227 research outputs found

    Contributions of Mammalian Chimeras to Pluripotent Stem Cell Research.

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    Chimeras are widely acknowledged as the gold standard for assessing stem cell pluripotency, based on their capacity to test donor cell lineage potential in the context of an organized, normally developing tissue. Experimental chimeras provide key insights into mammalian developmental mechanisms and offer a resource for interrogating the fate potential of various pluripotent stem cell states. We highlight the applications and current limitations presented by intra- and inter-species chimeras and consider their future contribution to the stem cell field. Despite the technical and ethical demands of experimental chimeras, including human-interspecies chimeras, they are a provocative resource for achieving regenerative medicine goals.British Heart Foundation Centre of Regenerative Medicine, Wellcome Trust, Medical Research Council Cambridge Stem Cell Institute, Cambridge NIHR Biomedical Research CentreThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.stem.2016.07.01

    Human-Mouse Chimerism Validates Human Stem Cell Pluripotency.

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    Pluripotent stem cells are defined by their capacity to differentiate into all three tissue layers that comprise the body. Chimera formation, generated by stem cell transplantation to the embryo, is a stringent assessment of stem cell pluripotency. However, the ability of human pluripotent stem cells (hPSCs) to form embryonic chimeras remains in question. Here we show using a stage-matching approach that human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs) have the capacity to participate in normal mouse development when transplanted into gastrula-stage embryos, providing in vivo functional validation of hPSC pluripotency. hiPSCs and hESCs form interspecies chimeras with high efficiency, colonize the embryo in a manner predicted from classical developmental fate mapping, and differentiate into each of the three primary tissue layers. This faithful recapitulation of tissue-specific fate post-transplantation underscores the functional potential of hPSCs and provides evidence that human-mouse interspecies developmental competency can occur.This work was supported by National Institutes of Health grant No. 1R21ID012228 (R.A.P.); Medical Research Council/British Heart Foundation grant No. G1000847 (R.A.P.); British Heart Foundation Ph.D. studentship (V.L.M.); British Heart Foundation Centre of Regenerative Medicine (Oxford grant RM/13/3/3015); core support from the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute; and the Cambridge NIHR Biomedical Research Centre.This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.stem.2015.11.01

    Influence of the ice structure on the soft UV photochemistry of PAHs embedded in solid water

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    The UV photoreactivity of polycyclic aromatic hydrocarbons (PAHs) in porous amorphous solid water has long been known to form both oxygenated photoproducts and photofragments. The aim of this study was to examine the influence of the ice structure upon reactivity under soft UV irradiation conditions. Mixtures of PAHs with amorphous solid water (porous and compact) and crystalline (cubic and hexagonal) ices were prepared in a high vacuum chamber and irradiated using a mercury lamp for up to 2.5 hours. The results show that the production of oxygenated PAHs is efficient only in amorphous water ice, while fragmentation can occur in both amorphous and crystalline ices. We conclude that the reactivity is driven by PAH-water interactions in favourable geometries, notably where dangling bonds are available at the surface of pores. These results suggest that the formation of oxygenated PAH molecules is most likely to occur in interstellar environments with porous (or compact) amorphous solid water and that this reactivity could considerably influence the inventory of aromatics in meteorites.Comment: Accepted for publication in A&

    AudioFunctions.web: Multimodal Exploration of Mathematical Function Graphs

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    We present AudioFunctions.web, a web app that uses sonifcation, earcons and speech synthesis to enable blind people to explore mathematical function graphs. The system is designed for personalized access through different interfaces (touchscreen, keyboard, touchpad and mouse) on both mobile and traditional devices, in order to better adapt to different user abilities and preferences. It is also publicly available as a web service and can be directly accessed from the teaching material through a hypertext link. An experimental evaluation with 13 visually impaired participants highlights that, while the usability of all the presented interaction modalities is high, users with different abilities prefer different interfaces to interact with the system. It is also shown that users with higher level of mathematical education are capable of better adapting to interaction modalities considered more diffcult by others

    Towards Large Scale Evaluation of Novel Sonification Techniques for Non Visual Shape Exploration

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    © 2015 ACM.There are several situations in which a person with visual impairment or blindness needs to extract information from an image. Examples include everyday activities, like reading a map, as well as educational activities, like exercises to develop visuospatial skills. In this contribution we propose a set of 6 sonification techniques to recognize simple shapes on touchscreen devices. The effectiveness of these sonification techniques is evaluated though Invisible Puzzle, a mobile application that makes it possible to conduct non-supervised evaluation sessions. Invisible Puzzle adopts a gamification approach and is a preliminary step in the development of a complete game that will make it possible to conduct a large scale evaluation with hundreds or thousands of blind users. With Invisible Puzzle we conducted 131 tests with sighted subjects and 18 tests with subjects with blindness. All subjects involved in the process successfully completed the evaluation session, with high engagement, hence showing the effectiveness of the evaluation procedure. Results give interesting insights on the differences among the sonification techniques and, most importantly, show that, after a short training, subjects are able to identify many different shapes

    Accessible Mathematics on Touchscreen Devices: New Opportunities for People with Visual Impairments

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    In recent years educational applications for touchscreen devices (e.g., tablets) become widespread all over the world. While these devices are accessible to people with visual impairments, educational applications to support learning of STEM subjects are often not accessible to visually impaired people due to inaccessible graphics. This contribution addresses the problem of conveying graphics to visual impaired users. Two approaches are taken into account: audio icons and image sonification. In order to evaluate the applicability of these approaches, we report our experience in the development of two didactic applications for touchscreen devices, specifically designed to support people with visual impairments or blindness while studying STEM subjects: Math Melodies and Audio Functions. The former is a commercial application to support children in primary school in an inclusive class. It adopts an interaction paradigm based on audio icons. The latter is a prototype application aimed at enabling visually impaired students to explore function diagrams and adopts an image sonification approach

    Insights on Assistive Orientation and Mobility of People with Visual Impairment Based on Large-Scale Longitudinal Data

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    Assistive applications for orientation and mobility promote independence for people with visual impairment (PVI). While typical design and evaluation of such applications involves small-sample iterative studies, we analyze large-scale longitudinal data from a geographically diverse population. Our publicly released dataset from iMove, a mobile app supporting orientation of PVI, contains millions of interactions by thousands of users over a year. Our analysis (i) examines common functionalities, settings, assistive features, and movement modalities in iMove dataset and (ii) discovers user communities based on interaction patterns. We find that the most popular interaction mode is passive, where users receive more notifications, often verbose, while in motion and perform fewer actions. The use of built-in assistive features such as enlarged text indicate a high presence of users with residual sight. Users fall into three distinct groups: (C1) users interested in surrounding points of interest, (C2) users interacting in short bursts to inquire about current location, and (C3) users with long active sessions while in motion. iMove was designed with C3 in mind, and one strength of our contribution is providing meaningful semantics for unanticipated groups, C1 and C2. Our analysis reveals insights that can be generalized to other assistive orientation and mobility applications

    EPIC: a Methodology for Evaluating Privacy Violation Risk in Cybersecurity Systems

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    Cybersecurity Systems (CSSs) play a fundamental role in guaranteeing data confidentiality, integrity, and availability. However, while processing data, CSSs can intentionally or unintentionally expose personal information to people that can misuse them. For this reason, privacy implications of a CSS should be carefully evaluated. This is a challenging task mainly because modern CSSs have complex architectures and components. Moreover, data processed by CSSs can be exposed to different actors, both internal and external to the organization. This contribution presents a methodology, called EPIC, that is specifically designed to evaluate privacy violation risks in cybersecurity systems. Differently, from other general purpose guidelines, EPIC is an operational methodology aimed at guiding security and privacy experts with step-by-step instructions from modeling data exposure in the CSS to the systematical identification of privacy threats and evaluation of their associated privacy violation risk. This contribution also shows the application of the EPIC methodology to the use case of a large academic organization CSS protecting over 15, 000 hosts

    Trace elements in stomach oil of Scopoli's shearwater (Calonectris diomedea) from Linosa's colony

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    Calonectris diomedea is a colonial Procellariiform breeding on Mediterranean islands. The stomach oil produced during chick rearing is a peculiar trait of this species. The composition of the stomach oil is likely to reflect the composition of the prey ingested and might reveal the contaminants uptake with prey becoming a possible tool for the marine pollution monitoring. We examined the concentration of 15 trace elements by ICP-MS and direct mercury analyser. The principal component analysis revealed a heterogeneous pattern of metal concentration, showing a significant separation between samples collected 20 and 70 days after hatching. The data obtained in this work give preliminary information on the feeding habits and breeding ecology of Linosa's colony of Scopoli's shearwater. The trace metals variability found suggest that the stomach oil may have a role as trophic markers to understand predator-prey relationships and to have evidence on the accumulation of pollutants in the latter
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