Energy dissipation in laser-based free form heading: a numerical approach

Cold forming generally allows the fast generation of parts with very low tolerances. In addition, mechanical properties are improved, if work hardening materials are used. Transferring the cold forming process to micro range leads to a decrease in the maximum achievable upset ratio so that the forming process becomes inefficient. Therefore, a laser-based free form heading process has been developed to generate preforms which can be calibrated in a secondary cold forming step. The achievable upset ratios reach values of several hundreds instead of 2.1 which is common for single step mechanical upsetting. In this article, heat losses arising in the material accumulation process using laser-based free form heading are analyzed and discussed. For this purpose, the process is modeled within the framework of continuum mechanics and simulated by a finite element method. By using a numerical approach, a systematic study on heat losses is performed in order to identify the influence of radiation, heat transfer due to convection and thermal conduction during laser irradiation time. The simulation results, which are validated with experimental data, show that the radiation is the most important mechanism reducing the efficiency of the accumulation process.     

Coupling Interrupted Fischer and Multicomponent Joullié-Ugi to Chase Chemical Diversity: from Batch to Sustainable Flow Synthesis of Peptidomimetics

The generation of peptidomimetic substructures for medicinal chemistry purposes requires effective and divergent synthetic methods. We present in this work an efficient flow process that allows quick modulation of reagents for Joullié-Ugi multicomponent reaction, using spiroindolenines as core motifs. This sterically hindered imine equivalent could successfully be diversified using various isocyanides and amino acids in generally good space-time yields. A telescoped flow process combining interrupted Fischer reaction for spiroindolenine synthesis and subsequent Joullié-Ugi-type modification resulted in product formation in very good overall yield in less than 2 hours compared to 48 hours required in batch mode. The developed protocol can be seen as a general tool for rapid and facile generation of peptidomimetic compounds. We also showcase preliminary biological assessments for the prepared compounds.     

A case study in the mechanical verification of fault tolerance

To date, there is little evidence that modular reasoning about fault-tolerant systems can simplify the verification process in practice. This question is studied using a prominent example from the fault tolerance literature: the problem of reliable broadcast in point-to-point networks subject to crash failures of processes. The experiences from this case study show how modular specification techniques and rigorous proof re-use can indeed help in such undertakings.     

The Role of Oncostatin M and Its Receptor Complexes in Cardiomyocyte Protection,Regeneration, and Failure

Oncostatin M (OSM), a member of the interleukin-6 family, functions as a major mediator of cardiomyocyte remodeling under pathological conditions. Its involvement in a variety of human cardiac diseases such as aortic stenosis, myocardial infarction, myocarditis, cardiac sarcoidosis, and various cardiomyopathies make the OSM receptor (OSMR) signaling cascades a promising therapeutic target. However, the development of pharmacological treatment strategies is highly challenging for many reasons. In mouse models of heart disease, OSM elicits opposing effects via activation of the type II receptor complex (OSMR/gp130). Short-term activation of OSMR/gp130 protects the heart after acute injury, whereas chronic activation promotes the development of heart failure. Furthermore, OSM has the ability to integrate signals from unrelated receptors that enhance fetal remodeling (dedifferentiation) of adult cardiomyocytes. Because OSM strongly stimulates the production and secretion of extracellular proteins, it is likely to exert systemic effects, which in turn, could influence cardiac remodeling. Compared with the mouse, the complexity of OSM signaling is even greater in humans because this cytokine also activates the type I leukemia inhibitory factor receptor complex (LIFR/gp130). In this article, we provide an overview of OSM-induced cardiomyocyte remodeling and discuss the consequences of OSMR/gp130 and LIFR/gp130 activation under acute and chronic conditions.     

Untersuchungen zum Transfer pharmakologisch wirksamer Substanzen aus der Nutztierhaltung in Porree und Weißkohl

Investigation on the transfer of pharmacologically active substances used in animal husbandry into leek and cabbage. The potential of leek and cabbage for uptake of highly prescribed veterinary drugs (antibiotics) was tested in hydroponically grown plants. For this purpose the antibiotics sulfadiazine (SFD), enrofloxacine (ENR), tetracycline (TC), chlortetracycline (CTC) and monensine (MON) were chosen. A further aim was to gain data on the situation of vegetables grown in agricultural practise with regard to antibiotic residues. The evident effects of the antibiotics on plants grown hydroponically (each antibiotic was administered at 5 μmol/l nutrient solution) were greatly different: With regard to leek there were no visible effects (MON, SFD), a weak bleaching of the younger leaf sections (CTC), and strong effects of ENR. The (phytotoxic) effects of antibiotics on cabbage were much more distinct. CTC caused a yellowing of the plant vasculature in cabbage. MON induced lesions on some leaves and finally led to leaf wilting. With administration of ENR a nearly complete bleaching of young leaves was observed. Using LC-MS/MS-methods (low-resolution and high-resolution MS) the administered antibiotics, as well as conversion products and metabolites, were separately identified and quantified in various organs of leek (roots, young and old sections of leaves) and cabbage (roots, stalks, young and old leaves). Depending on the type of antibiotic, vegetable species, and plant organ, the detected concentrations of antibiotic residues comprised several orders of magnitude ranging from μg/kg to mg/kg of fresh weight (fw). The highest concentrations of antibiotics were found in roots of both vegetable species: CTC and TC were detected at approximately 10 mg/kg fw in cabbage roots and at approximately 20 mg/kg fw in leek roots and ENR was determined at approximately 12 mg/kg fw in cabbage roots. Low amounts of ENR were metabolised to ciprofloxacine (CIP). ENR occurred at similar concentrations of approximately 7 mg/kg fw in roots and old leaves of cabbage, indicating a high transport rate of this antibiotic in the cabbage plant. In stalks, young and old leaves of cabbage and in young and old leaf sections of leek all administered antibiotics were detected. Within these antibiotics, ENR and CTC and their conversion products, e. g. demeclocycline (DMC) and TC, occurred at the highest concentrations. SFD and MON were found in considerably lower concentrations (<100 μg/kg fw). The results of our experiments in hydroponic cultures, using defined concentrations of antibiotics in the nutrient solution, evidently demonstrate that cabbage and leek have a very high potential for uptake of a number of veterinary antibiotic drugs, especially for tetracycline and ENR.     

Neuregelungen in Vorarlberg zu Spielräumen

Ein Ma?nahmenpaket, bestehend aus dem Spielraumgesetz, dem Beschluss von entsprechenden F?rderungsrichtlinien sowie Novellierungen des Baugesetzes und der Kinderspielplatzverordnung und einer überarbeitung der Wohnbaufondsrichtlinie, soll dazu beitragen, dass sich das Bundesland Vorarlberg als besonders kinder- und jugendfreundliche Region etabliert. Hiefür gilt es, ?ffentliche und private Spielpl?tze und Freir?ume bedarfsgerecht zu erhalten, zu sanieren, neu zu errichten und untereinander zu vernetzen.