L’avènement de la modernité est venu changer le processus d’attribution statutaire en laissant une plus grande marge de manœuvre à l’individu(alité). Plus exactement, à l’instar de Martuccelli (2002), nous avons remarqué qu’il se produit en société moderne une prolifération narrative, c’est-à-dire qu’Ego peut à présent recourir à une foule de topiques pour s’autoprésenter, créant ainsi une certaine variance attributive du statut. Cependant, celle-ci reste limitée en raison de contraintes et résistances se rapportant aux différentes positions statutaires, qui bien évidemment freinent son émergence (Martuccelli, 2002). Le processus identitaire donc, aujourd’hui plus que jamais, s’en trouve marqué par ce que nous appelons une dyade variance/constance relative attributive, à savoir qu’il présente des moments de changement et des temps d’invariance. La présente recherche entend donc contribuer à la discussion théorique du statut social en prolongeant l’œuvre de Martuccelli (2002; 2005). Plus précisément, nous souhaitons proposer une articulation des diverses composantes de cette dyade variance/constance relative attributive que sous-entend la question suivante : comment comprendre la dynamique d’attribution statutaire (inter)individuelle dans la société québécoise contemporaine traversée par l’individualisme ? À cette interrogation se greffent deux sous-questions. Primo, quelles sont les différentes dimensions de la dynamique attributive ? Secundo, comment s’articulent-elles les unes aux autres ?

Thesis (M.Med. (Radiation Oncology)) -- University of Limpopo, 2022 / Background Breast cancer is known to be a heterogeneous disease that demands patient centered care. Establishing the clinicopathological characteristics of breast cancer patients is a vital step in an effort to individualize their treatment. Aim The aim is to evaluate the clinicopathologic features of the different subtypes of breast cancer when classified according to immunohistochemistry markers in women attending Pietersburg hospital. Methods A retrospective review of medical records of women treated at Pietersburg hospital between 2010 and 2011 was done. Data collection was extracted on a customized data collection sheet. Chi square was used to determine association between clinicopathologic features and molecular subtypes. Analysis of variants was used to assess association between molecular types and age. Results The mean age of the population was 55.3 years (+/-14 standard deviation). The majority of patients were in stage III (46.9%) and IV (33.5%). The ER, PR, HER2/neu positive rate was 50.6%, 30% and 14,3 % respectively with a negative rate of 13,4%, 19,5% and 23,4% respectively. ER, PR and HER2/neu was unknown in 18%, 19, 5% and 23,4% respectively. The most common molecular subtype was luminal A (53,6%) followed by triple negative (27.2%), HER2/neu (11, 4%) and luminal B (7. 9%).There was no association between the subtypes and tumour stage (p=0.578).The rate of distant metastasis was similar across the subtypes being 37,9%,35%, 32,4% and 31,9% in HER2/neu, luminal B ,luminal A and TNBC, respectively. All four molecular subtypes had high rate of axillary lymph node involvement (p=0.886) Luminal A had the least percentage of high grade tumours with TNBC having the highest. Five-year overall survival for the cohort was 25, 6% with luminal A and B having a better 5 year overall survival of 27,2% and 25% respectively, whereas HER2/neu and TNBC had lower 5 year OS of 24% and 23,3%. Conclusion The findings of this study suggest that luminal A subtype is the most predominant and the majority might benefit from hormonal therapy. However, some patients could not be classified due to missing IHC marker test results. The outcome across all four subtypes is poor and more effort should be put towards improving the diagnosis and treatment individualization and follow-up in these patients.

Humanity as for now is living in the future and sustainability issues are the daily challenges for the planet, and not a future problem any longer. The trend for sustainable development is pointing in the wrong direction and the pressure on natural resources is increasing. Research suggests stakeholders demand and reward responsibility from companies. The work for sustainable development requires extensive cooperation between companies, and people. Adopting a stakeholder perspective and meeting demands of various stakeholder groups means that companies today have even more relationships that they engage in than before. Companies rely on each other to be able to make an impact. An individual alone cannot make any changes but rather the society needs to act united to deal with these sustainable issues our world faces. Earlier studies emphasize that relationship marketing has the potential to assist sustainable efforts positively. Therefore, the purpose of this study is to understand the role of relationship marketing in the sustainable development context, focusing on customers’ and the network’s view on sustainability. The theoretical framework is based on relationship marketing, co-creation and the key mediating variables of relationship marketing model and was inspired by both the empirical data and previous research. Further, to explain sustainable development, concepts such as stakeholder perspective and triple bottom line were used. To achieve the study’s purpose, empirical data was collected through conducting an inductive qualitative case study using non-probability sampling in the outdoor furniture industry. Data collected consists of field observations and semi-structured interviews. Data was processed and analyzed through transcription and coding. Findings imply strong relationships and cooperation are essential for effective sustainable efforts. The concept of sustainable development is diffuse and difficult to grasp. It was also implied that there is a disconnect in shared core values regarding sustainability between the business network and the market in this case study. However, theory suggests the role of relationship marketing is to push the narrative of sustainability, even if demand is low. Practical implications and recommendations suggest adopting co-creation processes to increase mutual learning and understanding of complex concepts such as sustainable development.

Selective killing of tumor cells requires the identification of drug targets critical to pathways that drive or support cancer progression. Protein kinases are an important class of intracellular enzymes involved in the regulation of biochemical pathways, deregulation of these kinases has been strongly implicated in cancer progression. To identify possible oncogenic kinases to which tumor cells might be selectively addicted, we screened the ON108 series of ATP-mimetic small molecule inhibitors in various triple negative breast cancer (TNBC) and normal cell lines. This approach led us to the identification of a novel kinase inhibitor, ON108600. We first examined the in vitro and in vivo effects of ON108600. ON108600 was found to be a potent inhibitor of Casein Kinase 2 (CK2) and the Dual-Specificity-Tyrosine (Y)-Phosphorylation-Regulated-Kinase (DYRK) family of serine-threonine kinases, both of which have been implicated in cancer progression. ON108600 showed broad-spectrum anti-proliferative and cytotoxic activity in multiple TNBC cell lines whilst having little or no effect on normal cells. Treatment of cancer cells with ON108600 resulted in inhibition of downstream signaling mediated by substrates of CK2. Further, ON108600 selectively arrested cancer cells in the mitotic phase of the cell cycle and activated the caspase-signaling cascade. We next performed x-ray crystallographic studies of ON108600-CK2 to determine the structural basis of ON108600-CK2 interaction. The co-crystal structure of ON108600-CK2 revealed that ON108600 binds in the active site pocket of CK2α wherein it mimics the binding of ATP and GTP in the CK2 active site. Notably, ON108600 mimics not only the shape and electrostatics of ATP/GTP, but also their hydration patterns in the CK2 active site pocket. Structural studies further revealed that ON108600 induces a conformational change in the β4-β5 loop of the catalytic subunit, which is known to interact with the β-regulatory subunit of CK2 and is critical for substrate recognition and activation. Lastly, we examined the efficacy of ON108600 in Triple Negative Breast Cancer (TNBC) and its ability to target and eliminate chemo-resistant Tumor-Initiating Stem Cells (TI-SCs) in TNBC. Clonogenic survival and sphere forming ability of purified CD44high CD24-/low TI-SCs from MDAMB-231 and Hs578t cells was potently inhibited by ON108600 treatment. We also observed that paclitaxel-resistant MDAMB-231 cells had increased levels of the CD44high CD24-/low stem cell- like population that correlated with increased expression of kinases CK2α2, DYRK1A and DYRK1B and these cells were sensitive to ON108600 treatment. Significantly, ON108600 showed robust antitumor efficacy as a single agent in a highly aggressive orthotopic TNBC xenograft model showing ~60% tumor growth inhibition. Immunohistochemical analysis of ON108600 treated tumors showed that a significant percentage of cells were apoptotic, indicating that activation of caspase mediated apoptosis contributes to the mechanism of action of ON108600 in vivo. Taken together, our results demonstrate that ON108600 is a novel and potent inhibitor of the CK2α1, CK2α2, DYRK1A and DYRK1B kinases. ON108600 binds in the active site pocket of CK2α and mimics ATP-GTP binding. ON108600 inhibits CK2-mediated signaling; arrests cancer cells in mitosis and induces apoptotic cell death via activation of caspases. Importantly, ON108600 is able to effectively kill the CD44high CD24-/low breast-cancer stem cell like population from TNBC cells. Finally, taxol-resistant MDAMB-231 TNBC cells express high levels of CD44, CK2α2, DYRK1a and DYRK1b and are sensitive to ON108600 treatment. Our study represents the first attempt to associate protein kinase CK2, DYRK1A and DYRK1B with TNBC and TI-SCs in TNBC and identifies a novel kinase inhibitor, ON108600 which effectively kills TI-SCs and taxol-resistant cells in TNBC. / Molecular Biology and Genetics

Gastroparesis is a disorder characterized by delayed gastric emptying due to chronic abnormal gastric motility. Prokinetic agents such as domperidone and metoclopramide are the cornerstone in treatment of gastroparesis. Although these medications have been used for decades, essential information about their metabolism is not available. Lack of knowledge about the metabolites formed in the body upon administration of the aforementioned medications as well as the enzymes involved in their metabolism limits key information needed to make sound medical decisions. Accurate and comprehensive identification of the metabolites along with reaction phenotyping of prokinetic agents will ensure safe and effective use of these drugs and hence enhance the clinical outcome. The thesis starts with an introductory chapter which comprises a comprehensive literature review on gastroparesis and the available pharmacological treatment options. The chapter also emphasizes the importance of metabolic profiling of prokinetic agents (domperidone and metoclopramide) and its impact on enhancing the safety and efficacy of these medications. Chapter 2 of this project was aimed to determine phase oxidative and conjugative metabolites of domperidone in the plasma and urine of gastroparesis patients using tandem mass spectrometry. First, the metabolites were identified in in-vitro human subcellular fractions. The knowledge gained in this experiment helped identifying the metabolites in the biological fluids of patients. In total, 12 metabolites including 7 new metabolites were identified, 5 of which were not reported previously. Chapter 3 aimed to identify the cytochrome P450 (CYP) enzymes responsible for the metabolism of metoclopramide. The parent depletion approach was used and a novel LC-MS/MS method was developed and validated to enable metoclopramide quantification. CYP2D6 was showed to the predominant isoform in metoclopramide metabolism; other isoforms also contribute to a minor extent. Chapter 4 discusses the possibility of potential drug-drug interaction (DDI) in the current management practice of gastroparesis. We identified and investigated some frequently used drug combinations that are known to share common metabolic pathways. Domperidone in combination with pioglitazone and ondansetron was evaluated. Results showed that pioglitazone inhibited domperidone metabolism in-vitro. Our experiments did not predict a DDI for the domperidone - ondansetron combination. In summary, the ultimate goal of this thesis was to improve the management of gastroparesis by increasing information about the metabolic disposition of prokinetic agents and to investigate the magnitude of putative drug combinations. The knowledge provided by this work will help in making more effective and less hazardous clinical decisions which will ultimately lead to more successful gastroparesis management. / Pharmaceutical Sciences

Collagen is one of the most important and abundant proteins in mammals. It consists of three left-handed PPII helixes coiled along a common axis to form a very compact right-handed super helix. The primary structure is shown to be (Gly-Xaa-Yaa)n repeats with high content of prolyl residues at both Xaa and Yaa positions. <i>Cis-trans</i> isomerization of the prolyl amide bonds is one of the rate-limiting steps during collagen triple helix folding. The conformationally locked alkene isosteres Fmoc-Gly-Ψ[(E)CH=C]-Pro-Hyp(tBu)-OH and Fmoc-Pro-Ψ[(E)CH=C]-Pro-OH were designed and synthesized. The synthesis of the Gly-Pro isostere had no stereo-control, and the two diastereomers of the tripeptide isostere Fmoc-Gly-Ψ[(E)CH=C]-Pro-Hyp(tBu)-OBn were separated by normal phase HPLC. Although the stereoselectivity of the asymmetric reduction was not good for the Pro-Pro isostere, the resulting diastereomers was separable by flash chromatography, and the absolute stereochemistry of the two diastereomers was determined by Mosher's method. The Gly-Pro alkenyl peptides, and their control peptide Ac-(Gly-Pro-Hyp)8-Gly-Gly-Tyr-NH2 were synthesized and purified. All three peptides showed a maximum around 225 nm and a minimum close to 200 nm in the CD spectra, which indicated the formation of PPII helixes. The Tm value of the control peptide was determined to be 50.0 °C. The peptide with Gly-Ψ[(E)CH=C]-L-Pro-Hyp as the guest triplet formed a stable triple helix with a Tm value of 28.3 °C. The peptide with Gly-Ψ[(E)CH=C]-D-Pro-Hyp as the guest triplet showed a linear decrease in the ellipticity with increasing temperature, which indicated that no triple helix was formed. The Pro-Pro alkenyl peptide and its control peptide H-(Pro-Pro-Gly)₁₀-OH were synthesized and purified. The T_m value of control peptide was determined to be 31.6 °C by extrapolation to 0 M TMAO in PBS buffer, which was very close to the measured value of 31.5 °C. The Pro-Pro alkenyl peptide began to show a maximum around 225 nm in the CD spectra when the concentration of TMAO was higher than 2.5 M. After extrapolation to 0 M TMAO, the T_m value was determined to be –22.0 °C. These results indicate that the backbone inter-chain hydrogen bond is one of the major forces in stabilizing the collagen triple helix, while <i>cis-trans</i> isomerization has limited contribution. The intrinsic properties of the amide bond may have huge influence on the stability of the collagen triple helix. The helix-turn-helix motif is an important tertiary structure in DNA-binding proteins. Stepwise modifications of the Antennapedia HTH peptide (27-55) were performed to improve the helicity and stability. The peptide with more side-chain ion-pairs was over 4 times more helical than the native Antp peptide, while the Ala-based peptide was over 9 times more helical than the native peptide. A 12-membered ring, Fmoc-protected HTH-turn mimic was designed and synthesized, and was ready for solid phase peptide synthesis. The solubility of the cyclic peptide was very poor, and the purification of the final product was very difficult. The solubility problem might also affect solid phase peptide synthesis in the future. / Ph. D.

CUORE is one of the world-leading experiments to search for neutrinoless double beta decay. The excellent energy resolution and the stability of the detectors at CUORE also allow for other rare event searches. This thesis describes an experimental analysis undertaken to search for baryon number violation in 130Te using the data acquired by the CUORE detector. The conservation of the baryon number in the Standard Model relies on an accidental symmetry rather than being deduced from fundamental principles. If there is evidence suggesting a breach of this symmetry, it would significantly impact our understanding of the universe, especially concerning the origin of the matter-antimatter asymmetry. One possible way for this conservation principle to be violated is through tri-nucleon decay, where three nucleons decay simultaneously within a nucleus. For 130Te, the resulting decay products would be emitted with energy in the GeV range, making them a promising signal for detection in the CUORE experiment. This thesis describes the search signatures, the relevant background, and the analysis techniques used in this investigation, and results for an exposure of 236.6 kg·yr are presented. The daughter nucleus of the decay (127In) is unstable, and its decay chain can offer an secondary signature coinciding with the emitted energy. The viability of adding this secondary signature is also presented. / Doctor of Philosophy / Since the beginning of scientific thought, humankind has asked why there is something in the Universe instead of nothing. As our understanding of the working principles of the Universe deepened, this question has been refined and focused on an intriguing imbalance easily ob- served around us: The imbalance of the quantity of matter over anti-matter. We have never observed anti-matter galaxies or stars, and we never observe anti-matter manifesting around us in our daily lives. There are many ideas physicists have developed to explain this mysteri- ous absence of anti-matter, and one of them involves searching for an extremely rare radioac- tive process called triple nucleon decay. This thesis uses the data acquired by the nuclear experiment CUORE, situated in the Gran Sasso mountains in Italy, to look for this process.

[EN] The choosing of an adequate structural typology for a building in its design stage is a complex problem due to different tangible and intangible factors and the multiple alternatives that exist. Nowadays sustainability, defined by triple bottom line englobing economic, social and environmental criteria, gains more and more relevance. However, in the construction sector, companies keep applying tools based on traditional bottom line referenced to one metric (financial performance or cost), to evaluate projects, ignoring, or underestimating, environmental or social values and forgetting about long-term impact on quality life of present and future generations. Moreover technological advances allow the development of new industrial solutions with a higher productivity rate and a lower impact, but construction is a sector that struggles to innovate and traditional solutions are still often applied without considering the solutions provided by industry. Multicriteria methods are being set higher each day as key tools, capable of incorporating environmental and social matters to the decision- making process. Tools using multicriteria evaluation to assess sustainability of finished buildings and sustainability of a certain type of structures already exist. The objective of this thesis is to develop a hybrid method of multiple criteria, combining AHP with the Delphi method and the VIKOR technique, to apply economic, social and environmental criteria in the selection of a structural typology for medium spanned buildings, taking into account both the construction and the operation stages. Using AHP, a hierarchical structure is defined from judgements emitted by a panel of experts, with the following levels: goal, criteria, sub-criteria and alternatives. From this hierarchy, also following AHP and with the judgements emitted by the panel of experts, a priority vector of the sub-criteria with respect to the goal and the priority vectors' matrix of the alternatives with respect to each sub-criterion are obtained. The Delphi technique is used in order to handle the surveys in which experts emit their judgements, until consensus is reached. From the priority vectors, applying the VIKOR method, the compromise solution is reached, being this the closest to ideal. For the elaboration of this tool, tangible criteria, like manufacturing cost, transport and assembly cost, emissions impact and embodied energy and operating energy; and intangible criteria like roof maintenance cost, aesthetic, satisfactory fireproofing and the use of local materials, have been considered. The specific case of a 17 m span sports hall in a recreational level has been studied. Five alternatives have been evaluated: both of the traditional Prefabricated concrete and purlins and Steel lattice and purlins options and other three applying technological innovations developed by the building industry: Prefabricated concrete and self-supporting curved system, Self-supporting curved system and Laminated wood and purlins, being the Self-supporting curved system roof option obtained as the optimal solution. Lastly, a computer tool is designed in which, for any medium spanned building, introducing data from companies offering the five studied alternatives, a compromise solution is obtained, taking into account sustainability criteria. The developed tool will serve as help towards the choosing of a structural typology, applying sustainability criteria for the roof a medium spanned building. / [ES] La selección de una tipología estructural adecuada para un edificio en la etapa de diseño es un problema complejo, debido a los diferentes factores tangibles e intangibles y a las múltiples alternativas que existen. Hoy en día la sostenibilidad, definida por el triple principio, que engloba criterios económicos, sociales y ambientales, es cada vez más relevante. Sin embargo, en el sector de la construcción las empresas siguen aplicando herramientas basadas en análisis de costes y beneficios para evaluar proyectos, ignorando o subestimando valores medioambientales o sociales y olvidando el impacto a largo plazo sobre la calidad de vida de las generaciones presentes y futuras. Además, los avances tecnológicos han permitido el desarrollo de nuevas soluciones industriales con una mayor productividad y un menor impacto, pero la construcción es un sector al que le cuesta innovar y a menudo se siguen aplicando soluciones tradicionales sin considerar las distintas soluciones proporcionadas por la industria. Los métodos multicriterio se están posicionando cada vez más como herramientas clave, capaces de incorporar cuestiones medioambientales y sociales en el proceso de toma de decisiones. Ya existen herramientas que utilizan métodos de evaluación multicriterio para evaluar la sostenibilidad de los edificios terminados y la sostenibilidad de las estructuras de un tipo determinado, comparándolas con las mejores técnicas disponibles. El objetivo de esta tesis es desarrollar un modelo híbrido de criterios múltiples, que combina el AHP con el método Delphi y la técnica VIKOR, para aplicar criterios económicos, sociales y ambientales en la selección de una tipología estructural para edificios de luces medias, teniendo en cuenta tanto la etapa de construcción como la de funcionamiento. Utilizando AHP se define una estructura jerárquica, a partir de juicios emitidos por un panel de expertos, con los siguientes niveles: objetivo, criterios, sub-criterios y alternativas. A partir de esta jerarquía, siguiendo también el AHP y con los juicios emitidos por el panel de expertos, se obtiene el vector de prioridad de los sub-criterios respecto del objetivo y la matriz de vectores de prioridad de las alternativas respecto de cada criterio. Para gestionar las encuestas en las que los expertos emiten sus juicios, hasta alcanzar el consenso, se utiliza la técnica Delphi. A partir de los vectores de prioridad, aplicando el método VIKOR, se obtiene la solución de consenso, que es la más cercana a la ideal. Para la elaboración de esta herramienta se han considerado criterios tangibles como el coste de fabricación y el de transporte y montaje, el impacto de las emisiones y las energías interna y de funcionamiento y criterios intangibles como el coste de mantenimiento de la cubierta, el aspecto estético, la resistencia al fuego y el uso de materiales locales. Se ha estudiado el caso concreto de un pabellón polideportivo de 17 m de luz, evaluando cinco alternativas: las dos tradicionales de vigas celosía y correas metálicas y vigas y correas prefabricadas de hormigón pretensado y otras tres que aplican las innovaciones tecnológicas desarrolladas por la industria de la construcción: vigas de hormigón prefabricado con cubierta tipo membrana, cubierta metálica autoportante y estructura de madera laminada, obteniéndose como solución óptima la cubierta metálica autoportante. Por último, se diseña una herramienta informática en la que, para cualquier edificio con una luz media, introduciendo datos obtenidos de ofertas de empresas de las cinco alternativas estudiadas, se obtiene la solución de consenso teniendo en cuenta criterios de sostenibilidad. La herramienta desarrollada mediante hojas de cálculo servirá de ayuda para elegir una tipología estructural, aplicando criterios de sostenibilidad, para la cubierta de un edificio con una luz media. / [CA] La selecció d'una tipologia estructural adequada per a un edifici en l'etapa de disseny és un problema complex, a causa dels diferents factors tangibles i intangibles i a les múltiples alternatives que existeixen. Avui dia la sostenibilitat, definida pel triple principi, que engloba criteris econòmics, socials i ambientals, és cada vegada més rellevant. No obstant açò, en el sector de la construcció les empreses segueixen aplicant eines basades en anàlisis de costos i beneficis per a avaluar projectes, ignorant o subestimant valors mediambientals o socials i oblidant l'impacte a llarg termini sobre la qualitat de vida de les generacions presents i futures. A més, els avanços tecnològics han permès el desenvolupament de noves solucions industrials amb una major productivitat i un menor impacte, però la construcció és un sector al que li costa innovar i sovint se segueixen aplicant solucions tradicionals sense considerar les diferents solucions proporcionades per la indústria. Els mètodes multicriterio s'estan posicionant cada vegada més com a eines clau, capaces d'incorporar qüestions mediambientals i socials en el procés de presa de decisions. Ja existeixen eines que utilitzen mètodes d'avaluació multicriterio per a avaluar la sostenibilitat dels edificis acabats i la sostenibilitat de les estructures d'un tipus determinat, comparant-les amb les millors tècniques disponibles. L'objectiu d'aquesta tesi és desenvolupar un model híbrid de criteris múltiples, que combina el AHP amb el mètode Delphi i la tècnica VIKOR, per a aplicar criteris econòmics, socials i ambientals en la selecció d'una tipologia estructural per a edificis de llums mitjanes, tenint en compte tant l'etapa de construcció com la de funcionament. Utilitzant AHP es defineix una estructura jeràrquica, a partir de judicis emesos per un panell d'experts, amb els següents nivells: objectiu, criteris, sub-criteris i alternatives. A partir d'aquesta jerarquia, seguint també el**AHP i amb els judicis emesos pel panell d'experts, s'obté el vector de prioritat dels sub-criteris respecte de l'objectiu i la matriu de vectors de prioritat de les alternatives respecte de cada criteri. Per a gestionar les enquestes en les quals els experts emeten els seus judicis, fins a aconseguir el consens, s'utilitza la tècnica Delphi. A partir dels vectors de prioritat, aplicant el mètode**VIKOR, s'obté la solució de compromís, que és la més propera a la ideal. Per a l'elaboració d'aquesta eina s'han considerat criteris tangibles com el cost de fabricació i el de transport i muntatge, l'impacte de les emissions i les energies interna i de funcionament i criteris intangibles com el cost de manteniment de la coberta, l'aspecte estètic, la resistència al foc i l'ús de materials locals. S'ha estudiat el cas concret d'un pavelló poliesportiu de 17 m de llum, avaluant cinc alternatives: les dos tradicionals de bigues gelosia i corretges metàl·liques i bigues i corretges prefabricades de formigó pretesat i altres tres que apliquen les innovacions tecnològiques desenvolupades per la indústria de la construcció: bigues de formigó prefabricat amb coberta tipus membrana, coberta metàl·lica autoportant i estructura de fusta laminada, obtenint-se com a solució òptima la coberta metàl·lica autoportant. Finalment, es dissenya una ferramenta informàtica en la qual, per a qualsevol edifici amb una llum mitjana, introduint dades obtingudes d'ofertes d'empreses de les cinc alternatives estudiades, s'obté la solució de compromís tenint en compte criteris de sostenibilitat. La ferramenta desenvolupada servirà d'ajuda per a triar una tipologia estructural, aplicant criteris de sostenibilitat, per a la coberta d'un edifici amb una llum mitjana. / Martínez García, MP. (2015). Implementación de criterios de sostenibilidad económica, social y medioambiental para la selección de la cubierta en edificios de luces medias [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/56761

Yes / Background: miRNAs (microRNAs) play a key role in triple-negative breast cancer (TNBC) progression, and its heterogeneity at the expression, pathological and clinical levels. Stratification of breast cancer subtypes on the basis of genomics and transcriptomics profiling, along with the known biomarkers’ receptor status, has revealed the existence of subgroups known to have diverse clinical outcomes. Recently, several studies have analysed expression profiles of matched mRNA and miRNA to investigate the underlying heterogeneity of TNBC and the potential role of miRNA as a biomarker within cancers. However, the miRNA-mRNA regulatory network within TNBC has yet to be understood. Results and Findings: We performed model-based integrated analysis of miRNA and mRNA expression profiles on breast cancer, primarily focusing on triple-negative, to identify subtype-specific signatures involved in oncogenic pathways and their potential role in patient survival outcome. Using univariate and multivariate Cox analysis, we identified 25 unique miRNAs associated with the prognosis of overall survival (OS) and distant metastases-free survival (DMFS) with “risky” and “protective” outcomes. The association of these prognostic miRNAs with subtype-specific mRNA genes was established to investigate their potential regulatory role in the canonical pathways using anti-correlation analysis. The analysis showed that miRNAs contribute to the positive regulation of known breast cancer driver genes as well as the activation of respective oncogenic pathway during disease formation. Further analysis on the “risk associated” miRNAs group revealed significant regulation of critical pathways such as cell growth, voltage-gated ion channel function, ion transport and cell-to-cell signalling. Conclusion: The study findings provide new insights into the potential role of miRNAs in TNBC disease progression through the activation of key oncogenic pathways. The results showed previously unreported subtype-specific prognostic miRNAs associated with clinical outcome that may be used for further clinical evaluation. / EPSRC (EP/R043787/1).

Cardiovascular diseases, including heart attacks and strokes, are leading causes of mortality worldwide. A significant contributor to these conditions is the formation of blood clots obstructing blood flow to critical organs. This study looks specifically at the blood flow in the left ventricle (LV) using simulations with Finite Element Method (FEM). Computational simulations of blood flow offer valuable insights into potential risks, aiding in pre-surgical assessments. However, interpreting simulation results, often presented as ambiguous velocity fields, can be difficult. This study examines two different post-processing measurements, triple decomposition of the velocity gradient tensor and E-wave propagation index (EPI), that can turn these complexities into simpler scalar fields and values. This study confirms that both measurements are computable and most likely useful given a velocity vector field. Further studies, particularly by medical professionals, need to be done to analyse the effects of the measurements and verify its usefulness by comparison to the same measurements in real, not simulated, patients. Some specific studies are proposed to address this. With the triple decomposition implemented some basic analysis was done. High levels of shear were observed in certain areas, particularly around the papillary muscles, where strain was also present.