[EN] Self-incompatibility (SI) comprises a compendium of molecular intraspecific barriers, controlled by the S-locus, which enhances outcrossing and prevents inbreeding. Solanaceae, Plantaginaceae and Rosaceae exhibit the Gametophytic SI (GSI) type where specific recognition is controlled by S-RNases and S-locus F-box (SFB) proteins as the female and male S-determinants, respectively. On the other hand, unlinked S-locus genes known as modifier factors are also completely necessary for the mechanism to function. The GSI system seems to be basically preserved in Prunus but striking differences with Solanaceae and other Rosaceae have also been observed. On the basis of this background, this thesis is focused on the identification and characterization of modifiers involved in Prunus GSI to improve our understanding of the underlying mechanism. Previous works in apricot showed that an S-locus unlinked mutation expressed in pollen and located at the distal end of chr. 3 (M-locus) confers self-compatibility in the cv. 'Canino'. In this work, another self-compatible apricot cultivar, named 'Katy', was molecular and genetically analyzed. Similarly, an S-locus unlinked pollen-part mutation was found to cause the loss of self-incompatible response. A mapping strategy based on segregation distorted loci mapped 'Katy' mutation (referred as m-mutation) at the distal end of chr. 3, in a region overlapping with that identified for 'Canino' M-locus. A new screening was carried out to identify additional self-compatible mutants in apricot cultivar/accessions from germplasm banks. Through S-genotyping, three uncategorized S-alleles were recovered and two new mutations putatively conferring self-compatibility (SC) by affecting the male S-determinant SFB were detected. Additionally, M-genotyping showed that the same mutated m-haplotype was shared by 'Canino' and 'Katy', but also by 17 cultivars more from North-America and Western-Europe. A widely distributed haplotype M1-0 was proposed as the putative m-haplotype ancestor suggesting that it arose much later in time than SC-allele, a mutation in the S-locus also conferring SC in apricot. In order to identify this mutation, an integrative genetic, genomic and transcriptomic approach based on NGS data from 'Canino', 'Katy' and the self-incompatible apricot cultivar 'Goldrich' was carried out. This approach led to identify a unique polymorphism able to explain the self-compatible phenotype, a FaSt insertion type of 358-bp in coupling with the m-haplotype within a gene encoding a disulfide bond A-like oxidoreductase (named PaMDOr). PaMDOr was found to be differentially over expressed in mature anthers and the FaSt insertion is predicted to produce a truncated protein. These two findings also support PaMDOr as the pollen-part mutated modifier conferring SC in apricot. Furthermore, phylogenetic analyses suggest PaMDOr as a putative paralog of its contiguous gene (PaM-8), that emerged after the split of the Rosaceae and Solanaceae and which function became essential for the proper functioning of the GSI system in Prunus. Aimed to shed light on the differences and similarities between the S-RNase-based GSI systems in Rosaceae and Solanaceae, orthology relationships were analyzed for modifiers. Putative orthologs were found for NaTrxh, SBP1 and MdABCF in Prunus but a more complex evolutionary pattern was detected for 120K, NaStEP and NaPCCP. Thus, in spite of the differences, it can be hypothesized that part of the GSI modifier factors are shared by both families. As a whole, the multidisciplinary strategy developed in this thesis has allowed us to identify a novel modifier factor (PaMDOr) essential for the self-incompatible response in Prunus as the most significant contribution. In addition, new sources of SC have been detected in apricot and the orthology analysis helped to deepen our understanding on evolutionary aspects of the S-RNase-based GSI system exhibited by Prunus. / [ES] La autocompatibilidad (AI) comprende un conjunto de barreras moleculares intraespecíficas, controladas por el locus S, que favorecen la polinización cruzada y previenen de la endogamia. Solanáceas, Plantagináceas y Rosáceas presentan la llamada AI gametofítica (AIG) donde el reconocimiento específico está controlado por ARNasas-S y proteínas F-box del locus S (SFB) como los determinantes femenino y masculino, respectivamente. Por otra parte, genes no ligados al locus S, conocidos como factores modificadores, son también totalmente necesarios para la correcta regulación del mecanismo. El sistema AIG parece estar básicamente conservado en Prunus pero se han observado notables diferencias con Solanáceas y otras Rosáceas. Con estos antecedentes, el trabajo realizado en esta tesis se ha centrado en la identificación y caracterización de factores modificadores de la AIG en Prunus con el fin de mejorar nuestro conocimiento del mecanismo subyacente. Trabajos previos en albaricoquero mostraron la existencia de una mutación expresada en el polen y no ligada al locus S, que se localiza en el extremo distal del cr.3 (locus M) y que es capaz de conferir autocompatibilidad (AC) en el cultivar 'Canino'. En esta tesis, otro cultivar de albaricoquero autocompatible llamado 'Katy' fue genética y molecularmente analizado. De manera parecida a 'Canino', una mutación que afectaba a un factor no ligado al locus S expresado en el polen era el causante de la pérdida de la respuesta autoincompatible. La mutación en 'Katy' se consiguió mapear en el extremo distal del cr.3 (mutación m), una región que solapa con la identificada para 'Canino'. Una búsqueda para la identificación de nuevo mutantes autocompatibles en cultivares/accesiones de albaricoquero procedentes de bancos de germoplasma fue realizado. Por medio del genotipado del locus S, 3 alelos S no clasificados con anterioridad fueron hallados, mientras que 2 nuevas mutaciones autocompatibles que parecen haber afectado al determinante S masculino SFB fueron detectadas. Adicionalmente, el genotipado para el locus M mostró que el mismo haplotipo m mutado está compartido por 'Canino' y 'Katy' y 17 cultivares más del norte de América y el oeste de Europa. El haplotipo M1-0 ha sido propuesto como posible ancestro del haplotipo m, sugiriendo que éste surgió mucho más tarde que el alelo Sc, mutación del locus S que también confiere AC en albaricoquero. Con el objetivo de identificar esta mutación, un abordaje integral tanto a nivel genético como genómico y transcriptómico mediante datos NGS procedentes de 'Canino', 'Katy' y del cultivar de albaricoquero autoincompatible 'Goldrich' fue llevado a cabo. Esta aproximación sirvió para identificar un único polimorfismo capaz de explicar el fenotipo de AC, una inserción tipo FaSt de 358 pb en acoplamiento con el haplotipo m en un gen que codifica para una disulfide bond A-like oxidoreductase (PaMDOr). PaMDOr mostró estar diferencialmente sobre-expresado en anteras maduras, mientras que la inserción FaSt predice la formación de una proteína truncada. Estos dos hechos apoyan a PaMDOr como el factor modificador de la parte del polen que confiere AC en albaricoquero. Adicionalmente, análisis filogenéticos sugieren que PaMDOr podría ser un parálogo del gen contiguo (PaM-8) que surgió después de la división de Rosáceas y Solanáceas, cuya función ha llegado a ser esencial para el correcto funcionamiento del sistema en Prunus. A fin de arrojar cierta luz en las diferencias y similitudes entre los sistemas de AIG basado en ARNasas-S de Rosáceas y Solanáceas, las relaciones de ortología para factores modificadores fueron estudiadas. Ortólogos candidatos fueron encontrados para NaTrxh, SBP1 y MdABCF, sin embargo, un patrón evolutivo más complejo fue observado para NaStEP, 120K y NaPCCP. De modo que, a pesar de las diferencias, se puede hipotetizar que una parte de los modificadores de la AIG están comparti / [CAT] L'autocompatibilitat (AI) comprèn un conjunt de barreres moleculars intraespecífiques, controlades pel locus S, que afavorixen la pol·linització creuada i prevé de l'endogàmia. Solanàcies, Plantaginàcies i Rosàcies presenten l'anomenada AI gametofítica (AIG) on el reconeixement específic està controlat per ARNases-S i proteïnes F-box del locus S (SFB) com a determinants femení i masculí, respectivament. Per un altra banda, gens no lligats al locus S, coneguts com factors modificadors, són també totalment necessaris per a la correcta regulació del mecanisme. El sistema AIG pareix estar bàsicament conservat en Prunus, però s'han observat notables diferències amb Solanàcies i altres Rosàcies. Amb estos antecedents, el treball realitzat durant aquesta tesi se ha focalitzat en la identificació i caracterització de factors modificadors de l'AIG en Prunus a fi d millorar el nostre enteniment del mecanisme subjacent. Treballs previs a l'albercoquer mostraren l'existència d'una mutació expressada al pol·len no lligada al locus S, la qual està localitzada a l'extrem distal del cr.3 (locus M) i es capaç de conferir autocompatibilitat (AC) al cultivar 'Canino'. En aquest treball, un altre cultivar d'albercoquer autocompatible anomenat 'Katy' va ser genètica i molecularment analitzat. De manera pareguda a 'Canino', una mutació que afecta a un factor no lligat al locus S expressat al pol·len era la causa de la perduda de la resposta autoincompatible. La mutació a 'Katy' es va mapetjar a l'extrem distal del cr.3 (mutació m) en una regió solapant amb la identificada per a 'Canino'. Una recerca per a la identificació de nous mutants autocompatibles en cultivars i/o accessions d'albercoquer procedents de bancs de germoplasma va ser portada a terme. Mitjançant el genotipatge del locus S, 3 al·lels S no classificats amb anterioritat van ser trobats, mestres que dos noves mutacions AC que pareixen haver afectat al determinant S masculí SFB varen ser detectades. Amés, el genotipatge del locus M va mostrar que el mateix haplotip m mutat està compartit per 'Canino' i 'Katy', però també per 17 cultivars més del nord d'Amèrica i l'oest d'Europa. El haplotip M1-0, ampliamente distribuït, ha sigut proposat com a possible ancestre del haplotip m, sugerint que aquest va sorgir més tard que el al·lel Sc, una mutació al locus S que també conferix AC a l'albercoquer. Amb l'objectiu d'identificar aquesta mutació, un abordatge integral tant a nivell genètic com genòmic i transcriptòmic mitjançant diversos tipus de dades NGS provinents de 'Canino', 'Katy' i del cultivar d'albercoquer autoincompatible 'Goldrich' va ser portat terme. Aquesta aproximació va permetre identificar un únic polimorfisme capaç d'explicar el fenotip AC, es tracta d'una inserció de 358 pb en adaptament amb el haplotip m en un gen que codifica per a disulfide bond A-like oxidoreductase (PaMDOr). PaMDOr va mostrar estar diferencialment sobre-expressat en anteres madures, mentres que la inserció FaSt prediu la formació d'una proteïna truncada. Estos dos fets recolzen a PaMDOr com al factor modificador de la part del pol·len que conferix AC en albercoquer. A més a més, anàlisis filogenètics suggerixen que PaMDOr podria ser un paràlog del seu gen contigu (anomenat PaM-8) que va sorgir després de la divisió de Rosàcies i Solanàcies, en la qual la funció ha arribat a ser fonamental per al correcte funcionament del sistema d'AIG a Prunus. A fi de tirar certa llum en quant a les diferències i similituds entre els sistemes d'AIG basats en ARNases-S de Rosàcies i Solanàcies, les relacions d'ortologia per als factors modificadors va ser estudiat. Ortòlogs candidat van ser trobats per a NaTrxh, SBP1 i MdABCF, no obstant, un patró evolutiu més complex va ser observat per a NaSTeP, 120K i NaPCCP. De tal manera que, a pesar de les diferències, es pot plantejar la hipòtesi de que una part dels modificadors de l'AIG estan / Muñoz Sanz, JV. (2016). Crossability barriers in Prunus: the role of modifiers in the regulation of the gametophytic self-incompatibility system [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/68489 / TESIS

One of the characteristics of German scientific language is the frequent use of noun phrases containing multiple modifiers. A common type of modifier in German scientific writing is the NP modifier in genitival case. Although not uncommon in the Swedish language, these so-called genitival modifiers are found more frequently in German texts, not only because of the grammatical differences between the two languages, but also due to the German preference for a more nominal writing style. This study focuses on the translation of German genitival modifiers into Swedish. The first aim of the study was to determine which syntactic structures can be used to translate German genitival modifiers into Swedish, as well as to establish the most frequently used translation structure or structures. The second aim was to identify the factors that prevented the direct transfer of a genitival modifier. For the purposes of this study, a section of Wolfgang Mertens popular scientific book Traum und Traumdeutung was translated into Swedish, after which it was analyzed with the above-mentioned aims in mind. The study has shown that about a third of the genitival modifiers found in the source text were translated using prepositional modifiers. Another third were translated with a corresponding Swedish genitival modifier. For the translation of the remaining genitival modifiers six additional types of structures were used. The main factors that prevented a direct translation were the grammatical inability to use certain types of genitival modifiers in the target language as well as the preference of the target language for more verbal expressions.

<p>This essay deals with translation issues arising when translating a German source text – situated within the field of media communication and political science – into Swedish. More specifically, it focuses on translation problems and solutions in regard to extended participial modifiers and metaphorical expressions.From a translation perspective, complex German pre-nominal participial modifiers are known to pose a challenge to Swedish translators. This depends on language-specific restrictions within the nominal domain. In linguistic translation literature, it is commonly held, that complex pre-nominal participial modifiers cause – in Vinay & Darbelnet’s (1977) terminology – 'transpositions', yielding a Swedish relative clause. This widely held assumption again proved to be right. In some cases, however, other structural options were made use of such as abbreviated (participial) clauses. Also, depending on the complexity of the modifier, transpositions were involved which crossed one or more sentence boundaries. In contrast to complex nominal phrases with pre-nominal participial modifiers, metaphors are usually considered to be stylistically inappropriate in academic discourse. However, a closer examination of the metaphorical expressions appearing in the source text showed that they are almost without exception lexicalized or conventionalized and, therefore, not particularly artistic or daring. The analysis of the translation procedures involved when translating metaphorical expressions was limited to metaphors linked to the area of politics and career, mainly stemming from the conceptual domains: POLITICS IS WAR/A GAME and CAREER IS A JOURNEY. The analysis shows that German and Swedish have similar metaphors, building on those exact concepts. Still, literal translation was not applied in each and every case. In some cases, a neutral periphrasis or a formal equivalent was employed which resulted in a loss or change of some of the semantic aspects inherent to the original metaphor.</p><p>Keywords: <em>translation, nominal phrases, extended modifiers, metaphors</em></p>

Mechanical ventilation, a lifesaving intervention for patients with acute respiratory distress syndrome (ARDS), also unfortunately contributes to excessive mechanical stress and impaired lung physiological and structural integrity. We have elsewhere established the pivotal role of increased nicotinamide phosphoribosyltransferase (NAMPT) transcription and secretion as well as its direct binding to the toll-like receptor 4 (TLR4) in the progression of this devastating syndrome; however, regulation of this critical gene in ventilator-induced lung injury (VILI) is not well characterized. On the basis of an emerging role for epigenetics in enrichment of VILI and CpG sites within the NAMPT promoter and 5'UTR, we hypothesized that NAMPT expression and downstream transcriptional events are influenced by epigenetic mechanisms. Concomitantly, excessive mechanical stress of human pulmonary artery endothelial cells or lipopolysaccharide (LPS) treatment led to both reduced DNA methylation levels in the NAMPT promoter and increased gene transcription. Histone deacetylase inhibition by trichostatin A or Sirt-1-silencing RNA attenuates LPS-induced NAMPT expression. Furthermore, recombinant NAMPT administration induced TLR4-dependent global H3K9 hypoacetylation. These studies suggest a complex epigenetic regulatory network of NAMPT in VILI and ARDS and open novel strategies for combating VILI and ARDS.

This thesis investigates how male and female athletes competing in the 2016 Olympic Games in Rio de Janeiro were portrayed in two British and two American newspapers (The Daily Telegraph, The Independent, Los Angeles Times and The Washington Post). It also examines how the total amount of coverage was distributed between athletes of each gender. Previous studies have shown that female athletes are not given as much space as male athletes (Jones, 2004, Caple, Greenwood, &amp; Lumby, 2011, Godoy-Pressland 2014) and that when they are reported on, not portrayed in the same way as male athletes (Eagleman, 2015). This can have negative effects for athletes and their sport (Knight &amp; Giuliano, 2011). For this essay, a corpus was created out of articles from the four newspapers, which were subsequently analysed quantitatively and qualitatively. The findings showed a greater equality in the amount of coverage provided by newspapers than had been shown by previous studies, but with such a small sample, results could not be generalised widely. For the qualitative analysis, articles from two specific events were analysed and determined to not contain any major differences between males and females, with only one exception, which was Los Angeles Times’ article on the women’s artistic gymnastics team all-around event.

In this thesis, the performance of a miniaturised field asymmetric waveform ion mobility spectrometry (FAIMS) device hyphenated with time-of-flight mass spectrometry is studied and evaluated for analysis of a variety of compounds in different sample matrices. FAIMS is a selective spectrometer which is highly orthogonal to mass spectrometry and has the potential for enhancing sensitivity and improve selectivity of rapid analyses. In Chapter 2, the performance of the miniaturised FAIMS device is tested for stability and transmission under a wide range of ion source conditions. An investigation of three different systems, including pairs of isobaric, isomeric and near-mass ions shows that miniaturised FAIMS has the ability to distinguish between analytes that are challenging to separate by mass spectrometry. Chapter 3 explores the effect of changing the composition of the carrier gas by observing the effect of adding gas modifiers on the FAIMS spectra of small molecules, peptides and proteins. Chapter 4 investigates the advantages of combining a fast FAIMS separation with mass spectrometry in the analysis of nitrogen-containing pharmaceutical impurities, where FAIMS is found to offer additional selectivity. In Chapter 5, the development of a UHPLC-FAIMS-MS method for the quantitative determination of a drug metabolite in urine is reported. UHPLC-FAIMS-MS shows improvements in signal-to noise and linear dynamic range as well as a reduction in chemical noise, demonstrating the potential of combining FAIMS with mass spectrometry.

A thesis submitted to the Faculty of Science, University of the Witwatersrand, in fulfilment of the requirements for the degree of Doctor of Philosophy Johannesburg, 2011. / The phosphotidylinositide-3-kinase (PI3K) pro-survival signalling pathway is critical in the development of cancer. Major contributors to the proliferative and/or anti-proliferative signalling in human oesophageal squamous cell carcinoma (HOSCC) are currently unknown. Based on the Ser473 phosphorylation state of PKB (pPKB), this study dissects the overall activation status of the PI3K/PKB pathway. Despite the prevalent membrane expression of PI3K determined through western blotting and immunofluorescence, pPKB levels were shown to be surprisingly low. Activation of EGFR did not produce a hyperactivation of the PI3K/PKB pathway. Neither PI3K nor PKB sequence isolated from the 5 HOSCC cell lines possessed any of the ―hotspot‖ mutations described previously for other tumours. Inhibiting phosphatase protein 2A (PP2A), an integral antagonist of PKB, indicated that its activity in respect of PKB is diminished in HOSCC cells. Despite the low concentration of pPKB, the reciprocal relationship with PTEN expression was not evident in the WHCO and SNO HOSCC series. Moreover, reversible oxidization and inhibition of PTEN served to augment the activation of the PI3K/PKB pathway. Since oxidation of PTEN is imperative for effective signal propagation from activated EGFR and PI3K, these data reveal an aberrant EGFR-PI3K-H2O2 mediated PTEN inhibition in HOSCC. Allied to this discovery, was the finding that HOSCC cells are highly susceptible to oxidative stress induced by H2O2. This was suggested to play an essential part in maintaining the low PI3K/PKB activation status. Although the decrease in PTEN activity was required for the induction of pPKB, PTEN may not be the only limiting component for the activation of the PI3K/PKB pathway in HOSCC. In addition to its overexpressed EGFR status, the WHCO and SNO HOSCC series have the propensity to appropriate nuclear β-catenin. Interruption of the PI3K/PKB signalling pathway caused a small, yet significant, depression in the nuclear localization of β-catenin in 3 of the HOSCC cell lines. Together, this work greatly expands our understanding of the major influences behind the proliferative and/or anti-proliferative signalling in HOSCC, primarily that, the EGFR overexpression status does not propagate these transforming capabilities via activation of the PI3K/PKB pathway, and that this may be a reflection of its transformation potential. The findings derived from this study are likely to have a profound impact on future therapeutic targets for this disease.

Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1991. / Vita. Abstract. Includes bibliographical references (leaves 167-170). Also available via the Internet.

The objective of this study was to compare different modifiers in two asphalt cements, namely Cold Lake 80/100 obtained from the Edmonton, Alberta refinery of Imperial Oil Limited and a PG 58-28 obtained from a now closed refinery in the Montreal, Quebec area. The modifiers investigated were polyphosphoric acid (PPA), styrene-butadiene-styrene (SBS), and reactive ethylene terpolymer (Elvaloy® RET). The comparisons were done based on both unaged and laboratory-aged materials. The investigation covers high temperature grading using a dynamic shear rheometer (DSR), low temperature grading using a bending beam rheometer (BBR), ductile strain tolerance as measured in the double-edge-notched tension (DENT) test and percentage recovered strain using multiple shear creep recovery (MSCR) test. The Superpave® performance grade span was increased for all modifiers with substantial increases in the high temperature rutting parameter G*/sin while the BBR parameters, T(S = 300 MPa) and T(m = 0.3), remained largely unchanged. In the PG 58-28 base asphalt, Elvaloy® modifiers were able to reduce the intermediate Superpave® grade temperature by significant amounts. All polymer modifiers were good at improving the ductile strain tolerance as measured in the DENT test. In contrast, PPA alone reduces the strain tolerance due to the formation of extra asphaltenes and the likely gelation of the asphaltene-rich phase. Nearly all the modified samples passed the MSCR test except those with poor compatibility (i.e. SBS blended with Cold Lake without sulfur, Elvaloy® systems without acid catalyst, and pure PPA modified systems) or no modifier, which did not reach the required elastic recovery at high levels of non-recoverable compliance. In the BBR test done at low temperatures, all modified systems showed similar elastic recovery and viscous (non-recoverable) compliance. However, in the ductile-to-brittle range the Elvaloy® RET-modified binders showed a definite advantage of a few degrees over the unmodified base asphalts. Finally, chemical aging tendencies, as measured by weight gain and carbonyl formation, turned out to be very similar for all the investigated compositions. / Thesis (Master, Chemistry) -- Queen's University, 2010-12-13 13:29:45.173

Rail corrugation is a periodic wear pattern that develops on the wheel and rail contacting surfaces in railway systems. It is a commonly observed phenomenon worldwide and is a serious problem because it causes degradation of the track and its components and is a significant source of noise. Currently the only reliable method of ameliorating the negative effects of rail corrugation is to periodically regrind the rail surface to a smooth profile, at great expense to the railway operator. It is therefore of interest to investigate other possible control strategies to reduce corrugation growth through an understanding of the mechanism of corrugation formation. This thesis presents an investigation into the effect of speed variation on the corrugation formation mechanism. The research presented is intended to highlight the significant role that speed variation has on corrugation formation via a disruption of the feedback mechanism which leads to corrugation growth over successive train passages. This discovery motivates the investigation the feasibility of altered speed variation as a novel corrugation control method, due to the large effect that the variance of train speed has on corrugation growth rates. The effect of variable pass speed on corrugation formation has been investigated in this thesis through the use of efficient models of corrugation formation in straight track and cornering conditions. These models are simple enough to readily perform corrugation control studies without neglecting any relevant physics, obscuring the corrugation formation mechanism with overly detailed modelling or imposing a significant computational burden on performing control studies. These novel models have been outlined and their predictions elucidated in detail. A theoretical investigation into the effect of speed variation in the presence of a resonance free mechanism for corrugation growth via a contact filter has been performed and shown to only be important when the dynamic wavelength of formation approaches the size of the contact patch. The results of these corrugation models have been validated via test rig and field experiments. An investigation of the effectiveness of speed variation as a corrugation growth control measure has also been investigated via test rig experiments. The results of this thesis have formed the basis of an industry supported field trail of this technique for corrugation mitigation that is currently in progress.