En aquest treball es presenten dues mesures, una de la constant d'acoblament forta i l'altra d'aquesta mateixa constant conjuntament amb els anomenats factors de color. Les dades foren recollides pel detector ALEPH durant els anys 1994-95 a energies al voltant dels 91.2 GeV.Per a les dues mesures s´usaren obervables de quatre jets. La mesura de la constant d´acoblament forta a partir de la taxa de sucesos a quatre jets fou la primera realitzada a partir d´un observable de quatre jet i en resultà una de les mesures més precises fins avui.La mesura conjunta de la constant d´acoblament i els factors de color representa un prova rigorosa de la teoria de les interaccions fortes, la cromodinàmica quántica. Els resultats, amb incerteses molt competitives, estan en acord absolut amb els valors esperats per la teoria i també amb els resultats d'altres col·laboracions. / In this work two measurements are presented. One is the measurement of the strong coupling constant alone, and the other the combined measurement of the strong coupling constant and the, so called, colour factors. Data were collected by the ALEPH detector during years 1994-95 at energies around 91.2 GeV.Both measurements made use of four-jet observables. The measurement of the strong coupling constant from the four-jet rate was the first ever made from a four-jet observable, and represents one of the most precise measurements at present.The combined measurement of the strong coupling constant and the colour factors is a stringent test of the theory, quantum chromodynamics. The results, with very competitive uncertainties, are in exact agreement both with the values expected by the theory and the results from other collaborations.

3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") 3' is a 'psychedelic amphetamine' that has gained popularity over the past 20 years because of its ability to produce strong feelings of comfort, empathy, and connection to others. MDMA analysis in blood and urine samples have been consistently used for clinical pharmacology studies and forensic science cases. However, new developments in clinical toxicology require new analytical approaches and the use of alternative biological matrices for establishing whether individuals have consumed the drug, when and/or if they have been acting under the effect of the drug.It is postulated that MDMA physic-chemical properties: (i) pKa of around 9.9 corresponding to a weak base that facilitates the transfer of MDMA from plasma (pH=7.4) to fluids/matrices with a favourable pH gradient, (ii) high liposolubility with volumes of distribution between 6 and 7 liters per kilogram, (iii) low protein binding, favour its distribution to biological matrices in humans. Several non-conventional biological matrices such as hair, sweat and saliva, because of drug accumulation due to its physico-chemical properties, might be of use for the detection of past and recent exposure to MDMA.Three different studies were set-up. The study 1 investigating the pharmacokinetics of MDMA in saliva after a single oral dose administration of 100 mg to eight healthy volunteers, the second investigating the pharmacokinetics of MDMA in sweat after a single dose administration of 100 mg to eight healthy volunteers, and finally a study on segmental analysis of MDMA in hair of thirteen drug consumers with different patterns of consumption..The first study evidenced that MDMA is excreted in saliva, after a single 100 mg dose administration, with concentrations (range 1728.9-6510 µg/ml at 1.5 h after drug intake) one order of magnitude higher than those observed in plasma (range 134.9-223 µg/ml at 1.5 h after drug intake) and following a time course kinetics which parallels that of plasma and that of subjective effects and psychomotor performance. On-site testing by Drugwipe device proved suitable to detect individuals under the influence of drug effects in the first 6 hours after drug intake by non-invasive and rapid collection of salivary specimens.The second study showed that MDMA appears in sweat and can be quantified already in the first few hours after a single dose administration, when subjective effects are apparent (concentration range 3.2-1326 ng/pacth). This result makes:the sweat patch technology useful for monitoring MDMA accumulation in sweat at least during the 24 hours after a single administration, On-site sweat testing by drugwipe device suitable to detect individuals under the influence of drug effects by non-invasive and rapid collection of minute amounts of sweat.MDMA appears in hair from consumers (concentration range 1.2-12.6 ng/mg hair) and can be detected in hair segments corresponding to the last one, six and twelve month of repeated drug use. For this reason:Hair analysis of MDMA can be used to evaluate exposure or abstinence to the drug in the last months, hair concentration of MDMA in different hair segments can predict levels of drug use(r2=0.92) and can be eventually associated to chronic psychophysical effects induced by the repeated drug use.The measurement of MDMA in saliva is a valuable alternative to determination of plasma drug concentrations both in clinical and toxicological studies A common characteristic of the three different matrices is that the parent drug MDMA was always the principal, most abundant analyte detected, whose concentration could be associated with drug-induced effects and drug history. As already assessed, drug analysis in hair extends the information of drug consumption to a wider time-window than that of other non-invasive biological matrices, such as saliva and sweat. These latter two matrices can account for acute pharmacological effects induced by the drug, while results from hair testing can be used to assess repeated exposure to drug and eventual association with long term drug induced effects, such as neurotoxicity and psychological performance in the specific case of MDMA.

Development of displacement El objetivo de este trabajo es explorar y explotar los principios de funcionamiento de un Inmunosensor Electroquímico de Desplazamiento [(Displacement Electrochemical Immunosensor (DEI)] y también del ELISA Indirecto Competitivo [(Indirect Competitive ELISA (ICE)] para la detección de 2,4,6-tricloroanisol (TCA). Para tal fin, se lleva a cabo el desarrollo racional de un ELISA Indirecto Competitivo. El ensayo desarrollado resulta capaz de detectar TCA en concentraciones 1ppt a 1 ppm, con un limite de detección de 4.2 ppt. El ensayo desarrollado puede tener un particular interés comercial en situaciones donde el tiempo experimental requerido es de menos de 80 minutos.Se desarrolla también un modelo matemático (MM) cuyo principal objetivo es permitir el desarrollo racional de un Inmunosensor Electroquímico de Desplazamiento (DEI). A pesar de las bajas constantes de afinidad observadas en los anticuerpos obtenidos para este trabajo, se logra desarrollar un DEI funcional cuyo limite de detección de TCA (0.2 ppm) se corresponde con los valores obtenidos a través del MM.La adsorción inespecífica (NSA) de proteínas es identificada como uno de los problemas críticos que impidieron alcanzar limites de detección más bajos. El uso del electroquímicamente compatible Cu UPD como barrera/control de la NSA, junto con la detección amperométrica del desplazamiento son propuestos en este trabajo como base o punto de partida para el desarrollo de inmunosensores que puedan ser operados sin necesidad de marcaje (labelling) o la adición de otros componentes diferentes de la muestra de interés (reagentless and labelless immunosensors). / The purpose of this work is to explore and exploit the principles of Displacement Electrochemical Immunosensing (DEI) and Indirect Competitive ELISA (ICE) to detect 2,4,6-trichloroanisole (TCA). The rational design of indirect competitive ELISA for TCA detection is attempted. The developed assay detects TCA at concentrations from 1ppt to 1 ppm, with a limit of detection of 4.2 ppt. The assay can be commercially useful in situations where less than 80 minutes total assay time is required. A mathematical model (MM) is developed for the rational design of an electrochemical displacement immunosensor (DEI). Despite the low affinity constants of the antibodies obtained for this work a functional DEI is developed with the predicted by the MM high limit of detection for TCA (0.2 ppm). The non-specific adsorption (NSA) of proteins is identified as a critical problem inhibiting further optimization of the DEI. The use non-insulating Cu UPD as NSA controller or electrochemically compatible blocking, together with amperometric displacement detection are proposed as a platform that could permit further development of reagentless and labelless immunosensors.

En aquest treball s'ha desenvolupat una metodologia eficaç envers la síntesi de diferents derivats pirimidínics amb un alt grau de diversitat molecular. Aquesta metodologia es basa en la S-alquilació selectiva dels 2-tiouracils (2) utilitzats com a material de partida. Aquesta reacció es realitza amb bromur de benzil quan es treballa en dissolució, o bé amb la reïna de Merrifield quan la química és sobre suport sòlid. Seguidament, s'alquila selectivament l'àtom d'oxigen de les benzilsulfanilpirimidinones (3) mitjançant la reacció de Mitsunobu, o bé utilitzant diferents halurs d'alquil en presència d'una base. Amb les 4-alcoxipirimidines (4) es realitzen diverses transformacions químiques, per exemple, addicions de Grignard, reducció i posterior metilació del grup carbonil (quan R2 = CH2COPh), etc. Posteriorment, s'oxida el grup sulfanil a sulfona utilitzant m-CPBA. Finalment es desplaça la funció sulfona amb diversos nucleòfils.Gràcies a aquesta metodologia s'han preparat diferents 2-amino-4-alcoxipirimidines (7, Nu = RR'N) en dissolució i sobre suport sòlid. Mitjançant algunes variacions s'han pogut obtenir altres derivats pirimidínics: - 4(3H)-pirimidinones 2,6-disubstituïdes (8, Nu = RR'N, ArO, RR'R''C), preparades a partir de la hidròlisi del grup alcòxid (OR5) dels compostos (7) en medi àcid.- imidazo[1,2-a]pirimidinones (9 o 10, n = 1) i pirimido[1,2-a]pirimidinones (9 o 10, n = 2). Els compostos (9) s'han obtingut selectivament a través d'una ciclació intramolecular de les pirimidines (7, Nu = aminoalcohols) utilitzant àcid sulfúric. Quan s'han ciclat els compostos (8, Nu = aminoalcohols) mitjançant una reacció de Mitsunobu intramolecular, s'han obtingut els regioisòmers (9) i (10) en diferents proporcions en funció dels grups presents en l'anell.- pirimidines funcionalitzades amb restes d'-arilglina (11). La funció arilglicina s'ha preparat mitjançant la condensació d'amines (4, R2 = CH2CHR3NHR4) amb àcid glioxàlic i àcids arilborònics (reacció de Petasis). L'oxidació del grup sulfanil dels compostos (11) a sulfona utilitzant m-CPBA ha provocat també l'oxidació de l'àtom de nitrogen de l'arilglicina.Alguns d'aquests derivats pirimidínics han mostrat ser inhibidors del Mycobacterium tuberculosis. / We have developed an efficient methodology that allows the synthesis of pyrimidine derivatives with a high degree of molecular diversity. We have shown that easily available 2-thiouracils of type (2) can be used as versatile building blocks toward the preparation of substituted 4-alkoxypyrimidine (4) through a simple O-alkylation reaction. The steric effects have a remarkable influence over the regioselectivity of the reaction, both using alkyl halides in basic conditions and with alcohols under Mitsunobu conditions. Optionally, further suitable manipulations over the substituents at the 4-position would enhance the introduction of additional diversity. Finally, oxidation of the thioether moiety to the corresponding sulfone 6 and nucleophilic displacement by different nucleophiles would produce the corresponding highly molecular diverse pyrimidines of type (7).The methodology developed in solution has been, successfully, transferred to the solid support (benzyl bromide replaced by Merrifield resin). A small library of molecularly diverse 4-alkoxypyrimidines has been prepared in parallel on solid support. The final products, 2-amino-4-alkoxypyrimidines (7), have been obtained in good overall yields.The study of the nucleophilic ipso-substitution reaction in 4-isopropoxypyrimidines (5, R5 = (CH3)2CH) has been expanded using a wide variety of nucleophiles (N-, C- and O-). The cleavage of 4-isopropoxy group afforded a collection of 2,6-disubstituted 4(3H)-pyrimidinones (8) (Figure 1).The introduction of several - and -aminoalcohols at the position 2- on the pyrimidine ring and the subsequent intramolecular cyclisation afforded different imidazo- and pyrimido[1,2-a]pyrimidinones (9 and 10). Intramolecular cyclisation of 4(3H)-pyrimidininones (8, Nu = aminoalcohols) under Mitsunobu conditions, afforded a separable mixture of the regioisomeric compounds (9) and (10) (Figure 1). Cyclisation of 4-isopropoxypyrimidines (7, Nu = aminoalcohols) with H2SO4 yielded the regioisomers (9) as the only products.Fynally, a little collection of -arylglycines linked to the pyrimidinone ring (11) (Figure 1) has been prepared using the Petasis reaction.Several pyrimidine derivatives have shown inhibitory activity against Mycobacterium tuberculosis.

We apply branched covering techniques to construct minimal simply-connected symplectic 4-manifolds with small χ_h values. We also use these constructions to provide an alternate proof that for each s ≥ 0, there exists a positive integer λ(s) such that each pair (j,8j+s) with j ≥ λ(s) is realized as (χ_h(M),c_1^2(M)) for some minimal simply-connected symplectic M. The smallest values of λ(s) currently known to the author are also explicitly computed for 0 ≤ s ≤ 99. Our computations in these cases populate 19 952 points in the (χ,c)-plane not previously realized in the existing literature.

SAAB Support and Services, som är servicecenter för flygplanskomponenter, utför idag huvuddelar av sina mätningar manuellt, mätningar som ibland kan ta upp till fyra dagar. För att höja noggrannheten samt öka effektiviteten köpte de år 2007 in ett automatiskt testkoncept från MK Test systems. I examensarbetet har vi först undersökt den inköpta utrustningen. Sedan har vi tagit fram rutiner för kalibrering av utrustningen som klarar SAAB:s krav. Därefter har vi arbetat fram kravspecifikationer och instruktioner för hur utrustningen ska användas. Under arbetets gång har vi samlat in information för att kunna göra en utvärdering av hur lämplig utrustningen är att använda för att testa flygplanskomponenter. Arbetet resulterade huvudsakligen i tre st manualer som går igenom tre olika områden; kalibrering, kablagetest och ett standardtest för t.ex. paneler och styrboxar. / SAAB Support & Services, a service centre for air plane components, perform most of their measurements manually. These measurements can sometimes take up to four days to perform. In 2007 an automatic concept for testing from MK Test systems was purchased in order to enhance the accuracy and increase the efficiency. In our thesis we have initially examined the automatic concept for testing and then developed standards for how to calibrate this equipment, standards that meets SAAB:s requirements. Thereafter we have developed specifications and instructions on how to use the equipment. During our work we have gathered information for an evaluation of how fitting it is to use the F1500 for testing air plane components. The main outcome of our work consists of three manuals for three different areas; calibration, harness test and a standard test for example panels and controller units.

We apply branched covering techniques to construct minimal simply-connected symplectic 4-manifolds with small χ_h values. We also use these constructions to provide an alternate proof that for each s ≥ 0, there exists a positive integer λ(s) such that each pair (j,8j+s) with j ≥ λ(s) is realized as (χ_h(M),c_1^2(M)) for some minimal simply-connected symplectic M. The smallest values of λ(s) currently known to the author are also explicitly computed for 0 ≤ s ≤ 99. Our computations in these cases populate 19 952 points in the (χ,c)-plane not previously realized in the existing literature.

The cytotoxic effects of exposure to low concentrations of the herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D) that are typically found in groundwater were investigated, in vitro. Most 2,4-D toxicology studies use high concentrations of the herbicide that are above those typically found in groundwater and measure overt biological endpoints. In contrast, this thesis examines the effects of low concentrations of 2,4-D and measures more subtle and sensitive endpoints such as gene expression and the generation of reactive oxygen species. This work derives from recent cDNA microarray analysis conducted in our laboratory that revealed significant alterations in the expression of 238 genes in cells exposed to nanomolar (nM) concentrations of a commercial formulation of 2,4-D. These findings are extended in this thesis to include the in vitro cytotoxic effects of low concentrations of both technical and commercial 2,4-D on two cell lines. Cells derived from liver (HepG2) and kidney (HEK293) respectively, were chosen, since liver and kidney are known to metabolize 2,4-D in vivo. Cell viability was measured using the Resazurin assay, reactive oxygen species (ROS) were measured with 2,7-dichlorofluorescin diacetate (2,7-DCFH-DA), and real timepolymerase chain reaction (RT-PCR) was used to assess changes in mRNA expression while protein expression was examined by Western blot.<p>Cell viability studies revealed that low environmental concentrations (0.1 to 100 nM) of 2,4-D induced small, but statistically significant decreases in cell viability. No concentration or time-dependent decreases in cell viability were observed in cells exposed to either forms of low environmental 2,4-D concentrations. HEK293 cells were more susceptible than HepG2 cells to the toxic effects of both forms of 2,4-D, having statistically significant lower viability at all exposure concentrations and durations. Both forms of 2,4-D reduced cell viability in both cell lines, suggesting that cytotoxicity was induced directly by 2,4-D, and not by the inert ingredients in the commercial formulation.<p>The ROS assays illustrated that 2,4-D induced statistically significant ROS production in HepG2 and HEK293 cell cultures at concentrations greater than 10 µM and 100 nM respectively. This was both a concentration and time-dependent effect in both cell lines. Although HEK293 cells were more susceptible to 2,4-D, they had 50 to 70% less ROS production than HepG2 cells, at all exposure concentrations and times.<p>The RT-PCR and Western blot analyses showed that exposure of HepG2 and HEK293 cells to low 2,4-D concentrations induced (< 2 fold) alterations in mRNA and protein levels of FTL, FTH1 and PCNA however these changes did not consistently vary with concentration.<p>Taken together, cell viability, ROS and gene expression studies show that low environmental 2,4-D concentrations induced subtle in vitro cytotoxic effects. However we have no evidence that these subtle changes pose a serious health threat to exposed humans.

This thesis presents the study of biodegradation factors of a candidate naphthenic acid compound, the trans isomer of 4-methyl-1-cyclohexane carboxylic acid (trans-4MCHCA). Low molecular weight components of naphthenic acids such as trans-4MCHCA are known to be toxic in aquatic environments and there is a need to better understand the factors controlling the kinetics of their biodegradation. In this study, a relatively low molecular weight naphthenic acid compound and a microbial culture developed in our laboratory (primarily Alcaligenes paradoxus and Pseudomonas aeruginosa) were used to study the biodegradation of this candidate naphthenic acid. The purpose of the research was to evaluate the kinetic parameters and model the biodegradation of this compound in three bioreactor systems: batch reactors, a continuously stirred tank reactor and immobilized cell reactors. <p>In batch reactors, the maximum specific growth rate (0.52±0.04 d-1) of the consortium at 23oC and neutral pH was not highly variable over various initial substrate concentrations (50 to 750 mg/L). Batch experiments indicated that biodegradation can be achieved at low temperatures; however, the biodegradation rate at 4oC was only 22% of that at room temperature (23oC). Biodegradation at various pH values indicated a maximum specific growth rate of 1.69±0.40 d-1 and yield (0.41±0.06 mg/mg) at a pH of 10. <p>Study of the candidate substrate using a continuously stirred tank reactor and the microbial culture developed in the batch experimentations revealed that the kinetics of the candidate naphthenic acid are best described by the Monod expression with a maximum specific growth rate of 1.74±0.004 d-1 and a half saturation constant of 363±17 mg/L. The continuously stirred tank reactor achieved a maximum reaction rate of 230 mg/(L∙d) at a residence time of 1.6 d-1 (39 h).<p>Two high porosity immobilized cell reactors operating continuously over three months were found to consume trans-4MCHCA at a rate almost two orders of magnitude higher than a continuously stirred tank reactor. The immobilized cell systems attained a maximum reaction rate of 22,000 mg/(L∙d) at a residence time of 16 minutes. High porosity immobilized cell reactors were shown to effectively remove a single naphthenic acid substrate in continuously fed operation to dilution rates of 90 d-1. A plug flow model best represented the degradation in the immobilized cell systems and was demonstrated to be a useful tool for studying the effects of parameter variation and prediction of reactor performance. This work highlights the potential of augmented bioremediation systems for the degradation of naphthenic acids.

Denna studie har som mål att undersöka hur produktplaceringar i spelet Metal Gear Solid 4 kan ha för roll i narrativet, vad dessa tillför spelet och vilken roll de har för karaktärerna i berättelsen. Studien undersöker även om dessa produktplaceringar visas på ett sätt som förstärker produktens eller varumärkets status men även för att se om stereotyper nyttjas för att upphöja deras effekt. Denna studie bygger på en kvalitativ textanalys med semiotiska och narrativa inslag där jag tillsammans med valda teorier om bland annat narratologi och produktplacering kommer att svara på uppsatsens frågeställning: Hur används och integrerar varumärken/produkterna med narrativet och karaktärerna i Metal Gear Solid 4?  Resultatet visar att de produkter och varumärken som finns med i spelet har varit viktiga för både narrativet och karaktärerna. Dessa produktplaceringar har bland annat gjort spelets berättelse och dess karaktärer mer verkliga då de har hjälpt att skapa en länk mellan fiktion och verklighet. Produkterna har spelat en stor roll i narrativets story och händelseförlopp då de har varit viktiga instrument som har underlättat spelandet och fört narrativet framåt samtidigt som de har använts av spelets karaktärer och gjort det möjligt för dem att kunna uppnå det slutgiltiga målet i narrativet, vilket är som många andra berättelser idag, världsfred.