21 research outputs found

    Recurrent Segmentation for Variable Computational Budgets

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    State-of-the-art systems for semantic image segmentation use feed-forward pipelines with fixed computational costs. Building an image segmentation system that works across a range of computational budgets is challenging and time-intensive as new architectures must be designed and trained for every computational setting. To address this problem we develop a recurrent neural network that successively improves prediction quality with each iteration. Importantly, the RNN may be deployed across a range of computational budgets by merely running the model for a variable number of iterations. We find that this architecture is uniquely suited for efficiently segmenting videos. By exploiting the segmentation of past frames, the RNN can perform video segmentation at similar quality but reduced computational cost compared to state-of-the-art image segmentation methods. When applied to static images in the PASCAL VOC 2012 and Cityscapes segmentation datasets, the RNN traces out a speed-accuracy curve that saturates near the performance of state-of-the-art segmentation methods

    A standardized kinesin nomenclature

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    In recent years the kinesin superfamily has become so large that several different naming schemes have emerged, leading to confusion and miscommunication. Here, we set forth a standardized kinesin nomenclature based on 14 family designations. The scheme unifies all previous phylogenies and nomenclature proposals, while allowing individual sequence names to remain the same, and for expansion to occur as new sequences are discovered

    Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

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    The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

    Celebrating music in the local community : an academic service-learning project to bring music into children's lives in the local primary school

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    Academic service learning, or community engagement, has been developed by universities to provide mutually beneficial outcomes to the local communities using the expertise of their students who, through their engagement with the community enhance their knowledge, understanding and reflection skills. This paper describes a primary school based academic service learning project in which six undergraduate music students focussed on using and extending their knowledge and expertise in music and other art forms, by teaching the creative arts in a culturally diverse, low socio-economic primary school, and reflecting on their experiences. The students had no teacher education training, but were hoping to enrol in a teacher education course when they completed their B. Arts (Music) degree. Throughout the service-learning project the students worked with the teachers to present music-based creative arts lessons across different grades, as well as presenting music and drama workshops in an After School Arts Programme, thus providing the children with creative arts experiences which they may not have had otherwise. As the students reflected on their experiences, they developed their understanding of the children and their diverse backgrounds as well as enhancing and strengthening their own reflective and higher order thinking skills, their self-awareness and confidence in teaching and their learning and implementing effective teaching strategies in relation to music and the other creative arts. Mutually beneficial outcomes were achieved both by students and the school community, as a result of this academic service-learning project

    Mapping the Distinctive Populations of Lymphatic Endothelial Cells in Different Zones of Human Lymph Nodes

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    <div><p>The lymphatic sinuses in human lymph nodes (LNs) are crucial to LN function yet their structure remains poorly defined. Much of our current knowledge of lymphatic sinuses derives from rodent models, however human LNs differ substantially in their sinus structure, most notably due to the presence of trabeculae and trabecular lymphatic sinuses that rodent LNs lack. Lymphatic sinuses are bounded and traversed by lymphatic endothelial cells (LECs). A better understanding of LECs in human LNs is likely to improve our understanding of the regulation of cell trafficking within LNs, now an important therapeutic target, as well as disease processes that involve lymphatic sinuses. We therefore sought to map all the LECs within human LNs using multicolor immunofluorescence microscopy to visualize the distribution of a range of putative markers. PROX1 was the only marker that uniquely identified the LECs lining and traversing all the sinuses in human LNs. In contrast, LYVE1 and STAB2 were only expressed by LECs in the paracortical and medullary sinuses in the vast majority of LNs studied, whilst the subcapsular and trabecular sinuses lacked these molecules. These data highlight the existence of at least two distinctive populations of LECs within human LNs. Of the other LEC markers, we confirmed VEGFR3 was not specific for LECs, and CD144 and CD31 stained both LECs and blood vascular endothelial cells (BECs); in contrast, CD59 and CD105 stained BECs but not LECs. We also showed that antigen-presenting cells (APCs) in the sinuses could be clearly distinguished from LECs by their expression of CD169, and their lack of expression of PROX1 and STAB2, or endothelial markers such as CD144. However, both LECs and sinus APCs were stained with DCN46, an antibody commonly used to detect CD209.</p></div

    CD209 expression in lymphatic sinuses.

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    <p>CD169<sup>+</sup> APCs also expressed CD209 (A–D). Rare CD169<sup>+</sup> CD209<sup>−</sup> APCs were detected in one of the LNs assessed (B: middle panel marked with asterisk). CD209<sup>+</sup>CD169<sup>−</sup> cells in the paracortical and medullary sinuses are likely to represent LECs (C–D). Serial LN sections stained with anti-CD209 (E) and DCN46 (F) showed that far fewer cells were stained by anti-CD209 antibody than by DCN46. Blue represents DAPI staining of cell nuclei (A–B, E–F). C,capsule; S, sinus. All scale bars represent 50 µm.</p

    Assessing the phenotype of the APCs and LECs in the lymphatic sinuses.

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    <p>Within the sinuses in the paracortex and medulla, the PROX1<sup>+</sup>CD169<sup>−</sup> LECs expressed the lymphatic marker LYVE1. The majority of PROX1<sup>−</sup>CD169<sup>+</sup> APCs in the paracortical and medullary sinuses lacked LYVE1 expression (A), although rare cells in these sinuses appeared to co-express CD169 and LYVE1 (B). CD169<sup>+</sup> APCs in the subcapsular and trabecular sinuses lacked LYVE1 (B). LYVE1 was expressed by a subset of the DCN46<sup>+</sup> cells in the medullary sinuses, which are likely to represent the LECs (C). CD169<sup>+</sup>STAB2<sup>−</sup> APCs were closely associated with the CD169<sup>−</sup>STAB2<sup>+</sup> LECs in the paracortical and medullary sinuses (D–E). The subcapsular and trabecular sinuses did not express STAB2 (F), although CD169<sup>+</sup> APCs were present. Blue represents DAPI staining of cell nuclei (D–F). C,capsule; T, trabecula; S, sinus. Scale bars represent 50 µm (A, C–E) and 100 µm (B, F).</p

    Heterogeneous expression of LYVE1 and STAB2 by endothelial cells in lymphatic sinuses of human LNs.

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    <p>Low magnification images demonstrated that LYVE1 expression is restricted to the paracortical and medullary sinuses whilst the other sinuses in the superficial areas lack expression of this marker (A). PROX1<sup>+</sup>CD31<sup>+</sup> LECs of the paracortical and medullary sinuses express LYVE1 (B) and STAB2 (D), whereas the LECs in the subcapsular and trabecular sinuses are negative for LYVE1 (C) and STAB2 (E). Blue represents DAPI staining of cell nuclei (A). P, paracortex; M, medulla; C, capsule; T, trabecula; S, sinus. All scale bars represent 100 µm.</p
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