607 research outputs found

    User centered ecological interface design (UCEID): A novel method applied to the problem of safe and user-friendly interaction between drivers and autonomous vehicles

    Get PDF
    © Springer International Publishing AG 2018. User Centered Ecological Interface Design (UCEID) is a novel Human Factors method that integrates relationships between Ecological Interface Design (EID) and inclusive Human Centered Design. It combines existing methodology from the Cognitive Work Analysis (CWA) framework [1–3] and Inclusive User Centered Design [4, 5]. This paper offers a practical guide to UCEID by providing a high-level summary for practitioners using the example of vehicle to driver handover in a BASt Level 3 autonomous vehicle

    Phylogeography of Japanese encephalitis virus:genotype is associated with climate

    Get PDF
    The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate

    Involvement in teaching improves learning in medical students: a randomized cross-over study

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Peer-assisted learning has many purported benefits including preparing students as educators, improving communication skills and reducing faculty teaching burden. But comparatively little is known about the effects of teaching on learning outcomes of peer educators in medical education.</p> <p>Methods</p> <p>One hundred and thirty-five first year medical students were randomly allocated to 11 small groups for the Gastroenterology/Hematology Course at the University of Calgary. For each of 22 sessions, two students were randomly selected from each group to be peer educators. Students were surveyed to estimate time spent preparing as peer educator versus group member. Students completed an end-of-course 94 question multiple choice exam. A paired t-test was used to compare performance on clinical presentations for which students were peer educators to those for which they were not.</p> <p>Results</p> <p>Preparation time increased from a mean (SD) of 36 (33) minutes baseline to 99 (60) minutes when peer educators (Cohen's <it>d </it>= 1.3; p < 0.001). The mean score (SD) for clinical presentations in which students were peer educators was 80.7% (11.8) compared to77.6% (6.9) for those which they were not (<it>d </it>= 0.33; <it>p </it>< 0.01).</p> <p>Conclusion</p> <p>Our results suggest that involvement in teaching small group sessions improves medical students' knowledge acquisition and retention.</p

    The social and scientific values that shape national climate scenarios: a comparison of the Netherlands, Switzerland and the UK

    Get PDF
    This paper seeks to understand why climate information is produced differently from country to country. To do this, we critically examined and compared the social and scientific values that shaped the production of three national climate scenarios in the Netherlands, Switzerland and the UK. A comparative analysis of documentary materials and expert interviews linked to the climate scenarios was performed. Our findings reveal a new typology of use-inspired research in climate science for decision-making: (i) innovators, where the advancement of science is the main objective; (ii) consolidators, where knowledge exchanges and networks are prioritised; and (iii) collaborators, where the needs of users are put first and foremost. These different values over what constitutes ‘good’ science for decision-making are mirrored in the way users were involved in the production process: (i) elicitation, where scientists have privileged decision-making power; (ii) representation, where multiple organisations mediate on behalf of individual users; and (iii) participation, where a multitude of users interact with scientists in an equal partnership. These differences help explain why climate knowledge gains its credibility and legitimacy differently even when the information itself might not be judged as salient and usable. If the push to deliberately co-produce climate knowledge is not sensitive to the national civic epistemology at play in each country, scientist–user interactions may fail to deliver more ‘usable’ climate information

    Molecular Genetic Analysis of 103 Sporadic Colorectal Tumours in Czech Patients

    Get PDF
    The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in Europe. To evaluate whether sporadic CRCs in Czech patients have specific mutational profiles we analysed somatic genetic changes in known CRC genes (APC, KRAS, TP53, CTNNB1, MUTYH and BRAF, loss of heterozygosity (LOH) at the APC locus, microsatellite instability (MSI), and methylation of the MLH1 promoter) in 103 tumours from 102 individuals. The most frequently mutated gene was APC (68.9% of tumours), followed by KRAS (31.1%), TP53 (27.2%), BRAF (8.7%) and CTNNB1 (1.9%). Heterozygous germline MUTYH mutations in 2 patients were unlikely to contribute to the development of their CRCs. LOH at the APC locus was found in 34.3% of tumours, MSI in 24.3% and MLH1 methylation in 12.7%. Seven tumours (6.9%) were without any changes in the genes tested. The analysis yielded several findings possibly specific for the Czech cohort. Somatic APC mutations did not cluster in the mutation cluster region (MCR). Tumours with MSI but no MLH1 methylation showed earlier onset and more severe mutational profiles compared to MSI tumours with MLH1 methylation. TP53 mutations were predominantly located outside the hot spots, and transitions were underrepresented. Our analysis supports the observation that germline MUTYH mutations are rare in Czech individuals with sporadic CRCs. Our findings suggest the influence of specific ethnic genetic factors and/or lifestyle and dietary habits typical for the Czech population on the development of these cancers

    X-ray emission from the Sombrero galaxy: discrete sources

    Get PDF
    We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

    p53 Interacts with RNA Polymerase II through Its Core Domain and Impairs Pol II Processivity In Vivo

    Get PDF
    The tumor suppressor p53 principally functions as a gene-specific transcription factor. p53 triggers a variety of anti-proliferative programs by activating or repressing the transcription of effector genes in response to genotoxic stress. To date, much effort has been placed on understanding p53's ability to affect transcription in the context of its DNA-binding activity. How p53 regulates transcriptional output independent of DNA binding is less well understood. Here we provide evidence that human p53 can physically interact with the large subunit of RNA polymerase II (Pol II) both in in vitro interaction assays and in whole cell extracts, and that this interaction is mediated (at least in part) through p53's core DNA-binding domain and the Ser5-phosphorylated CTD of Pol II. Ectopic expression of p53, combined with mutations in transcription elongation factors or exposure to drugs that inhibit Pol II elongation, elicit sickness or lethality in yeast cells. These phenotypes are suppressed by oncogenic point mutations within p53's core domain. The growth phenotypes raise the possibility that p53 impairs Pol II elongation. Consistent with this, a p53-dependent increase in Pol II density is seen at constitutively expressed genes without a concomitant increase in transcript accumulation. Additionally, p53-expressing yeast strains exhibit reduced transcriptional processivity at an episomal reporter gene; this inhibitory activity is abolished by a core domain point mutation. Our results suggest a novel mechanism by which p53 can regulate gene transcription, and a new biological function for its core domain that is susceptible to inactivation by oncogenic point mutations
    • …
    corecore