Bivalent EGFR-Targeting DARPin-MMAE Conjugates

Epidermal growth factor receptor (EGFR) is a validated tumor marker overexpressed in various cancers such as squamous cell carcinoma (SSC) of the head and neck and gliomas. We constructed protein-drug conjugates based on the anti-EGFR Designed Ankyrin Repeat Protein (DARPin) E01, and compared the bivalent DARPin dimer (DD1) and a DARPin-Fc (DFc) to the monomeric DARPin (DM) and the antibody derived scFv425-Fc (scFvFc) in cell culture and a mouse model. The modular conjugation system, which was successfully applied for the preparation of protein-drug and -dye conjugates, uses bio-orthogonal protein-aldehyde generation by the formylglycine-generating enzyme (FGE). The generated carbonyl moiety is addressed by a bifunctional linker with a pyrazolone for a tandem Knoevenagel reaction and an azide for strain-promoted azide-alkyne cycloaddition (SPAAC). The latter reaction with a PEGylated linker containing a dibenzocyclooctyne (DBCO) for SPAAC and monomethyl auristatin E (MMAE) as the toxin provided the stable conjugates DD1-MMAE (drug-antibody ratio, DAR = 2.0) and DFc-MMAE (DAR = 4.0) with sub-nanomolar cytotoxicity against the human squamous carcinoma derived A431 cells. In vivo imaging of Alexa Fluor 647-dye conjugates in A431-xenografted mice bearing subcutaneous tumors as the SCC model revealed unspecific binding of bivalent DARPins to the ubiquitously expressed EGFR. Tumor-targeting was verified 6 h post-injection solely for DD1 and scFvFc. The total of four administrations of 6.5 mg/kg DD1-MMAE or DFc-MMAE twice weekly did not cause any sequela in mice. MMAE conjugates showed no significant anti-tumor efficacy in vivo, but a trend towards increased necrotic areas (p = 0.2213) was observed for the DD1-MMAE (n = 5).     

Relation between microstructure and glass transition temperature of poly[(methyl methacrylate)‐co‐(ethyl acrylate)]

The glass transition temperature of a series of samples of the poly[(methyl methacrylate)‐co‐(ethyl acrylate)] copolymer, synthesized at low conversion, were calculated theoretically using the equations of Barton and Johnston. The values obtained are more precise when the probabilities of the compositional diads are derived from the ¹³C NMR data instead of the classical method utilizing reactivity ratios. This can be observed more clearly when the copolymer samples are synthesized at high conversion. Introduction of configuration (tacticity) at the diad level confirms the above observations and slightly improves the calculated values of T_g compared to the initial formulae which were only taking into account the compositional sequences of the copolymer. © 2001 Society of Chemical Industry     

Tape Casting of Anode Supports for Solid Oxide Fuel Cells at Forschungszentrum Jülich

This contribution describes the development of tape casting for solid oxide fuel cells (SOFCs) anode supports starting with the characterization of the powders and ending with manufacturing of cells for stack testing. After casting the support, full cells were prepared by screen printing and sintering of the functional layers. The results of single‐cell and stack tests of the novel SOFC will be discussed. The new cell showed excellent electrochemical performance in single‐cell tests with more than 1.5 A/cm² (800°C, 0.7 V). Furthermore, stack tests showed no significant difference from earlier standard cells when operated at 800°C with a current density of 0.5 A/cm².     

Accelerated Visualization of Dynamic Molecular Surfaces

Molecular surfaces play an important role in studying the interactions between molecules. Visualizing the dynamic behavior of molecules is particularly interesting to gain insights into a molecular system. Only recently it has become possible to interactively visualize dynamic molecular surfaces using ray casting techniques. In this paper, we show how to further accelerate the construction and the rendering of the solvent excluded surface (SES) and the molecular skin surface (MSS). We propose several improvements to reduce the update times for displaying these molecular surfaces. First, we adopt a parallel approximate Voronoi diagram algorithm to compute the MSS. This accelerates the MSS computation by more than one order of magnitude on a single core. Second, we demonstrate that the contour‐buildup algorithm is ideally suited for computing the SES due to its inherently parallel structure. For both parallel algorithms, we observe good scalability up to 8 cores and, thus, obtain interactive frame rates for molecular dynamics trajectories of up to twenty thousand atoms for the SES and up to a few thousand atoms for the MSS. Third, we reduce the rendering time for the SES using tight‐fitting bounding quadrangles as rasterization primitives. These primitives also accelerate the rendering of the MSS. With these improvements, the interactive visualization of the MSS of dynamic trajectories of a few thousand atoms becomes for the first time possible. Nevertheless, the SES remains a few times faster than the MSS.     

Cofiring of Thin Zirconia Films During SOFC Manufacturing

High-performance solid oxide fuel cells require a thin and gas-tight electrolyte membrane that must be coated on a porous and relatively rough support. A pretreatment of the delivered submicronmeter electrolyte powder of 8 mol%-yttria-stabilized zirconia (8YSZ) yielded a reduced sintering mismatch between the anode substrate made from NiO/8YSZ and the electrolyte coating. Furthermore, it also enhanced the powder packing inside the green film. Constrained sintering usually leads to inadequate film density and an unfavorable pore deformation and orientation. It was demonstrated that these limitations can be resolved by using a coshrinking substrate in a planar cell design. Relative densities of >97% were achieved, which are higher than those for free-standing layers. Additionally, the camber behavior was investigated in dependence of the temperature program with and without gravity effects, giving an overall suggestion for the cofiring parameters of the electrolyte.     

A system for automatic measurement of circadian activity deviations in telemedicine

A system for the automatic measurement of the circadian activity deviations in telemedicine has been developed within the framework of a "Health Integrated Smart Home Information System" (HIS2). HIS2 is an experimental platform for the evaluation and the development of technologies in order to ensure the security and quality of life for patients who need home based medical monitoring. Location sensors are placed in each room of the HIS2, allowing the monitoring of patient's successive activity phases within the patient's home environment. We proceeded with a sampling in an hourly schedule to detect weak rhythmic variations. Based on numerous measurements, we established a mean value with confidence limits. These also allowed us to define a zone within which the patient's activity is qualified to be "predictable." Alerts are set off if the patient's activity deviates from this zone.     

Der Schlanke mit der gro?en Bildfl?che

Firmen&;ProdukteNeuer 16-ZOLL-LCD-Monitor

Der Schlanke mit der gro?en Bildfl?che