CUBA: Artificial conviviality and user-behaviour analysis in web-feeds

Conviviality is a concept of great depth that plays an important role in any social interaction. A convivial relation between individuals is one that allows the participating individuals to behave and interact with each other following a set of conventions that are shared, commonly agreed upon, or at least understood. This presupposes an implicit or an explicit regulation mechanism based on consensus or social contracts and applies to the behaviours and interactions of participating individuals. With respect to an intelligent web-based system, an applicable social contribution is the give of assistance to other users in situations that are unclear and in guiding him to find the right decision whenever a conflict arises. Such a convivial social biotope deeply depends on both implicit and explicit co-operation and collaboration of natural users inside a community. Here, the individual conviviality may benefit from “The Wisdom of Crowds”, which fosters a dynamic understanding of the user’s behaviour and a strong influence of an individual’s well being to another person(s). The web-based system CUBA focus on such a behavioural analysis through profiling and demonstrates a convivial stay within a web-based feed system

GraphArchive - An Online Graph Data Store

In this report, we present our approach 'GraphArchive'. The solution attempts to enable researchers to exchange and archive graphs. The software is developed as an online platform using modern web technologies. In the document, features and architecture of GraphArchive are presented and the former approach 'GraphDB' is compared to the new system. Also, reader are taken on a typical walk through the system using a common use case for GraphArchive. News and development status of the system can be also visited at http://www.graph-archive.org

Reliable wet-chemical cleaning of natively oxidized high-efficiency Cu(In,Ga)Se2 thin-film solar cell absorbers

Currently, Cu-containing chalcopyrite-based solar cells provide the highest conversion efficiencies among all thin-film photovoltaic (PV) technologies. They have reached efficiency values above 20%, the same performance level as multi-crystalline silicon-wafer technology that dominates the commercial PV market. Chalcopyrite thin-film heterostructures consist of a layer stack with a variety of interfaces between different materials. It is the chalcopyrite/buffer region (forming the p-n junction), which is of crucial importance and therefore frequently investigated using surface and interface science tools, such as photoelectron spectroscopy and scanning probe microscopy. To ensure comparability and validity of the results, a general preparation guide for “realistic” surfaces of polycrystalline chalcopyrite thin films is highly desirable. We present results on wet-chemical cleaning procedures of polycrystalline Cu(In1-xGax)Se2 thin films with an average x = [Ga]/([In] + [Ga]) = 0.29, which were exposed to ambient conditions for different times. The hence natively oxidized sample surfaces were etched in KCN- or NH3-based aqueous solutions. By x-ray photoelectron spectroscopy, we find that the KCN treatment results in a chemical surface structure which is – apart from a slight change in surface composition – identical to a pristine as-received sample surface. Additionally, we discover a different oxidation behavior of In and Ga, in agreement with thermodynamic reference data, and we find indications for the segregation and removal of copper selenide surface phases from the polycrystalline material

Single-nucleus RNA sequencing of plant tissues using a nanowell‐based system

Single-cell genomics provides unprecedented potential for research on plant development and environmental responses. Here, we introduce a generic procedure for plant nucleus isolation combined with nanowell-based library preparation. Our method enables the transcriptome analysis of thousands of individual plant nuclei. It serves as an alternative to the use of protoplast isolation, which is currently a standard methodology for plant single-cell genomics, although it can be challenging for some plant tissues. We show the applicability of our nucleus isolation method by using different plant materials from different species. The potential of our single-nucleus RNA sequencing method is shown through the characterization of transcriptomes of seedlings and developing flowers from Arabidopsis thaliana. We evaluated the transcriptome dynamics during the early stages of anther development, identified stage-specific activities of transcription factors regulating this process, and predicted potential target genes of these transcription factors. Our nucleus isolation procedure can be applied in different plant species and tissues, thus expanding the toolkit for plant single-cell genomics experiments.Peer Reviewe

Evaluierung klimaaktiv 2013-2020. Die österreichische Klimaschutzinitiative des Bundesministeriums für Klimaschutz, Umwelt, Energie, Mobilität, Innovation und Technologie

Die Klimaschutzinitiative klimaaktiv hat in der vergangenen Programmperiode 2013 bis 2020 erfolgreich zur Unterstützung, Beratung, Kommunikation und Umsetzung von Maßnahmen zum Klimaschutz, insbesondere zur Reduktion der Treibhausgasemissionen, zur Steigerung der Energieeffizienz sowie zur Erhöhung des Anteils erneuerbarer Energieträger und zur Förderung der klimafreundlichen und aktiven Mobilität in Österreich beigetragen. Mit einheitlicher Organisation und effizienter Koordination verfügt die Initiative über ein leistungsfähiges Dachmanagement, das Impulse zur laufenden Weiterentwicklung der Initiative liefert. Um die Transformation zu einer klimaneutralen Gesellschaft zu begleiten, sollte klimaaktiv in der kommenden Programmperiode ambitioniert weiterentwickelt werden. Noch stärker als bisher sollte das Programm koordiniertes Handeln ermöglichen, Netzwerke stärken und passgenaue Werkzeuge in Abstimmung mit anderen Politikinstrumenten entwickeln. Um Zielgruppen noch besser zu erreichen, sollte klimaaktiv starke, programmübergreifende Kernbotschaften formulieren und kommunizieren. Die Qualitätsstandards von klimaaktiv sollten in zukünftige ordnungspolitische Vorgaben integriert werden und zugleich ambitioniertere freiwillige Standards entwickelt werden. Mit neuen und erweiterten Instrumenten könnte die Effektivität der Initiative steigen, etwa durch Bonus-Systeme in Form von Förderungen oder niedrigschwellig erreichbare Online-Schulungen. Die Anzahl der Angebote wie Beratungen, Ausbildungen und Zertifizierungen sollte erhöht werden, um flächendeckende Wirksamkeit zu erlangen. Durch die Integration neuer Themen und Handlungsfelder sowie der Vertiefung bestehender Maßnahmen kann klimaaktiv ebenfalls dazu beitragen, seine Effekte zu vergrößern. Hierzu gehören etwa Photovoltaik und Speicher, IKT, Integrierte Mobilitätssysteme, Kreislaufwirtschaft, Klimawandelanpassung und andere Themenfelder. Die Förderungen und zielgruppenorientierten Beratungsangebote im Rahmen von klimaaktiv mobil sollen ausgebaut und weiterentwickelt werden, um die Verkehrswende hin zu klimafreundlicher Mobilität zu beschleunigen. Die Implikationen der Corona-Pandemie sollten bei der Weiterentwicklung integral einbezogen werden. Hierbei sind besonders die Aspekte Digitalisierung, Lokalität und Resilienz von Bedeutung. Bestehende Partnerschaften sollten gestärkt und neue Partnerschaften geschlossen werden, um das Netzwerk um starke Multiplikator*innen zu ergänzen und die Koordination im Mehrebenensystem weiter zu verbessern

Reversible Host–Guest Crosslinks in Supramolecular Hydrogels for On‐Demand Mechanical Stimulation of Human Mesenchymal Stem Cells

Stem cells are regulated not only by biochemical signals but also by biophysical properties of extracellular matrix (ECM). The ECM is constantly monitored and remodeled because the fate of stem cells can be misdirected when the mechanical interaction between cells and ECM is imbalanced. A well-defined ECM model for bone marrow-derived human mesenchymal stem cells (hMSCs) based on supramolecular hydrogels containing reversible host–guest crosslinks is fabricated. The stiffness (Young\u27s modulus E) of the hydrogels can be switched reversibly by altering the concentration of non-cytotoxic, free guest molecules dissolved in the culture medium. Fine-adjustment of substrate stiffness enables the authors to determine the critical stiffness level E* at which hMSCs turn the mechano-sensory machinery on or off. Next, the substrate stiffness across E* is switched and the dynamic adaptation characteristics such as morphology, traction force, and YAP/TAZ signaling of hMSCs are monitored. These data demonstrate the instantaneous switching of traction force, which is followed by YAP/TAZ signaling and morphological adaptation. Periodical switching of the substrate stiffness across E* proves that frequent applications of mechanical stimuli drastically suppress hMSC proliferation. Mechanical stimulation across E* level using dynamic hydrogels is a promising strategy for the on-demand control of hMSC transcription and proliferation

Dysregulation of Hypoxia-Inducible Factor by Presenilin/ Gamma-Secretase Loss-of-Function Mutations

Presenilin (PSEN) 1 and 2 are the catalytic components of the Gamma-secretase complex, which cleaves a variety of proteins, including the amyloid precursor protein (APP). Proteolysis of APP leads to the formation of the APP intracellular domain (AICD) and amyloid Beta that is crucially involved in the pathogenesis of Alzheimer’s disease. Prolyl-4-hydroxylase-domain (PHD) proteins regulate the hypoxia inducible factors (HIFs), the master regulators of the hypoxic response.Wepreviously identified the FK506 binding protein 38 (FKBP38)as a negative regulator of PHD2. Genetic ablation of PSEN1/2 has been shown to increase FKBP38 protein levels. Therefore, we investigated the role of PSEN1/2 in the oxygen sensing pathway using a variety of genetically modified cell and mouse lines. Increased FKBP38 protein levels and decreased PHD2 protein levels were found in PSEN1/2-deficient mouse embryonic fibroblasts and in the cortex of forebrain-specific PSEN1/2 conditional double knock-out mice. Hypoxic HIF-1alpha protein accumulation and transcriptional activity were decreased, despite reduced PHD2 protein levels. Proteolytic gamma-secretase function ofPSEN1/2wasneeded for proper HIF activation. Intriguingly, PSEN1/2 mutations identified in Alzheimer patients differentially affected the hypoxicresponse, involving the generation of AICD. Together,our results suggest a direct role for PSEN in the regulation of the oxygen sensing pathway via the APP/AICD cleavage cascade

Identification of dihydromyricetin as a natural DNA methylation inhibitor with rejuvenating activity in human skin

Changes in DNA methylation patterning have been reported to be a key hallmark of aged human skin. The altered DNA methylation patterns are correlated with deregulated gene expression and impaired tissue functionality, leading to the well-known skin aging phenotype. Searching for small molecules, which correct the aged methylation pattern therefore represents a novel and attractive strategy for the identification of anti-aging compounds. DNMT1 maintains epigenetic information by copying methylation patterns from the parental (methylated) strand to the newly synthesized strand after DNA replication. We hypothesized that a modest inhibition of this process promotes the restoration of the ground-state epigenetic pattern, thereby inducing rejuvenating effects. In this study, we screened a library of 1800 natural substances and 640 FDA-approved drugs and identified the well-known antioxidant and anti-inflammatory molecule dihydromyricetin (DHM) as an inhibitor of the DNA methyltransferase DNMT1. DHM is the active ingredient of several plants with medicinal use and showed robust inhibition of DNMT1 in biochemical assays. We also analyzed the effect of DHM in cultivated keratinocytes by array-based methylation profiling and observed a moderate, but significant global hypomethylation effect upon treatment. To further characterize DHM-induced methylation changes, we used published DNA methylation clocks and newly established age predictors to demonstrate that the DHM-induced methylation change is associated with a reduction in the biological age of the cells. Further studies also revealed re-activation of age-dependently hypermethylated and silenced genes in vivo and a reduction in age-dependent epidermal thinning in a 3-dimensional skin model. Our findings thus establish DHM as an epigenetic inhibitor with rejuvenating effects for aged human skin

Phase I clinical study of the recombinant antibody toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas

INTRODUCTION: ScFv(FRP5)-ETA is a recombinant antibody toxin with binding specificity for ErbB2 (HER2). It consists of an N-terminal single-chain antibody fragment (scFv), genetically linked to truncated Pseudomonas exotoxin A (ETA). Potent antitumoral activity of scFv(FRP5)-ETA against ErbB2-overexpressing tumor cells was previously demonstrated in vitro and in animal models. Here we report the first systemic application of scFv(FRP5)-ETA in human cancer patients. METHODS: We have performed a phase I dose-finding study, with the objective to assess the maximum tolerated dose and the dose-limiting toxicity of intravenously injected scFv(FRP5)-ETA. Eighteen patients suffering from ErbB2-expressing metastatic breast cancers, prostate cancers, head and neck cancer, non small cell lung cancer, or transitional cell carcinoma were treated. Dose levels of 2, 4, 10, 12.5, and 20 μg/kg scFv(FRP5)-ETA were administered as five daily infusions each for two consecutive weeks. RESULTS: No hematologic, renal, and/or cardiovascular toxicities were noted in any of the patients treated. However, transient elevation of liver enzymes was observed, and considered dose limiting, in one of six patients at the maximum tolerated dose of 12.5 μg/kg, and in two of three patients at 20 μg/kg. Fifteen minutes after injection, peak concentrations of more than 100 ng/ml scFv(FRP5)-ETA were obtained at a dose of 10 μg/kg, indicating that predicted therapeutic levels of the recombinant protein can be applied without inducing toxic side effects. Induction of antibodies against scFv(FRP5)-ETA was observed 8 days after initiation of therapy in 13 patients investigated, but only in five of these patients could neutralizing activity be detected. Two patients showed stable disease and in three patients clinical signs of activity in terms of signs and symptoms were observed (all treated at doses ≥ 10 μg/kg). Disease progression occurred in 11 of the patients. CONCLUSION: Our results demonstrate that systemic therapy with scFv(FRP5)-ETA can be safely administered up to a maximum tolerated dose of 12.5 μg/kg in patients with ErbB2-expressing tumors, justifying further clinical development

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348