170 research outputs found

    How can humans understand their automated cars? HMI principles, problems and solutions

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    As long as vehicles do not provide full automation, the design and function of the Human Machine Interface (HMI) is crucial for ensuring that the human “driver” and the vehicle-based automated systems collaborate in a safe manner. When the driver is decoupled from active control, the design of the HMI becomes even more critical. Without mutual understanding, the two agents (human and vehicle) will fail to accurately comprehend each other’s intentions and actions. This paper proposes a set of design principles for in-vehicle HMI and reviews some current HMI designs in the light of those principles. We argue that in many respects, the current designs fall short of best practice and have the potential to confuse the driver. This can lead to a mismatch between the operation of the automation in the light of the current external situation and the driver’s awareness of how well the automation is currently handling that situation. A model to illustrate how the various principles are interrelated is proposed. Finally, recommendations are made on how, building on each principle, HMI design solutions can be adopted to address these challenges

    Green Tea Polyphenols Rescue of Brain Defects Induced by Overexpression of DYRK1A

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    Individuals with partial HSA21 trisomies and mice with partial MMU16 trisomies containing an extra copy of the DYRK1A gene present various alterations in brain morphogenesis. They present also learning impairments modeling those encountered in Down syndrome. Previous MRI and histological analyses of a transgenic mice generated using a human YAC construct that contains five genes including DYRK1A reveal that DYRK1A is involved, during development, in the control of brain volume and cell density of specific brain regions. Gene dosage correction induces a rescue of the brain volume alterations. DYRK1A is also involved in the control of synaptic plasticity and memory consolidation. Increased gene dosage results in brain morphogenesis defects, low BDNF levels and mnemonic deficits in these mice. Epigallocatechin gallate (EGCG) — a member of a natural polyphenols family, found in great amount in green tea leaves — is a specific and safe DYRK1A inhibitor. We maintained control and transgenic mice overexpressing DYRK1A on two different polyphenol-based diets, from gestation to adulthood. The major features of the transgenic phenotype were rescued in these mice

    Cdx4 and Menin Co-Regulate Hoxa9 Expression in Hematopoietic Cells

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    BACKGROUND: Transcription factor Cdx4 and transcriptional coregulator menin are essential for Hoxa9 expression and normal hematopoiesis. However, the precise mechanism underlying Hoxa9 regulation is not clear. METHODS AND FINDINGS: Here, we show that the expression level of Hoxa9 is correlated with the location of increased trimethylated histone 3 lysine 4 (H3K4M3). The active and repressive histone modifications co-exist along the Hoxa9 regulatory region. We further demonstrate that both Cdx4 and menin bind to the same regulatory region at the Hoxa9 locus in vivo, and co-activate the reporter gene driven by the Hoxa9 cis-elements that contain Cdx4 binding sites. Ablation of menin abrogates Cdx4 access to the chromatin target and significantly reduces both active and repressive histone H3 modifications in the Hoxa9 locus. CONCLUSION: These results suggest a functional link among Cdx4, menin and histone modifications in Hoxa9 regulation in hematopoietic cells

    Are Women Who Work in Bars, Guesthouses and Similar Facilities a Suitable Study Population for Vaginal Microbicide Trials in Africa?

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    BACKGROUND: A feasibility study was conducted to investigate whether an occupational at-risk cohort of women in Mwanza, Tanzania are a suitable study population for future phase III vaginal microbicide trials. METHODOLOGY/PRINCIPAL FINDINGS: 1573 women aged 16-54 y working in traditional and modern bars, restaurants, hotels, guesthouses or as local food-handlers were enrolled at community-based reproductive health clinics, provided specimens for HIV/STI and pregnancy testing, and asked to attend three-monthly clinical follow-up visits for 12-months. HIV positive and negative women were eligible to enter the feasibility study and to receive free reproductive health services at any time. HIV prevalence at baseline was 26.5% (417/1573). HIV incidence among 1156 sero-negative women attending at baseline was 2.9/100PYs. Among 1020 HIV sero-negative, non-pregnant women, HIV incidence was 2.0/100PYs, HSV-2 incidence 12.7/100PYs and pregnancy rate 17.8/100PYs. Retention at three-months was 76.3% (778/1020). Among 771 HIV sero-negative, non-pregnant women attending at three-months, subsequent follow-up at 6, 9 and 12-months was 83.7%, 79.6%, and 72.1% respectively. Older women, those who had not moved home or changed their place of work in the last year, and women working in traditional bars or as local food handlers had the highest re-attendance. CONCLUSIONS/SIGNIFICANCE: Women working in food outlets and recreational facilities in Tanzania and other parts of Africa may be a suitable study population for microbicide and other HIV prevention trials. Effective locally-appropriate strategies to address high pregnancy rates and early losses to follow-up are essential to minimise risk to clinical trials in these settings

    Arcuate Fasciculus Abnormalities and Their Relationship with Psychotic Symptoms in Schizophrenia

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    Disruption of fronto-temporal connections involving the arcuate fasciculus (AF) may underlie language processing anomalies and psychotic features such as auditory hallucinations in schizophrenia. No study to date has specifically investigated abnormalities of white matter integrity at particular loci along the AF as well as its regional lateralization in schizophrenia. We examined white matter changes (fractional anisotropy (FA), axial diffusivity (AD), asymmetry indices) along the whole extent of the AF and their relationship with psychotic symptoms in 32 males with schizophrenia and 44 healthy males. Large deformation diffeomorphic metric mapping and Fiber Assignment Continuous Tracking were employed to characterize FA and AD along the geometric curve of the AF. Our results showed that patients with schizophrenia had lower FA in the frontal aspects of the left AF compared with healthy controls. Greater left FA and AD lateralization in the temporal segment of AF were associated with more severe positive psychotic symptoms such as delusions and hallucinations in patients with schizophrenia. Disruption of white matter integrity of the left frontal AF and accentuation of normal left greater than right asymmetry of FA/AD in the temporal AF further support the notion of aberrant fronto-temporal connectivity in schizophrenia. AF pathology can affect corollary discharge of neural signals from frontal speech/motor initiation areas to suppress activity of auditory cortex that may influence psychotic phenomena such as auditory hallucinations and facilitate elaboration of delusional content

    Sexual Dimorphism in Healthy Aging and Mild Cognitive Impairment: A DTI Study

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    Previous PET and MRI studies have indicated that the degree to which pathology translates into clinical symptoms is strongly dependent on sex with women more likely to express pathology as a diagnosis of AD, whereas men are more resistant to clinical symptoms in the face of the same degree of pathology. Here we use DTI to investigate the difference between male and female white matter tracts in healthy older participants (24 women, 16 men) and participants with mild cognitive impairment (21 women, 12 men). Differences between control and MCI participants were found in fractional anisotropy (FA), radial diffusion (DR), axial diffusion (DA) and mean diffusion (MD). A significant main effect of sex was also reported for FA, MD and DR indices, with male control and male MCI participants having significantly more microstructural damage than their female counterparts. There was no sex by diagnosis interaction. Male MCIs also had significantly less normalised grey matter (GM) volume than female MCIs. However, in terms of absolute brain volume, male controls had significantly more brain volume than female controls. Normalised GM and WM volumes were found to decrease significantly with age with no age by sex interaction. Overall, these data suggest that the same degree of cognitive impairment is associated with greater structural damage in men compared with women

    A Ceratopsian Dinosaur from the Lower Cretaceous of Western North America, and the Biogeography of Neoceratopsia

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    Competing interests: Andrew A. Farke has read the journal's policy and the authors of this manuscript have the following competing interests: Andrew A. Farke is a volunteer section editor and academic editor for PLOS ONE. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.Acknowledgments It is a pleasure to offer our most heartfelt thanks to Scott K. Madsen, who found OMNH 34557 and prepared it with consummate skill. We are grateful to James Taylor, Jack Owen, the Keebler family, and the Montana Bureau of Land Management for access to outcrops of the Cloverly Formation. We thank Xu Xing (IVPP) and Hai-Lu You (formerly CAGS-IG) for facilitating access to specimens, Mark Loewen, Joseph Frederickson, Darren Naish, and Leonardo Maiorino for productive discussion and comments, and Roger Burkhalter for assistance in photography. Gary Wisser, from the scientific visualization center at Western University of Health Sciences, is gratefully acknowledged for the high resolution scan of the cranium. Reviews by Peter Makovicky, Hai-Lu You, and editor Peter Wilf improved the manuscript.Author Contributions Conceived and designed the experiments: AAF WDM RLC. Performed the experiments: AAF WDM RLC. Analyzed the data: AAF WDM RLC MJW. Contributed reagents/materials/analysis tools: AAF WDM RLC MJW. Wrote the paper: AAF WDM RLC MJW.The fossil record for neoceratopsian (horned) dinosaurs in the Lower Cretaceous of North America primarily comprises isolated teeth and postcrania of limited taxonomic resolution, hampering previous efforts to reconstruct the early evolution of this group in North America. An associated cranium and lower jaw from the Cloverly Formation (?middle–late Albian, between 104 and 109 million years old) of southern Montana is designated as the holotype for Aquilops americanus gen. et sp. nov. Aquilops americanus is distinguished by several autapomorphies, including a strongly hooked rostral bone with a midline boss and an elongate and sharply pointed antorbital fossa. The skull in the only known specimen is comparatively small, measuring 84 mm between the tips of the rostral and jugal. The taxon is interpreted as a basal neoceratopsian closely related to Early Cretaceous Asian taxa, such as Liaoceratops and Auroraceratops. Biogeographically, A. americanus probably originated via a dispersal from Asia into North America; the exact route of this dispersal is ambiguous, although a Beringian rather than European route seems more likely in light of the absence of ceratopsians in the Early Cretaceous of Europe. Other amniote clades show similar biogeographic patterns, supporting an intercontinental migratory event between Asia and North America during the late Early Cretaceous. The temporal and geographic distribution of Upper Cretaceous neoceratopsians (leptoceratopsids and ceratopsoids) suggests at least intermittent connections between North America and Asia through the early Late Cretaceous, likely followed by an interval of isolation and finally reconnection during the latest Cretaceous.Funding was received from the National Science Foundation (DEB 9401094, 9870173, http://www.nsf.gov); National Geographic Society (5918-97, http://www.nationalgeographic.com/); and American Chemical Society (PRF #38572-AC8, http://www.acs.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Yeshttp://www.plosone.org/static/editorial#pee
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