Interleukin‐4‐Clicked Surfaces Drive M2 Macrophage Polarization

Driving macrophage (M?) polarization into the M2 phenotype provides potential against inflammatory diseases. Interleukin‐4 (IL‐4) promotes polarization into the M2‐M? phenotype, but its systemic use is constrained by dose‐limiting toxicity. Consequently, we developed IL‐4‐decorated surfaces aiming at sustained and localized activity. IL‐4 muteins were generated by genetic code expansion; Lys42 was replaced by unnatural amino acids (uAAs). Both muteins showed cell‐stimulation ability and binding affinity to IL4Rα similar to those of wt‐IL‐4. Copper‐catalyzed (CuAAC) and copper‐free strain‐promoted (SPAAC) 1,3‐dipolar azide–alkyne cycloadditions were used to site‐selectively anchor IL‐4 to agarose surfaces. These surfaces had sustained IL‐4 activity, as demonstrated by TF‐1 cell proliferation and M2, but not M1, polarization of M‐CSF‐generated human M?. The approach provides a blueprint for the engineering of cytokine‐activated surfaces profiled for sustained and spatially controlled activity.     

Development and Validation of an Artificial Mechanical Skin Model for the Study of Interactions between Skin and Microneedles

Microneedles are small needle‐like structures that are almost invisible to the naked eye. They have an immense potential to serve as a valuable tool in many medical applications, such as painless vaccination. Microneedles work by breaking through the stratum corneum, the outermost barrier layer of the skin, and providing a direct path for drug delivery into the skin. A lot of research has been presented over the past two decades on the applications of microneedles, yet the fundamental mechanism of how they interact, pressure, and penetrate the skin in its native state is worth examining further. As such, a major difficulty with understanding the mechanism of microneedle–skin interaction is the lack of an artificial mechanical human skin model to use as a standardized substrate. In this research news, the development of an artificial mechanical skin model based on a thorough mechanical study of fresh human and porcine skin samples is presented. The artificial mechanical skin model can be used to study the mechanical interactions between microneedles and skin, but not diffusion of molecules across skin. This model can assist in improving the performance of microneedles by enhancing the reproducibility of microneedle depth insertions for optimal drug delivery and biosensing.

     

Prototype and Chimera-Type Galectins in Placentas with Spontaneous and Recurrent Miscarriages

Galectins are galactose binding proteins and, in addition, factors for a wide range of pathologies in pregnancy. We have analyzed the expression of prototype (gal-1, -2, -7, -10) and chimera-type (gal-3) galectins in the placenta in cases of spontaneous abortions (SPA) and recurrent abortions (RA) in the first trimester. Fifteen placental samples from healthy pregnancies were used as a control group. Nine placentas were examined for spontaneous abortions, and 12 placentas for recurrent abortions. For differentiation and evaluation of different cell types of galectin-expression in the decidua, immunofluorescence was used. For all investigated prototype galectins (gal-1, -2, -7, -10) in SPA and RA placenta trophoblast cells the expression is significantly decreased. In the decidua/extravillous trophoblast only gal-2 expression was significantly lowered, which could be connected to its role in angiogenesis. In trophoblasts in first-trimester placentas and in cases of SPA and RA, prototype galectins are altered in the same way. We suspect prototype galectins have a similar function in placental tissue because of their common biochemical structure. Expression of galectin 3 as a chimera type galectin was not found to be significantly altered in abortive placentas.     

Investigation of the Antiproliferative Properties of Natural Sesquiterpenes from Artemisia asiatica and Onopordum acanthium on HL-60 Cells in Vitro

Plants and plant extracts play a crucial role in the research into novel antineoplastic agents. Four sesquiterpene lactones, artecanin (1), 3β-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guaia-11(13)-en-12,6α-olide (2), iso-seco-tanapartholide 3-O-methyl ether (3) and 4β,15-dihydro-3-dehydrozaluzanin C (4), were isolated from two traditionally used Asteraceae species (Onopordum acanthium and Artemisia asiatica). When tested for antiproliferative action on HL-60 leukemia cells, these compounds exhibited reasonable IC₅₀ values in the range 3.6–13.5 μM. Treatment with the tested compounds resulted in a cell cycle disturbance characterized by increases in the G1 and G2/M populations, while there was a decrease in the S phase. Additionally, 1–3 elicited increases in the hypodiploid (subG1) population. The compounds elicited concentration-dependent chromatin condensation and disruption of the membrane integrity, as revealed by Hoechst 33258–propidium staining. Treatment for 24 h resulted in significant increases in activity of caspases-3 and -9, indicating that the tested sesquiterpenes induced the mitochondrial pathway of apoptosis. The proapoptotic properties of the sesquiterpene lactones were additionally demonstrated withannexin V staining. Compounds 1 and 2 increased the Bax/Bcl-2 expression and decreased the expressions of CDK1 and cyclin B2, as determined at the mRNA level by means of RT-PCR. These experimental results indicate that sesquiterpene lactones may be regarded as potential starting structures for the development of novel anticancer agents.     

Heads or Tails: Genotyping of Hepatitis C Virus Concerning the 2k/1b Circulating Recombinant Form

As different hepatitis C virus (HCV) genotypes respond differently to initiated therapy, correct HCV genotyping is essential. A potential risk for misclassification of the intergenotypic HCV circulating recombinant form (CRF) 2k/1b strains exists, depending on the genotyping method used. The aim was to investigate the differences in HCV genotyping methods with regard to CRF 2k/1b and to gain insight in the prevalence of the CRF 2k/1b. Genotyping results by Versant HCV Genotype Assay were compared with nonstructural protein 5B (NS5B) sequencing. In total, from November 2001 until March 2015, 3296 serum samples were analyzed by Versant HCV Genotype Assay. As misclassified CRF is harbored among HCV genotype 2, we further focused our search on 142 (4.3%) samples positive for HCV genotype 2. On 116 (81.7%) retrieved samples, the NS5B sequencing was performed. Twelve out of the 116 retrieved samples (10.3%) were classified as CRF 2k/1b by sequencing of the NS5B region. Ten of these 12 samples were originally misclassified as genotype 2a or 2c, while 2 of them were misclassified as genotype 2. Our results show that the current prevalence of CRF 2k/1b is underestimated. The importance of correct HCV genotyping is emphasized, considering the tailored choice of treatment regimen and overall prognosis.     

Effect of blend ratio on the dynamic mechanical and thermal degradation behavior of polymer–polymer composites from low density polyethylene and polyethylene terephthalate

Microfibrillar polymer–polymer composites (MFCs) based on low-density polyethylene (LDPE) and polyethylene terephthalate (PET) were prepared by cold drawing-isotropization technique. The weight percentage of PET was varied from 5 to 45 %. Microfibrils with uniform diameter distribution were obtained at 15 to 25 wt% of PET as evident from the scanning electron microscopy (SEM) results. Dynamic mechanical properties such as storage modulus (E′), loss modulus (E″) damping behavior (tan δ) were examined as a function of blend composition. The E′ values were found to be increasing up to 25 wt% of PET. An effort was made to model the storage modulus and damping characteristics of the MFCs using the classical equations used for short-fiber reinforced composites. The presence of PET microfibrils influenced the damping characteristics of the composite. The peak height at the β-transitions of loss modulus was lower for MFCs with 25 % PET, showing that they had superior damping characteristics. This phenomenon could be correlated with the PET microfibrils morphology. The thermal degradation characteristics of LDPE, neat blends and microfibrillar blends (MFBs) were compared. The determination of activation energy for thermal degradation was carried out using the Horowitz and Metzger method. The activation energy for thermal degradation of microfibrillar blends was found to be higher than that for the corresponding neat blends and MFCs. The long PET microfibrils present in MFBs could prevent the degradation and enhance the activation energy.     

A look behind the curtain: Measuring the complex economic effects of regional structural funds in Germany

This paper investigates the mutual impact channels of Germany's major regional policy instrument (GRW) on regional economic development. Different from earlier studies which have predominately focused on a partial assessment of output effects, we explicitly endogenize the factor inputs of the underlying production function. This allows us to comprehensively assess the role of the GRW in driving per capita output, employment, human and physical capital intensities as well as the region's technological growth. The results from a spatial panel vector autoregressive model show that GRW funding has significant positive effects on regional output, the employment rate and human capital intensity.     

Sanierung eines PCE-Schadens in einem makroskopisch oxischen Grundwasserleiter durch Stimulation anaerober dehalogenierender Bakterien

Grundwasser - Eine erfolgreiche biologische In-situ-Sanierung von PCE-kontaminierten Grundwasserleitern erfordert hinreichend reduzierende Bedingungen sowie die Anwesenheit von molekularem...     

3D reconstruction of existing concrete bridges using optical methods

Routine bridge inspections usually consist of visual observations. These inspections are time-consuming and subjective. There is a need to identify new inspection techniques for infrastructure that reduce traffic disturbance, and improve the efficiency and reliability of the acquired data. This study compared the performance of three different imaging technologies for the three-dimensional (3D) geometric modeling of existing structures: terrestrial laser scanning, close-range photogrammetry, and infrared scanning. Each technology was used to assess six existing concrete railway bridges. The technologies were compared in terms of geometric deviations, visualization capabilities, the level of the inspector’s experience, and degree of automation. The results suggest that all methods investigated can be used to create 3D models, however, with different level of completeness. Measurements such as span length, deck widths, etc. can be extracted with good accuracy. Although promising, a full off-site inspection is currently not feasible as some areas of the bridges were difficult to capture mainly due to restricted access and narrow spaces. Measurements based on terrestrial laser scanning were closer to the reality compared to photogrammetry and infrared scanning. The study indicates the no special training is needed for photogrammetry and infrared scanning to generate a 3D geometric model.