291 research outputs found

    RAPL: A Relation-Aware Prototype Learning Approach for Few-Shot Document-Level Relation Extraction

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    How to identify semantic relations among entities in a document when only a few labeled documents are available? Few-shot document-level relation extraction (FSDLRE) is crucial for addressing the pervasive data scarcity problem in real-world scenarios. Metric-based meta-learning is an effective framework widely adopted for FSDLRE, which constructs class prototypes for classification. However, existing works often struggle to obtain class prototypes with accurate relational semantics: 1) To build prototype for a target relation type, they aggregate the representations of all entity pairs holding that relation, while these entity pairs may also hold other relations, thus disturbing the prototype. 2) They use a set of generic NOTA (none-of-the-above) prototypes across all tasks, neglecting that the NOTA semantics differs in tasks with different target relation types. In this paper, we propose a relation-aware prototype learning method for FSDLRE to strengthen the relational semantics of prototype representations. By judiciously leveraging the relation descriptions and realistic NOTA instances as guidance, our method effectively refines the relation prototypes and generates task-specific NOTA prototypes. Extensive experiments demonstrate that our method outperforms state-of-the-art approaches by average 2.61% F1F_1 across various settings of two FSDLRE benchmarks.Comment: Accepted to EMNLP 202

    Changes in axial length in anisometropic children wearing orthokeratology lenses

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    PurposeThere is a particular anisometropia occurring in one eye with myopia, while the other eye has very low myopia, emmetropia, or very low hyperopia. It is unclear how the binocular axial length changes when these children wear unilateral OK lenses only in the more myopic eyes. This study investigates the changes in the axial elongation of both eyes.MethodsThis is a 1-year retrospective study. In total, 148 children with myopic anisometropia were included. The more myopic eyes were wearing orthokeratology lenses (treated eyes), whereas the contralateral eyes were not indicated for visual correction (untreated eyes). The untreated eyes were classified into three subgroups based on the spherical equivalent refraction (SER): low myopia (≤ -0.50 D, n = 37), emmetropia (+0.49 to −0.49 D, n = 76), and low hyperopia (≥0.50 D, n = 35). Changes in the axial length (AL) were compared between the untreated and treated eyes and among the three subgroups.ResultsThe axial elongation was 0.14 ± 0.18 mm and 0.39 ± 0.27 mm in all treated and untreated eyes, respectively (p < 0.001). The interocular AL difference decreased significantly from 1.09 ± 0.45 mm at the baseline to 0.84 ± 0.52 mm at 1 year (p < 0.001). The baseline median (Q1, Q3) SER of the untreated eyes were −0.75 D (−0.56, −0.88 D), 0.00 D (0.00, −0.25 D), and +0.75 D (+1.00, +0.62 D) in low myopia, emmetropia, and low hyperopia subgroups, respectively. The axial elongation was 0.14 ± 0.18 mm, 0.15 ± 0.17 mm, and 0.13 ± 0.21 mm (p = 0.92) in the treated eyes and 0.44 ± 0.25 mm, 0.35 ± 0.24 mm, and 0.41 ± 0.33 mm in the untreated eyes (p = 0.11) after 1 year. Multivariate linear regression analyses only showed significant differences in axial elongation between the emmetropia and low myopia subgroups of untreated eyes (p = 0.04; p > 0.05 between other subgroups).ConclusionUnilateral orthokeratology lenses effectively reduced axial elongation in the more myopic eyes and reduced interocular AL differences in children with myopic anisometropia. The refractive state of the untreated eyes did not affect the axial elongation of the more myopic eye wearing the orthokeratology lens. In the untreated eyes, AL increased faster in the low myopia subgroup than in the emmetropia subgroup

    Function and dysfunction of the PI system in membrane trafficking

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    The phosphoinositides (PIs) function as efficient and finely tuned switches that control the assembly–disassembly cycles of complex molecular machineries with key roles in membrane trafficking. This important role of the PIs is mainly due to their versatile nature, which is in turn determined by their fast metabolic interconversions. PIs can be tightly regulated both spatially and temporally through the many PI kinases (PIKs) and phosphatases that are distributed throughout the different intracellular compartments. In spite of the enormous progress made in the past 20 years towards the definition of the molecular details of PI–protein interactions and of the regulatory mechanisms of the individual PIKs and phosphatases, important issues concerning the general principles of the organisation of the PI system and the coordination of the different PI-metabolising enzymes remain to be addressed. The answers should come from applying a systems biology approach to the study of the PI system, through the integration of analyses of the protein interaction data of the PI enzymes and the PI targets with those of the ‘phenomes' of the genetic diseases that involve these PI-metabolising enzymes

    Stabilization of ribozyme-like cis-noncoding rRNAs induces apoptotic and nonapoptotic death in lung cells

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    Bidirectional non-protein-coding RNAs are ubiquitously transcribed from the genome. Convergent sense and antisense transcripts may regulate each other. Here, we examined the convergent cis-noncoding rRNAs (nc-rRNAs) in A5 and E9 lung cancer models. Sense nc-rRNAs extending from rDNA intergenic region to internal transcribed spacer of around 10 kb in length were identified. nc-rRNAs in sense direction exhibited in vitro characteristics of ribozymes, namely, degradation upon incubation with MgCl2 and stabilization by complementary oligonucleotides. Detection of endogenous cleavage-ligation products carrying internal deletion of hundreds to thousands nucleotides by massively parallel sequencing confirmed the catalytic properties. Transfection of oligonucleotides pairing with antisense nc-rRNAs stabilized both target and complementary transcripts, perturbed rRNA biogenesis, and induced massive cell death via apoptotic and/or nonapoptotic mechanisms depending on cell type and treatment. Oligonucleotides targeting cellular sense transcripts are less responsive. Spontaneously detached cells, though rare, also showed accumulation of nc-rRNAs and perturbation of rRNA biogenesis. Direct participation of nc-rRNAs in apoptotic and nonapoptotic death was demonstrated by transfection of synthetic nc-rRNAs encompassing the rDNA promoter. In sum, convergent cis-nc-rRNAs follow a feed-forward mechanism to regulate each other and rRNA biogenesis. This opens an opportunity to disrupt rRNA biogenesis, commonly upregulated in cancers, via inhibition of ribozyme-like activities in nc-rRNAs

    Dendritic glycopolymers based on dendritic polyamine scaffolds: view on their synthetic approaches, characteristics and potential for biomedical applications

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    In this review we highlight the potential for biomedical applications of dendritic glycopolymers based on polyamine scaffolds. The complex interplay of the molecular characteristics of the dendritic architectures and their specific interactions with various (bio)molecules are elucidated with various examples. A special role of the individual sugar units attached to the dendritic scaffolds and their density is identified, which govern ionic and H-bond interactions, and biological targeting, but to a large extent are also responsible for the significantly reduced toxicity of the dendritic glycopolymers compared to their polyamine scaffolds. Thus, the application of dendritic glycopolymers in drug delivery systems for gene transfection but also as therapeutics in neurodegenerative diseases has great promisePublikacja w ramach programu Royal Society of Chemistry "Gold for Gold" 2014 finansowanego przez Uniwersytet Łódzk

    The ocean sampling day consortium

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    Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

    Spatial Mapping of Myeloid Cells and Macrophages by Multiplexed Tissue Staining

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    An array of phenotypically diverse myeloid cells and macrophages (MC&M) resides in the tumor microenvironment, requiring multiplexed detection systems for visualization. Here we report an automated, multiplexed staining approach, named PLEXODY, that consists of five MC&M-related fluorescently-tagged antibodies (anti - CD68, - CD163, - CD206, - CD11b, and - CD11c), and three chromogenic antibodies, reactive with high- and low-molecular weight cytokeratins and CD3, highlighting tumor regions, benign glands and T cells. The staining prototype and image analysis methods which include a pixel/area-based quantification were developed using tissues from inflamed colon and tonsil and revealed a unique tissue-specific composition of 14 MC&M-associated pixel classes. As a proof-of-principle, PLEXODY was applied to three cases of pancreatic, prostate and renal cancers. Across digital images from these cancer types we observed 10 MC&M-associated pixel classes at frequencies greater than 3%. Cases revealed higher frequencies of single positive compared to multi-color pixels and a high abundance of CD68+/CD163+ and CD68+/CD163+/CD206+ pixels. Significantly more CD68+ and CD163+ vs. CD11b+ and CD11c+ pixels were in direct contact with tumor cells and T cells. While the greatest percentage (~70%) of CD68+ and CD163+ pixels was 0–20 microns away from tumor and T cell borders, CD11b+ and CD11c+ pixels were detected up to 240 microns away from tumor/T cell masks. Together, these data demonstrate significant differences in densities and spatial organization of MC&M-associated pixel classes, but surprising similarities between the three cancer types

    Acute kidney disease and renal recovery : consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

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    Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of > 90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD
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