IGSR analysis protocols and addresses the limited storage time of OGSR. Since GC-MS instruments are readily available in most analytical laboratories, implementation of the proposed protocol is feasible.

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Chen, Zewei. "Authentication of Complex Botanical Materials by Chemometrics and Chemical Profiling." Ohio University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1617010785195628.

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Charlton, Thomas. "Chemical proteomic profiling to investigate lipoprotein biogenesis in Clostridium difficile." Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/29661.

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Bacterial lipoproteins feature an N-terminal Type II signal peptide, containing a lipobox motif which targets these proteins for post-translational lipidation. Following secretion, pre-prolipoprotein diacylglyceryl transferase (Lgt) catalyses the addition of an S-diacylglyceryl moiety to the lipobox cysteine thiol. The signal peptide sequence is then cleaved by a lipoprotein signal peptidase (Lsp), leaving the modified cysteine as the N-terminal residue of the mature Gram-positive lipoprotein. Lipoproteins are surface exposed and play an important role at the host-pathogen interface, as well as being implicated in nutrient uptake, sporulation and antibiotic resistance. Clostridium difficile is a Gram-positive, spore forming, obligate anaerobe which causes severe gastrointestinal disease in humans. Spores are the transmissible agent of C. difficile, with infection typically occurring via the faecal-oral route. Lipoproteins of C. difficile are known to function in nutrient uptake and adhesion and the lipoproteome is likely to be important in transmission and colonisation. Bacterial lipidation is difficult to study by traditional methods, however, metabolic tagging with bioothogonally-tagged lipid analogues has recently emerged as a powerful method to study lipidated proteins. This thesis describes the development and optimisation of metabolic tagging and quantitative chemical proteomics to investigate lipidation in C. difficile. The application of this approach to profile the lipoproteomes of 630 Δerm and the clinically relevant 'hypervirulent' strain R20291 is described. This work includes the use of these probes, in combination with genetic and chemical inactivation of lgt, lspA and lspA2, to investigate lipoprotein biogenesis in C. difficile and to demonstrate the presence of two active Lsps. A combination of quantitative proteomics and phenotypic analysis has identified new functions for the C. difficile lipoproteome, including a role in the regulation of flagella and toxin production and in the initiation of sporulation.

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Silva, Saliya Sudharshana 1976. "Transcriptional profiling and flux measurements of polyhydroxybutyrate production in Synechocystis." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/28657.

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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2004.
Includes bibliographical references (leaves 39-41).
(cont.) to determine the CO₂ uptake rates and PHB production rates of strains engineered for enhanced CO₂ fixation and PHB production respectively.
The metabolism of Synechocystis PCC6803 cells has been investigated using full-genome DNA micro-arrays and C14 tracer techniques. Full-genome (3169 genes) DNA micro-arrays were used to probe transcript levels of Synechocystis cells grown under a variety of medium conditions. Canonical discriminant analysis was used to identify transcript levels that allowed discrimination between growth media conditions, and allowed predictions of polyhydroxybutyrate (PHB) levels. Phosphate-related genes were found to alter in response to phosphate limitation and were found to include differentially regulated multi-gene families. Nitrogen-related genes were not found to be substantially reflective of nitrogen limitation under the conditions studied. Finally, transcription of PHA biosynthetic pathway genes were found to reflect the media conditions of greatest PHB accumulation, suggesting that constitutive over-expression of the PHA biosynthetic genes may lead to greater PHB accumulation levels. A methodology using C14 tracers was developed for the accurate measurement of CO₂ uptake rates and the partitioning of the fixed carbon into different biosynthetic fractions. These techniques were applied to the characterization of WT Synechocystis cells in late exponential phase. A stoichiometric model of Synechocystis metabolism was used to determine constraints between the measurements. A balance on C14 counts was obtained and significant levels of secreted compounds were not detected. The measured carbon fixation rates were found to be consistent with the observed growth rates, but inconsistent with measurements of oxygen evolution in the light and uptake in the dark made using a Clarke Electrode apparatus. These techniques may be used in future studies
by Saliya Sudharshana Silva.
S.M.

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Kates, Lisa Natasha. "Chemical profiling and environmental modelling of waste from clandestine methylamphetamine laboratories." Thesis, University of Strathclyde, 2013. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=22542.

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Methylamphetamine (MA) is an illicit drug abused by millions of people worldwide. MA can be manufactured easily using a variety of household chemicals and several different methods. The illicit manufacture of MA produces large amounts of waste: one kilogram of MA produces five to seven kilograms of toxic waste, which is illegally disposed of in a number of different ways, creating a source of pollution. MA waste contains many harmful components, however it has never been characterised. In this work, MA was synthesised following three different synthetic routes. The waste were collected and subject to chemical profiling using gas chromatography-mass spectrometry. Key marker compounds of the waste were identified which may aid in the detection and prosecution of an illicit dumpsite. Those key marker compounds include MA, 1-phenyl-2-propanone, Nformylmethylamphetamine, and 2,6-di-tert-butylphenol. Environmental partition coefficients were measured experimentally for several of the i dentified waste components. The octanol-water partition coefficient (KOW) and the organic carbon partition coefficient (KOC) were measured following standard methods. The KOW values were found to be in accordance with computer estimated values produced from the environmental modelling programme, EPI SuiteTM, while the KOC values were calculated as a function of organic carbon content from collected sediment samples. Using the measured KOW values and calculated KOC values, a fugacity model of the waste was generated using EPI SuiteTM to predict the distribution of the waste once it enters the environment. It was determined that the majority of the waste components will partition predominantly into the water compartment. This study encompasses the first research on waste generated from the illicit manufacture of MA, with the aim to provide information to law enforcement personnel and environment agencies to allow clandestine manufacturers to be prosecuted under environmental legislation in addition to drugs legislation.

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Taylor, Michael. "To F-SIMS/XPS chemical depth profiling of synthetic polymer hydrogels." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/38755/.

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Over the last decade the beneficial properties of hydrogels as artificial cell culture supports have been extensively investigated. Certain synthetic hydrogels have been proposed to be similar in composition and structure to the native extracellular matrix of the stem cell niche, their in vivo cell habitat, which is a powerful component in controlling stem cell fate. The stem cell differentiation pathway taken is influenced by many factors. When culturing cells within or upon hydrogels the choice can be strongly dependent on the underlying 3D hydrogel chemistry which strongly influences hydrogel-cell interactions. The interrelationship between hydrogel chemistry and that of biomolecules in controlling cellular response ideally requires analysis methods to characterise the chemistry without labels and normally in 3D. Time-of-flight secondary ion mass spectrometry (ToF SIMS) has the potential to be utilised for through thickness characterisation of hydrogels. The frozen-hydrated sample format is well suited to minimise changes associated with dehydration or the complication of chemical ‘fixation’. There is however significant challenges associated with this sample format. Frost formation occurs on cold samples in the ambient atmosphere affecting the quality of chemical information acquired from depth profiling frozen hydrogel samples. We develop a simple method to remove this frost by blowing with gas prior to entry into the instrument which is shown to produce remarkably good profiles on a poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel film where a model protein, lysozyme, is incorporated to demonstrated how biomolecule distribution within hydrogels can be determined. A comparison of lysozyme incorporation is made between the situation where the protein is present in the polymer dip coating solution and lysozyme is a component of the incubation medium. It is shown that protonated water clusters H(H2O)n+ where n=5-11 that are indicative of ice are detected through the entire thickness of the pHEMA and the lysozyme distribution through the pHEMA hydrogel films can be determined using the intensity of characteristic fragment secondary ions. Quantitative TOF-SIMS analysis is highly desirable in biomaterial analysis as the amount and type of molecule in the material analysed may be determined. This has significant interest in hydrogel chemical analysis as cellular development on or within hydrogels may be highly influenced by the concentration and type of soluble molecule. Unfortunately, the matrix effect in SIMS changes the measured signal intensity of the analyte, preventing accurate quantitation. For this reason, we apply X-Ray Photoelectron Spectroscopy (XPS) on the equivalent samples as the ToF-SIMS in an attempt to correlate molecular ion yields to exact elemental concentrations. Similarly to ToF-SIMS the frozen-hydrated format in XPS is however still relatively unexplored. We apply the developed preparatory procedure in 3D XPS analysis of pHEMA/lysozyme hydrogel films in a hydrated state. We show that this format is suitable for alternative high vacuum analysis techniques. Furthermore, we show that lysozyme ingression and concentration can be determined through XPS. This work describes the first example of the characterisation of a hydrogel by ToF-SIMS and XPS in a frozen hydrated format, characterising hydrogels in a format most reflecting its native hydrated state at culture conditions. The described procedure allows for the mapping of biomolecules in a label free manner in 3D, furthermore allowing quantitative determination of biomolecule concentrations in hydrogels.

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Zhao, Jianping. "Chemical profiling of botanical supplements : Maca (Lepidium Meyenii) and Damiana (Turnera Diffusa) /." Full text available from ProQuest UM Digital Dissertations, 2007. http://0-proquest.umi.com.umiss.lib.olemiss.edu/pqdweb?index=0&did=1414122821&SrchMode=1&sid=1&Fmt=2&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1221157623&clientId=22256.

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Yarandi, Niousha. "Evaluation of the antioxidant composition of teas via chemical and biological profiling." Thesis, Kingston University, 2016. http://eprints.kingston.ac.uk/39269/.

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The health benefits of tea, one of the most consumed beverages in the world, are largely attributed to phenolic constituents and their antioxidant properties. Teas have been shown to neutralise free radicals, prevent oxidative stress, and act as inhibitors of proteinases involved in cellular degradation, which has led to the platform for this study. The aim of this study was to investigate the antioxidant activities of phenolics and other components of major types of tea (white, green and black) using various assays, for screening components of these three types, for their antioxidant activity and for their anti-inflammatory abilities. A new functional High Performance Thin Layer Chromatography approach was adapted and employed to (i) separate and identify antioxidant components of tea, (ii) compare the antioxidant profiles of major types of tea, and (iii) screen the antioxidant activities of identified compounds in tea via treatment with redox-active metal ions. Twelve phenolic compounds were identified which were grouped according to their reactivity towards redox-active metal ions. In addition, non-phenolic constituents were identified as antioxidants and assigned as chlorophyll analogues by comparison to reference compounds. A further key finding was that the coutner ion to the metal salt could play a marked role in antioxidant assays used with chloride, but not sulfate, enhancing antioxidant depletion. The HPTLC observations were supported by HPLC profiling to compare the constituents of tea types and phenolic loss upon challenge with oxidants. The predominant phenolics were (-)-EGCG, caffeine, (-)-ECG and quercetin - the latter two being the most active against oxidant challenge. Metal ion analysis by ICP-MS revealed the teas contained several redox-active metal ions and black tea had significantly higher levels of redox-active Mn ions. The antioxidant enzyme activity (catalase and superoxide dismutase) of the teas and selected compounds was also investigated, a variety of activity across the tea samples and the selected compounds with regards to their Catalase activity and SOD inhibitory/activity capabilities was observed. Chlorophyll showed the highest catalase activity, and black and green teas showed the highest superoxide dismutase activity. The effect of tea extracts and selected compounds on immortalised human keratinocyte cells (HaCaT) and human cervical carcinoma cells (CaSki), and their abilities to guard against oxidative damage in cell lines was also investigated. White tea (Wt), green tea (Gt), Black tea (Bt), EC, ECG, EGCG, quercetin and chlorophyll a and b showed powerful antioxidant activities in HaCaT cells both H[sub]2O[sub]2- and paraquat-induced cell death and for CaSki cells H[sub]2O[sub]2- induced cell death. These promising data demonstrate that teas and the individual components of tea have the potential to act as antioxidants and anti-inflamatory agents both in vitro and in vivo, and therefore further investigation of their bioactive effects may prove beneficial.

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Wang, Xinyi. "Characterization of Botanicals by Nuclear Magnetic Resonance and Mass Spectrometric Chemical Profiling." Ohio University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1521718129716851.

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Heiney, John P. (John Patrick). "Optimization of preclinical profiling operations in drug discovery." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/39595.

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Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; and, (S.M.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering; in conjunction with the Leaders for Manufacturing Program at MIT, 2007.
Includes bibliographical references (p. 55-56).
In early-stage drug discovery, thousands of compounds must be tested using in vitro assays to determine their exposure and safety characteristics. This data is used to guide the selection of potential drug candidates and to help chemists in optimize the properties of those compounds. At Novartis, an internal service organization called Preclinical Compound Profiling (PCP) provides these services to the company as a whole. The purpose of this internship was to help PCP make significant improvements in cycle time and cost effectiveness without reducing the quality of information provided to their customers. The project utilized a series of deterministic and stochastic models to predict the impact of multiple operational changes on cost and cycle time. The data from each model was synthesized to create a unified view allowing combinations of changes to be analyzed together. This data was evaluated in the context of the customer needs and organizational strategy to present recommendations. Changes were implemented that will reduce materials spending by $500,000 per year while simultaneously increasing capacity, reducing cycle time, and improving customer value. Additional recommendations were developed that will enable further improvements.
by John P. Heiney.
S.M.
M.B.A.

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Newton, Richard. "Vertical profiling in the west Pacific warm pool." Thesis, University of Manchester, 2018. https://www.research.manchester.ac.uk/portal/en/theses/vertical-profiling-in-the-west-pacific-warm-pool(8c89d0ef-dc88-44d6-ad49-81cc34d5e662).html.

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This thesis consists of three distinct parts of CAST, CONTRAST and ATTREX, which were aircraft and field campaigns in the West Pacific in January-March 2014. The first section comprises of ozonesonde measurements from Manus Island, Papua New Guinea. A contamination issue affected the first 14 ozonesondes, and so particular care was required to characterize the background current, and as a result, a 'hybrid' background current correction was developed, which combines a constant correction with a pressure dependent correction. Collocated measurements with the CONTRAST aircraft - the NCAR Gulfsteam V - suggests the new hybrid correction produces better ozonesonde profiles than the other corrections that are found in the literature. The results of the ozonesonde measurements revealed a low-ozone event, with minimum ozone concentrations of ~12 ppbv, which was coincident with an easterly jet, and traced back to an area of deep convection: clean marine boundary layer air was uplifted into the tropical tropopause layer (TTL) and then advected in the easterly jet across to Manus Island. The second section attempted to find more examples of low-ozone conditions in the TTL from the aircraft data. The ATTREX aircraft - the NASA Northrop Grumman Global Hawk - observed ozone concentrations of ~10 ppbv in the Southern Hemisphere in proximity of tropical storm Lusi. Whole air samples from all three aircraft suggests the low-ozone air had recently encountered the boundary layer, with enhanced concentrations of surface-generated very short lived substances (VSLSs) compared to air with higher ozone concentrations. No low-ozone events were found in the Northern Hemisphere, even in the vicinity of tropical cyclone Faxai. The third section explores the low-ozone events in the WRF-Chem (Weather Research and Forecasting - with chemistry) in order to see whether the model was capable of recreating the low-ozone event measured by the ozonesondes on 21-23 February as a case study. The WRF-Chem simulation did correctly reproduce the large convective storm in a similar area to that observed by satellites, and surface tracers were uplifted in large quantities as hypothesized. However, no evidence of injection of air into the stratosphere was found in the simulation, and, rather than uplift directly from the surface, mixing of air in the boundary layer followed by uplift into the TTL was the main mechanism for producing the low-ozone event.

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Willingham, David George Winograd Nicholas. "Strong-field photoionization of sputtered neutral molecules for chemical imaging and depth profiling." [University Park, Pa.] : Pennsylvania State University, 2009. http://etda.libraries.psu.edu/theses/approved/WorldWideIndex/ETD-4536/index.html.

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Schmauder, Gretchen C. "Thermal and chemical profiling of the Bald Mountain District, White Pine County, Nevada /." abstract and full text PDF (free order & download UNR users only), 2005. http://0-wwwlib.umi.com.innopac.library.unr.edu/dissertations/fullcit/1433099.

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Thesis (M.S.)--University of Nevada, Reno, 2005.
"August, 2005." Includes bibliographical references. Library also has microfilm. Ann Arbor, Mich. : ProQuest Information and Learning Company, [2005]. 1 microfilm reel ; 35 mm. Online version available on the World Wide Web.

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Couvertier, Shalise Monique. "Chemical-proteomic strategies to study cysteine posttranslational modifications." Thesis, Boston College, 2016. http://hdl.handle.net/2345/bc-ir:107200.

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Thesis advisor: Eranthie Weerapana
Cysteine residues on proteins play important catalytic and regulatory roles in complex proteomes. These functional residues can be modified under physiological conditions by posttranslational modifications (PTMs) to regulate protein activities and modulate cysteine reactivity. Many PTMs are highly labile and dynamic, rendering it difficult to detect modified proteins within complex systems. To contribute to the chemical-proteomic methods currently available, chemical probe-Mass Spectrometry (MS) platforms were developed to study oxidative cysteine modifications. A MS platform for the assessment of S-nitrosation in vitro identified Cys329 of Cathepsin D (CTSD) as highly sensitive to S-nitrosothiol formation. To achieve a more physiological relevant representation of S-nitrosation, this platform was later adapted for study in live cells using a caged electrophile, Caged BK. Additionally, oscillation of cysteine oxidation as a function of circadian rhythm in Drosophila melanogaster and human samples was explored. As a compliment to these MS platforms, a 4-aminopiperidine-based cysteine-reactive probe library was developed. These probes have been used to target specific reactive cysteines as an alternate way to regulate protein function and can be used as tools to provide insight into the roles of these residues in protein activities
Thesis (PhD) — Boston College, 2016
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry

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Van, Antwerpen Lindi. "Chemical and sensory profiling of dry and semi-dry South African Chenin blanc wines." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71853.

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Thesis (MSc)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: Chenin blanc wine is of economic importance to South Africa and a range of diverse dry and semi-dry wines are locally produced in this genre. Currently, the use of three distinctly different style names, each aimed at providing consumers with information about the flavour of the wines, is encouraged by the South African (SA) wine industry. The styles are fresh and fruity (FF), rich and ripe unwooded (RRUW) and rich and ripe wooded (RRW). Feedback from retail sectors over the past few years, however, repeatedly suggested that the style names are perceived as confusing by SA consumers. This master study was undertaken to re-evaluate the FF, RRUW and RRW style classification, based on both the volatile fermentation-derived aroma composition and the sensory attributes of a set of wines containing all the styles under investigation. For the purposes of chemical profiling, a set of 105 commercial Chenin blanc wines, selected to be representative of these three styles and originating from the major SA wine producing areas, were analysed by Gas Chromatography (GC) to quantify fermentation-derived volatile aroma compounds in the wines. ANOVA performed on the chemical data showed that 29 compounds represent significant differences between at least two of the 3 styles (FF, RRUW and RRW). Principal component analysis (PCA) of the volatile compounds showed a large degree differentiation between FF and RRW wine styles, however, RRUW wine styles overlapped with the other two styles. Considering vintage effects, ANOVA indicated no significant differences within FF (vintages 2009 and 2010) and RRW (vintages 2008 and 2009) styles, whereas only 2 esters and 4 terpenes showed significant differences between the three wine producing regions investigated for this purpose, Paarl/Wellington, Breede River and Stellenbosch. Volatile aroma compounds generated for Chenin blanc were included in the Winetech database consisting of the most important cultivars of South Africa. Combining the data for the volatiles for Chardonnay and Sauvignon blanc from this database and the data for Chenin blanc obtained in this study, a PCA indicated a clear separation between Chenin blanc and the other two white cultivars. Sensory evaluation of the style classification was done by two separate sensory tests. Firstly, a sorting task was performed by wine industry experts to categorise 21 Chenin blanc wines (FF, RRUW and RRW) based on their similarity. The results showed a differentiation between FF and RRW styles, however, RRUW was mostly classified together with FF wines. This indicated a possible continuum between the three styles, as opposed to three distinct different categories, currently suggested by the style names. The second sensory analysis test, Descriptive Sensory Analysis (DSA), was performed by a trained panel to generate sensory profiles for 42 wines. ANOVA of the flavour attribute intensities between different styles once again showed significant differences between FF and RRW, with RRUW wines forming a continuum between the FF and RRW styles. These results provide valuable information that could be used by the wine industry for labelling purposes.
AFRIKAANSE OPSOMMING: Chenin blanc is van ekonomiese belang vir Suid Afrika en ‘n wye reeks droë en semi-droë wyne word plaaslik geproduseer in hierdie kategorie. Tans word die gebruik van drie duidelike verskillende stylbenamings, elkeen daarop gemik om aan die verbruiker inligting te verskaf oor die geur van die wyn, deur die Suid Afrikaanse (SA) wynindustrie aangemoedig. Die style is vars en vrugtig, ryk en ryp ongehout en ryk en ryp gehout. Terugvoer van die handelssektor oor die afgelope aantal jare, het daarop gedui dat die stylbenamings tot verwarring onder SA verbruikers lei. Hierdie meestersstudie is onderneem om die stylklassifikasie, vars en vrugtig, ryk en ryp ongehout en ryk en ryp gehout, te her-evalueer op grond van die vlugtige aroma komponente wat tydens die fermentasie proses gevorm word, asook die sensoriese eienskappe van ‘n verteenwoordigende stel wyne van elk van die style wat ondersoek is. Vir die doel van die chemiese profilering, is ‘n stel van 105 kommersiële wyne, wat geselekteer is om verteenwoordigend te wees van die drie style ondersoek en ook afkomstig is van die vernaamste SA wynproduserende streke, gebruik. Die wyne is met behulp van gas chromatografie ontleed om die vlugtige komponente wat van die fermentasie proses afkomstig is, te kwantifiseer. Die analise van variansie, het getoon dat 29 komponente statisties beduidend verskil het tussen die drie style. Hoofkomponent analise van die vlugtige komponente, het getoon dat die vars en vrugtige wyne en ryk en ryp gehoute wyne, duidelik onderskeibaar was van mekaar op grond van die vlugtige data, maar die ryk en ryp ongehoute wyne het met die ander twee style oorvleuel. In terme van oesjaar effekte, was daar geen beduidende verskille in die aroma profiele van die vars en vrugtige styl (oesjare 2009 en 2010) en ryk en ryp ongehoute styl (oesjare 2008 en 2009) nie, terwyl die konsentrasie van slegs twee esters en 4 terpene statisties beduidend verskil het tussen die wynproduserende streke Paarl/Wellington, Breederivier en Stellenbosch. Resultate van die gekwantifiseerde vlugtige komponente is in die databasis van Winetech gevoeg, waar die konsentrasies van soortgelyke komponente van die vernaamste SA wynkultivars reeds vervat is. Hoofkomponent analises van die gekombineerde resultate vir Chenin blanc, Chardonnay en Sauvignon blanc wyne, het getoon dat daar ‘n duidelike verkil tussen Chenin blanc en die ander twee wit wynkultivars was. Die sensoriese evaluerings is uitgevoer deur van twee verskillende metodes gebruik te maak. Eerstens is 21 wyne (met al drie style verteenwoordig) deur wynindustrie eksperts gesorteer op grond van die waargenome eendersheid van die onderskeie wyne en die resultate is grafies geprojekteer. Die resultate het getoon dat daar ‘n duidelike verskil waargeneem is deur die assessors tussen die vars en vrugtige styl en ryk en ryp gehoute styl. Die ryk en ryp ongehoute wyne het in die analises meer met die vars en vrugtige style geassosieer, as die ryk en ryp gehoute wyne. Die tweede sensoriese metode is uitgevoer deur sensoriese paneel wat vir die doel van hierdie studie opgelei is om die geur eienskappe van 42 wyne (al drie style verteenwoordig) te profileer. Analise van statistiese beduidende verskille tussen die voorkoms van die geurkomponente en hul intensiteite vir elke styl, het weereens aangedui dat daar ‘n kontinuum bestaan tussen die style. Hierdie resultate kan van waarde vir die wynindustrie wees in besluite rakende etikettering.

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Bathgate, Hilary. "The development of chemical and biological profiling for the forensic provenancing of Norfolk soils." Thesis, University of East Anglia, 2014. https://ueaeprints.uea.ac.uk/53458/.

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Soils are frequently analysed by forensic laboratories by comparing a suspect sample to an especially collected control sample. As yet, they cannot be compared to a central database, unless the area in question has already been identified; with the use databases being highly contested within the field of forensic geosciences. There is a need for a method of soil profiling that allows an unknown sample to be tested and assigned a quantitative likelihood that it originated from a given region. Spatial models can then be created using geographical information systems to house multiple datasets and be used to map soils across geographical areas. Generally, the more variables available with which to compare items, the greater the certainty a forensic analyst can have when asserting their similarity; this applies to geological materials. Equally, soil profiling methods can be used to exclude soil samples from each other or an area. This research involves a number of chemical and biological profiling methods that have been used to build up a unique signature for soils from different locations across Norfolk. All analyses have been carried out on a single source sample. 87Sr/86Sr ratios have been measured using MC-ICP-MS, and trace element concentrations measured using ICP-MS. The 87Sr/86Sr ratios are significantly different at each of the sample locations; although there is some variation in the replicates collected at each location this variation is smaller than the regional variation. The correlation between the isotope chemistry of the topsoil and the underlying geology is poor, indicating that other sources such as land-use, vegetation cover and additions to the soil contribute to the 87Sr/86Sr. Therefore, trace element concentrations have been used to spatially discriminate samples and to investigate the effect of fertilisers on the elemental composition of the topsoil. The biological techniques used to aid discrimination are soil DNA analysis using the chloroplast-located matK gene and MALDI-ToF-MS, palynology and the creation of Norfolk vegetation maps showing all of the plant species recorded in the area; each additional independent dataset allows for an increasing signature of each sample to be built up which can be used for assessing similarity or exclusionary purposes.

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Peschel, Wieland. "Cannabis Extracts for medicinal use - chemical profiling and in vitro cytotoxic and anti-inflammatory effects." Thesis, University College London (University of London), 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.510076.

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Siheri, Weam Fathi. "Libyan Propolis : a comprehensive chemical, in vitro biological investigation and metabolomic profiling of antiprotozoal activity." Thesis, University of Strathclyde, 2017. http://digitool.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=28767.

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Propolis (bee-glue) is collected by bees from plants as a defensive substance in response to environmental pressures which include a range of microorganisms and parasites. These parasites are known to include the protozoal species Crithidia. Since it is collected by bees for the specific purpose of providing chemotherapeutic protection this increases the likelihood of finding active compounds in propolis compared with random screening of plants. Twelve samples of Libyan propolis (P1-P12) were collected from different geographic zones of Libya. Ethanolic extracts of the twelve propolis samples were prepared and these were profiled initially by NMR which gave some general indication of the type of compounds which might be found in them providing signals typical of diterpene aldehydes and cycloartane triterpenoids depending on the origin of the sample. There were limited signals in the aromatic region between 6 and 8 ppm in contrast to Northern European samples where many signals from flavonoid compounds would be expected. The extracts were profiled by high resolution LC-MS and the LC-MS data was extracted and modelled by SIMCA-P software using PCA with HCA, which separated the samples into five main groups based on their chemical composition. The groups were according to Geographic origin which the samples from North East, North West, South East and Southwest Libya grouping together. The sample extracts were tested against a wide range of microorganisms including T. brucei, L. donovani, P. falciparum, C. fasiculata, M. marinum, S. aureus, K. pneumoniae and T. spiralis. In addition, cell based assays for cytotoxicity and anti-inflammatory activities were carried out. Eighteen isolated compounds were isolated including: eight diterpenes (1) 13-epi-torulosal, (2) 13-O- acetyl epi-cupressic acid, (3) 13-epicupressic acid, (4) 13-epitorulosol, (15) acetylisocuppressic acid, (16) Agathadiol, (17) Isocupressic acid and, (18) isoagatholal, three lignans; (5) sesamin, (6) Demethylpiperitol, (7) 5’, methoxy piperitol, (8) the flavonoid flavanone taxifolin-3-acetate-4’-methyl ether and five triterpenes of the cyclo artane type; (9) cycloartanol, (10) mangiferolic acid, (11) mangiferonic acid, (12) ambolic acid, (13) 27-hydroxymangeferonic acid and the resorcinol (14) cardol. Both the crude extracts and isolated compounds exhibited activity against the range of microorganisms were tested such as T. brucei, L. donovani, P. falciparum, C. fasiculata, M. marinum, S. aureus, K. pneumoniae and T. spiralis.

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Zonyane, Samkele. "The antimicrobial interactions of Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus combination and their chemical profiling." Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/95465.

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Thesis (MSc)--Stellenbosch University, 2013.
ENGLISH ABSTRACT: In traditional medicine, there is a long-standing culture of combining herbal drugs to increase the therapeutic efficacy. The improved medical action is thought to be due to synergistic interactions between different plant bioactive components. The aim of this study was to test the pharmacological interactions in a medicinal plant combination which consisted of Agathosma crenulata, Dodonaea viscosa and Eucalyptus globulus. The rationale for the analysis of this particular mixture is that it had noteworthy antibacterial activity and exhibited the highest activity out of seven medicinal plant mixtures previously investigated. Using chromatographic analysis, the phytochemistry of the plants was also assessed. The chloroform: methanol (1:1; v/v) extracts or hydo-distilled essential oils (A. crenulata and E. globulus) were screened individually and in combinations (double and triple plant combination) for activity against five respiratory pathogens using a microdilution assay. The antimicrobial interactions in combinations were assessed with the fractional inhibitory concentration (FIC) and the isobolograms. The organic extracts generally showed the highest antimicrobial activity with E. globulus having the highest activity with MIC values below 1 mg ml-1 representing noteworthy activity. The overall activity of the aqueous extracts was poor. The essential oil activity of E. globulus was mostly noteworthy (0.5 to 2 mg ml-1) while A. crenulata essential oil displayed moderate activity (1 to 4 mg ml-1). The ΣFIC values for double combinations (1:1) of A. crenulata with D. viscosa, A. crenulata with E. globulus and D. viscosa with E. globulus were calculated from the minimum inhibitory concentration (MIC) data and the interactions were classified as synergistic, additive, indifferent and antagonistic. The highest synergistic interactions observed were for a 1:1 combination of A. crenulata with E. globulus against K. pneumoniae, S. aureus and B. subtilis with ΣFIC values of 0.07. There was only one incident of antagonism noted in the study for D. viscosa with E. globulus (1:1) against C. neoformans with ΣFIC value of 4.25. The double combinations against selective pathogens (K. pneumoniae, S. aureus and E. coli) were further analysed for interactions using isobolograms. Mostly, the antimicrobial interactions as presented by the isobolograms were congruent with FIC results which further validated the occurrence of relevant antimicrobial interactions in those combinations. The ΣFIC values for triple combinations (1:1:1) revealed mostly synergistic interactions. When the triple combinations were analysed further against certain pathogens based on the predictions of the Design of Experiments software program (MODDE 9.1®), the MIC values remained the same despite the different combinations that were tested Thin layer chromatography (TLC) was used for a quick chemical fingerprinting of the plant extracts. This was followed by a bio-autographic assay. The chemical profiles of the organic extracts and essential oils from two of the study aromatic plants (A. crenulata and E. globulus) were further analysed with liquid chromatography mass spectrometry (LC-MS) and gas chromatography mass spectrometry (GC-MS) respectively. For combined plant extracts, a multivariate data analysis using principal component analysis (PCA) and hierarchical clustering analysis (HCA) was used to determine the relationship of the chemical make-up of combinations with that of individual plant extracts. According to the TLC analysis, E. globulus extracts had more compounds than the other two plants in the study. For the bio-autographic assay, E. globulus and combinations that included this plant showed greater inhibition zones than A. crenulata and D. viscosa. For the LC-MS analysis, PCA and HCA showed a close relationship between A. crenulata with D. viscosa, D. viscosa with E. globulus and the triple combination. Twenty one components were identified in the essential oil of A. crenulata representing 88.83% of the total oil composition. The oil was dominated by oxygen-containing monoterpenes (46.25%). In the essential oil of E. globulus, twenty six compounds were identified making up to 95.62% of the oil composition. Oxygen-containing monoterpenes (32.98%) also dominated the E. globulus essential oil. There was no great variation in essential oil metabolites of the individual plants and their combination as shown by both PCA and HCA. The enhanced in vitro antimicrobial activity and pharmacological interactions (synergy and additivity) in some of the combinations (double and triple) that were tested in this study adds scientific support to the use of medicinal plant combinations in Western Cape traditional medicine. The metabolic profiles of plants in combination might be unique due to interaction of the different plant bioactive molecules and thus result into defined antimicrobial activity.
AFRIKAANSE OPSOMMING: In tradisionele geneeskunde is dit ’n lank bestaande kultuur om kruiemiddels te kombineer om die terapeutiese werking daarvan te verhoog. Dié verbeterde mediese werking word toegeskryf aan die oënskynlik sinergistiese interaksies tussen verskillende bioaktiewe plantkomponente. Die doel van hierdie studie was om die farmakologiese interaksies in medisinale plantkombinasies van Agathosma crenulata, Dodonaea viscosa en Eucalyptus globulus te bestudeer. Daar is op die ontleding van hierdie spesifieke mengsel besluit omdat dit oor beduidende antibakteriese waarde beskik en omdat dit uit sewe medisinale plantmengsels wat voorheen bestudeer is, as die doeltreffendste een aangewys is. Die fitochemie van die plante is ook met behulp van chromatografiese ontleding beoordeel. Deur middel van ’n mikroverdunningstoets is die chloroform:metanol- (1:1; v/v-)ekstrakte of hidrogedistilleerde vlugtige olies (A. crenulata en E. globulus) individueel sowel as in kombinasie (dubbele en drievoudige plantkombinasies) nagegaan vir hul werking met betrekking tot vyf respiratoriese patogene. Die gekombineerde antimikrobiese interaksies is met behulp van fraksioneel stremmende konsentrasie (FIC) en isobologramme ondersoek. Die organiese ekstrakte het oor die algemeen die meeste antimikrobiese aktiwiteit by E. globulus getoon, met MIC-waardes onder 1 mg ml-1 wat as noemenswaardige aktiwiteit beskou is. Die algehele aktiwiteit van die waterekstrakte was swak. Die vlugtige-olieaktiwiteit van E. globulus was merendeels noemenswaardig (0,5 tot 2 mg ml-1), terwyl die vlugtige olie van A. crenulata matige aktiwiteit getoon het (1 tot 4 mg ml-1). Die ΣFIC-waardes vir dubbelkombinasies (1:1) van A. crenulata en D. viscosa, A. crenulata en E. globulus, en D. viscosa en E. globulus is uit die minimum stremmende konsentrasie (MIC) bereken en die interaksies is as sinergisties, additief, neutraal en antagonisties geklassifiseer. Die sterkste sinergistiese interaksies is by ’n 1:1-kombinasie van A. crenulata en E. globulus met betrekking tot K. pneumoniae, S. aureus en B. subtilis opgemerk, met ΣFIC-waardes van 0,07. Die studie het slegs een geval van antagonisme opgelewer, naamlik by D. viscosa en E. globulus (1:1) met betrekking tot C. neoformans, wat ’n ΣFIC-waarde van 4,25 geregistreer het. Die werking van die dubbelkombinasies met betrekking tot gekose patogene (K. pneumoniae, S. aureus en E. coli) is voorts met behulp van isobologramme vir interaksies nagegaan. Die antimikrobiese interaksies wat uit die isobologramme geblyk het, was meestal in pas met FIC-resultate, wat die bestaan van tersaaklike antimikrobiese interaksies in daardie kombinasies verder bevestig het. Die ΣFIC-waardes vir die drievoudige kombinasies (1:1:1) het meestal sinergistiese interaksies aan die lig gebring. Toe die drievoudige kombinasies verder op grond van die voorspellings van die sagteware Design of Experiments (MODDE 9.1®) met betrekking tot sekere patogene ontleed is, het die MIC-waardes onveranderd gebly, ondanks verskillende toetskombinasies. Dunlaagchromatografie (TLC) is vir ’n vinnige chemiese ontleding van die plantekstrakte gebruik en is gevolg deur ’n bio-outografiese toets. Die chemiese profiele van die organiese ekstrakte en vlugtige olies van twee van die aromatiese plante in die studie (A. crenulata en E. globulus) is verder met vloeistofchromatografie-massaspektrometrie (LC-MS) en gaschromatografie-massaspektrometrie (GC-MS) onderskeidelik ontleed. Vir gekombineerde plantekstrakte is veelveranderlike-ontleding in die vorm van hoofkomponentontleding (PCA) en hiërargiese groepsontleding (HCA) gebruik om die verhouding van die chemiese samestelling van kombinasies in vergelyking met dié van individuele plantekstrakte te bepaal. Volgens die TLC-ontleding beskik E. globulus-ekstrakte oor meer verbindings as die ander twee plante in die studie. Vir die bio-outografiese toets het E. globulus en kombinasies daarmee groter stremmingsones as A. crenulata en D. viscosa getoon. In die LC-MS-ontleding het PCA en HCA op ’n hegte verhouding tussen A. crenulata en D. viscosa, D. viscosa en E. globulus, en die drievoudige kombinasie daarvan gedui. Een-en-twintig komponente is in die vlugtige olie van A. crenulata gevind, wat 88,83% van die algehele oliesamestelling uitmaak. Die olie is deur suurstofhoudende monoterpene (46,25%) oorheers. Die vlugtige olie van E. globulus het 26 verbindings opgelewer, wat 95,62% van die oliesamestelling uitmaak. Suurstofhoudende monoterpene (32,98%) het ook die vlugtige olie van E. globulus oorheers. Nóg PCA nóg HCA het op enige beduidende variasie in die metaboliete van die vlugtige olies van die individuele plante en hul kombinasies gedui. Die verhoogde in vitro- antimikrobiese aktiwiteit en farmakologiese interaksies (sinergie en additiwiteit) in van die kombinasies (dubbel én drievoudig) wat in hierdie studie getoets is, bied wetenskaplike stawing vir die gebruik van medisinale plantkombinasies in Wes-Kaapse tradisionele geneeskunde. Die metaboliese profiele van plantkombinasies kan verander weens die interaksie van die verskillende bioaktiewe plantmolekules, en kan baie bepaalde antimikrobiese aktiwiteit tot gevolg hê.

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Abubakar, Mohamed Rania. "Tracing a compound with ecological importance for Ficus species and profiling the chemical constituents of Ficus obtusifolia." Thesis, Uppsala universitet, Avdelningen för farmakognosi, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-434985.

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Hanekom, Evette. "Chemical, sensory and consumer profiling of a selection of South African Chenin blanc wines produced from bush vines." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71812.

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Thesis (MScFoodSc)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: Twenty five commercial Chenin blanc wines produced solely from bush vine vineyards and including three vintages, three styles and five production areas, were sourced for this study. Descriptive sensory analysis (DSA) and chemical analyses including GC-FID (gas chromatography fitted with a flame ionisation detector) and FTMIR (Fourier transform mid-infrared) spectroscopy were employed to establish the sensory and chemical characteristics, whereas consumer tests were conducted to determine consumer perception and liking of bush vine Chenin blanc wines. DSA (a profiling technique) was also compared to the sorting task (a classification technique) with a description assignment to evaluate the sorting task’s ability to profile wines. According to the results of DSA, the wines separated into two groups. One group associated with sensory attributes which can be considered indicative of the Fresh and Fruity Chenin blanc style. The other group associated with sensory attributes which can be considered indicative of the Rich and Ripe style of Chenin blanc. No separation between the wooded and unwooded Rich and Ripe styles was apparent. According to the results of the chemical analyses, the wines also separated into two groups. This separation seemed to be caused by vintage and the chemical changes associated with ageing as the wines from the youngest vintage (2010) was strongly associated with high levels of esters and malic acid. The older wines were situated farthest away from these attributes indicating low concentrations. When comparing the results from the sorting task and DSA, it could be seen that similar wine style groupings formed, indicating that DSA can also be regarded as an effective tool when categorising wines. The differences in the positioning of some of the wines and attributes on the DSA multivariate plots and the sorting task plots could be attributed to the difference in panels used. The sorting task was conducted using an expert panel with persons illustrating significant technical knowledge of Chenin blanc wines. Experience, exposure and technical knowledge tend to establish a common language amongst wine experts which could have caused the expert panel to perceive some wines differently when comparing the results of the latter panel to that of the trained panel. DSA was found to remain the most effective method for establishing a comprehensive sensory profile. Consumer analyses showed that regular white wine drinkers prefer the unwooded styles (Fresh and Fruity and Rich and Ripe unwooded) of Chenin blanc more than the wooded style. It was also found that consumers with a higher level of objective wine knowledge tend to associate the terms ‘bush vine’ and ‘old bush vine’ with the Rich and Ripe style of Chenin blanc, whereas consumers with a lower level of objective wine knowledge associated ‘old bush vine’ with the Fresh and Fruity style. Since all the wines used in the consumer analysis were produced from old bush vines, it is evident that consumer education on the impact of bush vine training system and vine age on wine quality is needed. Better understanding of these principles could lead to elevated product appraisals and consumer satisfaction.
AFRIKAANSE OPSOMMING: Vyf en twintig kommersiële Chenin blanc wyne, uitsluitlik van bosstok wingerde geproduseer, is bekom vir hierdie studie. Die wyne het drie style, drie oesjare en vyf produksiestreke ingesluit. Beskrywende sensoriese analise (BSA) en chemiese analises, wat GC-FID (gas chromatografie gekoppel met vlam-ioniserende deteksie) en FTMIR (Fourier-transformering mid-infrarooi) spektroskopie insluit, is uitgevoer om onderskeidelik die sensoriese en chemiese eienskappe van die wyne te bepaal. Verbruikerstoetse is ook uitgevoer om verbruikerspersepsie en -voorkeure vir bosstok Chenin blanc wyne te bepaal. BSA (‘n profilerings tegniek) was ook vergelyk met ‘n sorterings taak (‘n klassifikasie tegniek) met ‘n beskrywings opdrag, primêr om die sorterings taak se vermoë om wyne te profileer te ondersoek. Volgens die resultate van BSA, het die wyne in twee groepe verdeel. Een groep het met die sensoriese eienskappe wat op ‘n Vars-en-Vrugtige-styl dui, geassosieër. Die ander groep het met sensoriese eienskappe geassosieër wat met die Volrond-styl verband hou. Geen verdeling tussen die gehoute en ongehoute wyne binne die Volrond-styl was sigbaar nie. Volgens die resultate van die chemiese analises, het die wyne ook in twee groepe verdeel. Die verdeling blyk asof dit veroorsaak is deur oesjaar en die chemiese veranderinge wat met wynveroudering gepaard gaan. Wyne van die jongste oesjaar (2010) het ‘n sterk verband met hoë vlakke van esters en appelsuur getoon. Die ouer wyne was verder weg van hierdie eienskappe geleë, wat op laer ester en appelsuur konsentrasies dui. Wanneer die meerveranderlike resultate van die sorterings taak (met en sonder die aanduiding van sensoriese eienskappe) en dit van BSA vergelyk word, kon soortgelyke groeperings gesien word. Dit is ‘n aanduiding dat BSA ook wyne effektief kan kategoriseer. Die verskil in posisionering van sommige wyne tussen die BSA en sorterings taak resultate, kan toegeskryf word aan die verskillende panele wat gebruik is om die tegnieke uit te voer. ‘n Deskundige paneel (wynkenners) is gebruik om die sortingstaak uit te voer. Ervaring, blootstelling en tegniese kennis is geneig om te lei tot die vestiging van ‘n gemeenskaplike taal onder wynkenners. Hierdie gemeenskaplike taal kan as rede aangevoer word vir die uiteenlopende analise van sommige wyne wanneer die resultate van die deskundige paneel met dié van die opgeleide paneel (in BSA gebruik) vergelyk word. Dit is gevind dat BSA, wanneer ‘n omvattende sensoriese profiel bepaal moet word, die mees effektiefste metode bly. Verbruikerstoetse het getoon dat gereelde witwyn-verbruikers die ongehoute Chenin blanc style (Vars-en-Vrugtig en ongehoute Volrond) bo die gehoute styl verkies. Dit is ook bepaal dat verbruikers met ‘n hoër vlak van objektiewe wynkennis neig om die terme ‘bosstok’ en ‘ou bosstok’ met die Volrond-styl van Chenin blanc te assosieer, terwyl verbruikers met ‘n laer vlak van objektiewe wynkennis die term ‘ou bosstok’ met die Vars-en-Vrugtige Chenin blanc styl assosieër. Aangesien al die wyne wat in die verbruikerstoetse ingesluit is van ou bosstok wingerde geproduseer is, is dit duidelik dat verbruikeropvoeding insake die effek van die gebruik van bosstokke en ou wingerdstokke op wynkwaliteit noodsaaklik is. ‘n Beter begrip van hierdie beginsels sal lei tot verhoogde produkwaardasie, asook ‘n toename in verbruikertevredenheid.

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26

Katele, Zongwe Felix. "Chemical profiling of cultivated and wild African ginger and absolute configurations of compounds from mangroves and Ancistrocladus species." Diss., University of Pretoria, 2015. http://hdl.handle.net/2263/53504.

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Medicinal plants and natural products have played a pivotal role as a source of drug leads that has led to improving health conditions and have provided humankind with numerous pharmacologically active drugs. Other than the biological screening and chemical profiling of plant extracts, the isolation, purification and elucidation of the full absolute structures of natural compounds are some of the key areas required in the time-consuming process of drug discovery based on natural products. Elucidation of the absolute configuration (AC) of chiral natural products represents one of the most challenging tasks in the determination of full molecular structures but still remains an essential concept in drug discovery as enantiomers do not always exhibit the same pharmacological activities. The present study successively investigated the UPLC MS and GC MS chemical profiles of organic extracts from the wild and cultivated popular, but threatened medicinal plant, African ginger {i.e., Siphonochilus aethiopicus (Schweinf.) B.L. Burtt} and the absolute configurations of limonoids, diterpenoid and dimeric naphthylisoquinoline (NIQ) alkaloids isolated from mangroves and Ancistrocladus species. The first part of the study aimed at exploring the similarities and/or differences between the UPLC MS and GC MS chemical profiles of wild and cultivated African ginger rhizomes and evaluating the antimalarial activity of extracts from both sources taking into account that traditional healers are not unanimous on using the cultivated material for medicinal purposes. UPLC MS chemical profiling of n-hexane/DCM (1:1) extracts from air-dried rhizomes has revealed the presence of additional peaks in the chromatographic profiles of wild plants but also confirmed the major peak in the profiles of both wild and cultivated rhizomes to be the common furanoterpenoid (4), known as Siphonochilone. The compound was unexpectedly observed to be highly unstable and generated artefact sesquiterpenoids after autoxidation. Autoxidation was observed for the pure compound, as well as in dried and powdered rhizomes. The latter aspect confirmed that the artefact sesquiterpenoids only form after autoxidation and do not occur in the fresh plant as reported in many publications. GC MS analyses of n-hexane extracts from fresh, air-dried and oven-dried plants confirmed the presence of Siphonochilone (4) from both sources but further revealed the presence of eucalyptol, which was significantly depleted after drying. Antimalarial screenings of n-hexane/DCM (1:1) extracts against the chloroquine-sensitive (CQS) strain of Plasmodium falciparum (NF54) did not show substantial change in the IC50 values for both sources. The second part of the study aimed at elucidating the absolute configurations of two limonoids, one diterpenoid and two NIQ dimers. This was tackled by conducting quantum-chemical calculations of chiroptical spectroscopy, such as circular dichroism. Absolute configurations were deduced from the comparison between experimental chiroptical data with the curves predicted for the possible enantiomers. The absolute configurations of the limonoids thaixylomolin A (12) and B (13) were respectively revealed as 1R,5R,8R,9R,10R,13S,14R,15S,17S and 1R,2R,3S,4R,5S,9S,10R,13R,17R while that of the diterpenoid decandrinin (14) was 5S,9S,10R and those for the NIQ dimers mbandakamines A (15a) and B (15b) validated published data.
Dissertation (MSc)--University of Pretoria, 2015.
Chemistry
MSc
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27

Vemulakonda, Padma Prasuna S. "Comparative Characterization of Superconducting Thin Films Fabricated by Different Techniques." Wright State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=wright1176576035.

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28

Oz, Tufan M. "Microarray Based Expression Profiling Of Barley Under Boron Stress And Cloning Of 3h Boron Tolerance Gene." Phd thesis, METU, 2012. http://etd.lib.metu.edu.tr/upload/12614203/index.pdf.

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Both deficiency and toxicity of the essential micronutrient boron (B) lead to reduced crop yield in agriculture. However, our understanding of the molecular responses of plants under B stresses to tackle the yield loss is limited. Therefore, in the present study, transcriptional alterations in sensitive and tolerant barley cultivars under B deficiency and toxicity were investigated in order to reveal the molecular responses. Transcriptomes were monitored at seedling stage by global expression profiling using oligonucleotide microarrays. In the context of the study, we have determined that response to B toxicity in barley involved jasmonic acid and various components of biotic stress responses. Examination of expression profiles indicated that B toxicity and deficiency resulted in significant global changes in the transcriptomes of leaf and root tissues, respectively. Inter-varietal comparison of sensitive and tolerant genotypes of barley revealed that a combinatorial effect of transcription factors on regulation could alter the gene expression patterns in tolerant cultivar and provide B toxicity tolerance. Furthermore, mechanisms of vacuolar sorting or efflux by transporters and aquaporins might be contributing to the tolerance to B stresses in barley according to the results of this study. Additionally, we have identified and cloned the HvBor1a gene encoding a putative B transporter in barley using candidate gene approach and functionally characterized its roles in the tolerance to B stresses. The full length coding sequence and also the non-coding regions of the gene were identified. It was demonstrated that the protein product of HvBor1a was localized to the plasma membrane and it displayed B transporter activity. High transcript abundances in leaf tissues of barley suggested a role for HvBor1a in re-distribution of B within the plant tissues. Interestingly, examination of last intron of HvBor1a has led to the identification of an alternatively spliced variant in certain cultivars of barley. Furthermore, interval mapping and positional cloning was performed to locate the HvBor1a on 3H B tolerance QTL and a novel CAPS marker was developed to narrow the genetic distances at the locus. As a conclusion, this work presents, for the first time, the transcriptome profiling of a member of Triticeae under B toxicity and deficiency. The data generated should enlighten succeeding studies to unravel molecular mechanisms and signaling networks of tolerance to B stresses especially in crops like barley and wheat. The results of the study will provide novel tools and genes for conventional and biotechnological approaches for the reduction of yield loss due to B toxicity or deficiency.

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29

Mortensen, Anne Skjetne. "Toxicogenomics of Aryl Hydrocarbon- and Estrogen Receptor Interactions in Fish : Mechanisms and Profiling of Gene Expression Patterns in Chemical Mixture Exposure Scenarios." Doctoral thesis, Norwegian University of Science and Technology, Department of Biology, 2007. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-1900.

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Almost without exception, biological processes such as overt morphological changes, development (both reproductive and growth), toxicological responses and clinical manifestation to disease, have molecular basis. From our perspective (i.e. toxicological perspective), the evidence of receptor-mediated mechanisms of xenobiotic-induced effects is provided if the effect is tissue specific, predictable, if increases in the transactivation of specific genes can be demonstrated, transcriptional responses occur rapidly, compounds bind reversibly to intracellular macromolecules or compounds are stereo-specific. Thus, the primary objective of toxicological in vitro studies on cells and tissues is to characterize cellular and molecular substrates and pathways that contribute to adverse effects in an organism after toxicant exposure. The estrogenic and xenobiotic biotransformation gene expressions are receptor-mediated processes that are ligand structure-dependent interactions with estrogen-receptor (ER) and aryl hydrocarbon receptor (AhR). The anti-estrogenic activities of AhR agonists have been reported in vitro and in vivo studies. In teleost species, exposure to AhR agonists has been associated with reduced vitellogenin (Vtg) synthesis or impaired gonadal development. Recently, several studies have shown that AhR-agonists directly activate ERs and induce estrogenic responses in mammalian in vitro systems. The overall objective of this thesis was to develop diagnostic gene and protein response tools in the study of the molecular mechanisms of gene expression patterns of xenoestrogens and xenobiotic interactions in wildlife species. Contaminants known to be estrogenic (ethynylestradiol; EE2 and nonylphenol; NP) and/or anti-estrogenic (PCBs), either by direct ER or indirect AhR mechanistic pathways, were used as model xenobiotics and evaluated either singly or in combination using in vitro and in vivo test systems.

Suppressive subtractive hybridization (SSH) was used to create a cDNA library of clones containing differentially expressed genes from Atlantic salmon (Salmo salar) separately exposed to ER and AhR agonists. Based on differentially expressed genes from the library, a targeted cDNA array (SalArray) was developed. Cellular in vitro systems, like cell and tissue models, facilitate the investigation of the direct molecular mechanisms accounting for predictable adverse effects of xenobiotic compounds on wildlife and humans. Consequently, in the studies presented primary hepatocyte cultures were isolated from the liver of trout and salmon by the collagenase perfusion method. The targeted SalArray and quantitative real-time PCR (q-PCR) were used to demonstrate that exposure of salmon hepatocytes to the ER-agonist NP singly or in combination with the produced differential gene expression patterns in salmon liver.Exposure of hepatocytes to NP mainly altered genes involved in the estrogenic pathway, including genes involved in steroid hormone synthesis and metabolism. The anti-estrogenic properties of PCB77 were demonstrated in the array analysis as NP induced gene expressions decreased by exposure of hepatocytes to PCB77. Our data showed a reciprocal inhibitory interaction between ER- and AhR-agonists. PCB77 produced anti-estrogenic effects by decreasing the mRNA expression of ER-responsive genes, and NP produced anti-AhR mediated effects as inhibitor of AhRR, Arnt, CYP1A1 and UGT expression. In vivo exposure of salmon to EE2 produced a significant decrease of CYP1A1 expression and these effects paralleled EROD activity and AhRR mRNA, suggesting a direct role of EE2 in controlling the cellular detoxification machinery.

While a clear pattern of negative effects on ER-mediated gene expression was found in hepatocytes exposed to PCB77, exposure of cells to the more potent AhR-agonist and dioxinlike PCB126 induced transcriptional activation of ER signalling demonstrated by increased Vtg and ERα mRNA and ERα protein levels. The decreased levels of ERα and Vtg expression in cells treated with PCB126 in the presence of ICI is novel, indicating a possible, but not conclusive “ER-hijacking” not previously reported in any fish species or lower vertebrate. Different gene expression patterns were obtained at similar time-interval with fish from different seasons, demonstrating the complexity of AhR-ER interactions. Thus, the direct estrogenic actions of PCB126 observed contribute new insight on the complexity of the mechanisms involved in ER-AhR crosstalk, prompting a new wave of discussion on whether AhR-mediated anti-estrogenicity is an exception, rather than a rule of action. This thesis demonstrates a complex mode of interactions between two different classes of ligandactivated receptors and provides novel mechanistic insights on signalling pathways. Therefore, the degree of simultaneous interactions between the ER and AhR gene transcripts demonstrated support the concept of cross-talk between these signalling pathways, in addition to generating new hypotheses that need to be evaluated empirically. AhR-agonist PCB77

Paper I and V reprinted with kind permission of Elsevier, sciencedirect.com

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30

Helm, Dominic F. J. G. G. [Verfasser], Bernhard [Akademischer Betreuer] Küster, and Stephan [Akademischer Betreuer] Sieber. "Mass spectrometry based chemical proteomics for drug selectivity profiling / Dominic F. J. G. G. Helm. Gutachter: Bernhard Küster ; Stephan Sieber. Betreuer: Bernhard Küster." München : Universitätsbibliothek der TU München, 2015. http://d-nb.info/1075858194/34.

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31

Grove, Jason Andrew. "Assessment of the Potential Functional Diversity of the Bacterial Community in a Biofilter." Thesis, University of Waterloo, 2006. http://hdl.handle.net/10012/850.

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A biofilter removes biodegradable contaminants from air by passing it through a biologically-active packed bed. The microorganism community is of fundamental interest but has been the focus of few studies. This work is an investigation of the bacterial community based on the potential functional diversity of the community.

A number of experiments were performed in laboratory-scale biofilters using ethanol as a model contaminant. All biofilters were able to remove the ethanol with elimination capacities in the range 80 to 200gVOCm^-3h^-1; these values are comparable with published literature. Natural organic media (peat or compost) was used as packing.

The potential functional diversity of the community was assessed by Community-Level Physiological Profiling (CLPP) using sole-Carbon Source Utilisation Profile (CSUP). Community samples were used to inoculate Biolog EcoPlates^TM: microplates containing a selection of 31 different carbon-substrates and an indicator dye responding to bacterial growth. This technique was found to be sensitive to changes in the community structure over time and location.

Results showed that the community in samples taken close together (over a scale of a few centimetres) are similar and that relatively small media samples (0. 5 to 1 g) provide reproducible information. A study of a single biofilter indicated stratification of the community occurring with the community near the inlet diverging from that near the middle and outlet of the unit; this is attributed to the ethanol being degraded in the upper part of the column and the lower part of the column not being subjected to ethanol loading. In a study of two units at a higher loading rate, stratification was not observed over a period of weeks; it is suggested that the stratification may develop over this timescale as a result of the presence or absence of the Volatile Organic Compound (VOC) and not due to differences in concentration.

An acclimation period of 7 to 10 days was observed before near-complete removal of ethanol was attained. Monitoring of the community suggested a subsequent shift in diversity. It is suggested that the initial acclimation period is due to biofilm formation and the subsequent shift in community diversity is due to re-organisation of the community as species specialise. In a portion of the biofilter with minimal ethanol exposure, a sudden shift in community is observed after a period of some weeks. This may reflect changes as a result of starvation and indicates that periods of shut-down (when the biofilter is not loaded) may affect the community.

Two studies of biofilters operating in parallel were carried out. The first provided evidence of a divergence in the communities over a period of two weeks. In the second, communities in the two units underwent changes over time but observations from both units at any one time were similar. This demonstrates that biofilters set-up and operated in a similar manner may maintain similar communities but that this is not necessarily the case. This has implications for the reproducibility of laboratory experiments and for the variation of community structure with horizontal position in industrial units.

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32

Tummala, Manorama. "Surfactant-Aided Matrix Assisted Laser Desorption/Ionization Mass Spectrometry (SA-MALDI MS)." University of Cincinnati / OhioLINK, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1100672049.

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33

Gregori, Puigjané Elisabet. "A new Ligand-Based approach to virtual screening, and prolifing or large chemical libraries." Doctoral thesis, Universitat Pompeu Fabra, 2008. http://hdl.handle.net/10803/7166.

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La representació de les molècules per mitjà de descriptors moleculars és la base de moltes de les eines computacionals pel disseny de fàrmacs. Aquests mètodes computacionals es basen en l'abstracció de l'estructura química per resumir aquelles característiques rellevants sent al mateix temps eficients en la comparació de grans llibreries de molècules. Una característica molt important d'aquests descriptors és la seva habilitat de capturar la informació rellevant per la interacció amb qualsevol proteïna independentment de l'esquelet del compost. Això permet detectar com a similars qualsevol parella de compostos amb les mateixes característiques ordenades de la mateixa manera al voltant d'esquelets essencialment diferents, una propietat a la qual hom es refereix com a "scaffold hopping". Tenint en compte això, un nou conjunt de descriptors basat en la distribució de parelles de característiques farmacofòriques centrades en els àtoms per mitjà del concepte de teoria de la informació de l'entropia de Shannon [1], anomenats SHED, s'han desenvolupat.
Aquests descriptors han sigut usats amb èxit en nombroses aplicacions importants en el procés de descoberta de fàrmacs. Després de la implementació de noves tecnologies in vitro com ara el "high-throughput screening" i la química combinatòria, la capacitat de sintetitzar i assajar compostos va augmentar exponencialment però alhora la necessitat d'una selecció racional dels compostos va fer-se patent. La priorització dels compostos en termes de la predicció de la seva probabilitat de mostrar la activitat desitjada és per tant una de les primeres aplicacions del perfilat virtual basat en lligands usant els descriptors SHED.
En realitat, aquesta metodologia es pot estendre al punt de vista quimiogenòmic del procés de descoberta de fàrmacs, usant els descriptors per generar models basats en ligands de totes les proteïnes amb informació de lligands. Aquesta aproximació més ampla, el perfilat virtual de proteïnes, és un pas més per completar la matriu d'activitat entre tots els possibles compostos químics i totes les proteïnes rellevants. A més, una anàlisi més aprofundida d'aquesta matriu completa generada per mitjà del perfilat virtual de proteïnes pot dur-nos a una perspectiva de farmacologia en xarxa del procés de descoberta de fàrmacs. Aquesta direcció pot ser seguida afegint a aquesta informació de lligands i proteïnes la informació relativa a rutes de reaccions i anàlisi de sistemes, donant lloc a l'anomenada biologia química de sistemes que pot ajudar a entendre els processos biològics com un conjunt i a identificar de manera més racional noves i prometedores dianes terapèutiques.
The representation of molecules by means of molecular descriptors is the basis of most of the computational tools for drug design. These computational methods are based on the abstraction from the chemical structure to summarize its relevant features while being efficient in the comparison of large molecule libraries. A very important feature of these descriptors is their ability to capture the information relevant for the interaction with any target independently from the scaffold of the compound. This will allow detecting as similar any two compounds with the same features arranged in the same way around essentially different scaffolds, a property referred to as scaffold hopping. With this in mind, a new set of descriptors based on the distribution of atom-centred pharmacophoric feature pairs by means of the information theory concept of Shannon entropy [1], called SHED, have been developed.
These descriptors have been successfully used in a number of applications important in the drug discovery process. After the implementation of novel in vitro technologies like high-throughput screening and combinatorial chemistry, the capacity of synthesizing and testing compounds increased exponentially but the need for a rational selection of the compounds arose as well. The prioritisation of compounds in terms of their predicted chances of displaying the targeted activity is thus one of the first applications of the ligand-based virtual ligand screening based on SHED descriptors. This application has shown very good results, both in terms of enrichment of actives in the hit list and in terms of scaffold hopping ability, i.e. the novelty of the scaffolds of the found actives in the top ranked compounds.
Actually, this methodology can be extended to a chemogenomics view of the drug discovery process, using the descriptors to build ligand-based models of all the proteins with any ligand information. This broader approach, the virtual target profiling, is a step towards completing the activity matrix between all possible chemical compounds and all relevant targets. Moreover, a deeper analysis of this complete matrix generated by virtual target profiling can lead us to a network pharmacology perspective of the drug discovery process. This direction can be further followed by adding to ligand-target information the information about pathways and systems approaches, leading to a systems chemical biology approach that could help understanding biological processes as a whole and identifying more rationally novel and promising drug targets.

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Dias, Daniel Anthony, and danieldias@iprimus com au. "Natural Product Studies of Terrestrial and Marine Organisms." RMIT University. Applied Sciences, 2009. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20091019.161302.

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This thesis describes the isolation and structure elucidation of ten novel secondary metabolites from one fungus (Pycnoporus cinnabarinus), four lichens (Chrysothrix xanthina, Candelaria concolor, Ramalina glaucescens and Xanthoria parietina), three algae (Plocamium mertensii, Laurencia filiformis and Laurencia elata), two plants (Haemodorum simplex and Dianella callicarpa) and one sponge (Dactylospongia sp). The structures of these isolated compounds were elucidated by a combination of spectroscopic and chemical methods. This thesis also reports two new crystal structures, the identification of two new methylsilylated derivatives as well as the isolation of thirty seven previously reported compounds in which the complete structural assignment by one and two dimensional nuclear magnetic resonance spectroscopy (NMR) has been carried out on known compounds with incomplete or no NMR spectroscopic data. Furthermore, detailed spectroscopic analyses resulted in the re assignment of 1H and 13C chemical shifts for several previously isolated natural products. The biological screening (antimicrobial, antiviral and antitumor assays) of crude extracts and isolated natural products has also been presented. The application of chemical profiling techniques including GCxGC and high pressure liquid chromatography-nuclear magnetic resonance (HPLC-NMR) were utilised to assist with the natural product dereplication process (chemical profiling), monitor chemical degradations in situ and to identify the presence of new natural products and artefacts. In total, fifteen separate terrestrial and marine organisms were investigated.

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35

Bhattacharyya, Souryadeep. "Synthetic sensing systems in Saccharomyces cerevisiae." Thesis, Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/54016.

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The yeast Saccharomyces cerevisiae is a major chemical production platform in the biotechnological industry. It is also increasingly being used as a whole cell biosensor. One method of developing such whole cell biosensors in yeast is by exploiting its mating pathway, which is normally induced by secreted pheromones leading to downstream expression of various genes. Functional expression of different recognition elements or receptors and their coupling to the yeast mating pathway can enable sensing of a variety of ligands. In this work, we have engineered a yeast strain to functionally express a heterologous human olfactory receptor gene which can be coupled to the pheromone signaling pathway, allowing yeast to detect medium chain length fatty acids, alcohols and aldehydes for the first time. Functionally expressing heterologous olfactory receptors in yeast is a challenging task because no definitive method exists on how to express such receptors on the yeast cell surface and couple them to the downstream signaling pathway. We explore in this work how the yeast cell can selectively respond to two activating ligands via two different receptors. We also demonstrate in this work that a synthetic transcription factor can substitute for the native transcription factor in the yeast mating pathway. We believe our biosensor will not only have various uses as a versatile sensor but also aid in the design of synthetic genetic circuits.

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Kim, Dong Hyun. "Investigation of HIV anti-viral drug effect on HPV16 E6 expressing cervical carcinoma cells using advanced metabolomics methods." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/investigation-of-hiv-antiviral-drug-effect-on-hpv16-e6-expressing-cervical-carcinoma-cells-using-advanced-metabolomics-methods(d52b3b66-2a7b-4577-a334-b74bc12b27cc).html.

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Metabolomics approaches have recently been used to understand the complex molecular interactions of biological systems. One popular area in which these methods are being developed is to understand the biochemical changes during abiotic and biotic stresses; for example, how a cell may respond to a drug. Since metabolites are the end products of gene expression, these can be used to indicate the result of the activities and interaction of the cell or organism with its environment. The investigation of the level and compositional changes of metabolites against metabolic stresses such as chemotherapeutic treatment (drug exposure) are required to understand more fully abiotic perturbation to biological systems. The aim of this project was to understand the metabolic effect that the anti-viral drugs indinavir and lopinavir (currently used by HIV patients) have on HPV-related cervical cancer cell lines by measuring changes in metabolism using a wide range of analytical techniques; including Fourier transform infrared (FT-IR) and Raman spectroscopies, and gas and liquid chromatography-mass spectrometry (GC and LC-MS). The analyses and interpretation of the large volumes of complex multidimensional data generated by metabolomics approaches were performed with a combination of multivariate data analysis techniques such as principal components analysis (PCA) and canonical variates analysis (CVA), as well as univariate approaches such as N-Way analysis of variance (ANOVA). By combining biochemical imaging, metabolite fingerprinting and footprinting, and metabolite profiling, with multi- and uni-variate analyses, the actions and effects of the anti-viral drugs were investigated. FT-IR spectroscopy was initially used to generate global biochemical finger- and foot-prints, and Raman spectroscopy was employed to investigate intracellular distribution of metabolites, and other cellular species, as well as the localisation of drug molecules within cells. FT-IR spectroscopy ascertained that the intra- and extra-cellular metabolomes were being directly influenced in a fashion that correlated with increasing anti-viral dosing; these effects were phenotypic rather than measurements of the drug level. Raman imaging spectroscopy indicated that the indinavir but not lopinavir was being compartmentalised within the cell nucleus, but only in HPV early protein 6 (E6) expressing cells. This observation was further confirmed by fractionation of cell samples into nuclear and cytoplasmic fractions and assessing the indinavir concentrations via LC-MS. Finally, LC-MS and GC-MS metabolite profiling were employed to investigate changes in the intracellular metabolome in response to the anti-viral compounds across a range of physiologically relevant concentrations and in the presence and absence of the E6 oncoprotein. General effects of both anti-viral compounds included the regulation of metabolites such as glutathione, octenedionoic and octadecenoic acids, which may be involved in stress related responses, reduced levels of sugars and sugar-phosphates indicating a potential arrest of glycolysis, and reduced levels of malic acid indicating potential decreased flux into the TCA cycle; all indicating that central metabolism was being reduced. Finally, LC-MS based quantification indicated that in the presence of E6, lopinavir was actively removed from the cell, whereas the indinavir intracellular concentration increased concomitantly with the level of dosing. These investigations have revealed that metabolomics approaches are an apt tool for the study of anti-viral effects within cell cultures, but improvements need to be made with respect to the major limitation of metabolite identification.

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Tran, Thi Thuy. "Compact-disc microfluidic methods for characterization of therapeutic antibodies : Analysis of post-translational modifications." Doctoral thesis, Stockholms universitet, Institutionen för analytisk kemi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-83355.

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Characterization of post-translational modifications (PTMs) of therapeutic proteins is very important during the bioprocess development to maintain desired product quality and during the submission process to regulatory authorities for product approval. Monitoring glycosylation in pharmacokinetic studies can be useful to evaluate the dependence of clearance rates on different glycoforms. The cost and efficiency of characterization affect the speed to market of biopharmaceutical proteins. A reduction in the number of manual processing steps, cost of reagents and consumption of sample, as well as the time required for chemical analysis, is therefore necessary. The research presented in this thesis is focused on the potential of using microfluidic discs for automated, miniaturized, parallel and rapid sample preparation for PTM characterization of therapeutic monoclonal antibodies. Paper I describes the method development for N-linked glycosylation profiling. Several sample preparation steps have been performed in an integrated process in the microfluidic compact disc (CD). Paper II demonstrates the use of the method presented in paper I in combination with multivariate statistics for discrimination of glycosylation profiles of different therapeutic antibodies and simulation of a real case of quality control. Paper III is focused on a method for monitoring changes in glycosylation profiles of therapeutic antibodies in serum over time by incubation with an exoglycosidase enzyme. Paper IV describes the method for peptide mapping of therapeutic antibodies. In addition, recent work (unpublished results) assesses the potential of this method for methionine oxidation detection. The developed methods were fast, robust with low sample/reagent consumption. Generation of glycosylation profile data for one sample was established in approximately 2 h. The amount of samples and antigens loaded into the CD platform for one replicate was less than 0.3 μg and approximately 0.06 μg, respectively. Furthermore, considering the parallel function of the CD, conducting the analysis for 54 samples can be completed within a day.

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.

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Ballentine, Regina. "Chemical Characterization of Pseudognaphalium obtusifolium by Gas Chromatography - Mass Spectrometry (GC-MS) to Assess Potential Therapeutic Phytochemicals and Toxicological Concerns Using Simulated Use Conditions." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/6052.

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Chemical Characterization of Pseudognaphalium obtusifolium by Gas Chromatography – Mass Spectrometry (GC-MS) to Assess Potential Therapeutic Phytochemicals and Toxicological Concerns Using Simulated Use Conditions By Regina Ballentine Virginia Commonwealth University, 2019 Director: Sarah C. Rutan, Professor, Department of Chemistry Currently, there is an increasing demand for natural therapies and herbal products to treat various ailments. It is generally believed that natural therapies have fewer side-effects than traditional western medicine; however, they are often used in different strengths and formulations without consistency of the levels of target compounds or knowledge about toxicity. Due to this growing trend, a comprehensive chemical evaluation of plants used for medicinal purposes is necessary. Pseudognaphalium obtusifolium is a plant that has been used historically by Native Americans as an herbal medicine. It is a flowering plant belonging to the Asteraceae family indigenous to the Eastern United States. There are documented accounts of the Native Americans using the herb therapeutically. Reportedly, they used the plant to prepare tea and as filler for bedding. Additionally, they smoked the plant material. To date, there has been little research published on the chemical composition of this plant. Thus, the objective of this work was to conduct a chemical survey of P. obtusifolium using methodologies that would simulate the three historical routes of administration (tea, bedding material, and smoke inhalation). To determine the types of compounds that may be found in the plant, initial experiments using pressurized solvent extraction (PSE) with an ethanolic solvent were performed followed by analysis using gas chromatography – mass spectrometry (GC-MS) in scan mode. This extraction technique enabled a broad range of compounds to be identified. For the analysis of the tea, the leaves and the flowers were ground and analyzed separately. The “tea” simulation was then performed using a water extraction which was then back extracted into dichloromethane for GC-MS analysis in Selected Ion Monitoring (SIM) mode. Seventeen target compounds (terpenes, terpinoids, flavanoids, etc.) were quantified using this method. A bedding material simulation was performed using headspace solid phase micro-extraction (HS-SPME) to collect the volatile and/or semi-volatile components of the headspace. The compounds collected on the SPME fiber were then analyzed by GC-MS in scan and SIM modes to qualitatively and quantitatively determine the types of chemical compounds (most of which were terpenes) that may be off-gassed from bedding material. This analysis compared levels of compounds in two different crop years and four terpene compounds were quantified. To simulate smoking of the plant material, the leaves and flowers were fashioned into smoking articles. Sample collection was performed by a smoking machine and smoke condensate was collected. The smoke condensate was then analyzed by GC-MS in scan mode. As combustion and pyrolysis of plant material are known to produce toxic products, specific potentially harmful compounds were investigated and quantified. This chemical analysis of P. obtusifolium identified target compounds that can be found in the three simulated usage forms. Identification of these compounds gives insight on why the Native Americans may have used P. obtusifolium as an herbal medicine. Among the detected compounds, there were many unknowns. Elucidating these unknown compounds will be important in the effort to understand the full chemical profile of this plant.

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Lapachinske, Silvio Fernandes. "Análises físicas e químicas de comprimidos de ecstasy apreendidos no município de São Paulo." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/9/9141/tde-17072009-114817/.

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Drug profiling, isto é, a caracterização de amostras de drogas apreendidas no sentido de estabelecer conexões entre apreensões realizadas em diferentes épocas e/ou locais a uma origem comum de produção clandestina, tem sido um objetivo dos órgãos governamentais responsáveis pela prevenção/repressão. Especificamente tratando-se de comprimidos de ecstasy, o conhecimento de suas propriedades físicas e químicas é de relevante importância para discriminar a apreensão de diferentes lotes. Nesse contexto, o presente trabalho propõe uma nova abordagem para estabelecer conexões entre apreensões de comprimidos de ecstasy, por meio da calorimetria exploratória diferencial (DSC), termogravimetria (TG) e difratometria de raios-X (DRX). Também foi realizada a caracterização física de todos os comprimidos (logotipo, coloração, massa, diâmetro e espessura), bem como a identificação/quantificação dos constituintes ativos por cromatografia em fase gasosa acoplada à espectrometria de massas (GC-MS) e o perfil de dissolução in vitro. Além disso, foi desenvolvido um método empregando a extração líquido-líquido para o isolamento da 3,4-metilenodioximetanfetamina (MDMA) dos comprimidos de ecstasy, que posteriormente foi cristalizada para cloridrato de MDMA (MDMA.HCl). Foram analisados dezessete diferentes lotes de comprimidos de ecstasy de diversos logotipos e colorações apreendidos no município de São Paulo, Brasil. Apenas um lote apresentou como única substância ativa a clorofenilpiperazina (CPP). Os outros continham apenas MDMA e o conteúdo de MDMA variou de 29 a 115-mg/comprimido. Os valores de massa dos comprimidos variaram de 143 a 341-mg, a espessura de 3,2 a 5,8-mm e o diâmetro de 7,0 a 9,5-mm. A comparação das curvas obtidas, tanto por calorimetria exploratória diferencial (DSC) como pelos difratogramas de raios-X (DRX), permitiu discriminar aqueles com perfis semelhantes, importante para identificar a origem de produção. O baixo grau de cristalinidade do MDMA.HCl de alguns comprimidos de ecstasy não impediu a caracterização por DSC e DRX. Esses resultados podem ser úteis para a aplicação no trabalho de inteligência forense.
Drug profiling or the characterization of seized drug samples to link seizures made at different times and/or locations to their common clandestine origin, has long been a goal of law enforcement agencies. Considering the trafficking of ecstasy tablets, the knowledge of chemical and physical properties is of utmost importance to discriminate between different seizures. In this context this study proposed a new approach to establish links among seizures of ecstasy tablets by using differential scanning calorimetry (DSC), thermogravimetry (TG) and X-ray diffraction (XRD). Besides this characterization, physical appearance (logotype, color, weight, diameter and thickness), identification/quantification of active constituents by gas chromatography/ mass spectrometry (GC/MS) and in vitro drug dissolution assays were performed too. A method employing liquid-liquid extraction was also developed for the isolation of 3,4-methylenedioxymethamphetamine (MDMA) from ecstasy tablets and afterwards MDMA was crystallized to MDMA hydrochloride (MDMA.HCl). Seventeen different lots of various logotypes and colors of confiscated ecstasy tablets from seizures in São Paulo city, Brazil, were analyzed. Chlorophenylpiperazine (CPP) was found only as an active ingredient in one batch. The others tablets contained only MDMA and the content of MDMA varied from 29 to 115-mg/tablet. The weight values of tablets varied from 143 to 341-mg, the thickness from 3,2 to 5,8-mm and the diameter from 7,0 to 9,5-mm. DSC/TG curves and X-ray difratograms of the ecstasy tablets allowed distinguishing those with similar profile, for both techniques, which is important to identify the source of production. The low degree of MDMA.HCl crystallinity of some ecstasy tablets didnt prevent DSC and XRD characterization. These results can be useful for forensic intelligence work application.

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Sobhani, Negin. "Applications, performance analysis, and optimization of weather and air quality models." Diss., University of Iowa, 2017. https://ir.uiowa.edu/etd/5996.

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Atmospheric particulate matter (PM) is linked to various adverse environmental and health impacts. PM in the atmosphere reduces visibility, alters precipitation patterns by acting as cloud condensation nuclei (CCN), and changes the Earth’s radiative balance by absorbing or scattering solar radiation in the atmosphere. The long-range transport of pollutants leads to increase in PM concentrations even in remote locations such as polar regions and mountain ranges. One significant effect of PM on the earth’s climate occurs while light absorbing PM, such as Black Carbon (BC), deposits over snow. In the Arctic, BC deposition on highly reflective surfaces (e.g. glaciers and sea ices) has very intense effects, causing snow to melt more quickly. Thus, characterizing PM sources, identifying long-range transport pathways, and quantifying the climate impacts of PM are crucial in order to inform emission abatement policies for reducing both health and environmental impacts of PM. Chemical transport models provide mathematical tools for better understanding atmospheric system including chemical and particle transport, pollution diffusion, and deposition. The technological and computational advances in the past decades allow higher resolution air quality and weather forecast simulations with more accurate representations of physical and chemical mechanisms of the atmosphere. Due to the significant role of air pollutants on public health and environment, several countries and cities perform air quality forecasts for warning the population about the future air pollution events and taking local preventive measures such as traffic regulations to minimize the impacts of the forecasted episode. However, the costs associated with the complex air quality forecast models especially for simulations with higher resolution simulations make “forecasting” a challenge. This dissertation also focuses on applications, performance analysis, and optimization of meteorology and air quality modeling forecasting models. This dissertation presents several modeling studies with various scales to better understand transport of aerosols from different geographical sources and economic sectors (i.e. transportation, residential, industry, biomass burning, and power) and quantify their climate impacts. The simulations are evaluated using various observations including ground site measurements, field campaigns, and satellite data. The sector-based modeling studies elucidated the importance of various economical sector and geographical regions on global air quality and the climatic impacts associated with BC. This dissertation provides the policy makers with some implications to inform emission mitigation policies in order to target source sectors and regions with highest impacts. Furthermore, advances were made to better understand the impacts of light absorbing particles on climate and surface albedo. Finally, for improving the modeling speed, the performances of the models are analyzed, and optimizations were proposed for improving the computational efficiencies of the models. Theses optimizations show a significant improvement in the performance of Weather Research and Forecasting (WRF) and WRF-Chem models. The modified codes were validated and incorporated back into the WRF source code to benefit all WRF users. Although weather and air quality models are shown to be an excellent means for forecasting applications both for local and hemispheric scale, further studies are needed to optimize the models and improve the performance of the simulations.

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Wagner, Louis. "Precise nuclear data of the 14N(p,gamma)15O reaction for solar neutrino predictions." Helmholtz-Zentrum Dresden-Rossendorf, 2018. https://tud.qucosa.de/id/qucosa%3A31122.

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The 14N(p,gamma)15O reaction is the slowest stage of the carbon-nitrogen-oxygen cycle of hydrogen burning and thus determines its reaction rate. Precise knowledge of its rate is required to improve the model of hydrogen burning in our sun. The reaction rate is a necessary ingredient for a possible solution of the solar abundance problem that led to discrepancies between predictions of the solar standard model and helioseismology. The solar 13N and 15O neutrino fluxes are used as independent observables that probe the carbon and nitrogen abundances in the solar core. This could settle the disagreement, if the 14N(p,gamma)15O reaction rate is known with high precision. After a review of several measurements its cross section was revised downward due to a much lower contribution by one particular transition, capture to the ground state in 15O. The evaluated total relative uncertainty is still 7.5%, in part due to an unsatisfactory knowledge of the excitation function over a wide energy range. The present work reports experimentally determined cross sections as astrophysical S-factor data at twelve energies between 0.357 - 1.292 MeV for the strongest transition, capture to the 6.79 MeV excited state in 15O with lower uncertainties than before and at ten energies between 0.479 - 1.202 MeV for the second strongest transition, capture to the ground state in 15O. In addition, an R-matrix fit is performed to estimate the impact of the new data on the astrophysical relevant energy range. The recently suggested slight S-factor enhancement at the Gamow window could not be confirmed and differences to previous measurements at energies around 1 MeV were observed. The present extrapolated zero-energy S-factors are S_6.79(0) = (1.19+-0.10) keV b and S_GS(0) = (0.25+-0.05) keV b and they are within the uncertainties consistent with values recommended by the latest review.
Die 14N(p,gamma)15O Reaktion ist die langsamste Phase im Bethe-Weizsäcker-Zyklus des Wasserstoffbrennens und bestimmt deshalb die Reaktionsrate des gesamten Zyklus. Präzise Werte für die Reaktionsrate sind notwendig um das Wasserstoffbrennen in unserer Sonne besser zu verstehen. Besonders das Problem widersprüchlicher Ergebnisse aus Vorhersagen des aktuellen Sonnenmodells und helioseismologischen Experimenten könnte durch genauer bekannte 14N(p,gamma)15O Reaktionsraten aufgelöst werden. Dafür soll der solare 13N und 15O Neutrinofluss von den beta+-Zerfällen als direkter Informationsträger über die Häufigkeit von Stickstoff und Kohlenstoff im Sonneninneren genutzt werden. Der für die Berechnung der Häufigkeiten benötigte Wirkungsquerschnitt der 14N(p,gamma)15O Reaktion wurde in einer Evaluation verschiedener Messungen reduziert, da der Anteil des direkten Protoneneinfang mit Übergang in den Grundzustand deutlich weniger zum gesamten Wirkungsquerschnitt beiträgt als zuvor angenommen. Die evaluierte relative Gesamtunsicherheit ist mit 7.5% dennoch hoch, was zu einem großen Teil an ungenügendem Wissen über die Anregungsfunktion in einem weiten Energiebereich liegt. In der vorliegenden Arbeit werden experimentell ermittelte Wirkungsquerschnitte in Form von astrophysikalischen S-Faktoren für zwei Übergänge vorgestellt. Für den stärksten Übergang, den Protoneneinfang zum angeregten Zustand bei 6.79 MeV in 15O, wurden zwölf S-Faktoren bei Energien zwischen 0.357 – 1.292 MeV mit geringeren Unsicherheiten als zuvor ermittelt und für den direkten Übergang in den Grundzustand zehn Werte zwischen 0.479 – 1.202 MeV. Außerdem wurde ein R-Matrix Fit durchgeführt um den Einfluss der neuen Daten auf Extrapolationen zum astrophysikalisch relevanten Energiebereich zu prüfen. Die kürzlich vorgeschlagene Erhöhung des S-Faktors im Gamow-Fenster konnte nicht bestätigt werden und es wurden auch Unterschiede zu bisherigen Messungen im Energiebereich um 1 MeV deutlich. Die neuen extrapolierten S-Faktoren sind S679(0) = (1.19±0.10) keV b und SGS(0) = (0.25 ± 0.05) keV b und sie stimmen mit den von der Evaluation empfohlenen Werten im Rahmen ihrer Unsicherheiten überein.

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42

Song, Shin Miin, and shinmiin@singnet com sg. "Comprehensive two-dimensional gas chromatography (GCxGC ) for drug analysis." RMIT University. Applied Sciences, 2006. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20080627.114511.

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Separation technologies have occupied a central role in the current practices of analytical methods used for drug analysis today. As the emphasis in contemporary drug analysis shifts towards ultra-trace concentrations, the contribution from unwanted matrix interferences takes on greater significance. In order to single out a trace substance with confidence from a rapidly expanding list of drug compounds (and their metabolites) in real complex specimens, analytical technologies must evolve to keep up with such trends. Today, the task of unambiguous identification in forensic toxicology still relies heavily upon chromatographic methods based on mass spectrometric detection, in particular GC-MS in electron ionisation (EI) mode. Although the combined informing power of (EI) GC-MS has served faithfully in a myriad of drug application studies to date, we may ask if (EI) GC-MS will remain competitive in meeting the impending needs of ultra-trace drug analysis in the fut ure? To what extent of reliability can sample clean-up strategies be used in ultra-trace analysis without risking the loss of important analytes of interest? The increasing use of tandem mass spectrometry with one-dimensional (1D) chromatographic techniques (e.g. GC-MS/MS) at its simplest, considers that single-column chromatographic analysis with mass spectrometry alone is not sufficient in providing unambiguous confirmation of the identity of any given peak, particularly when there are peak-overlap. Where the mass spectra of the individual overlapping peaks are highly similar, confounding interpretation of their identities may arise. By introducing an additional resolution element in the chromatographic domain of a 1D chromatographic system, the informing power of the analytical system can also be effectively raised by the boost in resolving power from two chromatographic elements. Thus this thesis sets out to address the analytical challenges of modern drug analysis through the application of high resolut ion comprehensive two-dimensional gas chromatography (GCeGC) to a series of representative drug studies of relevance to forensic sciences.

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Leslie, Kevin A. "Evaluation and Adaptation of Live-Cell Interferometry for Applications in Basic, Translational, and Clinical Research." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5562.

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Cell mass is an important indicator of cell health and status. A diverse set of techniques have been developed to precisely measure the masses of single cells, with varying degrees of technical complexity and throughput. Here, the development of a non-invasive, label-free optical technique, termed Live-Cell Interferometry (LCI), is described. Several applications are presented, including an evaluation of LCI’s utility for assessing drug response heterogeneity in patient-derived melanoma lines and the measurement of CD3+ T cell kinetics during hematopoietic stem cell transplantation. The characterization of mast cells during degranulation, the measurement of viral reactivation kinetics in Kaposi’s Sarcoma, and drug response studies in patient-derived xenograft models of triple-negative breast cancer are also discussed. Taken together, data from these studies highlight LCI’s versatility as a tool for clinical, translational, and basic research applications.

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Hojati, Ashkhan. "Pharmacologic profiling of novel compounds via fluorometric analyses of monoamine transporter responses." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5983.

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In humans and other organisms, monoaminergic systems are crucial in neuronal function and behavior. The monoamine transporters (MATs), which can be found on the presynaptic plasma membrane of neurons in the central nervous system (CNS), are crucial in the regulation of neurotransmitter concentration in the synaptic cleft. As the duration and concentration of neurotransmitters in the cleft affect further downstream signaling responses, these proteins are important targets for both understanding neuronal physiology and compounds of interest. Multiple theories exist proponing the contribution of MATs to a variety of mental and neurological disorders, including depression. This theory establishes that depression is caused by imbalances in monoamine neurotransmitters. Compounds such as Fluoxetine (FLX) are classified as selective serotonin reuptake inhibitors (SSRIs), these drugs selectively block the reuptake of neurotransmitters at the serotonin transporter (SERT). Since differences in MAT selectivity of inhibitory compounds are influential to selecting efficacious antidepressant treatments, we utilized a unique fluorescent analysis technique to explore three therapeutic compounds of interest (in-vitro) which contain structural similarity to FLX. Our results confirm the selectivity of FLX at SERT, and classify the novel compounds studied into different potential categories of reuptake inhibitors. We hope these compounds will be studied further to elucidate their potentially therapeutic roles and mitigation of undesired side effects seen in other medications.

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Nahle, Sara. "Réponse macrophagique aux nanomatériaux carbonés : effets de leur caractéristiques physiques et chimiques sur le transcriptome Carbon-based nanomaterials induce inflammation and autophagy in rat alveolar macrophages Single wall and multiwall carbon nanotubes induce different toxicological responses in rat alveolar macrophages Gene expression profiling of alveolar macrophages exposed to non-functionalized, anionic or cationic multi-walled carbon nanotubes shows three different mechanisms of toxicity Cytotoxicity and global transcriptional responses induced by zinc oxide nanoparticles NM 110 in PMA-differentiated THP-1 cells Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles." Thesis, Université de Lorraine, 2019. http://www.theses.fr/2019LORR0142.

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Les nanomatériaux carbonés (NMC) sont très utilisés dans le monde industriel et leurs applications, nombreuses, sont en plein développement. L’absence de réglementation pour leur préparation et leur emploi fait qu’il est nécessaire comme pour tous les nano-objets, de déterminer le risque qu’une exposition fait courir à l’Homme et d’adapter la législation en conséquence. Une meilleure connaissance de leur potentiel toxique est donc nécessaire. Les difficultés de plus en plus grandes pour utiliser les modèles animaux, rend nécessaire le développement d’études avec des lignées cellulaires au sein desquelles les macrophages ont une place prépondérante. Ces NMC sont très légers et forment facilement des aérosols et les modèles préférés sont les macrophages alvéolaires. Cependant il n’existe pas à l’heure actuelle de lignées de macrophages alvéolaires humains à la différence de cellules de rat. Le sujet de ma thèse porte sur l’étude de la réponse macrophagique aux NMC et la compréhension des effets de leurs caractéristiques physiques et chimiques sur leur transcriptome. Les NMC étudiés sont les nanotubes de carbone (NTC) multi feuillets, les NTC mono feuillets, le noir de carbone et l’oxyde de graphène. Nos résultats montrent que tous les NMC étudiés déclenchent une réaction inflammatoire dans les cellules NR8383 et les cellules THP-1 différenciées, et certains d’entre eux induisent une cytotoxicité importante. La taille, la fonctionnalisation et la forme contrôlent les mécanismes de toxicité induits par les NMC. Des NTC de tailles similaires altèrent des voies de signalisation identiques, une fonctionnalisation par des groupements amines produit un stress des lysosomes tandis que la fonctionnalisation par des groupements carboxyle entraine un stress du réticulum endoplasmique (RE). Les nanotubes induisent une désorganisation du cytosquelette plus importante que les nanoparticules sphériques. Nous avons également mis en évidence une accumulation de lipides chez les cellules NR8383 suite à un stress du RE induit par le Mitsui-7, un NTC multi feuillet. Le même NTC induit aussi une fusion de ces macrophages. La formation de ces cellules spumeuses et des cellules géantes à multi-noyaux sont des évènements clés entrainant la formation de granulomes. Les résultats obtenus présentent un support important pour la compréhension des effets des NMC montrant une certaine toxicité non négligeable de point de vue moléculaire. Cette toxicité est dépendante des caractéristiques physiques et chimiques de ces nanomatériaux. Ainsi, en se basant sur ce type de données, on pourra s’orienter vers une fabrication safe-by-design pour limiter les risques liés à leur exposition
Carbon nanomaterials (CNM) are widely used in the industrial world and they have many applications. The absence of legislation controlling their preparation and uses makes necessary, as for all nano-objects, the study of their toxicity in order to determine the risk of human exposure and to adapt legislation accordingly. Therefore, a better knowledge of their toxic potential is necessary. The increasing difficulties in using animal models make necessary the development of studies using cell lines especially macrophages that play a predominant role. These CNM are very light and form easily aerosols, reason why the preferred models for toxicity studies are alveolar macrophages. However, there are no human alveolar macrophage lines currently but rat cells exist. The subject of my thesis is to study macrophages response to CNM and the understanding of the effect of their physical and chemical characteristics on the transcriptome. The CNM studied are multiwall carbon nanotubes (CNT), single wall CNT, carbon black and graphene oxide. Our results show that all CNM studied trigger an inflammatory reaction in NR8383 and differentiated THP-1 cells, also some of them induce cytotoxicity. Size, functionalization and form control CNM toxicity mechanisms: CNT with similar size alter identical signaling pathways, amino group functionalization produces lysosomal stress, whereas functionalization with carboxyl groups causes reticulum endoplasmic (RE) stress, nanotubes induce cytoskeleton disorganization more than spherical nanoparticles. Otherwise, we identified lipid accumulation in NR8383 cells due to RE stress induced by Mitsui-7, a multiwall CNT. There was also a fusion of these macrophages. The formation of these foam cells and giant multi-nucleus cells are key events leading to granulomas formation. The results obtained are an important support for understanding CNM effects, showing some significant toxicity at molecular level. This toxicity is dependent on the physical and chemical characteristics of these nanomaterials. Thus, based on this type of data, we can move towards a safer manufacture to avoid the risks associated with their exposure

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Gregorauskienė, Virgilija. "Cheminių elementų kiekių kaitos dėsningumai Lietuvos dirvožemio profilyje." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2012. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2012~D_20121227_090556-03063.

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Disertaciniame darbe analizuojama Lietuvos dirvožemio cheminės sudėties vertikali kaita, paremta akredituotose laboratorijose nustatytais Lietuvos teritorijoje gautais duomenimis, analizuotais taikant standartizuotus matematinius–statistinius metodus. Tai leido objektyviai pagrįsti vertikalaus cheminių elementų pasiskirstymo dirvožemyje bendrus dėsningumus ir išryškinti Lietuvos dirvožemio vertikalios geocheminės sudėties specifiką tarptautiniame kontekste. Dirvožemio granuliometrinės sudėties ir išskirtų frakcijų cheminės sudėties analizė išryškino sąsajas tarp dirvožemio granuliometrinės ir cheminės sudėties. Disertacijoje apibendrintos dirvodarinių uolienų bei atskirų jų litologinių tipų pirminės cheminės sudėties savybės ir šių savybių vaidmuo dirvožemio profilio formavimesi. Apžvelgiant geocheminės sudėties kaitą atskiruose dirvožemio profiliuose, atskleista įvairių dirvodaros procesų bei žmogaus veiklos įtaka vertikaliam elementų persiskirstymui dirvožemyje. Lietuvos teritorijoje tolygiai išdėstytų dirvožemio kasinių geocheminių tyrimų duomenys leido korektiškai suformuoti tipinius smėlio–priesmėlio ir molio–priemolio dirvožemio geocheminius profilius ir atskleisti jų būdingąsias savybes. Realių duomenų pagrindu sudarytas tipinio Lietuvos dirvožemio geocheminio profilio modelis ir išryškintos esminės dirvožemio vertikalios geocheminės sudėties kaičiosios savybės – Lietuvos dirvožemyje vyrauja daugumos elementų išplovimas ir išnešimas už profilio ribų.
Vertical alternation of chemical composition in Lithuanian soil profile has been investigated in the study. Investigations are based on the certified analytical data, by applying standard mathematical–statistical data processing that enables to justify the vertical distribution patterns of trace and major elements and obtain internationally comparable concluding results on the national soil geochemistry. Soil grain size analysis and chemical analysis of separated sand, silt and clay particles revealed the relation between the soil grain size and chemical composition. Investigation of chemical composition of the soil parent material reflected its dominance as soil forming factor. Geochemical survey of the 74 individual soil profiles, representing all soil regions and main soil types, allowed to expose various soil forming processes and on its background to generalize geochemical features and ascertain the dominant ones in the sand–loamy sand and the loam–clay soil of Lithuania. On the base of original geochemical data the model geochemical soil profile was created and the dominant geochemical process was determined – element depletion and removal out of soil profile prevails in Lithuania.

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Jones, Christina Michele. "Applications and challenges in mass spectrometry-based untargeted metabolomics." Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/54830.

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Metabolomics is the methodical scientific study of biochemical processes associated with the metabolome—which comprises the entire collection of metabolites in any biological entity. Metabolome changes occur as a result of modifications in the genome and proteome, and are, therefore, directly related to cellular phenotype. Thus, metabolomic analysis is capable of providing a snapshot of cellular physiology. Untargeted metabolomics is an impartial, all-inclusive approach for detecting as many metabolites as possible without a priori knowledge of their identity. Hence, it is a valuable exploratory tool capable of providing extensive chemical information for discovery and hypothesis-generation regarding biochemical processes. A history of metabolomics and advances in the field corresponding to improved analytical technologies are described in Chapter 1 of this dissertation. Additionally, Chapter 1 introduces the analytical workflows involved in untargeted metabolomics research to provide a foundation for Chapters 2 – 5. Part I of this dissertation which encompasses Chapters 2 – 3 describes the utilization of mass spectrometry (MS)-based untargeted metabolomic analysis to acquire new insight into cancer detection. There is a knowledge deficit regarding the biochemical processes of the origin and proliferative molecular mechanisms of many types of cancer which has also led to a shortage of sensitive and specific biomarkers. Chapter 2 describes the development of an in vitro diagnostic multivariate index assay (IVDMIA) for prostate cancer (PCa) prediction based on ultra performance liquid chromatography-mass spectrometry (UPLC-MS) metabolic profiling of blood serum samples from 64 PCa patients and 50 healthy individuals. A panel of 40 metabolic spectral features was found to be differential with 92.1% sensitivity, 94.3% specificity, and 93.0% accuracy. The performance of the IVDMIA was higher than the prevalent prostate-specific antigen blood test, thus, highlighting that a combination of multiple discriminant features yields higher predictive power for PCa detection than the univariate analysis of a single marker. Chapter 3 describes two approaches that were taken to investigate metabolic patterns for early detection of ovarian cancer (OC). First, Dicer-Pten double knockout (DKO) mice that phenocopy many of the features of metastatic high-grade serous carcinoma (HGSC) observed in women were studied. Using UPLC-MS, serum samples from 14 early-stage tumor DKO mice and 11 controls were analyzed. Iterative multivariate classification selected 18 metabolites that, when considered as a panel, yielded 100% accuracy, sensitivity, and specificity for early-stage HGSC detection. In the second approach, serum metabolic phenotypes of an early-stage OC pilot patient cohort were characterized. Serum samples were collected from 24 early-stage OC patients and 40 healthy women, and subsequently analyzed using UPLC-MS. Multivariate statistical analysis employing support vector machine learning methods and recursive feature elimination selected a panel of metabolites that differentiated between age-matched samples with 100% cross-validated accuracy, sensitivity, and specificity. This small pilot study demonstrated that metabolic phenotypes may be useful for detecting early-stage OC and, thus, supports conducting larger, more comprehensive studies. Many challenges exist in the field of untargeted metabolomics. Part II of this dissertation which encompasses Chapters 4 – 5 focuses on two specific challenges. While metabolomic data may be used to generate hypothesis concerning biological processes, determining causal relationships within metabolic networks with only metabolomic data is impractical. Proteins play major roles in these networks; therefore, pairing metabolomic information with that acquired from proteomics gives a more comprehensive snapshot of perturbations to metabolic pathways. Chapter 4 describes the integration of MS- and NMR-based metabolomics with proteomics analyses to investigate the role of chemically mediated ecological interactions between Karenia brevis and two diatom competitors, Asterionellopsis glacialis and Thalassiosira pseudonana. This integrated systems biology approach showed that K. brevis allelopathy distinctively perturbed the metabolisms of these two competitors. A. glacialis had a more robust metabolic response to K. brevis allelopathy which may be a result of its repeated exposure to K. brevis blooms in the Gulf of Mexico. However, K. brevis allelopathy disrupted energy metabolism and obstructed cellular protection mechanisms including altering cell membrane components, inhibiting osmoregulation, and increasing oxidative stress in T. pseudonana. This work represents the first instance of metabolites and proteins measured simultaneously to understand the effects of allelopathy or in fact any form of competition. Chromatography is traditionally coupled to MS for untargeted metabolomics studies. While coupling chromatography to MS greatly enhances metabolome analysis due to the orthogonality of the techniques, the lengthy analysis times pose challenges for large metabolomics studies. Consequently, there is still a need for developing higher throughput MS approaches. A rapid metabolic fingerprinting method that utilizes a new transmission mode direct analysis in real time (TM-DART) ambient sampling technique is presented in Chapter 5. The optimization of TM-DART parameters directly affecting metabolite desorption and ionization, such as sample position and ionizing gas desorption temperature, was critical in achieving high sensitivity and detecting a broad mass range of metabolites. In terms of reproducibility, TM-DART compared favorably with traditional probe mode DART analysis, with coefficients of variation as low as 16%. TM-DART MS proved to be a powerful analytical technique for rapid metabolome analysis of human blood sera and was adapted for exhaled breath condensate (EBC) analysis. To determine the feasibility of utilizing TM-DART for metabolomics investigations, TM-DART was interfaced with traveling wave ion mobility spectrometry (TWIMS) time-of-flight (TOF) MS for the analysis of EBC samples from cystic fibrosis patients and healthy controls. TM-DART-TWIMS-TOF MS was able to successfully detect cystic fibrosis in this small sample cohort, thereby, demonstrating it can be employed for probing metabolome changes. Finally, in Chapter 6, a perspective on the presented work is provided along with goals on which future studies may focus.

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Oliver, Lauren Elizabeth. "Genetic, chemical and visible color profiling of teinturier grape varieties." Diss., 2009. http://proquest.umi.com/pqdweb?did=1987504941&sid=1&Fmt=2&clientId=48051&RQT=309&VName=PQD.

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Shabtai, Daniel. "An Algorithm for Chemical Genomic Profiling that Minimizes Batch Effects: Bucket Evaluations." Thesis, 2011. http://hdl.handle.net/1807/32921.

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Chemical genomics is an interdisciplinary field that combines small molecule perturbation with genomics to understand gene function and to study the mode(s) of drug action. Existing methods for correlating chemical genomic profiles are not ideal as they often require one to define the disrupting effects, commonly known as batch effects. These effects are not always known, and they can mask true biological differences. I present a method, Bucket Evaluations (BE), which surmounts these problems. This method is a non-parametric correlation approach, which is suitable for locating correlations in somewhat perturbed datasets such as chemical genomic profiles. BE can be used on other datasets such as those obtained via gene expression profiling and performs well on both array-based and sequence based readouts. Using BE, along with various correlation methods, on a collection of datasets, showed it to be highly accurate for locating similarity between experiments.

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Lemos, Margarida Barbosa Pereira de. "Ageing profiling of commercial and craft beers: a sensorial and chemical overview." Master's thesis, 2014. http://hdl.handle.net/1822/35438.

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Dissertação de mestrado integrado em Engenharia Biológica (área de especialização em Tecnologia Química e Alimentar)
Beer is a beverage obtained by alcoholic fermentation, containing alcohol, extract and carbon dioxide. It is prepared from barley malt, hops, brewing water, and yeasts (from which derive the predominant influences on overall beer types). Since different beer styles result from the combination and relationships between several factors (ingredients, processing, packaging, marketing and culture), the final flavor will be different. However, the beer flavor is not static but in a continuous changing state. The point where maturation ends and deterioration begins is undoubtedly different for different beers and probably different for each consumer. The aim of this study was to investigate the changes that occur during the storage/ageing of six different of beers: four craft (Weiss, Pilsner, Stout, Red Ale) and two commercial beers (Weiss and Pilsner). The main differences between these beers are the fact that craft beers are made exclusively of natural raw material, no preservatives or additives are added and are they are not pasteurized or filtered (containing the yeast in the bottle). The beers were analyzed sensory and chemically (major and minor compounds) once a month over six months. Minor compounds were analyzed for the first and sixth month. Craft beers showed an aromatic profile much more intense than the commercial beers and kept the profile constant over the six months (as the commercial beers). The results allowed to conclude that the craft beers maintain the quality of a commercial beer, over six months, with the benefit of having most intense flavors and aromas. Through the analysis of major compounds, no clear trends for ethanol and sugars concentrations were obtained. The concentration of organic acids on craft beers was higher than the concentrations typically found in commercial beers. The results of minor compounds analysis were in line with the aromatic profiles obtained by sensory analysis, as well as those portrayed in the literature. The results showed that most of the principal aging markers reported were not found in the beers studied. However other compounds were found like higher alcohols, ketones and acids. The validation of the method of extraction of minor compounds (used to analysis by gas chromatography–mass spectrometry) was conducted. To validate the method several parameters were studied: linearity, sensitivity, detection and quantification limits, precision (repeatability and intermediate precision), matrix effect, time effect and accuracy (spiking test). The results showed that the method satisfies the specifications determined for each validation parameter. This means that the validation of the extraction method was a success.
A cerveja é uma bebida obtida por fermentação alcoólica que contem álcool, extrato e dióxido de carbono. É preparada a partir de malte de cereais, lúpulo, água e leveduras (a partir dos quais derivam as influências predominantes dos diferentes tipos de cerveja). Uma vez que os diferentes tipos de cervejas resultam da combinação e relação entre vários fatores (ingredientes, processamento, embalagem, marketing, cultura) o aroma final será diferente para cada uma delas. No entanto, o aroma não é estático mas em estado constante de mudança. O ponto em que a maturação acaba e a deterioração começa é sem dúvida diferente para diferentes cervejas e provavelmente diferente para cada consumidor. O objetivo deste trabalho foi estudar as alterações que ocorrem durante o armazenamento/envelhecimento de seis cervejas diferentes: quatro artesanais (Weiss, Pilsner, Stout, Red Ale) e duas comerciais (Weiss e Pilsner). As principais diferenças entre estas cervejas é o facto de as artesanais serem feitas exclusivamente a partir de matéria-prima natural, não serem adicionados aditivos nem conservantes e não ser pasteurizada nem filtrada (contendo a levedura na garrafa). As cervejas foram analisadas sensorial e quimicamente (compostos maioritários e minoritários) uma vez por mês ao longo de seis meses. Os compostos minoritários foram analisados no primeiro e no último mês. As cervejas artesanais mostraram um perfil aromático muito mais intenso do que as comerciais e mantiveram o perfil constante ao longo dos seis meses de armazenamento (assim como as comerciais). Os resultados permitiram concluir que as cervejas artesanais mantêm a qualidade de uma cerveja comercial, ao longo de seis meses, com a vantagem de terem os sabores e aromas mais intensos. A análise dos compostos maioritários não permitiram determinar tendências claras acerca da concentração de etanol e de açúcares. As concentrações de ácidos orgânicos mostraram ser mais elevadas do que as concentrações tipicamente encontradas nas cervejas comerciais. Os resultados da análise dos compostos minoritários vão de encontro aos perfis aromáticos obtidos pela análise sensorial assim como os retratados na literatura. Estes resultados mostraram que a maioria dos principais marcadores de maturação reportados não foram encontrados nas cervejas, no entanto outros compostos foram encontrados tas como álcoois superiores, cetonas e ácidos. Foi realizada a validação do método de extração de compostos minoritários, utilizado para a análise por Cromatografia Gasosa- Espectrometria de Massa. De forma a validar o método foram estudados vários parâmetros: linearidade, sensibilidade, limites de deteção e quantificação, precisão (precisão intermédia e repetibilidade), efeito matriz e efeito do tempo e exatidão (teste de recuperação). Os resultados mostraram que o método satisfaz as especificações determinadas para cada parâmetro de validação, o que significa que a validação do método de extração foi um sucesso.

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Dissertations / Theses on the topic 'Chemical profiling'

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