Exogenous Integrin αIIbβ3 Inhibitors Revisited: Past,Present and Future Applications

The integrin αIIbβ3 is the most abundant integrin on platelets. Upon platelet activation, the integrin changes its conformation (inside-out signalling) and outside-in signalling takes place leading to platelet spreading, platelet aggregation and thrombus formation. Bloodsucking parasites such as mosquitoes, leeches and ticks express anticoagulant and antiplatelet proteins, which represent major sources of lead compounds for the development of useful therapeutic agents for the treatment of haemostatic disorders or cardiovascular diseases. In addition to hematophagous parasites, snakes also possess anticoagulant and antiplatelet proteins in their salivary glands. Two snake venom proteins have been developed into two antiplatelet drugs that are currently used in the clinic. The group of proteins discussed in this review are disintegrins, low molecular weight integrin-binding cysteine-rich proteins, found in snakes, ticks, leeches, worms and horseflies. Finally, we highlight various oral antagonists, which have been tested in clinical trials but were discontinued due to an increase in mortality. No new αIIbβ3 inhibitors are developed since the approval of current platelet antagonists, and structure-function analysis of exogenous disintegrins could help find platelet antagonists with fewer adverse side effects.     

Uric Acid: The Sperm-Release Pheromone of the Marine Polychaete Platynereis dumerilii

In the marine polychaete, Platynereis dumerilii, reproductive behavior in the two sexes is synchronized by the consecutive discharge of male and female sex-specific pheromones. After the female releases the eggs into the free water column, immediate fertilization is achieved by several males circling around the eggs emitting sperm clouds. We report the isolation and identification of the sperm-release pheromone present in the coelomic fluid of sexually mature females. Each step in isolation was guided by bioassay. Isolation methods included extraction and solvent partitioning and separation methods included ultrafiltration and high-performance liquid chromatography. Uric acid was identified as the sperm-release pheromone that is discharged by the female with release of the eggs. The threshold concentration for sperm release by males was determined as 0.6 M.     

Ultraviolet photodetectors and readout based on a-IGZO semiconductor technology

In this work, real-time ultraviolet photodetectors are realized through metal–semiconductor–metal (MSM) structures. Amorphous indium gallium zinc oxide (a-IGZO) is used as semiconductor material and gold as metal electrodes. The readout of an individual sensor is implemented by a transimpedance amplifier (TIA) consisting of an all-enhancement a-IGZO thin-film transistor (TFT) operational amplifier and a switched capacitor (SC) as feedback resistance. The photosensor and the transimpedance amplifier are both manufactured on glass substrates. The measured photosensor possesses a high responsivity R , a low response time t _{R E S} , and a good noise equivalent power value NEP .     

Low retaining force optical viewport seal

We report on the experimental realization of an ultrahigh vacuum (UHV) indium sealing between a conflat knife edge and an optical window. The sealing requires a very low clamping force and thus allows for the use of very thin and fragile windows.     

Semi‐Solid Processing of Metal Alloys

Semi‐solid metal casting is an innovative technology for the production of near‐net‐shape parts with demanding mechanical properties. The paper describes different processing routes and materials for semi‐solid‐metal casting (SSM), which have been investigated and also partially developed at the Foundry‐Institute of Aachen University. The standard thixocasting process for aluminium, highly reactive magnesium alloys and steel alloys with high melting points was investigated under variation of a wide range of process parameters. Specially adapted pre‐material production and reheating methods were developed for different materials and their application and future potential is pointed out. The thixocasting experiments were executed on a modified high pressure die‐casting machine with a specially designed “step‐die” providing wall thicknesses from 0.5 to 25 mm. The mechanical properties were tested in dependence of the wall thickness and the metal velocity. The results of these examination show high tensile strength values in combination with very good elongations. The rheocasting process is a new SSM‐forming method with liquid melt as feed‐stock and a high recycling potential. The research results of RCP‐technology (Rheo‐Container‐Process) invented at the Foundry‐Institute and of the Cooling‐Channel‐Process for aluminium and magnesium alloys are promising and are presented in this paper. Studies on semi‐solid processing of magnesium alloys and mixtures of them were conducted by Thixomolding^TM. To establish the most adequate process parameters, the temperature and the mixture relations were varied. Using a mould for tensile test specimens, the mechanical properties and the microstructure evolution could be evaluated. The chemical composition of the different phases was determined using SEM and EDX technologies. Evaluations of the flowing properties were conducted using a spiral mould with a total length of 2m and a cross section of 20mm x 1.5mm.     

Microstructural and microwave dielectric properties of LZT (Li2ZnTi3O8) ceramics sintered in presence of bismuth borate glass for LTCC applications

In the present research, the Li₂ZnTi₃O₈(LZT) ceramics were synthesized throughout solid-state ceramic processing, then mixed with bismuth borate (BiBO) glass prepared based on conventional melt quenching method. Wetting behavior of BiBO glass on the LZT ceramic substrate was monitored by hot stage microscopy. Afterward, dielectric LZT ceramics containing different amounts of BiBO glass (0.25–6 wt%) were sintered at various temperatures. X-ray diffraction and electron back scatter diffraction examinations revealed the presence of two crystalline phases of Li₂ZnTi₃O₈ and Bi₂Ti₂O₇. The maximum value of relative density (above 95%) was obtained in the case of specimens contained more than 5 wt% glass. The microwave dielectric properties of the finally sintered BiBO glass containing LZT ceramics were as follows: dielectric constant (ε_r) = 21.44–25.09, quality factor (Q × f) = 10839–54708 GHz and temperature coefficient of resonant frequency (τ_f) = (? 15.58) ? (? 12.86)ppm/°C.     

An approach to mechanistic event recognition applied on monitoring organic matter depletion in SBRs

A fundamental practice in process engineering is monitoring the state dynamics of a system. Unfortunately, observability of some states is related to high costs, time, and efforts. The mechanistic event recognition (MER) aims to detect an event (defined as a change of the system with specific significance to the operation of the process) that cannot be directly observed but has some predictable effect on the dynamics of the systems. MER attempts to apply fault diagnosis techniques using mechanistic “recognition” models to describe the process. A systematic method for building recognition models using optimal experimental design tools is presented. As proof of concept, the MER approach to detect organic matter depletion in sequencing batch reactors, measuring only ammonia, dissolved oxygen, and nitroxides is applied. The event, that is, consumption of organic matter to a level below 50 gCOD/m³, was successfully detected even though microbial activity is known to continue after organic matter depletion. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3460–3472, 2014     

Creep compliance mapping by atomic force microscopy

We present a method for mapping the spatial distribution of viscoelastic properties of heterogeneous samples using the atomic force microscope (AFM). By applying a force step load protocol to induce time dependent sample indentations we measured the local creep compliance of the sample. The creep compliance was quantified in terms of the standard linear solid model to give maps of the instant glassy modulus, the equilibrium rubbery modulus, and the retardation time. To reduce the influence of plastic deformations, the sample was preformed with an initial preload step. Different polymer samples with a homogeneous or a heterogeneous material composition on a microscopic scale were investigated.     

Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation

Traditional antithrombotic agents commonly share a therapy-limiting side effect, as they increase the overall systemic bleeding risk. A novel approach for targeted antithrombotic therapy is nanoparticles. In other therapeutic fields, nanoparticles have enabled site-specific delivery with low levels of toxicity and side effects. Here, we paired nanotechnology with an established dimeric glycoprotein VI-Fc (GPVI-Fc) and a GPVI-CD39 fusion protein, thereby combining site-specific delivery and new antithrombotic drugs. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles, NP-BSA, NP-GPVI and NP-GPVI-CD39 were characterized through electron microscopy, atomic force measurements and flow cytometry. Light transmission aggregometry enabled analysis of platelet aggregation. Thrombus formation was observed through flow chamber experiments. NP-GPVI and NP-GPVI-CD39 displayed a characteristic surface coating pattern. Fluorescence properties were identical amongst all samples. NP-GPVI and NP-GPVI-CD39 significantly impaired platelet aggregation. Thrombus formation was significantly impaired by NP-GPVI and was particularly impaired by NP-GPVI-CD39. The receptor-coated nanoparticles NP-GPVI and the bifunctional molecule NP-GPVI-CD39 demonstrated significant inhibition of in vitro thrombus formation. Consequently, the nanoparticle-mediated antithrombotic effect of GPVI-Fc, as well as GPVI-CD39, and an additive impact of CD39 was confirmed. In conclusion, NP-GPVI and NP-GPVI-CD39 may serve as a promising foundation for a novel therapeutic approach regarding targeted antithrombotic therapy.