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Structure-property relationships in poly(2-oxazoline)/poly(2-oxazine) based drug formulations / Struktur-Eigenschafts-Beziehungen in Poly(2-oxazolin)/Poly(2-oxazin) basierten WirkstoffformulierungenLübtow, Michael M. January 2020 (has links) (PDF)
According to estimates, more than 40% of all new chemical entities developed in pharmaceutical industry are practically insoluble in water. Naturally, the demand for excipients which increase the water solubility and thus, the bioavailability of such hydrophobic drugs is enormous. Poly(2-oxazoline)s (POx) are currently intensively discussed as highly versatile class of biomaterials. Although selected POx based micellar drug formulations exhibit extraordinarily high drug loadings > 50 wt.% enabling high anti-tumor efficacies in vivo, the formulation of other hydrophobic compounds has failed. This casts doubt on the general understanding in which a hydrophobic active pharmaceutical ingredient is dissolved rather unspecifically in the hydrophobic core of the micelles following the fundamental concept of “like dissolves like”. Therefore, a closer look at the interactions between all components within a formulation becomes increasingly important. To do so, a large vehicle platform was synthesized, loaded with various hydrophobic drugs of different structure, and the formulations subsequently characterized with conventional and less conventional techniques. The obtained in-depth insights helped to develop a more thorough understanding about the interaction of polymer and incorporated API finally revealing morphologies deviating from a classical core/shell structure. During these studies, the scarcely investigated polymer class of poly(2-oxazine)s (POzi) was found as promising drug-delivery vehicle for hydrophobic drugs. Apart from this fundamental research, the anti-tumor efficacy of the two APIs curcumin and atorvastatin has been studied in more detail. To increase the scope of POx and POzi based formulations designed for intravenous administration, a curcumin loaded hydrogel was developed as injectable drug-depot. / Schätzungen zufolge sind mehr als 40% aller „new chemical entities“, welche in der pharmazeutischen Industrie entwickelt werden, wasserunlöslich. Aus diesem Grund ist der Bedarf an Zusatzstoffen, welche die Wasserlöslichkeit und dadurch die Bioverfügbarkeit erhöhen, enorm. Poly(2-oxazolin)e (POx) werden derzeitig intensiv als vielseitig einsetzbare Biomaterialien untersucht. Obwohl bestimmte POx basierte, mizellare Wirkstoffformulierungen außergewöhnlich hohe Beladungskapazitäten > 50 Gew.% aufwiesen und dadurch ausgeprägte anti-Tumor Effektivität in vivo ermöglichten, schlug die Formulierung anderer hydrophober Stoffe fehl. Dies lässt Zweifel an dem altbewährten Konzept aufkommen, in welchem hydrophobe Arzneistoffe mehr oder weniger unspezifisch im hydrophoben Kern einer Mizelle gelöst werden. Aus diesem Grund ist ein genauerer Blick auf die Interaktionen zwischen allen Bestandteilen einer Formulierung vonnöten. Deshalb wurde eine große Polymerplattform synthetisiert, mit verschiedenen hydrophoben Wirkstoffen unterschiedlicher Struktur beladen und die Formulierungen im Anschluss mit herkömmlichen und weniger herkömmlichen Methoden charakterisiert. Die daraus erhaltenen Einblicke ermöglichten es ein umfassenderes Verständnis über die Interaktionen von Polymer und Wirkstoff zu entwickeln. Innerhalb dieser Studien wurden Aggregate charakterisiert, welche von einer klassischen Kern/Schale Morphologie abwichen. Des Weiteren konnte die kaum erforschte Polymerklasse der Poly(2-oxazin)e (POzi) als vielversprechende Wirkstoffträgerplattform für hydrophobe Wirkstoffe charakterisiert werden. Von dieser Grundlagenforschung abgesehen, wurde die anti-Tumor Effektivität von Curcumin und Atorvastatin Nanoformulierungen untersucht. Um den Anwendungsbereich der POx und POzi basierten Wirkstoffformulierungen, welche für intravenöse Verabreichung entwickelt wurden, zu erweitern, wurde ein Curcumin beladenes Hydrogel als injizierbares Wirkstoffdepot entwickelt.
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Solid-state NMR Spectroscopic, X-Ray Diffraction and Quantum Chemical Investigations of the Crystalline Cancer Drug Paclitaxel and Paclitaxel incorporated into Polymer Micelles / Festkörper-NMR-, Röntgendiffraktometrie- und quantenchemische Untersuchungen des kristallinen Krebs-Wirkstoffs Paclitaxel und Paclitaxel eingebettet in PolymermizellenGrüne, Marvin January 2022 (has links) (PDF)
Paclitaxel (PTX) is one of the leading drugs against breast and ovarian cancer. Due to its low solubility, treatment of the patients with this drug requires a very well-suited combination with a soluble pharmaceutical excipient to increase the bioavailability and reduce the strong side ef-fects. One efficient way to achieve this in the future could be the incorporation of PTX into pol-ymeric micelles composed of poly(2-oxazoline) based triblock copolymers (POL) which ena-bles PTX loadings of up to 50 wt.%. However, structural information at an atomic level and thus the knowledge of interaction sites within these promising but complex PTX-POL formula-tions were not yet available. Such results could support the future development of improved excipients for PTX and suitable excipients for other pharmaceutical drugs. Therefore, a solid-state MAS NMR investigation of these amorphous formulations with different POL-PTX com-positions was performed in this thesis as this gives insights of the local structure at an atomic level in its solid state. NMR in solution showed very broad 13C signals of PTX for this system due to the reduced mobility of the incorporated drug which exclude this as an analytical meth-od.
In a first study, crystalline PTX was structurally characterized by solid-state NMR as no com-plete 13C spectrum assignment and no 1H NMR data existed for the solid state. In addition, the asymmetric unit of the PTX crystal structure consists of two molecules (Z'=2) that can only be investigated in its solid state. As crystalline PTX in total has about 100 different 13C and 1H chemical shifts with very small differences due to Z’=2, and furthermore, its unit cell consisting of more than 900 atoms, accompanying GIPAW (CASTEP) calculations were required for NMR signal assignments. These calculations were performed using the first three available purely hydrous and anhydrous PTX structures, which were determined by XRD and published by Vel-la-Zarb et al. in 2013. Within this thesis, is was discovered that two investigated batches of commercially available PTX from the same supplier both contained an identical and so far un-known PTX phase that was elucidated by PXRD as well as solid-state NMR data. One of the two batches consists of an additional phase that was shown to be very similar to a known hy-drated phase published in 2013.[1] By heating the batch with the mixture of the two phases un-der vacuum, it is transformed completely to the new dry phase occurring in both PTX batches. Since the drying conditions to obtain anhydrous PTX in-situ on the PXRD setup described by Vella-Zarb et. al.[1] were much softer than ours, we identify our dry phase as a relaxed version of their published anhydrate structure. The PXRD data of the new anhydrate phase was trans-ferred into a new structural model, which currently undergoes geometry optimization. Based on solid-state NMR data at MAS spinning frequencies up to 100 kHz, a 13C and a partial 1H signal assignment for the new anhydrous structure were achieved. These results provided sufficient structural information for further investigations of the micellar POL-PTX system.
In a second study, the applicability and benefit of two-dimensional solid-state 14N-1H HMQC MAS NMR spectra for the characterization of amorphous POL-PTX formulations was investi-gated. The mentioned technique has never been applied to a system of similar complexity be-fore and was chosen because around 84% of the small-molecule drugs contain at least one nitrogen atom. In addition, the number of nitrogen atoms in both POL and PTX is much smaller than the number of carbons or hydrogens, which significantly reduces the spectral complexity. 14N has a natural abundance of 99.6% but leads to quadrupolar broadening due to its nuclear spin quantum number I = 1. While this is usually undesirable due to broadening in the resulting 1D 14N NMR spectra, this effect is explicitly used in the 2D 14N-1H HMQC MAS experiment. The indirect 14N measurement can avoid the broadening while maintaining the advantage of the high natural abundance and making use of the much more dispersed signals due to the additional quadrupolar shifts as compared to 15N.
This measurement method could be successfully applied to the complex amorphous POL-PTX mixtures. With increasing PTX loading of the formulations, additional peaks arise as spatial proximities of the amide nitrogens of POL to NH or OH groups of PTX. In addition, the 14N quadrupolar shift of these amide nitrogens decreases with increasing PTX content indicating a more symmetric nitrogen environment. The latter can be explained by a transformation of the trigonal planar coordination of the tertiary amide nitrogen atoms in pure POL towards a more tetrahedral environment upon PTX loading induced by the formation of hydrogen bonds with NH/OH groups of PTX.
In the third and last project, the results of the two abovementioned studies were used and ex-tended by solid state 13C and two-dimensional 1H-13C as well as 1H-1H MAS NMR data with the aim to derive a structural model of the POL-PTX formulations at an atomic level. The knowledge of the NMR signal assignments for crystalline PTX was transferred to amorphous PTX (present in the micelles of the formulations). The 13C solid-state NMR signals were evalu-ated concerning changes in chemical shifts and full widths of half maximum (FWHM) for the different PTX loadings. In this way, the required information about possible interaction sites at an atomic level becomes available. Due to the complexity of these systems, such proximities often cannot be assigned to special atoms, but more to groups of atoms, as the individual de-velopments of line widths and line shifts are mutually dependent. An advantageous aspect for this analysis was that pure POL already forms unloaded micelles. The evaluation of the data showed that the terminal phenyl groups of PTX seem to be most involved in the interaction by the establishment of the micelle for lowest drug loading and that they are likely to react to the change in the amount of PTX molecules as well. For the incorporation of PTX in the micelles, the following model could be obtained: For lowest drug loading, PTX is mainly located in the inner part of the micelles. Upon further increasing of the loading, it progressively extends to-ward the micellar shell. This could be well shown by the increasing interactions of the hydro-phobic butyl chain of POL and PTX, proceeding in the direction of the polymer backbone with rising drug load. Furthermore, due to the size of PTX and the hydrodynamic radius of the mi-celles, even at the lowest loading, the PTX molecules partially reach the core-shell interface of the micelle. Upon increasing the drug loading, the surface coverage with PTX clusters increas-es based on the obtained model approach. The latter result is supported by DLS and SANS data of this system. The abovementioned results of the 14N-1H HMQC MAS investigation of the POL-PTX formulations support the outlined model.
As an outlook, the currently running geometry optimization and subsequently scheduled calcu-lation of the chemical shieldings of the newly obtained anhydrous PTX crystal structure can further improve the solid-state NMR characterization through determination of further spatial proximities among protons using the existing 2D 1H(DQ)-1H(SQ) solid-state MAS NMR spec-trum at 100 kHz rotor spinning frequency. The 2D 14N-1H HMQC MAS NMR experiments were shown to have great potential as a technique for the analysis of other disordered and amor-phous drug delivery systems as well. The results of this thesis should be subsequently applied to other micellar systems with varying pharmaceutical excipients or active ingredients with the goal of systematically achieving higher drug loadings (e.g., for the investigated PTX, the similar drug docetaxel or even different natural products). Additionally, it is planned to transfer the knowledge to another complex polymer system containing poly(amino acids) which offers hy-drogen bonding donor sites for additional intermolecular interactions. Currently, the POL-PTX system is investigated by further SANS studies that may provide another puzzle piece to the model as complementary measurement method in the future. In addition, the use of MD simu-lations might be considered in the future. This would allow a computerized linking of the differ-ent pieces of information with the aim to determine the most likely model. / Paclitaxel (PTX) ist eines der führenden Medikamente gegen Brust-und Eierstockkrebs. Aufgrund seiner geringen Löslichkeit erfordert die Behandlung der Patienten mit diesem Medikament eine sehr gut geeignete Kombination mit einem löslichen pharmazeutischenHilfsstoff, um die Bioverfügbarkeit zu erhöhen und die starken Nebenwirkungen zu reduzieren. Ein effizienter Weg, dies in Zukunft zu erreichen, könnte der Einbau von PTX in polymere Mizellen sein, die aus Poly(2-oxazolin)-basierten Triblock-Copolymeren (POL) bestehen und PTX-Beladungen von bis zu 50 Gew.-% ermöglichen. Strukturelle Informationen auf atomarer Ebene und damit die Kenntnis von Wechselwirkungeninnerhalb dieser vielversprechenden, aber komplexen PTX-POL-Formulierungen waren jedoch bisher nichtverfügbar. Solche Ergebnisse könnten die zukünftige Entwicklung von verbesserten Hilfsstoffen für PTX und von geeigneten Hilfsstoffen für andere pharmazeutische Wirkstoffe unterstützen. Aus diesem Grund wurdenin der vorliegenden DissertationFestkörper-NMR-Untersuchungen andiesenamorphen Formulierungen mit unterschiedlichen POL-PTX Zusammensetzungen durchgeführt, weil damit Einblickein die lokale Struktur auf atomarer Ebene im festen Zustand erhalten werden können. Aufgrund der verringerten Mobilität des eingebrachten Wirkstoffs in diesem System ergeben NMR-Messungen in Lösung sehr breite 13C-PTX-Signale, was diese Technikals Analysemethode ausschließt. ...
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Isolation and selection of nitrifying bacteria with high biofilm formation for treatment of ammonium polluted aquaculture water / Phân lập và tuyển chọn vi khuẩn nitrate hóa hình thành màng sinh học để xử lý nước nuôi trồng thủy sản bị ô nhiễm ammoniumHoang, Phuong Ha, Nguyen,, Hong Thu, Trung, Trung Thanh, Tran, Thanh Tung, Do, Lan Phuong, Le, Thi Nhi Cong 24 August 2017 (has links) (PDF)
A biofilm is any group of microorganisms in which cells stick to each other and adhere to a surface by excreting a matrix of extracellular polymeric substances (EPS). The chemoautotrophic nitrifying bacteria hardly form biofilms due to their extremely low growth rate; however, biofilm formation of nitrifying bacteria trends to attach in carrier by extracellular polysaccharides that facilitate mutual adhesion, the forming biofilm is also beneficial in nitrogen removal in biological filter systems, especially in aquaculture water treatment systems. The microbial activity within bio-carrier is a key factor in the performance of biofilm reactor. Selection the nitrifier bacteria that biofilm formation and immobilization on the carrier for application in ammonium polluted water treatment technologies, especially in aquaculture is our research objective. Therefore, in this study, ten and six strains of ammonia oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) respectively were isolated from six different aquaculture water samples collected from Quang Ninh and Soc Trang. Basing on their high nitrification activity and biofilm forming capacity, six bacterial strains have been selected to take photo by scanning electron microscope (SEM) and carry out in 2 – liter tanks with and without carriers. As the results, the system with carriers (30% of total volume) increased nitrogen compounds elimination efficiency from 1.2 times to 2 times in comparison with the system without carrier. Two representatives of ammonia oxidizing bacterial group (B1.1; G2-1.2) were classification based on characteristics and they were classified as Nitrosomonas sp. and Nitrosococcus sp. / Màng sinh học được hình thành từ vi sinh vật nhờ các tế bào tiết ra các chất cao phân tử ngoại bào (EPS) và dính vào nhau đồng thời được gắn lên một bề mặt vật thể lỏng hoặc rắn. Vi khuẩn nitrate hóa tự dưỡng có thể tạo ra màng sinh học nhưng khá khó khăn do tỷ lệ sinh trưởng rất chậm của chúng. Tuy nhiên vi khuẩn nitrate hóa tạo màng sinh học thường có xu thế bám lên giá thể nhờ sự gắn kết của các polisaccarit ngoại bào. Sự hình thành màng sinh học cũng là lợi thế để loại bỏ các hợp chất nitơ trong các hệ thống lọc sinh học, đặc biệt là trong các hệ thống xử lý nước nuôi trồng thủy sản. Hoạt tính vi sinh vật cùng với giá thể sinh học là một yếu tố quan trọng để thực hiện trong các bể phản ứng màng sinh học. Trong nghiên cứu này, mục tiêu của chúng tôi là lựa chọn được các vi khuẩn nitrate hóa có khả năng tạo màng sinh học và cố định chúng lên giá thể để ứng dụng trong các công nghệ xử lý nước bị ô nhiễm ammonia đặc biệt là trong nuôi trồng thủy sản. Kết quả cho thấy, từ sáu mẫu nước nuôi trồng thủy sản khác nhau từ Quảng Ninh và Sóc Trăng, 10 chủng vi khuẩn oxy hóa ammonia (AOB) và 6 chủng vi khuẩn oxy hóa nitrite (NOB) đã được phân lập. Dựa vào hoạt tính nitrate hóa và khả năng tạo màng sinh học của các chủng vi khuẩn phân lập được 6 chủng điển hình đã được lựa chọn để chụp ảnh kính hiển vi điện tử quét và được ứng dụng trong hai bể sinh học với dung tích 2 lít có chứa và không chứa chất mang (giá thể). Sau 7 ngày, hệ thống sinh học chứa giá thể (chiếm 30% thể tích) có hiệu suất loại bỏ các hợp chất nitơ tăng hơn từ 1,2 đến 2 lần so với bể sinh học không chứa chất mang. Hai đại diện của nhóm vi khuẩn oxy hóa ammonia (B-1.1 và G2-1.2) đã được phân loại sơ bộ dựa vào một số đặc điểm sinh học và chúng đã được xác định thuộc chi Nitrosomonas và chi Nitrosococcus.
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Isolation and selection of nitrifying bacteria with high biofilm formation for treatment of ammonium polluted aquaculture water: Research articleHoang, Phuong Ha, Nguyen,, Hong Thu, Trung, Trung Thanh, Tran, Thanh Tung, Do, Lan Phuong, Le, Thi Nhi Cong 24 August 2017 (has links)
A biofilm is any group of microorganisms in which cells stick to each other and adhere to a surface by excreting a matrix of extracellular polymeric substances (EPS). The chemoautotrophic nitrifying bacteria hardly form biofilms due to their extremely low growth rate; however, biofilm formation of nitrifying bacteria trends to attach in carrier by extracellular polysaccharides that facilitate mutual adhesion, the forming biofilm is also beneficial in nitrogen removal in biological filter systems, especially in aquaculture water treatment systems. The microbial activity within bio-carrier is a key factor in the performance of biofilm reactor. Selection the nitrifier bacteria that biofilm formation and immobilization on the carrier for application in ammonium polluted water treatment technologies, especially in aquaculture is our research objective. Therefore, in this study, ten and six strains of ammonia oxidizing bacteria (AOB) and nitrite oxidizing bacteria (NOB) respectively were isolated from six different aquaculture water samples collected from Quang Ninh and Soc Trang. Basing on their high nitrification activity and biofilm forming capacity, six bacterial strains have been selected to take photo by scanning electron microscope (SEM) and carry out in 2 – liter tanks with and without carriers. As the results, the system with carriers (30% of total volume) increased nitrogen compounds elimination efficiency from 1.2 times to 2 times in comparison with the system without carrier. Two representatives of ammonia oxidizing bacterial group (B1.1; G2-1.2) were classification based on characteristics and they were classified as Nitrosomonas sp. and Nitrosococcus sp. / Màng sinh học được hình thành từ vi sinh vật nhờ các tế bào tiết ra các chất cao phân tử ngoại bào (EPS) và dính vào nhau đồng thời được gắn lên một bề mặt vật thể lỏng hoặc rắn. Vi khuẩn nitrate hóa tự dưỡng có thể tạo ra màng sinh học nhưng khá khó khăn do tỷ lệ sinh trưởng rất chậm của chúng. Tuy nhiên vi khuẩn nitrate hóa tạo màng sinh học thường có xu thế bám lên giá thể nhờ sự gắn kết của các polisaccarit ngoại bào. Sự hình thành màng sinh học cũng là lợi thế để loại bỏ các hợp chất nitơ trong các hệ thống lọc sinh học, đặc biệt là trong các hệ thống xử lý nước nuôi trồng thủy sản. Hoạt tính vi sinh vật cùng với giá thể sinh học là một yếu tố quan trọng để thực hiện trong các bể phản ứng màng sinh học. Trong nghiên cứu này, mục tiêu của chúng tôi là lựa chọn được các vi khuẩn nitrate hóa có khả năng tạo màng sinh học và cố định chúng lên giá thể để ứng dụng trong các công nghệ xử lý nước bị ô nhiễm ammonia đặc biệt là trong nuôi trồng thủy sản. Kết quả cho thấy, từ sáu mẫu nước nuôi trồng thủy sản khác nhau từ Quảng Ninh và Sóc Trăng, 10 chủng vi khuẩn oxy hóa ammonia (AOB) và 6 chủng vi khuẩn oxy hóa nitrite (NOB) đã được phân lập. Dựa vào hoạt tính nitrate hóa và khả năng tạo màng sinh học của các chủng vi khuẩn phân lập được 6 chủng điển hình đã được lựa chọn để chụp ảnh kính hiển vi điện tử quét và được ứng dụng trong hai bể sinh học với dung tích 2 lít có chứa và không chứa chất mang (giá thể). Sau 7 ngày, hệ thống sinh học chứa giá thể (chiếm 30% thể tích) có hiệu suất loại bỏ các hợp chất nitơ tăng hơn từ 1,2 đến 2 lần so với bể sinh học không chứa chất mang. Hai đại diện của nhóm vi khuẩn oxy hóa ammonia (B-1.1 và G2-1.2) đã được phân loại sơ bộ dựa vào một số đặc điểm sinh học và chúng đã được xác định thuộc chi Nitrosomonas và chi Nitrosococcus.
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Beitrag zum Tragverhalten hybrider Träger aus Glas und Kunststoff / Contribution to studies on the structural behavior of hybrid beams made of glass and plasticsHärth-Großgebauer, Kristina 19 August 2013 (has links) (PDF)
Glasträger sind in einer auf Transparenz ausgerichteten Bauweise zunehmend gefragt. Üblicherweise bestehen diese lastabtragenden Elemente aus mehreren Glasscheiben, verbunden mit Polyvinylbutyral-Folie (PVB-Folie), und gleichen in ihrem Aufbau somit Verbund-Sicherheitsglas (VSG). VSG-Träger besitzen bei vollständigem Glasbruch keine Resttragfähigkeit und werden daher in Dicke und Aufbau mit dem Ziel ausgelegt, vollständigen Glasbruch zu vermeiden. Hybride Glasträger kombinieren in der Regel Glas mit einem duktilen Material und besitzen im Falle des vollständigen Glasbruchs ein duktiles Versagensverhalten. Sie stellen damit eine vielversprechende Option zur Erfüllung des geforderten Sicherheitsniveaus bei Glasträgern dar. Die in der vorliegenden Arbeit betrachteten hybriden Träger entstehen durch die flächige Verklebung von Glas- und transparenten Kunststoffscheiben mit einem ebenfalls transparenten Klebstoff. Bei vollständigem Glasbruch stellt sich ein Tragverhalten ein, bei dem infolge des Klebstoffverbunds der Kunststoff die Zugspannungen und das gebrochene Glas weiterhin Druckspannungen aufnimmt. Die erste Auswahl von Klebstoff und Kunststoff basiert auf Voruntersuchungen an kleinformatigen Prüfkörpern. Die erforderliche Kantenqualität von Floatglas wurde anhand von Vierpunkt-Biegeuntersuchungen bestimmt. Zur weiteren Beurteilung der Eignung des Klebstoffs dienen Klimawechseltests an kleinformatigen Hybridbauteilen, da zwischen Glas und Kunststoff deutliche Unterschiede in der Temperaturausdehnung vorliegen. Aufbauend auf den durchgeführten Untersuchungen wurden das Kunststoffmaterial Polycarbonat und ein niedrigviskoser UV- und strahlungshärtender Acrylatklebstoff, der im ausgehärteten Zustand über hohe Nachgiebigkeit verfügt, für die weiteren mechanischen Untersuchungen an Prüfkörpern im Bauteilformat ausgewählt. Kurzzeitversuche mit kraftgesteuerter Belastungsaufbringung und unter Variation von Polycarbonatdicke, Trägerhöhe und Glasart geben Aufschluss über das Trag- und Resttragfähigkeitsverhalten. Sie stellen die prinzipielle Wirkweise der Hybridträger vor und nach Bruch dar. Vergleichende Versuche an VSG-Trägern demonstrieren die fehlende Resttragfähigkeit dieser Elemente. Belastungsversuche an reinen Polycarbonatscheiben verdeutlichen die Notwendigkeit der Stabilisierung der Hybridträger durch das gebrochene Glas. Langzeitversuche fanden bei statischer Belastung der intakten und gebrochenen Hybridträger statt. Lasthöhe und Belastungsdauer der gebrochenen Träger orientieren sich an realistischen Einsatzbedingungen. Die Versuche zeigen die Unterschiede bei der Entwicklung des Bruchbilds aufgrund der geringeren Last und ermöglichen die Untersuchung des Resttragfähigkeitsverhaltens unter Dauerlast sowie des Ablaufs und der Hintergründe des Trägerversagens. Aufbauend auf den durchgeführten Versuchen erfolgt eine Einteilung der unterschiedlichen Trägerzustände in drei Stadien mit Angaben zu einer einfachen analytischen Betrachtung. Die Diskussion der erhaltenen Ergebnisse sowie ein Ausblick auf weiteren Untersuchungsbedarf schließen die Arbeit ab. / In transparency-oriented architecture, glass beams are increasingly in demand. These load-bearing elements usually consist of multiple glass panes, bonded with polyvinyl butyral foil (PVB foil), and are comparable to laminated safety glass. These glass beams do not assure any level of post-breakage performance after complete glass breakage. Therefore glass thickness and assembly of the beams are chosen with the objective of avoiding complete glass breakage at all costs. Hybrid glass beams typically combine glass with a ductile material and offer a ductile failure mode in case of complete glass breakage. For this reason they represent a promising solution to meet the required safety levels for glass beams. This study deals with hybrid glass beams which are made by bonding panes of glass and transparent plastics using a transparent adhesive. In case of complete glass breakage the plastic material, which is connected to the glass by the adhesive bond, bears the tensile stress whereas the glass is still able to carry the compressive stress. The pre-selection of plastic and adhesive is based on preliminary tests on small specimens. The required quality of the edges of annealed glass was determined by specific four-point bending tests. Because of the considerable difference in thermal expansion between glass and plastics, alternating climate tests were executed on small hybrid components to further evaluate the suitability of the adhesive. Based on the research conducted, the plastic material polycarbonate and a UV- and light-curing acrylate adhesive, which shows a very flexible behavior when hardened, were chosen for further mechanical tests on larger specimens. Short-term tests with constantly increasing load and varying polycarbonate thickness, beam height and glass type provide information on the load-bearing capacity before and the residual load-bearing capacity after glass breakage of the hybrid beams. Comparative tests on laminated glass beams demonstrate the missing residual load-bearing capacity of these components. Loading tests on polycarbonate panes illustrate the need for stabilization of the hybrid beams by the broken glass. Long-term tests were executed by static loading of the intact and broken hybrid beams. The load level and the load duration of the broken beams are based on realistic working conditions. The tests show the difference in the development of the fracture pattern resulting of the lower load and allow the examination of the residual load-bearing capacity at continuous load as well as the process and the reasons behind the beam failure. Based on the tests conducted, three different states of the hybrid beams are categorized and detailed for their easy analytical approach. A discussion of the obtained results and an outlook on further needed research complete the study.
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Kollektive und Menschenrechte als moralische Rechte / Ein Beitrag zur philosophischen Diskussion um die Begründung kollektiver Menschenrechte / Collective and human rights as moral rights / A contribution to the philosophical debate about the justification of collective human rightsDávila, Johnny Antonio 11 December 2012 (has links)
Sowohl aus juristischem als auch moralischem Blickwinkel sind Menschenrechte ein unerlässliches Element der aktuellen normativen Realität. Im Bereich der moralischen Philosophie gibt es die deutliche Tendenz, Menschen als Individuen für die einzigen Träger von Menschenrechten zu halten. Die Erfahrung zeigt uns dennoch, dass das Menschenleben sich in das Kollektive widerspiegelt und dass es Kollektive wie Staaten, indigene Völker usw. gibt, deren Existenz lebenswichtig für ihre Mitglieder ist. In Anbetracht der Wichtigkeit bestimmter Kollektive im Menschenleben befasst sich diese Arbeit mit der Frage, wie es möglich ist, kollektive Menschenrechte moralisch zu begründen. Die Arbeit besteht aus drei Teilen, die begrifflich miteinander zusammenhängen. Der erste Teil konzentriert sich auf die Festlegung eines Begriffs von Menschenrechten und die Hauptthese ist, dass Menschenrechte als moralische Rechte, als nicht-juristische Rechte vor allem verstanden werden sollten. Der zweite Teil legt die wichtigsten Argumente gegen die Idee kollektiver Menschenrechte dar und es wird ebenfalls erklärt, warum diese Argumente unzulänglich sind. Es handelt sich denn um eine indirekte Argumentation für kollektive Menschenrechte. Der dritte Teil bringt Argumente vor, die die Idee kollektiver Menschenrechte direkt unterstützen. In diesem Sinne wird hier eine direkte Argumentation für diese Rechte vorgelegt.
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Kritická reflexe české divadelní kultury 1945-1948. Kontinuita a diskontinuita. / Critical reflection of Czech theater culture 1945 - 1948: Continuity and discontinuityDrexler, Otto January 2020 (has links)
The diploma thesis deals with the journalistic work of the theatre critic Josef Träger in the period of the so-called Third Republic (1945-1948). It describes the process of forming attitudes of the journalist towards post-war theatre, presents a representation of the dominant discourse and its transformation during the given period. This thesis focuses on the content analysis of theatre papers, conceived as a kind of "case study", it relates to the basic themes and problems of Czech post-war theatre. It is argued that this approach enables the analyst to pose questions concerning the ideological character of theatre criticism. This thesis discusses ideas of avant-garde creators and theorists, in whose public work it identifies the main source of inspiration for the revolutionary transformation of Czech theatre in 1945. It explores the influence of the Communist Party in the given period, targeted interventions in the Czech media and theatre system and manipulative practices leading to the strengthening of its power in the post-war state. The text also deals with the manifestations of the emerging socio-political disposition in theatre journalism, the form of the reception of post-war hegemonic formation by the journalist, and to structure the results of the analysis into a broader political-media...
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Damit's wirklich bunt bleibt - Freie Schulen in Sachsen13 May 2019 (has links)
In Deutschland soll es kein staatliches Schulmonopol geben. Darum ist die Errichtung und der Betrieb von Schulen in freier Trägerschaft grundgesetzlich verankert. Um sicher zu stellen, dass Schulen in freier Trägerschaft gleichwertige Bildungsziele verfolgen, wissenschaftlich ausgebildete Lehrkräfte beschäftigen und Schülerinnen und Schüler nicht aufgrund der Einkommensverhältnisse ihrer Eltern ausgeschlossen werden, bedürfen sie einer Genehmigung. Die Länder haben bei der Ausgestaltung der Einzelheiten der Genehmigungspraxis, der Regelung der Finanzierung und der Ausübung der Aufsicht einen großen Entscheidungs- und Ermessensspielraum. Schulen in freier Trägerschaft müssen jedoch laut Bundesverfassungsgericht „im Kern“ gleiche Kenntnisse und Fähigkeiten vermitteln und zu staatlichen Abschlüssen führen. Schulen in freier Trägerschaft sind längst auch ein fester Bestandteil der sächsischen Schullandschaft geworden. Alternative Schulkonzepte werden auch von Eltern in Sachsen gewünscht und angenommen.
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Beitrag zum Tragverhalten hybrider Träger aus Glas und KunststoffHärth-Großgebauer, Kristina 21 February 2013 (has links)
Glasträger sind in einer auf Transparenz ausgerichteten Bauweise zunehmend gefragt. Üblicherweise bestehen diese lastabtragenden Elemente aus mehreren Glasscheiben, verbunden mit Polyvinylbutyral-Folie (PVB-Folie), und gleichen in ihrem Aufbau somit Verbund-Sicherheitsglas (VSG). VSG-Träger besitzen bei vollständigem Glasbruch keine Resttragfähigkeit und werden daher in Dicke und Aufbau mit dem Ziel ausgelegt, vollständigen Glasbruch zu vermeiden. Hybride Glasträger kombinieren in der Regel Glas mit einem duktilen Material und besitzen im Falle des vollständigen Glasbruchs ein duktiles Versagensverhalten. Sie stellen damit eine vielversprechende Option zur Erfüllung des geforderten Sicherheitsniveaus bei Glasträgern dar. Die in der vorliegenden Arbeit betrachteten hybriden Träger entstehen durch die flächige Verklebung von Glas- und transparenten Kunststoffscheiben mit einem ebenfalls transparenten Klebstoff. Bei vollständigem Glasbruch stellt sich ein Tragverhalten ein, bei dem infolge des Klebstoffverbunds der Kunststoff die Zugspannungen und das gebrochene Glas weiterhin Druckspannungen aufnimmt. Die erste Auswahl von Klebstoff und Kunststoff basiert auf Voruntersuchungen an kleinformatigen Prüfkörpern. Die erforderliche Kantenqualität von Floatglas wurde anhand von Vierpunkt-Biegeuntersuchungen bestimmt. Zur weiteren Beurteilung der Eignung des Klebstoffs dienen Klimawechseltests an kleinformatigen Hybridbauteilen, da zwischen Glas und Kunststoff deutliche Unterschiede in der Temperaturausdehnung vorliegen. Aufbauend auf den durchgeführten Untersuchungen wurden das Kunststoffmaterial Polycarbonat und ein niedrigviskoser UV- und strahlungshärtender Acrylatklebstoff, der im ausgehärteten Zustand über hohe Nachgiebigkeit verfügt, für die weiteren mechanischen Untersuchungen an Prüfkörpern im Bauteilformat ausgewählt. Kurzzeitversuche mit kraftgesteuerter Belastungsaufbringung und unter Variation von Polycarbonatdicke, Trägerhöhe und Glasart geben Aufschluss über das Trag- und Resttragfähigkeitsverhalten. Sie stellen die prinzipielle Wirkweise der Hybridträger vor und nach Bruch dar. Vergleichende Versuche an VSG-Trägern demonstrieren die fehlende Resttragfähigkeit dieser Elemente. Belastungsversuche an reinen Polycarbonatscheiben verdeutlichen die Notwendigkeit der Stabilisierung der Hybridträger durch das gebrochene Glas. Langzeitversuche fanden bei statischer Belastung der intakten und gebrochenen Hybridträger statt. Lasthöhe und Belastungsdauer der gebrochenen Träger orientieren sich an realistischen Einsatzbedingungen. Die Versuche zeigen die Unterschiede bei der Entwicklung des Bruchbilds aufgrund der geringeren Last und ermöglichen die Untersuchung des Resttragfähigkeitsverhaltens unter Dauerlast sowie des Ablaufs und der Hintergründe des Trägerversagens. Aufbauend auf den durchgeführten Versuchen erfolgt eine Einteilung der unterschiedlichen Trägerzustände in drei Stadien mit Angaben zu einer einfachen analytischen Betrachtung. Die Diskussion der erhaltenen Ergebnisse sowie ein Ausblick auf weiteren Untersuchungsbedarf schließen die Arbeit ab. / In transparency-oriented architecture, glass beams are increasingly in demand. These load-bearing elements usually consist of multiple glass panes, bonded with polyvinyl butyral foil (PVB foil), and are comparable to laminated safety glass. These glass beams do not assure any level of post-breakage performance after complete glass breakage. Therefore glass thickness and assembly of the beams are chosen with the objective of avoiding complete glass breakage at all costs. Hybrid glass beams typically combine glass with a ductile material and offer a ductile failure mode in case of complete glass breakage. For this reason they represent a promising solution to meet the required safety levels for glass beams. This study deals with hybrid glass beams which are made by bonding panes of glass and transparent plastics using a transparent adhesive. In case of complete glass breakage the plastic material, which is connected to the glass by the adhesive bond, bears the tensile stress whereas the glass is still able to carry the compressive stress. The pre-selection of plastic and adhesive is based on preliminary tests on small specimens. The required quality of the edges of annealed glass was determined by specific four-point bending tests. Because of the considerable difference in thermal expansion between glass and plastics, alternating climate tests were executed on small hybrid components to further evaluate the suitability of the adhesive. Based on the research conducted, the plastic material polycarbonate and a UV- and light-curing acrylate adhesive, which shows a very flexible behavior when hardened, were chosen for further mechanical tests on larger specimens. Short-term tests with constantly increasing load and varying polycarbonate thickness, beam height and glass type provide information on the load-bearing capacity before and the residual load-bearing capacity after glass breakage of the hybrid beams. Comparative tests on laminated glass beams demonstrate the missing residual load-bearing capacity of these components. Loading tests on polycarbonate panes illustrate the need for stabilization of the hybrid beams by the broken glass. Long-term tests were executed by static loading of the intact and broken hybrid beams. The load level and the load duration of the broken beams are based on realistic working conditions. The tests show the difference in the development of the fracture pattern resulting of the lower load and allow the examination of the residual load-bearing capacity at continuous load as well as the process and the reasons behind the beam failure. Based on the tests conducted, three different states of the hybrid beams are categorized and detailed for their easy analytical approach. A discussion of the obtained results and an outlook on further needed research complete the study.
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Tissue Engineering von Knochen-Vergleichende Untersuchung der Differenzierung humaner Knochenmarkstromazellen (hBMSC) auf Kalziumkarbonat-Biomaterialien unter Verwendung zweier unterschiedlicher Besiedelungstechniken / Bone Tissue Engineering- comparative study of human bone marrow stroma cells (hBMSC) differentiation in calcium carbonate scaffolds using two different seeding methodsLohse, Nils 19 October 2011 (has links)
No description available.
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