148 research outputs found

    A Whisper of Espionage: Wolfgang Kohler and the Apes of Tenerife

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    Differential Protection by Two Sunscreens from UV Radiation–Induced Immunosuppression

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    A controversy has arisen concerning the ability of sunscreens to protect mice from the immunosuppressive effects of UV radiation. We have assessed the photoprotection in hairless mice of two sun protection factor (SPF) 15 sunscreens containing different UVB (280-320-nm) absorbers, namely, octyl-N-dimethyl-p-aminobenzoate (o-PABA) or 2-ethyl-hexyl-p-methoxycinnamate (2-EHMC). Following three minimum erythemal exposures to UV radiation, both systemic suppression of contact hypersensitivity to 2, 4-dinitrofluorobenzene and inductin of susceptibility to transplanted UV radiation-induced tumor cells was established. Topically applied 2-EHMC sunscreen protected totally From both forms of immunosuppression, but the o-PABA sunscreen failed to protect, although both sunscreens were equally effective in protection from UV radiation-induced erythema and edema

    Catch and release’ cascades: a resin-mediated three-component cascade approach to small molecules

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    The application of a ‘catch and release’ approach to palladium-catalysed multi-component cascade reactions leads to diverse libraries of pharmacologically interesting small molecules in high yield and with excellent purity

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

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    Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

    Human Perception of Fear in Dogs Varies According to Experience with Dogs

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    To investigate the role of experience in humans’ perception of emotion using canine visual signals, we asked adults with various levels of dog experience to interpret the emotions of dogs displayed in videos. The video stimuli had been pre-categorized by an expert panel of dog behavior professionals as showing examples of happy or fearful dog behavior. In a sample of 2,163 participants, the level of dog experience strongly predicted identification of fearful, but not of happy, emotional examples. The probability of selecting the “fearful” category to describe fearful examples increased with experience and ranged from.30 among those who had never lived with a dog to greater than.70 among dog professionals. In contrast, the probability of selecting the “happy” category to describe happy emotional examples varied little by experience, ranging from.90 to.93. In addition, the number of physical features of the dog that participants reported using for emotional interpretations increased with experience, and in particular, more-experienced respondents were more likely to attend to the ears. Lastly, more-experienced respondents provided lower difficulty and higher accuracy self-ratings than less-experienced respondents when interpreting both happy and fearful emotional examples. The human perception of emotion in other humans has previously been shown to be sensitive to individual differences in social experience, and the results of the current study extend the notion of experience-dependent processes from the intraspecific to the interspecific domain

    Scaffolded contributions, active meetings and scaled engagement: How technology shapes informal learning practices in healthcare SME networks

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    The importance of informal learning in modern, fast paced work environments has long been recognised. While technology support has been suggested for informal learning by individuals and in organisations, it is only more recently, that we have been able to study in more detail how technology can support such learning in real workplaces. This paper examines technology supported informal workplace learning in the relatively unexplored context of cross-organisational networks of small and medium-sized enterprises (SMEs). We developed an informal learning tool, using a participative, co-design approach found useful for engaging such networks. We analyse qualitative data on tool usage, collected over six months from 30 professionals, working in three different cross-organisational healthcare SME networks. We identify three changes in practice: (1) scaffolded contributions, (2) active meetings and (3) scaled engagement. We explain how and why some functionalities in the tool contributed to these changed practices while others were unused. The changed practices are linked to three stages of organisational knowledge creation: making individual knowledge explicit, group knowledge integration and institutionalisation. We propose three associations between tool functionalities and these processes that contribute to our understanding of technology support for informal learning in early stages of knowledge creation in cross-organisational networks
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