Nowadays, telecommunication services are commonly deployed in private networks, which are controlled and maintained by the telecommunication operators themselves, by co-location services providers, or, to some extent, by their hardware and software providers. However, with the present development of cloud computing resources, one might consider if these services could and should be implemented in the Cloud, thus taking advantage of cloud computing’s high availability, geographic distribution, and ease of usage. Additionally, this migration could reduce the telecommunication operators’ concerns in terms of hardware and network maintenance, leaving those to the Cloud computing providers who will need to supply a highly available and consistent service, to fulfill the telecommunication services’ requirements. Furthermore, virtualization provides the possibility of easily and rapidly changing the Cloud network topology facilitating the addition and removal of machines and services, allowing telecommunication services providers to adapt to their demands on the fly. The aim of this thesis project is to analyze and evaluate the level of performance, from the network point of view, that can be achieved when using Cloud computing resources to implement a telecommunication service, carrying out practical experiments both in laboratory and real environments. These measurements and analyses were conducted using an Ericsson prototype mobile switching center server (MSC-S) application, although the results obtained could be adapted to other applications with similar requirements. In order to potentially test this approach in a real environment, a prior providers’ survey was utilized to evaluate their services based on our requirements in terms of hardware and network characteristics, and thus select a suitable candidate environment for our purposes. One cloud provider was selected and its service was further evaluated based on the MSC-S application requirements. We report the results of our bench-marking process in this environment and compare them to the results of testing in a laboratory environment. The results of both sets of testing were well correlated and indicate potential for hosting telecommunication services in a Cloud environment, providing the Cloud meets the requirements imposed by the telecom services. / Actualmente, los servicios de telecomunicaciones se implementan comúnmente en redes privadas, controladas y mantenidas por los operadores de telecomunicaciones, por proveedores de servicios de colocación o, hasta cierto punto, por proveedores de hardware y software. Sin embargo, con el presente desarrollo de la tecnología de ’Cloud computing’, se puede considerar la posibilidad de implementar servicios de telecomunicaciones en la nube, aprovechando su alta disponibilidad, distribución geográfica y facilidad de uso. Además, este cambio puede reducir las preocupaciones de los operadores en relación al mantenimiento del hardware y de la red, delegando en los proveedores del servicio de ’Cloud computing’, los cuáles deberán proporcionar un servicio consistente, cumpliendo así con los requisitos de los servicios de telecomunicaciones. Por otra parte, la virtualización propociona la posibilidad de cambiar rápida y fácilmente la topología de la red, facilitando la adición y supresión de maquinas y servicios, y, por tanto, permitiendo a los operadores adaptarse a sus necesidades sobre la marcha. El objetivo de esta tésis es analizar y evaluar en nivel de rendimiento, desde el punto de vista de la red, que se puede conseguir usando recursos de ’Cloud computing’ para implementar un servicio de telecomunicaciones, llevando a cabo experimentos tanto en el laboratorio como en un entorno real. Estos análisis fueron realizados utilizando un prototipo de un servidor de conmutación móvil (MSC-S) de Ericsson, aunque los resultados pueden adaptarse a otras aplicaciones con unos requisitos similares. Para probar esta propuesta en un entorno real, se realizó una encuesta de proveedores de servicios de ’Cloud computing’, con el objetivo de evaluar sus servicios teniendo en cuenta nuestros requisitos de hardware y red. Finalmente, un proveedor fue escogido y su servicio evaluado basándonos en los requisitos de la aplicación MSC-S. En este documento proporcionamos los resultados de esa evaluación y los comparamos con los obtenidos en el laboratorio. Los resultados de ambas evaluaciones fueron satisfactorios e indican la posibilidad de implementar servicios de telecomunicaciones en la nube, siempre que la nube cumpla los requisitos impuestos por dichos servicios de telecomunicaciones. / Nuförtiden är telekommunikationstjänster ofta uppsatta i privata nätverk, som kontrolleras och underhålls av teleoperatörerna själva, av samlokaliserande tjänsteleverantörer eller i viss utsträckning av deras hårdvaruoch programvaru-leverantörer. Med den nuvarande utvecklingen av Cloud Computing-resurser kan man dock överväga om dessa tjänster kan och bör genomföras i ett Cloud, vilket drar fördel av Cloud Computings höga tillgänglighet, geografiska spridning, och enkla användning. Denna migration minskar även teleoperatörernas oro angående hårdvaru- och nätverks-underhåll genom att överlåta detta till Cloud Computing-leverantörerna, som kommer att behöva leverera en hög tillgänglighet och konsekvent service för att uppfylla telekommunikationstjänsternas krav. Dessutom ger virtualisering möjlighet att enkelt och snabbt ändra ett Clouds nätverkstopologi, vilket underlättar tillägg och borttagning av maskiner och tjänster, vilket hjälper teleoperatörer att snabbt anpassa sig till deras krav. Målet med examensarbetet är att analysera och uppskatta prestandan, från nätets perspektiv, som kan uppnås vid användning av Cloud Computingresurser för att genomföra en teletjänst, genom praktiska experiment både i laboratorium och i verkligheten. Dessa mätningar och analyser utfördes med en prototyp av en Ericsson mobilomkopplingscentralserverapplikation (MSCS), även om de erhållna resultaten skulle kunna anpassas till andra program med liknande krav. För att potentiellt kunna testa denna metod i en verklig miljö användes en tidigare leverantörs undersökning för att utvärdera deras tjänster baserat på våra krav på hårdvara och nätverksegenskaper, och genom detta välja en lämplig kandidatmiljö för våra syften. En Cloud-leverantör valdes och dess tjänster utvärderades vidare baserat på MSC-Ss applikationskrav. Vi redovisar resultatet av vår testprocess i den här miljön och jämför det med resultaten av tester i laboratoriemiljö. Resultaten från båda uppsättningarna av tester var väl korrelerade och visar på potentialen av att implementera telekommunikationstjänster i en Cloud-miljö, om detta Cloud uppfyller de kraven som ställs av telekommunikationtjänsterna.

Der Bedarf an modernen Konzepten der regenerativen Medizin für die Therapie von Knochensubstanzdefekten steigt zunehmend angesichts unserer sich demographisch wandeln-den Gesellschaft und der damit einhergehenden, steigenden Zahl altersrelevanter orthopädisch-unfallchirurgischer Erkrankungen. Die wissenschaftlichen Erkenntnisse der letzten Jahrzehnte erlauben es, grundlegende biologische Prozesse der Knochenregeneration nicht nur besser zu verstehen, sondern diese auch durch gezielte Einflussnahme zu nutzen. Auf Grundlage dieser Erkenntnisse fokussiert die Forschung die Entwicklung moderner bioaktiver Biomaterialien mit dem intrinsischen Potenzial, die körpereigene Geweberegeneration lokal im Defektbereich – in situ – zu stimulieren. Die Stimulation zellulärer Regenerationsmechanismen kann entweder direkt durch Zell-Material-Interaktion induziert werden (in situ Regeneration), oder durch chemotaktische Attraktion von Zellen mit regenerativem Potenzial aus dem umliegenden Gewebe, welche ihrerseits die Geweberegeneration induzieren (in situ Tissue Engineering). Ohne extrakorporale Besiedlung der Scaffolds und deren in vitro-Kultivierung vor der Implantation umgehen diese in situ-Strategien mehrere Limitationen und Herausforderungen des klassischen Tissue Engineering-Konzepts. Dem in situ-Konzept folgend wurden im Rahmen dieser Dissertation zwei Strategien zur gezielten Funktionalisierung eines Knochenersatzmaterials aus mineralisiertem Kollagen unter-sucht: I) Zum einen wurde mineralisiertes Kollagen mit dem osteoanabol wirksamen Erdalkalimetall Strontium modifiziert, um lokal die Osteogenese zu stimulieren. II) Zum anderen wurden poröse Scaffolds aus mineralisiertem Kollagen mit einem zentralen Depot funktionalisiert, welches mit einem Wirkstoffgemisch beladen wurde, welches aus dem Sekretom Hypoxie-konditionierter hBMSC (HCM) generiert wurde. Durch gezielte Attraktion von Zellen mit regenerativem Potenzial und gleichzeitiger Stimulation der Vaskularisierung soll dieses Scaffoldsystem gezielt die Knochendefektheilung induzieren. Für die Strontium-Modifikation wurde während der Scaffoldsynthese das Calcium der Mineralphase sukzessive durch Strontium substituiert und die hergestellten Scaffolds eingehend materialwissenschaftlich charakterisiert (Publikation 2.1; Quade et al., 2018a). Die simultane Fibrillierung und Mineralisierung von Kollagen führte zur Bildung von Nanokompositen, wobei die Mineralphasen von nanokristallinem Hydroxylapatit (Sr0), über schwach kristalline Strontium-reiche Phasen zu einer gemischten Mineralphase (Sr100) aus amorphem Strontiumphosphat und hochkristallinem Strontiumhydroxylapatit verschoben wurde. Freisetzungsversu-che über 28 Tage zeigten, dass die getesteten Varianten Sr50 und Sr100 anhaltend Sr2+-Ionen in einem Konzentrationsbereich freisetzten, in dem sowohl die Knochenneubildung stimuliert, als auch die zelluläre Knochenresorption gehemmt wird. In vitro zeigte sich der osteoanabole Effekt Strontium-modifizierter mineralisierter Kollagenscaffolds durch eine signifikant gesteigerte Proliferation und osteogene Differenzierung von hBMSC. In vivo – als Knochenersatzmaterial im murinen segmentalen FemurdefektModell – zeigten Strontium-modifizierte Scaffolds aus mineralisiertem Kollagen zwar ein tendenziell gesteigertes Knochenvolumen mit erhöhter Osteoblastenzahl, signifikant weniger Osteoklasten und signifikant gesteigerter Vaskularisierung, jedoch war der Effekt verhältnismäßig schwach und allein nicht ausreichend für eine knöcherne Überbrückung des Defektbereiches (Publikation 2.2; Quade et al., 2020a). Durch Kombination von Sr-Modifikation und BMP-2-Funktionalisierung konnte die Qualität des neugebildeten Knochens signifikant gesteigert werden. Um das Konzept des neuartigen Wirkstoffdepot-basierten Scaffoldsystems zu testen, wurde das zentrale Depot zunächst mit dem Modell-Wachstumsfaktor VEGF beladen. Der Einsatz der Biopolymere Alginat, Hyaluronsäure und Heparin als Depotbildner erlaubt die Modulation der Wirkstofffreisetzung. Während die Hydrogele Alginat und Hyaluronsäure dabei als physikalischen Barriere fungieren, ermöglichte die hohe ionische Bindungsaffinität von Heparin und VEGF dessen nahezu lineare Freisetzung über den Versuchszeitraum von 28 Tagen. Im Migrationsversuch bewirkte die retardierte VEGF-Freisetzung und damit die Stabilisierung des Wirkstoffgradienten die gerichtete Migration von HDMEC in den Scaffold. Je verzögerter die VEGF-Freisetzung – und damit je steiler der Wirkstoffgradient – desto tiefer migrierten HDMEC in die Scaffolds (Publikation 2.3; Quade et al., 2017a). Entscheidend für eine effiziente Knochenregeneration ist sowohl die Attraktion von Zellen mit regenerativem Potenzial, als auch die Stimulation der Vaskularisierung, um den Gasaustausch, die Nähstoffversorgung und den Abtransport metabolischer Nebenprodukte der Zel-len im Defektbereich zu gewährleisten. Im Sinne des in situ Tissue Engineering-Konzepts wurde das zentrale Wirkstoffdepot mit einem natürliche Wirkstoffgemisch, welches aus dem Sekretom Hypoxie-konditionierter hBMSC (HCM) gewonnen wurde, beladen (Publikation 2.4; (Quade et al., 2020b). Unter hypoxischen Bedingungen sezernieren hBMSC einen Wirkstoffcocktail, der unter anderem Wachstumsfaktoren, Chemokine, Hormone und Exosomen enthält und ein starkes angiogenes und chemotaktisches Potenzial gegenüber hBMSC zeigt. Um das Wirkstoffdepot möglichst effizient zu beladen, wurde zum einen die Wirkstoffausbeute von HCM durch Anpassung der Herstellungsparameter optimiert. Gemessen am Wachstumsfaktor VEGF konnte so die Ausbeute bis zu 100-fach gesteigert werden. Des Weiteren konnte durch Dialyse, Gefriertrocknung und Resuspension mit dem Depot-bildenden Biopolymer zusätzlich eine bis zu 50-fache Konzentrierung des Wirkstoffgemisches erreicht wer-den ohne Verlust der Bioaktivität. Mit steigender HCM-Konzentration im Depot konnte sowohl eine tiefere Migration von hBMSC, als auch eine Verbesserung der Angiogenese erzielt wer-den. Zusätzlich bewirkte die retardierte HCM-Freisetzung aus Alginat-basierten Depots eine signifikante Steigerung von Länge, Dichte und Einsprosstiefe prävaskulärer Strukturen. Zwar ist die Charakterisierung und standardisierte Herstellung des natürlichen HCM-basierten Wirkstoffgemisches eine Herausforderung, jedoch ist davon auszugehen, dass dessen be-deutendes therapeutisches Potenzial gerade durch die Komplexität der sezernierten Faktoren und deren synergistisches Zusammenspiel bedingt wird. Die Standardisierung der HCM-basierten Wirkstoffherstellung, sowie eine bessere Quantifizierung und Charakterisierung der sezernierten Proteine sollte in zukünftigen Studien forciert werden. Beide Strategien, die im Rahmen dieser Dissertation untersucht wurden, haben das Potenzial, als zellfreie „ready-to-use“-Knochenersatzmaterialien zu erschwinglichen Kosten, bei geringerer regulatorischer Komplexität und mit gleichbleibend hoher Qualität produziert zu wer-den. Während Strontium-modifiziertes mineralisiertes Kollagen allein in vivo nur ein schwaches osteoinduktives Potenzial zeigte, konnte die Qualität und Festigkeit des neugebildeten Knochengewebes in Kombination mit BMP-2 signifikant verbessert werden. Als leicht-osteogenes Biomaterial könnte dieses zur Unterstützung etablierter therapeutischer Konzepte eingesetzt werden – vor allem bei Patienten mit systemischen Knochenerkrankungen wie beispielsweise Osteoporose. Das komplexere Depot-basierte Scaffoldsystem hingegen hat ein großes Potenzial für die klinische Translation. Zum einen kann das Depot je nach Bedarf mit verschiedensten Wirkstoffen beladen werden, deren Freisetzung in Abhängigkeit des Depot-bildenden Biopolymers manipuliert werden kann. Beladen mit dem natürlichen HCM-basierten Wirkstoffgemisch zeigte das Scaffoldsystem ein beeindruckendes chemotaktisches und angiogenes Potenzial. Gegenüber etablierten rhBMP-2-Applikationen, stellt dieser in situ Tissue Engineering-Ansatz damit eine vielversprechende Alternative für die Knochen-defekt-Therapie dar, bei gleichzeitig deutlich reduzierten Kosten und Nebenwirkungen. Zu-künftige in vivo-Studien im Großtiermodell sollten das regenerative Potenzial des Depot-basierten Scaffoldsystems umfassend verifizieren. / Our demographically changing society causes a rising number of age-related orthopaedic and trauma surgical diseases. Modern approaches following the concept of regenerative medicine are needed for the therapeutical treatment of bone defects. Scientific findings of the last decades not only allow for a better understanding of fundamental biological processes in the field of bone regeneration, but also to use this knowledge for effective therapeutic concepts. Therefore, research is focusing on the development of modern bioactive biomaterials with the intrinsic potential to locally stimulate the body's own regeneration capacity - in situ. The stimulation of tissue regeneration can either be induced directly by cell-material interaction (in situ regeneration), or by chemotactic attraction of cells with regenerative potential from the surrounding tissue, which would in turn induce local tissue regeneration (in situ tissue engineering). Since these in situ strategies forgo the extracorporeal seeding and in vitro cultivation of scaffolds prior implantation, several limitations and challenges of the classical tissue engineering concept can be circumvented. Within the scope of this dissertation two strategies were investigated. Following the in situ concept, scaffolds based on mineralized collagen were specifically functionalized in order to locally induce bone defect healing: I) On the one hand, mineralised collagen was modified with strontium to locally stimulate osteogenesis. II) On the other hand, porous scaffolds of mineralised collagen were functionalised with a central depot loaded with a cocktail of signalling factors generated from the secretome of hypoxia-conditioned hBMSC (HCM). By specifically attracting cells with regenerative potential and simultaneously stimulating vascularisation, this scaffold-system could actively induce bone defect healing. For the strontium modification, the calcium of the mineral phase was successively substituted by strontium during the scaffold synthesis. The generated scaffolds were characterised in detail from a material science perspective (publication 2.1; Quade et al.et al., 2018a). In all tested approaches simultaneous collagen fibrillation and mineralisation led to the formation of nanocomposites. With rising strontium substitution, the mineral phases shifted from nanocrystalline hydroxylapatite (Sr0), via weakly crystalline strontium-rich phases to a mixed mineral phase of amorphous strontium phosphate and highly crystalline strontium hydroxylapatite (Sr100). Release experiments showed that the scaffold variants Sr50 and Sr100 released Sr2+-ions continuously over 28 days in a range, which is known to exploit the dual effect of strontium by simultaneously promoting proliferation and osteogenic differentiation as well as inhibiting the osteoclastic bone resorption without impairing the osteoclastogenesis. In vitro, the osteoanabolic effect of strontium-modified mineralised collagen scaffolds was demonstrated by significantly increased proliferation and osteogenic differentiation of hBMSC. In vivo - in the murine segmental femoral defect model - strontium-modified scaffolds made of mineralised collagen showed a tendency to increase bone volume with an increased number of osteoblasts, significantly reduced osteoclasts and significantly increased vascularisation. However, the effect was relatively weak and not sufficient to cause a bridging of the defect area (publication 2.2; Quade et al., 2020a). By combining Sr modification and BMP-2 functionalisation, the quality of the newly formed bone was significantly improved. To test the concept of the novel depot-based scaffold system, the central depot was loaded with the model growth factor VEGF. The use of the biopolymers alginate, hyaluronic acid and heparin as depot-forming agents allowed the modulation of drug release. While the hydrogels alginate and hyaluronic acid act as a physical barrier, the high ionic binding affinity of heparin and VEGF facilitated an almost linear VEGF-release over the experimental period of 28 days. In migration experiments, the retarded VEGF release and thus the stabilisation of the VEGF- gradient caused the directed migration of HDMEC into the scaffolds. The slower the VEGF release - and thus the steeper the drug gradient - the deeper HDMEC migrated into the scaffolds (publication 2.3; Quade et al., 2017). Crucial for an efficient bone regeneration is both the attraction of cells with regenerative potential and the stimulation of vascularisation to ensure gas exchange, nutrient supply and removal of metabolic by-products in the defect area. In line with the in situ tissue engineering concept, the central depot was loaded with a natural factor mix obtained from the secretome of hypoxia-conditioned hBMSC (HCM) (publication 2.4; (Quade et al., 2020b). Under hypoxic conditions, hBMSC secrete a cocktail of active substances that contains, among others, growth factors, chemokines, hormones and exosomes. This factor mix shows a strong angiogenic potential and is highly chemo-attractive to hBMSC. In order to load the scaffold depot as efficiently as possible, the signalling factor-yield of HCM was optimised by adjusting the cultivation settings for HCM-generation. Measured by VEGF as a model growth factor, the yield was increased up to 100 times. In addition, dialysis, freeze-drying and resuspension with the depot-forming biopolymer made it possible to achieve another 50-fold concentration without loss of bioactivity. With increasing HCM-concentration in the depot, both a deeper migration of hBMSC and an improvement in angiogenesis could be achieved. In addition, the retarded release of HCM from alginate-based depots resulted in a significant increase in length, density and sprouting depth of prevascular structures. Although the characterisation and standardised production of the natural HCM-based signalling factor cocktail is challenging, it can be assumed that its significant therapeutic potential relies particularly on that complexity of the secreted factors and their synergistic interaction. The standardized production of HCM-derived signalling factor cocktails, as well as a better quantification and characterisation of the secreted proteins should be focused by future studies. Both strategies investigated in this dissertation have the potential to be produced as cell-free 'ready-to-use' bone substitute materials at affordable costs, with less regulatory complexity and with consistently high quality. While strontium-modified mineralised collagen alone showed only a weak osteoinductive potential in vivo, the quality and strength of the newly formed bone tissue was significantly improved in combination with BMP-2. This light-osteogenic biomaterial could be used to support established therapeutic concepts - especially in patients with systemic bone diseases such as osteoporosis. The more complex depot-based scaffold system on the other hand has great potential for clinical translation. Depending on the application, the depot can be loaded with a wide variety of active substances – their release kinetics in turn can be manipulated depending on the depot-forming biopolymer. Loaded with the natural HCM-derived cocktail of signalling molecules, the scaffold system showed an impressive chemotactic and angiogenic potential. Compared to established rhBMP-2 applications, this in situ tissue engineering approach represents a promising alternative for bone defect therapy, at significantly reduced costs and side effects. Future in vivo studies in large animal models should verify the regenerative potential of the herewith developed depot-based scaffold system.

his work deals with the methods of creating computational models for the analysis of the chain drive of camshafts in combustion engines. Methods are compared of the simulation of the drive mechanism; a new method is also presented for the simulation of the tensioning and guide bar by means of a modal reduction of an elastic body in the Multibody system. The work describes individual parts of the chain gear and the mathematical formulation of differential equations of motion. Algorithms are also indicated describing the mutual interaction of bodies in contact. Computations are here described for the determination of individual parameters necessary for setting up a chain drive model. The tensile characteristics of the chain is determined by the FEM programme. The chain model is analyzed in several alternatives of arrangement. FEM calculations are described here of the rigidity of contacts between the chain and the chain wheels and between the chain and the guide bars. The computational model has been created in the MSC ADAMS programme. The computation is carried out for a stabilized speed of the crankshaft of 3,000, 4,500 and 6,000 rpm and for a continuous start from the idle state up to the speed of 6,000 rpm with a constant load of the crankshafts by the torsion moment. Computation is also carried out for loading the crankshafts with a torsion moment deduced from the cam shape. The courses of the quantity obtained are processed by means of FFT; Campbell diagrams have been constructed for their evaluation. The results have been compared with the modal analyses of the individual parts of the chain gear for the determination of their mutual interaction.

The mesenchymal stromal cell (MSC) is of great interest for its immunomodulatory and regenerative properties. However, to research and use these MSCs it is essential to identify and characterize them as such. They need to fulfill the MSCs' minimal criteria which assess the differentiation potential, cell surface markers, and adherence. In this study, cells donated from human bone marrow were identified as MSC according to the minimal criteria. Methods used were flow cytometry, immunofluorescent staining, and ELISA. Furthermore, the population was cultured in three different media (DMEM-LG with either 10% FBS, 2% FBS, or 10% FBS supplemented with 10% conditioned media from human urinary bladder carcinoma cells (T24)) for 21 days whereupon tested for the mesenchymal characteristics, cells were counted and size measured at every passage. All cultures maintained their mesenchymal character, however, cells grown in 2% FBS became a considerably more heterogenous population regarding cell size and granularity, perhaps because of senescence. Additionally, these cells somewhat decreased in proliferation and resulted in 1 x 106 cells after 21 days, however, this was not a significant decrease when compared to the 10% FBS culture which had 2.16 x 106 cells after 21 days (p=0.061). On the contrary, the culture supplemented with T24 conditioned media resulted in a significantly higher cell count with 4.75 x 106 cells (p=0.008). Further studies could investigate which components in the conditioned media contributed to the proliferation. Moreover, the cell population in this study could not be characterized as MSC with certainty as additional cell surface markers should be tested.

Osteoarthritis (OA) is a progressive cartilage degeneration disease with a complex pathologic mechanism. Although OA has devastating effects on patient quality of life and places a significant burden on the healthcare system, no disease-modifying drugs have been found, and surgical treatment options are often unsustainable. 3D bioprinting is a novel field within tissue engineering that focuses on developing biocompatible constructs that can be implanted to replace an organ or tissue. Such constructs have a great potential to become treatments for OA. Understanding cell mobility within hydrogels could play a vital role in advancing the development of biocompatible constructs. However, due to the novelty of bioprinting, limited research on cell mobility within hydrogels is available. Therefore, this project aims to fill the gap in existing research regarding cell mobility within bioprinted constructs with varying mechanical properties. To achieve this goal, green fluorescent protein-tagged mesenchymal stromal cells (MSCs) were developed to assess progenitor cell mobility in bioprinted hydrogel constructs. Constructs were printed with three zones: hydrogel with embedded chondrocytes or MSCs; hydrogel spacer; and chemoattractant. Designed constructs were bioprinted (BioAssemblyBot, Advanced Solutions) using GelMA:HAMA bioinks containing photoinitiator with varying bioink percentages. Cell viability and directional mobility within constructs were assessed by fluorescence viability assay and time-lapse fluorescence microscopy. The protocol to evaluate cell mobility in bioprinted constructs and optimized bioprinting settings for GelMA:HAMA bioinks were gained through this project. Overall, this project allowed us to fill the gap in existing knowledge regarding MSC and chondrocyte mobility in hydrogels and contribute to developing a novel treatment method for OA.

This study compared seven syntactic measures which can be automatically generated by the Computerized Profiling (CP) software: Mean Length of Utterance in morphemes or words (MLUm or MLUw), Mean Syntactic Length (MSL), the Index of Productive Syntax (IPSyn), the Picture Elicited Scoring Procedure (PESP) for the Language Analysis Remediation and Screening Profile (LARSP), the Syntactic Complexity Score (MSC) scoring of LARSP, and Developmental Sentence Scoring (DSS). Language samples came from 192 children, 106 typically developing children, ages 5;6 to 11;2 and 86 children with language impairment, ages 5;6 to 11;1. Patterns of correlation were consistent for children with or without language impairment. All measures were computed with CP software, and all coding decisions that were made by the software were accepted. The three measures of length (MLUm, MLUw, and MSL) were highly intercorrelated. MSC correlated with the measures of length and with DSS. DSS correlated with the length measures, though not as highly as MSC. DSS also correlated with IPSyn. IPSyn correlated moderately with PESP, correlated less with MSC, and correlated the least with the measures of length. PESP correlated moderately with each measure. PESP, DSS, and IPSyn correlated more highly for the children with language impairment. These measures correlated highly sometimes and sometimes they did not correlate much. This suggests that they are measuring different aspects of syntactic ability.

Doxorubicin (DOX) is an incessantly used chemotherapeutic drug that can cause detrimental dose-dependent effects such as cardiotoxicity and congestive heart failure. Studies have focused on therapeutic strategies such as exosomes derived from embryonic stem cell (ES-Exos) and antioxidants for example resveratrol; however, the function of mesenchymal stem cell-derived exosomes (MSC-Exos) have never been examined in DOX-induced pyroptosis. MSC-Exos maintains the therapeutic potential of exosome therapy without the ethical concerns. Hence, the current study focuses on determining whether MSC-Exos has the potential to ameliorate inflammation-induced cell death pyroptosis in our established in vitro DOX-induced cardiotoxicity (DIC) model. Rat embryonic cardiomyocytes (H9c2) were first exposed to DOX to stimulate pyroptosis, followed by subsequent treatment with MSC-Exos, with further analysis performed through immunocytochemistry, western blotting, and RT-PCR. We evaluated the therapeutic potential of MSC-Exos by investigating the pyroptotic initiator HMGB1 which binds to TLR4 resulting in the formation of the NLRP3 inflammasome that initiates pyroptosis by activating the pyroptotic markers, caspase-1, IL-1β and IL-18, and the pyroptotic executioner GSDMD. Our data depicted that treatment with MSC-Exos significantly (p

[ES] El infarto agudo de miocardio (IAM) es una de las principales causas de morbilidad y mortalidad en los países desarrollados. A lo largo de los últimos años se ha visto que la respuesta inflamatoria que ocurre tras desencadenarse el IAM es muy importante en el desarrollo clínico de esta patología. Si se produce una respuesta inflamatoria exacerbada aumenta el riesgo de remodelado cardiaco adverso y fallo cardiaco, pero el hecho de que no se desencadene la respuesta inflamatoria también tiene consecuencias negativas. Debido a la importancia de la respuesta inflamatoria en el IAM, recientemente se han intentado desarrollar terapias dirigidas frente componentes celulares o moleculares que participan en esta respuesta. Dentro de estas terapias, la terapia celular con células mesenquimales estromales (MSC) se ha postulado como un buen candidato. Las MSC se caracterizan fundamentalmente por su capacidad inmunomoduladora, lo que ha conducido a su empleo como agentes terapéuticos en diferentes enfermedades que cursan con procesos inflamatorios. Sin embargo, a lo largo de los últimos años, numerosos estudios han mostrado que el efecto terapéutico de las MSC está mediado fundamentalmente por las vesículas extracelulares (EVs) que liberan. Estas EVs recapitulan los efectos terapéuticos de las células de origen, por lo que también presentan efectos inmunomoduladores. El empleo de las EVs de MSC como agentes terapéuticos presenta ventajas respecto al uso de las MSC como, por ejemplo, una mayor bioseguridad. No obstante, el uso clínico de las EVs todavía tiene que hacer frente a retos como la obtención de grandes cantidades de EVs que constituyan un producto clínico estable y homogéneo. En este trabajo se ha querido evaluar, por un lado, si las EVs obtenidas de diferentes biopsias de la misma fuente tisular de MSC pueden constituir un producto biológico homogéneo que presente las mismas características y funcionalidad. Por otro lado, se ha evaluado si estas EVs se pueden emplear como agente terapéutico frente a la respuesta inflamatoria que se desencadena tras el IAM. Para ello se ha estudiado el efecto inmunomodulador de las EVs sobre células del sistema inmune, fundamentalmente macrófagos, in vitro y en un modelo in vivo de IAM en ratas. Los resultados mostraron que las EVs favorecen la diferenciación de los macrófagos M1 proinflamatorios hacia un fenotipo similar al M2, aumentando la expresión de marcadores M2 y reduciendo la secreción de citocinas proinflamatorias. Además, las EVs promovieron la activación de neutrófilos in vitro y la reducción de su estrés oxidativo. La administración de EVs en ratas sometidas a IAM amortiguó la caída de la función cardiaca y limitó la extensión de la zona infartada a los 7 y 21 días postinfarto. Las EVs también redujeron el número de macrófagos y neutrófilos proinflamatorios dentro de la zona infartada, favoreciendo la resolución de la inflamación. En conclusión, las EVs empleadas en este trabajo han demostrado ser un producto biológico estable con independencia de la biopsia de la que proceden, y han demostrado ser capaces de ejercer respuestas pro-resolutivas eficaces en un modelo de isquemia miocárdica, lo que las convierte en potenciales agentes terapéuticos para tratar la inflamación en el IAM. / [CA] L'infart agut de miocardi (IAM) és una de les principals causes de morbiditat i mortalitat als països desenvolupats. Al llarg dels darrers anys s'ha vist que la resposta inflamatòria que passa després de desencadenar-se l'IAM és molt important en el desenvolupament clínic d'aquesta patologia. Si es produeix una resposta inflamatòria exacerbada augmenta el risc de remodelat cardíac advers i fallada cardíaca, però el fet que no es desencadeni la resposta inflamatòria també té conseqüències negatives. A causa de la importància de la resposta inflamatòria a l'IAM, recentment s'han intentat desenvolupar teràpies dirigides davant de components cel·lulars o moleculars que participen en aquesta resposta. Dins aquestes teràpies, la teràpia cel·lular amb cèl·lules mesenquimals estromals (MSC) s'ha postulat com un bon candidat. Les MSC es caracteritzen fonamentalment per la seva capacitat immunomoduladora, cosa que ha conduït a la seva ocupació com a agents terapèutics en diferents malalties que cursen amb processos inflamatoris. Tot i això, al llarg dels últims anys, nombrosos estudis han mostrat que l'efecte terapèutic de les MSC està intervingut fonamentalment per les vesícules extracel·lulars (EVs) que alliberen. Aquestes EVs recapitulen els efectes terapèutics de les cèl·lules dorigen, per la qual cosa també presenten efectes immunomoduladors. L'ús de les EVs de MSC com a agents terapèutics presenta avantatges respecte a l'ús de les MSC com, per exemple, una bioseguretat més gran. Tot i això, l'ús clínic de les EVs encara ha de fer front a reptes com l'obtenció de grans quantitats d'EVs que constitueixin un producte clínic estable i homogeni. En aquest treball s'ha volgut avaluar, d'una banda, si les EV obtingudes de diferents biòpsies de la mateixa font tissular de MSC poden constituir un producte biològic homogeni que presenti les mateixes característiques i funcionalitat. D'altra banda, s'ha avaluat si aquestes EVs es poden fer servir com a agent terapèutic davant de la resposta inflamatòria que es desencadena després de l'IAM. Per això s'ha estudiat l'efecte immunomodulador de les EV sobre cèl·lules del sistema immune, fonamentalment macròfags, in vitro i en un model in vivo d'IAM en rates. Els resultats van mostrar que les EVs afavoreixen la diferenciació dels macròfags M1 proinflamatoris cap a un fenotip similar al M2, augmentant l'expressió de marcadors M2 i reduint la secreció de citocines proinflamatòries. A més, les VE van promoure l'activació de neutròfils in vitro i la reducció del seu estrès oxidatiu. L'administració d'EVs en rates sotmeses a IAM va esmorteir la caiguda de la funció cardíaca i va limitar l'extensió de la zona infartada als 7 i 21 dies postinfart. Les EVs també van reduir el nombre de macròfags i neutròfils proinflamatoris dins de la zona infartada, afavorint la resolució de la inflamació. En conclusió, les EVs emprades en aquest treball han demostrat ser un producte biològic estable amb independència de la biòpsia de què procedeixen, i han demostrat ser capaços d'exercir respostes pro-resolutives eficaces en un model d'isquèmia miocàrdica, cosa que les converteix en agents terapèutics potencials per tractar la inflamació a l'IAM. / [EN] Acute myocardial infarction (AMI) is one of the main causes of morbidity and mortality in developed countries. Over the last few years, it has been shown that the inflammatory response that occurs after AMI is triggered is very important in the clinical development of this pathology. If an exacerbated inflammatory response occurs, the risk of adverse cardiac remodeling and heart failure increases, but failure to trigger the inflammatory response also has negative consequences. Because of the importance of the inflammatory response in AMI, recent attempts have been made to develop therapies that target cellular or molecular components involved in this response. Within these therapies, cell therapy with mesenchymal stromal cells (MSC) has been postulated as a good candidate. MSC are mainly characterized by their immunomodulatory capacity, which has led to their use as therapeutic agents in different diseases involving inflammatory processes. However, in recent years, numerous studies have shown that the therapeutic effect of MSCs is mainly mediated by the extracellular vesicles (EVs) they release. These EVs recapitulate the therapeutic effects of the cells of origin and therefore also have immunomodulatory effects. The use of MSC-EVs as therapeutic agents has advantages over the use of MSC, such as increased biosafety. However, the clinical use of EVs still faces challenges such as obtaining large quantities of EVs that constitute a stable and homogeneous clinical product. The aim of this study was to evaluate, on the one hand, whether EVs obtained from different biopsies of the same MSC tissue source can constitute a homogeneous biological product with the same characteristics and functionality. On the other hand, we have evaluated whether these EVs can be used as a therapeutic agent against the inflammatory response triggered after AMI. To this end, the immunomodulatory effect of EVs on immune system cells, mainly macrophages, was studied in vitro and in an in vivo model of AMI in rats. The results showed that EVs favored the differentiation of proinflammatory M1 macrophages towards an M2-like phenotype, increasing the expression of M2 markers and reducing the secretion of proinflammatory cytokines. In addition, EVs promoted the activation of neutrophils in vitro and the reduction of their oxidative stress. The administration of EVs in rats subjected to AMI blunted the decline in cardiac function and limited the extent of the infarct zone at 7- and 21-days post-infarction. EVs also reduced the number of proinflammatory macrophages and neutrophils within the infarct zone, favoring the resolution of inflammation. In conclusion, the EVs used in this work have been shown to be a stable biological product regardless of the biopsy from which they are derived and have been shown to be able to exert effective pro-resolving responses in a model of myocardial ischemia, making them potential therapeutic agents to treat inflammation in AMI. / Amaro Prellezo, E. (2024). Las vesículas extracelulares derivadas de células mesenquimales estromales de pulpa dental como producto terapéutico frente a la respuesta inmune que se desencadena tras el infarto agudo de miocardio [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/202973

This thesis project is conducted in collaboration with Swepart Transmission AB, aimed to dynamically simulate the compact gearbox design with planetary gears meant to be used in robots. The primary objective of this project is to analyze operational principles of planetary gears and their suitability for mitigating lost motion (backlash). Simulations have been carried out using MSC Adams software where the input speed is 1400 rpm on the pinion gear, which is equal to 1100 deg/s when applied to the sun gear. An adjustment gear is mounted atop sun gear, which is used to adjust the position of the planet gears and it is locked with different variations of 0, 5 and 10 degrees of angular displacement to adjust the planet gears. Additionally, one of the planet gears is selected and the position of teeth in that planet gear is deviated by 10, 20, 30 and 40 micrometers and these new gears are then placed in position of the existing planet gear one by one. These models are then simulated to study the variations and effects of angular velocity on the ring gears, angular velocity of the adjustment gear, displacement in radial direction of the planet gear after it is adjusted, force and torque generated on contact between the planet gear and the ring gear over a period of 5 seconds using 1000 time steps.

Surface Acoustic Wave (SAW) devices have been under research for over half a century due to their excellent performance characteristics in the fields of signal processing and communications. In particular, it has been show that SAW devices can operate as sensors that are both wireless and passive. For a sensor that is wireless, it is important to develop a coding scheme that allows for the identification of an individual sensor in a multiple sensor environment. For SAW sensors, orthogonal frequency coding (OFC) has been demonstrated as a method to provide a large number of unique identification codes. This system relies on an array of frequency selective reflectors (chips) in the SAW propagation path. The reflectors are ordered such that no two SAW sensors contain an array of reflection gratings in the same frequency order. One way to increase the number of usable codes in an OFC sensor is to increase the number of OFC chips on the sensor. With this technique it is necessary to increase the delay between the transducer and the OFC chips while keeping the length of the device small. Multiple surface wave propagation tracks can be utilized to slightly increase the width of the die instead of the length. This research aims to investigate methods to extend delay time in a coded SAW device by utilizing two propagation tracks. It will be shown that the reflective multistrip coupler (RMSC) can accomplish this goal with low loss. The design, fabrication, and characterization of the RMSC will be given with applications shown in an OFC SAW device.