501 research outputs found

    Personalised Visual Art Recommendation by Learning Latent Semantic Representations

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    In Recommender systems, data representation techniques play a great role as they have the power to entangle, hide and reveal explanatory factors embedded within datasets. Hence, they influence the quality of recommendations. Specifically, in Visual Art (VA) recommendations the complexity of the concepts embodied within paintings, makes the task of capturing semantics by machines far from trivial. In VA recommendation, prominent works commonly use manually curated metadata to drive recommendations. Recent works in this domain aim at leveraging visual features extracted using Deep Neural Networks (DNN). However, such data representation approaches are resource demanding and do not have a direct interpretation, hindering user acceptance. To address these limitations, we introduce an approach for Personalised Recommendation of Visual arts based on learning latent semantic representation of paintings. Specifically, we trained a Latent Dirichlet Allocation (LDA) model on textual descriptions of paintings. Our LDA model manages to successfully uncover non-obvious semantic relationships between paintings whilst being able to offer explainable recommendations. Experimental evaluations demonstrate that our method tends to perform better than exploiting visual features extracted using pre-trained Deep Neural Networks.Comment: Accepted at SMAP202

    Le gĂšne hairless de la souris : Fonctions Ă  la racine du poil et au coeur d’une subtile plĂ©iotropie

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    Le gĂšne hairless (hr) des mammifĂšres code pour une protĂ©ine nuclĂ©aire impliquĂ©e dans le contrĂŽle du renouvellement du follicule pileux. Cette protĂ©ine est un cofacteur de rĂ©cepteurs nuclĂ©aires d’hormones qui rĂ©gulent la transcription de gĂšnes cibles au cours de la diffĂ©rentiation de l’épiderme et du cycle du poil. La protĂ©ine Hairless (HR) fait partie de grands complexes multiprotĂ©iques capables de rĂ©primer la transcription, en association avec des facteurs de remodelage de la chromatine comme les histones dĂ©sacĂ©tylases. Chez les mammifĂšres, le locus hairless est la cible de nombreuses mutations allĂ©liques dont les effets sont plĂ©iotropiques. Ces altĂ©rations entraĂźnent l’apparition d’un phĂ©notype cutanĂ© complexe, caractĂ©risĂ© par la perte progressive et irrĂ©versible d’un pelage d’apparence normale au cours des premiĂšres semaines de vie post-natale. L’analyse de la littĂ©rature sur le gĂšne hairless chez la souris et chez l’homme permet d’attribuer des diffĂ©rences morphologiques spĂ©cifiques Ă  chaque mutant, aussi bien au niveau de l’épiderme et du follicule pileux que dans d’autres tissus oĂč le gĂšne est exprimĂ© au cours du dĂ©veloppement. Ces rĂ©sultats suggĂšrent que l’intĂ©gritĂ© du gĂšne hairless est requise pour le dĂ©roulement correct de la morphogenĂšse d’organes aussi diffĂ©rents que l’épiderme, l’oreille interne, l’ovaire ou le thymus. Le gĂšne hairless semble ainsi faire partie de circuits et de cascades d’interactions gĂ©niques dont le contrĂŽle molĂ©culaire est fondamentalement inconnu. La variĂ©tĂ© des phĂ©notypes allĂ©liques souligne l’importance de l’analyse molĂ©culaire du locus hairless pour identifier les altĂ©rations gĂ©niques impliquĂ©es dans les diffĂ©rentes mutations dĂ©tectĂ©es. Les recherches concernant la mutation hairless ont Ă©tĂ© particuliĂšrement dynamiques pendant les derniĂšres annĂ©es, depuis que l’homologue de ce gĂšne a pu ĂȘtre mis en Ă©vidence chez l’homme. Cependant, un bon nombre de questions reste en suspens, notamment quant au site exact d’activitĂ© du gĂšne hairless au sein des nombreuses populations cellulaires du follicule pileux, son rĂŽle prĂ©cis au cours de la morphogenĂšse, sa localisation au sein des voies de signalisation, ainsi que l’identitĂ© des partenaires et des cibles de la protĂ©ine Hairless.The hairless gene in mammals encodes a nuclear factor that is highly expressed in skin and appears to control hair follicle integrity and cycling. In the absence of a normal and functional Hairless (Hr) protein, the hair bulb undergoes premature apoptosis during the first catagen stage of the hair cycle. The most striking effects of the mutation are loss of hair follicles and formation of epidermal utricles and dermal cysts. The hairless gene expression appears to be widespread and temporally regulated. The gene is strongly expressed in different compartments of the brain. Hairless mRNAs were detected in cartilage, gonads, thymus and colon. In addition to alopecia, hairless mice strains show subtle defects in the development and differentiation of various tissues and organs. The Hr protein is localised in cell nuclei and functions as a transcriptional regulator. Although its role has not been resolved in molecular terms, it was demonstrated that Hr is able to interact with multiple nuclear hormone receptors. Hr seems to be a part of a large multiprotein complex capable to repress transcription by its association to chromatin remodelling factors such as histone deacetylases. Recent experimental data suggest that Hr might be involved in Hox gene regulation, cell adhesion modulation and progenitor cells identity. At least in the skin, but probably in other organs, the Hr repressor seems to be responsible for the timing of epithelial cells differentiation

    Regulation of CD4+NKG2D+ Th1 cells in patients with metastatic melanoma treated with sorafenib : role of IL-15Rα and NKG2D triggering

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    Beyond cancer-cell intrinsic factors, the immune status of the host has a prognostic impact on patients with cancer and influences the effects of conventional chemotherapies. Metastatic melanoma is intrinsically immunogenic, thereby facilitating the search for immune biomarkers of clinical responses to cytotoxic agents. Here, we show that a multi-tyrosine kinase inhibitor, sorafenib, upregulates interleukin (IL)-15Rα in vitro and in vivo in patients with melanoma, and in conjunction with natural killer (NK) group 2D (NKG2D) ligands, contributes to the Th1 polarization and accumulation of peripheral CD4+NKG2D+ T cells. Hence, the increase of blood CD4+NKG2D+ T cells after two cycles of sorafenib (combined with temozolomide) was associated with prolonged survival in a prospective phase I/II trial enrolling 63 patients with metastatic melanoma who did not receive vemurafenib nor immune checkpoint-blocking antibodies. In contrast, in metastatic melanoma patients treated with classical treatment modalities, this CD4+NKG2D+ subset failed to correlate with prognosis. These findings indicate that sorafenib may be used as an "adjuvant" molecule capable of inducing or restoring IL-15Rα/IL-15 in tumors expressing MHCclass I-related chain A/B (MICA/B) and on circulating monocytes of responding patients, hereby contributing to the bioactivity of NKG2D+ Th1 cells.peer-reviewe

    Widespread anti-CRISPR proteins in virulent bacteriophages inhibit a range of Cas9 proteins

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    International audienceCRISPR-Cas systems are bacterial anti-viral systems, and bacterial viruses (bacteriophages, phages) can carry anti-CRISPR (Acr) proteins to evade that immunity. Acrs can also fine-tune the activity of CRISPR-based genome-editing tools. While Acrs are prevalent in phages capable of lying dormant in a CRISPR-carrying host, their orthologs have been observed only infrequently in virulent phages. Here we identify AcrIIA6, an Acr encoded in 33% of virulent Streptococcus thermophilus phage genomes. The X-ray structure of AcrIIA6 displays some features unique to this Acr family. We compare the activity of AcrIIA6 to those of other Acrs, including AcrIIA5 (also from S. thermophilus phages), and characterize their effectiveness against a range of CRISPR-Cas systems. Finally, we demonstrate that both Acr families from S. thermophilus phages inhibit Cas9-mediated genome editing of human cells

    A comprehensive dataset of annotated brain metastasis MR images with clinical and radiomic data.

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    Brain metastasis (BM) is one of the main complications of many cancers, and the most frequent malignancy of the central nervous system. Imaging studies of BMs are routinely used for diagnosis of disease, treatment planning and follow-up. Artificial Intelligence (AI) has great potential to provide automated tools to assist in the management of disease. However, AI methods require large datasets for training and validation, and to date there have been just one publicly available imaging dataset of 156 BMs. This paper publishes 637 high-resolution imaging studies of 75 patients harboring 260 BM lesions, and their respective clinical data. It also includes semi-automatic segmentations of 593 BMs, including pre- and post-treatment T1-weighted cases, and a set of morphological and radiomic features for the cases segmented. This data-sharing initiative is expected to enable research into and performance evaluation of automatic BM detection, lesion segmentation, disease status evaluation and treatment planning methods for BMs, as well as the development and validation of predictive and prognostic tools with clinical applicability

    A survey of orphan enzyme activities

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    <p>Abstract</p> <p>Background</p> <p>Using computational database searches, we have demonstrated previously that no gene sequences could be found for at least 36% of enzyme activities that have been assigned an Enzyme Commission number. Here we present a follow-up literature-based survey involving a statistically significant sample of such "orphan" activities. The survey was intended to determine whether sequences for these enzyme activities are truly unknown, or whether these sequences are absent from the public sequence databases but can be found in the literature.</p> <p>Results</p> <p>We demonstrate that for ~80% of sampled orphans, the absence of sequence data is bona fide. Our analyses further substantiate the notion that many of these enzyme activities play biologically important roles.</p> <p>Conclusion</p> <p>This survey points toward significant scientific cost of having such a large fraction of characterized enzyme activities disconnected from sequence data. It also suggests that a larger effort, beginning with a comprehensive survey of all putative orphan activities, would resolve nearly 300 artifactual orphans and reconnect a wealth of enzyme research with modern genomics. For these reasons, we propose that a systematic effort to identify the cognate genes of orphan enzymes be undertaken.</p

    The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance

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    It has been recently shown that increased oxidative phosphorylation, as reflected by increased mitochondrial activity, together with impairment of the mitochondrial stress response, can severely compromise hematopoietic stem cell (HSC) regeneration. Here we show that the NAD(+)-boosting agent nicotinamide riboside (NR) reduces mitochondrial activity within HSCs through increased mitochondrial clearance, leading to increased asymmetric HSC divisions. NR dietary supplementation results in a significantly enlarged pool of progenitors, without concurrent HSC exhaustion, improves survival by 80%, and accelerates blood recovery after murine lethal irradiation and limiting-HSC transplantation. In immune-deficient mice, NR increased the production of human leucocytes from hCD34+ progenitors. Our work demonstrates for the first time a positive effect of NAD(+)-boosting strategies on the most primitive blood stem cells, establishing a link between HSC mitochondrial stress, mitophagy, and stem-cell fate decision, and unveiling the potential of NR to improve recovery of patients suffering from hematological failure including post chemo- and radiotherapy.Peer reviewe
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