A causal inference and Bayesian optimisation framework for modelling multi-trait relationships—Proof-of-concept using Brassica napus seed yield under controlled conditions

The improvement of crop yield is a major breeding target and there is a long history of research that has focussed on unravelling the mechanisms and processes that contribute to yield. Quantitative prediction of the interplay between morphological traits, and the effects of these trait-trait relationships on seed production remains, however, a challenge. Consequently, the extent to which crop varieties optimise their morphology for a given environment is largely unknown. This work presents a new combination of existing methodologies by framing crop breeding as an optimisation problem and evaluates the extent to which existing varieties exhibit optimal morphologies under the test conditions. In this proof-of-concept study using spring and winter oilseed rape plants grown under greenhouse conditions, we employ causal inference to model the hierarchically structured effects of 27 morphological yield traits on each other. We perform Bayesian optimisation of seed yield, to identify and quantify the morphologies of ideotype plants, which are expected to be higher yielding than the varieties in the studied panels. Under the tested growth conditions, we find that existing spring varieties occupy the optimal regions of trait-space, but that potentially high yielding strategies are unexplored in extant winter varieties. The same approach can be used to evaluate trait (morphology) space for any environment

Specific oncolytic activity of herpesvirus saimiri in pancreatic cancer cells

The potential use of oncolytic viruses in the treatment of cancer has been investigated for some time. A variety of agents have been studied, including some which appear to be selectively replication-competent in cancer cell lines. In this study, we have investigated the ability of herpesvirus saimiri to specifically lyse selected human cancer cell lines. Upon infection with a replication-competent virus carrying the EGFP reporter gene and a neomycin resistance marker, the pancreatic cancer lines MIAPACA and PANC-1 exhibited definite cytopathic effects. In contrast, the colonic carcinoma cell lines SW480 and HCT116 were phenotypically unaltered. In addition, stable cell lines could not be generated from PANC-1 infected cultures, in marked contrast to cultures of cells from other human tissues. Virus recovery assays demonstrated that all of the cell lines produced a small amount of virus post-infection, but that virus replication was minimal after 1 week in culture. In addition, treatment with acyclovir inhibited virus replication but paradoxically increased cytopathic effect. These data suggest that herpesvirus saimiri may have potential as an oncolytic agent for the treatment of pancreatic cancer. © 2000 Cancer Research Campaig

Integrating Multiple Sources of Knowledge for the Intelligent Detection of Anomalous Sensory Data in a Mobile Robot

For service robots to expand in everyday scenarios they must be able to identify and manage abnormal situations intelligently. In this paper we work at a basic sensor level, by dealing with raw data produced by diverse devices subjected to some negative circumstances such as adverse environmental conditions or difficult to perceive objects. We have implemented a probabilistic Bayesian inference process for deducing whether the sensors are working nominally or not, which abnormal situation occurs, and even to correct their data. Our inference system works by integrating in a rigorous and homogeneous mathematical framework multiple sources and modalities of knowledge: human expert, external information systems, application-specific and temporal. The results on a real service robot navigating in a structured mixed indoor-outdoor environment demonstrate good detection capabilities and set a promising basis for improving robustness and safety in many common service tasks.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Views on social media and its linkage to longitudinal data from two generations of a UK cohort study

Background: Cohort studies gather huge volumes of information about a range of phenotypes but new sources of information such as social media data are yet to be integrated. Participant’s long-term engagement with cohort studies, as well as the potential for their social media data to be linked to other longitudinal data, could provide novel advances but may also give participants a unique perspective on the acceptability of this growing research area. Methods: Two focus groups explored participant views towards the acceptability and best practice for the collection of social media data for research purposes. Participants were drawn from the Avon Longitudinal Study of Parents and Children cohort; individuals from the index cohort of young people (N=9) and from the parent generation (N=5) took part in two separate 90-minute focus groups. The discussions were audio recorded and subjected to qualitative analysis. Results: Participants were generally supportive of the collection of social media data to facilitate health and social research. They felt that their trust in the cohort study would encourage them to do so. Concern was expressed about the collection of data from friends or connections who had not consented. In terms of best practice for collecting the data, participants generally preferred the use of anonymous data derived from social media to be shared with researchers. Conclusion: Cohort studies have trusting relationships with their participants; for this relationship to extend to linking their social media data with longitudinal information, procedural safeguards are needed. Participants understand the goals and potential of research integrating social media data into cohort studies, but further research is required on the acquisition of their friend’s data. The views gathered from participants provide important guidance for future work seeking to integrate social media in cohort studies

Anaplastic malignant melanoma of the tail in non-grey horses

Information regarding signalment, clinical findings, treatment, and outcome of 5 previously reported cases of anaplastic malignant melanoma of the tail in non-grey horses and of 5 additional cases are summarized. Age was recorded for 9 horses and mean age was 16 years, range 8 to 23 years. Gender was recorded for 8 horses and 6 of these 8 horses were male horses over 14 years of age. The most common coat colour was bay (6 horses). Other coat colours were palomino (1 horse), chestnut (1 horse), and black (1 horse); coat colour of 1 non-grey horse was not specified. Follow up information was available for 9 horses and only 1 horse, a palomino, survived more than 10 months following diagnosis and tail amputation. Surgical excision, including tail amputation and medical therapy with oral cimetidine, was not effective in non-grey, non-palomino horses. Tumour recurred on tail tissue remaining after amputation in 2 horses, widespread metastases were documented in 4 cases, and metastasis was suspected at the time of death or euthanasia in 3 cases, including 1 case with amputation site regrowth. No subjective histopathologic differences were detected in the palomino that survived as compared to horses of other coat colours. Findings suggest that anaplastic malignant melanoma of the tail in bay, chestnut, and black horses is most often a very aggressive neoplasm, but that there are rare exceptions.Keywords: malignant melanoma, neoplasia, hors

Genes Induced Late in Infection Increase Fitness of Vibrio cholerae after Release into the Environment

The facultative pathogen Vibrio cholerae can exist in both the human small bowel and in aquatic environments. While investigation of the infection process has revealed many factors important for pathogenesis, little is known regarding transmission of this or other water-borne pathogens. Using a temporally controlled reporter of transcription, we focus on bacterial gene expression during the late stage of infection and identify a unique class of V. cholerae genes specific to this stage. Mutational analysis revealed limited roles for these genes in infection. However, using a host-to-environment transition assay, we detected roles for six of ten genes examined for the ability of V. cholerae to persist within cholera stool and/or aquatic environments. Furthermore, passage through the intestinal tract was necessary to observe this phenotype. Thus, V. cholerae genes expressed prior to exiting the host intestinal tract are advantageous for subsequent life in aquatic environments

Abacavir inhibits but does not cause self-reactivity to HLA-B*57:01-restricted EBV specific T cell receptors

Pre-existing pathogen-specific memory T cell responses can contribute to multiple adverse outcomes including autoimmunity and drug hypersensitivity. How the specificity of the T cell receptor (TCR) is subverted or seconded in many of these diseases remains unclear. Here, we apply abacavir hypersensitivity (AHS) as a model to address this question because the disease is linked to memory T cell responses and the HLA risk allele, HLA-B*57:01, and the initiating insult, abacavir, are known. To investigate the role of pathogen-specific TCR specificity in mediating AHS we performed a genome-wide screen for HLA-B*57:01 restricted T cell responses to Epstein-Barr virus (EBV), one of the most prevalent human pathogens. T cell epitope mapping revealed HLA-B*57:01 restricted responses to 17 EBV open reading frames and identified an epitope encoded by EBNA3C. Using these data, we cloned the dominant TCR for EBNA3C and a previously defined epitope within EBNA3B. TCR specificity to each epitope was confirmed, however, cloned TCRs did not cross-react with abacavir plus self-peptide. Nevertheless, abacavir inhibited TCR interactions with their cognate ligands, demonstrating that TCR specificity may be subverted by a drug molecule. These results provide an experimental road map for future studies addressing the heterologous immune responses of TCRs including T cell mediated adverse drug reactions