Targeted of cannabinoids in hair and androgens in saliva and untargeted profiling of the effects of exercise

The thesis is made up of four chapters. The first chapter is the general introduction to prepare biological samples for analysis, including extraction methods, derivatization and LC-MS instrumentation, including separation techniques. In addition, description of metabolomics approaches which are deployed in order to determine and/or quantify any changes to the metabolites which occur within a biological system in response to different stimuli such as diet, lifestyle and physical activity. The second chapter describes the quantification of cannabinoids in human hair through derivatization and liquid chromatography-tandem mass spectrometry. Cannabinol (CBN), Δ9-Tetrahydrocannabinol (THC) and its main metabolite 11nor-Δ9- Tetrahydrocannabinol carboxylic acid (THC-COOH) which are the most popular indicators of cannabis use. The use of this drug is widespread around the world and causes a serious social and health problems. In this study, a method based on solid-phase extraction (SPE) and liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was developed and validated. In this procedure, hair samples were extracted and derivatized with 2fluoro-1-methyl pyridinium-p-toluenesulfonate (FMP-TS) before injecting into the LC-MS-MS. The method showed excellent linearity with a coefficient of determination (r2) better than 0.99 for the analytes of interest. The extractionrecovery was between 81% and 105 % for all compounds. The limit of detection (LOD) and quantification (LOQ) were 2 and 20 pg/mg respectively for both CBN and THC and was 0.1 and 0.2 pg/mg for THC-COOH. Intra- and inter-assay precision were always lower than 4% and 11%, respectively, for these cannabinoids. Whereas the intra- and inter-assay bias were between (14% and 18 %) and (15 and -12 %), respectively.;Twenty-seven hair specimens from cannabis consumers were investigated using the optimized and validated method. Ultimately, CBN and THC were detected in all specimens, whereas THC-COOH was quantified in 13 specimens. Unlike CBN and THC, THC-COOH was semi-quantifiable (all values less than the limit of quantification (LOQ), but more than the limit of detection (LOD)) in 3 samples and was not detected in 11 samples. The levels of CBN, THC and THC-COOH on average were (0.022-2.562 ng/mg), (0.049-0.431 ng/mg) and (0.222-4.867 pg/mg) respectively. The median levels were (0.054 ng/mg), (0.087 ng/mg) and (0.34 pg/mg) for CBN, THC and THC-COOH respectively. Detection at least of THCCOOH metabolite in hair, especially in routine work seems to be compulsory in addition to THC and other main cannabinoids in order to distinguish between active ingestion and passive exposure.;In the last decade, high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) combined with electrospray ionization (ESI) has beenwidely used for determining low concentrations of steroids, and derivatization has often been employed to enhance detection. The third chapter describes the development of a derivatization method for quantification of testosterone and dehydroepiandrosterone in saliva samples from young professional soccer players, pre- and post-Training, using tandem mass spectrometry. In the present study, endogenous steroids were extracted using a Strata-XL polymeric reversephase cartridge. The isolated steroids were reacted with 2-hydrazino-1- methylpyridine (HMP). A liquid chromatography-tandem mass spectrometry (LCMS/MS) was used in a positive mode with multiple reaction monitoring (MRM) for the quantification of testosterone (T) and its biosynthetic precursor, dehydroepiandrosterone (DHEA), in saliva samples collected from twenty young Saudi professional soccer players. The extraction recovery during the pretreatment was >89% and gave 89% and gave <±20% for inter- and intra-assay precision and accuracy. The limits of quantification (LOQ) were found to be 20 pg/mL for (T and DHEA) and 50 pg/mL for Epitestosterone (EPI). The results showed no significant variation in the concentration of T between pre and post-training, whereas DHEA was significantly increased after short-term exercise. EPI could not be detected in the saliva samples.;The fourth chapter is about metabolomics profiling of plasma, urine and saliva after short-term training in young professional football players in Saudi Arabia.Urine, plasma and saliva were collected on two days pre- and post-training. An Orbitrap Exactive mass spectrometer was used to analyse the samples. A reversed-phase (RP) column was used for the analysis of nonpolar plasma components, and a ZICpHILIC column was used for the analysis of polar metabolites in plasma, saliva and urine. There was no marked variation in the metabolite profiles between pre day1 and 2 nor between post day1 and 2 according to principal components analysis (PCA). When orthogonal partial least squares (OPLS-DA) modelling was used then the models separating pre- and posttraining samples could be fitted based on the total number of significant metabolites 75, 16 and 32 for urine, plasma and saliva using hydrophilic interaction chromatography (HILIC) and 6 for plasma analysed on a reversedphase (RP) column respectively

Developing a preliminary recharge model of the Nile Basin to help interpret GRACE data

GRACE data provides a new and exciting opportunity to gain a direct and independent measure of water mass variation on a regional scale, but the data must be combined with hydrological modelling to indicate in which part of the water cycle the mass change has occurred. Processing GRACE data through a series of spectral filters indicates a seasonal variation to gravity mass (±0.005 mGal) thought to relate to the downstream movement of water in the catchment, and delayed storage from groundwater, following the wet season in the upper catchment. To help interpret these data a groundwater recharge model was developed for the Nile Catchment using the model ZOODRM (a distributed modelling code for calculating spatial and temporal variations in groundwater recharge). ZOODRM was an appropriate model to use for this work, due to the lower data demands of the model, relative to other groundwater models, the ability of the model to use entirely remotely-sensed input data, and the added functionality of runoff routing. Rainfall (NOAA data) and ET data were sourced from the FEWS NET African Data Dissemination Service. Geological data was sourced from the digital geology map of the world, landuse data from the USGS and the DEM data from ESRI. Initial model results indicate groundwater recharge across the basin of 0-4mma-1, with obvious considerable spatial variability. The results indicate the importance of groundwater in storing rainfall, and releasing it slowly throughout the year in different parts of the catchment. Only by modelling this process can GRACE data be reliably interpreted hydrologically. Despite only a qualitative interpretation of the GRACE data having been achieved within this preliminary study, the work has indicated that the ZOODRM model can be used with entirely remotely-sensed data, and that sufficient data exists for the Nile Basin to construct a plausible recharge model. Future work is now required to properly calibrate the model to enable closer comparison of the Nile GRACE data

Violation of Equivalence Principle and Solar Neutrinos

We have updated the analysis for the solution to the solar neutrino problem by the long-wavelength neutrino oscillations induced by a tiny breakdown of the weak equivalence principle of general relativity, and obtained a very good fit to all the solar neutrino data.Comment: 3 pages, 5 figures, uses espcrc2.sty, Talk presented by H. Nunokawa at Europhysics Neutrino Oscillation Workshop (NOW2000), Otranto, Italy, September 9-16, 200

Computing with and without arbitrary large numbers

In the study of random access machines (RAMs) it has been shown that the availability of an extra input integer, having no special properties other than being sufficiently large, is enough to reduce the computational complexity of some problems. However, this has only been shown so far for specific problems. We provide a characterization of the power of such extra inputs for general problems. To do so, we first correct a classical result by Simon and Szegedy (1992) as well as one by Simon (1981). In the former we show mistakes in the proof and correct these by an entirely new construction, with no great change to the results. In the latter, the original proof direction stands with only minor modifications, but the new results are far stronger than those of Simon (1981). In both cases, the new constructions provide the theoretical tools required to characterize the power of arbitrary large numbers.Comment: 12 pages (main text) + 30 pages (appendices), 1 figure. Extended abstract. The full paper was presented at TAMC 2013. (Reference given is for the paper version, as it appears in the proceedings.

Phytochemical investigation of Rhus tripartita and its activity against cyclooxygenases and acetylcholinesterase

Purpose: To investigate the inhibitory activity of crude methanol extract, fractions and two pure compounds from Rhus tripartita stem cyclooxygenases (COX-1 and COX-2) and acetylcholinesterase (AChE); also, to evaluate their antioxidant properties in in-vitro assays.Methods: R. tripartita extract and fractions were examined as inhibitors of COX-1 and COX-2 and AChE. Their antioxidant properties were also evaluated using various antioxidant tests, including free radical scavenging, nitric oxide, and total antioxidant capacity.Results: Ethyl acetate fraction (RT2), aqueous fraction (RT4), subfraction RT2-II, and subfraction RT2-III had a potent inhibitory effect on AChE with low IC50 values. At the same time, a subfraction (RT2-III) was an effective COX-2 inhibitor (94.5 % at 10 μg/mL) followed by ethyl acetate fraction (RT2; 79.39 %), aqueous fraction (RT4; 70 %), total extract (RT; 66.18 %), subfraction RT2-III (64.08 %), compound 5 (epicatechin; 61.25 %), compound 2 (taxifolin; 55.63 %), subfraction RT2-II (46.85 %), and butanol fraction (RT3; 40.80%). RT2, RT4, RT2-II, RT2-III, and compound 2 each showed 100 % inhibition at 20 μg/mL.Conclusion: The ethyl acetate fraction (RT2), aqueous fraction (RT4) and subfractions RT2-II and RT2- III are effective natural inhibitors of AChE. Subfraction RT2-III is the best COX-2 inhibitor, followed by ethyl acetate fraction RT2 and aqueous fraction (RT4). These bioactive materials can be considered natural COX-2 and AChE inhibitorsKeywords: Cyclooxygenase, Anti-nflammatory, Acetylcholinesterase, Anacardiaceous, Taxifolin, Epicatechi

High Quality InSb Microcrystal Hall Sensor Doped with Te or Bi

InSb microcrystal doped with Cr, Al or Sn, which were radiation-resistant and were applied as magnetic microsensors in Satellites. The magnetic field sensitivity, , as a function of temperature was determined for both Bi and Te doped InSb microcrystals. Tellurium doping of InSb microcrystals at 3 x10 17 cm-3 leads to increase of the magnetic field sensitivity, , to ? 1.1 V/AT, but it decreases to ? 0.45 V/AT at 450K. On the other hand doping with Bi at 1 x 1017 cm-3 gives ? 1 V/AT. The charge carriers mobility of the investigated microcrystals varies from about 2.11m2/V.s to 3.4 m2/V.s, for Te doped samples and from 3.2 m2/V.s to 4.3 m2/V.s for Bi doped samples at room temperature. The electrical resistivity variation with temperature was also studied

Synthesis and properties of polyelectrolyte multilayered microcapsules reinforced smart coatings

The present research work focuses on the synthesis, characterization and properties of novel polyelectrolyte multilayered microcapsules used as smart additives in organic coatings for corrosion protection of steel parts. Urea formaldehyde microcapsules encapsulated with linalyl acetate (UFMCs), sensitive to mechanical stimulus, were synthesized by in situ emulsion polymerization technique. In the next step, dodecylamine, working as a pH stimulus corrosion inhibitor, was loaded into layers of polyelectrolyte molecules, polyethylenimine (PEI) and sulfonated polyether ether ketone (SPEEK). These were applied layer-by-layer over the microcapsules to form inhibitor containing multilayered urea formaldehyde microcapsules (MLUFMCs). In the next step, MLUFMCs (5.0 wt%) and UFMCs (5.0 wt%) were thoroughly dispersed into the epoxy resin and coated on cleaned steel. A comparison of the structural, thermal and anticorrosive properties indicates that coatings modified with multilayered capsules (PMLSCs) demonstrate good thermal stability, improved self-healing characteristics and higher corrosion resistance compared to the coating modified with urea formaldehyde microcapsules. The improved properties of PMLSCs can be attributed to efficient release of the encapsulated self-healing agent and corrosion inhibitor from the MLUFMCs. Therefore, epoxy coatings modified with the novel multilayered capsules may be attractive for corrosion protection of steel parts used in oil and gas and related industries. - 2019, The Author(s).Open Access funding provided by the Qatar National Library. This publication was made possible by NPRP Grant 9–080-2-039 from Qatar National Research Fund (a member of the Qatar Foundation). Statements made herein are solely the responsibility of the authors. R. A. Shakoor would like to acknowledge the financial support of QU internal grant-QUCG-CAM-2018/2019-3 and the Core Labs, QEERI for their SEM and TEM imaging. M.F. Mon-temor thanks Fundac¸ão para a Ciência e a Tecnologia (FCT, Portugal) for financial support under the projects PEst-OE/QUI/UI0100/2013.Scopu

Experimental feasibility of measuring the gravitational redshift of light using dispersion in optical fibers

This paper describes a new class of experiments that use dispersion in optical fibers to convert the gravitational frequency shift of light into a measurable phase shift or time delay. Two conceptual models are explored. In the first model, long counter-propagating pulses are used in a vertical fiber optic Sagnac interferometer. The second model uses optical solitons in vertically separated fiber optic storage rings. We discuss the feasibility of using such an instrument to make a high precision measurement of the gravitational frequency shift of light.Comment: 11 pages, 12 figure

Atmospheric Neutrino Oscillations and New Physics

We study the robustness of the determination of the neutrino masses and mixing from the analysis of atmospheric and K2K data under the presence of different forms of phenomenologically allowed new physics in the nu_mu--nu_tau sector. We focus on vector and tensor-like new physics interactions which allow us to treat, in a model independent way, effects due to the violation of the equivalence principle, violations of the Lorentz invariance both CPT conserving and CPT violating, non-universal couplings to a torsion field and non-standard neutrino interactions with matter. We perform a global analysis of the full atmospheric data from SKI together with long baseline K2K data in the presence of nu_mu -> nu_tau transitions driven by neutrino masses and mixing together with sub-dominant effects due to these forms of new physics. We show that within the present degree of experimental precision, the extracted values of masses and mixing are robust under those effects and we derive the upper bounds on the possible strength of these new interactions in the nu_mu--nu_tau sector.Comment: 22 pages, LaTeX file using RevTEX4, 5 figures and 4 tables include