Using internal domain-specific languages to inherit tool support and modularity for model transformations

Software and Systems Modeling - Model-driven engineering (MDE) has proved to be a useful approach to cope with today’s ever-growing complexity in the development of software systems;...     

Salmonella in eggs: From shopping to consumption—A review providing an evidence-based analysis of risk factors

Nontyphoidal salmonellae are among the most prevalent foodborne pathogens causing gastrointestinal infections worldwide. A high number of cases and outbreaks of salmonellosis are associated with the consumption of eggs and egg products, and several of these occur at the household level. The aim of the current study is to critically evaluate the current status of knowledge on Salmonella in eggs from a consumer's perspective, analyzing the hazard occurrence and the good practices that should be applied to reduce salmonellosis risk. Following a HACCP (Hazard Analysis and Critical Control Point) based approach, some steps along the food journey were identified as Critical Consumer Handling (CCH)—steps in which consumers, through their behavior or choice, can significantly reduce the level of Salmonella in eggs and egg products. From shopping/collecting to consumption, each of these steps is discussed in this review to provide an evidence-based overview of risk factors of human salmonellosis related to egg consumption. The main message to consumers is to choose Salmonella-free eggs (those that some official entity or producer guarantees that does not contain Salmonella), when available, especially for dishes that are not fully heat treated. Second, as guaranteed Salmonella-free eggs are only available in a few countries, refrigerated storage from the point of collection and proper cooking will significantly reduce the risk of salmonellosis. This will require a revision of the actual recommendations/regulations, as not all ensure that eggs are maintained at temperatures that prevent growth of Salmonella from collection until the time of purchasing.     

Proteome profiling of exosomes derived from plasma of heifers with divergent genetic merit for fertility

The current study evaluated exosomes isolated from plasma of heifers bred to have high or low fertility through developing extreme diversity in fertility breeding values, however, key animal traits (e.g., body weight, milk production, and percentage of North American genetics) remained similar between the 2 groups. The exosomes were isolated by a combined ultracentrifugation and size exclusion chromatography approach and characterized by their size distribution (nanoparticle tracking analysis), morphology (transmission electron microscopy), and presence of exosomal markers (immunoblotting). In addition, a targeted mass spectrometry approach was used to confirm the presence of 2 exosomal markers, tumor susceptibility gene 101 and flotillin 1. The number of exosomes from plasma of high fertility heifers was greater compared with low fertility heifers. Interestingly, the exosomal proteomic profile, evaluated using mass spectrometry, identified 89 and 116 proteins in the high and low fertility heifers respectively, of which 4 and 31 were unique, respectively. These include proteins associated with specific biological processes and molecular functions of fertility. Most notably, the tetratricopeptide repeat protein 41-related, glycodelin, and kelch-like protein 8 were identified in plasma exosomes unique to the low fertility heifers. These proteins are suggested to play a role in reproduction; however, the role of these proteins in dairy cow reproduction remains to be elucidated. Their identification underscores the potential for proteins within exosomes to provide information on the fertility status and physiological condition of the cow. This may potentially lead to the development of prognostic tools and interventions to improving dairy cow fertility.     

Click-Chemistry (CuAAC) Trimerization of an αvβ6 Integrin Targeting Ga-68-Peptide: Enhanced Contrast for in-Vivo PET Imaging of Human Lung Adenocarcinoma Xenografts

α_vβ₆ Integrin is an epithelial transmembrane protein that recognizes latency-associated peptide (LAP) and primarily activates transforming growth factor beta (TGF-β). It is overexpressed in carcinomas (most notably, pancreatic) and other conditions associated with α_vβ₆ integrin-dependent TGF-β dysregulation, such as fibrosis. We have designed a trimeric Ga-68-labeled TRAP conjugate of the α_vβ₆-specific cyclic pentapeptide SDM17 (cyclo[RGD-Chg-E]-CONH₂) to enhance α_vβ₆ integrin affinity as well as target-specific in-vivo uptake. Ga-68-TRAP(SDM17)₃ showed a 28-fold higher α_vβ₆ affinity than the corresponding monomer Ga-68-NOTA-SDM17 (IC₅₀ of 0.26 vs. 7.4 nM, respectively), a 13-fold higher IC₅₀-based selectivity over the related integrin α_vβ₈ (factors of 662 vs. 49), and a threefold higher tumor uptake (2.1 vs. 0.66 %ID/g) in biodistribution experiments with H2009 tumor-bearing SCID mice. The remarkably high tumor/organ ratios (tumor-to-blood 11.2; -to-liver 8.7; -to-pancreas 29.7) enabled high-contrast tumor delineation in PET images. We conclude that Ga-68-TRAP(SDM17)₃ holds promise for improved clinical PET diagnostics of carcinomas and fibrosis.     

Effects of timing of formative feedback in computer-assisted learning environments

This study examines the effects of timing of corrective formative feedback on processing text information on question-answering. Undergraduate students read an expository text and answered questions in two attempts. Students were randomly assigned to a no feedback, immediate feedback and delayed feedback conditions. Students in the feedback conditions received feedback on the correctness of their answer after the first attempt and were informed about the right answer after the second attempt. Students were prompted to restudy the text after failing in their first attempt. However, students in the no feedback condition were just prompted to search the text. All students were tested on question-answering, corrective probability and a post-test cued-recall test. Results showed that: (a) feedback reduced the initial time reading the text; (b) feedback increased performance on question answering and cued-recall; (c) delayed feedback produced no advantages over immediate feedback. Theoretical and practical implications of these results are discussed.     

Neutrophils Enable Local and Non-Invasive Liposome Delivery to Inflamed Skeletal Muscle and Ischemic Heart

Uncontrolled inflammation is a major pathological factor underlying a range of diseases including autoimmune conditions, cardiovascular disease, and cancer. Improving localized delivery of immunosuppressive drugs to inflamed tissue in a non-invasive manner offers significant promise to reduce severe side effects caused by systemic administration. Here, a neutrophil-mediated delivery system able to transport drug-loaded nanocarriers to inflamed tissue by exploiting the inherent ability of neutrophils to migrate to inflammatory tissue is reported. This hybrid system (neutrophils loaded with liposomes ex vivo) efficiently migrates in vitro following an inflammatory chemokine gradient. Furthermore, the triggered release of loaded liposomes and reuptake by target macrophages is studied. The migratory behavior of liposome-loaded neutrophils is confirmed in vivo by demonstrating the delivery of drug-loaded liposomes to an inflamed skeletal muscle in mice. A single low-dose injection of the hybrid system locally reduces inflammatory cytokine levels. Biodistribution of liposome-loaded neutrophils in a human-disease-relevant myocardial ischemia reperfusion injury mouse model after i.v. injection confirms the ability of injected neutrophils to carry loaded liposomes to inflammation sites. This strategy shows the potential of nanocarrier-loaded neutrophils as a universal platform to deliver anti-inflammatory drugs to promote tissue regeneration in inflammatory diseases.     

Blends of Two Perylene Derivatives: Mesogenic Properties and Application As Emitter Materials in OLEDs

Blends consisting of two components, namely a liquid crystalline perylene ester and a bilaterally extended perylene ester, were studied. The liquid crystalline properties of these blends were investigated in detail by means of polarized optical microscopy and differential scanning calorimetry. The resulting phase diagram was used to explore the potential of these blends as emitter layers in OLEDs, which were prepared via thermal evaporation in a vacuum and spin coating of solutions.     

Linear and cyclic oligomers in polybutylene terephthalate for food contact materials

Polybutylene terephthalate (PBT) is a polyester (PES) gaining more importance on the food contact material (FCM) market. However, little is known about the potential migration of PBT oligomers which are formed during polymer production. In this work, PBT pellets and a slotted spoon manufactured from this material by injection moulding were analysed on extractable oligomers and their migration potential into hydrophilic foods. Overall 27 oligomers (cycles and linears) could be identified in different extracts by HPLC-DAD/ESI-MS data, but without confirmation by reference substances. The oligomers were quantified by HPLC-DAD using bis(2-hydroxyethyl) terephthalate (BHET) as external standard and the total amount of oligomers isolated by reprecipitation from the pellets and the spoon were 0.69 and 0.71%, respectively. While cyclic oligomers made up for approximately 90% of the extractable oligomers, linear oligomers proved to be more relevant for migration into aqueous foodstuffs. Furthermore, it was shown that hydrolysis of oligomers can take place in water at elevated temperatures. Consequently, the qualitative and quantitative composition of PBT oligomers in aqueous foods from FCMs does not only depend on migration but also on hydrolysis. Migration testing of the PBT spoon under repeat use conditions with water at 100°C for 2 h resulted in 0.29 mg item^?1 of linear oligomers and 0.05 mg item^?1 of the cyclic PBT dimer in the third migrate.