Systematic analysis of video data from different human-robot interaction studies: A categorisation of social signals during error situations

Human–robot interactions are often affected by error situations that are caused by either the robot or the human. Therefore, robots would profit from the ability to recognize when error situations occur. We investigated the verbal and non-verbal social signals that humans show when error situations occur in human–robot interaction experiments. For that, we analyzed 201 videos of five human–robot interaction user studies with varying tasks from four independent projects. The analysis shows that there are two types of error situations: social norm violations and technical failures. Social norm violations are situations in which the robot does not adhere to the underlying social script of the interaction. Technical failures are caused by technical shortcomings of the robot. The results of the video analysis show that the study participants use many head movements and very few gestures, but they often smile, when in an error situation with the robot. Another result is that the participants sometimes stop moving at the beginning of error situations. We also found that the participants talked more in the case of social norm violations and less during technical failures. Finally, the participants use fewer non-verbal social signals (for example smiling, nodding, and head shaking), when they are interacting with the robot alone and no experimenter or other human is present. The results suggest that participants do not see the robot as a social interaction partner with comparable communication skills. Our findings have implications for builders and evaluators of human–robot interaction systems. The builders need to consider including modules for recognition and classification of head movements to the robot input channels. The evaluators need to make sure that the presence of an experimenter does not skew the results of their user studies

The Effect of RNA Secondary Structures on RNA-Ligand Binding and the Modifier RNA Mechanism: A Quantitative Model

RNA-ligand binding often depends crucially on the local RNA secondary structure at the binding site. We develop here a model that quantitatively predicts the effect of RNA secondary structure on effective RNA-ligand binding activities based on equilibrium thermodynamics and the explicit computations of partition functions for the RNA structures. A statistical test for the impact of a particular structural feature on the binding affinities follows directly from this approach. The formalism is extended to describing the effects of hybridizing small \modifier RNAs' to a target RNA molecule outside its ligand binding site. We illustrate the applicability of our approach by quantitatively describing the interaction of the mRNA stabilizing protein HuR with AU-rich elements [Meisner et al. (2004), Chem. Biochem. in press]. We discuss our model and recent experimental findings demonstrating the ffectivity of modifier RNAs in vitro in the context of the current research activities in the field of non-coding RNAs. We speculate that modifier RNAs might also exist in nature; if so, they present an additional regulatory layer for fine-tuning gene expression that could evolve rapidly, leaving no obvious traces in the genomic DNA sequences

Beyond germline genetic testing - heterozygous pathogenic variants in PMS2 in two children with osteosarcoma and ependymoma

Background Lynch syndrome (LS) is not considered part of childhood cancer predisposition syndromes. Case presentation Analysis of a pediatric osteosarcoma (OS) displayed hypermutation (16.8), alternative lengthening of telomeres (ALT), loss of PMS2 expression in tumor tissue (retained in non-neoplastic cells), PMS2 loss of heterozygosity (LOH), and high-degree of microsatellite instability (MSI) tested by PCR. A heterozygous duplication c.1076dup p.(Leu359Phefs*6) in exon 10 of NM_000535.6:PMS2 was detected by SNV analysis in peripheral blood, confirming diagnosis of LS in the patient. The tumor molecular features suggest LS-associated development of OS. In a second case, whole-genome sequencing identified a heterozygous SNV c.1 A > T p.? in exon 1 of PMS2 in tumor and germline material of a girl with ependymoma. Tumor analysis displayed evidence for ALT and low mutational burden (0.6), PMS2 expression was retained, MSI was low. Multiplex ligation-dependent probe amplification identified no additional PMS2 variant and germline MSI testing did not reveal increased gMSI ratios in the patient´s lymphocytes. Thus, CMMRD was most closely excluded and our data do not suggest that ependymoma was related to LS in the child. Conclusions Our data suggest that the LS cancer spectrum may include childhood cancer. The importance of LS in pediatric cancers necessitates prospective data collection. Comprehensive molecular workup of tumor samples is necessary to explore the causal role of germline genetic variants

Colon cancer cell-derived 12(S)-HETE induces the retraction of cancer-associated fibroblast via MLC2, RHO/ROCK and Ca2+ signalling

Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models. In order to elucidate how CAFs support CRC invasion, tumour spheroid-induced CAF retraction and free intracellular Ca2+ levels were measured and pharmacological-or siRNA-based inhibition of selected signalling cascades was performed. CRC spheroids caused the retraction of CAFs, generating entry gates in the adjacent surrogate stroma. The responsible trigger factor 12(S)-HETE provoked a signal, which was transduced by PLC, IP3, free intracellular Ca2+, Ca(2+)calmodulin-kinase-II, RHO/ROCK and MYLK which led to the activation of myosin light chain 2, and subsequent CAF mobility. RHO activity was observed downstream as well as upstream of Ca2+ release. Thus, Ca2+ signalling served as central signal amplifier. Treatment with the FDA-approved drugs carbamazepine, cinnarizine, nifedipine and bepridil HCl, which reportedly interfere with cellular calcium availability, inhibited CAF-retraction. The elucidation of signalling pathways and identification of approved inhibitory drugs warrant development of intervention strategies targeting tumour-stroma interaction

The relation between learners' experience in simulations and diagnostic accuracy: generalizability across medical and teacher education

Simulation-based learning is being increasingly implemented across different domains of higher education to facilitate essential skills and competences (e.g. diagnostic skills, problem-solving, etc.). However, the lack of research that assesses and compares simulations used in different contexts (e.g., from design perspective) makes it challenging to effectively transfer good practices or establish guidelines for effective simulations across different domains. This study suggests some initial steps to address this issue by investigating the relations between learners' experience in simulation-based learning environments and learners' diagnostic accuracy across several different domains and types of simulations, with the goal of facilitating cross-domain research and generalizability. The findings demonstrate that used learners' experience ratings are correlated with objective performance measures, and can be used for meaningful comparisons across different domains. Measures of perceived extraneous cognitive load were found to be specific to the simulation and situation, while perceived involvement and authenticity were not. Further, the negative correlation between perceived extraneous cognitive load and perceived authenticity was more pronounced in interaction-based simulations. These results provide supporting evidence for theoretical models that highlight the connection between learners' experience in simulated learning environments and their performance. Overall, this research contributes to the understanding of the relationship between learners’ experience in simulation-based learning environments and their diagnostic accuracy, paving the way for the dissemination of best practices across different domains within higher education

Identification of Novel SNPs in Glioblastoma Using Targeted Resequencing

High-throughput sequencing opens avenues to find genetic variations that may be indicative of an increased risk for certain diseases. Linking these genomic data to other “omics” approaches bears the potential to deepen our understanding of pathogenic processes at the molecular level. To detect novel single nucleotide polymorphisms (SNPs) for glioblastoma multiforme (GBM), we used a combination of specific target selection and next generation sequencing (NGS). We generated a microarray covering the exonic regions of 132 GBM associated genes to enrich target sequences in two GBM tissues and corresponding leukocytes of the patients. Enriched target genes were sequenced with Illumina and the resulting reads were mapped to the human genome. With this approach we identified over 6000 SNPs, including over 1300 SNPs located in the targeted genes. Integrating the genome-wide association study (GWAS) catalog and known disease associated SNPs, we found that several of the detected SNPs were previously associated with smoking behavior, body mass index, breast cancer and high-grade glioma. Particularly, the breast cancer associated allele of rs660118 SNP in the gene SART1 showed a near doubled frequency in glioblastoma patients, as verified in an independent control cohort by Sanger sequencing. In addition, we identified SNPs in 20 of 21 GBM associated antigens providing further evidence that genetic variations are significantly associated with the immunogenicity of antigens

Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma

Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing

Women and ARVâ based prevention: opportunities and challenges

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138349/1/jia29419.pd