A CAD/CAM concept for High Speed Cutting compatible rough machining in die, mould and pattern manufacturing

Die, mould and pattern manufacturing plays a central role in the production of capital and consumer goods. Ever-shorter product life cycles and the expanding diversity of features require continued cuts in production lead times. Recently, these developments in the market, accompanied by a simultaneous demand for improved quality at a lower cost, are becoming clearly noticeable. Along with the streamlining of organizational structures and advanced technological developments, it is above all the introduction of CAD/CAM software that offers great potential for reducing lead times for components with free surfaces. The role of milling in the integrated process chain of die, mould and pattern manufacturing is steadily gaining importance. This is due to the ongoing further development of milling-machine technology, the cutting tools and their coatings, and of the CAD /CAM systems themselves. Generally speaking, the milling process is divided into the operations of roughing and finishing. For rough milling, efficient machining means high stock-removal rates together with close contour approximation and low tool wear. Rough milling is normally carried out layer by layer, i.e. in a 2.SD machining operation with constant depth per cut because the rate of material removal and process reliability are usually highest when this method is used. High-speed cutting (HSC), which has been the subject of extensive university research for far more than ten years, has meanwhile become established as a finishing process in many companies. However, the application of HSC demands the observance of geometric and, above all, technological constraints. A considerable degree of optimization can be achieved when these constraints are applied to rough milling. In the integrated process chain, the CAD/CAM system performs the task of calculating NC programs based on CAD data which meet the requirements posed by rough and finish machining operations. While general interest was focused on the development of CAM strategies for HSC finish machining, advanced development of technology-oriented CAM modules for upstream roughing operations was neglected. The paper at hand deals with the development of a CAM module for rough-machining complex components in die, mould and pattern manufacturing. It provides an insight into the process-technological demands made on HSC operations and their application in rough machining, from which guidelines and requirements on technologically oriented NC functions for CAM software were derived. These encompass both the complete development of an interactive, dialogue-based user guidance function and the algorithmic conversion of the calculation routines. The concept at hand was almost entirely implemented and integrated in the CAD/CAM system developed by Tebis AG, Germany, which was conceived especially for die, mould and pattern manufacturing and is scheduled for introduction to the free market starting in April 2001

Development of In Vitro Models and Analytical Methods to Assess the In Vivo Stability of Therapeutic Proteins

Maintaining the stability of therapeutic proteins is a hallmark of successful drug product (DP) development. The stability of DPs is closely monitored during various stages such as development, manufacturing, and in clinical preparation. However, the stability of a DP can change considerably after administration (in vivo stability). Assessing protein stability under physiologic conditions can improve the safety and efficacy profile of commercial DPs. The first part of the thesis focuses on protein aggregation and fragmentation of monoclonal antibodies (mAbs), after simulated intravenous administration. The molecules showed markedly different stability in human serum with some mAbs being subjected to substantial fragmentation, while others remained stable. Moreover, substantial sub-visible particle formation in serum was detected with developed methods such as fluorescence microscopy and flow cytometry. In the second part of this thesis, we simulated the subcutaneous administration of mAbs without fluorescence labeling. In line with our previous observations, mAb candidates had substantial differences in their stability under physiologic conditions. Furthermore, we showed that phosphate-buffered saline does not stress mAbs to the same extent as bicarbonate-buffers and human serum. The in vivo stability of therapeutic proteins should be an integral part of holistic stability assessments during early stages of development

On the application of projection methods for computing optical flow fields

Detecting optical flow means to find the apparent displacement field in a sequence of images. As starting point for many optical flow methods serves the so called optical flow constraint (OFC), that is the assumption that the gray value of a moving point does not change over time. Variational methods are amongst the most popular tools to compute the optical flow field. They compute the flow field as minimizer of an energy functional that consists of a data term to comply with the OFC and a smoothness term to obtain uniqueness of this underdetermined problem. In this article we replace the smoothness term by projecting the solution to a finite dimensional, affine subspace in the spatial variables which leads to a smoothing and gives a unique solution as well. We explain the mathematical details for the quadratic and nonquadratic minimization framework, and show how alternative model assumptions such as constancy of the brightness gradient can be incorporated. As basis functions we consider tensor products of B-splines. Under certain smoothness assumptions for the global minimizer in Sobolev scales, we prove optimal convergence rates in terms of the energy functional. Experiments are presented that demonstrate the feasibility of our approach

Central corneal thickness in spectral-domain OCT and associations with ocular and systemic parameters

Background. Optical coherence tomography (OCT) allows quantitative analysis of the anterior segment of the eye with a noncontact examination. The aim of this study is to analyze associations of central corneal thickness (CCT) as measured by OCT with ocular and systemic cardiovascular parameters. Methods. A cross-sectional study of 734 persons was performed in a working age population. Only healthy eyes were included. A comprehensive ophthalmological examination including refraction, noncontact tonometry, and imaging of the anterior segment by SD-OCT was performed. In parallel, a broad range of systemic cardiovascular parameters were measured. Associations were analyzed using a generalized estimating equations&#039; model. Results. CCT measurements showed a significant association with corneal curvature and intraocular pressure: a thinner CCT was associated with a flatter cornea and with lower intraocular pressure (p < 0.001). Age was positively associated with CCT (p < 0.001); all other cardiovascular parameters were not associated. Conclusion. A thinner cornea is associated with a flatter surface and with lower intraocular pressure readings, while there are no independent associations with refraction and systemic cardiovascular parameters. Our findings highlight the value of SD-OCT CCT measurements as a standard tool in anterior segment analysis

Robustness and epistasis in mutation-selection models

We investigate the fitness advantage associated with the robustness of a phenotype against deleterious mutations using deterministic mutation-selection models of quasispecies type equipped with a mesa shaped fitness landscape. We obtain analytic results for the robustness effect which become exact in the limit of infinite sequence length. Thereby, we are able to clarify a seeming contradiction between recent rigorous work and an earlier heuristic treatment based on a mapping to a Schr\"odinger equation. We exploit the quantum mechanical analogy to calculate a correction term for finite sequence lengths and verify our analytic results by numerical studies. In addition, we investigate the occurrence of an error threshold for a general class of epistatic landscape and show that diminishing epistasis is a necessary but not sufficient condition for error threshold behavior.Comment: 20 pages, 14 figure