663 research outputs found

    Anomalous spin dynamics in charge ordered, 'two-electron' doped manganite Ca_0.9Ce_0.1MnO_3 : consequence of a spin-liquid phase?

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    The 'two-electron' doped rare earth mangnites Ca_1-x Ce_x MnO_3 (x = 0.1,0.2) are probed using resistivity, ac susceptibility and electron paramagnetic resonance (EPR) measurements across their respective charge ordering (CO) temperatures T_CO = 173 K and 250 K. The EPR 'g' factor and intensity as well as the transport and magnetic behaviours of the two compositions are qualitatively similar and are as expected for CO systems. However, the EPR linewidth, reflective of the spin dynamics, for x = 0.1, shows a strongly anomalous temperature dependence, decreasing with decreasing temperature below T_CO in contrast with the sample with x = 0.2 and other CO systems. Keeping in view the evidence for magnetic frustration in the system, we propose that the anomalous temperature dependence of the linewidth is the signature of the occurrence of a disorder driven spin liquid phase, present along with charge ordering.Comment: 19 pages including 4 figure

    Safe Learning of Linear Time-Invariant Systems

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    We consider safety in simultaneous learning and control of discrete-time linear time-invariant systems. We provide rigorous confidence bounds on the learned model of the system based on the number of utilized state measurements. These bounds are used to modify control inputs to the system via an optimization problem with potentially time-varying safety constraints. We prove that the state can only exit the safe set with small probability, provided a feasible solution to the safety-constrained optimization exists. This optimization problem is then reformulated in a more computationally-friendly format by tightening the safety constraints to account for model uncertainty during learning. The tightening decreases as the confidence in the learned model improves. We finally prove that, under persistence of excitation, the tightening becomes negligible as more measurements are gathered.Comment: Accepted in NeurIPS 2021 Workshop on Safe and Robust Control of Uncertain System

    sIR: siRNA Information Resource, a web-based tool for siRNA sequence design and analysis and an open access siRNA database

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    <p>Abstract</p> <p>Background</p> <p>RNA interference has revolutionized our ability to study the effects of altering the expression of single genes in mammalian (and other) cells through targeted knockdown of gene expression. In this report we describe a web-based computational tool, siRNA Information Resource (sIR), which consists of a new open source database that contains validation information about published siRNA sequences and also provides a user-friendly interface to design and analyze siRNA sequences against a chosen target sequence.</p> <p>Results</p> <p>The siRNA design tool described in this paper employs empirically determined rules derived from a meta-analysis of the published data; it uses a weighted scoring system that determines the optimal sequence within a target mRNA and thus aids in the rational selection of siRNA sequences. This scoring system shows a non-linear correlation with the knockdown efficiency of siRNAs. sIR provides a fast, customized BLAST output for all selected siRNA sequences against a variety of databases so that the user can verify the uniqueness of the design. We have pre-designed siRNAs for all the known human genes (24,502) in the Refseq database. These siRNAs were pre-BLASTed against the human Unigene database to estimate the target specificity and all results are available online.</p> <p>Conclusion</p> <p>Although most of the rules for this scoring system were influenced by previously published rules, the weighted scoring system provides better flexibility in designing an appropriate siRNA when compared to the un-weighted scoring system. sIR is not only a comprehensive tool used to design siRNA sequences and lookup pre-designed siRNAs, but it is also a platform where researchers can share information on siRNA design and use.</p

    MFSD2A is a novel lung tumor suppressor gene modulating cell cycle and matrix attachment

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    <p>Abstract</p> <p>Background</p> <p>MFSD2A (major facilitator superfamily domain containing 2) gene maps on chromosome 1p34 within a linkage disequilibrium block containing genetic elements associated with progression of lung cancer.</p> <p>Results</p> <p>Here we show that MFSD2A expression is strongly downregulated in non-small cell lung cancer cell lines of different histotypes and in primary lung adenocarcinomas. Experimental modulation of MFSD2A in lung cancer cells is associated with alteration of mRNA levels of genes involved in cell cycle control and interaction with the extracellular matrix. Exogenous expression of MFSD2A in lung cancer cells induced a G1 block, impaired adhesion and migration <it>in vitro</it>, and significantly reduced tumor colony number <it>in vitro </it>(4- to 27-fold, P < 0.0001) and tumor volume <it>in vivo </it>(~3-fold, P < 0.0001). siRNA knockdown studies in normal human bronchial epithelial cells confirmed the role of MFSD2A in G1 regulation.</p> <p>Conclusion</p> <p>Together these data suggest that MFSD2A is a novel lung cancer tumor suppressor gene that regulates cell cycle progression and matrix attachment.</p

    Low-Dose CT Image Enhancement Using Deep Learning

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    The application of ionizing radiation for diagnostic imaging is common around the globe. However, the process of imaging, itself, remains to be a relatively hazardous operation. Therefore, it is preferable to use as low a dose of ionizing radiation as possible, particularly in computed tomography (CT) imaging systems, where multiple x-ray operations are performed for the reconstruction of slices of body tissues. A popular method for radiation dose reduction in CT imaging is known as the quarter-dose technique, which reduces the x-ray dose but can cause a loss of image sharpness. Since CT image reconstruction from directional x-rays is a nonlinear process, it is analytically difficult to correct the effect of dose reduction on image quality. Recent and popular deep-learning approaches provide an intriguing possibility of image enhancement for low-dose artifacts. Some recent works propose combinations of multiple deep-learning and classical methods for this purpose, which over-complicate the process. However, it is observed here that the straight utilization of the well-known U-NET provides very successful results for the correction of low-dose artifacts. Blind tests with actual radiologists reveal that the U-NET enhanced quarter-dose CT images not only provide an immense visual improvement over the low-dose versions, but also become diagnostically preferable images, even when compared to their full-dose CT versions

    NeuroD1 regulation of migration accompanies the differential sensitivity of neuroendocrine carcinomas to TrkB inhibition

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    The developmental transcription factor NeuroD1 is anomalously expressed in a subset of aggressive neuroendocrine tumors. Previously, we demonstrated that TrkB and neural cell adhesion molecule (NCAM) are downstream targets of NeuroD1 that contribute to the actions of neurogenic differentiation 1 (NeuroD1) in neuroendocrine lung. We found that several malignant melanoma and prostate cell lines express NeuroD1 and TrkB. Inhibition of TrkB activity decreased invasion in several neuroendocrine pigmented melanoma but not in prostate cell lines. We also found that loss of the tumor suppressor p53 increased NeuroD1 expression in normal human bronchial epithelial cells and cancer cells with neuroendocrine features. Although we found that a major mechanism of action of NeuroD1 is by the regulation of TrkB, effective targeting of TrkB to inhibit invasion may depend on the cell of origin. These findings suggest that NeuroD1 is a lineage-dependent oncogene acting through its downstream target, TrkB, across multiple cancer types, which may provide new insights into the pathogenesis of neuroendocrine cancers

    The ABCD of usability testing

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    We introduce a methodology for tracking and auditing feedback, errors and suggestions for software packages. This short paper describes how we innovate on the evaluation mechanism, introducing an (Antecedent, Barrier, Consequence and Development) ABCD form, embedded within an eParticipation platform to enable end users to easily report on any usability issues. This methodology will be utilised to improve the STEP cloud eParticipation platform (part of the current STEP Horizon2020 project http://step4youth.eu. The platform is currently being piloted in real life contexts, with the participation of public authorities that are integrating the eParticipation platform into their regular decision-making practices. The project is involving young people, through engagement and motivation strategies and giving them a voice in Environmental decision making at the local level. The pilot evaluation aims to demonstrate how open engagement needs to be embedded within public sector processes and the usability methodology reported here will help to identify the key barriers for wide scale deployment of the platform

    Three serendipitous pathways in E. coli can bypass a block in pyridoxal-5′-phosphate synthesis

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    Overexpression of seven different genes restores growth of a ΔpdxB strain of E. coli, which cannot make pyridoxal phosphate (PLP), on M9/glucose.None of the enzymes encoded by these genes has a promiscuous 4-phosphoerythronate dehydrogenase activity that can replace the activity of PdxB.Overexpression of these genes restores PLP synthesis by three different serendipitous pathways that feed into the normal PLP synthesis pathway downstream of the blocked step.Reactions in one of these pathways are catalyzed by low-level activities of enzymes of unknown function and a promiscuous activity of an enzyme that normally has a role in another pathway; one reaction appears to be non-enzymatic
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