146 research outputs found

    European Linguistic Monitor (ELM)

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    The European Linguistic Monitor (ELM) is a project conceived as an online system to collect data and to provide detailed up-to-date information on the linguistic situation and development in the various member state of the European Union. This paper discusses the criteria adopted and the third version of ELM

    Use of the sensors of a latest generation mobile phone for the three-dimensional reconstruction of an archaeological monument: The survey of the Intihuatana stone in Machu Picchu (Peru')

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    The survey of archaeological monuments presents particular needs and difficulties. Such surveys must in fact be as complete, geometrically correct and accurately geo-referenced as possible. These needs, however, often face problems of difficult accessibility, the need for rapid timing and complex logistical conditions. The latest generation of mobile phones are equipped with ultra-high resolution cameras up to 100 megapixel. Although they do not have the geometric characteristics of professional cameras, they can be used advantageously for the reconstruction of three-dimensional models using Structure from Motion methodologies . At the same time, the latest mobile phones are equipped with GPS/GNSS chips that allow a postprocessing of their positioning allowing to reach decimetric/centimetric accuracies. The use of sensors integrated in a mobile phone greatly simplify the survey both in terms of transportability but also in terms of authorizations by the competent authorities as the equipment is exactly the same that most tourists who visit the sites themselves bring with them. The approach proposed and made possible by these combined features in a latest generation mobile phone have been tested for a rapid survey of the Intihuatana stone in Machu Picchu (Peru), a site with considerable logistical and organizing complexity

    Use of the sensors of a latest generation mobile phone for the three-dimensional reconstruction of an archaeological monument: the survey of the Intihuatana stone in Machu Picchu (Peru’)

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    Abstract The survey of archaeological monuments presents particular needs and difficulties. Such surveys must in fact be as complete, geometrically correct and accurately geo-referenced as possible. These needs, however, often face problems of difficult accessibility, the need for rapid timing and complex logistical conditions. The latest generation of mobile phones are equipped with ultra-high resolution cameras up to 100 megapixel. Although they do not have the geometric characteristics of professional cameras, they can be used advantageously for the reconstruction of three-dimensional models using Structure from Motion methodologies . At the same time, the latest mobile phones are equipped with GPS/GNSS chips that allow a postprocessing of their positioning allowing to reach decimetric/centimetric accuracies. The use of sensors integrated in a mobile phone greatly simplify the survey both in terms of transportability but also in terms of authorizations by the competent authorities as the equipment is exactly the same that most tourists who visit the sites themselves bring with them. The approach proposed and made possible by these combined features in a latest generation mobile phone have been tested for a rapid survey of the Intihuatana stone in Machu Picchu (Peru), a site with considerable logistical and organizing complexity

    Solutions and limitations of the geomatic survey of an archaeological site in hard to access areas with a latest generation smartphone: the example of the Intihuatana stone in Machu Picchu (Peru)

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    Archaeological remains need to be geometrically surveyed and set in absolute reference systems in order to allow a "virtual visit" and to create "digital twins" useful in case of deterioration for proper restoration. Some countries (e.g., Peru) have a vast archaeological heritage whose survey requires optimized procedures that allow high productivity while maintaining high standards of geometric accuracy. A large part of Peru's cultural heritage is located in remote areas, at high altitudes and not easily accessible. For this reason, it is of great interest to study the possible applications of easily transportable instruments. In this study it was verified how the capabilities of the latest smartphones in terms of absolute differential positioning and photogrammetric acquisition can allow the acquisition of a geometrically correct and georeferenced three-dimensional model. The experimentation concerned a new survey of the Intihuatana stones at Machu Picchu and its comparison with a previous survey carried out with a much more complex laser scanning instrumentation. It is important to note that both the photogrammetric survey and the GPS/GNSS survey were carried out with the same smartphone taking full advantage of both features of the same mobile phone. Relative comparison to an existing point cloud provided differences of 2 millimeters in mean with an RMSE of 2 cm. The absolute positioning accuracy compared to a very large-scale cartography appears to be of the order of one metre as was expected mainly due to the high distance of the GPS/GNSS permanent stations

    Cortical thickness, surface area, and gyrification abnormalities in children exposed to maltreatment : neural markers of vulnerability?

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    Childhood maltreatment has been shown to significantly elevate the risk of psychiatric disorder. Previous neuroimaging studies of children exposed to maltreatment have reported atypical neural structure in several regions, including the prefrontal cortex and temporal lobes. These studies have exclusively investigated volumetric differences rather than focusing on genetically and developmentally distinct indices of brain structure

    Case Report: A Novel Activating FLT3 Mutation in Acute Myeloid Leukemia

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    FMS-like tyrosine kinase 3 (FLT3) is among the most common driver genes recurrently mutated in acute myeloid leukemia (AML), accounting for approximately 30% of cases. Activating mutations of the FLT3 receptor include internal tandem duplications (ITD) that map to the auto-inhibitory juxtamembrane (JM) domain or point mutations within the tyrosine kinase domain (TKD). Several FLT3 tyrosine kinase inhibitors have been developed in the last few years, but midostaurin is currently the only one approved for the treatment of newly diagnosed patients harboring FLT3 mutations. Here we describe for the first time a novel in-frame deletion in exon 14 (JM domain) of the FLT3 gene, that we identified in a young woman with CBFb-MYH11-positive AML. We demonstrated that this novel FLT3 variant is pathogenic, since it is responsible for constitutive activation of FLT3 receptor. Finally, ex-vivo studies demonstrated that this novel mutation is sensitive to midostaurin

    Site-Specific Fluorescence Polarization for Studying the Disaggregation of α-Synuclein Fibrils by Small Molecules

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    Fibrillar aggregates of the protein α-synuclein (αS) are one of the hallmarks of Parkinson’s disease. Here, we show that measuring the fluorescence polarization (FP) of labels at several sites on αS allows one to monitor changes in the local dynamics of the protein after binding to micelles or vesicles, and during fibril formation. Most significantly, these site-specific FP measurements provide insight into structural remodeling of αS fibrils by small molecules and have the potential for use in moderate-throughput screens to identify small molecules that could be used to treat Parkinson’s disease. © 2016 American Chemical Society

    Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

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    The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

    Androgen receptor condensates as drug targets

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    Transcription factors are among the most attractive therapeutic targets, but are considered largely undruggable. Here we provide evidence that small molecule-mediated partitioning of the androgen receptor, an oncogenic transcription factor, into phase-separated condensates has therapeutic effect in prostate cancer models. We show that the phase separation capacity of the androgen receptor is driven by aromatic residues and short unstable helices in its intrinsically disordered activation domain. Based on this knowledge, we developed tool compounds that covalently attach aromatic moieties to cysteines in the receptors’ activation domain. The compounds enhanced partitioning of the receptor into condensates, facilitated degradation of the receptor, inhibited androgen receptor-dependent transcriptional programs, and had antitumorigenic effect in models of prostate cancer and castration-resistant prostate cancer in vitro and in vivo. These results establish a generalizable framework to target the phase- separation capacity of intrinsically disordered regions in oncogenic transcription factors and other disease-associated proteins with therapeutic intent
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