153 research outputs found

    Restructuring the Austrian Energy System: An Extended Technology Wedges Approach

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    EU climate and energy policy defines ambitious objectives for the EU member countries requiring a fundamental change of energy systems. This paper suggests basing the analysis of restructuring options on energy services instead of energy flows. In order to provide the energy services in a sustainable way the guidelines "low energy - low carbon - low distance" should be used. This refers to an increase in energy efficiency, the reduction of fossil fuels and the reduction of (redundant) transport. An extended technology wedges approach is applied for Austria to illustrate emission reduction options through technological and behavioural changes. Two portfolios of technology wedges are quantified regarding their effects on energy flows and emissions as well as the economic impacts of investments required

    Venus transit 2004: Illustrating the capability of exoplanet transmission spectroscopy

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    The transit of Venus in 2004 offered the rare possibility to remotely sense a well-known planetary atmosphere using ground-based observations for absorption spectroscopy. Transmission spectra of Venus' atmosphere were obtained in the near infrared using the Vacuum Tower Telescope (VTT) in Tenerife. Since the instrument was designed to measure the very bright photosphere of the Sun, extracting Venus' atmosphere was challenging. CO_2 absorption lines could be identified in the upper Venus atmosphere. Moreover, the relative abundance of the three most abundant CO_2 isotopologues could be determined. The observations resolved Venus' limb, showing Doppler-shifted absorption lines that are probably caused by high-altitude winds. This paper illustrates the ability of ground-based measurements to examine atmospheric constituents of a terrestrial planet atmosphere which might be applied in future to terrestrial extrasolar planets.Comment: 7 pages, 5 figures, 1 tabl

    Enhancing preschoolers' executive functions through embedding cognitive activities in shared book reading

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    Given evidence that early executive functioning sets the stage for a broad range of subsequent outcomes, researchers have sought to identify ways to foster these cognitive capacities. An increasingly common approach involves computerized ‘brain training’ programs, yet there are questions about whether these are well suited for fostering the early development of executive functions (EFs). The current series of studies sought to design, develop, and provide evidence for the efficacy of embedding cognitive activities in a commonplace activity – shared reading of a children’s book. The book, Quincey Quokka’s Quest, required children to control their thinking and behaviour to help the story’s main character through a series of obstacles. The first study investigated effects of reading with embedded cognitive activities in individual and group contexts on young children’s executive functions (EFs). The second study compared reading with embedded cognitive activities against a more-active control condition (dialogic reading) that similarly engaged children in the reading process yet lacked clear engagement of EFs. The third study sought to investigate whether the effect of reading the story with embedded EF activities changed across differing doses of the intervention and whether effects persisted 2 months post-intervention. Findings provide converging evidence of intervention effects on working memory and shifting in as little as 3 weeks (compared to more traditional reading) and maintenance of these gains 2 months later. This suggests the efficacy of embedding cognitive activities in the context of everyday activities, thereby extending the range of users and contexts in which this approach can be used

    Exploiting Clinical Trial Data Drastically Narrows the Window of Possible Solutions to the Problem of Clinical Adaptation of a Multiscale Cancer Model

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    The development of computational models for simulating tumor growth and response to treatment has gained significant momentum during the last few decades. At the dawn of the era of personalized medicine, providing insight into complex mechanisms involved in cancer and contributing to patient-specific therapy optimization constitute particularly inspiring pursuits. The in silico oncology community is facing the great challenge of effectively translating simulation models into clinical practice, which presupposes a thorough sensitivity analysis, adaptation and validation process based on real clinical data. In this paper, the behavior of a clinically-oriented, multiscale model of solid tumor response to chemotherapy is investigated, using the paradigm of nephroblastoma response to preoperative chemotherapy in the context of the SIOP/GPOH clinical trial. A sorting of the model's parameters according to the magnitude of their effect on the output has unveiled the relative importance of the corresponding biological mechanisms; major impact on the result of therapy is credited to the oxygenation and nutrient availability status of the tumor and the balance between the symmetric and asymmetric modes of stem cell division. The effect of a number of parameter combinations on the extent of chemotherapy-induced tumor shrinkage and on the tumor's growth rate are discussed. A real clinical case of nephroblastoma has served as a proof of principle study case, demonstrating the basics of an ongoing clinical adaptation and validation process. By using clinical data in conjunction with plausible values of model parameters, an excellent fit of the model to the available medical data of the selected nephroblastoma case has been achieved, in terms of both volume reduction and histological constitution of the tumor. In this context, the exploitation of multiscale clinical data drastically narrows the window of possible solutions to the clinical adaptation problem

    Caenorhabditis elegans N-glycan Core β-galactoside Confers Sensitivity towards Nematotoxic Fungal Galectin CGL2

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    The physiological role of fungal galectins has remained elusive. Here, we show that feeding of a mushroom galectin, Coprinopsis cinerea CGL2, to Caenorhabditis elegans inhibited development and reproduction and ultimately resulted in killing of this nematode. The lack of toxicity of a carbohydrate-binding defective CGL2 variant and the resistance of a C. elegans mutant defective in GDP-fucose biosynthesis suggested that CGL2-mediated nematotoxicity depends on the interaction between the galectin and a fucose-containing glycoconjugate. A screen for CGL2-resistant worm mutants identified this glycoconjugate as a Galβ1,4Fucα1,6 modification of C. elegans N-glycan cores. Analysis of N-glycan structures in wild type and CGL2-resistant nematodes confirmed this finding and allowed the identification of a novel putative glycosyltransferase required for the biosynthesis of this glycoepitope. The X-ray crystal structure of a complex between CGL2 and the Galβ1,4Fucα1,6GlcNAc trisaccharide at 1.5 Å resolution revealed the biophysical basis for this interaction. Our results suggest that fungal galectins play a role in the defense of fungi against predators by binding to specific glycoconjugates of these organisms

    Transiting exoplanets from the CoRoT space mission XVII. The hot Jupiter CoRoT-17b: a very old planet

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    We report on the discovery of a hot Jupiter-type exoplanet, CoRoT-17b, detected by the CoRoT satellite. It has a mass of 2.43±0.302.43\pm0.30\Mjup and a radius of 1.02±0.071.02\pm0.07\Rjup, while its mean density is 2.82±0.382.82\pm0.38 g/cm3^3. CoRoT-17b is in a circular orbit with a period of 3.7681±0.00033.7681\pm0.0003 days. The host star is an old (10.7±1.010.7\pm1.0 Gyr) main-sequence star, which makes it an intriguing object for planetary evolution studies. The planet's internal composition is not well constrained and can range from pure H/He to one that can contain \sim380 earth masses of heavier elements.Comment: Published (A&A 531, A41, 2011

    Evolutionarily Conserved Herpesviral Protein Interaction Networks

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    Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species

    Identification and Characterization of a Mef2 Transcriptional Activator in Schistosome Parasites

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    Myocyte enhancer factor 2 protein (Mef2) is an evolutionarily conserved activator of transcription that is critical to induce and control complex processes in myogenesis and neurogenesis in vertebrates and insects, and osteogenesis in vertebrates. In Drosophila, Mef2 null mutants are unable to produce differentiated muscle cells, and in vertebrates, Mef2 mutants are embryonic lethal. Schistosome worms are responsible for over 200 million cases of schistosomiasis globally, but little is known about early development of schistosome parasites after infecting a vertebrate host. Understanding basic schistosome development could be crucial to delineating potential drug targets. Here, we identify and characterize Mef2 from the schistosome worm Schistosoma mansoni (SmMef2). We initially identified SmMef2 as a homolog to the yeast Mef2 homolog, Resistance to Lethality of MKK1P386 overexpression (Rlm1), and we show that SmMef2 is homologous to conserved Mef2 family proteins. Using a genetics approach, we demonstrate that SmMef2 is a transactivator that can induce transcription of four separate heterologous reporter genes by yeast one-hybrid analysis. We also show that Mef2 is expressed during several stages of schistosome development by quantitative PCR and that it can bind to conserved Mef2 DNA consensus binding sequences

    A53T-alpha-synuclein-overexpression in the mouse nigrostriatal pathway leads to early increase of 14-3-3 epsilon and late increase of GFAP

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    Parkinson’s disease (PD) is a neurodegenerative disorder frequent at old age characterized by atrophy of the nigrostriatal projection. Overexpression and A53T-mutation of the presynaptic, vesicle-associated chaperone alpha-synuclein are known to cause early-onset autosomal dominant PD. We previously generated mice with transgenic overexpression of human A53T-alpha-synuclein (A53T-SNCA) in dopaminergic substantia nigra neurons as a model of early PD. To elucidate the early and late effects of A53T-alpha-synuclein on the proteome of dopaminergic nerve terminals in the striatum, we now investigated expression profiles of young and old mice using two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) and mass spectrometry. In total, 15 proteins were upregulated and 2 downregulated. Mice before the onset of motor anomalies showed an upregulation of the spot containing 14-3-3 proteins, in particular the epsilon isoform, as well as altered levels of chaperones, vesicle trafficking and bioenergetics proteins. In old mice, the persistent upregulation of 14-3-3 proteins was aggravated by an increase of glial fibrillary acidic protein (GFAP) suggesting astrogliosis due to initial neurodegeneration. Independent immunoblots corroborated GFAP upregulation and 14-3-3 upregulation for the epsilon isoform, and also detected significant eta and gamma changes. Only for 14-3-3 epsilon a corresponding mRNA increase was observed in midbrain, suggesting it is transcribed in dopaminergic perikarya and accumulates as protein in presynapses, together with A53T-SNCA. 14-3-3 proteins associate with alpha-synuclein in vitro and in pathognomonic Lewy bodies of PD brains. They act as chaperones in signaling, dopamine synthesis and stress response. Thus, their early dysregulation probably reflects a response to alpha-synuclein toxicity
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