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Malignant primary brain tumors are a group of highly aggressive and often infiltrating tumors that lack adequate therapeutic treatments to achieve long time survival. Complete tumor removal is one precondition to reach this goal. A promising approach to optimize resection margins and eliminate remaining infiltrative so-called guerilla cells is photodynamic therapy (PDT) using organic photosensitizers that can pass the disrupted blood–brain-barrier and selectively accumulate in tumor tissue. Hypericin fulfills these conditions and additionally offers outstanding photophysical properties, making it an excellent choice as a photosensitizing molecule for PDT. However, the actual hypericin-induced PDT cell death mechanism is still under debate. In this work, hypericin-induced PDT was investigated by employing the three distinct fluorescent probes hypericin, resorufin and propidium iodide (PI) in fluorescence-lifetime imaging microscopy (FLIM). This approach enables visualizing the PDT-induced photodamaging and dying of single, living glioma cells, as an in vitro tumor model for glioblastoma. Hypericin PDT and FLIM image acquisition were simultaneously induced by 405 nm laser irradiation and sequences of FLIM images and fluorescence spectra were recorded to analyze the PDT progression. The reproducibly observed cellular changes provide insight into the mechanism of cell death during PDT and suggest that apoptosis is the initial mechanism followed by necrosis after continued irradiation. These new insights into the mechanism of hypericin PDT of single glioma cells may help to adjust irradiation doses and improve the implementation as a therapy for primary brain tumors.
Im Bereich Gewässerschutz sowie beim Schutz unserer Trinkwasserressourcen wurden bis heute große Fortschritte erzielt, die insbesondere auf Reinigungsmaßnahmen, städtebaulichen Maßnahmen und auf einer konsequenten analytischen Überwachung basieren. Neben der Einführung einer 4. Reinigungsstufe zur Elimination von Mikroverunreinigungen bei immer mehr Kläranlagen sind hier allgemein die Kanalanbindungen und Regenwasserrückhaltebecken sowie eine systematische analytische Überwachung mittels verschiedener on- und offline arbeitender Methoden der Wasseranalytik zu nennen. Dabei hat auch insbesondere die nationale und EU weite Gesetzgebung große Anstrengungen unternommen, die Qualität von Oberflächen- und Bewässerungswässern durch entsprechende Grenzwertvorgaben (EU Umweltqualitätsnormen 2008/105/EG; Nitratrichtlinie 91/676/EG) zu sichern. Dies hat bundesweit zu spürbaren Verbesserungen der Oberflächenwasserqualitäten, dem verbesserten Schutz der aquatischen Flora und Fauna und damit zu einem verbesserten Schutz der Rohwässer geführt. Hierdurch wird neben der Sicherung der Trinkwassergewinnung auch der gesellschaftlich bedeutsame Schutz einer intakten Umwelt im Einklang mit einer verträglichen Nutzung bis hin zu den Badegewässern durch Privatpersonen gewährleistet.
Protein kinases promote cell processes such as cell growth and proliferation similarly in tumor cells and healthy cells. Pharmaceutical research aims at developing small molecules that inhibit tumor growth binding in the ATP-binding pocket of specific protein kinases. To understand the specificity of the inhibitor, thermodynamic and kinetic data of the kinase-inhibitor binding process are important. A broad range of analytical methods may investigate the interactions between protein kinases and inhibitors. Today, however, there is no comprehensive strategy to provide information on both specificity screening and binding kinetics. The purpose of this review is to summarize analytical methods used not only to monitor the protein kinase inhibition, but also to provide kinetic and thermodynamic data on the basis of screening applications. A focus is set on optical biosensing as the most promising techniques. We discuss, that intelligent combinations of methods can provide comprehensive
information on protein kinases interacting with inhibitors.
"Optofluidics : Process Analytical Technology" offers in its 2nd edition a distinctive foundational introduction to the realms of materials, photonics, fluidics, and sensors. The work serves to unify the disparate disciplines, integrating the requisite fundamental knowledge with applied science. It thus establishes a new standard and definition for both the academic and industrial fields.
It encompasses the requisite in-depth knowledge of smart materials, semiconductor processing, optical waveguiding and fluid dynamics. The objective of this distinctive publication is to present information in a readily comprehensible format that can be readily applied in everyday situations. It is truly interdisciplinary but not overloading with information, providing the highly required and relevant information to become an expert in this exciting area, which is gaining more and more relevance and recognition in the context of sensing, material science and automation in biotechnology and pharmaceutical manufacturing.
The concept of the book is to serve as a textbook for advanced beginners from all life science, engineering and physics disciplines, providing self-assessment questions and further reading recommendations for further guidance and in-depth learning.
An epoxy compound’s polymer structure can be characterized by the glass transition temperature (Tg) which is often seen as the primary morphological characteristic. Determining the Tg after manufacturing thermoset-molded parts is an important objective in material characterization. To characterize quantitatively the dependence of Tg on the degree of cure, the DiBenedetto equation is usually used. Monitoring polymer network formation during molding processes is therefore one of the most challenging tasks in polymer processing and can be achieved using dielectric analysis (DEA). In this study, the morphological properties of an epoxy resin-based molding compounds (EMC) were optimized for the molding process using response surface analysis. Processing parameters such as curing temperature, curing time, and injection rate were investigated according to a DoE strategy and analyzed as the main factors affecting Tg as well as the degree of cure. A new method to measure the Tg at a certain degree of cure was developed based on warpage analysis. The degree of cure was determined inline via dielectric analysis (DEA) and offline using differential scanning calorimetry (DSC). The results were used as the response in the DoE models. The use of the DiBenedetto equation to refine the response characteristics for a wide range of process parameters has significantly improved the quality of response surface models based on the DoE approach.
Monitoring of molding processes is one of the most challenging future tasks in polymer processing. In this work, the in situ monitoring of the curing behavior of highly filled EMCs (silica filler content ranging from 73 to 83 wt%) and the effect of filler load on curing kinetics are investigated. Kinetic modelling using the Friedman approach was applied using real-time process data obtained from in situ DEA measurements, and these online kinetic models were compared with curing analysis data obtained from offline DSC measurements. For an autocatalytic fast-reacting material to be processed above the glass transition temperature Tg and for an autocatalytic slow-reacting material to be processed below Tg, time–temperature–transformation (TTT) diagrams were generated to investigate the reaction behavior regarding Tg progression. Incorporating a material containing a lower silica filler content of 10 wt% enabled analysis of the effects of filler content on sensor sensitivity and curing kinetics. Lower silica particle content (and a larger fraction of organic resin, respectively) favored reaction kinetics, resulting in a faster reaction towards Tg1. Kinetic analysis using DEA and DSC facilitated the development of highly accurate prediction models using the Friedman model-free approach. Lower silica particle content resulted in enhanced sensitivity of the analytical method, leading, in turn, to more precise prediction models for the degree of cure.
Composite polymer/wax coatings as a corrosion barrier of bioresorbable magnesium coronary stents
(2024)
Magnesium and its alloys are suitable materials for biodegradable biomedical implants such as cardiovascular stents. Here we introduce an innovative composite polyelectrolyte multilayer/wax coating applied to commercial coronary Mg-based stents serving as a barrier layer effectively retarding corrosion. This hydrophobic coating, build by layer-by-layer technology, appeared very thin, smooth, homogeneous, strongly adherent and completely covering the surface of the Mg-stent. In-vitro degradation tests showed greater resistance to degradation of coated Mg-stents compared to uncoated and passivated ones. Cytocompatibility studies proved that Mg-stent coated with the composite coating was non-cytotoxic and improved fibroblast cell viability compared to the uncoated Mg-stent.
T cell migration plays an essential role in the immune response and T cell-based therapies. It can be modulated by chemical and physical cues such as electric fields (EFs). The mechanisms underlying electrotaxis (cell migration manipulated by EFs) are not fully understood and systematic studies with immune cells are rare. In this in vitro study, we show that direct current EFs with strengths of physiologically occurring EFs (25–200 mV/mm) can guide the migration of primary human CD4+ and CD8+ T cells on 2D substrates toward the anode and in a 3D environment differentially (CD4+ T cells show cathodal and CD8+ T cells show anodal electrotaxis). Overall, we find that EFs present a potent stimulus to direct T cell migration in different microenvironments in a cell-type-, substrate-, and voltage-dependent manner, while not significantly influencing T cell differentiation or viability.
The peripherical protons of the dye molecule hypericin can undergo structural interconversion (tautomerization) between different isomers separated by a low energy barrier with rates that depends sensitively on the interaction with local chemical environment defined by the nature of host material. We investigate the deuterium (D) isotope effect of hypericin tautomerism at the single‐molecule level to avoid ensemble averaging in different polymer matrices by a combined spectroscopic and computational approach. In the ′innocent′ PMMA matrix only intramolecular isotope effects on the internal conversion channel and tautomerization are observed; while PVA specifically interacts with the probe via H‐ and D‐bonding. This establishes a single molecular picture on intra‐ and intermolecular nano‐environment effects to control chromophore photophysics and ‐chemistry.
The in-line control of curing during the molding process significantly improves product quality and ensures the reliability of packaging materials with the required thermo-mechanical and adhesion properties. The choice of the morphological and thermo-mechanical properties of the molded material, and the accuracy of their determination through carefully selected thermo-analytical methods, play a crucial role in the qualitative prediction of trends in packaging product properties as process parameters are varied. This work aimed to verify the quality of the models and their validation using a highly filled molding resin with an identical chemical composition but 10 wt% difference in silica particles (SPs). Morphological and mechanical material properties were determined by dielectric analysis (DEA), differential scanning calorimetry (DSC), warpage analysis and dynamic mechanical analysis (DMA). The effects of temperature and injection speed on the morphological properties were analyzed through the design of experiments (DoE) and illustrated by response surface plots. A comprehensive approach to monitor the evolution of ionic viscosity (IV), residual enthalpy (dHrest), glass transition temperature (Tg), and storage modulus (E) as a function of the transfer-mold process parameters and post-mold-cure (PMC) conditions of the material was established. The reliability of Tg estimation was tested using two methods: warpage analysis and DMA. The noticeable deterioration in the quality of the analytical signal for highly filled materials at high cure rates is discussed. Controlling the temperature by increasing the injection speed leads to the formation of a polymer network with a lower Tg and an increased storage modulus, indicating a lower density and a more heterogeneous structure due to the high heating rate and shear heating effect.
