934 research outputs found

    Homology and Cohomology of E-infinity Ring Spectra

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    Every homology or cohomology theory on a category of E-infinity ring spectra is Topological Andre-Quillen homology or cohomology with appropriate coefficients. Analogous results hold for the category of A-infinity ring spectra and for categories of algebras over many other operads

    Azumaya Objects in Triangulated Bicategories

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    We introduce the notion of Azumaya object in general homotopy-theoretic settings. We give a self-contained account of Azumaya objects and Brauer groups in bicategorical contexts, generalizing the Brauer group of a commutative ring. We go on to describe triangulated bicategories and prove a characterization theorem for Azumaya objects therein. This theory applies to give a homotopical Brauer group for derived categories of rings and ring spectra. We show that the homotopical Brauer group of an Eilenberg-Mac Lane spectrum is isomorphic to the homotopical Brauer group of its underlying commutative ring. We also discuss tilting theory as an application of invertibility in triangulated bicategories.Comment: 23 pages; final version; to appear in Journal of Homotopy and Related Structure

    Mobile Architecture and Built Environment Laboratory (MABEL) - a building performance evaluation tool

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    This paper describes the Mobile Architecture and Built Environment Laboratory (MABEL) and its application for systematic building performance evaluation for compliance testing, commissioning, strategic and operational facility management and continuous improvement in the built environment.The first part of the paper introduces the application areas of on-site building performance evaluation and discusses the shortcomings in this regard in current practice. It emphasises the need for on-site investigations to generate information on \u27as built performance\u27 for the \u27feedback\u27 loop between design, operation and occupancy of new buildings, retrofit or adjustment.The second part introduces the Energy-Comfort-Behaviour Framework for \u27across-the-board\u27 building evaluation and discusses MABEL\u27s role in this scheme. MABEL\u27s objectives, procedures and the performance measurement matrix are explained and discussed. <br /

    Modules in Monoidal Model Categories

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    This paper studies the existence of and compatibility between derived change of ring, balanced product, and function module derived functors on module categories in monoidal model categories

    Improving your target-template alignment with MODalign

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    Summary: MODalign is an interactive web-based tool aimed at helping protein structure modelers to inspect and manually modify the alignment between the sequences of a target protein and of its template(s). It interactively computes, displays and, upon modification of the target-template alignment, updates the multiple sequence alignments of the two protein families, their conservation score, secondary structure and solvent accessibility values, and local quality scores of the implied three-dimensional model(s). Although it has been designed to simplify the target-template alignment step in modeling, it is suitable for all cases where a sequence alignment needs to be inspected in the context of other biological information

    Effects of bone marrow‐derived mesenchymal stromal cells on gene expression in human alveolar type II cells exposed to TNF‐α, IL‐1ÎČ, and IFN‐γ

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    The acute respiratory distress syndrome (ARDS) is common in critically ill patients and has a high mortality rate. Mesenchymal stromal cells (MSCs) have demonstrated therapeutic potential in animal models of ARDS, and their benefits occur in part through interactions with alveolar type II (ATII) cells. However, the effects that MSCs have on human ATII cells have not been well studied. Using previously published microarray data, we performed genome‐wide differential gene expression analyses of human ATII cells that were (1) unstimulated, (2) exposed to proinflammatory cytokines (CytoMix), or (3) exposed to proinflammatory cytokines plus MSCs. Findings were validated by qPCR. Alveolar type II cells differentially expressed hundreds of genes when exposed either to proinflammatory cytokines or to proinflammatory cytokines plus MSCs. Stimulation with proinflammatory cytokines increased expression of inflammatory genes and downregulated genes related to surfactant function and alveolar fluid clearance. Some of these changes, including expression of some cytokines and genes related to surfactant, were reversed by exposure to MSCs. In addition, MSCs induced upregulation of other potentially beneficial genes, such as those related to extracellular matrix remodeling. We confirmed several of these gene expression changes by qPCR. Thus, ATII cells downregulate genes associated with surfactant and alveolar fluid clearance when exposed to inflammatory cytokines, and mesenchymal stromal cells partially reverse many of these gene expression changes.Mesenchymal stromal cells (MSCs) have therapeutic potential for the acute respiratory distress syndrome, and their benefits occur in part through interactions with alveolar type II (ATII) cells. We performed genome‐wide differential gene expression analyses of human ATII cells that were (1) unstimulated, (2) exposed to proinflammatory cytokines (CytoMix), or (3) exposed to CytoMix plus MSCs. Stimulation with CytoMix increased expression of inflammatory genes and downregulated genes related to surfactant function and alveolar fluid clearance, and several gene expression changes were reversed by exposure to MSCs.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145579/1/phy213831_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145579/2/phy213831.pd

    A Model for Emission Yield from Planar Photocathodes Based on Photon-Enhanced Thermionic Emission or Negative-Electron-Affinity Photoemission

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    A general model is presented for electron emission yield from planar photocathodes that accounts for arbitrary cathode thickness and finite recombination velocities at both front and back surfaces. This treatment is applicable to negative electron affinity emitters as well as positive electron affinity cathodes, which have been predicted to be useful for energy conversion. The emission model is based on a simple one-dimensional steady-state diffusion treatment. The resulting relation for electron yield is used to model emission from thin-film cathodes with material parameters similar to GaAs. Cathode thickness and recombination at the emissive surface are found to strongly affect emission yield from cathodes, yet the magnitude of the effect greatly depends upon the emission mechanism. A predictable optimal film thickness is found from a balance between optical absorption, surface recombination, and emission rate

    The SWISS-MODEL Repository: new features and functionalities

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    The SWISS-MODEL Repository is a database of annotated 3D protein structure models generated by the SWISS-MODEL homology-modelling pipeline. As of September 2005, the repository contained 675 000 models for 604 000 different protein sequences of the UniProt database. Regular updates ensure that the content of the repository reflects the current state of sequence and structure databases, integrating new or modified target sequences, and making use of new template structures. Each Repository entry consists of one or more 3D models accompanied by detailed information about the target protein and the model building process: functional annotation, a detailed template selection log, target-template alignment, summary of the model building and model quality assessment. The SWISS-MODEL Repository is freely accessible at

    Critical assessment of methods of Protein Structure Prediction (CASP) – Round XIII

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    CASP (Critical Assessment of Structure Prediction) assesses the state of the art in modeling protein structure from amino acid sequence. The most recent experiment (CASP13 held in 2018) saw dramatic progress in structure modeling without use of structural templates (historically ‘ab initio’ modeling). Progress was driven by the successful application of deep learning techniques to predict inter-residue distances. In turn, these results drove dramatic improvements in three-dimensional structure accuracy: With the proviso that there are an adequate number of sequences known for the protein family, the new methods essentially solve the long-standing problem of predicting the fold topology of monomeric proteins. Further, the number of sequences required in the alignment has fallen substantially. There is also substantial improvement in the accuracy of template-based models. Other areas - model refinement, accuracy estimation, and the structure of protein assemblies - have again yielded interesting results. CASP13 placed increased emphasis on the use of sparse data together with modeling and chemical crosslinking, SAXS, and NMR all yielded more mature results. This paper summarizes the key outcomes of CASP13. The special issue of PROTEINS contains papers describing the CASP13 assessments in each modeling category and contributions from the participants

    Antigenic diversity is generated by distinct evolutionary mechanisms in African trypanosome species

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    Antigenic variation enables pathogens to avoid the host immune response by continual switching of surface proteins. The protozoan blood parasite Trypanosoma brucei causes human African trypanosomiasis ("sleeping sickness") across sub-Saharan Africa and is a model system for antigenic variation, surviving by periodically replacing a monolayer of variant surface glycoproteins (VSG) that covers its cell surface. We compared the genome of Trypanosoma brucei with two closely related parasites Trypanosoma congolense and Trypanosoma vivax, to reveal how the variant antigen repertoire has evolved and how it might affect contemporary antigenic diversity. We reconstruct VSG diversification showing that Trypanosoma congolense uses variant antigens derived from multiple ancestral VSG lineages, whereas in Trypanosoma brucei VSG have recent origins, and ancestral gene lineages have been repeatedly co-opted to novel functions. These historical differences are reflected in fundamental differences between species in the scale and mechanism of recombination. Using phylogenetic incompatibility as a metric for genetic exchange, we show that the frequency of recombination is comparable between Trypanosoma congolense and Trypanosoma brucei but is much lower in Trypanosoma vivax. Furthermore, in showing that the C-terminal domain of Trypanosoma brucei VSG plays a crucial role in facilitating exchange, we reveal substantial species differences in the mechanism of VSG diversification. Our results demonstrate how past VSG evolution indirectly determines the ability of contemporary parasites to generate novel variant antigens through recombination and suggest that the current model for antigenic variation in Trypanosoma brucei is only one means by which these parasites maintain chronic infections
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