'It's Almost Like Talking to a Person': Student Disclosure to Pedagogical Agents in Sensitive Setting

Online chatbots (also known as pedagogical agents or virtual assistants) are becoming embedded into the fabric of technology, both in educational and commercial settings. Yet understanding of these technologies is inchoate and often untheorised, influenced by individuals’ willingness to trust technologies, aesthetic appearance of the chatbot and technical literacy, among other factors. This paper draws upon data from two research studies that evaluated students’ experiences of using pedagogical agents in education using responsive evaluation. The findings suggest that emotional connections with pedagogical agents were intrinsic to the user’s sense of trust and therefore likely to affect levels of truthfulness and engagement. They also indicate that the topic of the pedagogical agent-student interaction is key to the student’s experience. The implications of these studies are that truthfulness, personalisation and emotional engagement are all vital components in using pedagogical agents to enhance online learning

Cyber Enigmas? Passive Detection and Pedagogical Agents: Can Students Spot the Fake?

This paper presents a study that was undertaken to examine human interaction with a pedagogical agent and the passive and active detection of such agents within a synchronous, online environment. A pedagogical agent is a software application which can provide a human like interaction using a natural language interface. These may be familiar from the smartphone interfaces such as ‘Siri’ or ‘Cortana’, or the virtual online assistants found on some websites, such as ‘Anna’ on the Ikea website. Pedagogical agents are characters on the computer screen with embodied life-like behaviours such as speech, emotions, locomotion, gestures, and movements of the head, the eye, or other parts of the body. The passive detection test is where participants are not primed to the potential presence of a pedagogical agent within the online environment. The active detection test is where participants are primed to the potential presence of a pedagogical agent. The purpose of the study was to examine how people passively detected pedagogical agents that were presenting themselves as humans in an online environment. In order to locate the pedagogical agent in a realistic higher education online environment, problem-based learning online was used. Problem-based learning online provides a focus for discussions and participation, without creating too much artificiality. The findings indicated that the ways in which students positioned the agent tended to influence the interaction between them. One of the key findings was that since the agent was focussed mainly on the pedagogical task this may have hampered interaction with the students, however some of its non-task dialogue did improve students' perceptions of the autonomous agents’ ability to interact with them. It is suggested that future studies explore the differences between the relationships and interactions of learner and pedagogical agent within authentic situations, in order to understand if students' interactions are different between real and virtual mentors in an online setting

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

Carprofen elicits pleiotropic mechanisms of bactericidal action with the potential to reverse antimicrobial drug resistance in tuberculosis

Background The rise of antimicrobial drug resistance in Mycobacterium tuberculosis coupled with the shortage of new antibiotics has elevated TB to a major global health priority. Repurposing drugs developed or used for other conditions has gained special attention in the current scenario of accelerated drug development for several global infectious diseases. In a similar effort, previous studies revealed that carprofen, a non-steroidal anti-inflammatory drug, selectively inhibited the growth of replicating, non-replicating and MDR clinical isolates of M. tuberculosis. Objectives We aimed to reveal the whole-cell phenotypic and transcriptomic effects of carprofen in mycobacteria. Methods Integrative molecular and microbiological approaches such as resazurin microtitre plate assay, high-throughput spot-culture growth inhibition assay, whole-cell efflux inhibition, biofilm inhibition and microarray analyses were performed. Analogues of carprofen were also synthesized and assessed for their antimycobacterial activity. Results Carprofen was found to be a bactericidal drug that inhibited mycobacterial drug efflux mechanisms. It also restricted mycobacterial biofilm growth. Transcriptome profiling revealed that carprofen likely acts by targeting respiration through the disruption of membrane potential. The pleiotropic nature of carprofen’s anti-TB action may explain why spontaneous drug-resistant mutants could not be isolated in practice. Conclusions This immunomodulatory drug and its chemical analogues have the potential to reverse TB antimicrobial drug resistance, offering a swift path to clinical trials of novel TB drug combinations

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The contribution of different uracil-DNA glycosylases to removal of uracil from DNA in different mouse organs - the significance of sequence context and proliferative status

Uracil is a non-canonical base in DNA that can arise through misincorporation of dUMP instead of dTMP during replication or from cytosine deamination. Uracil in DNA can be removed by the four different DNA glycosylases UNG, SMUG1, TDG or MBD4 as the first step in base excision repair. These glycosylases have different catalytic efficiencies, different substrate preferences and different expression patterns. We wanted to elucidate the contribution of the different DNA glycosylases in removal of uracil, using protein extracts from mouse brain, small intestine, kidney, liver, lung and muscle. Importantly, UNG+/+ and UNG-/- mice were available for these studies. Furthermore, we used the UNG-specific inhibitor Ugi to inhibit UNG-activity and an anti-SMUG1 antibody PSM1 to inhibit SMUG1 activity. In addition, we used a combination of Ugi and PSM1 to inhibit both UNG and SMUG1 activities. To investigate the contribution of the DNA glycosylases in different sequence contexts, we used uracil-containing DNA substrates with uracil in a U:G mismatch, a U:A pair, or in single stranded DNA. We found that UNG was by far the most important DNA glycosylase removing uracil from U:A pairs and from single-stranded DNA, even in extracts from non-proliferative tissues such as brain and muscle. However, we found that UNG and SMUG1 are almost equally active in removal of uracil from a U:G context in extracts from non-proliferative tissues. In contrast, SMUG1 contributed very little to the removal of uracil from small intestines, which presumably contain a higher fraction of rapidly dividing cells. Furthermore, we detected essentially no residual uracil-DNA glycosylase activity when both UNG and SMUG1 were specifically inhibited, indicating that TDG and MBD4 do not contribute measurable activity in any of the organs investigated under the conditions used here. Possibly these DNA glycosylases can only contribute in sequence patterns that have not been investigated here. We also carried out a preliminary study on the possible correlation between genomic uracil contents (measured by mass spectrometry) and uracil excision activities, but failed to observe a significant positive correlation or inverse correlation. In conclusion, UNG is the dominant uracil-DNA glycosylase in proliferating tissues in removal of uracil from a U:G context, whereas in non-proliferating tissues the contribution of UNG and SMUG1 is essentially similar. Furthermore, UNG is the only glycosylase removing uracil from U:A and single stranded DNA contexts