Manufacturing of integrative membrane carriers by novel powder injection molding

Although offering distinctive economic benefits the mass fabrication of carrier devices incorporating membranes as quasi-monolithic devices reveals strong technological challenges. Powder injection molding would be an effective process for this purpose, however, manufacturing parts of considerable wall thickness variations and to meet strong precision demands remains problematic. To evaluate novel ways of process conducts as well as to determine influencing parameters a demonstrator design had been developed which enabled the generation of thin membranes by controlled piston movement. Suitable lay-out of the runner system had been determined with the help of simulation calculations. The combined injection + embossing process conduct enabled to reduce minimum membrane thickness to about a half. Investigation of parameter influence showed that embossing force and gap width before injection have an ameliorative effect on membrane quality whereas the embossing delay time had no significant impact.     

Characterization of a miniaturized liquid bridge for nL sample infusion: a comparative study of sample flush-out behavior using flow simulations and direct ESI-MS analysis

In this work we shed light on the microfluidics of a miniaturized liquid bridge that forms the central part of a so-called “capillary gap sampler,” a novel device for rapid and seamless injection of nanoliter sample volumes into an electrospray ionization mass spectrometer (ESI-MS). Parameters relevant for sample flush-out at the liquid bridge and in the spray capillary were identified by systematic variation of the capillary dimensions, the linear buffer flow rate (2.1–34 mm/s) and molecular weight of the analytes (0.5–30 kDa). We found that a reduction in capillary wall thickness by a factor of 1.6 significantly influences analyte peak shapes, leads to an inversion of the relationship between peak width and analyte molecular weight, and allows a fivefold decrease in peak width for large molecules down to 5 s. The results could be verified and explained by simulations, in which the presence of diffusion-controlled “dead zones” at the liquid bridge and dispersion in the spray tip that depend on analyte molecular weight were identified as key factors relevant for the sample flush-out process. The merging of simulations and experimental data gives useful hints toward the re-design of a spray tip as built-in ESI-MS interface for an optimized gap sampler performance.     

Structures of the N-Terminal Domain of PqsA in Complex with Anthraniloyl- and 6-Fluoroanthraniloyl-AMP: Substrate Activation in Pseudomonas Quinolone Signal (PQS) Biosynthesis

Pseudomonas aeruginosa, a prevalent pathogen in nosocomial infections and a major burden in cystic fibrosis, uses three interconnected quorum-sensing systems to coordinate virulence processes. At variance with other Gram-negative bacteria, one of these systems relies on 2-alkyl-4(1H)-quinolones (Pseudomonas quinolone signal, PQS) and might hence be an attractive target for new anti-infective agents. Here we report crystal structures of the N-terminal domain of anthranilate-CoA ligase PqsA, the first enzyme of PQS biosynthesis, in complex with anthraniloyl-AMP and with 6-fluoroanthraniloyl-AMP (6FABA-AMP) at 1.4 and 1.7 Å resolution. We find that PqsA belongs to an unrecognized subfamily of anthranilate-CoA ligases that recognize the amino group of anthranilate through a water-mediated hydrogen bond. The complex with 6FABA-AMP explains why 6FABA, an inhibitor of PQS biosynthesis, is a good substrate of PqsA. Together, our data might pave a way to new pathoblockers in P. aeruginosa infections.     

Stevia – Ein natürliches Sü?ungsmittel mit gesundheitlichem Zusatznutzen?

Eine Besonderheit der natürlichen Sü?stoffe aus Stevia rebaudiana soll ihre vorteilhafte pharmakologische Wirkung sein. In der wissenschaftlichen Literatur wird immer wieder ein Einfluss auf den menschlichen Blutzuckergehalt und den Blutdruck genannt. Dies w?re ein Novum: Ein Sü?ungsmittel mit Heilwirkung.     

Der Verdacht der Simulation

The Suspicion of Simulation. A Psychiatric Case History between Appropriation and Disciplinary Action at the End of the 19th Century. This case history explores how the question of agency was dealt with historically in two developing, normative orders of deviant behaviour. Examining the institutional career of the supposed adulterer, marriage swindler, and craft baker, we can trace the different observation regimes and systems of knowledge acquisition in the prison and in psychiatry. In both institutions there was talk of simulated madness; the explanations, however, were different. For the prison doctors and civil servants, the baker was a criminal; his deviant behaviour was a matter of consciously planned-out deception. For the examining psychiatrist, on the other hand, he was mentally ill and could not be held responsible for his own behaviour.     

Diamantartige Kohlenstoffschichten steigern die Effizienz

Diamond‐like carbon thin films enhance efficiency — laser arc deposition of ta‐C Rising prices for fossil fuels as well as the increasing effects of the climate change due to the emission of greenhouse gases reveal the necessity of saving energy. Low friction coatings have an enormous potential in saving energy. Carbon based coatings — named as DLC coatings — are especially well suited for low friction coatings. In particular hydrogen‐free tetrahedral amorphous carbon (ta‐C) coatings are of great interest due to their extraordinary low wear properties. In addition they show excellent low friction properties and especially in combination with specific lubricants the so‐called super low friction effect. For the deposition of ta‐C coatings PVD methods have to be applied instead of CVD methods as it is the case for conventional DLC coatings. We have developed a deposition method which is based on a pulsed arc steered by a laser (Laser‐Arc). This allows us to use large cathodes resulting in a high long‐term stability. Furthermore, the carbon plasma source can be combined with a filtering unit removing almost all droplets and particles, which usually are characteristic for an arc process. The resulting Laser‐Arc source allows for the deposition of smooth and virtually defect‐free ta‐C coatings with a competitive deposition rate.     

High‐Temperature Neutron Diffraction,Raman Spectroscopy,and First‐Principles Calculations of Ti3SnC2 and Ti2SnC

Herein, we report—for the first time—on the additive‐free bulk synthesis of Ti₃SnC₂. A detailed experimental study of the structure of the latter together with a secondary phase, Ti₂SnC, is presented through the use of X‐ray diffraction (XRD), and high‐resolution transmission microscopy (HRTEM). A previous sample of Ti₃SnC₂, made using Fe as an additive and Ti₂SnC as a secondary phase, was studied by high‐temperature neutron diffraction (HTND) and XRD. The room‐temperature crystallographic parameters of the two MAX phases in the two samples are quite similar. Based on Rietveld analysis of the HTND data, the average linear thermal expansion coefficients of Ti₃SnC₂ in the a and c directions were found to be 8.5 (2)·10^?6 K^?1 and 8.9 (1)·10^?6 K^?1, respectively. The respective values for the Ti₂SnC phase are 10.1 (3)·10^?6 K^?1 and 10.8 (6)·10^?6 K^?1. Unlike other MAX phases, the atomic displacement parameters of the Sn atoms in Ti₃SnC₂ are comparable to those of the Ti and C atoms. When the predictions of the atomic displacement parameters obtained from density functional theory are compared to the experimental results, good quantitative agreement is found for the Sn atoms. In the case of the Ti and C atoms, the agreement is more qualitative. We also used first principles to calculate the elastic properties of both Ti₂SnC and Ti₃SnC₂ and their Raman active modes. The latter are compared to experiment and the agreement was found to be good.     

On the Cooling Rate-Microstructure Relationship in Molten Metal Gas Atomization

Metallurgical and Materials Transactions A - Gas atomization is the most used powder production technique since it provides good control on particles shape, surface oxidation and dimension. It is a...     

Anti-Inflammatory Characteristics of Local Anesthetics: Inhibition of TNF-α Secretion of Lipopolysaccharide-Stimulated Leucocytes in Human Blood Samples

Background. Local anesthetics (LAs) have potent anti-inflammatory properties. Inflammatory down-regulation is crucial in diseases with overactive immune reactions, such as acute respiratory distress syndrome (ARDS) and chronic inflammation. We investigated the influence of four LAs, procaine, lidocaine, mepivacaine, and bupivacaine, on the reduction of tumor necrosis factor-alpha (TNF-α) secretion in lipopolysaccharide (LPS)-activated human leucocytes. Methods. Blood samples of 28 individuals were stimulated with LPS. The reduction of TNF-α production by each of the four LAs added (0.5 mg/mL) was measured and correlated with biometric variables. A response was defined as reduction to <85% of initial levels. Results. All four LAs down-regulated the TNF-α secretion in 44–61%: Bupivacaine (44.4%), lidocaine (61.5%), mepivacaine (44.4%), and procaine (50% of the individuals, “responders”). The TNF-α secretion was reduced to 67.4, 68.0, 63.6, and 67.1% of the initial values in responders. The effects in both patients and healthy persons were the same. Interindividual responses to LAs were not correlated with the duration or type of complaints, basal TNF-α serum level, sex, BMI, or age of responders. Conclusions. Four clinically relevant LAs (amid-LA and ester-LA) attenuate the inflammatory response provoked by LPS. They are potential candidates for drug repositioning in treating overactive immune reactions and chronic inflammation.     

Stabilizing and destabilizing effects of drug-excipient interactions in spray-dried,freeze-dried,and granulated Sennae fructus extracts

Abstract

The objective of this study was to compare spray-dried and freeze-dried extracts of Sennae fructus regarding the stability of the sennosides. Therefore, the influence of the addition of maltodextrin (MD) not only before the drying processes but also during fluidized bed granulation was investigated. Analysis of the hygroscopicities, the simultaneous TGA-DSC-MS data, and the influence of storage revealed that spray-dried extracts are more stable than freeze-dried extracts. The addition of MD led to an even better stability of the extracts. Lower amounts of MD are sufficient if applied onto the surface of the native extract during fluidized bed granulation.