Die Analyse der Inhibition des Monozyten chemotaktischen Proteins-1 (MCP-1) und der Stimulation durch MCP-1 auf die Koloniebildung und die Zytokinexpression von Plattenepithelkarzinomen der Kopf-Hals-Region im FLAVINO-Assay

Das Monozyten chemotaktische Protein-1 (MCP-1) ist ein CC-Chemokin, das in seiner Rolle als Chemoattraktor auf Monozyten in der Genese von Malignomen eine wesentliche Rolle spielt. Dabei kann es sowohl zur lokalen Tumorabwehr als auch zur Tumorgenese, Tumor-angiogenese und Metastasierung beitragen. Die vorliegende Arbeit untersucht die MCP-1-Inhibition und die Stimulation durch MCP-1 auf die Koloniebildung und die Zytokinexpression von Plattenepithelkarzinomen der Kopf-Hals-Region (HNSCC) im FLAVINO-Assay. Dieser ist ein klonogener, qualitätskontrollierter Ex-vivo-Koloniebildungsassay, der an der Klinik für Hals-Nasen-Ohrenheilkunde der Universität Leipzig etabliert und patentiert wurde und unter flavinschützenden Bedingungen durchgeführt wird. Weiterhin wird die Eignung von MCP-1, Interleukin-6 (IL-6), Interleukin-8 (IL-8) und des Vascular endothelial growth factor (VEGF) als Biomarker in HNSCC, die mithilfe von ELISA in Seren und Kulturüberständen quantifiziert wurden, untersucht. Durch die Stimulation durch MCP-1 und dessen Blockade sowie durch in vivo tolerierbare Konzentrationen von Cisplatin, Docetaxel, Cilengitide und Temsirolimus wurde die Expression der untersuchten Zytokine in den Kulturüberständen der HNSCC unterschiedlich moduliert. Cisplatin und MCP-1 supprimierten die Koloniebildung signifikant, während unter Docetaxel und Temsirolimus eine insignifikante Reduktion und durch Cilengitide eine insignifikante Stimulation der Koloniebildung beobachtet wurde. Die MCP-1-Blockade durch einen Anti-MCP-1-Antikörper führte zu keiner signifikanten Modulation der Koloniebildung. MCP-1 und der Anti-MCP-1-Antikörper senkten die Zytokinexpression, während bis auf Cisplatin alle Zytostatika die Zytokinexpressionen steigerten. Bezüglich der kombinierten Testung der Zytostatika und der MCP-1-Blockade bzw. Stimulation unterschieden sich die Proben, sodass additive, synergistische und antagonistische Effekte resultierten. Da durch MCP-1 gesteuerte tumorassoziierte Makrophagen das Mikromilieu eines Tumors wesentlich beeinflussen, gebührt diesen ebenfalls eine besondere Aufmerksamkeit. In dieser Arbeit wurden unter MCP-1 antitumoröse Effekte beobachtet, sodass weitere klinische Testungen der antitumorösen Wirkung des MCP-1 auf HNSCC lohnenswert erscheinen. Die individuelle Chemoresponse-Testung kann dabei helfen, das biologisch heterogene Verhalten der HNSCC besser zu verstehen. In diesem Sinne wäre die klinische Validierung solcher Testsysteme wertvoll

Wrought Al - Cast Al compound casting based on zincate treatment for aluminum wrought alloy inserts

AbstractThe surface properties of solid inserts are critical to the development of a reaction zone in compound castings. In contrast to prior works (based on Al99.5) the goal of this paper is to apply the zincate treatment to different aluminum wrought alloys. This enables the possibility to create compound structures with enhanced mechanical properties. During zincate treatment the aluminum oxide layers are dissolved and a thin layer of zinc (<500nm) prevents reoxidation. Coating parameters are optimized especially for compound castings: maximum coverage of the surface and high coating adhesion implemented by double zincate treatment. The pretreated inserts are embedded in an aluminum component by high pressure die casting. A sound metallic bonding between both aluminum alloys develops due to diffusion and reaction zones. Mechanical tests confirm a sound metallic bonding. Depending on the integrated wrought alloy enhanced mechanical properties of the compound structure can be achieved. Microprobe and fracture analysis provide detailed information about the interface properties of the compound structure, which can be enhanced by thermal treatment

Electron-optical in-situ metrology for electron beam powder bed fusion: calibration and validation

AbstractA major advantage of metal additive manufacturing is the possibility for tool-free production of complex shaped parts. Currently, the geometrical and dimensional accuracy of these parts can only be reliably controlled by time and cost intensive post-process inspection, e.g. using x-ray computed tomography (XCT). The current investigation demonstrates the first in-situ metrology technique for electron beam powder bed fusion (PBF-EB) using electron-optical imaging (ELO). After a calibration experiment, the approach was validated for a PBF-EB build job by comparing in-situ ELO imaging data to XCT data of an as-built part. The quantitative comparison showed a remarkable high agreement between both imaging techniques. It is demonstrated that ELO imaging is capable of making accurate predictions on the geometrical and dimensional accuracy of the as-build part. This result is the basis of new possibilities for in-situ process and quality control in PBF-EB

Structure Design of Soft Magnetic Materials Using Electron‐Beam‐Based Additive Manufacturing

Fe93.5Si6.5 (wt%) soft magnetic materials in toroidal shape are additively manufactured by means of electron beam powder bed fusion (PBF‐EB). Different hatching strategies are applied to realize specific patterns of molten material alternating with non‐molten powder particles. The specimens produced using different hatching strategies show identical relative densities but various structural features resulting in different magnetic properties. The magnetic performance of the specimens is characterized by determining hysteresis loops (B–H curves), power losses, and maximum magnetic flux density at frequencies between 50 and 1000 Hz. At constant mass, the different structures induced by using various hatching strategies have a strong influence on the hysteresis losses. These losses can be significantly reduced by applying a targeted structure design. The modified specimens show superior magnetic properties at sub‐kHz compared to some soft magnetic materials fabricated by means of conventional methods and laser powder bed fusion (PBF‐L).Fe93.5Si6.5 (wt%) toroidal cores with tailored structures fabricated by electron beam powder bed fusion using specifically developed hatching strategies (i.e., radial hatching and circle hatching) show promising magnetic properties (i.e., low power losses and high maximum magnetic flux density), outperforming some soft magnetic materials produced by conventional techniques and laser powder bed fusion. image China Scholarship Council http://dx.doi.org/10.13039/50110000454

A Single Crystal Process Window for Electron Beam Powder Bed Fusion Additive Manufacturing of a CMSX-4 Type Ni-Based Superalloy

Using suitable scanning strategies, even single crystals can emerge from powder during additive manufacturing. In this paper, a full microstructure map for additive manufacturing of technical single crystals is presented using the conventional single crystal Ni-based superalloy CMSX-4. The correlation between process parameters, melt pool size and shape, as well as single crystal fraction, is investigated through a high number of experiments supported by numerical simulations. Based on these results, a strategy for the fabrication of high fraction single crystals in powder bed fusion additive manufacturing is deduced

Modeling and Simulation of Microstructure Evolution for Additive Manufacturing of Metals: A Critical Review

Abstract Beam-based additive manufacturing (AM) of metallic components is characterized by extreme process conditions. The component forms in a line-by-line and layer-by-layer process over many hours. Locally, the microstructure evolves by rapid and directional solidification. Modeling and simulation is important to generate a better understanding of the resultant microstructure. Based on this knowledge, the AM process strategy can be adapted to adjust specific microstructures and in this way different mechanical properties. In this review, we explain the basic concepts behind different modeling approaches applied to simulate AM microstructure evolution of metals. After a critical discussion on the range of applicability and the predictive power of each model, we finally identify future tasks

Design and Additive Manufacturing of 3D Phononic Band Gap Structures Based on Gradient Based Optimization

We present a novel approach for gradient based maximization of phononic band gaps. The approach is a geometry projection method combining parametric shape optimization with density based topology optimization. By this approach, we obtain, in a two dimension setting, cellular structures exhibiting relative and normalized band gaps of more than 8 and 1.6, respectively. The controlling parameter is the minimal strut size, which also corresponds with the obtained stiffness of the structure. The resulting design principle is manually interpreted into a three dimensional structure from which cellular metal samples are fabricated by selective electron beam melting. Frequency response diagrams experimentally verify the numerically determined phononic band gaps of the structures. The resulting structures have band gaps down to the audible frequency range, qualifying the structures for an application in noise isolation

A new approach of preheating and powder sintering in electron beam powder bed fusion

Preheating is an essential process step in electron beam powder bed fusion. It has the purpose of establishing a sintered powder bed and maintaining an elevated temperature. The sintered powder bed reduces the risk of smoke and in combination with the elevated temperature improves the processability. Today, the line-ordering preheating scheme is widely used. This scheme does not take the previously built layers into account and results in an inhomogeneous elevated temperature and consequently in a variety of sinter degrees, which is disadvantageous for the process. The main challenge is now to modify this scheme to establish a homogeneous temperature distribution. This study addresses this challenge and analyses as well as optimises this scheme. A GPU-parallelised thermal model reveals a heterogeneous temperature distribution during preheating because of varying thermal conditions within a build job. In addition, a work-of-sintering model predicts that the sinter degree of the current powder layer on top of previously consolidated material is smaller than on top of the surrounding powder bed. This work aims to invert this trend to improve powder re-usage and material consolidation. Consequently, this work proposes an extension of the current scheme, compensating for the specific energy loss with local adjustments to the energy input. This adaption results in a uniform temperature distribution and advantageous sintering. Applying the proposed numerical model proves to be an effective method to analyse the evolving process conditions and tailor the local energy input, thereby improving the efficiency of the preheating step