37 results on '"Christian Pich"'
Search Results
2. From multiallele fish to nonstandard environments, how ZFIN assigns phenotypes, human disease models, and gene expression annotations to genes
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Yvonne M Bradford, Ceri E Van Slyke, Douglas G Howe, David Fashena, Ken Frazer, Ryan Martin, Holly Paddock, Christian Pich, Sridhar Ramachandran, Leyla Ruzicka, Amy Singer, Ryan Taylor, Wei-Chia Tseng, and Monte Westerfield
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Genetics - Abstract
Danio rerio is a model organism used to investigate vertebrate development. Manipulation of the zebrafish genome and resultant gene products by mutation or targeted knockdown has made the zebrafish a good system for investigating gene function, providing a resource to investigate genetic contributors to phenotype and human disease. Phenotypic outcomes can be the result of gene mutation, targeted knockdown of gene products, manipulation of experimental conditions, or any combination thereof. Zebrafish have been used in various genetic and chemical screens to identify genetic and environmental contributors to phenotype and disease outcomes. The Zebrafish Information Network (ZFIN, zfin.org) is the central repository for genetic, genomic, and phenotypic data that result from research using D. rerio. Here we describe how ZFIN annotates phenotype, expression, and disease model data across various experimental designs, how we computationally determine wild-type gene expression, the phenotypic gene, and how these results allow us to propagate gene expression, phenotype, and disease model data to the correct gene, or gene related entity.
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- 2023
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3. Zebrafish information network, the knowledgebase for Danio rerio research
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Douglas G. Howe, Christian Pich, Yvonne M. Bradford, Ken Frazer, David Fashena, Ceri E. Van Slyke, Holly Paddock, Sridhar Ramachandran, Amy Singer, Leyla Ruzicka, Ryan Martin, Anne E. Eagle, and Monte Westerfield
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Transcription activator-like effector nuclease ,animal structures ,Genome ,Morpholino ,biology ,ved/biology ,ved/biology.organism_classification_rank.species ,fungi ,Danio ,Computational biology ,Genomics ,biology.organism_classification ,ComputingMethodologies_PATTERNRECOGNITION ,Gene Ontology ,Databases, Genetic ,Genetics ,CRISPR ,Animals ,Zebrafish Information Network genome database ,Model organism ,Zebrafish - Abstract
The Zebrafish Information Network (zfin.org) is the central repository for Danio rerio genetic and genomic data. The Zebrafish Information Network has served the zebrafish research community since 1994, expertly curating, integrating, and displaying zebrafish data. Key data types available at the Zebrafish Information Network include, but are not limited to, genes, alleles, human disease models, gene expression, phenotype, and gene function. The Zebrafish Information Network makes zebrafish research data Findable, Accessible, Interoperable, and Reusable through nomenclature, curatorial and annotation activities, web interfaces, and data downloads. Recently, the Zebrafish Information Network and 6 other model organism knowledgebases have collaborated to form the Alliance of Genome Resources, aiming to develop sustainable genome information resources that enable the use of model organisms to understand the genetic and genomic basis of human biology and disease. Here, we provide an overview of the data available at the Zebrafish Information Network including recent updates to the gene page to provide access to single-cell RNA sequencing data, links to Alliance web pages, ribbon diagrams to summarize the biological systems and Gene Ontology terms that have annotations, and data integration with the Alliance of Genome Resources.
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- 2022
4. Alliance of Genome Resources Portal: unified model organism research platform
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Adam Wright, Paul W. Sternberg, Daniela Raciti, Monika Tutaj, Josh Goodman, Ken Frazer, Paul Thomas, Scott Cain, Raymond Lee, Judith A. Blake, Patrick Kalita, Ajay Shrivatsav, Julie Agapite, Marek S. Skrzypek, Hans-Michael Mueller, Wen J. Chen, Karen Yook, Gillian Millburn, Joanna Argasinska, David Fashena, Kevin Schaper, Joel E. Richardson, Douglas G. Howe, Barbara Dunn, Yvonne M. Bradford, Nathan Dunn, Jaehyoung Cho, Ranjana Kishore, Kalpana Karra, Sabrina Toro, Anne E. Eagle, Norbert Perrimon, Anushya Muruganujan, Beverley B. Matthews, Christian A. Grove, Edith D. Wong, Monte Westerfield, Olin Blodgett, Gary Williams, Jose-Maria Urbano, Marie-Claire Harrison, Steven J Marygold, Tremayne Mushayahama, Marek Tutaj, Susan Russo Gelbart, Jennifer R. Smith, Felix Gondwe, Dustin Ebert, Juancarlos Chan, J. Michael Cherry, Ceri E. Van Slyke, Christopher J. Tabone, L. Sian Gramates, Madeline A. Crosby, Robert S. Nash, Kevin A. MacPherson, Patrick Ng, Christian Pich, Suzi Aleksander, Monika Tomczuk, Brian R. Calvi, Todd W. Harris, Cynthia L. Smith, Stan Laulederkind, Jyothi Thota, Gilberto dos Santos, Matt Simison, Kimberly Van Auken, Mary E. Dolan, Karen R. Christie, Stacia R. Engel, Leyla Ruzicka, Carol J. Bult, Kevin L. Howe, Stuart R. Miyasato, Shur-Jen Wang, David R. Shaw, Mary Shimoyama, Valerio Arnaboldi, Matthew Russell, Michael Paulini, Sibyl Gao, Sagar Jha, Jeff De Pons, Christopher J. Mungall, Seth Carbon, James A. Kadin, Sierra A. T. Moxon, Susan M. Bello, Thomas C. Kaufman, Laurent-Philippe Albou, Shuai Weng, and Helen Attrill
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NAR Breakthrough Article ,Saccharomyces cerevisiae ,Biology ,Genome ,Data modeling ,Mice ,User-Computer Interface ,03 medical and health sciences ,0302 clinical medicine ,Resource (project management) ,Databases, Genetic ,Genetics ,Animals ,Humans ,Caenorhabditis elegans ,Alleles ,Zebrafish ,Organism ,030304 developmental biology ,Internet ,0303 health sciences ,Genome, Human ,Computational Biology ,Genomics ,Data science ,Rats ,Variety (cybernetics) ,Drosophila melanogaster ,Gene Ontology ,Data access ,Alliance ,Workflow ,Software ,030217 neurology & neurosurgery - Abstract
The Alliance of Genome Resources (Alliance) is a consortium of the major model organism databases and the Gene Ontology that is guided by the vision of facilitating exploration of related genes in human and well-studied model organisms by providing a highly integrated and comprehensive platform that enables researchers to leverage the extensive body of genetic and genomic studies in these organisms. Initiated in 2016, the Alliance is building a central portal (www.alliancegenome.org) for access to data for the primary model organisms along with gene ontology data and human data. All data types represented in the Alliance portal (e.g. genomic data and phenotype descriptions) have common data models and workflows for curation. All data are open and freely available via a variety of mechanisms. Long-term plans for the Alliance project include a focus on coverage of additional model organisms including those without dedicated curation communities, and the inclusion of new data types with a particular focus on providing data and tools for the non-model-organism researcher that support enhanced discovery about human health and disease. Here we review current progress and present immediate plans for this new bioinformatics resource.
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- 2019
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5. Navigating taxonomic complexity: A use-case report on FAIR scientific name-matching service usage in ENVRI Research Infrastructures
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Sharif Islam, Dario Papale, Lucia Vaira, Ilaria Rosati, Johannes Peterseil, and Christian Pichot
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scientific names ,taxonomy ,biodiversity ,FAIR ,EN ,Science - Abstract
This paper presents a use-case conducted within the ENVRI FAIR project, examining challenges and opportunities in deploying FAIR-aligned (ensuring Findability, Accessibility, Interoperability and Reusability) scientific name-matching services across Environmental Research Infrastructures (RIs). Six services were tested using various name variations, revealing inconsistencies in match types, status reporting and handling of canonical forms and typos. These diversities pose challenges for RI data pipelines and interoperability. The paper underscores the importance of standardised tools, enhanced communication, training, collaboration and shared resources. Addressing these needs can facilitate more effective FAIR implementation within the ENVRI community and biodiversity research. This, in turn, will empower RIs to seamlessly integrate and leverage scientific names, unlocking the full potential of their data for research and policy implementation.
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- 2024
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6. The Zebrafish Information Network: new support for non-coding genes, richer Gene Ontology annotations and the Alliance of Genome Resources
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Ryan Martin, Sabrina Toro, Holly Paddock, Anne E. Eagle, Patrick Kalita, Monte Westerfield, Yvonne M. Bradford, David Fashena, Xiang Shao, Christian Pich, Prita Mani, Sierra A. T. Moxon, Sridhar Ramachandran, Douglas G. Howe, Ceri E. Van Slyke, Kevin Schaper, Ken Frazer, Amy Singer, and Leyla Ruzicka
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animal structures ,ved/biology.organism_classification_rank.species ,Mutant ,Gene Expression ,Computational biology ,Biology ,Genome ,03 medical and health sciences ,0302 clinical medicine ,Databases, Genetic ,Genetics ,Database Issue ,Animals ,Humans ,Model organism ,Genome Reference Consortium ,Gene ,Zebrafish ,030304 developmental biology ,0303 health sciences ,ved/biology ,Molecular Sequence Annotation ,Genomics ,biology.organism_classification ,Phenotype ,Gene Ontology ,Mutation ,Zebrafish Information Network genome database ,030217 neurology & neurosurgery - Abstract
The Zebrafish Information Network (ZFIN) (https://zfin.org/) is the database for the model organism, zebrafish (Danio rerio). ZFIN expertly curates, organizes and provides a wide array of zebrafish genetic and genomic data, including genes, alleles, transgenic lines, gene expression, gene function, mutant phenotypes, orthology, human disease models, nomenclature and reagents. New features at ZFIN include increased support for genomic regions and for non-coding genes, and support for more expressive Gene Ontology annotations. ZFIN has recently taken over maintenance of the zebrafish reference genome sequence as part of the Genome Reference Consortium. ZFIN is also a founding member of the Alliance of Genome Resources, a collaboration of six model organism databases (MODs) and the Gene Ontology Consortium (GO). The recently launched Alliance portal (https://alliancegenome.org) provides a unified, comparative view of MOD, GO, and human data, and facilitates foundational and translational biomedical research.
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- 2018
7. A 14-year series of leaf phenological data collected for European beech (Fagus sylvatica L.) and silver fir (Abies alba Mill.) from their geographic range margins in south-eastern France
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Frederic Jean, Hendrik Davi, Sylvie Oddou-Muratorio, Bruno Fady, Ivan Scotti, Caroline Scotti-Saintagne, Julien Ruffault, Valentin Journe, Philippe Clastre, Olivier Marloie, William Brunetto, Marianne Correard, Olivier Gilg, Mehdi Pringarbe, Franck Rei, Jean Thevenet, Norbert Turion, and Christian Pichot
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Phenology ,Forest ,Bud development ,Leaf senescence ,Marginal population ,Climate change ,Forestry ,SD1-669.5 - Abstract
Key message Phenology is of increasing interest to climate change science and adaptation ecology. Here, we provide bud development, leafing, and leaf senescence data, collected on 772 European beech and silver fir trees between 2006 and 2019 on Mont Ventoux, France. Dataset access is at https://doi.org/10.15454/TRFMZN . Associated metadata are available at https://metadata-afs.nancy.inra.fr/geonetwork/srv/fre/catalog.search#/metadata/a33c8375-9a90-4bc3-a0d7-19317160b68f .
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- 2023
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8. Survival Outcomes of Patients With Breast Cancer in a Mexican Population
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Rocio Grajales-Alvarez, Alicia Gutiérrez-Mata, Christian Pichardo-Piña, Marcos Gutiérrez-De la Barrera, and Karim Dip-Borunda
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
PURPOSEThe Instituto Mexicano del Seguro Social is a tripartite contribution providing care to more than 74 million beneficiaries, representing more than 50% of the country's general population. This study aims to describe the survival outcomes and clinicopathologic characteristics of patients with breast cancer at our Center.METHODSA retrospective cohort of patients with breast cancer treated between January 2012 and December 2020 was conducted. Survival outcomes were assessed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using a Cox proportional hazards model.RESULTSThere were 5,264 patients included with a median follow-up of 54.9 months. Forty-three percent (n = 2,274) were diagnosed in stage I-IIA, 43.1% (n = 2,269) in stage IIB-III, and 7% (n = 383) in stage IV. At 5 years, disease-free survival was 74.9% (95% CI, 73.5 to 76.3) and overall survival (OS) 90.4% (95% CI, 89.4 to 91.3). For stage IV, it was 22.7% (95% CI, 17.3 to 28.5). High histologic grade (hazard ratio, 1.51 [95% CI, 1.34 to 1.7]; P < .001) and lymphovascular invasion (LVI; hazard ratio, 1.85 [95% CI, 1.62 to 2.1]; P < .001) were associated with a higher risk of recurrence.CONCLUSIONHistologic grade and LVI should be considered in the decision to treat with adjuvant chemotherapy in sites where genomic signatures are not available. Our OS data are comparable with other Mexican series; however, it is lower in stage IV. Much remains to be done at the national level, mainly regarding access to additional therapies for each breast cancer subtype. This work contributes to the evaluation of areas for improvement in outcomes in our population.
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- 2024
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9. ZFIN, The zebrafish model organism database: Updates and new directions
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Amy Singer, Douglas G. Howe, Christian Pich, Sridhar Ramachandran, Leyla Ruzicka, Prita Mani, Holly Paddock, David Fashena, Yvonne M. Bradford, Xiang Shao, Sabrina Toro, Anne E. Eagle, Monte Westerfield, Kevin Schaper, Ceri E. Van Slyke, Ken Frazer, Patrick Kalita, Sierra A. T. Moxon, Jonathan Knight, and Ryan Martin
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Genetics ,Gene knockdown ,biology ,Cell Biology ,Computational biology ,Ontology (information science) ,biology.organism_classification ,computer.software_genre ,Phenotype ,Endocrinology ,Zebrafish Model Organism Database ,Zebrafish Information Network genome database ,Web service ,Gene ,Zebrafish ,computer - Abstract
The Zebrafish Model Organism Database (ZFIN; http://zfin.org) is the central resource for genetic and genomic data from zebrafish (Danio rerio) research. ZFIN staff curate detailed information about genes, mutants, genotypes, reporter lines, sequences, constructs, antibodies, knockdown reagents, expression patterns, phenotypes, gene product function, and orthology from publications. Researchers can submit mutant, transgenic, expression, and phenotype data directly to ZFIN and use the ZFIN Community Wiki to share antibody and protocol information. Data can be accessed through topic-specific searches, a new site-wide search, and the data-mining resource ZebrafishMine (http://zebrafishmine.org). Data download and web service options are also available. ZFIN collaborates with major bioinformatics organizations to verify and integrate genomic sequence data, provide nomenclature support, establish reciprocal links, and participate in the development of standardized structured vocabularies (ontologies) used for data annotation and searching. ZFIN-curated gene, function, expression, and phenotype data are available for comparative exploration at several multi-species resources. The use of zebrafish as a model for human disease is increasing. ZFIN is supporting this growing area with three major projects: adding easy access to computed orthology data from gene pages, curating details of the gene expression pattern changes in mutant fish, and curating zebrafish models of human diseases.
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- 2015
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10. Explorative Visualization of Citation Patterns in Social Network Research
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Christian Pich and Ulrik Brandes
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Bibliometric analysis ,Sociology and Political Science ,Social network ,Computer science ,business.industry ,05 social sciences ,lcsh:HM401-1281 ,Social Sciences ,Network science ,01 natural sciences ,Data science ,Bibliographic coupling ,Visualization ,010104 statistics & probability ,lcsh:Sociology (General) ,0501 psychology and cognitive sciences ,Multidimensional scaling ,ddc:004 ,0101 mathematics ,business ,Representation (mathematics) ,Citation ,Social Sciences (miscellaneous) ,050104 developmental & child psychology - Abstract
We propose a visual representation of bibliographic data based on shared references. Our method employs a distance metric that is derived from bibliographic coupling and then subjected to fast approximate multidimensional scaling. Its utility is demonstrated by an explorative analysis of social network publications that, most notably, depicts the genesis of an area now commonly referred to as network science. However, the example also illustrates some common pitfalls in bibliometric analysis.
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- 2020
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11. GPS Tracking Reveals the White-Tailed Eagle Haliaeetus albicilla as an Ambassador for the Natura 2000 Network
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Remo Probst, Matthias Schmidt, Michael McGrady, and Christian Pichler
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Natura 2000 ,SPA ,conservation ,dispersal ,satellite telemetry ,habitat use ,Biology (General) ,QH301-705.5 - Abstract
The Natura 2000 network of protected areas is the backbone of species conservation in the European Union. We investigated whether Austrian-hatched white-tailed eagles (Haliaeetus albicilla) make particular use of this multinational network during their natal dispersal, and what habitats were of importance to the eagles. We analyzed the utilization distribution of 907,466 GPS locations from 38 dispersing white-tailed eagles using a dynamic Brownian Bridge Movement Model. Eagles ranged over a huge area of central-eastern Europe. Natura 2000 sites overlapped with 67% of the resulting 50% isopleth; i.e., a high probability of utilization of Natura 2000 areas by white-tailed eagles was found. White-tailed eagles used wetlands, waterbodies, and deciduous forests adjacent to wet habitats disproportionately often. Coniferous forests and settlements were avoided. Anthropogenically caused mortalities hardly occurred within Natura 2000 sites. Our study suggests that the Natura 2000 network is a crucial tool for conserving the white-tailed eagle. This top predator is an ambassador for the Natura 2000 idea during all life stages, and should continue to be a conservation priority of the network.
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- 2024
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12. A scientist's guide for submitting data to ZFIN
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Leyla Ruzicka, Sridhar Ramachandran, Yvonne M. Bradford, Sabrina Toro, Anne E. Eagle, Monte Westerfield, David Fashena, Doug Howe, Kelly A. Frazer, Kevin Schaper, Patrick Kalita, Xiang Shao, Sierra A. T. Moxon, Amy Singer, Holly Paddock, C. Van Slyke, Prita Mani, Ryan Martin, and Christian Pich
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0301 basic medicine ,Genetics ,Information retrieval ,Genome ,Genomic data ,Genomics ,Biology ,Data type ,Article ,Morpholinos ,Set (abstract data type) ,Animals, Genetically Modified ,03 medical and health sciences ,030104 developmental biology ,Research community ,Central repository ,Databases, Genetic ,Mutation ,Zebrafish Model Organism Database ,Transgenic lines ,Animals ,Zebrafish Information Network genome database ,Zebrafish - Abstract
The Zebrafish Model Organism Database (ZFIN; zfin.org) serves as the central repository for genetic and genomic data produced using zebrafish (Danio rerio). Data in ZFIN are either manually curated from peer-reviewed publications or submitted directly to ZFIN from various data repositories. Data types currently supported include mutants, transgenic lines, DNA constructs, gene expression, phenotypes, antibodies, morpholinos, TALENs, CRISPRs, disease models, movies, and images. The rapidly changing methods of genomic science have increased the production of data that cannot readily be represented in standard journal publications. These large data sets require web-based presentation. As the central repository for zebrafish research data, it has become increasingly important for ZFIN to provide the zebrafish research community with support for their data sets and guidance on what is required to submit these data to ZFIN. Regardless of their volume, all data that are submitted for inclusion in ZFIN must include a minimum set of information that describes the data. The aim of this chapter is to identify data types that fit into the current ZFIN database and explain how to provide those data in the optimal format for integration. We identify the required and optional data elements, define jargon, and present tools and templates that can help with the acquisition and organization of data as they are being prepared for submission to ZFIN. This information will also appear in the ZFIN wiki, where it will be updated as our services evolve over time.
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- 2016
13. ZFIN, the Zebrafish Model Organism Database: increased support for mutants and transgenics
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Holly Paddock, Ceri E. Van Slyke, Brock Sprunger, Douglas G. Howe, Amy Singer, Christian Pich, Barbara J. Ruef, Prita Mani, Tom Conlin, Ken Frazer, Leyla Ruzicka, Sierra A. T. Moxon, Kevin Schaper, Anne E. Eagle, Monte Westerfield, Ryan Martin, Sridhar Ramachandran, Yvonne M. Bradford, Jonathan Knight, Xiang Shao, and David Fashena
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Morpholino ,Transgene ,ved/biology.organism_classification_rank.species ,Mutant ,Animals, Genetically Modified ,03 medical and health sciences ,0302 clinical medicine ,Databases, Genetic ,Genetics ,Animals ,Model organism ,Zebrafish ,030304 developmental biology ,Internet ,0303 health sciences ,biology ,ved/biology ,Genomics ,Articles ,biology.organism_classification ,Phenotype ,Models, Animal ,Mutation ,Zebrafish Model Organism Database ,Zebrafish Information Network genome database ,030217 neurology & neurosurgery - Abstract
ZFIN, the Zebrafish Model Organism Database (http://zfin.org), is the central resource for zebrafish genetic, genomic, phenotypic and developmental data. ZFIN curators manually curate and integrate comprehensive data involving zebrafish genes, mutants, transgenics, phenotypes, genotypes, gene expressions, morpholinos, antibodies, anatomical structures and publications. Integrated views of these data, as well as data gathered through collaborations and data exchanges, are provided through a wide selection of web-based search forms. Among the vertebrate model organisms, zebrafish are uniquely well suited for rapid and targeted generation of mutant lines. The recent rapid production of mutants and transgenic zebrafish is making management of data associated with these resources particularly important to the research community. Here, we describe recent enhancements to ZFIN aimed at improving our support for mutant and transgenic lines, including (i) enhanced mutant/transgenic search functionality; (ii) more expressive phenotype curation methods; (iii) new downloads files and archival data access; (iv) incorporation of new data loads from laboratories undertaking large-scale generation of mutant or transgenic lines and (v) new GBrowse tracks for transgenic insertions, genes with antibodies and morpholinos.
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- 2012
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14. Knowledge sharing and discovery across heterogeneous research infrastructures [version 3; peer review: 2 approved, 1 not approved]
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Siamak Farshidi, Doron Goldfarb, Xiaofeng Liao, Markus Stocker, Barbara Magagna, Peter Thijsse, Keith Jeffery, Andreas Petzold, Na Li, Christian Pichot, and Zhiming Zhao
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Knowledge base ,knowledge management ,search engine ,research infrastructure ,software development lifecycle ,eng ,Science ,Social Sciences - Abstract
Research infrastructures play an increasingly essential role in scientific research. They provide rich data sources for scientists, such as services and software packages, via catalog and virtual research environments. However, such research infrastructures are typically domain-specific and often not connected. Accordingly, researchers and practitioners face fundamental challenges introduced by fragmented knowledge from heterogeneous, autonomous sources with complicated and uncertain relations in particular research domains. Additionally, the exponential growth rate of knowledge in a specific domain surpasses human experts’ ability to formalize and capture tacit and explicit knowledge efficiently. Thus, a knowledge management system is required to discover knowledge effectively, automate the knowledge acquisition based on artificial intelligence approaches, integrate the captured knowledge, and deliver consistent knowledge to agents, research communities, and end-users. In this study, we present the development process of a knowledge management system for ENVironmental Research Infrastructures, which are crucial pillars for environmental scientists in their quest for understanding and interpreting the complex Earth System. Furthermore, we report the challenges we have faced and discuss the lessons learned during the development process.
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- 2023
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15. The Zebrafish Information Network: the zebrafish model organism database provides expanded support for genotypes and phenotypes
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David Fashena, Nathan Dunn, Yvonne M. Bradford, Judy Sprague, Melissa A. Haendel, Monte Westerfield, Amy Singer, Tom Conlin, Ceri E. Van Slyke, Xiang Shao, Sridhar Ramachandran, Jonathan Knight, Erik Segerdell, Christian Pich, Brock Sprunger, Kevin Schaper, Douglas G. Howe, Sierra A. T. Moxon, Ken Frazer, Peiran Song, Leyla Bayraktaroglu, and Prita Mani
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animal structures ,Genotype ,Morpholino ,Computational biology ,Ontology (information science) ,User-Computer Interface ,03 medical and health sciences ,0302 clinical medicine ,Databases, Genetic ,Genetics ,Animals ,Allele ,Zebrafish ,Gene ,030304 developmental biology ,Internet ,0303 health sciences ,biology ,Articles ,biology.organism_classification ,Phenotype ,Systems Integration ,Models, Animal ,Mutation ,Zebrafish Model Organism Database ,Zebrafish Information Network genome database ,Sequence Alignment ,030217 neurology & neurosurgery - Abstract
The Zebrafish Information Network (ZFIN, http://zfin.org), the model organism database for zebrafish, provides the central location for curated zebrafish genetic, genomic and developmental data. Extensive data integration of mutant phenotypes, genes, expression patterns, sequences, genetic markers, morpholinos, map positions, publications and community resources facilitates the use of the zebrafish as a model for studying gene function, development, behavior and disease. Access to ZFIN data is provided via web-based query forms and through bulk data files. ZFIN is the definitive source for zebrafish gene and allele nomenclature, the zebrafish anatomical ontology (AO) and for zebrafish gene ontology (GO) annotations. ZFIN plays an active role in the development of cross-species ontologies such as the phenotypic quality ontology (PATO) and the gene ontology (GO). Recent enhancements to ZFIN include (i) a new home page and navigation bar, (ii) expanded support for genotypes and phenotypes, (iii) comprehensive phenotype annotations based on anatomical, phenotypic quality and gene ontologies, (iv) a BLAST server tightly integrated with the ZFIN database via ZFIN-specific datasets, (v) a global site search and (vi) help with hands-on resources.
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- 2007
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16. Surrounding water vapor induced diffusion and physisorption of water within thermoplastic polyurethane TPU samples: A critical analysis of DVS data
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Christian Pichler, Stefan Oberparleiter, and Roman Lackner
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Water-vapor sorption/desorption ,Water-vapor ,Diffusion coefficient ,Physisorption ,Polymers and polymer manufacture ,TP1080-1185 - Abstract
In this paper, dynamic vapor sorption (DVS) experiments on thermoplastic polyurethane (TPU) samples are presented. Experiments were conducted at different constant temperatures – at 15, 25, and 35 degrees C – giving access to the sorption isotherm showing almost no temperature dependency. As the specimens were prepared with a defined geometry (disc’ with different thicknesses from 600 to 1600 μm and a diameter of 30 mm), the recorded mass history in response to a quasi-instantaneous change of the sample-enclosing humidity was employed to backcalculate diffusivity in narrow ranges for the prescribed externally assigned relative humidities, with a step-wise increase (or decrease) of ten percent. The backcalculated diffusion coefficients show dependency on (i) the temperature what is well described in Arrhenius plots and (ii) the relative humidity range. The influence of sample thickness is marginal, indicating that the surface resistance to mass transfer, as quantified by the Biot number, is negligible when interpreting DVS data presented in this paper. Furthermore, the order of magnitude of the backcalculated diffusion coefficients and their temperature dependency in terms of the associated activation energies is discussed, depending on whether the physi-sorbed water content within the polymer network or the (externally) assigned water vapor content is employed as potential/state variable for the mathematical description of the diffusion process (gradients of the state variable represent the driving force of the diffusion process). When water vapor content is employed, the slope of the sorption isotherm has to be considered in the diffusion analysis.
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- 2023
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17. A structural basis for the diverse linkage specificities within the ZUFSP deubiquitinase family
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Thomas Hermanns, Christian Pichlo, Ulrich Baumann, and Kay Hofmann
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Science - Abstract
ZUFSP-type enzymes cleave ubiquitin chains in a linkage-specific fashion, but members from different organisms have different specificities. Using an inter-kingdom comparison of activities and structures, the authors identify the domains responsible for this discrepancy.
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- 2022
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18. Correction: Corrigendum: InterMOD: integrated data and tools for the unification of model organism research
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J. Michael Cherry, Quang M. Trinh, Andrew Vallejos, Lincoln Stein, Jelena Aleksic, Gos Micklem, Richard N. Smith, Benjamin C. Hitz, Pushkala Jayaraman, Rachel Lyne, Howie Motenko, Joel Richardson, Christian Pich, Elizabeth A. Worthey, Gail Binkley, Simon N. Twigger, Kalpana Karra, J. D. Wong, Rama Balakrishnan, Steven B. Neuhauser, Todd W. Harris, Julie Sullivan, Monte Westerfield, and Sierra A. T. Moxon
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Multidisciplinary ,Unification ,Computer science ,ved/biology ,ved/biology.organism_classification_rank.species ,computer.software_genre ,Data science ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Data mining ,Model organism ,computer ,030217 neurology & neurosurgery - Abstract
CORRIGENDUM: InterMOD: integrated data and tools for the unification of model organism research
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- 2013
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19. InterMOD: integrated data and tools for the unification of model organism research
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Richard N. Smith, Pushkala Jayaraman, Rama Balakrishnan, Elizabeth A. Worthey, Steven B. Neuhauser, Gail Binkley, Julie Sullivan, Lincoln Stein, J. D. Wong, Jelena Aleksic, Sierra A. T. Moxon, J. Michael Cherry, Monte Westerfield, Todd W. Harris, Quang M. Trinh, Rachel Lyne, Benjamin C. Hitz, Gos Micklem, Simon N. Twigger, Andrew Vallejos, Howie Motenko, Joel Richardson, Christian Pich, and Kalpana Karra
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Unification ,Databases, Factual ,media_common.quotation_subject ,ved/biology.organism_classification_rank.species ,Biology ,computer.software_genre ,Article ,Data modeling ,03 medical and health sciences ,Consistency (database systems) ,0302 clinical medicine ,Comparative research ,Databases, Genetic ,Animals ,Function (engineering) ,Model organism ,030304 developmental biology ,media_common ,0303 health sciences ,Multidisciplinary ,Genome ,Models, Genetic ,ved/biology ,Genomics ,Data science ,Data warehouse ,DECIPHER ,Data mining ,computer ,030217 neurology & neurosurgery - Abstract
Model organisms are widely used for understanding basic biology and have significantly contributed to the study of human disease. In recent years, genomic analysis has provided extensive evidence of widespread conservation of gene sequence and function amongst eukaryotes, allowing insights from model organisms to help decipher gene function in a wider range of species. The InterMOD consortium is developing an infrastructure based around the InterMine data warehouse system to integrate genomic and functional data from a number of key model organisms, leading the way to improved cross-species research. So far including budding yeast, nematode worm, fruit fly, zebrafish, rat and mouse, the project has set up data warehouses, synchronized data models and created analysis tools and links between data from different species. The project unites a number of major model organism databases, improving both the consistency and accessibility of comparative research, to the benefit of the wider scientific community.
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- 2013
20. ZFIN: enhancements and updates to the Zebrafish Model Organism Database
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Christian Pich, Holly Paddock, Holle A. Bauer Schaper, Kevin Schaper, Amy Singer, Ceri E. Van Slyke, Yvonne M. Bradford, Monte Westerfield, David Fashena, Ken Frazer, Douglas G. Howe, Barbara J. Ruef, Nathan Dunn, Jonathan Knight, Tom Conlin, Leyla Ruzicka, Ryan Martin, Xiang Shao, Prita Mani, Sierra A. T. Moxon, Judy Sprague, Brock Sprunger, and Sridhar Ramachandran
- Subjects
Gene Expression ,Genomics ,Genome browser ,Computational biology ,Genome ,Antibodies ,03 medical and health sciences ,0302 clinical medicine ,Databases, Genetic ,Genetics ,Animals ,RNA, Messenger ,Zebrafish ,030304 developmental biology ,0303 health sciences ,biology ,Articles ,biology.organism_classification ,Phenotype ,Central repository ,Models, Animal ,Zebrafish Model Organism Database ,Zebrafish Information Network genome database ,030217 neurology & neurosurgery ,Dynamic resource - Abstract
ZFIN, the Zebrafish Model Organism Database, http://zfin.org, serves as the central repository and web-based resource for zebrafish genetic, genomic, phenotypic and developmental data. ZFIN manually curates comprehensive data for zebrafish genes, phenotypes, genotypes, gene expression, antibodies, anatomical structures and publications. A wide-ranging collection of web-based search forms and tools facilitates access to integrated views of these data promoting analysis and scientific discovery. Data represented in ZFIN are derived from three primary sources: curation of zebrafish publications, individual research laboratories and collaborations with bioinformatics organizations. Data formats include text, images and graphical representations. ZFIN is a dynamic resource with data added daily as part of our ongoing curation process. Software updates are frequent. Here, we describe recent additions to ZFIN including (i) enhanced access to images, (ii) genomic features, (iii) genome browser, (iv) transcripts, (v) antibodies and (vi) a community wiki for protocols and antibodies.
- Published
- 2010
21. Exploring Zebrafish genomic, functional and phenotypic data using ZFIN
- Author
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Christian Pich, Sridhar Ramachandran, Judy Sprague, and Barbara J. Ruef
- Subjects
Genetics ,Genome ,biology ,Extramural ,education ,Anatomical structures ,Gene Expression ,Genomics ,General Medicine ,Computational biology ,biology.organism_classification ,Phenotype ,Article ,ComputingMethodologies_PATTERNRECOGNITION ,Databases, Genetic ,Zebrafish Model Organism Database ,Animals ,Zebrafish Information Network genome database ,Zebrafish - Abstract
The zebrafish model organism database (ZFIN) provides a Web resource of zebrafish genomic, genetic, developmental, and phenotypic data. ZFIN curates and integrates data from current literature and from direct data submissions from laboratories. In addition, ZFIN collaborates with other bioinformatics organizations to provide links to other relevant data. These data can be accessed through a variety of Web-based search and display tools. This unit focuses on some of the basic methods to search, visualize, and analyze ZFIN data, including genes, gene expression, mutants, morphants, transgenics, anatomical structures, and antibodies. ZFIN's GBrowse genome viewer, BLAST, and protocol and antibody wikis are also discussed.
- Published
- 2010
22. More flexible radial layout
- Author
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Ulrik Brandes and Christian Pich
- Subjects
Scheme (programming language) ,Structure (mathematical logic) ,Mathematical optimization ,General Computer Science ,Operations research ,Computer science ,A-weighting ,Concentric ,Topology ,Computer Science Applications ,Theoretical Computer Science ,Set (abstract data type) ,Computational Theory and Mathematics ,Graph drawing ,Node (computer science) ,Graph (abstract data type) ,Multidimensional scaling ,Geometry and Topology ,Stress majorization ,ddc:004 ,Undirected graph ,Centrality ,computer ,Mathematics ,computer.programming_language - Abstract
We describe an algorithm for radial layout of undirected graphs, in which nodes are constrained to concentric circles centered at the origin. Such constraints are typical, e.g., in the layout of social networks, when structural centrality is mapped to geometric centrality or when the pri- mary intention of the layout is the display of the vicinity of a distinguished node. Our approach is based on an extension of stress minimization with a weighting scheme that gradually imposes radial constraints on the inter-mediate layout during the majorization process, and thus is an attempt to preserve as much information about the graph structure as possible.
- Published
- 2010
23. Drawing Directed Graphs Clockwise
- Author
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Christian Pich
- Subjects
Modular decomposition ,Discrete mathematics ,Efficient algorithm ,Preprocessor ,Clockwise ,Directed graph ,Layering ,Eigendecomposition of a matrix ,Graph ,MathematicsofComputing_DISCRETEMATHEMATICS ,Mathematics - Abstract
We present a method for clockwise drawings of directed cyclic graphs. It is based on the eigenvalue decomposition of a skew-symmetric matrix associated with the graph and draws edges clockwise around the center instead of downwards, as in the traditional hierarchical drawing style. The method does not require preprocessing for cycle removal or layering, which often involves computationally hard problems. We describe an efficient algorithm which produces optimal solutions, and we present some application examples.
- Published
- 2010
- Full Text
- View/download PDF
24. An Experimental Study on Distance-Based Graph Drawing
- Author
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Christian Pich and Ulrik Brandes
- Subjects
Theoretical computer science ,business.industry ,Computer science ,Voltage graph ,Strength of a graph ,Machine learning ,computer.software_genre ,Graph bandwidth ,Graph drawing ,Graph (abstract data type) ,Artificial intelligence ,Force-directed graph drawing ,Lattice graph ,business ,computer ,Moral graph - Abstract
In numerous application areas, general undirected graphs need to be drawn, and force-directed layout appears to be the most frequent choice. We present an extensive experimental study showing that, if the goal is to represent the distances in a graph well, a combination of two simple algorithms based on variants of multidimensional scaling is to be preferred because of their efficiency, reliability, and even simplicity. We also hope that details in the design of our study help advance experimental methodology in algorithm engineering and graph drawing, independent of the case at hand.
- Published
- 2009
- Full Text
- View/download PDF
25. Visualizing Internet Evolution on the Autonomous Systems Level
- Author
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Krists Boitmanis, Ulrik Brandes, and Christian Pich
- Subjects
business.industry ,Computer science ,Distributed computing ,Physical Internet ,Visualization ,Graph drawing ,Large networks ,Computer graphics (images) ,Border Gateway Protocol ,Graph (abstract data type) ,The Internet ,Stress majorization ,ddc:004 ,business - Abstract
We propose a visualization approach for large dynamic graph structures with high degree variation and low diameter. In particular, we reduce visual complexity by multiple modes of representation in a single-level visualization rather than abstractions of lower levels of detail. This is useful for non-interactive display and eases dynamic layout, which we address in the online scenario. Our approach is illustrated on a family of large networks featuring all of the above structural characteristics, the physical Internet on the autonomous systems level over time.
- Published
- 2008
26. Eigensolver Methods for Progressive Multidimensional Scaling of Large Data
- Author
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Ulrik Brandes and Christian Pich
- Subjects
Layout algorithm ,Theoretical computer science ,Test graph ,Graph drawing ,Computation ,Sampling (statistics) ,Multidimensional scaling ,ddc:004 ,Mathematics - Abstract
We present a novel sampling-based approximation technique for classical multidimensional scaling that yields an extremely fast layout algorithm suitable even for very large graphs. It produces layouts that compare favorably with other methods for drawing large graphs, and it is among the fastest methods available. In addition, our approach allows for progressive computation, i.e. a rough approximation of the layout can be produced even faster, and then be refined until satisfaction.
- Published
- 2007
- Full Text
- View/download PDF
27. Centrality Estimation in Large Networks
- Author
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Christian Pich and Ulrik Brandes
- Subjects
Theoretical computer science ,Applied Mathematics ,Network science ,Network theory ,Complex network ,Network controllability ,Random walk closeness centrality ,Betweenness centrality ,Modeling and Simulation ,Katz centrality ,ddc:004 ,Centrality ,Engineering (miscellaneous) ,Mathematics - Abstract
Centrality indices are an essential concept in network analysis. For those based on shortest-path distances the computation is at least quadratic in the number of nodes, since it usually involves solving the single-source shortest-paths (SSSP) problem from every node. Therefore, exact computation is infeasible for many large networks of interest today. Centrality scores can be estimated, however, from a limited number of SSSP computations. We present results from an experimental study of the quality of such estimates under various selection strategies for the source vertices.
- Published
- 2007
28. Pore space of steatite ceramics triggered by the allowance of natural fibers: High-resolution X-ray microscopy analysis and related thermo-mechanical properties
- Author
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Lukas Perfler, Lukas Peyker, Martin Hörtnagl, Nikolaus Weinberger, Christian Pichler, Roland Traxl, and Roman Lackner
- Subjects
Steatite ceramics ,X-ray microscopy ,Pore space analysis ,Spectroscopic characterization ,Phase analysis ,Thermal properties ,Materials of engineering and construction. Mechanics of materials ,TA401-492 - Abstract
A large number (greater than 150) of porous steatite ceramic rods were prepared using different types of renewable plant fiber products as pore-forming agent with mass contents ranging from 2 to 10%. In addition, dense steatite ceramics were synthesized for comparison within a gas furnace at sintering temperatures between 1300 and 1350 °C. High-resolution 3D X-ray microscopy facilitated a non-destructive, direct investigation of the three-dimensional pore space and microstructure. By using image-based pore space analysis, various pore space parameters, such as, e.g., pore volume, pore-size distribution, and pore connectivity were determined. In addition to the characterization of the pore space, phase analysis, structural and chemical investigations were carried out by X-ray powder diffraction, electron microscopy, Fourier-transform infrared, Raman and X-ray spectroscopy. Finally, to evaluate the influence of characteristics on the physical properties, elastic, strength and thermal properties were determined. With the increase of porosity, the flexural strength and thermal conductivity values decrease from σf = 123 ± 8 to 37 ± 5 MPa and λ = 3.22 ± 0.02 to 1.77 ± 0.02 W/(m·K), respectively. The obtained experimental results were discussed by means of micromechanical models, highlighting the effect of pore-space morphologies on the physical performance of porous steatite ceramics.
- Published
- 2022
- Full Text
- View/download PDF
29. GraphML Transformation
- Author
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Christian Pich and Ulrik Brandes
- Subjects
computer.internet_protocol ,Programming language ,Computer science ,Style sheet ,Graph drawing ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,Graph (abstract data type) ,XSLT ,ddc:004 ,computer.software_genre ,computer ,XML ,computer.programming_language - Abstract
The efforts put into XML-related technologies have exciting consequences for XML-based graph data formats such as GraphML. We here give a systematic overview of the possibilities offered by XSLT style sheets for processing graph data, and illustrate that many basic tasks required for tools used in graph drawing can be implemented by means of style sheets, which are convenient to use, portable, and easy to customize.
- Published
- 2005
30. Loss of GFAT-1 feedback regulation activates the hexosamine pathway that modulates protein homeostasis
- Author
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Sabine Ruegenberg, Moritz Horn, Christian Pichlo, Kira Allmeroth, Ulrich Baumann, and Martin S. Denzel
- Subjects
Science - Abstract
Mutations in the hexosamine pathway key enzyme glutamine fructose-6-phosphate amidotransferase (GFAT-1) improve protein quality control and extend C. elegans lifespan. Here the authors present the crystal structures of full-length human GFAT-1 alone and with bound ligands and perform activity assays, which show that gain-of-function in the longevity-associated G451E variant is caused by a loss of feedback regulation.
- Published
- 2020
- Full Text
- View/download PDF
31. Die österreichische Geschichtsreifeprüfung: Zur Einschätzung fachlicher Kompetenzen
- Author
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Christian Pichler
- Subjects
school leaving examination ,higher education qualification ,competences ,methodological competences ,orientation competences ,evidence of reflectivity ,History (General) and history of Europe - Abstract
The Austrian higher education entrance qualification was reformed in 2012 with the objective of showing subject specific skills/competencies. This article examines demonstrations and levels of development of historical-political competencies of high school graduates, as seen in oral final exams. The epistemological basis of this study is the competence model of “FUER Geschichtsbewusstsein”, a working group for historical awareness, as it was incorporated into school curricula. The research process consists of two steps. First, subject-specific skills are examined using content analysis, then this evidence is rated in level range levels. The gradual range of the thus collected competencies is, on average, at basic level, thus missing the expected target.
- Published
- 2021
- Full Text
- View/download PDF
32. Phase diagrams, critical and multicritical behavior of hard-core Bose-Hubbard models
- Author
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Christian Pich and Erwin Frey
- Subjects
Physics ,Condensed matter physics ,Statistical Mechanics (cond-mat.stat-mech) ,FOS: Physical sciences ,Multicritical point ,Relative strength ,Square lattice ,Universality (dynamical systems) ,Supersolid ,Condensed Matter::Strongly Correlated Electrons ,Statistical physics ,Anisotropy ,Quantum ,Condensed Matter - Statistical Mechanics ,Phase diagram - Abstract
We determine the zero-temperature phase diagram of the hard-core Bose-Hubbard model on a square lattice by mean-field theory supplemented by a linear spin-wave analysis. Due to the interplay between nearest and next-nearest neighbor interaction and cubic anisotropy several supersolid phases with checkerboard, stripe domain or intermediate symmetry are stabilized. The phase diagrams show three different topologies depending on the relative strength of nearest and next-nearest neighbor interaction. We also find a rich variety of new quantum critical behavior and multicritical points and discuss the corresponding effective actions and universality classes., Comment: 19 pages, ReVTeX, 18 figures included, submitted to PRB
- Published
- 1997
- Full Text
- View/download PDF
33. Valoriser et renforcer les mécanismes d’évolution génétique par la sylviculture, pour l’adaptation au changement climatique
- Author
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François Lefèvre, Thomas Boivin, Aurore Bontemps, François Courbet, Hendrik Davi, Marion Durand-Gillmann, Bruno Fady, Julie Gauzere, Cindy Gidoin, Marie-Joe Karam, Hadrien Lalagüe, Sylvie Oddou-Muratorio, and Christian Pichot
- Subjects
Forestry ,SD1-669.5 - Abstract
L’adaptation est un enjeu majeur de la gestion forestière dans le contexte du changement climatique La diversité génétique qui caractérise les arbres forestiers leur confère un potentiel adaptatif très important mais pas illimité Prendre en compte les mécanismes de l’évolution dans les pratiques de gestion forestière adaptative renforcera la capacité des forêts gérées à répondre aux changements et aux aléas induits par le climat. En mettant l’accent sur le cas des forêts en régénération naturelle, nous proposons un cadre conceptuel général permettant d’intégrer la connaissance de ces mécanismes dans la prise de décision, dans une démarche de sylviculture par et pour l’évolution Ce cadre général pourra être décliné dans des situations locales diverses et complexes en s’appuyant sur la connaissance du contexte qu’ont les gestionnaires forestiers Nous développons une grille d’analyse simple, basée sur un petit nombre de paramètres caractérisant les mécanismes de l’évolution, pour comprendre l’impact des pratiques sylvicoles sur la dynamique de la diversité génétique et le maintien du potentiel d’évolution des populations d’arbres forestiers Après avoir rappelé l’état des connaissances sur les mécanismes de l’évolution chez les arbres forestiers, nous examinons les effets attendus de pratiques forestières actuelles ou innovantes sur ces mécanismes Pour illustrer la complexité des mécanismes en interaction, nous développons plus en détail les conséquences évolutives des interactions biotiques et celles d’un environnement fortement hétérogène La sylviculture par et pour l’évolution peut contribuer à l’adaptation des forêts au changement climatique Elle nécessite de combiner des objectifs à court et à long terme Nous proposons des pistes de recherche et d’expérimentation pour accompagner cette démarche.
- Published
- 2020
- Full Text
- View/download PDF
34. A family of unconventional deubiquitinases with modular chain specificity determinants
- Author
-
Thomas Hermanns, Christian Pichlo, Ilka Woiwode, Karsten Klopffleisch, Katharina F. Witting, Huib Ovaa, Ulrich Baumann, and Kay Hofmann
- Subjects
Science - Abstract
Deubiquitinating enzymes (DUBs) are essential to modulate ubiquitin signaling. While known DUBs can be grouped into six families, the authors here present biochemical and structural evidence for a seventh DUB family, defining determinants of substrate specificity for two representative enzymes.
- Published
- 2018
- Full Text
- View/download PDF
35. How to Integrate Experimental Research Approaches in Ecological and Environmental Studies: AnaEE France as an Example
- Author
-
Jean Clobert, André Chanzy, Jean-François Le Galliard, Abad Chabbi, Lucile Greiveldinger, Thierry Caquet, Michel Loreau, Christian Mougin, Christian Pichot, Jacques Roy, and Laurent Saint-André
- Subjects
research infrastructure ,experimentation ,continental ecosystems ,global changes ,environmental sciences ,open-access platforms ,Evolution ,QH359-425 ,Ecology ,QH540-549.5 - Abstract
Human activities have altered continental ecosystems worldwide and generated a major environmental crisis, prompting urgent societal questions on how to best produce goods while at the same time securing sustainable ecological services and raising needs to better understand and predict biodiversity and ecosystems dynamics under global changes. To tackle these questions, experimentation on ecosystems is necessary to improve our knowledge of processes and to propose scientifically sound management strategies. Experimental platforms able to manipulate key factors of global change and including state of the art observation methodologies are available worldwide but how to best integrate them has been rarely addressed. Here, we present and discuss the case of the national research infrastructure AnaEE France dedicated to the study of continental ecosystems and designed to congregate complementary experimental approaches in order to facilitate their access and use through a range of distributed and shared services. The conceptual design of AnaEE France includes five modules. Three modules gather experimental facilities along a gradient of experimental control ranging from highly controlled Ecotron facilities, semi-natural field mesocosms to in natura experimental sites covering major continental ecosystems (forests, croplands, grasslands, and lakes). In addition, AnaEE France also includes shared instruments that can be implemented in experiments and analytical platforms specifically dedicated to environmental biology. To promote reuse of data, generalize results and improve predictive models, AnaEE France further gathers modeling and information systems. The implementation of AnaEE France allowed for mutual synergies, improved the technical skills, stimulated new experiments and helped our scientific community to enter into the big data sharing era.
- Published
- 2018
- Full Text
- View/download PDF
36. Design, Synthesis and Biological Evaluation of Isoxazole-Based CK1 Inhibitors Modified with Chiral Pyrrolidine Scaffolds
- Author
-
Andreas Luxenburger, Dorian Schmidt, Chiara Ianes, Christian Pichlo, Marc Krüger, Thorsten von Drathen, Elena Brunstein, Graeme J. Gainsford, Ulrich Baumann, Uwe Knippschild, and Christian Peifer
- Subjects
protein kinase CK1 ,formerly known as casein kinase 1 ,chiral kinase inhibitors ,iminoribitol ,ribose pocket ,3,4-diaryl-isoxazole ,Pictet-Spengler cyclization ,Organic chemistry ,QD241-441 - Abstract
In this study, we report on the modification of a 3,4-diaryl-isoxazole-based CK1 inhibitor with chiral pyrrolidine scaffolds to develop potent and selective CK1 inhibitors. The pharmacophore of the lead structure was extended towards the ribose pocket of the adenosine triphosphate (ATP) binding site driven by structure-based drug design. For an upscale compatible multigram synthesis of the functionalized pyrrolidine scaffolds, we used a chiral pool synthetic route starting from methionine. Biological evaluation of key compounds in kinase and cellular assays revealed significant effects of the scaffolds towards activity and selectivity, however, the absolute configuration of the chiral moieties only exhibited a limited effect on inhibitory activity. X-ray crystallographic analysis of ligand-CK1δ complexes confirmed the expected binding mode of the 3,4-diaryl-isoxazole inhibitors. Surprisingly, the original compounds underwent spontaneous Pictet-Spengler cyclization with traces of formaldehyde during the co-crystallization process to form highly potent new ligands. Our data suggests chiral “ribose-like” pyrrolidine scaffolds have interesting potential for modifications of pharmacologically active compounds.
- Published
- 2019
- Full Text
- View/download PDF
37. Tuberculosis in Undocumented Migrants, Geneva
- Author
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Sigiriya A. Perone, Patrick Bovier, Christian Pichonnaz, Thierry Rochat, and Louis Loutan
- Subjects
letter ,tuberculosis ,migrant ,resistance ,Switzerland ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Published
- 2005
- Full Text
- View/download PDF
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