Cost-benefit analysis for disruption prevention in low-volume assembly

Manufacturing companies face rising pressure due to increased competition. Traditionally, companies have merely concentrated on offering impeccable, cost-efficient products. Today, however, flexibility and on-time delivery are additional requirements to satisfy the customers. At the same time, disruptions in production, especially in low-volume assembly, still frequently occur, leading to economic losses and delayed customer deliveries. The approach proposed in this paper strives for improving the disruption situation in low-volume assemblies. A detailed disruption management methodology has been developed, aiming at realizing an efficient reduction of disruptions, while at the same time considering the specific characteristics of low-volume assembly. The methodology is supported by a catalog of pre-emptive measures. These measures are known to reduce the disruptions’ occurrence or to diminish their consequences. In general, the approach pursues the basic idea to implement particularly those measures, which have the best cost-benefit-ratio. Based on the analysis of the cost-benefit-ratio of each measure, the developed methodology aims at improving the disruption situation in assembly and thus providing a high on-time delivery rate. The usability of the methodology for the low-volume assembly context has been confirmed by assembly experts on the basis of an application of the methodology in an exemplary case study.     

Blends of thermoplastic polyurethane and maleic-anhydride grafted polyethylene. I: Morphology and mechanical properties

Thermoplastic polyurethane elastomers (TPU) and polyethylene (PE) form immiscible blends with an extremely low compatibility. In order to improve the dispersion, stability, and properties of these blends, polyethylene was grafted with maleic anhydride (PE-g-MA). Subsequently, it was blended with a commercial polyester - type TPU in a twin-screw extruder. With PE-g-MA as blend component, the particle size was dramatically reduced in comparison with PE. Coalescence was significantly reduced and the increase in particle size with composition was less pronounced than in blends with PE. In addition, the phase adhesion and the mechanical properties were improved by using PE-g-MA as minor component. Grafting of the MA onto the PE leads to a decrease of the molecular weight, the melt viscosity, and the mechanical properties of the pure PE. Hence, the reactive blend system exhibits a lower viscosity ratio. Comparison of these results with those from uncompatibilized blends with different viscosity ratios revealed that the reduction in viscosity ratio has a big influence on the blend morphology and because of that on the mechanical properties. In addition, there is a further effect on morphology and properties caused by the reduction in interfacial tension, which results from the compatibilizer formed at the interface.     

Fluorous Iminoalditols: A New Family of Glycosidase Inhibitors and Pharmacological Chaperones

A collection of new reversible glycosidase inhibitors of the iminoalditol type featuring N‐substituents containing perfluorinated regions has been prepared for evaluation of physicochemical, biochemical and diagnostic properties. The vast variety of feasible oligofluoro moieties allows for modular approaches to customised structures according to the intended applications, which are influenced by the fluorine content as well as the distance of the fluorous moiety from the ring nitrogen. The first examples, in particular in the D ‐galacto series, exhibited excellent inhibitory activities. A preliminary screen with two human cell lines showed that, at subinhibitory concentrations, they are powerful pharmacological chaperones enhancing the activities of the catalytically handicapped lysosomal D ‐galactosidase mutants associated with GM1 gangliosidosis and Morquio B disease.     

Interaction of hIAPP with Model Raft Membranes and Pancreatic β‐Cells: Cytotoxicity of hIAPP Oligomers

Type II diabetes mellitus (T2DM) is associated with β‐cell failure, which correlates with the formation of pancreatic islet amyloid deposits. The human islet amyloid polypeptide (hIAPP) is the major component of islet amyloid and undergoes structural changes followed by self‐association and pathological tissue deposition during aggregation in T2DM. There is clear evidence that the aggregation process is accelerated in the presence of particular lipid membranes. Whereas hIAPP aggregation has been extensively studied in homogeneous model membrane systems, especially negatively charged lipid bilayers, information on the interaction of hIAPP with heterogeneous model raft membranes has been missing until now. In the present study, we focus on the principles of aggregation and amyloid formation of hIAPP in the presence of model raft membranes. Time‐lapse tapping mode AFM and confocal fluorescence microscopy experiments followed membrane permeabilization and localization of hIAPP in the raft membrane. Together with the ThT and WST‐1 assay, the data revealed elevated cytotoxicity of hIAPP oligomers on INS‐1E cells.     

Absorbable polymer stent technologies for vascular regeneration

Stents are structural implants with widespread clinical use in vascular intervention to re‐open stenotic vessels for the treatment of coronary artery disease and peripheral arterial occlusive disease. Apart from their mechanical function, current drug‐eluting stents (DES) utilize local drug delivery from a drug‐incorporated permanent polymer coating to prevent in‐stent restenosis. This delayed closure of the stented vessel is considered one of the major limitations of conventional bare metal stents (BMS). The long‐term safety of DES, however, is still under debate, with reported cases of delayed healing, late thrombosis and hypersensitivity demanding further evolution in this field. A promising approach to circumvent the limitations of first generation DES is the application of degradable polymer coatings in second generation DES, and fully absorbable polymer stents. From a materials and engineering perspective, this paper provides a mini‐review of current clinically relevant DES technology and recent advancements in the development of stents from degradable polymeric materials as an alternative to permanent BMS and DES. This review, includes work on degradable stents and coatings based on blends of polylactic acid and the microbially‐produced poly(4‐hydroxybutyrate). Copyright © 2009 Society of Chemical Industry     

Application of cross-flow microfiltration to semi-hard cheese production from milk retentates

In the cheese industry, the concentration of milk using ultrafiltration for continuous soft and fresh cheese production is standard technology. The object of the work presented here was to produce a semi-hard cheese of quality and composition comparable to that of traditionally made cheese from highly concentrated microfiltered milk retentate. Two different membrane systems were tested for the production of high viscous milk retentate with high dry matter content. For milk containing 3.2% fat and skim milk, a concentration factor of 6.6 and 9.1 respectively was obtained using the MF/UF/UF pilot plant fitted with cassette modules. Milk containing 3.2% fat was concentrated in batches by a factor of 5.7 in the pilot plant using a ceramic membrane. Using minimal curd separation, a semi-hard one day old cheese with a dry matter of 533 g/kg, moisture on a fat-free basis (MFFB) of 626 g/kg and fat on a dry basis (FDB) value of 478 g/kg was made from the milk retentate produced with the ceramic module. The ripened cheese fulfilled the legal requirements of a traditionally produced semi-hard cheese with superb sensory qualities. Using the MF/UF/UF plant, a dry matter of 495 g/kg (MFFB 669 g/kg, FDB 493 g/kg) was achieved in a semi-hard cheese made from skim milk retentate. Our results suggest that by using a larger spacer distance in the last loop of the MF/UF/UF plant, combined with new hybrid technologies, semi-hard cheese production from full concentrate milk will soon become possible.     

Efficiency improvement of dye-sensitized solar cells based on electrodeposited TiO2 films by low temperature post-treatment

Porous crystalline TiO₂ films can be prepared at low temperatures (80 °C) by surfactant-assisted electrodeposition from TiCl₃ solution. Nevertheless, up to now calcination at high temperatures (typically 450 °C) was still necessary to establish a good performance of these films in dye-sensitized solar cells (DSSC). With this study we report that water vapour treatment at much lower temperatures (150 °C) for 1 week improves the performance of the films in DSSC to the same degree as calcination although the overall crystallinity remains lower. Reason for the good efficiency is that the porous structure stays intact and thus the dye molecules can be better adsorbed. Avoiding high temperatures during the preparation process of TiO₂ films for the application in DSSC enables the use of polymer substrates for the fabrication of flexible solar cells.     

Characterization of Apo-Form Selective Inhibition of Indoleamine 2,3-Dioxygenase**

Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As it is an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of IDO1 inhibitors with various mechanisms of inhibition is of great interest. Comparison of an apo-form-binding IDO1 inhibitor (GSK5628) to the heme-coordinating compound, epacadostat (Incyte), allows us to explore the details of the apo-binding inhibition of IDO1. Herein, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1), whereas epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, previously undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition might help design superior inhibitors or could confer a unique competitive advantage over other IDO1 inhibitors vis-à-vis specificity and pharmacokinetic parameters.     

Synthesis and Pharmacological In Vitro Investigations of Novel Shikonin Derivatives with a Special Focus on Cyclopropane Bearing Derivatives

Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGlo^TM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma.     

Boson peak and structural heterogeneity in ternary SiO2-Al2O3-B2O3 glasses

We use low-temperature heat capacity, low-frequency Raman scattering, and THz time domain spectroscopy in order to scale the vibrational density of states and the Boson peak in SiO₂-Al₂O₃-B₂O₃ Yb-laser host glasses. When substituting B₂O₃ for SiO₂ at constant Al₂O₃ dopant level, we find an optimal value for the ratio of B/Al in terms of mixture stability, at which the excess in the electron donor capability of Al₂O₃ (relative to the SiO₂ backbone) is compensated by the more acidic B₂O₃. At this composition, Al₂O₃ plays a mediating role in the structure of aluminoborosilicate glasses, facilitating dissolution of Yb₂O₃ and admixture of B₂O₃ into the SiO₂ network.