197 research outputs found

    Human ES Cell Culture Conditions Fail to Preserve the Mouse Epiblast State

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    Mouse embryonic stem cells (mESCs) and mouse epiblast stem cells (mEpiSCs) are the pluripotent stem cells (PSCs), derived from the inner cell mass (ICM) of preimplantation embryos at embryonic day 3.5 (E3.5) and postimplantation embryos at E5.5-E7.5, respectively. Depending on their environment, PSCs can exist in the so-called naive (ESCs) or primed (EpiSCs) states. Exposure to EpiSC or human ESC (hESC) culture condition can convert mESCs towards an EpiSC-like state. Here, we show that the undifferentiated epiblast state is however not stabilized in a sustained manner when exposing mESCs to hESC or EpiSC culture condition. Rather, prolonged exposure to EpiSC condition promotes a transition to a primitive streak- (PS-) like state via an unbiased epiblast-like intermediate. We show that the Brachyury-positive PS-like state is likely promoted by endogenous WNT signaling, highlighting a possible species difference between mouse epiblast-like stem cells and human Embryonic Stem Cells

    Die Klimaschutzwirkung der Flottenverbrauchsnorm in Deutschland : Möglichkeiten zur Erhöhung der Ambition und flankierende Politikinstrumente

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    Im Folgenden wird die Klimaschutzwirkung der aktuellen Flottenverbrauchsnorm der EuropĂ€ischen Kommission fĂŒr Deutschland diskutiert und in den Kontext der im Jahr 2020 signifikant angestiegenen Zahl von verkauften Pkw mit Elektromotor gesetzt. Dabei wird die aktuelle Entwicklung der Pkw-Flotte in Deutschland mit mehreren Szenarien verglichen. Erstens wird eine mögliche VerschĂ€rfung aktuell gĂŒltigen Rechts im Sinne eines European Green Deal angedacht. Zweitens wird dieser eher technische Zugang verglichen mit der Möglichkeit, durch Vermeidung und Verlagerung auf Fahrten mit dem Pkw zu verzichten. Drittens wird die Rolle von Plug-In-Hybriden diskutiert. Auf dieser Basis werden Politikempfehlungen ausgesprochen, wie die Flottenverbrauchsnorm weiterentwickelt werden kann, um die Klimaschutzambition zu erhöhen

    A 37 kb region upstream of brachyury comprising a notochord enhancer is essential for notochord and tail development

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    The node-streak border region comprising notochord progenitor cells (NPCs) at the posterior node and neuro-mesodermal progenitor cells (NMPs) in the adjacent epiblast is the prime organizing center for axial elongation in mouse embryos. The T-box transcription factor brachyury (T) is essential for both formation of the notochord and maintenance of NMPs, and thus is a key regulator of trunk and tail development. The T promoter controlling T expression in NMPs and nascent mesoderm has been characterized in detail; however, control elements for T expression in the notochord have not been identified yet. We have generated a series of deletion alleles by CRISPR/Cas9 genome editing in mESCs, and analyzed their effects in mutant mouse embryos. We identified a 37 kb region upstream of T that is essential for notochord function and tailbud outgrowth. Within that region, we discovered a T-binding enhancer required for notochord cell specification and differentiation. Our data reveal a complex regulatory landscape controlling cell type-specific expression and function of T in NMP/nascent mesoderm and node/notochord, allowing proper trunk and tail development

    Development of Harmonized Indicators and Estimation Procedures for Forests with Protective Functions against Natural Hazards in the Alpine Space

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    The present study was developed in the context of Regulation (EC) 2152/2003 on the monitoring of forest and environmental interactions, the so-called "Forest Focus" Regulation. The specific objective of this study was to explore the possible contribution of the national forest inventories (NFIs) to assess protective functions of for-ests in the alpine space. Key components of protective functions could be determined with the help of on-going national and international studies and processes. In order to grant consistency, definitions of forest area, dam-age potential and hazard potential had to be harmonised. Based on those, a strategy for monitoring and report-ing aspects of protective functions of mountain forests in the alpine space was proposed. Estimation procedures based on existing NFI data and field assessments and their integration in different remote sensing techniques were tested for harmonised monitoring. Final results are presented in this report.JRC.DDG.H.7-Land management and natural hazard

    CoCAS: a ChIP-on-chip analysis suite

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    Motivation: High-density tiling microarrays are increasingly used in combination with ChIP assays to study transcriptional regulation. To ease the analysis of the large amounts of data generated by this approach, we have developed ChIP-on-chip Analysis Suite (CoCAS), a standalone software suite which implements optimized ChIP-on-chip data normalization, improved peak detection, as well as quality control reports. Our software allows dye swap, replicate correlation and connects easily with genome browsers and other peak detection algorithms. CoCAS can readily be used on the latest generation of Agilent high-density arrays. Also, the implemented peak detection methods are suitable for other datasets, including ChIP-Seq output

    Tidal Evolution of Close-in Planets

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    Recent discoveries of several transiting planets with clearly non-zero eccentricities and some large inclinations started changing the simple picture of close-in planets having circular and well-aligned orbits. Two major scenarios to form such planets are planet migration in a disk, and planet--planet interactions combined with tidal dissipation. The former scenario can naturally produce a circular and low-obliquity orbit, while the latter implicitly assumes an initially highly eccentric and possibly high-obliquity orbit, which are then circularized and aligned via tidal dissipation. We investigate the tidal evolution of transiting planets on eccentric orbits. We show that the current and future orbital evolution of these systems is likely dominated by tidal dissipation, and not by a more distant companion. Although most of these close-in planets experience orbital decay all the way to the Roche limit, there are two characteristic evolution paths for them, depending on the relative efficiency of tidal dissipation inside the star and the planet. We point out that the current observations may be consistent with one of them. Our results suggest that at least some of the close-in planets with non-zero orbital eccentricity may have been formed by tidally circularizing an initially eccentric orbit. We also find that even when the stellar spin-orbit misalignment is observed to be small at present, some systems could have had a highly misaligned orbit in the past. Finally, we also re-examine the recent claim by Levrard et. al., who found that all orbital and spin parameters evolve on a similar timescale to orbital decay.Comment: Accepted for publication in ApJ, 22 pages, 19 figures, 2 tables, Corrupted figures are fixe

    Pleasure and meaningful discourse: an overview of research issues

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    The concept of pleasure has emerged as a multi-faceted social and cultural phenomenon in studies of media audiences since the 1980s. In these studies different forms of pleasure have been identified as explaining audience activity and commitment. In the diverse studies pleasure has emerged as a multi-faceted social and cultural concept that needs to be contextualized carefully. Genre and genre variations, class, gender, (sub-)cultural identity and generation all seem to be instrumental in determining the kind and variety of pleasures experienced in the act of viewing. This body of research has undoubtedly contributed to a better understanding of the complexity of audience activities, but it is exactly the diversity of the concept that is puzzling and poses a challenge to its further use. If pleasure is maintained as a key concept in audience analysis that holds much explanatory power, it needs a stronger theoretical foundation. The article maps the ways in which the concept of pleasure has been used by cultural theorists, who have paved the way for its application in reception analysis, and it goes on to explore the ways in which the concept has been used in empirical studies. Central to our discussion is the division between the ‘public knowledge’ and the ‘popular culture’ projects in reception analysis which, we argue, have major implications for the way in which pleasure has come to be understood as divorced from politics, power and ideology. Finally, we suggest ways of bridging the gap between these two projects in an effort to link pleasure to the concepts of hegemony and ideology

    The economics of debt clearing mechanisms

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    We examine the evolution of decentralized clearinghouse mechanisms from the 13th to the 18th century; in particular, we explore the clearing of non- or limitedtradable debts like bills of exchange. We construct a theoretical model of these clearinghouse mechanisms, similar to the models in the theoretical matching literature, and show that specific decentralized multilateral clearing algorithms known as rescontre, skontrieren or virement des parties used by merchants were efficient in specific historical contexts. We can explain both the evolutionary self-organizing emergence of late medieval and early modern fairs, and its robustness during the 17th and 18th century

    Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

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    BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223
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