Deep Joint Entity Disambiguation with Local Neural Attention

We propose a novel deep learning model for joint document-level entity disambiguation, which leverages learned neural representations. Key components are entity embeddings, a neural attention mechanism over local context windows, and a differentiable joint inference stage for disambiguation. Our approach thereby combines benefits of deep learning with more traditional approaches such as graphical models and probabilistic mention-entity maps. Extensive experiments show that we are able to obtain competitive or state-of-the-art accuracy at moderate computational costs.Comment: Conference on Empirical Methods in Natural Language Processing (EMNLP) 2017 long pape

MR-guided percutaneous angioplasty: Assessment of tracking safety, catheter handling and functionality

Purpose: Magnetic resonance (MR)-guided percutaneous vascular interventions have evolved to a practical possibility with the advent of open-configuration MR systems and real-time tracking techniques. The purpose of this study was to assess an MR-tracking percutaneous transluminal angioplasty (PTA) catheter with regard to its safety profile and functionality. Methods: Real-time, biplanar tracking of the PTA catheter was made possible by incorporating a small radiofrequency (RF) coil in the catheter tip and connecting it to a coaxial cable embedded in the catheter wall. To evaluate potentially hazardous thermal effects due to the incorporation of the coil, temperature measurements were performed within and around the coil under various canning and tracking conditions at 1.5 Tesla (T). Catheter force transmission and balloon-burst pressure of the MR-tracking PTA catheter were compared with those of a standard PTA catheter. The dilatative capability of the angioplasty balloon was assessed in vitro as well as in vivo, in an isolated femoral artery segment in a swine. Results: The degree of heating at the RF coil was directly proportional to the power of the RF pulses. Heating was negligible with MR tracking, conventional spin-echo and low-flip gradient-echo sequences. Sequences with higher duty cycles, such as fast spin echo, produced harmful heating effects. Force transmission of the MR-tracking PTA catheter was slightly inferior to that of the standard PTA catheter, while balloon-burst pressures were similar to those of conventional catheters. The MR-tracking PTA catheter functioned well both in vitro and in vivo. Conclusion: The in vivo use of an MR-tracking PTA catheter is safe under most scanning condition

First Magnetic Resonance Imaging-Guided Aortic Stenting and Cava Filter Placement Using a Polyetheretherketone-Based Magnetic Resonance Imaging-Compatible Guidewire in Swine: Proof of Concept

The purpose of this study was to demonstrate feasibility of percutaneous transluminal aortic stenting and cava filter placement under magnetic resonance imaging (MRI) guidance exclusively using a polyetheretherketone (PEEK)-based MRI-compatible guidewire. Percutaneous transluminal aortic stenting and cava filter placement were performed in 3 domestic swine. Procedures were performed under MRI-guidance in an open-bore 1.5-T scanner. The applied 0.035-inch guidewire has a PEEK core reinforced by fibres, floppy tip, hydrophilic coating, and paramagnetic markings for passive visualization. Through an 11F sheath, the guidewire was advanced into the abdominal (swine 1) or thoracic aorta (swine 2), and the stents were deployed. The guidewire was advanced into the inferior vena cava (swine 3), and the cava filter was deployed. Postmortem autopsy was performed. Procedural success, guidewire visibility, pushability, and stent support were qualitatively assessed by consensus. Procedure times were documented. Guidewire guidance into the abdominal and thoracic aortas and the inferior vena cava was successful. Stent deployments were successful in the abdominal (swine 1) and thoracic (swine 2) segments of the descending aorta. Cava filter positioning and deployment was successful. Autopsy documented good stent and filter positioning. Guidewire visibility through applied markers was rated acceptable for aortic stenting and good for venous filter placement. Steerability, pushability, and device support were good. The PEEK-based guidewire allows either percutaneous MRI-guided aortic stenting in the thoracic and abdominal segments of the descending aorta and filter placement in the inferior vena cava with acceptable to good device visibility and offers good steerability, pushability, and device suppor

Competitive Reporter Monitored Amplification (CMA) - Quantification of Molecular Targets by Real Time Monitoring of Competitive Reporter Hybridization

Background: State of the art molecular diagnostic tests are based on the sensitive detection and quantification of nucleic acids. However, currently established diagnostic tests are characterized by elaborate and expensive technical solutions hindering the development of simple, affordable and compact point-of-care molecular tests. Methodology and Principal Findings: The described competitive reporter monitored amplification allows the simultaneous amplification and quantification of multiple nucleic acid targets by polymerase chain reaction. Target quantification is accomplished by real-time detection of amplified nucleic acids utilizing a capture probe array and specific reporter probes. The reporter probes are fluorescently labeled oligonucleotides that are complementary to the respective capture probes on the array and to the respective sites of the target nucleic acids in solution. Capture probes and amplified target compete for reporter probes. Increasing amplicon concentration leads to decreased fluorescence signal at the respective capture probe position on the array which is measured after each cycle of amplification. In order to observe reporter probe hybridization in real-time without any additional washing steps, we have developed a mechanical fluorescence background displacement technique. Conclusions and Significance: The system presented in this paper enables simultaneous detection and quantification of multiple targets. Moreover, the presented fluorescence background displacement technique provides a generic solution fo

Bioassays to Monitor Taspase1 Function for the Identification of Pharmacogenetic Inhibitors

Background: Threonine Aspartase 1 (Taspase1) mediates cleavage of the mixed lineage leukemia (MLL) protein and leukemia provoking MLL-fusions. In contrast to other proteases, the understanding of Taspase1's (patho)biological relevance and function is limited, since neither small molecule inhibitors nor cell based functional assays for Taspase1 are currently available. Methodology/Findings: Efficient cell-based assays to probe Taspase1 function in vivo are presented here. These are composed of glutathione S-transferase, autofluorescent protein variants, Taspase1 cleavage sites and rational combinations of nuclear import and export signals. The biosensors localize predominantly to the cytoplasm, whereas expression of biologically active Taspase1 but not of inactive Taspase1 mutants or of the protease Caspase3 triggers their proteolytic cleavage and nuclear accumulation. Compared to in vitro assays using recombinant components the in vivo assay was highly efficient. Employing an optimized nuclear translocation algorithm, the triple-color assay could be adapted to a high-throughput microscopy platform (Z'factor = 0.63). Automated high-content data analysis was used to screen a focused compound library, selected by an in silico pharmacophor screening approach, as well as a collection of fungal extracts. Screening identified two compounds, N-[2-[(4-amino-6-oxo-3H-pyrimidin-2-yl)sulfanyl]ethyl]benzenesulfonamideand 2-benzyltriazole-4,5-dicarboxylic acid, which partially inhibited Taspase1 cleavage in living cells. Additionally, the assay was exploited to probe endogenous Taspase1 in solid tumor cell models and to identify an improved consensus sequence for efficient Taspase1 cleavage. This allowed the in silico identification of novel putative Taspase1 targets. Those include the FERM Domain-Containing Protein 4B, the Tyrosine-Protein Phosphatase Zeta, and DNA Polymerase Zeta. Cleavage site recognition and proteolytic processing of these substrates were verified in the context of the biosensor. Conclusions: The assay not only allows to genetically probe Taspase1 structure function in vivo, but is also applicable for high-content screening to identify Taspase1 inhibitors. Such tools will provide novel insights into Taspase1's function and its potential therapeutic relevance