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In open angle glaucoma, dysfunction of the trabecular meshwork (TM) results in impaired aqueous humour outflow leading to an elevated intraocular pressure (IOP) that underlies optic nerve damage and irreversible blindness. Currently, no curative treatment is available for the disease. Indeed, most pharmacological and surgical interventions usually provide only temporary relief from elevated IOP while little progress has been made in targeting the root cause of this disease: correcting the dysfunctional TM. In this context, we hypothesized that regeneration/refunctionalization of the TM may represent an effective therapeutic option to halt disease progression or even reverse the pathologic process. We previously demonstrated in a rat model of glaucoma that the injection of mesenchymal stromal cells (MSCs) cultured under hypoxic conditions or their conditioned media (MSC-CM) into laser-damaged TM area results in tissue regeneration. Injection of MSC or conditioned media in our glaucoma model led to activation and proliferation of ocular progenitor cells culminating in TM regeneration and a decrease in IOP. However, the mechanistic basis for this regenerative process remained elusive. Thus, the aim of this thesis is to elucidate the mechanistic basis of MSC secretome-mediated TM regeneration and the subsequent decrease in IOP. We now demonstrate that injection of hypoxic MSC-CM into laser-induced glaucomatous eyes resulted in massive immune cell recruitment. We also demonstrate that these hypoxic MSC-CM conditioned cells produced pro-regenerative factors in vitro and in vivo. Next, employing a proteomic approach, we identified and verified the pro-regenerative effect of several factors secreted by hypoxic MSC-CM recruited cells, which in turn induced the activation/proliferation of ocular progenitor cells leading to TM regeneration and decreased IOP. Upon individual injection of the purified factors into glaucomatous rat eyes, we observed a partial and delayed but significant decrease in IOP that correlated with an increase in the activation and proliferation of neuronal progenitor cells in the TM area. The co-injection of these factors resulted in a significant decrease in IOP compared with individual factor injection. Importantly, this drop in IOP was associated with restoration of retinal functionality, thus demonstrating the importance of these factors in the TM regeneration process and disease control. The findings presented in this thesis provide a novel acellular therapeutic approach for glaucoma treatment via in situ TM regeneration. Moreover, the knowledge gained here could have a lasting impact on how we induce tissue regeneration in other degenerative diseases and lead to novel therapeutic advances in regenerative medicine. / Dans le glaucome à angle ouvert, le dysfonctionnement du trabéculum (TM), un tissu nécessaire à la filtration de l'humeur aqueuse, entraîne une élévation de la pression intraoculaire (PIO). Ceci cause des lésions au niveau du nerf optique et une cécité irréversible. Présentement, aucun traitement curatif n'a été développé pour cette maladie. Nous émettons l'hypothèse que la régénération et re-fonctionnalisation du trabéculum peut représenter une option thérapeutique efficace pour arrêter ou inverser la progression de la maladie dans de nombreux cas de glaucome. Nous avons précédemment démontré les effets régénérateurs des cellules mésenchymateuses (MSCs) et de leurs milieux conditionnés par l'hypoxie (MSC-CM) dans la régénération du TM suite à un dommage par laser. Ce processus a conduit à l'activation et à la prolifération des cellules progénitrices oculaires résultant en une diminution de la PIO dans un modèle de glaucome induit par laser chez le rat. Cependant, la base mécanistique de ce processus de régénération reste encore inconnue. Ainsi, le but de cette thèse de recherche est d'élucider cette base mécanistique de la régénération du TM médiée par le sécrétome des MSC et la diminution subséquente de la PIO. À cette fin, l'injection de MSC-CM hypoxique dans les yeux glaucomateux induits par laser a entraîné un important recrutement de cellules immunitaires. Sous l’action du MSC-CM, ces cellules produisent des facteurs pro-régénératifs in vitro et in vivo. Ensuite, nous avons utilisé une approche protéomique et vérifié l'effet pro-régénératif des facteurs sécrétés par ces cellules exposées au MSC-CM hypoxique, sur l'activation et la prolifération des cellules progénitrices oculaires et la PIO. Lors de l'injection de ces facteurs chez le rat glaucomateux, nous avons observé une augmentation significative de l'activation et de la prolifération des cellules progénitrices neuronales présentes dans la zone du TM, résultant en une diminution de la PIO. De plus, l’injection combinée de ces facteurs résulte en une diminution synergique importante de la PIO. Cette baisse de la PIO était associée à une restauration de la fonction rétinienne, démontrant ainsi l'importance de ces facteurs dans le processus de régénération du TM et de contrôle de la maladie. Les résultats présentés dans cette thèse pourraient amener à une nouvelle approche thérapeutique acellulaire pour le traitement du glaucome via la régénération du TM. De plus, les connaissances acquises au cours de cette thèse pourraient avoir un impact durable sur la manière d’aborder la régénération tissulaire dans d'autres maladies dégénératives et amener des avancées thérapeutiques nouvelles en médecine régénératrice

Transforming growth factor beta 3 (TGF3) promotes tenogenic differentiation and may enhance tendon regeneration in vivo. This study aimed to apply TGF3 absorbed in decellularized equine superficial digital flexor tendon scaffolds, and to investigate the bioactivity of scaffold-associated TGF3 in an in vitro model. TGF3 could effectively be loaded onto tendon scaffolds so that at least 88% of the applied TGF3 were not detected in the rinsing fluid of the TGF3-loaded scaffolds. Equine adipose tissue-derived multipotent mesenchymal stromal cells (MSC) were then seeded on scaffolds loaded with 300 ng TGF3 to assess its bioactivity. Both scaffold-associated TGF3 and TGF3 dissolved in the cell culture medium, the latter serving as control group, promoted elongation of cell shapes and scaffold contraction (p < 0.05). Furthermore, scaffold-associated and dissolved TGF3 affected MSC musculoskeletal gene expression in a similar manner, with an upregulation of tenascin c and downregulation of other matrix molecules, most markedly decorin (p < 0.05). These results demonstrate that the bioactivity of scaold-associated TGF3 is preserved, thus TGF3 application via absorption in decellularized tendon scaffolds is a feasible approach.

No description available.

No description available.

Zum Wintersemester 2019/2020 wird an der TU Bergakademie Freiberg ein neuer MSc- Studiengang „Geomatics for Mineral Resource Management“ angeboten. Dieser ist Teil eines internationalen Programmes unter Beteiligung der Universitäten Técnico Lisboa in Portugal, Delft University of Technology in den Niederlanden, TU Bergakademie Freiberg in Deutschland, Montanuniversität Leoben in Österreich sowie Wroclaw University of Science and Technology in Polen. Es ist vorgesehen, ein europaweit sichtbares Programm anzubieten, dass den Studierenden ein flexibles internationales Studium an jeweils zwei der Hochschulen ermöglicht und sie auf Führungsaufgaben im Bereich der Geomatik in der Rohstoffwirtschaft vorbereitet. Der Beitrag fasst das Konzept des internationalen Programmes zusammen und stellt die Möglichkeiten an der TU Freiberg konkret dar. / For the winter term 2019/2020, a new MSc program 'Geomatics for Mineral Resource Management' will be offered at the TU Bergakademie Freiberg. This is part of an international program involving the Universities of Técnico Lisboa in Portugal, Delft University of Technology in the Netherlands, TU Bergakademie Freiberg in Germany, Montanuniversität Leoben in Austria and Wroclaw University of Science and Technology in Poland. The ambition is to offer a Europe-wide visible program that enables students to study internationally flexibly at two of the universities being prepared for a leader role in geomatics for Mineral Resource Management. The article summarizes the concept of the international program and presents the possibilities at the TU Freiberg.

We establish the existence of a symmetry within the Gromov-Witten theory of CPn and its blowup along points. The nature of this symmetry is encoded in the Cremona transform and its resolution, which lives on the toric variety of the permutohedron. This symmetry expresses some difficult to compute invariants in terms of others less difficult to compute. We focus on enumerative implications; in particular this technique yields a one line proof of the uniqueness of the rational normal curve. Our method involves a study of the toric geometry of the permutohedron, and degeneration of Gromov-Witten invariants. / En este trabajo establecemos la existencia de una simetra en el marco de la teora de Gromov-Witten para CPn y su explosion a lo largo de puntos. La naturaleza de esta simetra queda codicada en la transformacion de Cremona y su resolucion en una variedad torica del permutoedro. Esta simetra expresa algunos invariantes difciles de calcular junto con otros que no lo son tanto. Nos centramos en implicaciones enumerativas; en particular esta tecnica ofrece una prueba enuna lnea de la unicidad de la curva racional normal. Nuestro metodo involucra un estudio de la geometra torica del permutoedro, as como el de la degeneracion de los invariantes de Gromov-Witten.

Background: Multipotent mesenchymal stromal cells (MSC) can be recovered from a variety of tissues in the body. Yet, their functional properties were shown to vary depending on tissue origin. While MSC have emerged as a favoured cell type for tendon regenerative therapies, very little is known about the influence of the MSC source on their properties relevant to tendon regeneration. The aim of this study was to assess and compare the expression of tendon extracellular matrix proteins and tendon differentiation markers in MSC derived from different sources as well as in native tendon tissue. MSC isolated from equine bone marrow, adipose tissue, umbilical cord tissue, umbilical cord blood and tendon tissue were characterized and then subjected to mRNA analysis by real-time polymerase chain reaction. Results: MSC derived from adipose tissue displayed the highest expression of collagen 1A2, collagen 3A1 and decorin compared to MSC from all other sources and native tendon tissue (p < 0.01). Tenascin-C and scleraxis expressions were highest in MSC derived from cord blood compared to MSC derived from other sources, though both tenascin-C and scleraxis were expressed at significantly lower levels in all MSC compared to native tendon tissue (p < 0.01). Conclusions: These findings demonstrate that the MSC source impacts the cell properties relevant to tendon regeneration. Adipose derived MSC might be superior regarding their potential to positively influence tendon matrix reorganization.

Additive manufacturing processes have been investigated for some years, and are commonly used industrially in the field of plastics for small- and medium-sized series. The use of metallic deposition material has been intensively studied on the laboratory scale, but the numerical prediction is not yet state of the art. This paper examines numerical approaches for predicting temperature fields, distortions, and mechanical properties using the Finite Element (FE) software MSC Marc. For process mapping, the filler materials G4Si1 (1.5130) for steel, and AZ31 for magnesium, were first characterized in terms of thermo-physical and thermo-mechanical properties with process-relevant cast microstructure. These material parameters are necessary for a detailed thermo-mechanical coupled Finite Element Method (FEM). The focus of the investigations was on the numerical analysis of the influence of the wire feed (2.5–5.0 m/min) and the weld path orientation (unidirectional or continuous) on the temperature evolution for multi-layered walls of miscellaneous materials. For the calibration of the numerical model, the real welding experiments were carried out using the gas-metal arc-welding process—cold metal transfer (CMT) technology. A uniform wall geometry can be produced with a continuous welding path, because a more homogeneous temperature distribution results.

Topologieoptimierte Geometrie wird vom Konstrukteur in einem Format benötigt, das im CAD verwendet werden kann. Die Herausforderung ist, dass man als Optimierungsergebnis eine STL-Geometrie bekommt, doch fürs CAD soll die Oberfläche möglichst glatt und vereinfacht sein. Die Software MSC Apex erzeugt aus einer STL-Geometrie eine echte, geglättete Parasolid-Geometrie. Eine spezielle Form der Topologieoptimierung ist die Topometrieoptimierung, welche die Rippenstruktur auf einem Blech vorschlägt. Auch hierfür ist Geometrierückführung möglich. Auch stark verformte Bauteile, z.B. Gummiteile, kann man als Geometrie im verformten Zustand ans CAD zurückgeben, um zu sehen, wie sie dann in die Baugruppe passen. / Topology optimized geometry must be provided to the designer in a format that can be used in CAD. The challenge is that the optimization result is typically an STL geometry, but for CAD the surface should be as smooth and simplified as possible. The MSC Apex software creates a real, smoothed parasolid geometry from an STL geometry. A special form of topology optimization is topometry optimization, which suggests the rib structure on a sheet. Reverse engineering is also possible for this. Even heavily deformed components, e.g. rubber parts, can be returned to CAD as geometry in the deformed state, to see how they fit into the assembly in this state.