An ELISA was set up using polyvinylchloride microtiter plates coated with rabbit anti-UK IgG's and affino-purified goat anti-UK IgG's as second antibody. Detection occurred with rabbit anti-goat IgG antibodies conjugated with alkaline phosphatase. The assay is specific for urokinase (UK) with a detection limit of 100 pg/ml sample. Tissue-type plasminogen activator, up to concentrations of 100 ng/ml, does not interfere. The assay measures the antigen of the inactive zymogen pro-UK, the active enzyme UK and the UK-inhibitor complex with equal efficiency and gives the total UK antigen present, irrespective of its molecular form. Culture media of fibroblasts, endothelial- and kidney cells showed, despite the absence of active UK, antigen levels of 1.2, 23 and 65 ng/ml, respectively. In human plasma the UK concentration was found to be 3.5 +/- 1.4 ng/ml (mean +/- SD, n = 54). The inter- and intra-assay variations were 20% and 6%, respectively.
The angiotensin receptor blocker telmisartan slows progression of kidney disease in patients with type 2 diabetes (T2D), yet many patients remain at high risk for progressive kidney function loss. The underlying mechanisms for this response variation might be attributed to differences in angiotensin-1 receptor occupancy (RO), resulting from individual variation in plasma drug exposure, tissue drug exposure, and receptor availability. Therefore, we first assessed the relationship between plasma telmisartan exposure and urinary-albumin-to-creatinine-ratio (UACR) in 10 patients with T2D and albuminuria (mean age 66 years, median UACR 297 mg/g) after 4 weeks treatment with 80 mg telmisartan once daily. Increasing telmisartan exposure associated with a larger reduction in UACR (Pearson correlation coefficient (PCC) = −0.64, P = 0.046, median change UACR: −40.1%, 95% confidence interval (CI): −22.9 to −77.4%, mean telmisartan area under the curve (AUC) = 2927.1 ng·hour/mL, 95% CI: 723.0 to 6501.6 ng·hour/mL). Subsequently, we assessed the relation among plasma telmisartan exposure, kidney distribution, and angiotensin-1 RO in five patients with T2D (mean age 60 years, median UACR 72 mg/g) in a separate positron emission tomography imaging study with [11C]Telmisartan. Individual plasma telmisartan exposure correlated with telmisartan distribution to the kidneys (PCC = 0.976, P = 0.024). A meaningful RO could be calculated in three patients receiving 120 mg oral telmisartan, and although high exposure seems related to higher RO, with AUC0–last of 31, 840, and 274 ng·hour/mL and corresponding RO values 5.5%, 44%, and 59%, this was not significant (P = 0.64). Together these results indicate, for the first time, a relationship among interindividual differences in plasma exposure, kidney tissue distribution, RO, and ultimately UACR response after telmisartan administration.
Inkjet printing is a rapidly growing technology for depositing functional materials in the production of organic electronics. Challenges lie among others in the printing of high resolution patterns with high aspect ratio of functional materials to obtain the needed functionality like e.g. conductivity. μPlasma printing is a technology which combines atmospheric plasma treatment with the versatility of digital on demand printing technology to selectively change the wetting behaviour of materials. In earlier research it was shown that with μPlasma printing it is possible to selectively improve the wetting behaviour of functional inks on polymer substrates using atmospheric air plasma. In this investigation we show it is possible to selectively change the substrate wetting behaviour using combinations of different plasmas and patterned printing. For air and nitrogen plasmas, increased wetting of printed materials could be achieved on both polycarbonate and glass substrates. A minimal track width of 320 μm for a 200 μm wide plasma needle was achieved. A combination of N2 with HMDSO plasma increases the contact angle for water up from <100 to 1050 and from 320 to 460 for DEGDMA making the substrate more hydrophobic. Furthermore using N2-plasma in combination with a N2/HMDSO plasma, hydrophobic tracks could be printed with similar minimal track width. Combining both N2 -plasma and N2/HMDSO plasma treatments show promising results to further decrease the track width to even smaller values.
Fontys University of Applied Science’s Institute of Engineering, and the Dutch Institute for Fundamental Energy Research (DIFFER) are proposing to set up a professorship to develop novel sensors for fusion reactors. Sensors are a critical component to control and optimise the unstable plasma of Tokamak reactors. However, sensor systems are particularly challenging in fusion-plasma facing components, such as the divertor. The extreme conditions make it impossible to directly incorporate sensors. Furthermore, in advanced reactor concepts, such as DEMO, access to the plasma via ports will be extremely limited. Therefore, indirect or non-contact sensing modalities must be employed. The research group Distributed Sensor Systems (DSS) will develop microwave sensor systems for characterising the plasma in a tokamak’s divertor. DSS will take advantage of recent rapid developments in high frequency integrated circuits, found, for instance, in automotive radar systems, to develop digital reflectometers. Access through the divertor wall will be achieved via surface waveguide structures. The waveguide will be printed using 3D tungsten printing that has improved precision, and reduced roughness. These components will be tested for durability at DIFFER facilities. The performance of the microwave reflectometer, including waveguides, will be tested by using it to analyse the geometry and dynamics of the Magnum PSI plasma beam. The development of sensor-based systems is an important aspect in the integrated research and education program in Electrical Engineering, where DSS is based. The sensing requirements from DIFFER offers an interesting and highly relevant research theme to DSS and exciting projects for engineering students. Hence, this collaboration will strengthen both institutes and the educational offerings at the institute of engineering. Furthermore millimeter wave (mmWave) sensors have a wide range of potential applications, from plasma characterisation (as in this proposal) though to waste separation. Our research will be a step towards realising these broader application areas.
HCA Groenvermogen NL vormt de aanleiding en het kader voor het aanstellen van Regionale Liaisons en het opstellen van Regionale Roadmapsin zes regio’s. Deze hebben als rol en functie de regio’s te mobiliseren voor Learning Communities en de uitwisseling binnen het Nationale Kennisplatform. Hierbij is Chemelot geïdentificeerd als één van die zes regio’s, en is Zuyd Hogeschool benaderd om een aanvraag voor te bereiden. ▪ Chemelot is een interessante locatie voor een doorgedreven inzet van Learning Communities op het gebied van waterstof. Waterstof is een belangrijk grondstof in de chemie en wordt vandaag geproduceerd uit aardgas. Ambitie is tegen 2050 duurzame waterstof zonder CO2- emissies te produceren. Samen met elektrificatie zal duurzame waterstof de energie- en grondstoffentransitie op Chemelot vormgeven. Daarnaast is op Chemelot reeds 10 jaar de Chemelot Innovation and Learning Labs (CHILL) actief, een publiek-private samenwerking tussen Universiteit Maastricht, Vista college, Zuyd Hogeschool en bedrijven als DSM, Sabic en Fibrant, en als dusdanig een Learning Community voor de verduurzaming van de chemie. ▪ De transitie naar een duurzame chemie is de inzet van de brede triple alliantie Chemelot Circular Hub (CCH) en haar Circulaire Economie Actieplan (CEAP). De CEAP vormt het referentiekader voor de verdere uitwerking van de Regionale Roadmap, met als focus het binden van talenten, aantrekken van gamechangers, topfaciliteiten voor onderzoek en innovatie incl. digitalisering. Het Regionale Liaisons-team is samengesteld uit experten vanuit de onderwijsinstellingen, CHILL, Brightsite en de CCH- programmamanager. Het team wordt ingebed in de CCH-governance, wat de afstemming met andere projecten binnen o.a. het Groeifonds en JTF borgt. Tot slot spiegelt onze aanpak zich aan de werkstromen binnen HCA GroenvermogenNL, dit in functie van een sterke synergie tussen regionale en nationale acties. Verdiepen van de kennisbasis, versterken van de samenwerking en versnellen van innovatieve onderwijs- en arbeidsmarktinitiatieven zijn hierin leidende principes.
Biotherapeutic medicines such as peptides, recombinant proteins, and monoclonal antibodies have successfully entered the market for treating or providing protection against chronic and life-threatening diseases. The number of relevant commercial products is rapidly increasing. Due to degradation in the gastro-intestinal tract, protein-based drugs cannot be taken orally but need to be administered via alternative routes. The parenteral injection is still the most widely applied administration route but therapy compliance of injection-based pharmacotherapies is a concern. Long-acting injectable (LAI) sustained release dosage forms such as microparticles allow less frequent injection to maintain plasma levels within their therapeutic window. Spider Silk Protein and Poly Lactic-co-Glycolic Acid (PLGA) have been attractive candidates to fabricate devices for drug delivery applications. However, conventional microencapsulation processes to manufacture microparticles encounter drawbacks such as protein activity loss, unacceptable residual organic solvents, complex processing, and difficult scale-up. Supercritical fluids (SCF), such as supercritical carbon dioxide (scCO2), have been used to produce protein-loaded microparticles and is advantageous over conventional methods regarding adjustable fluid properties, mild operating conditions, interfacial tensionless, cheap, non-toxicity, easy downstream processing and environment-friendly. Supercritical microfluidics (SCMF) depict the idea to combine strengths of process scale reduction with unique properties of SCF. Concerning the development of long-acting microparticles for biological therapeutics, SCMF processing offers several benefits over conventionally larger-scale systems such as enhanced control on fluid flow and other critical processing parameters such as pressure and temperature, easy modulation of product properties (such as particle size, morphology, and composition), cheaper equipment build-up, and convenient parallelization for high-throughput production. The objective of this project is to develop a mild microfluidic scCO2 based process for the production of long-acting injectable protein-loaded microparticles with, for example, Spider Silk Protein or PLGA as the encapsulating materials, and to evaluate the techno-economic potential of such SCMF technology for practical & industrial production.
