Les travaux de recherche menés dans cette thèse de doctorat se sont focalisés sur la compréhension des interactions graphène-plasma dans le cas de l’exposition de graphène polycristallin à un plasma d’argon pouvant contenant du diborane (B2H6). Une attention particulière est portée sur la cinétique de génération de dommage dans un plasma d’argon pur. Ainsi dans le cas d’un plasma continu, l’absence de seuil en énergie pour la génération de dommage due à un bombardement ionique est mis en évidence. Ceci ne peut s’expliquer que par une gravure à deux étapes, facilitée par la densité ionique élevée caractéristique des plasmas inductifs opérés en mode H. La caractérisation Raman des échantillons exposés au plasma montre une large distribution sur la petite zone sondée. Afin de relier ces fluctuations à l’état initial du graphène, l’imagerie Raman (RIMA) est adaptée dans le but d’extraire des données quantitatives sur l’état du graphène et utilisée pour le reste des travaux. Par la suite, l’étude temporelle des plasmas pulsés en puissance permet de trouver des conditions opératoires avec une fluence ionique drastiquement diminuée. Les traitements subséquents combinés aux analyses RIMA ont permis de suivre l’évolution de l’état du graphène et de distinguer l’état des joints du graphène des domaines de croissance. Ainsi, pour la première fois, l’autoréparation des joints de grains dans un matériau 2D est mis en évidence expérimentalement. Cet effet, théorisé dans les matériaux 3D mais difficilement observé expérimentalement, était effectivement prédis dans le cas du graphène. De plus, un contrôle fin des conditions opératoires du plasma pulsé d’argon a permis d’extraire des paramètres plasmas dans lesquels les métastables d’argons puis les photons VUV émis par les états résonants de l’argon sont les principaux vecteurs d’énergie. Suivant la même méthodologie que précédemment, ces traitements ont mis en lumière les rôles respectifs des ions, des métastables et des photons VUV dans la transmission d’énergie du graphène. Enfin, l’introduction de 5% de diborane a pour conséquence une modification radicale des paramètres physique du plasma. L’exposition de graphène à ce graphène à ce plasma démontre l’intérêt de cette technique pour l’incorporation élevé de bore tout en minimisant la génération de dommages / The research realized in this PhD thesis focuses on the understanding of plasma-graphene interactions during exposure of polycrystalline graphene films to a low-pressure argon RF plasma containing diborane (B2H6). A particular attention is devoted to the kinetics driving the damage formation dynamics. In the case of a continuous, argon plasma, the absence of energy threshold for the production of ion-induced damage is demonstrated. This is explained by two-step etching, facilitated by the high number density of charged species in the H-mode of RF plasmas. Raman characterization of plasma-treated graphene films shows a wide distribution over the small area surveyed. In order to link these fluctuations to the initial state of graphene, Raman imaging (RIMA) is adapted to extract quantitative data on the state of graphene before and after plasma treatment. Subsequently, the temporal study of argon RF plasmas in the pulsed regime makes it possible to find operating conditions with a drastically reduced fluence of charged species compared to the continuous regime; in combination with RIMA studies, this allows temporally- and spatially-resolved investigations of plasma-graphene interactions. For the first time, a preferential self-healing of ion-irradiation damage at grain boundaries of graphene films is experimentally demonstrated. Moreover, by using several electrical and optical diagnostics of the argon plasma in the pulsed regime, it is possible to determine operating conditions in which either the ions, the metastables or the VUV photons emitted by the resonant states become the main energy vectors. From these experiments, the respective roles of each of these species in the physics of plasma-graphene interactions could be highlighted. Finally, the introduction of 5% of diborane into the argon plasma induces a radical modification of the physicochemical properties of the plasma. Exposure of graphene films to this highly reactive plasma reveals high boron incorporation with minimal ion and hydrogen damage.

The doctoral thesis is dealing with the questions about synergy business which is understood as clusters, strategic alliances and franchise. It investigates the influence of the selected synergy business on the change of the company value (market value or the objective one). The topic reacts on the contemporary economic trends where fusions and grouping of companies is happening in more levels. One of them is the fusion and acquisition. Second one are various forms of alliances and groupings which allows to companies cooperation, sharing of knowledge, marketing, risks, know-how etc. They allow to the small and middle size companies to increase their competitiveness against the big firms. The doctoral thesis is treating the effect of using one of the form of the synergy business, namely the franchise, on the company value. Because just the increase of the company value should be one of its basic goals. In the framework of the doctoral thesis was made a research with the goal to identify the changes of selected value generators, which determine as a whole the company value. On the basis of the research results there was made in the final part of the work model evaluation of some variants, simulating the value change caused by the change of the selected value generator and there was quantified the synergy effect coming from the use of synergy enterprise. At the end of the work there are summarised the results of the research and of the model determination of the company value, possible benefits for the practice and theory and there are mentioned some possible starting points for the following scientific work in this field.

No description available.

This dissertation focuses on the identification and analysis of Corporate Social Responsibility (CSR) topoi in the travel and tourism industry. A sample set of six companies was selected for the study due to their size and prominence in the industry -- namely Disney, Hilton, Intercontinental, Marriott, Starwood, and Wyndham. Topoi were identified through a blended method of research that employed rhetorical analysis, modified grounded theory, and NVIVO content analysis software. The research followed three guiding principles to recognize textual cues and drive analysis: common and special topoi; topoi as heuristic; topoi for association and amplification; and topoi as fluid and movable. The common CSR topoi, triple bottom line and shared value, were also used as overarching categories for coding the texts. The results of the method yielded six unique topoi that were specific to each company; these included Inspiration, Higher Purpose, Collaborative Innovation, Leadership, The Age of Great Change, and Green. Results also included a set of seven special industry topoi that were common across all of the sample companies; these included Commitment, Management, Alignment, Environment, Engagement, Achievement, and Sustainability. The rhetorical synergy and topological levels identified through this research can inform other studies of CSR about the generative potential of topoi and its fluidity when viewed from different conceptual vantage points.

La leucémie lymphoblastique aiguë à cellules T (LLA-T) figure parmi les cancers infantiles les plus fréquents, représentant environ 15 % des cas de leucémie lymphoblastique aiguë pédiatrique et 25 % des cas chez les adultes. Cette maladie se caractérise par un blocage de la différenciation dans la lignée T et une accumulation de lymphoblastes non fonctionnels. Au cours des dernières décennies, les taux de survie se sont améliorés grâce à des protocoles de chimiothérapie agressifs. Cependant, ce traitement est associé à des effets secondaires graves qui affectent la qualité de vie des patients et imposent un fardeau important à leurs familles. De plus, les rechutes présentent un mauvais pronostic. Des travaux antécédents au laboratoire ont montré comment les oncogènes SCL et LMO1 reprogramment les thymocytes immatures au stade DN3 en cellules souches pré-leucémiques qui s’auto-renouvelent (pré-LSC). Les pré-LSCs sont à l'origine de la leucémie, elles sont résistantes à la chimiothérapie et causent des rechutes. Les pré-LSCs dépendent autant des oncogènes initiateurs que des signaux provenant de l'environnement thymique qui activent la voie NOTCH1/MYC. Finalement, un crible de petites molécules visant à inhiber les pré-LSCs dans leur niche a permis d’identifier le 2-MeOE2 comme un composé qui tue les pré-LSCs et diminue les niveaux de la protéine MYC. Dans cette thèse, nous avons cherché à comprendre les mécanismes de régulation de MYC dans les cellules pré-LSC, en utilisant le 2-MeOE2 comme outil pour des approches complémentaires pharmacologiques, génétiques et biochimiques. Ces stratégies nous ont amené à définir l'importance fonctionnelle d'affiner la régulation de MYC dans les cellules pré-LSC. Ainsi, la déstabilisation de MYC via une dégradation protéasomale affecte la viabilité des cellules pré-LSC, tandis qu'un MYC résistant au protéasome induit une signature génétique apoptotique et de sénescence. Ainsi, nos données expliquent l’absence de mutations MYC dans les leucémies LLA-T. Exploitant la capacité de 2-MeOE2 à réduire les niveaux de MYC, nous avons combiné ce médicament avec les principaux agents de chimiothérapie dans la LLA-T. Nos résultats démontrent que, tant dans un modèle murin de leucémie que dans des essais précliniques utilisant des échantillons primaires de leucémies humaines, 2-MeOE2 sensibilise les cellules pré-LSC et les cellules leucémiques à la chimiothérapie. Finalement, le crible de viabilité des pré-LSCs nous a permis aussi d’Identifier des inhibiteurs de la co-chaperone de type HSP90, Cdc37, qui réduisent les niveaux de DL1, le ligand de NOTCH1, exprimés par le stroma, et représentent ainsi de nouveaux régulateurs cellulaires non autonome de l'activité d'auto-renouvellement des cellules pré-LSCs. En effet, plusieurs inhibiteurs agissant sur CDC37/HSP90 in vitro et in vivo reproduisent le phénotype induit par la déplétion de Cdc37, y compris l'inhibition de l'activité des cellules pré-LSC. En conclusion, cette thèse met en lumière le potentiel de la dégradation de MYC en tant qu'approche prometteuse pour améliorer le traitement de la LLA-T en combinaison avec une chimiothérapie standard. De plus, une nouvelle stratégie ciblant le stroma thymique avec des inhibiteurs de Cdc37/Hsp90 a émergé, offrant une nouvelle approche pour inhiber les cellules pré-LSC. Ces découvertes font progresser notre compréhension de la LLA-T et ouvrent des perspectives pour des traitements plus efficaces et moins onéreux, dans le but ultime d'améliorer la qualité de vie des patients et les résultats du Traitement. / T acute lymphoblastic leukemia (T-ALL) is a common type of childhood cancer, representing approximately 15% of paediatric and 25% of adult Acute Lymphoblastic Leukemia cases. This disease is characterized by differentiation arrest in the T-lineage and excessive accumulation of non-functional lymphoblasts. During the last decades, survival rates have improved due to the intensification of chemotherapy regimens. However, we reached the limits of intensification, due to severe secondary effects that reduce the quality of life of patients and impose a burden on their families. Moreover, disease relapse is of poor outcomes. Previous work in the laboratory showed that the SCL and LMO1 oncogenes reprogram immature thymocytes at the DN3 stage into self-renewing pre-leukemic stem cells (pre-LSCs). Mechanistically, we showed that pre-LSCs depend on both the initiating oncogenes and the signals that these cells receive from the thymic microenvironment, triggering the NOTCH1/MYC pathway. Pre-LSCs give rise to leukemia, are chemoresistant and cause relapse. Previously, in a niche-based pre-LSCs inhibition screen we identified 2-MeOE2 as a compound that kills pre-LSCs and downregulated MYC. In this thesis, we aim to understand the mechanisms of regulation of MYC in pre-LSCs, using 2-MeOE2 as a tool compound for complementary pharmacological, genetic and biochemical approaches. These strategies led us to define the functional importance of fine-tuning MYC regulation in pre-LSCs. Indeed, destabilizing MYC via proteasomal degradation is lethal for pre-LSCs whereas a proteasome resistant MYC induces a senescent and apoptotic gene signature. Our results are consistent with the lack of MYC mutations in T-ALL, despite MYC essentiality. Then, we leveraged the capacity of 2-MeOE2 to decrease MYC levels and combined this drug with the main chemotherapeutic agents in T-ALL. We show that 2-MeOE2 sensitizes pre-LSCs to chemotherapy in our genetic model of leukemia and in pre-clinical models using primary human T-ALL samples xenografted in immune-deficient mice. Additionally, the niche-based viability screen identified a cluster of compounds that target the HSP90 co-chaperone CDC37, causing decreased expression of the NOTCH1 ligand, DL1 in the stroma, and therefore, decreased pre-LSC viability. Indeed, several inhibitors acting on CDC37/HSP90 both in vitro and in vivo reproduce the phenotype induced by depletion of Cdc37, including the inhibition of pre-LSC activity. Therefore, our work identified noncell autonomous inhibitors of pre-LSC self-renewal by their capacity to regulate DL1 in stroma cells. In conclusion, this thesis shed light on the potential of MYC degradation as a promising approach to enhance T-ALL treatment when combined with standard chemotherapy. Additionally, targeting the thymic stroma with CDC37/HSP90 inhibitors emerged as novel means to inhibit pre-LSCs. Collectively, these findings advance our understanding of T-ALL and open up avenues for more effective and less burdensome treatments, ultimately aiming to improve patient quality of life and treatment outcomes.

No description available.

Co-mentorship / Le cancer de l’ovaire est le cancer gynécologique le plus létal, et cinquième cause de mort attribuable au cancer chez les femmes nord-américaines. La létalité de cette maladie est due notamment à sa détection tardive, à sa forte hétérogénéité, et à sa résistance au traitement. L’amélioration du sort des patientes atteintes du cancer de l’ovaire passera donc par une meilleure caractérisation de la maladie, ce qui inclut la découverte de biomarqueurs et le développement de voies de traitement efficaces. Pour ce faire, des modèles d’étude représentatifs et bien caractérisés sont nécessaires, et la nature hétérogène du cancer de l’ovaire souligne le besoin d’un grand nombre de modèles diversifiés sous plusieurs aspects. Les modèles cellulaires sont une option peu dispendieuse et facile à entretenir, avec lesquels il est possible d’effectuer des expériences à haut débit. La fiabilité des modèles cellulaires se base sur l’abondance et la diversité, où un grand nombre de lignées cellulaires issues de contextes cliniques et moléculaires variés sont requises pour dresser un portrait représentatif de la maladie. Dans le cadre de cette thèse, dix nouveaux modèles de cancer épithélial de l’ovaire, incluant des lignées de deux sous-types rares, sont décrits et caractérisés rigoureusement. Ces modèles sont diversifiés en phénotypes et en génotypes, et sont démontrés comme représentatifs de la maladie de laquelle ils sont issus. Ces nouvelles lignées, s’ajoutant à plusieurs autres dérivées dans notre laboratoire, pourront servir à étudier le cancer de l’ovaire sous plusieurs aspects. Notamment, un nombre de ces lignées ont servi à l’étude de la résistance au traitement aux inhibiteurs de la polymérase de poly(ADP-ribose) (PARP), une voie thérapeutique émergente des dix dernières années. Malgré des études prometteuses, plusieurs patientes ne répondent pas au traitement initial, ou cessent de répondre après une durée de traitement, menant à une rechute. Ces deux phénomènes, dits résistance intrinsèque et résistance acquise respectivement, nuisent grandement à la survie des patientes. À l’aide de lignées cellulaires initialement sensibles, nous avons développés des modèles de résistance acquise aux inhibiteurs de PARP par exposition prolongée. Ces lignées dérivées, en combinaison avec des lignées intrinsèquement résistantes, ont mené à la découverte d’un traitement combiné synergique entre les inhibiteurs de PARP et une autre classe de molécule, les inhibiteurs de la nicotinamide phosphoribosyltransférase (NAMPT). Cette enzyme étant responsable de la synthèse du substrat de PARP, la combinaison de ces deux thérapies éradique de façon efficace les modèles résistants, autant à résistance acquise qu’intrinsèque, et ralentit la croissance tumorale en modèle murin. Les inhibiteurs de PARP étant déjà approuvés, et les inhibiteurs de NAMPT étant déjà en essais cliniques, la combinaison de ces voies thérapeutiques serait facilement envisageable en clinique, et l’universalité de son efficacité pourrait drastiquement améliorer le sort de patientes atteintes du cancer de l’ovaire, n’ayant aucun autre recours efficace. / Ovarian cancer is the most lethal gynecological cancer, and fifth leading cause of cancer-related deaths in North American women. The lethality of this disease is notably due to its late detection, its strong heterogeneity, and its resistance to treatment. Improving the fate of ovarian cancer patients will require a better characterization of the disease, which includes discovering biomarkers and effective treatment options. To this effect, representative and well characterized study models are required, and the heterogeneous nature of ovarian cancer underlines the need for a vast number of models with diverse characteristics. Cellular models are an inexpensive and easy to maintain option, with which high throughput experiments are possible. The reliability of cellular models depends on their abundance and diversity, where a large number of cell lines from various clinical and molecular contexts are required to accurately represent the disease. In the context of this thesis, ten new models of epithelial ovarian cancer, including cell lines of two rare subtypes, are described and rigorously characterized. These models are diverse in phenotype and genotype, and are shown to accurately represent the disease from which they are derived. These new cell lines, in addition to many others described in our laboratory, will serve to better study ovarian cancer and its many facets. Notably, a number of these cell lines were used to study resistance to poly(ADP-ribose) polymerase (PARP) inhibitor treatment, an emerging therapy of the past ten years. Despite encouraging studies, a number of patients do not respond initially, or cease to respond after a length of treatment, leading to relapse. These two phenomena, dubbed intrinsic and acquired resistance respectively, greatly hinder patient survival. Using initially sensitive cell lines, we developed models of acquired PARP inhibitor resistance by prolonged exposure. These derived cell lines, along with intrinsically resistant cell lines, served to discover a synergistic combination treatment between PARP inhibitors and another class of drugs, nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. NAMPT as an enzyme is mainly responsible for synthesizing PARP’s substrate, and the combination of these two therapies effectively inhibits models of both intrinsic and acquired resistance, and slows tumor growth in mice. PARP inhibitors are already routinely used in the clinic, and NAMPT inhibitors are currently undergoing clinical trials, making this combination of therapeutic options easily conceivable for clinical use in the future, and the universality of its efficacy could drastically improve the fate of ovarian cancer patients who are out of options.

One of the lesser explored research areas is the influence factors such as personal care products, cosmetics, and everyday routines have on skin microbiota. This study investigated the effects of propylene glycol, a widely used ingredient in cosmetics and self-care products, on a staphylococcal system ubiquitously distributed on human skin. The system, comprised of Staphylococcus hominis, Staphylococcus epidermidis, and Staphylococcus aureus, comes from a healthy donor, devoid of any skin afflictions. Because Staphylococcus aureus is part of this microbial community, it was of great interest to contribute to the understanding of the manner in which its growth is kept in check. To fulfill this task, a new methodology was developed. Purposely intended to be facile and easily scalable in laboratories around the world, it can be used for the study of microbial systems of variable dimensions alone or with the complementary use of other methods. Results indicate that the effects of propylene glycol are complex, as it acts on the skin, the resident microbiota, and at the microbiota-skin interface. Commensals such as Staphylococcus hominis and Staphylococcus epidermidis seem to have synergy of action with propylene glycol, increasing each other’s power in reducing the number of viable colonies of Staphylococcus aureus. Lastly, results seem to also reveal the incompletely understood role of Staphylococcus hominis on human skin. While Staphylococcus epidermidis and Staphylococcus aureus ravenously compete with each other, it is the contribution of Staphylococcus hominis that seems to limit the latter’s overgrowing. This speaks volumes of the extent, complexities, and unknowns of microbial interactions.

Tesis por compendio / [ES] El acceso a fuentes de energía moderna en las áreas rurales de la región andina es uno de los factores principales para disminuir la pobreza ya que su acceso proporcionaría beneficios ambientales, económicos y sociales. Pese a los esfuerzos de buscar fuentes alternativas para subsanar el déficit energético, aún existen millones de personas que sufren la falta de accesibilidad a fuentes de energía moderna, situación que se debe a los altos niveles de pobreza bajo los cuales se encuentran inmersos. Junto a este inconveniente se suma el enorme incremento de residuos agrícolas en las comunidades andinas. Residuos que provienen de las actividades agrícolas, y que podrían ser perjudiciales para el medio ambiente si no se toman medidas adecuadas. Lamentablemente, en muchos países en desarrollo donde se generan grandes cantidades de estos residuos, se sabe poco sobre sus posibles riesgos y beneficios si no se gestionan adecuadamente. Uno de los enfoques más interesantes para abordar esta problemática, es el desarrollo de la gestión sostenible de los residuos orgánicos agrícolas de la región, transformándolos en recursos para la generación de energía renovable (biogás) y fertilizantes orgánicos (digestato). Esta solución permitiría dar una valorización energética a los residuos de la agricultura de la zona, sobre la cual basan su economía, y a la vez contribuiría a una mayor gestión de los residuos evitando el incremento de la contaminación ambiental. Con la finalidad de contribuir al desarrollo energético y mejorar el paradigma de la gestión de residuos en el área andina de Guaranda (Ecuador), la presente Tesis Doctoral aborda la evaluación del potencial bioquímico de metano (BMP) de los residuos orgánicos agrícolas de la región. Se realiza una cuantificación sistemática de la producción de biogás mediante la transformación bioquímica de residuos orgánicos agrícolas, que comprenden: sustratos principales (residuos de estiércol de vicuña, llama y cuy, y residuos de matadero de ganado vacuno) y cosustratos (residuos de paja de amaranto, quinua y trigo). El objetivo general de esta investigación de doctorado se ha llevado a cabo en cuatro fases: (I) Caracterización de la materia prima mediante el análisis elemental y proximal a través de los cuáles se estimó el rendimiento teórico y la biodegradabilidad de los sustratos y cosustratos, (II) Rendimiento de la codigestión de residuos orgánicos agrícolas con mezclas de lodos de aguas residuales en biodigestores batch, (III) Análisis de los efectos sinérgicos y antagónicos durante la monodigestión y codigestión de las materias primas y (IV) Evaluación de la cinética microbiana de la digestión anaerobia mediante los modelos de Gompertz modificado, transferencia, ecuación logística, modelo del cono y Richards modificado. En la caracterización fisicoquímica se determinó que las relaciones SV/ST de los sustratos y cosustratos oscilaron entre 58 y 77% con una relación C/N entre 12 y 102, lo que indicó que estos residuos son materias primas adecuadas para la producción de metano. En todos los ensayos un aumento de la cantidad de inóculo mejoró la biodegradabilidad de los sustratos y por consiguiente la producción metano; así, en la monodigestión se tuvo incrementos de hasta 90% y en la codigestión incrementos del 71%. Todas las mezclas produjeron efectos sinérgicos, donde los mayores porcentajes de metano se dieron cuando las mezclas de residuos de amaranto, quinua y trigo fueron del 50 y 75% de sólidos volátiles. Independientemente de la SIR1:1 y la SIR 1:2 se mejoró la producción de metano de la codigestión al incrementar el porcentaje de cosustrato especialmente de residuos de amaranto y quinua. Los mejores resultados de todos los ensayos realizados se obtuvieron en los biodigestores compuestos por residuos de matadero y residuos de quinua, donde se obtuvieron producciones de metano entre 581 y 555 ml / [CA] L'accés a fonts d'energia moderna en les àrees rurals de la regió andina és un dels factors principals per a disminuir la pobresa ja que el seu accés proporcionaria beneficis ambientals, econòmics i socials. Malgrat els esforços de buscar fonts alternatives per a esmenar el dèficit energètic, encara existeixen milions de persones que pateixen la falta d'accessibilitat a fonts d'energia moderna, situació que es deu als alts nivells de pobresa sota els quals es troben immersos. Al costat d'aquest inconvenient se suma l'enorme increment de residus agrícoles en les comunitats andines. Residus que provenen de les activitats agrícoles, i que podrien ser perjudicials per al medi ambient si no es prenen mesures adequades. Lamentablement, en molts països en desenvolupament on es generen grans quantitats d'aquests residus, se sap poc sobre els seus possibles riscos i beneficis si no es gestionen adequadament. Un dels enfocaments més interessants per a abordar aquesta problemàtica, és el desenvolupament de la gestió sostenible dels residus orgànics agrícoles de la regió, transformant-los en recursos per a la generació d'energia renovable (biogàs) i fertilitzants orgànics (digestato). Aquesta solució permetria donar una valorització energètica als residus de l'agricultura de la zona, sobre la qual basen la seua economia, i alhora contribuiria a una major gestió dels residus evitant l'increment de la contaminació ambiental. Amb la finalitat de contribuir al desenvolupament energètic i millorar el paradigma de la gestió de residus en l'àrea andina de Guaranda (l'Equador), la present Tesi Doctoral aborda l'avaluació del potencial bioquímic de metà (BMP) dels residus orgànics agrícoles de la regió. Es realitza una quantificació sistemàtica de la producció de biogàs mitjançant la transformació bioquímica de residus orgànics agrícoles que comprenen: substrats principals (residus de fem de vicunya, flama i cuy, i residus d'escorxador de bestiar boví), *cosustratos (residus de palla d'amarant, quinua i blat). L'objectiu general d'aquesta investigació de doctorat s'ha dut a terme en quatre fases: (I) caracterització de la matèria primera mitjançant l'anàlisi elemental i proximal a través dels quals es va estimar el rendiment teòric i la biodegradabilitat dels substrats i cosustratos, (II) Rendiment de la codigestión de residus orgànics agrícoles amb mescles de llots d'aigües residuals en biodigestores batch, (III) Anàlisis dels efectes sinèrgics i antagònics durant la monodigestión i codigestión de les matèries primeres i (IV) Avaluació de la cinètica microbiana de la digestió anaeròbia mitjançant els models de Gompertz modificat, transferència, equació logística, model del con i Richards modificat. En la caracterització fisicoquímica es va determinar que les relacions SV/ST dels substrats i cosustratos van oscil·lar entre 58 i 77% amb una relació C/N entre 12 i 102, la qual cosa va indicar que aquests residus són matèries primeres adequades per a la producció de metà. En tots els assajos un augment de la quantitat d'inòcul va millorar la biodegradabilitat dels substrats i per consegüent la producció metà; així, en la monodigestión es va tindre increments de fins a 90% i en la codigestión increments del 71%. Totes les mescles van produir efectes sinèrgics, on els majors percentatges de metà es van donar quan les mescles de residus d'amarant, quinua i blat van ser del 50 i 75% de sòlids volàtils. Independentment de la SIR1:1 i la SIR 1:2 es va millorar la producció de metà de la codigestión en incrementar el percentatge de cosustrato especialment de residus d'amarant i quinua. Els millors resultats de tots els assajos realitzats es van obtindre en els biodigestores compostos per residus d'escorxador i residus de quinua, on es van obtindre produccions de metà entre 581 i 555 ml/g VS. / [EN] Access to modern energy sources in rural areas of the Andean region is one of the main factors to reduce poverty, since its access would provide environmental, economic and social benefits. Despite efforts to find alternative sources to correct the energy deficit, there are still millions of people who suffer from the lack of accessibility to modern energy sources, a situation that is due to the high levels of poverty under which they are immersed. Along with this inconvenience is added the enormous increase in agricultural residues in the Andean communities. Waste that comes from agricultural activities, and that could be harmful to the environment if adequate measures are not taken. Unfortunately, in many developing countries where large amounts of these wastes are generated, little is known about their potential risks and benefits if not managed properly. One of the most interesting approaches to address this problem is the development of sustainable management of agricultural organic waste in the region, transforming it into resources for the generation of renewable energy (biogas) and organic fertilizers (digestate). This solution would allow to give an energetic recovery to the agricultural residues of the area, on which they base their economy, and at the same time would contribute to a better management of the residues avoiding the increase of environmental pollution. To contribute to energy development and improve the paradigm of waste management in the Andean area of Guaranda (Ecuador), this Doctoral Thesis addresses the evaluation of the biochemical potential of methane (BPM) of agricultural organic waste in the region. A systematic quantification of biogas production is carried out through the biochemical transformation of agricultural organic waste that includes main substrates (vicuña, llama and guinea pig manure residues, and cattle slaughterhouse residues) and co-substrates (amaranth straw residues), quinoa and wheat). The general objective of this doctoral research has been carried out in four phases: (I) characterization of the raw material through elemental and proximal analysis through which the theoretical performance and biodegradability of substrates and co-substrates were estimated, (II) Performance of the co-digestion of agricultural organic waste with mixtures of sewage sludge in batch biodigesters, (III) Analysis of synergistic and antagonistic effects during monodigestion and co-digestion of raw materials and (IV) Evaluation of microbial kinetics of anaerobic digestion using modified Gompertz models, transfer, logistic equation, cone model and modified Richards. In the physicochemical characterization it was determined that the VS/TS ratios of the substrates and co-substrates ranged between 58 and 77% with a C/N ratio between 12 and 102, which indicated that these wastes are suitable raw materials to produce methane. In all the tests an increase in the amount of inoculum improved the biodegradability of the substrates and consequently the methane production; thus, in monodigestion there were increases of up to 90% and in co-digestion increases of 71%. All the mixtures produced synergistic effects, where the highest percentages of methane occurred when the mixtures of amaranth, quinoa and wheat residues were 50 and 75% volatile solids. Regardless of SIR1:1 and SIR 1:2, the production of methane from co-digestion was improved by increasing the percentage of co-substrate, especially amaranth and quinoa residues. The best results of all the tests carried out were obtained in the biodigesters composed of slaughterhouse waste and quinoa waste, where methane productions between 581 and 555 ml/g VS were obtained. Regarding the kinetic modelling of the anaerobic digestion process, it was found that all the models fit the experimental values quite well with the predicted ones. In the monodigestion, in all the logistic models, the calculated asymptotes were adjusted very precisely for the specific yield (Me / This work has been carried out within the framework of the project “Analysis of the implementation of biomass exploitation chains in rural communities in the province of Bolívar (Ecuador)” of the ADSIEO-COOPERATION program of the Universitat Politècnica de València (UPV). The Ecuadorian Energy Exploitation Research Network of Biomass (ECUMASA) and the IBEROMASA Network (719RT0586) of the IberoAmerican Program of Science and Technology for Development (CYTED) have participated in this program / Meneses Quelal, WO. (2021). Optimization of Anaerobic Codigestion Processes of Lignocellulosic Materials of Difficult Degradation with Residues from Andean Livestock [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/171722 / Compendio

This dissertation addresses five fundamental resource allocation problems on networks, all of which have applications to support Homeland Security or industry challenges. In the first application, we model and solve the strategic problem of minimizing the expected loss inflicted by a hostile terrorist organization. An appropriate allocation of certain capability-related, intent-related, vulnerability-related, and consequence-related resources is used to reduce the probabilities of success in the respective attack-related actions, and to ameliorate losses in case of a successful attack. Given the disparate nature of prioritizing capital and material investments by federal, state, local, and private agencies to combat terrorism, our model and accompanying solution procedure represent an innovative, comprehensive, and quantitative approach to coordinate resource allocations from various agencies across the breadth of domains that deal with preventing attacks and mitigating their consequences. Adopting a nested event tree optimization framework, we present a novel formulation for the problem as a specially structured nonconvex factorable program, and develop two branch-and-bound schemes based respectively on utilizing a convex nonlinear relaxation and a linear outer-approximation, both of which are proven to converge to a global optimal solution. We also investigate a fundamental special-case variant for each of these schemes, and design an alternative direct mixed-integer programming model representation for this scenario. Several range reduction, partitioning, and branching strategies are proposed, and extensive computational results are presented to study the efficacy of different compositions of these algorithmic ingredients, including comparisons with the commercial software BARON. The developed set of algorithmic implementation strategies and enhancements are shown to outperform BARON over a set of simulated test instances, where the best proposed methodology produces an average optimality gap of 0.35% (compared to 4.29% for BARON) and reduces the required computational effort by a factor of 33. A sensitivity analysis is also conducted to explore the effect of certain key model parameters, whereupon we demonstrate that the prescribed algorithm can attain significantly tighter optimality gaps with only a near-linear corresponding increase in computational effort. In addition to enabling effective comprehensive resource allocations, this research permits coordinating agencies to conduct quantitative what-if studies on the impact of alternative resourcing priorities. The second application is motivated by the author's experience with the U.S. Army during a tour in Iraq, during which combined operations involving U.S. Army, Iraqi Army, and Iraqi Police forces sought to interdict the transport of selected materials used for the manufacture of specialized types of Improvised Explosive Devices, as well as to interdict the distribution of assembled devices to operatives in the field. In this application, we model and solve the problem of minimizing the maximum flow through a network from a given source node to a terminus node, integrating different forms of superadditive synergy with respect to the effect of resources applied to the arcs in the network. Herein, the superadditive synergy reflects the additional effectiveness of forces conducting combined operations, vis-à-vis unilateral efforts. We examine linear, concave, and general nonconcave superadditive synergistic relationships between resources, and accordingly develop and test effective solution procedures for the underlying nonlinear programs. For the linear case, we formulate an alternative model representation via Fourier-Motzkin elimination that reduces average computational effort by over 40% on a set of randomly generated test instances. This test is followed by extensive analyses of instance parameters to determine their effect on the levels of synergy attained using different specified metrics. For the case of concave synergy relationships, which yields a convex program, we design an inner-linearization procedure that attains solutions on average within 3% of optimality with a reduction in computational effort by a factor of 18 in comparison with the commercial codes SBB and BARON for small- and medium-sized problems; and outperforms these softwares on large-sized problems, where both solvers failed to attain an optimal solution (and often failed to detect a feasible solution) within 1800 CPU seconds. Examining a general nonlinear synergy relationship, we develop solution methods based on outer-linearizations, inner-linearizations, and mixed-integer approximations, and compare these against the commercial software BARON. Considering increased granularities for the outer-linearization and mixed-integer approximations, as well as different implementation variants for both these approaches, we conduct extensive computational experiments to reveal that, whereas both these techniques perform comparably with respect to BARON on small-sized problems, they significantly improve upon the performance for medium- and large-sized problems. Our superlative procedure reduces the computational effort by a factor of 461 for the subset of test problems for which the commercial global optimization software BARON could identify a feasible solution, while also achieving solutions of objective value 0.20% better than BARON. The third application is likewise motivated by the author's military experience in Iraq, both from several instances involving coalition forces attempting to interdict the transport of a kidnapping victim by a sectarian militia as well as, from the opposite perspective, instances involving coalition forces transporting detainees between interment facilities. For this application, we examine the network interdiction problem of minimizing the maximum probability of evasion by an entity traversing a network from a given source to a designated terminus, while incorporating novel forms of superadditive synergy between resources applied to arcs in the network. Our formulations examine either linear or concave (nonlinear) synergy relationships. Conformant with military strategies that frequently involve a combination of overt and covert operations to achieve an operational objective, we also propose an alternative model for sequential overt and covert deployment of subsets of interdiction resources, and conduct theoretical as well as empirical comparative analyses between models for purely overt (with or without synergy) and composite overt-covert strategies to provide insights into absolute and relative threshold criteria for recommended resource utilization. In contrast to existing static models, in a fourth application, we present a novel dynamic network interdiction model that improves realism by accounting for interactions between an interdictor deploying resources on arcs in a digraph and an evader traversing the network from a designated source to a known terminus, wherein the agents may modify strategies in selected subsequent periods according to respective decision and implementation cycles. We further enhance the realism of our model by considering a multi-component objective function, wherein the interdictor seeks to minimize the maximum value of a regret function that consists of the evader's net flow from the source to the terminus; the interdictor's procurement, deployment, and redeployment costs; and penalties incurred by the evader for misperceptions as to the interdicted state of the network. For the resulting minimax model, we use duality to develop a reformulation that facilitates a direct solution procedure using the commercial software BARON, and examine certain related stability and convergence issues. We demonstrate cases for convergence to a stable equilibrium of strategies for problem structures having a unique solution to minimize the maximum evader flow, as well as convergence to a region of bounded oscillation for structures yielding alternative interdictor strategies that minimize the maximum evader flow. We also provide insights into the computational performance of BARON for these two problem structures, yielding useful guidelines for other research involving similar non-convex optimization problems. For the fifth application, we examine the problem of apportioning railcars to car manufacturers and railroads participating in a pooling agreement for shipping automobiles, given a dynamically determined total fleet size. This study is motivated by the existence of such a consortium of automobile manufacturers and railroads, for which the collaborative fleet sizing and efforts to equitably allocate railcars amongst the participants are currently orchestrated by the \textit{TTX Company} in Chicago, Illinois. In our study, we first demonstrate potential inequities in the industry standard resulting either from failing to address disconnected transportation network components separately, or from utilizing the current manufacturer allocation technique that is based on average nodal empty transit time estimates. We next propose and illustrate four alternative schemes to apportion railcars to manufacturers, respectively based on total transit time that accounts for queuing; two marginal cost-induced methods; and a Shapley value approach. We also provide a game-theoretic insight into the existing procedure for apportioning railcars to railroads, and develop an alternative railroad allocation scheme based on capital plus operating costs. Extensive computational results are presented for the ten combinations of current and proposed allocation techniques for automobile manufacturers and railroads, using realistic instances derived from representative data of the current business environment. We conclude with recommendations for adopting an appropriate apportionment methodology for implementation by the industry. / Ph. D.