How Expressiveness of a Robotic Tutor is Perceived by Children in a Learning Environment

We present a study investigating the expressiveness of two different types of robots in a tutoring task. The robots used were i) the EMYS robot, with facial expression capabilities, and ii) the NAO robot, without facial expressions but able to perform expressive gestures. Preliminary results show that the NAO robot was perceived to be more friendly, pleasant and empathic than the EMYS robot as a tutor in a learning environment

PD-L1 blockade enhances response of pancreatic ductal adenocarcinoma to radiotherapy

Pancreatic ductal adenocarcinoma (PDAC) is considered a non‐immunogenic tumor, and immune checkpoint inhibitor monotherapy lacks efficacy in this disease. Radiotherapy (RT) can stimulate the immune system. Here, we show that treatment of KPC and Pan02 murine PDAC cells with RT and gemcitabine upregulated PD‐L1 expression in a JAK/Stat1‐dependent manner. In vitro, PD‐L1 inhibition did not alter radio‐ and chemosensitivity. In vivo, addition of anti‐PD‐L1 to high (12, 5 × 3, 20 Gy) but not low (6, 5 × 2 Gy) RT doses significantly improved tumor response in KPC and Pan02 allografts. Radiosensitization after PD‐L1 blockade was associated with reduced CD11b+Gr1+ myeloid cell infiltration and enhanced CD45+CD8+ T‐cell infiltration with concomitant upregulation of T‐cell activation markers including CD69, CD44, and FasL, and increased CD8:Treg ratio. Depletion of CD8+ T cells abrogated radiosensitization by anti‐PD‐L1. Blockade of PD‐L1 further augmented the effect of high RT doses (12 Gy) in preventing development of liver metastases. Exploring multiple mathematical models reveals a mechanism able to explain the observed synergy between RT and anti‐PD‐L1 therapy. Our findings provide a rationale for testing the use of immune checkpoint inhibitors with RT in PDAC

Are health assets associated with improved outcomes for hospitalised older adults? A systematic review

Objective Health assets are protective factors that support health and wellbeing, rather than risk factors that are associated with disease. This concept was developed in the community setting. In hospitalised older adults, the dominant approach has been to identify risk factors, with little examination of health assets. The purpose of this systematic review was to determine whether, in hospitalised older people, individual health assets decrease the risk of post hospital mortality, functional decline, new need for residential care, readmission or longer length of stay. Methods MEDLINE, EMBASE, CINAHL and PsycINFO were searched to identify studies examining outcomes for hospitalised older adults. Included studies examined at least one potential individual health asset, which was a psychosocial characteristic or health characteristic. Study quality was assessed, and findings are narratively described. Results Nine prospective cohort and two retrospective cohort studies were identified. subjective, functional and biological health assets were identified. Health assets were associated with decreased risk of post-hospital mortality, functional decline, new need for residential care and readmission. Conclusion The complex interplay between health status and psychological and social factors is incompletely understood. Health assets are associated with improved outcomes for hospitalised older adults. The small number of studies suitable for inclusion indicates the need for further research in this area

Identification of a major causative agent of human cercarial dermatitis, Trichobilharzia franki (Muller and Kimmig 1994), in southern England and its evolutionary relationships with other European populations.

Background Trichobilharzia is the most species rich and widely distributed genus of schistosomes and is known throughout Europe and North America as an agent of human cercarial dermatitis. The disease is caused by an acute allergic reaction in the skin that develops as a consequence of repeated contact with water containing schistosomatid cercariae. However, despite historical outbreaks of the disease, there are no published records of accurately identified Trichobilharzia species from the UK. Methods Two hundred Radix auricularia (L.) were sampled from a recreational fishing lake in Hampshire and emerging schistosomatid cercariae were collected for microscopy and DNA extraction. General morphological description of the cercariae was performed, alongside sequencing and phylogenetic analysis of the 28S ribosomal DNA for accurate species identification as well as comparisons of ITS1 in order to identify evolutionary affinities with other European populations. All molecular comparisons were performed using published sequences. Results The phylogenetic analysis of 28S sequences identified the cercariae as Trichobilharzia franki. Two unique British ITS1 haplotypes were identified which were most closely related to haplotypes of T. franki populations from France. Haplotype network analysis indicated the mixing of T. franki populations throughout Europe. It is suggested that parasite distribution is the probable result of the movement of migratory waterfowl. Conclusions This is the first accurate record of T. franki in the UK. The movement of T. franki with waterfowl could pose a considerable human health risk, as in mainland Europe, and signifies T. franki-associated human cercarial dermatitis as a re-emerging disease in the UK

Transcriptional changes in Huntington disease identified using genome-wide expression profiling and cross-platform analysis

Evaluation of transcriptional changes in the striatum may be an effective approach to understanding the natural history of changes in expression contributing to the pathogenesis of Huntington disease (HD). We have performed genome-wide expression profiling of the YAC128 transgenic mouse model of HD at 12 and 24 months of age using two platforms in parallel: Affymetrix and Illumina. The data from these two powerful platforms were integrated to create a combined rank list, thereby revealing the identity of additional genes that proved to be differentially expressed between YAC128 and control mice. Using this approach, we identified 13 genes to be differentially expressed between YAC128 and controls which were validated by quantitative real-time PCR in independent cohorts of animals. In addition, we analyzed additional time points relevant to disease pathology: 3, 6 and 9 months of age. Here we present data showing the evolution of changes in the expression of selected genes: Wt1, Pcdh20 and Actn2 RNA levels change as early as 3 months of age, whereas Gsg1l, Sfmbt2, Acy3, Polr2a and Ppp1r9a RNA expression levels are affected later, at 12 and 24 months of age. We also analyzed the expression of these 13 genes in human HD and control brain, thereby revealing changes in SLC45A3, PCDH20, ACTN2, DDAH1 and PPP1R9A RNA expression. Further study of these genes may unravel novel pathways contributing to HD pathogenesis. DDBJ/EMBL/GenBank accession no: GSE1967

Weighted protein interaction network analysis of frontotemporal dementia

The genetic analysis of complex disorders has undoubtedly led to the identification of a wealth of associations between genes and specific traits. However, moving from genetics to biochemistry one gene at a time has, to date, rather proved inefficient and under-powered to comprehensively explain the molecular basis of phenotypes. Here we present a novel approach, weighted protein−protein interaction network analysis (W-PPI-NA), to highlight key functional players within relevant biological processes associated with a given trait. This is exemplified in the current study by applying W-PPI-NA to frontotemporal dementia (FTD): We first built the state of the art FTD protein network (FTD-PN) and then analyzed both its topological and functional features. The FTD-PN resulted from the sum of the individual interactomes built around FTD-spectrum genes, leading to a total of 4198 nodes. Twenty nine of 4198 nodes, called inter-interactome hubs (IIHs), represented those interactors able to bridge over 60% of the individual interactomes. Functional annotation analysis not only reiterated and reinforced previous findings from single genes and gene-coexpression analyses but also indicated a number of novel potential disease related mechanisms, including DNA damage response, gene expression regulation, and cell waste disposal and potential biomarkers or therapeutic targets including EP300. These processes and targets likely represent the functional core impacted in FTD, reflecting the underlying genetic architecture contributing to disease. The approach presented in this study can be applied to other complex traits for which risk-causative genes are known as it provides a promising tool for setting the foundations for collating genomics and wet laboratory data in a bidirectional manner. This is and will be critical to accelerate molecular target prioritization and drug discovery

Werewolves, cheats, and cultural sensitivity

This paper discusses the design and evaluation of the system MIXER (Moderating Interactions for Cross-Cultural Empathic Relationships), which applies a novel approach to the education of children in cultural sensitivity. MIXER incorporates intelligent affective and interactive characters, including a model of a Theory of Mind mechanism, in a simulated virtual world. We discuss the relevant pedagogical approaches, related work, the underlying mind model used for MIXER agents as well as its innovative interaction interface utilising a tablet computer and a pictorial interaction language. We then consider the evaluation of the system, whether this shows it met its pedagogical objectives, and what can be learned from our results.</p

Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities.

The mammary epithelium depends on specific lineages and their stem and progenitor function to accommodate hormone-triggered physiological demands in the adult female. Perturbations of these lineages underpin breast cancer risk, yet our understanding of normal mammary cell composition is incomplete. Here, we build a multimodal resource for the adult gland through comprehensive profiling of primary cell epigenomes, transcriptomes, and proteomes. We define systems-level relationships between chromatin-DNA-RNA-protein states, identify lineage-specific DNA methylation of transcription factor binding sites, and pinpoint proteins underlying progesterone responsiveness. Comparative proteomics of estrogen and progesterone receptor-positive and -negative cell populations, extensive target validation, and drug testing lead to discovery of stem and progenitor cell vulnerabilities. Top epigenetic drugs exert cytostatic effects; prevent adult mammary cell expansion, clonogenicity, and mammopoiesis; and deplete stem cell frequency. Select drugs also abrogate human breast progenitor cell activity in normal and high-risk patient samples. This integrative computational and functional study provides fundamental insight into mammary lineage and stem cell biology