Script Knowledge Constrains Ellipses in Fragments - Evidence from Production Data and Language Modeling

We investigate the effect of script-based (Schank and Abelson 1977) extralinguistic context on the omission of words in fragments. Our data elicited with a production task show that predictable words are more often omitted than unpredictable ones, as predicted by the Uniform Information Density (UID) hypothesis (Levy & Jaeger 2007). We take into account effects of linguistic and extralinguistic context on predictability and propose a method for estimating the surprisal of words in presence of ellipsis. Our study extends previous evidence for UID in two ways: First, we show that not only local linguistic context, but also extralinguistic context determines the likelihood of omissions. Second, we find UID effects on the omission of content words

The promoter of human p22/PACAP response gene 1 (PRG1) contains functional binding sites for the p53 tumor suppressor and for NFκB

AbstractWe describe functional binding sites for the tumor suppressor p53 and for NFκB residing in the promoter of the novel human early response gene p22/PRG1 (IEX-1/DIF-2). Gel shift and supershift assays demonstrate binding of p53 and NFκB to their corresponding sites in vitro. CAT-reporter gene assays show transactivation of the human p22/PRG1 promoter by p53 in Hep3B cells stably transfected with a temperature-sensitive mutant p53, but not in p53-deficient Hep3B cells. TNFα induced NFκB dependent transactivation was shown in HepG2 cells or in 818-4 pancreatic cancer cells. These data imply that human p22/PRG1 is a target gene for p53 and NFκB involved in growth regulation and stress response

L1CAM expression in endometrial carcinomas is regulated by usage of two different promoter regions

<p>Abstract</p> <p>Background</p> <p>The L1 cell adhesion molecule (L1CAM) was originally identified as a neural adhesion molecule involved in axon guidance. In many human epithelial carcinomas L1CAM is overexpressed and thereby augments cell motility, invasion and metastasis formation. L1CAM positive carcinomas are associated with bad prognosis. Recent data point out that L1CAM is regulated in a fashion similar to epithelial-mesenchymal transition (EMT). Previous studies have implied the transcription factors Slug and/or β-catenin in <it>L1CAM </it>transcriptional regulation. However, the regulation of human L1CAM expression at the transcriptional level is not well understood.</p> <p>Results</p> <p>To better understand the molecular basis of <it>L1CAM </it>transcriptional regulation, we carried out a detailed characterization of the human <it>L1CAM </it>promoter. We identified two transcription start sites, the first in front of a non-translated exon 0 (promoter 1) and the other next to the first protein-coding exon 1 (promoter 2). Both sites could be verified in endometrial carcinoma (EC) cell lines and appear to be used in a cell-type specific manner. The two identified promoter regions showed activity in luciferase reporter assays. Chromatin-IP analyses confirmed the <it>in silico </it>predicted E-boxes, binding sites for transcription factors Snail and Slug, as well as Lef-1 sites, which are related to β-catenin-mediated transcriptional regulation, in both promoters. Overexpression of β-catenin exclusively augmented activity of promoter 1 whereas Slug enhanced promoter 1 and 2 activity suggesting that both promoters can be active. Overexpression of β-catenin or Slug could upregulate L1CAM expression in a cell-type specific manner.</p> <p>Conclusions</p> <p>Our results, for the first time, provide evidence that the L1CAM gene has two functionally active promoter sites that are used in a cell-type specific manner. Slug and β-catenin are involved <it>L1CAM </it>transcriptional regulation. Nevertheless, Slug rather than β-catenin levels are correlated with L1CAM expression in EC cell lines. Our findings suggest that the <it>L1CAM </it>transcriptional regulation is more complex than anticipated and this study provides the basis for a better understanding of L1CAM regulation in non-neuronal/tumor cells.</p

Gerechtigkeitspolitische Handlungsfelder in Deutschland: Relevante Probleme angemessen angehen

Zentrale verteilungspolitische Indikatoren in Deutschland haben sich seit dem Jahr 2005 wieder normalisiert oder sogar strukturell verbessert. Dennoch bleiben mindestens drei zentrale Herausforderungen: Erstens gelingt es nicht, die Langzeitarbeitslo-sigkeit stärker als bereits geschehen zurückzuführen. Zweitens geht die längerfristige Spreizung von Markteinkommen nicht wieder stärker zurück und nimmt die Auf-stiegsmobilität nicht strukturell zu, obwohl die Arbeitslosigkeit sich seit 2005 nahezu halbiert hat. Drittens gibt es auch mehr als 25 Jahre nach der deutschen Wiedervereinigung zwischen West und Ost und auch innerhalb von Bundesländern immer noch sehr ausgeprägte regionale Disparitäten. Zur Verringerung der Langzeitarbeitslosigkeit sind daher mehr Mittel im Rechtskreis SGB II sachgerecht, etwa durch befristete Lohnsubventionen und eine höhere Betreuungsdichte, insbesondere bei Jugendli-chen. Zur Förderung der Aufstiegsmobilität ist insbesondere die Bildungs- und Qualifizierungspolitik gefordert, etwa durch die Stärkung der frühkindlichen Bildung, der Ganztagsschulqualität und der Förderinfrastruktur sowie die Verbesserung der Anerkennung ausländischer Berufsabschlüsse und die Sprachförderung für Migranten. Zur Verminderung der regionalen Disparitäten sollte die Regionalpolitik mit anderen Programmen (Bildung, Städtebau, Gründungsförderung) verzahnt werden, die digitale Infrastruktur rasch ausgebaut und die Regionalförderung in Ostdeutschland auf Regionen mit stark unterdurchschnittlichen Lebensverhältnissen konzentriert werden.Central distributional indicators in Germany have re-normalized since the year 2005 or even improved structurally. Nevertheless, at least three key challenges remain: Firstly, the reduction of long-term unemployment does not keep up pace with average decline in unemployment. Secondly, the long-term upward mobility does not increase substantially although unemployment has almost halved since 2005. Thirdly, even more than 25 years after German reunification there are still very pronounced regional between West and East and also within the federal states. In order to reduce long-term unemployment, therefore more funds are appropriate in the basic income scheme. To foster upward mobility, education and qualification policies such as to strengthen early-childhood education, full-day schooling quality and support infrastructure, improving the recognition of foreign professional qualifications and language support for migrants are crucial. In order to reduce regional disparities, regional policy should be interlinked with other programs (education, urban development, start-ups), digital infrastructures should be expanded rapidly, and regional funding in Eastern Germany should be concentrated on regions with sub-average living conditions

Fidelity and level correlations in the transition from regularity to chaos

Mean fidelity amplitude and parametric energy--energy correlations are calculated exactly for a regular system, which is subject to a chaotic random perturbation. It turns out that in this particular case under the average both quantities are identical. The result is compared with the susceptibility of chaotic systems against random perturbations. Regular systems are more susceptible against random perturbations than chaotic ones.Comment: 7 pages, 1 figur

Identification of binding proteins for cholesterol absorption inhibitors as components of the intestinal cholesterol transporter

AbstractTo identify protein components of the intestinal cholesterol transporter, rabbit small intestinal brush border membrane vesicles were submitted to photoaffinity labeling using photoreactive derivatives of 2-azetidinone cholesterol absorption inhibitors. An integral membrane protein of Mr 145.3±7.5 kDa was specifically labeled in brush border membrane vesicles from rabbit jejunum and ileum. Its labeling was concentration-dependently inhibited by the presence of cholesterol absorption inhibitors whereas bile acids, D-glucose, fatty acids or cephalexin had no effect. The inhibitory potency of 2-azetidinones to inhibit photolabeling of the 145 kDa protein correlated with their in vivo activity to inhibit intestinal cholesterol absorption. These results suggest that an integral membrane protein of Mr 145 kDa is (a component of) the cholesterol absorption system in the brush border membrane of small intestinal enterocytes

Initiation of Pancreatic Cancer: The Interplay of Hyperglycemia and Macrophages Promotes the Acquisition of Malignancy-Associated Properties in Pancreatic Ductal Epithelial Cells

Pancreatic ductal adenocarcinoma (PDAC) is still one of the most aggressive solid malignancies with a poor prognosis. Obesity and type 2 diabetes mellitus (T2DM) are two major risk factors linked to the development and progression of PDAC, both often characterized by high blood glucose levels. Macrophages represent the main immune cell population in PDAC contributing to PDAC development. It has already been shown that pancreatic ductal epithelial cells (PDEC) undergo epithelial-mesenchymal transition (EMT) when exposed to hyperglycemia or macrophages. Thus, this study aimed to investigate whether concomitant exposure to hyperglycemia and macrophages aggravates EMT-associated alterations in PDEC. Exposure to macrophages and elevated glucose levels (25 mM glucose) impacted gene expression of EMT inducers such as IL-6 and TNF-α as well as EMT transcription factors in benign (H6c7-pBp) and premalignant (H6c7-kras) PDEC. Most strikingly, exposure to hyperglycemic coculture with macrophages promoted downregulation of the epithelial marker E-cadherin, which was associated with an elevated migratory potential of PDEC. While blocking IL-6 activity by tocilizumab only partially reverted the EMT phenotype in H6c7-kras cells, neutralization of TNF-α by etanercept was able to clearly impair EMT-associated properties in premalignant PDEC. Altogether, the current study attributes a role to a T2DM-related hyperglycemic, inflammatory micromilieu in the acquisition of malignancy-associated alterations in premalignant PDEC, thus providing new insights on how metabolic diseases might promote PDAC initiation