04 Fakultät Energie-, Verfahrens- und Biotechnik
Permanent URI for this collectionhttps://elib.uni-stuttgart.de/handle/11682/5
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Item Open Access A model-based framework for the assessment of energy-efficiency and CO2-mitigation measures in multi-cylinder paper drying(Stuttgart : Universität Stuttgart, Institut für Energiewirtschaft und Rationelle Energieanwendung, 2022) Godin, Hélène; Radgen, Peter (Prof. Dr.-Ing.)Thesis on the effect of energy-efficiency and CO2-mitigation measures in multi-cylinder paper drying.Item Open Access Untersuchung einer Augmented Reality Kollaborationssoftware in der verteilten agilen Arbeitsweise der Automobilentwicklung(2024) Dyhringer, Robert; Resch, Michael (Prof. Dr.-Ing. Dr. h.c. Dr. h.c. Prof. e.h)Der Begriff Metaverse motiviert seit 2021 neue Forschung in der Wissenschaft, insbesondere in der Automobilentwicklung. Die Kombination von agilen Arbeitsweisen und verteilter Zusammenarbeit wirft neue Herausforderungen auf, die durch den Einsatz einer kollaborativen Augmented Reality Software bewältigt werden können. Eine methodisch entwickelte Software und wissenschaftliche Studien zeigen in dieser Arbeit, dass die Technologie der Augmented Reality die gleichberechtigte Gruppenarbeit und die Kommunikation in einem agilen Setup verbessern kann.Item Open Access Engineered antibodies for the therapy of cancer and inflammatory diseases(2010) Zettlitz, Kirstin Anja; Kontermann, Roland (Prof. Dr.)Detailed knowledge of the antibody structure and function allows researchers to engineer antibodies on a rational basis to design therapeutic antibodies dependent on the target antigen, therapeutic strategy and clinical setting. The development of therapeutic antibodies is a rapidly growing field with more than 30 antibodies approved over the past 25 years. Thereof, cancers as well as autoimmune and inflammatory diseases are the main indications. The purpose of the first part of this thesis was the cloning, chimerization and humanization of the monoclonal antibody (mAb) cmHsp70.1. This mouse mAb is specific for heat shock protein 70 (Hsp70) and able to bind the plasma membrane bound form (mHsp70), associated with various cancers including breast cancer, head-and-neck cancer, and acute myeloid leukemia. Humanization of cmHsp70.1 by grafting the complementarity-determining regions onto homologous human germline genes resulted in an antibody (humex) possessing a similar affinity (3 nM) as the parental antibody and an improved production and thermal stability. Epitope mapping confirmed that the parental, chimeric, and humanized antibodies recognize the same region including amino acids 473-504 of the Hsp70 substrate binding domain (SBD). Hence, this humanized antibody provides a basis for further development of a mHsp70-specific antibody therapy. The purpose of the second part of this thesis was to evaluate an appropriate format and an optimization strategy for a humanized antibody (IZI-06.1) specific for human tumor necrosis factor receptor 1 (TNFR1). Selective inhibition of TNFR1 provides the opportunity to neutralize the pro-inflammatory activity of TNF while maintaining the advantageous immunological responses mediated by TNFR2. Here, this humanized antibody was converted into an IgG1 molecule (ATROSAB) containing a modified human Fc region deficient in mediating effector functions. IgG ATROSAB was compared to monovalent antibody derivatives fused to human serum albumin (HSA). Using chimeric human/mouse TNFR1 molecules, the epitope of ATROSAB was mapped to the N-terminal region (amino acid residues 1-70) comprising the first cysteine-rich domain (CRD1) and the A1 sub-domain of CRD2. Purified ATROSAB, produced in CHO cells, inhibited in vitro typical TNF-mediated responses like apoptosis induction and activation of NFκB-dependent gene expression such as IL-6 and IL-8 production. Moreover, ATROSAB showed strong binding to human and rhesus TNFR1-Fc fusion protein with an affinity identical to the parental mouse antibody H398. These findings open the way to further analyze the therapeutic activity of ATROSAB in relevant disease models in non-human primates. Furthermore, phage display technology was used for affinity maturation of the humanized variable domains by site directed mutagenesis of CDR1 and CDR2 of each VH and VL. Attempts towards affinity maturation resulted in a mutant (scFv IG11) showing a two-fold increase in antigen binding affinity which also translated into slightly improved inhibition of TNF-mediated cytotoxicity in vitro. The results of this study indicate that further engineering of ATROSAB could offer a number of benefits for its therapeutic efficacy. TNFR1-selective antagonist, such as ATROSAB, will permit new therapeutic options for diseases where anti-TNF therapeutics failed or even exacerbate disease progression and could be an especially useful therapeutic alternative in diseases already known to clinically respond to anti-TNF treatment and particularly in those diseases where specific blockage of TNFR1 and maintenance of TNFR2 function appears as a promising therapeutic approach.Item Open Access Enzymkatalysierte regioselektive N-Methylierung und N-Alkylierung von Pyrazolen(2021) Bengel, Ludwig L.; Hauer, Bernhard (Prof. Dr.)Item Open Access Development of a viscoplastic-damage model for creep-fatigue FE-calculations of the lead-free SnAgCu solder alloy for automotive applications(Stuttgart : Materialprüfungsanstalt (MPA), Universität Stuttgart, 2019) Métais, Benjamin; Weihe, Stefan (Prof. Dr.-Ing)Automotive electronic devices are exposed to substantially harsher thermomechanical loads compared to commercial consumer electronic products. Inside an electronic device, there is a large number of solder joints, supporting the electrical as well as the mechanical interconnections. In terms of mechanical properties, solder joints are a weak point of the whole device assembly and can ultimately determine its reliability. In the past two decades, significant efforts have been made to set up methodologies for lifetime prediction of solder joints in automotive applications. Finite Element Analysis (FEA) is being increasingly employed with the aim to support product design and qualification process. However, constitutive FE models for solder alloys capable of describing their mechanical behavior at the relevant conditions of automotive applications are still not widely established. The currently employed state of the art material models applied in industry and research are based on uni-axial stationary creep. Thus, they naturally fail to describe properly the complex cyclic time-, strain rate, and temperature dependent behavior under the full temperature range of accelerated qualification lab tests and operation conditions. Furthermore, intrinsic degradation processes due to cyclic thermo-mechanical loading are not still completely investigated and are not taken into account within FE-calculations. Current FE-reliability prediction methodologies for solder joints are not possible without the usage of lifetime models (e.g. Coffin-Manson) and their calibration on a substantial set of experimental data. Due to the lack of models mapping intrinsic material degradation, the current prediction methods remain strongly constraint to a single solder type and loading conditions used within the lifetime experiments. More advanced techniques, originally proposed for steel alloys, employ viscoplastic constitutive models and damage mechanics and provide a powerful framework for predictive FE-based lifetime assessment. The goal of the present work is to build on these concepts and extend them for usage in solder joint simulations. An important part of the methodology development is the advanced experimental characterization necessary to obtain the material behavior, which extends the currently available research activities on solder alloys. The experimental investigations are focused on the intrinsic mechanical and aging properties of a Sn-based solder alloy and used for the formulation of a suitable FE-material model within the frame of damage mechanics. Within the thesis, a material testing procedure has been developed in order to perform mechanical characterization on standardized specimens. The test program includes strain rate controlled cycling, stress relaxation phases, uniaxial and multiaxial Low Cycle Fatigue (LCF) as well as creep tests in the temperature range: -40°C up to 125°C. As a first step, the mechanical and microstructure properties of the material in the initial state prior degradation are investigated. A viscoplastic material model of two viscous functions originally proposed by Chaboche et al. has been numerically implemented for 3D simulations. The model maps the observed stress dependence on temperature, time and strain-rate of the alloy in both low and high strain rate regimes. A step by step procedure for calibration of the model parameters in the temperature range -40/125°C is detailed and discussed. As a second step, aging mechanisms are investigated by means of creep and fatigue tests. A lifetime concept based on creep-fatigue partitioning is worked out and applied for the lifetime assessment of a real Surface Mounted Device (SMD) chip resistor under temperature cycling. The method’s predictions are correlated to reported experimental lifetime data within the project LiVe [1]. The proposed creep-fatigue partitioning approach provides means for fast estimation of solder joint reliability and might be used as a support of the design process of electronic devices. Finally, a full Continuum Damage Mechanics (CDM) model, which involves intrinsic damage propagation inside the material, has been developed and implemented for 3D simulations. Based on the observed aging properties, the damage model formulation takes into account local material softening due to creep-fatigue interaction. The CDM-simulation reveals the evolution of degradation in the solder joint component throughout its complete loading history. The main findings are discussed and put into perspective for future works dedicated to the implementation of the CDM approach for reliability prognosis and engineering lifetime concepts.Item Open Access Charakterisierung einer Familie von Pry-Proteinen in Candida albicans(2010) Röhm, Marc; Brunner, Herwig (Prof. Dr.)Die Mitglieder der Superfamilie der CAP-Proteine sind ubiquitär verbreitet und zeichnen sich durch eine konservierte zentrale Domäne aus, die ihnen eine außerordentlich stabile drei-dimensionale Struktur verleiht und die den strukturellen Anforderungen extrazellulär wirkender Proteine entspricht. Der Grad der Sequenz- und Strukturhomologien dieser Proteine deutet auf einen ähnlichen Wirkmechanismus hin, die molekulare Funktion der CAP-Proteine ist bis heute jedoch unklar. In dieser Arbeit wurde eine bisher nicht beschriebene Familie von CAP-Proteinen in C. albicans identifiziert und deren Mitglieder funktionell charakterisiert. In Analogie zu S. cerevisiae sollen diese als Pry-Proteine bezeichnet werden (pathogenesis-related in yeast). Die Pry-Proteinfamilie in C. albicans umfasst 5 Mitglieder, die im Zusammenhang mit der Morphogenese von C. albicans (Hefe – Hyphe, white – opaque) differentiell reguliert sind. Alle 5 Familienmitglieder weisen spezifische strukturelle Merkmale sekretierter Proteine auf. Transkriptionelle Studien zeigen, dass die beiden Pry-Proteine Rbe1p und Rbt4p von den zentralen Regulatoren der Morphogenese in C. albicans, Efg1p und Tup1p, gegensätzlich reguliert werden. Dabei wird Rbe1p v.a. in Blastosporen und opaque-Zellen, Rbt4p degegen in Hyphen exprimiert. Die Promotorsequenz von RBE1 umfasst 1039 bp und enthält eine aktivierende und eine reprimierende Domäne für die Transkription. Obwohl diese mehrere mögliche Bindestellen für Efg1p aufweisen, bindet heterolog exprimiertes Efg1p offensichtlich nicht an den RBE1-Promotor, so dass die Regulation von RBE1 voraussichtlich indirekt durch Efg1p erfolgt. Massenspektrometrische Analysen des C. albicans-Sekretoms weisen Rbe1p und Rbt4p als sekretierte Proteine in C. albicans aus. Dabei ist Rbe1p ein spezifisch von Blastosporen sekretiertes Protein, während Rbt4p ein Bestandteil des Sekretoms von Blastosporen und Hyphen ist. Heterolog exprimiertes Rbe1p und Rbt4p zeigen keine für die CAP-Proteine postulierte Funktion als Protease. Deletionsstudien für RBE1 und RBT4 in SC5314 zeigen keinen Phänotyp auf gängigen Labormedien, sowie keine Beteiligung an der Adhäsion und Invasion humanen Epithelgewebes. In Kombination führt die Deletion beider Gene allerdings zu einer starken Attenuation der Virulenz in einem intravenösen Mausmodell für systemische Kandidosen. Diese tritt bei einer Deletion nur eines der beiden PRY-Gene nur schwach zutage, da in diesen Stämmen das jeweils andere PRY-Gen kompensatorisch induziert wird. Dieser synergistische Virulenzphänotyp spricht für eine ähnliche Funktion der beiden Proteine sowie für eine Regulation durch ähnliche Signalwege.