Objective: Pigment epithelium-derived factor (PEDF) is a multifunctional protein with neurotrophic and anti-angiogenic properties. More recently it became evident that PEDF is upregulated in patients ...with type 2 diabetes and also contributes to insulin resistance in mice. During characterization of the secretome of in vitro differentiated human adipocytes by two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization-MS, we found that PEDF is one of the most abundant proteins released by adipocytes. The aim of this study was to investigate the regulation and autocrine function of PEDF in human adipocytes and to determine its paracrine effects on human skeletal muscle cells (hSkMC) and human smooth muscle cells (hSMC). Methods and results: Human primary adipocytes secrete 130 ng ml-1 PEDF over 24 h from 1 million cells, which is extremely high as compared with adiponectin, interleukin-6 (IL-6) or IL-8. This release of PEDF is significantly higher than from other primary cells, such as adipose-tissue located macrophages (50-times), hSkMC and hSMC (5-times). PEDF protein expression significantly increases during adipogenesis, which is paralleled by increased PEDF secretion. Furthermore, tumor necrosis factor-alpha and hypoxia significantly downregulate PEDF protein levels. PEDF secretion was significantly reduced by troglitazone and hypoxia and significantly increased by insulin. Treatment of adipocytes and hSkMC with PEDF induced insulin resistance in adipocytes, skeletal and smooth muscle cells at the level of insulin-stimulated Akt phosphorylation, which was dose dependent and more prominent in adipocytes. Furthermore, inflammatory nuclear factor-κB (NF-κB) signaling was induced by PEDF. In hSMC, PEDF induced proliferation (1.7-fold) and acutely activated proliferative and inflammatory signaling pathways (NF-κB, p38 mitogen-activated protein kinase and mammalian target of rapamycin). Conclusion: PEDF is one of the most abundant adipokines and its secretion is inversely regulated by insulin and hypoxia. PEDF induces insulin resistance in adipocytes and hSkMC and leads to inflammatory signaling in hSMC. Because of these diverse actions, PEDF is a key adipokine, which could have an important role in diabetes and obesity-related disorders.
Surveillance systems for varicella in Europe are highly heterogeneous or completely absent. We estimated the varicella incidence based on seroprevalence data, as these data are largely available and ...not biased by under-reporting or underascertainment. We conducted a systematic literature search for varicella serological data in Europe prior to introduction of universal varicella immunization. Age-specific serological data were pooled by country and serological profiles estimated using the catalytic model with piecewise constant force of infection. From the estimated profiles, we derived the annual incidence of varicella infection (/100·000) for six age groups (<5, 5–9, 10–14, 15–19, 20–39 and 40–65 years). In total, 43 studies from 16 countries were identified. By the age of 15 years, over 90% of the population has been infected by varicella in all countries except for Greece (86·6%) and Italy (85·3%). Substantial variability across countries exists in the age-specific annual incidence of varicella primary infection among the <5 years old (from 7052 to 16 122 per 100 000) and 5–9 years old (from 3292 to 11 798 per 100 000). The apparent validity and robustness of our estimates highlight the importance of serological data for the characterization of varicella epidemiology, even in the absence of sampling or assay standardization.
The investigations of this article are showing the bonding performance after aging of hybrid fusion bonds in combination with a laser pre-treatment. The investigated materials are a galvanized steel ...(HX340 LAD Z100MB) and two glass fiber reinforced Polyamide 6 materials. In order to achieve a structural strength of the fusion bond a laser pre-treatment is used. The investigation is focusing on the changes from the laser pre-treatment to the galvanized surface by analyzing the steel surface with a scanning electron microscope, energy disperse X-ray spectroscopy, micro sections and surface roughness measurements. The composition of the applied thermoplastic materials is not in the focus of the article which is why different manufacturers for the fiber reinforced thermoplastic material have been chosen. The aging of the samples is done by a climate change (PV1200) and a salt spray (PV1210) test in order to evaluate different aging mechanisms. Furthermore the investigation is providing a crucial finding by showing the impact of a batch change on the achievable lap-shear strength by comparing two batches from the same manufacturer. The results of the laser surface pre-treatment show that the zinc coating of the steel adherend is reduced significantly and does not provide a closed coating. The climate change test after 100 cycles showed no decrease of lap-shear strength compared to the reference when the highest investigated pre-treatment intensity is applied to the surface. The salt spray test showed a corrosion of the pre-treated area for laser pre-treatment settings which generate a low amount of oxygen on the surface. The pre-treatment settings generating a more oxidized surface (medium and high intensity) showed only a minor influence on the achievable lap-shear strength after 90 cycles.
View quality measures compute scores for given views and are used to determine an optimal view in viewpoint selection tasks. Unfortunately, despite the wide adoption of these measures, they are ...rather based on computational quantities, such as entropy, than human preferences. To instead tailor viewpoint measures towards humans, view quality measures need to be able to capture human viewpoint preferences. Therefore, we introduce a large‐scale crowdsourced data set, which contains 58k annotated viewpoints for 3220 ModelNet40 models. Based on this data, we derive a neural view quality measure abiding to human preferences. We further demonstrate that this view quality measure not only generalizes to models unseen during training, but also to unseen model categories. We are thus able to predict view qualities for single images, and directly predict human preferred viewpoints for 3D models by exploiting point‐based learning technology, without requiring to generate intermediate images or sampling the view sphere. We will detail our data collection procedure, describe the data analysis and model training and will evaluate the predictive quality of our trained viewpoint measure on unseen models and categories. To our knowledge, this is the first deep learning approach to predict a view quality measure solely based on human preferences.
View quality measures compute scores for given views and are used to determine an optimal view in viewpoint selection tasks.
The aim of this investigation is to generate a basic understanding of the formation of the joining zone of fusion bonded hybrid joints made of press hardened steel (22MnB5) and polyamide 6 (PA6) ...glass mat reinforced thermoplastic (GMT). To this end, lap-shear samples are produced by varying the steel surface and the fusion bonding temperature. In order to evaluate the resulting joint properties, micrographs of the joining zone are analyzed. Moreover, roughness measurements, scanning electron microscope (SEM) and energy dispersive X-ray spectroscopy (EDS) investigations are used to characterize the steel surface and undercut geometries before joining. By correlating the results of the interface characterization with the mechanical joint strength, optimized fusion bonding parameters can be defined. The results outline the necessity of heating the metal above the melting temperature of the GMT material in order to prevent a solidification in the joining zone. Additionally, the GMT material has to be melted completely to allow the GMT to flow into the geometry undercuts of the AlSi surface. The maximum lap-shear strength is 22.9 ± 2.1 MPa. It was achieved with the samples showing to a metal temperature of 280°C and a GMT temperature of 260°C.
The prevalence of mental disorders and comorbidity with substance abuse and personality disorders is high in prisoners. Furthermore, drug abuse in prison is a widespread problem throughout prisons ...around the world. In this retrospective study, we analyzed the prison deaths over six years (2012–2017). For each death, we collected data of the Berlin prison system, the prison hospital and the State Institute for Forensic and Social Medicine Berlin and the Institute of Legal Medicine and Forensic Sciences, Charité Medical University Berlin. In total, 33 prisoners died during our study period, of which 24 committed suicide. In 25% of the suicide cases, forensic toxicology reports were positive for drugs without cases of lethal intoxication. A direct influence of drug intoxication on prisoner deaths and suicide was not common in our data. Small sample size, a missing control group, and the retrospective study design limit generalizability of the results.
The subject of the present study was to analyze the influence of genetic introgression on milk yield performance of the German local Vorderwald and Hinterwald cattle breeds. Deviations of milk yield, ...fat yield, and protein yield of cows as well as pedigree information were analyzed. A sire model was used to estimate genetic trend and effects of the migrant breeds. Migrant contributions to Vorderwald cattle were high and have been rising even in the recent past. The effects of these breeds on milk yield performance were positive. Montbéliarde cattle not only had the largest effect on milk production of Vorderwald cattle but also the highest genetic contribution to this breed. Genetic introgression with Montbéliarde continued until recently. This suggests that introgression of high-yielding breeds is still a preferred method for genetic improvement of local breeds, even though it diminishes their value for conservation. Hence, the current population management has too little focus on the preservation of genetic uniqueness. In comparison, migrant breed contributions to the Hinterwald cattle, a breed with a unique phenotype and an own niche, were moderate and almost constant over the time. For the Hinterwald cattle, no significant effect of migrant breeds could be detected, which suggests that population management has different priorities in different endangered breeds. We conclude that not only the registration of animals from local breeds but also the breeding programs themselves should be supported and need to be controlled.
Abstract Multi-material structures in the automotive industry hold great potential for lightweight design, body construction, and functionalization due to their favorable mechanical properties and ...reduced structural weight. The combination of metal and plastic, in particular, is commonly used to enhance the overall properties of the end product when compared to single-material structures. This paper describes a process development with a hot-stamping and an extrusion tool. By means of this tool, a thermally assisted extrusion process can be used to join GMT (Glass Mat reinforced Thermoplastics) and 22MnB5 steel in a single process step. Through adhesion, the GMT adheres to the rough surface of the AlSi(aluminum-silicon)-coated 22MnB5. Test components were manufactured and through static tests the influence of process parameters was evaluated. Assuming that the parameters determined for the reference component are already sufficient for a design in the vehicle, the reduction of the steel thickness of the structure from 1.5 mm to 1.2 mm can be recommended on the basis of the results obtained. This is accompanied by a reduction in the mass of the test structure used while maintaining or improving its dynamic and static properties. Further weight savings appear possible through further component and process optimization.
An uncharacterized plant cDNA coding for a polypeptide presumably having sesquiterpene synthase activity, was expressed in soluble and active form. Two expression strategies were evaluated in ...Escherichia coli. The enzyme was fused to a highly soluble SUMO domain, in addition to being produced in an unfused form by a cold-shock expression system. Yields up to ∼325mg/L−1 were achieved in batch cultivations. The 6x-His-tagged enzyme was purified employing an Ni2+-IMAC-based procedure. Identity of the protein was established by Western Blot analysis as well as peptide mass fingerprinting. A molecular mass of 64 kDa and an isoelectric point of pI 4.95 were determined by 2D gel electrophoresis. Cleavage of the fusion domain was possible by digestion with specific SUMO protease. The synthase was active in Mg2+ containing buffer and catalyzed the production of (+)-zizaene (syn. khusimene), a precursor of khusimol, from farnesyl diphosphate. Product identity was confirmed by GC–MS and comparison of retention indices. Enzyme kinetics were determined by measuring initial reaction rates for the product, using varying substrate concentrations. By assuming a Michaelis–Menten model, kinetic parameters of KM = 1.111 μM (±0.113), vmax = 0.3245 μM min−1 (±0.0035), kcat = 2.95min−1, as well as a catalytic efficiency kcat/KM = 4.43 × 104 M−1s−1 were calculated.
Fusion to a SUMO moiety can substantially increase soluble expression levels of certain hard to express terpene synthases in E. coli. The kinetic data determined for the recombinant synthase are comparable to other described plant sesquiterpene synthases and in the typical range of enzymes belonging to the secondary metabolism. This leaves potential for optimizing catalytic parameters through methods like directed evolution.
•Uncharacterized (+)-zizaene synthase from C. zizanoides was cloned and expressed.•Fusion to SUMO and cold-shock induction enhanced soluble yields in E. coli.•Ni2+-IMAC purification of the SUMO-fused and unfused enzyme.•(+)-Zizaene identified as main cyclization product by GC–MS.•Enzyme kinetic parameters comparable to related sesquiterpene synthases.
Boriding produce thick hard layers on cast iron components, which can improve their wear and corrosion behaviour. However, this potential cannot be fully exploited by a simple boriding due to the ...material specific presence of graphite. In that context, this paper presents results of two fundamentally different electron beam liquid surface treatments (remelting, cladding with nickel‐based additive) and their possibilities and limitations regarding subsequent boriding. The boriding behaviour under conventional high temperatures (760 °C–860 °C), and experiments on low‐temperature boriding (600 °C–700 °C) were investigated. Under identical treatment conditions, the compound layer thicknesses generated on the unalloyed surfaces (remelting) were approx. 50 %–75 % greater than those of the alloyed surfaces (cladding). A two‐layered boride layer structure were generated, though with different phase compositions. Nevertheless, the hardness of all borided layers were comparable. Surface hardness measurements revealed that the supporting effect of substrates plays a decisive role up to a boride layer thickness of approx. 57 μm. In this layer‐thickness range, the compound hardness of the alloyed substrates is higher than that of the unalloyed substrates. This knowledge should prove decisive for the selection of layer composites for corrosive and/or tribologically stressed components.
Translation
Beim Borieren können dicke, harte Schichten auf Gusseisenbauteilen generiert werden, die deren Verschleiß‐ und Korrosionsverhalten verbessern können. Dieses Potenzial kann jedoch durch ein einfaches Borieren aufgrund des werkstoffspezifischen Vorhandenseins von Graphit nicht vollständig ausgeschöpft werden. Desbezüglich werden in diesem Beitrag die Ergebnisse von zwei grundlegend unterschiedlichen Elektronenstrahl‐Flüssigphasen‐Randschichtbehandlungen (Umschmelzen, Auftragen mit Nickel‐Basis‐Zusatzstoff) und deren Möglichkeiten und Grenzen beim anschließenden Borieren vorgestellt. Es wurde das Borierverhalten bei konventionellen hohen Temperaturen (760 °C–860 °C) und Experimente zum Tieftemperaturborieren (600 °C–700 °C) untersucht. Unter identischen Behandlungsbedingungen waren die auf den unlegierten Oberflächen (Umschmelzen) erzeugten Verbindungsschichtdicken ca. 50 %–75 % dicker als die der legierten Oberflächen (Auftragen). Es entstand eine zweiphasige Boridschicht, allerdings mit unterschiedlicher Phasenzusammensetzung. Dennoch waren die Härtewerte aller Boridschichten vergleichbar. Oberflächenhärtemessungen ergaben, dass die Stützwirkung der Substrate bis zu einer Boridschichtdicke von ca. 57 μm eine entscheidende Rolle spielt. In diesem Schichtdickenbereich ist die Verbundhärte der legierten Substrate höher als die der unlegierten Substrate. Diese Erkenntnisse sind entscheidend für die Auswahl von Schichtverbunden für korrosiv und/oder tribologisch beanspruchte Bauteile.
Under comparable boriding conditions, the layer thickness generated on the unalloyed cast iron surface were approximately twice as thick as on the nickel cladded surface. For the unalloyed substrate, the well‐known iron borides were determined. The boride layer formed on the alloyed surface contained iron borides with dissolved nickel portions as well as additional fractions of nickel borides.
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