Automatic fragility curve evaluation of masonry churches accounting for partial collapses by means of 3D FE homogenized limit analysis

A novel 3D homogenized FE limit analysis software is proposed for the fragility curve evaluation of entire existing masonry churches. The approach is a two-step one. In the first phase homogenized masonry strength domains are obtained using a simplified kinematic procedure applied on a three-leaf unitary cell. In the second phase, homogenized domains are implemented at a structural level on a plate and cell kinematic FE software. The procedure is tested on two real scale existing churches located in Italy and compared to results provided by means of a conventional elastic approach performed by means of a standard commercial software. The global behavior at failure and the overall strength of the buildings are assessed through Monte Carlo simulations varying both masonry mechanical properties and direction of the equivalent seismic load.     

Correlation of the loss in photovoltaic module performance with the ageing behaviour of the backsheets used

The influence of the type of backsheet on the electrical performance of test modules was evaluated before and after increasing time of accelerated ageing (damp heat [DH] exposure). Besides the measurement of the electrical power of the modules and the performance of the cells by electroluminescence, the ageing‐induced changes within the polymeric encapsulate and backsheets were investigated by means of vibrational spectroscopy and by thermo analytical methods. In addition, the permeability of the backsheets in the original and aged state was determined. This wide set of test parameters and methods allowed for the detection of correlations between (i) physical and chemical properties as well as their ageing‐induced changes of the materials and (ii) the module performance. A clear dependence of the relative loss in power output upon exposure under DH conditions for 2000 h could be observed for a set of identical test modules varied in composition only in the type of back cover used. While the modules containing gas‐tight backsheets and glass experienced only little loss in the relative power output, some modules with permeable backsheets showed a significant relative decrease in the power output and fill factor in dependence of the backsheet type used. Cell degradation could be visualised by recording electroluminescence images before and after the accelerated ageing test. The permeation properties of the backsheet used and their ageing‐induced changes seem to have an influence on the module performance. However, the absolute values neither of the water vapour transmission rate (WVTR) nor of the oxygen transmission rate (OTR) are directly linked to the loss in power output upon accelerated ageing under DH conditions. It could be shown that the ageing‐induced changes (relative transmission rates) between WVTR and OTR can be correlated with the module performance. These ageing‐induced changes in the permeation behaviour of the backsheets can be explained by (i) physical changes (e.g. post‐crystallisation, changes in the crystal structure or the crystalline microstructure) and (ii) chemical ageing effects such as a decrease in the molecular mass of the polyester (PET) polymer chains because of hydrolytic polymer degradation leading to a change in the crystallisation behaviour of PET. Hydrolytic degradation (= chemical ageing) of the PET core layer was observed (with varying extent) for all PET‐based backsheets and can, thus, not be directly correlated with the loss in performance of the corresponding test modules. The physical ageing effects, however, were detected only for those backsheets showing (i) strong deviating changes in the relative permeation rates for oxygen and water vapour upon accelerated ageing and (ii) a clear loss in electrical performance. Copyright © 2015 John Wiley & Sons, Ltd.     

High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1–actin Complex as a New Potential Target for Therapy

Although the eukaryotic elongation factor eEF1A1 plays a role in various tumours, there is little information on its prognosis/therapeutic value in prostate carcinoma. In high-grade and castration-resistant prostate carcinoma (CRPC), the identification of novel therapeutic markers/targets remains a priority. The expression of eEF1A1 protein was determined in formalin-fixed, paraffin-embedded prostate cancer and hyperplasia tissue by IHC. The role of eEF1A1 was investigated in a cellular model using a DNA aptamer (GT75) we previously developed. We used the aggressive CRPC cancer PC-3 and non-tumourigenic PZHPV-7 lines. Cytotoxicity was measured by the MTS assay and eEF1A1 protein levels by in-cell Western assays. The mRNA levels of eEF1A1 were measured by qPCR and ddPCR. Higher expression of eEF1A1 was found in Gleason 7–8 compared with 4–6 tissues (Gleason ≥ 7, 87% versus Gleason ≤ 6, 54%; p = 0.033). Patients with a high expression of eEF1A1 had a worse clinical outcome. In PC-3, but not in PZHPV-7, GT75 decreased cell viability and increased autophagy and cell detachment. In PC-3 cells, but not in PZHPV-7, GT75 mainly co-localised with the fraction of eEF1A1 bound to actin. Overexpression of the eEF1A1 protein can identify aggressive forms of prostate cancer. The targeting of eEF1A1 by GT75 impaired cell viability in PC-3 cancer cells but not in PZHPV-7 non-tumourigenic cells, indicating a specific role for the protein in cancer survival. The eEF1A1–actin complexes appear to be critical for the viability of PC-3 cancer cells, suggesting that eEF1A1 may be an attractive target for therapeutic strategies in advanced forms of prostate cancer.     

Symposium review: The importance of the ruminal epithelial barrier for a healthy and productive cow

The stratified squamous ruminal epithelium is the main site for absorption of key nutrients (e.g., short-chain fatty acids; SCFA) and electrolytes (e.g., sodium and magnesium). The absorptive function has to be highly selective to prevent simultaneous entry of microbes and toxins from the rumen into the blood. As such, epithelial absorption is primarily transcellular, whereas the paracellular pathway appears rather tightly sealed. A network of tight junction (claudin-1, claudin-4, and occludin) and tight junction-associated proteins (e.g., zonula occludens) accomplishes the latter. When microbial fermentation activity is high such as with highly fermentable diets, rumen epithelial functions are often challenged by acidity, high osmolarity, toxins (e.g., endotoxin and histamine), and immune mediators (inflammatory mediators and cytokines) released during local and systemic inflammation. Epithelial damage by low pH in combination with high luminal SCFA concentrations is not immediately reversible and may initially aggravate upon return to physiological pH. In contrast, barrier opening upon hyperosmolarity is acutely transient. The initial insults set by luminal acidity and SCFA and the increasing concentrations of microbial-associated molecular patterns such as lipopolysaccharides are key factors that trigger inflammation not only in the rumen but also in the hindgut (cecum and colon), which reach out to the liver and other organs, causing systemic inflammation. Low feed intake during parturition, transportation, heat stress, or disease is the second most relevant challenge for the ruminal epithelial barrier. The barrier opening is usually only transient and quickly restored upon refeeding. Due to a rapid, dose-dependent, and prolonged decrease in absorption capacity for SCFA, however, any feed restriction increases the odds for postrestriction subacute ruminal acidosis. Inflammation due to acidosis can be alleviated by supplemental thiamine, yeasts, and plant bioactive (phytogenic) compounds. Butyrate is used in weaning calves to support ruminal barrier development; however, excess butyrate may promote hyperkeratosis, parakeratosis, and epithelial injury in the fully developed rumen of adult cows. Further research is needed to enhance the understanding of the various factors that counteract barrier impairment and help barrier restoration during acidogenic feeding, especially when concurring with unavoidable periods of feed restriction.     

Sensorische Analyse, Malat- und Saccharosegehalt und Fruchtfleischfestigkeit verschiedener Apfelsorten

Zusammenfassung Neben einer ausführlichen sensorischen Beurteilung der Frühsorte Jamba, der mittelspäten Sorten Holsteiner Cox und Roter Holsteiner Cox sowie der späten Sorte Gloster wurden parallel dazu der Malat- und Saccharosegehalt und die Fruchtfleischfestigkeit bestimmt. Die Korrelation dieser chemisch-physikalischen Parameter mit der Bewertung des Geschmacks und der Fruchtfleischstruktur sollte die Frage klären, ob eine Qualitätsaussage unter Umgehung der sensorischen Beurteilung möglich ist. Durch Vergleich ergab sich, daß für alle untersuchten Sorten der Malat- und/oder Saccharosegehalt wenig über die geschmacklichen Qualität der Früchte aussagt. Engere Beziehungen traten zwischen den Parametern sensorische Fruchtfleischbewertung und Festigkeit auf, wo bei einem Festigkeitswert von 5–5,3 kp/cm² und mehr das entsprechende senorische Urteil nicht schlechter als mittelmäßig ausfiel.

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Sensory evaluation, content of malate and sucrose, and fruit firmness of different apple varieties

Summary Parallel to a detailed sensory evaluation of the apple varieties Jamba, Holsteiner Cox, Red Holsteiner Cox and Gloster the content of malate and sucrose and fruit flesh firmness were measured. Comparisons between chemical and physical parameters and the sensory evaluation of taste and fruit flesh structure were performed to see, if apple quality can be determined without sensory assessment. The results for all samples show that content of malate and sucrose means little in relation to fruit taste. Recommendations for an optimum storage period could not be made. There was a closer relationship between sensory fruit flesh assessment and flesh firmness with a firmness of 5–5,3 kp/cm² or higher sensory evaluation was not worse than fair.

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Teil der Dissertation Mast, Kiel 1982     

Micro-RNA and Proteomic Profiles of Plasma-Derived Exosomes from Irradiated Mice Reveal Molecular Changes Preventing Apoptosis in Neonatal Cerebellum

Cell communication via exosomes is capable of influencing cell fate in stress situations such as exposure to ionizing radiation. In vitro and in vivo studies have shown that exosomes might play a role in out-of-target radiation effects by carrying molecular signaling mediators of radiation damage, as well as opposite protective functions resulting in resistance to radiotherapy. However, a global understanding of exosomes and their radiation-induced regulation, especially within the context of an intact mammalian organism, has been lacking. In this in vivo study, we demonstrate that, compared to sham-irradiated (SI) mice, a distinct pattern of proteins and miRNAs is found packaged into circulating plasma exosomes after whole-body and partial-body irradiation (WBI and PBI) with 2 Gy X-rays. A high number of deregulated proteins (59% of WBI and 67% of PBI) was found in the exosomes of irradiated mice. In total, 57 and 13 miRNAs were deregulated in WBI and PBI groups, respectively, suggesting that the miRNA cargo is influenced by the tissue volume exposed to radiation. In addition, five miRNAs (miR-99b-3p, miR-200a-3p, miR-200a, miR-182-5p, miR-182) were commonly overexpressed in the exosomes from the WBI and PBI groups. In this study, particular emphasis was also given to the determination of the in vivo effect of exosome transfer by intracranial injection in the highly radiosensitive neonatal cerebellum at postnatal day 3. In accordance with a major overall anti-apoptotic function of the commonly deregulated miRNAs, here, we report that exosomes from the plasma of irradiated mice, especially in the case of WBI, prevent radiation-induced apoptosis, thus holding promise for exosome-based future therapeutic applications against radiation injury.     

Optimized production of a high-performance hybrid biomaterial: biomineralized spider silk for bone tissue engineering

Silks have been widely used as biomaterials due to their biocompatibility, biodegradability, and excellent mechanical properties. In the present work, native spider silk was used as organic template for controlled nucleation of hydroxyapatite (HA) nano-coating that can act as biomimetic interface. Different bio-inspired neutralization methods and process parameters were evaluated to optimize the silk functionalization. The morphology and chemical composition were investigated by scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analysis and mechanical properties were studied through tensile tests. Results showed that the optimized protocol enabled a controlled and homogeneous nucleation of apatite nano-crystals while maintaining silk mechanical performances after mineralization. This study reports the optimization of a simple and effective bio-inspired nucleation process for precise nucleation of HA onto spider silk templates, suitable to develop high-performance hybrid interfaces for bone tissue engineering. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48739.     

Nitroreductase-Mediated Release of Inhibitors of Lysine-Specific Demethylase 1 (LSD1) from Prodrugs in Transfected Acute Myeloid Leukaemia Cells

Lysine-specific demethylase 1 (LSD1) has evolved as a promising therapeutic target for cancer treatment, especially in acute myeloid leukaemia (AML). To approach the challenge of site-specific LSD1 inhibition, we developed an enzyme-prodrug system with the bacterial nitroreductase NfsB (NTR) that was expressed in the virally transfected AML cell line THP1-NTR⁺. The cellular activity of the NTR was proven with a new luminescent NTR probe. We synthesised a diverse set of nitroaromatic prodrugs that by design do not affect LSD1 and are reduced by the NTR to release an active LSD1 inhibitor. The emerging side products were differentially analysed using negative controls, thereby revealing cytotoxic effects. The 2-nitroimidazolyl prodrug of a potent LSD1 inhibitor emerged as one of the best prodrug candidates with a pronounced selectivity window between wild-type and transfected THP1 cells. Our prodrugs are selectively activated and release the LSD1 inhibitor locally, proving their suitability for future targeting approaches.     

Rapid Biofabrication of Printable Dense Collagen Bioinks of Tunable Properties

Recent convergence of the 3D printing of tissue‐like bioinks and regenerative medicine offers promise in the high‐throughput engineering of in vitro tissue models and organoids for drug screening and discovery research, and of potentially implantable neo‐tissues with tailored structural, biological, and mechanical properties. However, the current printing approaches are not compatible with collagen, the native scaffolding material. Herein, a unique biofabrication approach that uses automated gel aspiration‐ejection (GAE) is reported to potentially overcome these challenges. Automated‐GAE generates highly defined, aligned, dense collagen gel bioinks of various geometries (i.e., cylindrical, quadrangular, and tubular), dimensions, as well as tunable microstructural and mechanical properties that modulate seeded cellular responses. By densifying initial naturally derived reconstituted collagen hydrogels incorporating cells, automated‐GAE generates mini‐tissue building blocks with tailored protein fibril density and alignment, as well as cell loading, density and orientation according to the intended use. Surprisingly, a simple mathematical relationship defining the bioink compaction factor is found to be highly effective in predicting the initial and temporal properties of the bioinks in culture. Therefore, automated‐GAE will potentially also enable a fourth dimension to biofabrication, where cell–cell communications and cell‐extracellular matrix interactions as a function of time in culture can be predicted and modeled.