Canada Research Chairs

People learning new concepts can often generalize successfully from just a single example, yet machine learning algorithms typically require tens or hundreds of examples to perform with similar accuracy. People can also use learned concepts in richer ways than conventional algorithms-for action, imagination, and explanation. We present a computational model that captures these human learning abilities for a large class of simple visual concepts: handwritten characters from the world's alphabets. The model represents concepts as simple programs that best explain observed examples under a Bayesian criterion. On a challenging one-shot classification task, the model achieves human-level performance while outperforming recent deep learning approaches. We also present several "visual Turing tests" probing the model's creative generalization abilities, which in many cases are indistinguishable from human behavior.

BACKGROUND: Scoping reviews are used to identify knowledge gaps, set research agendas, and identify implications for decision-making. The conduct and reporting of scoping reviews is inconsistent in the literature. We conducted a scoping review to identify: papers that utilized and/or described scoping review methods; guidelines for reporting scoping reviews; and studies that assessed the quality of reporting of scoping reviews. METHODS: We searched nine electronic databases for published and unpublished literature scoping review papers, scoping review methodology, and reporting guidance for scoping reviews. Two independent reviewers screened citations for inclusion. Data abstraction was performed by one reviewer and verified by a second reviewer. Quantitative (e.g. frequencies of methods) and qualitative (i.e. content analysis of the methods) syntheses were conducted. RESULTS: After searching 1525 citations and 874 full-text papers, 516 articles were included, of which 494 were scoping reviews. The 494 scoping reviews were disseminated between 1999 and 2014, with 45% published after 2012. Most of the scoping reviews were conducted in North America (53%) or Europe (38%), and reported a public source of funding (64%). The number of studies included in the scoping reviews ranged from 1 to 2600 (mean of 118). Using the Joanna Briggs Institute methodology guidance for scoping reviews, only 13% of the scoping reviews reported the use of a protocol, 36% used two reviewers for selecting citations for inclusion, 29% used two reviewers for full-text screening, 30% used two reviewers for data charting, and 43% used a pre-defined charting form. In most cases, the results of the scoping review were used to identify evidence gaps (85%), provide recommendations for future research (84%), or identify strengths and limitations (69%). We did not identify any guidelines for reporting scoping reviews or studies that assessed the quality of scoping review reporting. CONCLUSION: The number of scoping reviews conducted per year has steadily increased since 2012. Scoping reviews are used to inform research agendas and identify implications for policy or practice. As such, improvements in reporting and conduct are imperative. Further research on scoping review methodology is warranted, and in particular, there is need for a guideline to standardize reporting.

Cells chemically isolate molecules in compartments to both facilitate and regulate their interactions. In addition to membrane-encapsulated compartments, cells can form proteinaceous and membraneless organelles, including nucleoli, Cajal and PML bodies, and stress granules. The principles that determine when and why these structures form have remained elusive. Here, we demonstrate that the disordered tails of Ddx4, a primary constituent of nuage or germ granules, form phase-separated organelles both in live cells and in vitro. These bodies are stabilized by patterned electrostatic interactions that are highly sensitive to temperature, ionic strength, arginine methylation, and splicing. Sequence determinants are used to identify proteins found in both membraneless organelles and cell adhesion. Moreover, the bodies provide an alternative solvent environment that can concentrate single-stranded DNA but largely exclude double-stranded DNA. We propose that phase separation of disordered proteins containing weakly interacting blocks is a general mechanism for forming regulated, membraneless organelles.

Bromodomains (BRDs) are protein interaction modules that specifically recognize ε-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family.

The continued growth of mobile and interactive computing requires devices manufactured with low-cost processes, compatible with large-area and flexible form factors, and with additional functionality. We review recent advances in the design of electronic and optoelectronic devices that use colloidal semiconductor quantum dots (QDs). The properties of materials assembled of QDs may be tailored not only by the atomic composition but also by the size, shape, and surface functionalization of the individual QDs and by the communication among these QDs. The chemical and physical properties of QD surfaces and the interfaces in QD devices are of particular importance, and these enable the solution-based fabrication of low-cost, large-area, flexible, and functional devices. We discuss challenges that must be addressed in the move to solution-processed functional optoelectronic nanomaterials.

To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.

All animal embryos pass through a stage during which developmental control is handed from maternally provided gene products to those synthesized from the zygotic genome. This maternal-to-zygotic transition (MZT) has been extensively studied in model organisms, including echinoderms, nematodes, insects, fish, amphibians and mammals. In all cases, the MZT can be subdivided into two interrelated processes: first, a subset of maternal mRNAs and proteins is eliminated; second, zygotic transcription is initiated. The timing and scale of these two events differ across species, as do the cellular and morphogenetic processes that sculpt their embryos. In this article, we discuss conserved and distinct features within the two component processes of the MZT.

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTMicrobial and Animal Rhodopsins: Structures, Functions, and Molecular MechanismsOliver P. Ernst*†, David T. Lodowski‡, Marcus Elstner§, Peter Hegemann∥, Leonid S. Brown⊥, and Hideki Kandori#View Author Information† Departments of Biochemistry and Molecular Genetics, University of Toronto, 1 King’s College Circle, Medical Sciences Building, Toronto, Ontario M5S 1A8, Canada‡ Center for Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106, United States§ Institute for Physical Chemistry, Karlsruhe Institute of Technology, Kaiserstrasse 12, 76131 Karlsruhe, Germany∥ Institute of Biology, Experimental Biophysics, Humboldt-Universität zu Berlin, Invalidenstrasse 42, 10115 Berlin, Germany⊥ Department of Physics and Biophysics Interdepartmental Group, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G 2W1, Canada# Department of Frontier Materials, Nagoya Institute of Technology, Showa-ku, Nagoya 466-8555, Japan*E-mail: [email protected]. Phone: (416) 978-3849. Fax: (416) 978-8548.Cite this: Chem. Rev. 2014, 114, 1, 126–163Publication Date (Web):December 23, 2013Publication History Received14 July 2013Published online23 December 2013Published inissue 8 January 2014https://doi.org/10.1021/cr4003769Copyright © 2013 American Chemical SocietyRIGHTS & PERMISSIONSACS AuthorChoiceArticle Views17523Altmetric-Citations660LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (19 MB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Crystal structure,Ions,Isomerization,Peptides and proteins,Receptors Get e-Alerts

La declaración PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), publicada en 2009, se diseñó para ayudar a los autores de revisiones sistemáticas a documentar de manera transparente el porqué de la revisión, qué hicieron los autores y qué encontraron. Durante la última década, ha habido muchos avances en la metodología y terminología de las revisiones sistemáticas, lo que ha requerido una actualización de esta guía. La declaración prisma 2020 sustituye a la declaración de 2009 e incluye una nueva guía de presentación de las publicaciones que refleja los avances en los métodos para identificar, seleccionar, evaluar y sintetizar estudios. La estructura y la presentación de los ítems ha sido modificada para facilitar su implementación. En este artículo, presentamos la lista de verificación PRISMA 2020 con 27 ítems, y una lista de verificación ampliada que detalla las recomendaciones en la publicación de cada ítem, la lista de verificación del resumen estructurado PRISMA 2020 y el diagrama de flujo revisado para revisiones sistemáticas. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews. Full English text available from:www.revespcardiol.org/en

Abstract The primary objective of this glossary is to give clear definitions for those who contribute to studies relevant to these disciplines, or who must interpret them, but are not themselves reproductive physiologists or physicians. This applies especially to chemists who need to understand the literature of reproductive and teratogenic effects of substances without recourse to a multiplicity of other glossaries or dictionaries. The glossary includes terms related to basic and clinical reproductive biology and teratogenesis, insofar as they are necessary for a self-contained document, particularly terms related to diagnosing, measuring, and understanding the effects of substances on the embryo, the fetus, and on the male and female reproductive systems. The glossary consists of about 1200 primary alphabetical entries and includes Annexes of common abbreviations and examples of chemicals with known effects on human reproduction and development. The authors hope that toxicologists, pharmacologists, medical practitioners, risk assessors, and regulatory authorities are among the groups who will find this glossary helpful, in addition to chemists. In particular, the glossary should facilitate the worldwide use of chemical terminology in relation to occupational and environmental risk assessment.

The mature mammalian retina is thought to lack regenerative capacity. Here, we report the identification of a stem cell in the adult mouse eye, which represents a possible substrate for retinal regeneration. Single pigmented ciliary margin cells clonally proliferate in vitro to form sphere colonies of cells that can differentiate into retinal-specific cell types, including rod photoreceptors, bipolar neurons, and Müller glia. Adult retinal stem cells are localized to the pigmented ciliary margin and not to the central and peripheral retinal pigmented epithelium, indicating that these cells may be homologous to those found in the eye germinal zone of other nonmammalian vertebrates.

We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.

We have built a reliable and robust system that takes as input an astronomical image, and returns as output the pointing, scale, and orientation of that image (the astrometric calibration or WCS information). The system requires no first guess, and works with the information in the image pixels alone; that is, the problem is a generalization of the "lost in space" problem in which nothing--not even the image scale--is known. After robust source detection is performed in the input image, asterisms (sets of four or five stars) are geometrically hashed and compared to pre-indexed hashes to generate hypotheses about the astrometric calibration. A hypothesis is only accepted as true if it passes a Bayesian decision theory test against a background hypothesis. With indices built from the USNO-B Catalog and designed for uniformity of coverage and redundancy, the success rate is 99.9% for contemporary near-ultraviolet and visual imaging survey data, with no false positives. The failure rate is consistent with the incompleteness of the USNO-B Catalog; augmentation with indices built from the 2MASS Catalog brings the completeness to 100% with no false positives. We are using this system to generate consistent and standards-compliant meta-data for digital and digitized imaging from plate repositories, automated observatories, individual scientific investigators, and hobbyists. This is the first step in a program of making it possible to trust calibration meta-data for astronomical data of arbitrary provenance.

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson’s disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy. Medulloblastoma is the most common malignant brain tumour in children; having assembled over 1,000 samples the authors report that somatic copy number aberrations are common in medulloblastoma, in particular a tandem duplication of SNCAIP, a gene associated with Parkinson’s disease, which is restricted to subgroup 4α, and translocations of PVT1, which are restricted to Group 3. Medulloblastoma is the most common malignant brain tumour in children. Four papers published in the 2 August 2012 issue of Nature use whole-genome and other sequencing techniques to produce a detailed picture of the genetics and genomics of this condition. Notable findings include the identification of recurrent mutations in genes not previously implicated in medulloblastoma, with significant genetic differences associated with the four biologically distinct subgroups and clinical outcomes in each. Potential avenues for therapy are suggested by the identification of targetable somatic copy-number alterations, including recurrent events targeting TGFβ signalling in Group 3, and NF-κB signalling in Group 4 medulloblastomas.

There has been some uncertainty concerning the conditions under which a manufacturing system may be termed 'flexible'. To clarify this confusion eight types of flexibilities are defined and described.

The diffusion of DNA in cytoplasm is thought to be an important determinant of the efficacy of gene delivery and antisense therapy. We have measured the translational diffusion of fluorescein-labeled double-stranded DNA fragments (in base pairs (bp): 21, 100, 250, 500, 1000, 2000, 3000, 6000) after microinjection into cytoplasm and nucleus of HeLa cells. Diffusion was measured by spot photobleaching using a focused argon laser spot (488 nm). In aqueous solutions, diffusion coefficients of the DNA fragments in water (D(w)) decreased from 53 x 10(-8) to 0.81 x 10(-8) cm(2)/s for sizes of 21-6000 bp; D(w) was related empirically to DNA size: D(w) = 4.9 x 10(-6) cm(2)/s.[bp size](-0.72). DNA diffusion coefficients in cytoplasm (D(cyto)) were lower than D(w) and depended strongly on DNA size. D(cyto)/D(w) decreased from 0.19 for a 100-bp DNA fragment to 0.06 for a 250-bp DNA fragment and was <0.01 for >2000 bp. Diffusion of microinjected fluorescein isothiocyanate (FITC) dextrans was faster than that of comparably sized DNA fragments of 250 bp and greater. In nucleus, all DNA fragments were nearly immobile, whereas FITC dextrans of molecular size up to 580 kDa were fully mobile. These results suggest that the highly restricted diffusion of DNA fragments in nucleoplasm results from extensive binding to immobile obstacles and that the decreased lateral mobility of DNAs >250 bp in cytoplasm is because of molecular crowding. The diffusion of DNA in cytoplasm may thus be an important rate-limiting barrier in gene delivery utilizing non-viral vectors.

The primary objective of this Glossary of Terms Used in Neurotoxicology is to give clear definitions for those who contribute to studies relevant to neurotoxicology, or must interpret them, but are not themselves neurotoxicologists, neuroscientists or physicians. This applies especially to chemists who need to understand the literature of neurotoxic effects of substances without recourse to a multiplicity of other glossaries or dictionaries. The Glossary includes terms related to basic and clinical neurology insofar as they are necessary for a self-contained document, and particularly terms related to diagnosing, measuring, and understanding effects of substances on the central and peripheral nervous systems. The glossary consists of about 800 terms as primary alphabetical entries, and includes Annexes of common abbreviations, and examples of chemicals with known effects on the nervous system. The authors hope that among the groups who will find this glossary helpful, in addition to chemists, are toxicologists, pharmacologists, medical practitioners, risk assessors, and regulatory authorities. In particular, it should facilitate the worldwide use of chemistry in relation to occupational and environmental risk assessment.

The interactions of protein kinases and phosphatases with their regulatory subunits and substrates underpin cellular regulation. We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. The KPI network contained many dense local regions of interactions that suggested new functions. Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism, whereas interactions of the target of rapamycin complex 1 (TORC1) uncovered new effector kinases in nitrogen and carbon metabolism. An extensive backbone of kinase-kinase interactions cross-connects the proteome and may serve to coordinate diverse cellular responses.

BACKGROUND: Understanding sustainability is one of the significant implementation science challenges. One of the big challenges in researching sustainability is the lack of consistent definitions in the literature. Most implementation studies do not present a definition of sustainability, even when assessing sustainability. The aim of the current study was to systematically develop a comprehensive definition of sustainability based on definitions already used in the literature. METHODS: We searched for knowledge syntheses of sustainability and abstracted sustainability definitions from the articles identified through any relevant systematic and scoping reviews. The constructs in the abstracted sustainability definitions were mapped to an existing definition. The comprehensive definition of sustainability was revised to include emerging constructs. RESULTS: We identified four knowledge syntheses of sustainability, which identified 209 original articles. Of the 209 articles, 24 (11.5%) included a definition of sustainability. These definitions were mapped to three constructs from an existing definition, and nine new constructs emerged. We reviewed all constructs and created a revised definition: (1) after a defined period of time, (2) a program, clinical intervention, and/or implementation strategies continue to be delivered and/or (3) individual behavior change (i.e., clinician, patient) is maintained; (4) the program and individual behavior change may evolve or adapt while (5) continuing to produce benefits for individuals/systems. All 24 definitions were remapped to the comprehensive definition (percent agreement among three coders was 94%). Of the 24 definitions, 17 described the continued delivery of a program (70.8%), 17 mentioned continued outcomes (70.8%), 13 mentioned time (54.2%), 8 addressed the individual maintenance of a behavior change (33.3%), and 6 described the evolution or adaptation (25.0%). CONCLUSIONS: We drew from over 200 studies to identify 24 existing definitions of sustainability. Based on these definitions, we identified five key sustainability constructs, which can be used as the basis for future research on sustainability. Our next step is to identify sustainability frameworks and develop a meta-framework using a concept mapping approach to consolidate the factors and considerations across sustainability frameworks.

Orthologous relationships form the basis of most comparative genomic and metagenomic studies and are essential for proper phylogenetic and functional analyses. The third version of the eggNOG database (http://eggnog.embl.de) contains non-supervised orthologous groups constructed from 1133 organisms, doubling the number of genes with orthology assignment compared to eggNOG v2. The new release is the result of a number of improvements and expansions: (i) the underlying homology searches are now based on the SIMAP database; (ii) the orthologous groups have been extended to 41 levels of selected taxonomic ranges enabling much more fine-grained orthology assignments; and (iii) the newly designed web page is considerably faster with more functionality. In total, eggNOG v3 contains 721,801 orthologous groups, encompassing a total of 4,396,591 genes. Additionally, we updated 4873 and 4850 original COGs and KOGs, respectively, to include all 1133 organisms. At the universal level, covering all three domains of life, 101,208 orthologous groups are available, while the others are applicable at 40 more limited taxonomic ranges. Each group is amended by multiple sequence alignments and maximum-likelihood trees and broad functional descriptions are provided for 450,904 orthologous groups (62.5%).