Wet-Spinning of Biocompatible Core–Shell Polyelectrolyte Complex Fibers for Tissue Engineering

Polyelectrolyte complex fibers (PEC fibers) have great potential with regard to biomedical applications as they can be fabricated from biocompatible and water-soluble polyelectrolytes under mild process conditions. The present publication describes a novel method for the continuous fabrication of PEC fibers in a water-based wet-spinning process by interfacial complexation within a core–shell spinneret. This process combines the robustness and flexibility of nonsolvent-induced phase separation (NIPS) spinning processes conventionally used in the membrane industry with the complexation between oppositely charged polyelectrolytes. The produced fibers demonstrate a core–shell structure with a low-density core and a highly porous polyelectrolyte complex shell of ≈800 μm diameter. In the case of chitosan and polystyrene sulfonate (PSS), mechanical fiber properties could be enhanced by doping the PSS with poly(ethylene oxide) (PEO). The resulting CHI/PSS-PEO fibers present a Young modulus of 3.78 GPa and a tensile strength of 165 MPa, which is an excellent combination of elongation at break and break stress compared to literature. The suitability of the CHI/PSS-PEO fibers as a scaffold for cell culture applications is verified by a four-day cultivation of human HeLa cells on PEO-reinforced fibers with a subsequent analysis of cell viability by fluorescence-based live/dead assay. © 2020 The Authors. Published by Wiley-VCH Gmb

Transient spurious intrathecal immunoglobulin synthesis in neurological patients after therapeutic apheresis

Background The analysis of cerebrospinal fluid (CSF) is usually done under steady-state conditions, when proteins (e.g., immunoglobulins) reach diffusion equilibrium between blood and CSF. However, little data has been published on CSF analysis under non-steady-state conditions after therapeutic apheresis. By reducing serum proteins (e.g., immunoglobulins), while leaving CSF unchanged, therapeutic apheresis might cause spuriously altered intrathecal immunoglobulin fractions. Methods Based on the incidental finding of plasma exchange-induced increased intrathecal immunoglobulin fractions in a cohort of 12 unsystematically selected patients with various neurological disorders, we retrospectively investigated CSF results that had been raised during routine diagnostic work-up from 41 consecutive neurological patients (predominantly Guillain-Barré syndrome and autoimmune encephalitis) treated with plasmapheresis or immunoadsorption in a tertiary care university hospital in whom lumbar puncture (LP) was performed after a varying number of treatments of therapeutic apheresis. Results Only when LP was performed 1 day after therapeutic apheresis, spurious quantitative intrathecal immunoglobulin (Ig) synthesis of at least one subclass (IgG, IgA and/or IgM) was found in 68.4 % of the patients, irrespective of the number of treatments, in all age groups and independent of other previous immunotherapies (e.g., steroids). This phenomenon occurred only transiently and was almost always accompanied by an elevation of the IgG index. In one patient, an elevated IgG index was noticed even 2 days after plasmapheresis. Neither quantitative Ig synthesis, nor elevated IgG index was observed when the LP was performed three or more days after therapeutic apheresis. Conclusions Spurious quantitative intrathecal Ig synthesis and increased IgG index are common findings shortly after plasmapheresis or immunoadsorption due to altered serum immunoglobulin levels. Knowledge of this phenomenon is needed for clinicians to prevent false interpretations leading to unnecessary diagnostic and therapeutic procedures. Misdiagnoses can be avoided by considering the characteristic CSF constellation including absence of oligoclonal bands and the close temporal relation to therapeutic apheresi

Porous PEDOT:PSS Particles and their Application as Tunable Cell Culture Substrate

Due to its biocompatibility, electrical conductivity, and tissue-like elasticity, poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) constitutes a highly promising material regarding the fabrication of smart cell culture substrates. However, until now, high-throughput synthesis of pure PEDOT:PSS geometries was restricted to flat sheets and fibers. In this publication, the first microfluidic process for the synthesis of spherical, highly porous, pure PEDOT:PSS particles of adjustable material properties is presented. The particles are synthesized by the generation of PEDOT:PSS emulsion droplets within a 1-octanol continuous phase and their subsequent coagulation and partial crystallization in an isopropanol (IPA)/sulfuric acid (SA) bath. The process allows to tailor central particle characteristics such as crystallinity, particle diameter, pore size as well as electrochemical and mechanical properties by simply adjusting the IPA:SA ratio during droplet coagulation. To demonstrate the applicability of PEDOT:PSS particles as potential cell culture substrate, cultivations of L929 mouse fibroblast cells and MRC-5 human fibroblast cells are conducted. Both cell lines present exponential growth on PEDOT:PSS particles and reach confluency with cell viabilities above 95 vol.% on culture day 9. Single cell analysis could moreover reveal that mechanotransduction and cell infiltration can be controlled by the adjustment of particle crystallinity

Multi-object spectroscopy of stars in the CoRoT fields II: The stellar population of the CoRoT fields IRa01, LRa01, LRa02, and LRa06

With now more than 20 exoplanets discovered by CoRoT, it has often been considered strange that so many of them are orbiting F-stars, and so few of them K or M-stars. Although transit search programs are mostly sensitive to short-period planets, they are ideal for verifying these results. To determine the frequency of planets as a function of stellar mass, we also have to characterize the sample of stars that was observed. We study the stellar content of the CoRoT-fields IRa01, LRa01 (=LRa06), and LRa02 by determining the spectral types of 11466 stars. We used spectra obtained with the multi-object spectrograph AAOmega and derived the spectral types by using template spectra with well-known parameters. We find that 34.8+/-0.7% of the stars observed by CoRoT in these fields are F-dwarfs, 15.1+/-0.5% G-dwarfs, and 5.0+/-0.3% K-dwarfs. We conclude that the apparent lack of exoplanets of K- and M-stars is explained by the relatively small number of these stars in the observed sample. We also show that the apparently large number of planets orbiting F-stars is similarly explained by the large number of such stars in these fields. Our study also shows that the difference between the sample of stars that CoRoT observes and a sample of randomly selected stars is relatively small, and that the yield of CoRoT specifically is the detection one hot Jupiter amongst 2100+/-700 stars. We conclude that transit search programs can be used to study the relation between the frequency of planets and the mass of the host stars, and that the results obtained so far generally agree with those of radial velocity programs.Comment: 231 pages with 6 figures, A&A accepte

Sub-stellar companions of intermediate-mass stars with CoRoT: CoRoT–34b, CoRoT–35b, and CoRoT–36b

Theories of planet formation give contradicting results of how frequent close-in giant planets of intermediate mass stars (IMSs; 1.3≤M⋆≤3.2M⊙⁠) are. Some theories predict a high rate of IMSs with close-in gas giants, while others predict a very low rate. Thus, determining the frequency of close-in giant planets of IMSs is an important test for theories of planet formation. We use the CoRoT survey to determine the absolute frequency of IMSs that harbour at least one close-in giant planet and compare it to that of solar-like stars. The CoRoT transit survey is ideal for this purpose, because of its completeness for gas-giant planets with orbital periods of less than 10 d and its large sample of main-sequence IMSs. We present a high precision radial velocity follow-up programme and conclude on 17 promising transit candidates of IMSs, observed with CoRoT. We report the detection of CoRoT–34b, a brown dwarf close to the hydrogen burning limit, orbiting a 1.1 Gyr A-type main-sequence star. We also confirm two inflated giant planets, CoRoT–35b, part of a possible planetary system around a metal-poor star, and CoRoT–36b on a misaligned orbit. We find that 0.12±0.10 per cent of IMSs between 1.3≤M⋆≤1.6M⊙ observed by CoRoT do harbour at least one close-in giant planet. This is significantly lower than the frequency (⁠0.70±0.16 per cent⁠) for solar-mass stars, as well as the frequency of IMSs harbouring long-period planets (⁠∼8 per cent⁠)

Glial Activation Markers in CSF and Serum From Patients With Primary Progressive Multiple Sclerosis: Potential of Serum GFAP as Disease Severity Marker?

Background: In progressive multiple sclerosis (MS), glial activation is thought to be a relevant mechanism of disability progression. Therefore, in vivo assessment of the glial cell activity is, in the emerging treatment era of primary progressive MS (PPMS), more important than ever. Objectives: To test the association of cerebrospinal fluid (CSF) and serum markers of glial activation in PPMS patients;including glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (CHI3L1), soluble variant of triggering receptor expressed on myeloid cells 2 (sTREM2), and marker of neuroaxonal damage (Neurofilament light chain, NfL) as well as clinical severity. Methods: CSF and serum samples from PPMS patients were collected in the MS-centers at Universities of Freiburg (n = 49), Ulm (n = 27), Muenster (n = 11), and Rostock (n = 6). sTREM2 and CHI3L1 levels were measured using the previously reported ELISA assays, while NfL and GFAP were measured using SIMOA assays. Clinical data included age, gender, disease duration, treatment status, and Expanded Disability Status Scale (EDSS). Results: 93 CSF samples and 71 matching serum samples were analyzed. The median age of patients was 49 years and disease duration 4.5 years. GFAP(serum) correlated with EDSS after correction for age (beta = 0.3, p = 0.001). Furthermore, EDSS was higher in patients with a GFAP(serum) level >= 151.7 pg/ml compared to patients with GFAP(serum) below this cut-off (5.5 vs. 4.0, p = 0.009). Other markers did not correlate with the clinical severity. Moreover, we found a correlation between NfL(CSF) and GFAP(CSF), sTREM2 and CHI3L1 (rho = 0.4 for GFAP(CSF) and sTREM2, rho = 0.3 for CHI3L1, p < 0.01 for sTREM2 and CHI3L1 and <0.001 for GFAP(CSF)). CHI3L1 did not correlate with GFAP(CSF) but with sTREM2 (rho = 0.4, p < 0.01). Discussion: The correlation between the glial activation markers in CSF with the markers of neuroaxonal demise supports the notion of the glial involvement in PPMS. The positive correlation between GFAP(CSF) with disease duration and GFAP(serum) with the clinical severity of the disease may highlight a particular role of the astrocytes in PPMS and mark the potential of GFAPserum as a disease severity marker

The EBLM project – IX. Five fully convective M-dwarfs, precisely measured with CHEOPS and TESS light curves

Eclipsing binaries are important benchmark objects to test and calibrate stellar structure and evolution models. This is especially true for binaries with a fully convective M-dwarf component for which direct measurements of these stars’ masses and radii are difficult using other techniques. Within the potential of M-dwarfs to be exoplanet host stars, the accuracy of theoretical predictions of their radius and effective temperature as a function of their mass is an active topic of discussion. Not only the parameters of transiting exoplanets but also the success of future atmospheric characterization relies on accurate theoretical predictions. We present the analysis of five eclipsing binaries with low-mass stellar companions out of a subsample of 23, for which we obtained ultra-high-precision light curves using the CHEOPS satellite. The observation of their primary and secondary eclipses are combined with spectroscopic measurements to precisely model the primary parameters and derive the M-dwarfs mass, radius, surface gravity, and effective temperature estimates using the PYCHEOPS data analysis software. Combining these results to the same set of parameters derived from TESS light curves, we find very good agreement (better than 1 per cent for radius and better than 0.2 per cent for surface gravity). We also analyse the importance of precise orbits from radial velocity measurements and find them to be crucial to derive M-dwarf radii in a regime below 5 per cent accuracy. These results add five valuable data points to the mass–radius diagram of fully convective M-dwarfs