E-cadherin regulates cell growth by modulating proliferation-dependent β-catenin transcriptional activity

β-Catenin is essential for E-cadherin–mediated cell adhesion in epithelial cells, but it also forms nuclear complexes with high mobility group transcription factors. Using a mouse mammary epithelial cell system, we have shown previously that conversion of epithelial cells to a fibroblastoid phenotype (epithelial-mesenchymal transition) involves downregulation of E-cadherin and upregulation of β-catenin transcriptional activity. Here, we demonstrate that transient expression of exogenous E-cadherin in both epithelial and fibroblastoid cells arrested cell growth or caused apoptosis, depending on the cellular E-cadherin levels. By expressing E-cadherin subdomains, we show that the growth-suppressive effect of E-cadherin required the presence of its cytoplasmic β-catenin interaction domain and/or correlated strictly with the ability to negatively interfere with β-catenin transcriptional activity. Furthermore, coexpression of β-catenin or lymphoid enhancer binding factor-1 or T cell factor 3 with E-cadherin rescued β-catenin transcriptional activity and counteracted E-cadherin–mediated cell cycle arrest. Stable expression of E-cadherin in fibroblastoid cells decreased β-catenin activity and reduced cell growth. Since proliferating cells had a higher β-catenin activity than G1 phase–arrested or contact-inhibited cells, we conclude that β-catenin transcriptional activity is essential for cell proliferation and can be controlled by E-cadherin in a cell adhesion-independent manner

Concatenated Power Mean Word Embeddings as Universal Cross-Lingual Sentence Representations

Average word embeddings are a common baseline for more sophisticated sentence embedding techniques. However, they typically fall short of the performances of more complex models such as InferSent. Here, we generalize the concept of average word embeddings to power mean word embeddings. We show that the concatenation of different types of power mean word embeddings considerably closes the gap to state-of-the-art methods monolingually and substantially outperforms these more complex techniques cross-lingually. In addition, our proposed method outperforms different recently proposed baselines such as SIF and Sent2Vec by a solid margin, thus constituting a much harder-to-beat monolingual baseline. Our data and code are publicly available.Comment: Experiments/plots added: Normalization + Figure 1 (dimensionality vs. performance

Text Processing Like Humans Do: Visually Attacking and Shielding NLP Systems

Visual modifications to text are often used to obfuscate offensive comments in social media (e.g., "!d10t") or as a writing style ("1337" in "leet speak"), among other scenarios. We consider this as a new type of adversarial attack in NLP, a setting to which humans are very robust, as our experiments with both simple and more difficult visual input perturbations demonstrate. We then investigate the impact of visual adversarial attacks on current NLP systems on character-, word-, and sentence-level tasks, showing that both neural and non-neural models are, in contrast to humans, extremely sensitive to such attacks, suffering performance decreases of up to 82\%. We then explore three shielding methods---visual character embeddings, adversarial training, and rule-based recovery---which substantially improve the robustness of the models. However, the shielding methods still fall behind performances achieved in non-attack scenarios, which demonstrates the difficulty of dealing with visual attacks.Comment: Accepted as long paper at NAACL-2019; fixed one ungrammatical sentenc

Digitalisation anxiety: development and validation of a new scale

<jats:title>Abstract</jats:title><jats:p>The increasing spread of digital technologies and respective consequences for the way we live, work, and communicate can evoke feelings of tension and discomfort. This so-called digitalisation anxiety is related to existing and future technologies, includes the process of digitalisation in everyday life, and refers to multiple levels (the individual, organisations, and society). Existing scales measuring technology-related fears due not adequately reflect these features. Therefore, we developed the German version of the Digitalisation Anxiety Scale (DAS). Having generated items based on a qualitative interview study (Study 1, n = 26), we demonstrated the DAS’s factor structure, internal consistency and construct validity in Study 2a (n = 109) and test-retest reliability in Study 2b (n = 30). In Study 3 (n = 223), the scale’s structure was confirmed and correlates of digitalisation anxiety were examined. The final version of the DAS consists of 35 items with a four-factor structure (societal triggers for digitalisation anxiety, triggers related to interaction and leadership, triggers within oneself and triggers resulting from the digitalisation implementation process). Digitalisation Anxiety had negative relationships with well-being and performance. The scale allows practitioners and researchers to measure and benchmark individuals’ levels of digitalisation anxiety, and to track changes over time. The scale can inform interventions aiming at reducing digitalisation anxiety and stress resulting from digitalisation. </jats:p&gt

Structural brain anomalies in patients with FOXG1 syndrome and in Foxg1+/- mice

Objective FOXG1 syndrome is a rare neurodevelopmental disorder associated with heterozygous FOXG1 variants or chromosomal microaberrations in 14q12. The study aimed at assessing the scope of structural cerebral anomalies revealed by neuroimaging to delineate the genotype and neuroimaging phenotype associations. Methods We compiled 34 patients with a heterozygous (likely) pathogenic FOXG1 variant. Qualitative assessment of cerebral anomalies was performed by standardized re-analysis of all 34 MRI data sets. Statistical analysis of genetic, clinical and neuroimaging data were performed. We quantified clinical and neuroimaging phenotypes using severity scores. Telencephalic phenotypes of adult Foxg1+/- mice were examined using immunohistological stainings followed by quantitative evaluation of structural anomalies. Results Characteristic neuroimaging features included corpus callosum anomalies (82%), thickening of the fornix (74%), simplified gyral pattern (56%), enlargement of inner CSF spaces (44%), hypoplasia of basal ganglia (38%), and hypoplasia of frontal lobes (29%). We observed a marked, filiform thinning of the rostrum as recurrent highly typical pattern of corpus callosum anomaly in combination with distinct thickening of the fornix as a characteristic feature. Thickening of the fornices was not reported previously in FOXG1 syndrome. Simplified gyral pattern occurred significantly more frequently in patients with early truncating variants. Higher clinical severity scores were significantly associated with higher neuroimaging severity scores. Modeling of Foxg1 heterozygosity in mouse brain recapitulated the associated abnormal cerebral morphology phenotypes, including the striking enlargement of the fornix. Interpretation Combination of specific corpus callosum anomalies with simplified gyral pattern and hyperplasia of the fornices is highly characteristic for FOXG1 syndrome.Peer reviewe

Abschlussbericht des Forschungsprojekts "Broker für Dynamische Produktionsnetzwerke"

Der Broker für dynamische Produktionsnetzwerke (DPNB) ist ein vom Bundesministerium für Bildung und Forschung (BMBF) gefördertes und durch den Projektträger Karlsruhe (PTKA) betreutes Forschungsprojekt zwischen sieben Partnern aus Wissenschaft und Wirtschaft mit einer Laufzeit von Januar 2019 bis einschließlich Dezember 2021. Über den Einsatz von Cloud Manufacturing sowie Hard- und Software-Komponenten bei den teilnehmenden Unternehmen, sollen Kapazitätsanbieter mit Kapazitätsnachfrager verbunden werden. Handelbare Kapazitäten sind in diesem Falle Maschinen-, sowie Transport- und Montagekapazitäten, um Supply Chains anhand des Anwendungsfalls der Blechindustrie möglichst umfassend abzubilden. Der vorliegende Abschlussbericht fasst den Stand der Technik sowie die Erkenntnisse aus dem Projekt zusammen. Außerdem wird ein Überblick über die Projektstruktur sowie die Projektpartner gegeben

Whole-Day Schools - Management and Education

Ganztagsschulen haben durch ihr Mehr an Zeit einen größeren Spielraum, die Schulgestaltung an den Bedürfnissen der Beteiligten zu orientieren. In einer Auseinandersetzung mit anderen Perspektiven kann es gelingen, die Ausrichtung der eigenen Schule zu diskutieren, zu festigen und zu schärfen. Pädagogische Fortbildungsveranstaltungen bieten dazu eine Möglichkeit. Der zweite bayerische Ganztagsschulkongress Ganztagsschule gestalten – ganztags Unterricht organisieren am 3. und 4. März 2010 in Forchheim bot den Teilnehmerinnen und Teilnehmern anhand vielfältiger Vorträge und Workshops ein Forum zur Diskussion mit Perspektiven aus Wissenschaft, Schulpraxis und Bildungspolitik. Die Dokumentation der Veranstaltung liegt hiermit vor.All-day schools stand out against other types of schools due to the extended availability of time and therewith a wider range of possibilities to adjust the orientation of the school to the needs of the persons involved. Schools can evolve and strengthen their orientation by a discursive examination and discussion of different approaches. A good opportunity for advancing this discussion are events in pedagogical further education. During the second Bavarian all-day school congress "Modelling All-Day School - Organizing All-Day Tuition", held on the 3rd and 4th of March 2010 in Forchheim/Germany, participants had the opportunity to attend numerous workshops and presentations as well as a panel discussion featuring experts from the fields of educational science, educational policy and teaching. The documentation of the congress is now available

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