102 research outputs found

    Fast matrix computations for pair-wise and column-wise commute times and Katz scores

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    We first explore methods for approximating the commute time and Katz score between a pair of nodes. These methods are based on the approach of matrices, moments, and quadrature developed in the numerical linear algebra community. They rely on the Lanczos process and provide upper and lower bounds on an estimate of the pair-wise scores. We also explore methods to approximate the commute times and Katz scores from a node to all other nodes in the graph. Here, our approach for the commute times is based on a variation of the conjugate gradient algorithm, and it provides an estimate of all the diagonals of the inverse of a matrix. Our technique for the Katz scores is based on exploiting an empirical localization property of the Katz matrix. We adopt algorithms used for personalized PageRank computing to these Katz scores and theoretically show that this approach is convergent. We evaluate these methods on 17 real world graphs ranging in size from 1000 to 1,000,000 nodes. Our results show that our pair-wise commute time method and column-wise Katz algorithm both have attractive theoretical properties and empirical performance.Comment: 35 pages, journal version of http://dx.doi.org/10.1007/978-3-642-18009-5_13 which has been submitted for publication. Please see http://www.cs.purdue.edu/homes/dgleich/publications/2011/codes/fast-katz/ for supplemental code

    Recruitment of the Oncoprotein v-ErbA to Aggresomes

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    Aggresome formation, a cellular response to misfolded protein aggregates, is linked to cancer and neurodegenerative disorders. Previously we showed that Gag-v-ErbA (v-ErbA), a retroviral variant of the thyroid hormone receptor (TRα1), accumulates in and sequesters TRα1 into cytoplasmic foci. Here, we show that foci represent v-ErbA targeting to aggresomes. v-ErbA colocalizes with aggresomal markers, proteasomes, hsp70, HDAC6, and mitochondria. Foci have hallmark characteristics of aggresomes: formation is microtubule-dependent, accelerated by proteasome inhibitors, and they disrupt intermediate filaments. Proteasome-mediated degradation is critical for clearance of v-ErbA and T3-dependent TRα1 clearance. Our studies highlight v-ErbA\u27s complex mode of action: the oncoprotein is highly mobile and trafficks between the nucleus, cytoplasm, and aggresome, carrying out distinct activities within each compartment. Dynamic trafficking to aggresomes contributes to the dominant negative activity of v-ErbA and may be enhanced by the viral Gag sequence. These studies provide insight into novel modes of oncogenesis across multiple cellular compartments

    The disruption of proteostasis in neurodegenerative diseases

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    Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

    How Digital Are the Digital Humanities? An Analysis of Two Scholarly Blogging Platforms

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    In this paper we compare two academic networking platforms, HASTAC and Hypotheses, to show the distinct ways in which they serve specific communities in the Digital Humanities (DH) in different national and disciplinary contexts. After providing background information on both platforms, we apply co-word analysis and topic modeling to show thematic similarities and differences between the two sites, focusing particularly on how they frame DH as a new paradigm in humanities research. We encounter a much higher ratio of posts using humanities-related terms compared to their digital counterparts, suggesting a one-way dependency of digital humanities-related terms on the corresponding unprefixed labels. The results also show that the terms digital archive, digital literacy, and digital pedagogy are relatively independent from the respective unprefixed terms, and that digital publishing, digital libraries, and digital media show considerable cross-pollination between the specialization and the general noun. The topic modeling reproduces these findings and reveals further differences between the two platforms. Our findings also indicate local differences in how the emerging field of DH is conceptualized and show dynamic topical shifts inside these respective contexts

    Sourcing high tissue quality brains from deceased wild primates with known socio‐ecology

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    The selection pressures that drove dramatic encephalisation processes through the mammal lineage remain elusive, as does knowledge of brain structure reorganisation through this process. In particular, considerable structural brain changes are present across the primate lineage, culminating in the complex human brain that allows for unique behaviours such as language and sophisticated tool use. To understand this evolution, a diverse sample set of humans' closest relatives with varying socio-ecologies is needed. However, current brain banks predominantly curate brains from primates that died in zoological gardens. We try to address this gap by establishing a field pipeline mitigating the challenges associated with brain extractions of wild primates in their natural habitat. The success of our approach is demonstrated by our ability to acquire a novel brain sample of deceased primates with highly variable socio-ecological exposure and a particular focus on wild chimpanzees. Methods in acquiring brain tissue from wild settings are comprehensively explained, highlighting the feasibility of conducting brain extraction procedures under strict biosafety measures by trained veterinarians in field sites. Brains are assessed at a fine-structural level via high-resolution MRI and state-of-the-art histology. Analyses confirm that excellent tissue quality of primate brains sourced in the field can be achieved with a comparable tissue quality of brains acquired from zoo-living primates. Our field methods are noninvasive, here defined as not harming living animals, and may be applied to other mammal systems than primates. In sum, the field protocol and methodological pipeline validated here pose a major advance for assessing the influence of socio-ecology on medium to large mammal brains, at both macro- and microstructural levels as well as aiding with the functional annotation of brain regions and neuronal pathways via specific behaviour assessments.Output Status: Forthcoming/Available Online Additional authors: Richard McElreath, Alfred Anwander, Philipp Gunz, Markus Morawski, Angela D. Friederici, Nikolaus Weiskopf, Fabian H. Leendertz, Roman M. Wittig EBC Cosortium: Karoline Albig, Bala Amarasekaran, Sam Angedakin, Alfred Anwander, Daniel Aschoff, Caroline Asiimwe, Laurent Bailanda, Jacinta C. Beehner, Raphael Belais, Thore J. Bergman, Birgit Blazey, Andreas Bernhard, Christian Bock, PĂ©nĂ©lope Carlier, Julian Chantrey, Catherine Crockford, Tobias Deschner, Ariane DĂŒx1, Luke Edwards, Cornelius Eichner, GĂ©raldine Escoubas2, Malak Ettaj, Karina Flores, Richard Francke, Angela D. Friederici, CĂ©dric Girard-Buttoz, Jorge Gomez Fortun, Zoro Bertin GoneBi, Tobias GrĂ€ĂŸle, Eva Gruber-Dujardin, Philipp Gunz, Jess Hartel, Daniel B. M. Haun, Michael Henshall, Catherine Hobaiter, NoĂ©mie Hofman, Jenny E. Jaffe, Carsten JĂ€ger, Anna Jauch, Stomy Kahemere, Evgeniya Kirilina, Robert Klopfleisch, Tobias Knauf-Witzens, Kathrin S. Kopp, Guy Landry Mamboundou Kouima, Bastian Lange, Kevin Langergraber, Arne Lawrenz, Fabian H. Leendertz, Ilona Lipp, Matys Liptovszky, Tobias Loubser Theron, Christelle Patricia Lumbu, Patrice Makouloutou Nzassi, Kerstin MĂ€tz-Rensing, Richard McElreath, Matthew McLennan, Zoltan Mezö, Sophie Moittie, Torsten MĂžller, Markus Morawski, David Morgan, Timothy Mugabe, Martin Muller, Matthias MĂŒller, Inoussa Njumboket, Karin Olofsson-Sannö, Alain Ondzie, Emily Otali, Michael Paquette, Simone Pika, Kerrin Pine, Andrea Pizarro, Kamilla PlĂ©h, Jessica Rendel, Sandra Reichler-Danielowski, Martha M. Robbins, Alejandra Romero Forero, Konstantin Ruske, Liran Samuni, Crickette Sanz, AndrĂ© SchĂŒle, Ingo Schwabe, Katarina Schwalm, Sheri Speede, Lara Southern, Jonas Steiner, Marc Stidworthy, Martin Surbeck, Claudia Szentiks, Tanguy Tanga, Reiner Ulrich, Steve Unwin, Erica van de Waal, Sue Walker, Nikolaus Weiskopf, Gudrun Wibbelt, Roman M. Wittig, Kim Wood, Klaus ZuberbĂŒhle

    Sourcing high tissue quality brains from deceased wild primates with known socio‐ecology

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    The selection pressures that drove dramatic encephalisation processes through the mammal lineage remain elusive, as does knowledge of brain structure reorganisation through this process. In particular, considerable structural brain changes are present across the primate lineage, culminating in the complex human brain that allows for unique behaviours such as language and sophisticated tool use. To understand this evolution, a diverse sample set of humans' closest relatives with varying socio-ecologies is needed. However, current brain banks predominantly curate brains from primates that died in zoological gardens. We try to address this gap by establishing a field pipeline mitigating the challenges associated with brain extractions of wild primates in their natural habitat. The success of our approach is demonstrated by our ability to acquire a novel brain sample of deceased primates with highly variable socio-ecological exposure and a particular focus on wild chimpanzees. Methods in acquiring brain tissue from wild settings are comprehensively explained, highlighting the feasibility of conducting brain extraction procedures under strict biosafety measures by trained veterinarians in field sites. Brains are assessed at a fine-structural level via high-resolution MRI and state-of-the-art histology. Analyses confirm that excellent tissue quality of primate brains sourced in the field can be achieved with a comparable tissue quality of brains acquired from zoo-living primates. Our field methods are noninvasive, here defined as not harming living animals, and may be applied to other mammal systems than primates. In sum, the field protocol and methodological pipeline validated here pose a major advance for assessing the influence of socio-ecology on medium to large mammal brains, at both macro- and microstructural levels as well as aiding with the functional annotation of brain regions and neuronal pathways via specific behaviour assessments

    Insight into the evolution of the Solanaceae from the parental genomes of Petunia hybrida

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    Petunia hybrida is a popular bedding plant that has a long history as a genetic model system. We report the whole-genome sequencing and assembly of inbred derivatives of its two wild parents, P. axillaris N and P. inflata S6. The assemblies include 91.3% and 90.2% coverage of their diploid genomes (1.4 Gb; 2n = 14) containing 32,928 and 36,697 protein-coding genes, respectively. The genomes reveal that the Petunia lineage has experienced at least two rounds of hexaploidization: the older gamma event, which is shared with most Eudicots, and a more recent Solanaceae event that is shared with tomato and other solanaceous species. Transcription factors involved in the shift from bee to moth pollination reside in particularly dynamic regions of the genome, which may have been key to the remarkable diversity of floral colour patterns and pollination systems. The high-quality genome sequences will enhance the value of Petunia as a model system for research on unique biological phenomena such as small RNAs, symbiosis, self-incompatibility and circadian rhythms
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