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The HIV- and CMV-specific CD8 T cells that were sorted to perform the gene expression analysis are highlighted in pink in supplemental Tables 1 and 2 (available on the Blood Web site; see the Supplemental Materials link at the top of the online article). Total RNA was purified, amplified, and hybridized onto Illumina Human Ref-8 V3 BeadChips as described previously.25 Gene expression data were analyzed using Bioconductor and filtered; of the 24 526 initial probe set, 10 630 probes were left after the filtering steps. The resulting matrix of filtered genes was generated by log2 transformation and used as input for linear modeling. The Bioconductor's limma package was used at this step to estimate the fold change between groups of HIV-specific CD8 T cells in primary and chronic infection and CMV-specific CD8 T cells by fitting a linear model and using an empirical Bayes method to moderate SEs of the estimated log-fold changes for each gene expression values. P values from the resulting comparison were adjusted for multiple testing according to the method of Benjamini and Hochberg.26 Determination of regulated gene expression was based solely on the nominal P values. Ingenuity Pathways Analysis (Ingenuity Systems, www.ingenuity.com) was used to identify the biologic functions, canonical pathways, and transcription factor regulation using the genes from the dataset that met the P value cutoff of .05.
Self-determination theory has already been successfully applied in the contexts of games (see Rigby and Ryan 2011) and gamification (see Mekler et al. 2017; Sailer et al. 2017a). It postulates psychological needs for competence, autonomy, and social relatedness. The satisfaction of these needs is central for intrinsic motivation and subsequently for high-quality learning (see Ryan and Deci 2000), with self-determination theory emphasizing the importance of the environment in satisfying these psychological needs (Ryan and Deci 2002). Enriching learning environments with game design elements modifies these environments and potentially affects learning outcomes. From the self-determination perspective, different types of feedback can be central learning mechanisms triggered by game design elements. Constantly providing learners with feedback is a central characteristic of serious games (Wouters et al. 2013; Prensky 2001) and of gamification (Werbach and Hunter 2012). Although the effectiveness of feedback has been shown to vary depending on a variety of criteria such as the timing of feedback (immediate, delayed), frame of reference (criterial, individual, social), or level of feedback (task, process, self-regulation, self), feedback is among the most powerful factors in the relationship between educational interventions and learning in general (Hattie and Timperley 2007). Based on the theory of gamified learning as well as self-determination theory, gamification might influence learning outcomes in a positive way.
Liang Yue: The Quiet Room, 2012 International Premiere This serene installation by leading Chinese photographer and filmmaker Liang Yue recalls the most dramatic and ethereal of landscape-based art, profiling Canada in winter through both image and sound. The work focuses on the textures of snow and the mechanics of condensation, coupled with a surprisingly dramatic soundtrack of carefully recorded and amplified winter sounds. Presented in collaboration with the Gladstone Hotel, 1214 Queen Street West. September 6 to 16.
Health product packaging is an important factor in promoting the intended and proper use of a product. The type or format of a container often gives users a cue as to the intended route and method of administration.Footnote 8 If a health product container, its format, or its appearance looks similar to that of other products intended to be handled differently, errors may occur, and serious harm may result, as in the following examples.
The terms \"small container\" and \"small-volume container\" are reserved for containers with obvious restrictions on the amount of information that can appear on the product label or package.Footnote 47Footnote 139 This includes special containers that are too small to accommodate a full label.Footnote 4
Mock-up: In the context of medication labelling and packaging, a full-colour, actual-size copy of the labels and a colourrepresentation (e.g., photograph) of the packages intended to be used for the sale of the drug, including all presentation and design elements, proposed graphics, fonts, colours, and text (with a place holder for expiry date, DIN, and lot number).
White Space: \"the 'negative' area surrounding a letterform\" (Carter R, et al. Typographic design: Form and communication, fifth edition. 2012Footnote 12). Such white space on a product label or package refers to any space not covered by print, markings, coloured graphics, watermarks, or other elements of the label
User testing refers to a broad set of methods for assessing usability, identifying problems experienced by users, and developing solutions to eliminate or reduce the consequences of these problems. User testing simulates or mimics the circumstances of product use to provide a realistic view of how the label and package function within the intended environments. User testing is not quality assurance testing, nor is it market research. User testing is performed under controlled conditions to determine whether people can accomplish specific goals with the product or system of interest.
Information and links are provided below to a number of methodologies that may be used to assess labels and packages. With higher levels of risk, additional and more rigorous testing methods are typically recommended. Development of product-use process maps are an integral component of these methodologies.
Health product selection tasks can be used to assess or compare performance as affected by label or package design. This method has been used to compare existing labels against redesigned drug labels,Footnote 178 to assess the comprehension of common abbreviations,Footnote 179 and to determine whether inclusion of an additional sponsor logo will affect drug selection.Footnote 73
Australian Government. Department of Health, Therapeutic Goods Administration. TGA medicine labelling and packaging review. Consultation paper. Version 1 [Internet]. Symonston (Australia): The Administration; 2012 May [cited 2016 Mar 6].
Data were collected and analysed with Epi-Info 6 (Centers for Disease Control, Atlanta). Statistical significance was determined using the 2-tailed Fisher exact test for 22 tables for each of the categorical values. A non-parametric cumulative failure graph using the Kaplan-Meier method and the endpoint of antibiotic cessation was plotted using the statistics package Minitab (version 15) to model the proportion of antibiotics ceased over time due to complications.
Here we introduce tcR, a new R package, representing a platform for the advanced analysis of T cell receptor repertoires, which includes diversity measures, shared T cell receptor sequences identification, gene usage statistics computation and other widely used methods. The tool has proven its utility in recent research studies.
tcR is an R package for the advanced analysis of T cell receptor repertoires after primary TR sequences extraction from raw sequencing reads. The stable version can be directly installed from The Comprehensive R Archive Network ( -project.org/mirrors.html). The source code and development version are available at tcR GitHub ( ) along with the full documentation and typical usage examples.
Here, we introduce tcR: an R package for the analysis of TR repertoires that integrates widely used methods for individual repertoires analyses and TR repertoires comparison: gene usage comparison, customisable search for clonotypes shared among repertoires, spectratyping, random TR repertoire generation, various repertoire diversity measures and other commonly used approaches to the repertoire analysis.
In future we plan to continue adding new methods of repertoire comparisons, diversity estimation, to add parsers for data generated by Decombinator, IgBLAST and other software for extracting CDR3 sequences and aligning genes, and to optimise the package to efficiently handle large volumes of TR data for the analysis of massive repertoire data (tens of repertoires with millions of clonotypes). We plan to add more options for the automatic report generation, e.g. for tracking TR repertoires dynamics.
The R package tcR is a platform designed for the analysis of TR repertoire data, which has two major advantages. First, it consolidates a wide spectrum of possible approaches to TR repertoire analysis in a single package. Second, it offers new methods for the comparative analysis of TR repertoires. The package has been applied to the experimental NGS data and allowed to obtain valuable observations of the inter-individual similarity of TR repertoires. The developed package is providing a wide range of new opportunities for the TR repertoire data analysis. 153554b96e