<p>Kombuha je tradicionalni napitak koji se dobija fermentacijom zaslađenog crnog<br />ili zelenog čaja, fiziolo&scaron;kom aktivno&scaron;ću čajne gljive, koja predstavlja simbiozu<br />autohthonih vrsta kvasaca i bakterija sirćetnog vrenja. Cilj rada je bio da se ispita<br />biolo&scaron;ka aktivnost konzumnih kombuha napitaka (titrabilne kiselosti 3,5-4 g/L) od<br />crnog čaja (<em>Camellia sinensis</em> L), čaja ehinacee (<em>Echinacea purpurea</em> L.) i<br />rtanjskog čaja (<em>Satureja montana</em> L.). Za ispitivanje antimikrobne aktivnosti<br />kombuha napitaka upotrebljeni su sledeći sojevi bakterija, kvasaca i plesni:<br /><em>Pseudomonas aeruginosa</em>, <em>Staphylococcus aureus</em>, <em>Bacillus sp.</em>, <em>Salmonella<br />enteritidis, Proteus mirabilis, Escherichia coli, Sarcina lutea, Saccharomyces<br />cerevisiae, Candida pseudotropicalis, Rhodotorula sp., Penicillium<br />aurantiogriseum, Aspergillus niger i Aspergillus flavus</em>. Antioksidativna aktivnost<br />kombuha napitaka ispitana je na DPPH i OH radikale ESR spektralnom metodom.<br />Antiproliferativna aktivnost čajeva i kombuha napitaka od crnog i rtanjskog čaja<br />ispitana na tri ćelijske linije humanih karcinoma: HeLa (epitelni karcinom<br />cerviksa), MCF-7 (adenokarcinom dojke) i HT-29 (adenokarcinom debelog<br />creva). Pored istraživanja biolo&scaron;ke aktivnosti kombuha napitaka, cilj rada je bio da<br />se ispitaju i neki od osnovnih parametara kombuha fermentacije &ndash; optimalna<br />količina izvora ugljenika i azota u medijumu za kultivaciju, geometrijske<br />karakteristike fermentora, inokulacija starter kulturama. Definisanje kritičnih<br />parametara kombuha fermentacije je bio osnov za izvođenje matematičkog<br />modela za scale-up fermentativnog procesa.</p> / <p>Kombucha is a traditional beverage obtained by fermenting sweetned black or<br />green tea with tea fungus, which represents a symbiotic combination of acetic acid<br />bacteria and autochthonous yeast species. In this study, the antimicrobial,<br />antioxidative and antiproliferative activity of kombucha beverages (titratable<br />acidity 3,5-4 g/L) obtain from black tea (<em>Camellia sinensis</em> L), echinacea tea<br />(<em>Echinacea purpurea</em> L.) and rtanj tea (<em>Satureja montana</em> L.) were tested.<br /><em>Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus sp., Salmonella<br />enteritidis, Proteus mirabilis, Escherichia coli, Sarcina lutea, Saccharomyces<br />cerevisiae, Candida pseudotropicalis, Rhodotorula sp., Penicillium<br />aurantiogriseum, Aspergillus niger i Aspergillus flavus</em> were used as test<br />microorganisms for examination of antimicrobial activity. The antioxidant activity<br />of differently prepared kombucha beverages was examined agains DPPH and OH<br />radicals by ESR-spectrometry. Antiproliferative activity of black tea kombucha<br />and Satureja montana kokmbucka was measured by sulforhodamine B<br />colorimetric assay on HeLa (cervix epitheloid carcinoma), HT-29 (colon<br />adenocarcinoma), and MCF-7 (breast adenocarcinoma) cells line. Also, same<br />parametars of kombucha fermentation &ndash; optimal quantity of source of carbon and<br />nitrogen in cultivation medium, geometric characteristics of reactors and<br />inoculation by starter culture &ndash; were tested. Definition of critical parameters of<br />kombucha fermentation is important for derivation of mathematical model for<br />scaling-up fermentation process.</p>

La simulation devient un outil incontournable pour concevoir ou optimiser les procédés en biotechnologies. Elle est particulièrement pertinente pour permettre le changement d'échelle de l'échelle laboratoire à la mise en œuvre de cultures biologiques industrielles. Cette thèse se concentre sur le développement d'une structure de modèle pour les fermenteurs, qui ne néglige ni les problématiques de mélange, ni la complexité biologique, tout en permettant des simulations rapides. Pour intégrer l'ensemble des phénomènes couplés et dynamiques interagissant dans les bioréacteurs, l'approche proposée couple (i) un modèle métabolique dynamique pour décrire le comportement des cellules, (ii) un modèle de bilan de population pour suivre la diversité biologique et (iii) un modèle de compartiments pour décrire l'hydrodynamique du fermenteur. Une structure de modèle métabolique, générique et numériquement peu couteuse a été appliquée à E. coli et S. cerevisiae et été confrontée avec succès à de nombreuses données expérimentales. Parmi plusieurs méthodes numériques permettant de traiter les équations de bilan de population, la méthode EQMOM a été sélectionnée pour sa stabilité et sa précision et son coût a été réduit d'un facteur 10. L'hydrodynamique gaz-liquide d'un fermenteur industriel a été obtenue par simulations CFD et des outils ont été développés pour en extraire des modèles de compartiments. Le couplage de ces différents aspects a finalement été illustré par la simulation d'une culture industrielle. Ce travail ouvre la voie à la création d'outil de simulation rapide, ce qui permettra des études d'ingénierie de design et d'optimisation de procédés industriels. / Simulations are becoming an essential tool to design and improve processes in the field of biotechnologies. They are especially relevant to facilitate the scale-up of biological cultures from laboratory to industrial scales which is a key difficulty as of now. This thesis focuses on developping a model structure for fermenters, which does not neglect either mixing issues known to occur in industrial bioreactor, nor biological complexity inherent to micro-organisms, while enabling fast and low-cost simulations. To account for all coupled and dynamic phenomena that occur in bioreactors, the developed approach couples (i) a dynamic metabolic model to describe cells behaviour, (ii) a population balance model tracking biological cell-to-cell diversity and (iii) a compartment model to account for fermenter hydrodynamics. A structure for low-cost dynamic metabolic model has been developed, applied to E. coli and S. cerevisiae and successfully challenged against experimental data. Among multiple numerical methods tackling population balance equations, the EQMOM method has been selected for its stability and precision, and its algorithm has been improved by reducing its cost by a factor 10. The gas-liquid hydrodynamics of an industrial fermenter has been obtained through CFD simulations, and tools have been developed to extract compartment model from these simulation results. Finally, the coupling between all these modeling blocks has been demonstrated by simulating an actual industrial culture. This work paves the way to the emergence of fast bioreactor simulation tools, which will then enable new enginnering studies for designing and optimising industrial bio-processes.

Parmi les méthodes alternatives respectueuses de l'environnement pour la lutte contre les ravageurs et la protection des cultures agricoles, les bioinsecticides à base de Bacillus thuringiensis sont les plus largement utilisés. L’activité insecticide de B.thuringiensis réside dans la production d’inclusions cristallines protéiques appelées δ-endotoxines qui sont formées au cours de la sporulation. En préalable à ces travaux, de nouvelles souches de B.thuringiensis ont été isolées du sol libanais et ont montré un potentiel insecticide élevé, supérieur à des souches classiquement utilisées. Dans le cadre du développement d'une production industrielle, au Liban, de biopesticides à base de ces souches de B.thuringiensis, ce travail a visé à optimiser la production des δ-endotoxines afin d'augmenter les rendements et de réduire les coûts de production. A l'échelle industrielle, le milieu de culture des bactéries représente une part importante du coût de production. Ainsi, l'effet, sur la concentration des δ-endotoxines, de substitution des sources synthétiques coûteuses d'azote, de carbone et de minéraux, par un sous-produit de la minoterie de blé (le son de blé) a été étudié. L’efficacité de ce sous-produit agro-industriel comme source complète de nutriments, disponible localement à faible prix, a été prouvée pour des fermentations submergées de deux souches différentes toxiques contre des diptères ou des lépidoptères. La comparaison du milieu son de blé à d’autres milieux (synthétiques ou non), classiquement utilisés en bibliographie, a montré que ce milieu présente de nombreux avantages en termes de productivité, de rendement relatif des δ-endotoxines et de coût. Parallèlement à ce travail, une méthode simple et rapide de purification des cristaux a été développée de façon à obtenir des cristaux protéiques purs à 99 % nécessaires comme standards pour le dosage des cristaux dans le milieu de fermentation. Un autre objectif du travail a été d’analyser l'effet de l'aération sur la cinétique de croissance et de sporulation d'une nouvelle souche de B.thuringiensis var kurstaki. Les différentes conditions d’aération testées en fermenteurs de 2 L, caractérisées par le coefficient volumétrique de transfert de dioxygène (KLa), ont permis de montrer l’importance de ce paramètre et de l’optimiser pour obtenir la meilleure productivité en biopesticides. Le meilleur rendement en protéines de toxines a été obtenu dans un milieu son de blé 6 % (masse/volume) dans des conditions d’aération correspondant à un KLa de 65,5 h-1 alors que la meilleure productivité des protéines de toxines a été atteinte dans le milieu 9 % pour un KLa de 102 h-1. Sur la base de cette étude, le dimensionnement de la production de B.thuringiensis à l’échelle 1000 L a été réalisé. L’unité de production a été construite et les premiers essais réalisés ont permis de produire de façon satisfaisante des lots de biopesticides. L’ajustement des protocoles industriels reste à faire. / Among the safe and environment friendly methods for the fight against pests and agricultural crops protection, Bacillus thuringiensis based biopesticides are the most widely used. The insecticidal activity of B. thuringiensis resides in the production of protein crystal inclusions called δ-endotoxins, which are formed during sporulation. Preliminary to this work, new B. thuringiensis strains were isolated from Lebanese soil and showed higher insecticidal potential than the conventionally used strains. As part of the development of an industrial production, in Lebanon, of biopesticides based on these strains of B.thuringiensis, this work aimed to optimize the production of δ-endotoxins to increase yields and reduce the cost of mass production. At industrial scale, the bacteria culture medium represents a significant part of the production cost. Thus, the effect on the concentration of the δ-endotoxins, of substituting expensive synthetic sources of nitrogen, carbon, and minerals, with a byproduct of wheat mill (wheat bran) was studied. The effectiveness of this agro-industrial by-product available locally at low prices, as complete source of nutrients, in submerged fermentations of two different strains of B.thuringiensis toxic against Lepidoptera and Diptera, has been proven. The comparison of the wheat bran medium to other mediums (synthetic or not), conventionally used in the bibliography, has shown that this medium this medium has many advantages in terms of productivity, relative yield of δ-endotoxins and cost. In parallel to this work, a simple and quick method of crystal purification was developed to obtain pure protein crystals to 99 % required as standards for the determination of crystals concentration in the fermentation medium. Another objective of the study was to analyze the effect of aeration on growth and sporulation kinetics of a new strain of B.thuringiensis var kurstaki. The different aeration conditions tested in fermenters of 2 L, characterized by the volumetric oxygen transfer coefficient (KLa), permitted to show the importance of this parameter and to optimize it to get the best biopesticides productivity. The best yield of toxin proteins relative to the wheat bran ratio in the culture medium was obtained in the 6 % (weight/volume) medium in aeration conditions corresponding to a KLa of 65.5 h-1, while the highest productivity of toxin proteins has been reached in the 9 % medium for KLa of 102 h-1. On this study basis, the scale up of B. thuringiensis production was performed in a bioreactor of 1000 L. The production unit was built and the first tests carried out have produced satisfactory batches of biopesticides. Industrial protocols are still to be adjusted.

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No. of bitstreams: 1 TeseLJC.pdf: 3758058 bytes, checksum: 4551fb3e08abee5796d1f863288fd5ae (MD5) Previous issue date: 2016-02-04 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / In this work it was evaluated, firstly, the performance of four impellers configurations in the enzymatic hydrolysis of sugarcane bagasse. The configurations evaluated were: (1): Rushton turbine - Rushton turbine; (2): Elephant ear down-pumping and Rushton turbine; (3): Rushton turbine and Elephant ear up-pumping; (4): Elephant ear downpumping and Elephant ear up-pumping. The choice of the best impeller configuration was based in mixing efficiency, characterized by the mixing time. The configurations were also evaluated considering the conversion of cellulose to glucose, power consumption as well as the rheological behavior during hydrolysis. The hydrolysis experiments were carried out in batch stirred tank reactor (3 L) using 10% w/v of solids (pH 4.8; 50°C; 470 rpm), 10 FPU· g-1 biomassa for 96 h. The configuration (4) showed the lowest mixing time and energy efficiency values (ratio of conversion of cellulose to glucose and total energy consumption) of 78.9%·MJ-1. Further, to get a high concentration of glucose associated with low power consumption, it was investigated two operating modes: batch and fed-batch. The strategies evaluated were: E1 [20%]; E2 [10(E)+5+5%]; E3 [5(E)+5+5+5%]; E4 [5(E)+5+5+5%], and E5 5(E)+5(E)+5(E)+5(E)%]. The best energy efficiency was obtained for the E5 strategy in which substrate and enzyme were added simultaneously (0.35 kgglicose·kWh-1). This value was 52% higher than that obtained in the single batch operation (E1). In continuation of the work were carried out enzymatic hydrolysis of exploded and hydrothermal bagasse and cane straw submitted to hydrothermal pretreatment. The experiments were carried out under the conditions: solids loading of 10 (w/v), pH 4.8; 50 ° C; 470 rpm and 10 FPU·g-1 biomass for 96 h. The efficiency obtained in the enzymatic hydrolysis of steam explosion sugarcane bagasse proved to be 41 and 46% higher than the hydrolysis of hydrothermally pretreated sugarcane straw and bagasse, respectively. Finally, a scale-up protocol with a scale factor equal to 1000 was proposed. It was analyzed the maintenance of two parameters on larger scale: the constancy of the mixing time (tm) and the constancy of the power consumption per unit volume (P/V). In turn, maintenance P/V parameter constant, the mixing time and the new scale power consumption (3000L) were approximately 4 and 1000 times higher, respectively, than those values obtained in the smaller scale (3L). / Neste trabalho avaliou-se, primeiramente, o desempenho de quatro configurações de impelidores na hidrólise enzimática do bagaço explodido de cana-de-açúcar. As configurações avaliadas foram: (1): turbina Rushton – turbina Rushton; (2): Elephant ear down-pumping e turbina Rushton; (3): turbina Rushton e Elephant ear up-pumping; (4): Elephant ear down-pumping e Elephant ear up-pumping. A escolha da melhor configuração de impelidores foi baseada na eficiência de mistura, caracterizada pelo tempo de mistura. As configurações também foram avaliadas considerando a conversão de celulose em glicose, o consumo de potência, bem como o comportamento reológico durante a hidrólise. Os experimentos de hidrólise em batelada foram realizados em reator tipo tanque agitado (3 L) utilizando 10% m/v de sólidos (pH 4,8; 50°C; 470 rpm), 10 FPU·g-1 biomassa por 96 h. A configuração (4) apresentou os menores valores de tempo de mistura e uma eficiência energética de 78,9 %·MJ-1. Com o intuito de obter-se alta concentração de glicose associada a um baixo consumo de potência, investigou-se dois modos de operação: batelada e batelada alimentada. As estratégias avaliadas foram: E1 [20%]; E2 [10(E)+5+5%]; E3 [5(E)+5+5+5%]; E4 [5(E)+5+5+5%] e E5 [5(E)+5(E)+5(E)+5(E)%]. Os melhores resultados foi obtido na estratégia E5, obtendo uma eficiência energética de 0,35 kgglicose∙kWh-1. Este valor foi 52% maior do que o obtido na operação em batelada simples (E1). Na continuação do trabalho, foi realizada a hidrólise enzimática do bagaço explodido e hidrotérmico e a palha de cana submetida ao pré-tratamento hidrotérmico. Os experimentos foram realizados em um reator de 3 L nas seguintes condições: carga de sólidos de 10% m/v (pH 4,8; 50°C, 470rpm ) e 10 FPU·g-1 biomassa por 96 h. A eficiência energética obtida na hidrólise do bagaço explodido mostrou-se 41 e 46 % superior aos pré-tratados de bagaço e palha hidrotermicamente, respectivamente. Finalmente, foi proposto um protocolo de aumento de escala com um fator de escala igual a 1000. Analisou a manutenção de dois parâmetros na escala maior: tempo de mistura (tm) e do consumo de potência por unidade de volume (P/V). Com a manutenção do parâmetro P/V constante, o tempo de mistura e consumo de potência da nova escala (3000L) foram aproximadamente 4 e 1000 vezes maiores, respectivamente, do que o obtido na escala menor escala (3L). / FAPESP: 2011/23807-1

Un système consistant d'une simulation de mécanique des fluides numérique (MFN) couplée à un modèle de bilan de population (PBM) est développé afin d'étudier l'effet des paramètres variés sur la performance d'un procédé de polymérisation en émulsion qui conduit à la peoduction des particules de polymère dans un milieu aqueux continu.Comme une grande gamme des produits polymériques, des latexes sont les « produits par processus » (products-by-process), et leurs propriétés sont déterminés pendant la polymérisation. LA distribution de la taille des particules (PSD) est une des plus importants paramètres qui influence la qualité finale de latex. La modélisation d'évolution du PSD est généralement réalisée par l'addition un ensemble des PBEs au modèle cinétique. Le PBE fournit un moyen d'étudier la contribution des différents phénomènes dans l'évolution du PSD, comme la nucléation, la croissance des particules par la polymérisation, et la coagulation des particules à cause du mouvement brownien ou le mouvement du fluide (la coagulation Perikinetic et Orthokinetic, respectivement).Afin d'évaluer l'impact du mélange non homogène et les paramètres physiques du système sur l'évolution du PSD du latex, la simulation transitoire d'écoulement à été réalisé avec l'aide d'un progiciel commercial de MFN (Fluent® 15.0) pour munir dans chaque pas du temps, les concentrations locales des espèces ioniques (pour déterminer le taux de la coagulation Perikinetic modelé par le modèle de DLVO) ainsi que certains paramètres hydrodynamiques comme le taux de dissipation de la turbulence et le taux de cisaillement (afin de déterminer le taux de la coagulation Orthokinetic). Cette information est appliquée simultanément par le module complémentaire de PBM dans Fluent pour calculer le PSD pour le prochain pas du temps ; ainsi, un couplage complet entre le MFN et le PBM est assuré / A framework, consisting of a computational fluid dynamics (CFD) simulation model coupled to a population balance model (PBM) is developed to study the effect of various parameters on the performance of an emulsion polymerization process which leads to the production of a fine dispersion of polymer particles in a continuous aqueous medium.Like most polymer products, latexes are “products-by-process”, whose main properties are determined during polymerization. One of the main parameters influencing the final quality of the latexes is the particle size distribution (PSD). Modeling the evolution of PSD is usually accomplished through the addition of a set of PBEs to the kinetic model. PBE provides a means of considering the contribution of different phenomena in the PSD evolution, being nucleation, growth of polymer particles by polymerization, and coagulation of particles due to brownian or fluid motion (Perikinetic and Orthokinetic coagulation, respectively).To assess the impact of nonhomogeneous mixing and physical parameters of the system on the evolution of the latex PSD, the transient simulation of flow was performed with the aid of a commercial CFD Package (Fluent® 15.0) to provide in each time step, the local concentrations of ionic species (to determine the rate of perikinetic coagulation modeled by DLVO model) and certain hydrodynamic parameters such as turbulence dissipation rate and shear rate (to determine the rate of orthokinetic coagulation). This information is applied simultaneously by the PBE add-on module of Fluent to calculate the PSD for the next time step; thus a complete coupling between CFD and PBM is assured

Bakgrund: Utvecklingen inom informationsteknik (IT) har skapat många möjligheter för samhället, vilket har lett till framgångsrika IT-bolag som erbjuder digitala produkter och tjänster. IT-sektorn har en hög tillväxttakt vilket attraherar investeringar och skapar jobbmöjligheter. Trots detta är risken att misslyckas inom IT-sektorn hög, och många nystartade IT-bolag överlever inte de första åren på grund av den dynamiska och komplexa miljön de verkar i. Inom IT-sektorn finns det tusentals nystartade bolag, och begreppen 'start-up' och 'scale-up' används för att beskriva dessa. Ett start-ups är ett ungt bolag i ett tidigt utvecklingsstadie, medan scale-up är ett bolag som har nått nästa tillväxtfas och strävar efter att öka sin omsättning och etablera sin marknadsposition. Ledarskapet i dessa miljöer har visat sig spela en avgörande roll för framgång i både start-ups och scale-ups, då miljön är ytterst osäker och snabbföränderlig. Däremot är det fortfarande oklart vilken typ av ledare, och mer specifikt vilka ledarskapskompetenser, som bidrar till ett framgångsrikt start-up respektive scale-up. Tidigare forskning pekar även på att ledarskap är högst kontextrelaterat, och att de ledarskapskompetenser som är viktiga i en kontext inte behöver vara densamma i en annan. Ledarskapskompetenser bör därmed identifieras och utvecklas för att säkerställa att ledaren innehar rätt färdigheter, kunskap, beteende och egenskaper som krävs för att nå strategiska mål och prestationsförväntningar i den specifika miljön.  Syfte: Studiens syfte är att undersöka och få en ökad förståelse för vilka ledarskapskompetenser som associeras med framgång vid IT-bolags tillväxtfaser, start-up respektive scale-up. Metod: Studien har ett kvalitativt tillvägagångssätt och utgår från en hermeneutisk ansats eftersom den syftar till att förstå och tolka företeelser inom det valda forskningsområdet. Vidare används en abduktiv ansats, vilket medför att forskare i denna studie växlar mellan empirisk och teoretisk reflektion. För insamling av empiri har semistrukturerade intervjuer nyttjas med noga utvalda respondenter. Insamlad empiri har sedan analyserats genom en tematisk analys. Slutsats: Studiens resultat visar att det inte är någon markant skillnad mellan de ledarskapskompetenser som associeras med framgång i respektive tillväxtfas. Det tillkommer däremot några ledarskapskompetenser när bolaget skalar upp som relaterar till en ökad arbetsstyrka, vilket kräver mer fokus på struktur och omsorg av medarbetare. Vidare så pekar studiens resultat på att de ledarskapskompetenser som krävs i båda faserna kan behövas nyttjas annorlunda och till olika ändamål. De ledarskapskompetenser som anses krävas i båda tillväxtfaserna är visionär, uthållig, riskbenägen, strategisk, kundfokuserad, kunskapsorienterad, rekryteringsförmåga, omhändertagande, anpassningsbar och flexibel. De ledarskapskompetenser som tillkommer i scale-up är strukturförmåga, förtroende, kommunikativ och kunskapsöverförande.

Background: “Scale-ups”, characterised by their high growth and significant contribution to economic development, receive increasing attention in today's economies. They are often young and innovative SMEs that grow rapidly across international borders. “Scale-ups” achieve growth and improved performance through an accelerated organisational development process, which is based on their knowledge resources. Purpose: The purpose of this study is to explore and theorise what constitutes a scaling capability. Specifically, we will study knowledge acquisition and integration in SMEs that scale across international markets. Method: This study has an abductive research approach that considers the current theories on scaling and the knowledge-based view on strategic management and international business. To this end, we completed a multiple-case study of 4 innovative and internationalising scale-ups to accomplish our purpose. Conclusion: The study contributes with a view of scaling as a “scaling capability” that captures how innovative scale-ups manage the internal organisation of experiential knowledge. We develop frameworks that give a generalised understanding of how scale-ups in this particular context acquire and integrate knowledge resources during episodes of growth and improved performance. These frameworks show how scale-ups start their scaling journey with a full acquisition of specialised resources in technical, business and internationalisation knowledge, which they integrate through providing direction and organisational routines to organisational members. We address the importance of having different knowledge capital in symmetry to increase the common knowledge, and we suggest that the scaling capability enables a scale-up to adapt for their changing organisational needs, which is why we liken scaling to developing organisational capability. / Contexto: Las "scale-ups", caracterizadas por su elevado crecimiento y su importante contribución al desarrollo económico, reciben cada vez más atención en las economías de hoy. Suelen ser PYMES jóvenes e innovadoras que crecen rápidamente más allá de las fronteras internacionales. Las scale-ups logran crecer y mejorar su rendimiento mediante un proceso acelerado de desarrollo organizativo, basado en sus recursos de conocimiento. Propósito: El propósito de este estudio es explorar y teorizar lo que constituya una capacidad de escalamiento empresarial. En concreto, estudiaremos la adquisición e integración de conocimientos en las PYME que escalan por los mercados internacionales. Método: Este estudio tiene un enfoque de investigación abductiva que considera las teorías actuales sobre el concepto de escalamiento empresarial, o "scaling", y la teoría de la gestión estratégica y los negocios internacionales basada en el conocimiento. Para lograr nuestro propósito, realizamos un estudio de casos múltiples de cuatro scale-ups innovadoras que se internacionalizan. Conclusiones: El estudio contribuye con un enfoque del escalamiento como "capacidad de escalamiento" que capta cómo las scale-ups innovadoras gestionan la organización interna del conocimiento experiencial. Desarrollamos modelos que ofrecen una comprensión generalizada de cómo las scale-ups en este contexto adquieren e integran recursos de conocimiento durante los episodios de crecimiento y mejora del rendimiento. Los modelos muestran cómo las scale-ups inician su proceso de crecimiento con una adquisición completa de recursos especializados en conocimientos técnicos, empresariales y de internacionalización, que integran proporcionando dirección y rutinas organizativas a los miembros de la organización. Abordamos la importancia de contar con diferentes capitales de conocimiento en simetría para aumentar el conocimiento común, y sugerimos que la capacidad de escalamiento permite a una scale-up adaptarse a sus necesidades organizativas cambiantes, razón por la cual vemos el escalamiento como el desarrollo de la capacidad organizativa.

[pt] No presente trabalho foi investigada a microfabricação de reatores fotocatalíticos de polidimetilsiloxano (PDMS) para o estudo comparativo de aumento de escala entre micro- e mesorreatores, e lignocelulósicos de bambu para reação de cicloadição alcino-azida catalisada por cobre(I) (CuAAC) em fluxo contínuo. Nesse cenário, foi desenvolvida uma configuração experimental de scale-up e numbering-up de sistemas meso- e microfluídicos fotocatalíticos, respectivamente, para comparar a eficiência de fotodegradação de TiO2/P25 em rodamina B (RB) e azul de metileno (em inglês, Methylene Blue, MB) sob irradiação UV. Os resultados obtidos sugerem que o aumento do volume (scale-up) reduz os valores de D(por cento), enquanto que numbering-up mantém a eficiência fotocatalítica com redução significativa do tempo de reação. M6-60 (micro)L apresentou melhor desempenho entre os dispositivos, com degradação total do MB (1,2 x 10-5 mol L-1) em apenas 1h, e foto-oxidação total de fenol (1,2 x 10-4 mol L-1) em 4h. Além disto, M6-60 (micro)L apresentou menor consumo de energia elétrica por ordem (0,012 kWh m-3) e maior rendimento quântico (2,6 x 10-2) em comparação com os outros dispositivos. O desenvolvimento de suportes sólidos lignocelulósicos apresentou importantes características para os processos de funcionalização de TEMPO-TAL com íons Cu(II) e Zn(II) e CuNPs. Os suportes foram devidamente caracterizados por MEV/EDS e FT-IR. Os resultados para a reação de CuAAC mostraram rendimentos de 79-82 por cento com reciclabilidade de até 7 vezes e lixiviação média de cobre de 1,30 ppm, e foram importantes para o desenvolvimento do microrreator de bambu. A microfabricação do microrreator lignocelulósicos de bambu (L(micro)R) foi realizada a partir de etapas de cortes, sem utilização de técnicas caras e sala limpa. L(micro)R mostrou fácil prototipagem e rápida oxidação com N-oxil-2,2,6,6-tetrametilpiperidina (TEMPO) e funcionalização com íons cobre (Cu-L(micro)R) e nanopartículas de cobre (CuNPs-L(micro)R). O desempenho de CuAAC em fluxo contínuo do Cu-L(micro)R foi demonstrado através da realização de estudos de reciclabilidade e rendimentos em diferentes taxas de fluxo (0,1 a 0,8 mL min-1). Cu-L(micro)R apresentou rendimentos de 60 por cento a 96 por cento para 5 tipos de reações CuAAC, indicando promissora aplicação na área de catálise em dispositivos microfluídicos. Todas as reações foram realizadas em regime de fluxo com MeOH:H2O (2:1) e lixiviação de cobre inferior a 6,0 ppm, produzindo uma série de 5 derivados de 1,2,3-triazol 1,4-dissubstituídos com boa eficiência em um ambiente com poucos recursos. CuNPs-L(micro)R apresentou limitação para realização de CuAAC por não alcançar as condições ideais de aquecimento, exigidas para ocorrência da reação. / [en] The present work had two main objectives. The first refers to the development of polydimethylsiloxane photocatalytic microreactors (PDMS) for the comparative scale-up study between micro- and mesoreactors. The second focused on the development of bamboo lignocellulosic microreactors for copper(I) catalyzed alkine-azide cycloaddition reaction (CuAAC). In this scenario, an experimental scale-up and numbering-up configuration of photocatalytic meso- and microfluidic systems were developed, to compare, respectively, the photodegradation efficiency of TiO2-P25 in rhodamine B (RB) and methylene blue (MB) under UV irradiation. The obtained results suggest that the scale-up reduces the values of D (percent), while numbering-up maintains the photocatalytic efficiency with a significant reaction time reduction. The best photocatalytic microfluidic system was M6-60 (micro)L, which presented total MB degradation (1.2 x 10-5 mol L-1) in only 1h, and total phenol photo-oxidation (1,2 x 10-4 mol L-1) in 4h. Furthermore, M6-60 (micro)LM6 had lower electrical energy consumption (0,012 kWh m-3) and higher quantum yield (2,6 x 10-2) compared to others. The development of solid lignocellulosic supports showed important characteristics for the TEMPO-TAL functionalization processes with Cu(II), Zn(II) ions and CuNPs. The supports were properly characterized by SEM/ EDS and FT-IR. The results for the CuAAC reaction showed yields of 79-82 percent with recyclability of up to 7 times and average copper leaching of 1.30 ppm, and were important for the development of the bamboo microreactor. The microfabrication of the bamboo lignocellulosic microreactor (L(micro)R) was performed from cutting steps, without using expensive techniques and clean room. L(micro)R showed easy prototyping and rapid oxidation with N-oxyl-2,2,6,6-tetramethylpiperidine (TEMPO) and functionalization with copper ions (Cu-L(micro)R) and copper nanoparticles (CuNPs-L(micro)R). Cu-L(micro)R continuous flow CuAAC performance was demonstrated by conducting recyclability and yield studies at different flow rates (0.1 to 0.8 mL-1). Cu-L(micro)R presented 60 percent to 96 percent yields for 5 types of CuAAC reactions, indicating promising application in the area of catalysis in microfluidic devices. All reactions were performed under a MeOH:H2O (2:1) flow regime and copper leaching below 6.0 ppm, producing a series of 5 efficiently 1,4-disubstituted 1,2,3-triazols derivatives in a resource-poor environment. CuNPs-L(micro)R presented limitation for CuAAC because it did not reach the ideal heating conditions required for the reaction to occur.

Many organisations aim to grow and increase their profitability, yet not many start-ups manage to survive beyond birth. The transformation into a well-established enterprise is generally seen as a big obstacle to tackle. Further on, project based organisations faces several challenges during scale-up such as how to maintain customisation within customer projects and how to keep up across-functional integration. This thesis addresses how a start-up manufacturing enterprise can scale-up its customer project management. Accordingly, the aim of this thesis is to get a better understanding of the difference between a start-up and an incumbent enterprise, and in turn highlight how to maintain customised operations in a project based organisation. The basis for this thesis is a case study conducted at Northvolt, a lithium-ion battery manufacturing enterprise located in Sweden. The outcome was performed through a collaboration with Northvolt’s customer project management department, and an analysis of conducted best-practice interviews together with a literature review. The empirical findings can be summarised in the following: • First, a growing enterprise needs to implement industry quality standards through the identification of standardised modules. Likewise, an enterprise needs to find which layers to keep flexible and create an environment that enables customisation. • Second, the dynamics within organisational structures can be illustrated as a cradle moving back and forth. An external platform enables new product development. • Third, cross-functional integration is identified as a corner stone for scale-up, but also vital to maintain new product development and hence customisation. • Fourth, pushing down the ownership together with clear targets and milestones is crucial to facilitate a mindset that motivates the workforce in growing sustainable. At the end, this thesis provides Northvolt with some key aspects to have in mind while scaling-up their customer project management, and highlights the conceptual contribution. / En strävan efter uppskalning är vanligt förekommande för företag inom tillverkningsindustrin. Däremot är det inte en självklarhet att transformera ett start-up till ett väletablerat företag. Att omstrukturera verksamheten till en framstående och välfungerande organisation uppfattas i regel som en svår uppgift. Projektbaserade organisationer möter allt som oftast flera utmaningar under uppskalning, sa som att bibehålla kundanpassning inom kundprojekt samt att den tvärfunktionell kommunikationen ofta blir lidande. Den har uppsatsen adresserar huruvida ett tillverkningsföretag, som befinner sig inom start-upstadiet, kan skala upp sin kundprojektavdelning. Därmed syftar denna uppsats till är att ge en ökad förståelse av vad som skiljer ett start-up från ett väletablerat företag, samt identifiera huruvida det går att bibehålla kundanpassning inom växande projektbaserade organisationer. Grunden till denna uppsats är en fallstudie genomförd tillsammans med Northvolt, ett batteritillverkande företag baserat i Sverige. Resultatet är baserat på best-practice intervjuer samt en litteraturstudie, varav analysen ar utförd i samarbete med Nortvhvolts kundprojekt avdelning. Det empiriska resultatet kan kort sammanfattas enligt: • För det första, ett växande företag behöver implementera branschspecifika kvalitetsstandarder genom att identifiera vad som kan standardiseras. Likaså behöver ett företag specificera vilka delar som kan hållas flexibla för kundanpassning. • För det andra, en organisation pendlar allt som oftast mellan olika strukturer. Genom att skapa en extern plattform kan ett företag generera produktutveckling i allt högre grad. • För det tredje, tvärfunktionell kommunikation är en grundsten för uppskalning, men även en nyckel för att generera produktutveckling och därmed kundanpassning. • För det fjärde, att trycka ansvaret längre ner i hierarkin tillsammans med att implementera tydliga mål och hållpunkter utgör en grund för att ge arbetskraften den motivation som krävs för att växa hållbart. Till sist bidrar denna uppsats med några applicerbara verktyg som Northvolt kan ta tillhanda för att skala upp deras kundprojekt avdelning, och slutligen en redovisning av det konceptuella bidraget inom uppskalning av projektbaserade organisationer.

In the kingdom of Saudi Arabia (KSA), the current seawater desalination technologies are completely relying on burning unsustainable crude oil as their main energy driver. Saudi authorities have realized that the KSA is not going to be protected from the future global energy crisis and have started to set up a plan to diversify its energy resources. Membrane Distillation (MD) has emerged as an attractive alternative desalination process. It combines advantages from both thermal and membrane-based technologies and holds the potential of being a cost-effective separation process that can utilize low-grade waste heat or renewable energy. MD has four different configurations; among them is Air Gap Membrane Distillation (AGMD) which is the second most commonly tested and the most commercially available pilot-plant design. AGMD has a stagnant thin layer of air between the membrane and the condensation surface. This layer introduces a mass transfer resistance that makes the process require a large membrane surface area if a large quantity of fresh water is desired. This dissertation reports on experimental and theoretical work conducted to enhance the AGMD flux by removing non-condensable gases from the module and replacing it with either vacuum, liquid water or porous materials. At first, a mathematical model for AGMD was developed and validated experimentally to create a baseline for improvements that could be achieved after the removal of non-condensable gases. The mathematical model was then modified to simulate the process under vacuum where it showed a flux enhancement that reached 286%. The Water Gap Membrane Distillation (WGMD) configuration improved the flux by almost the same percentage. Since enhancing the flux is expected to increase temperature polarization effects, a theoretical study was conducted on the effect of temperature polarization in a Vacuum Membrane Distillation (VMD) configuration. The study showed that the effect of temperature polarization at small temperature difference (3-7) degree Celsius between the bulk feed and coolant temperatures is significantly high. This may indicate the importance of mitigating the effect of temperature polarization in large scale modules operating at small temperature difference across the membrane. The dissertation concluded with some recommendations for future work.