1,480 research outputs found

    Mind Your Writing: How to be a Professional Academic Writer

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    The author presents ten of the fundamental questions that every academic writer should be able to answer. He focuses on some questions which may appear trivial at first glance but will likely prove to have more impact on the writer's efficiency and success than initially expected. The author's main argument is that writers who become better acquainted with themselves become more productive and happier writers. By knowing their own skills and the specific challenges of academic writing, writing will become a task they can master. Because of its focus on these fundamental questions, the book differs from usual guide books on academic writing. It addresses writers irrespective of their disciplinary background.Um erfolgreich schreiben und publizieren zu können, müssen wissenschaftlich Schreibende sich über ihre Kompetenzen und ihre Rolle als Schreibende im Klaren sein. Sie müssen Grundsatzfragen über ihr Schreiben beantworten können, damit sie bewusste und strategische Entscheidungen treffen können. Nur so werden sie zu Schreibprofis, die ihren Beruf erfolgreich ausüben

    Mind Your Writing

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    In order to write and publish successfully, academic writers must be aware of their skills and their role as writers. They need to be able to answer fundamental questions about their writing, enabling them to make conscious and strategic decisions. Only in that way they will become writing professionals who successfully carry out their profession

    Targeting PI3Kδ and PI3Kγ signalling disrupts human AML survival and bone marrow stromal cell mediated protection

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    Phosphoinositide-3-kinase (PI3K) is an enzyme group, known to regulate key survival pathways in acute myeloid leukaemia (AML). It generates phosphatidylinositol-3,4,5-triphosphate, which provides a membrane docking site for protein kinaseB activation. PI3K catalytic p110 subunits are divided into 4 isoforms; α,β,δ and γ. The PI3Kδ isoform is always expressed in AML cells, whereas the frequency of PI3Kγ expression is highly variable. The functions of these individual catalytic enzymes have not been fully resolved in AML, therefore using the PI3K p110δ and p110γ-targeted inhibitor IPI-145 (duvelisib) and specific p110δ and p110γ shRNA, we analysed the role of these two p110 subunits in human AML blast survival. The results show that PI3Kδ and PI3Kγ inhibition with IPI-145 has anti-proliferative activity in primary AML cells by inhibiting the activity of AKT and MAPK. Pre-treatment of AML cells with IPI-145 inhibits both adhesion and migration of AML blasts to bone marrow stromal cells. Using shRNA targeted to the individual isoforms we demonstrated that p110δ-knockdown had a more significant anti-proliferative effect on AML cells, whereas targeting p110γ-knockdown significantly inhibited AML migration. The results demonstrate that targeting both PI3Kδ and PI3Kγ to inhibit AML-BMSC interactions provides a biologic rationale for the pre-clinical evaluation of IPI-145 in AML

    Lack of genetic structure suggests high connectivity of Parnassius phoebus between nearby valleys in the Alps

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    The spatial scale of intraspecific genetic connectivity and population structure are important aspects of conservation genetics. However, for many species these properties are unknown. Here we used genomic data to assess the genetic structure of the small Apollo butterfly (Parnassius phoebus Fabricius, 1793; Lepidoptera: Papilionidae) across three nearby valleys in the Central Swiss Alps. One of the valleys is currently used for hydropower production with future plans to raise the existing dam wall further. We found no significant genetic structure, suggesting a currently high connectivity of this species in our studied region

    Deconvolution of Buparlisib’s mechanism of action defines specific PI3K and tubulin inhibitors for therapeutic intervention

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    13 p.-7 fig. Bohnacker, Thomas et al.BKM120 (Buparlisib) is one of the most advanced phosphoinositide 3-kinase (PI3K) inhibitors for the treatment of cancer, but it interferes as an off-target effect with microtubule polymerization. Here, we developed two chemical derivatives that differ from BKM120 by only one atom.We show that these minute changes separate the dual activity of BKM120 into discrete PI3K and tubulin inhibitors. Analysis of the compounds cellular growth arrest phenotypes and microtubule dynamics suggest that the antiproliferative activity of BKM120 is mainly due to microtubule-dependent cytotoxicity rather than through inhibition of PI3K.Crystal structures of BKM120 and derivatives in complex with tubulin and PI3K provide insights into the selective mode of action of this class of drugs. Our results raise concerns over BKM120’s generally accepted mode of action, and provide a unique mechanistic basis for next-generation PI3K inhibitors with improved safety profiles and flexibility for use in combination therapies.This work was supported by the Swiss Commission for Technology and Innovation (CTI) by PFLS-LS grants 14032.1,15811.2 and 17241.1; the Stiftung für Krebsbekämpfung grant 341, Swiss National Science Foundation grants 310030_153211 and 316030_133860 (to M.P.W.), and 310030B_138659 and 31003A_166608 (to M.O.S.); in part by European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement 675392, and grants BIO2013-42984-R (Ministerio de Economia y Competitividad), S2010/BMD-2457 BIPEDD2 (Comunidad Autónoma de Madrid) to J.F.D.; and by the MRC to R.L.W. (U105184308Peer reviewe

    The Economic and Artistic Constitution of a Social Phenomenon

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    Employability 4.0. Arbeitsmarktfähigkeit in einer sich wandelnden Arbeitswelt

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    Megatrends führen zu einem fundamentalen Wandel in der Arbeitswelt und stellen Unternehmen vor große Herausforderungen. Die Arbeitsmarktfähigkeit von Mitarbeitenden kann dabei zum wichtigen Erfolgsfaktor für die langfristige Wettbewerbsfähigkeit werden. Gleichzeitig führen die Arbeitsweltveränderungen auch zu neuen Anforderungen an die individuelle Arbeitsmarktfähigkeit der Mitarbeitenden. Anhand eines qualitativen Forschungsdesigns wurde für Schweizer Tochterunternehmen eines Industriekonzerns untersucht, welche Entwicklungen in der Schweizer Arbeitswelt zu erwarten sind, wie sich diese auf die Arbeitsmarktfähigkeit von Mitarbeitenden auswirken und wie das Human Resource Management (HRM) zur Arbeitsmarktfähigkeit der Mitarbeitenden beitragen kann. Die Ergebnisse zeigen, dass die Digitalisierung als relevantester Megatrend in der Arbeitswelt wahrgenommen wird und dass Anpassungsfähigkeit sowie lebenslanges Lernen der Mitarbeitenden essenziell für die Erhaltung und Förderung ihrer Arbeitsmarktfähigkeit sind
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