5,355 research outputs found

    Encodings of Range Maximum-Sum Segment Queries and Applications

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    Given an array A containing arbitrary (positive and negative) numbers, we consider the problem of supporting range maximum-sum segment queries on A: i.e., given an arbitrary range [i,j], return the subrange [i' ,j' ] \subseteq [i,j] such that the sum of the numbers in A[i'..j'] is maximized. Chen and Chao [Disc. App. Math. 2007] presented a data structure for this problem that occupies {\Theta}(n) words, can be constructed in {\Theta}(n) time, and supports queries in {\Theta}(1) time. Our first result is that if only the indices [i',j'] are desired (rather than the maximum sum achieved in that subrange), then it is possible to reduce the space to {\Theta}(n) bits, regardless the numbers stored in A, while retaining the same construction and query time. We also improve the best known space lower bound for any data structure that supports range maximum-sum segment queries from n bits to 1.89113n - {\Theta}(lg n) bits, for sufficiently large values of n. Finally, we provide a new application of this data structure which simplifies a previously known linear time algorithm for finding k-covers: i.e., given an array A of n numbers and a number k, find k disjoint subranges [i_1 ,j_1 ],...,[i_k ,j_k ], such that the total sum of all the numbers in the subranges is maximized.Comment: 19 pages + 2 page appendix, 4 figures. A shortened version of this paper will appear in CPM 201

    Systemic delivery of microRNA-101 potently inhibits hepatocellular carcinoma in vivo by repressing multiple targets

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    Targeted therapy based on adjustment of microRNA (miRNA)s activity takes great promise due to the ability of these small RNAs to modulate cellular behavior. However, the efficacy of miR-101 replacement therapy to hepatocellular carcinoma (HCC) remains unclear. In the current study, we first observed that plasma levels of miR-101 were significantly lower in distant metastatic HCC patients than in HCCs without distant metastasis, and down-regulation of plasma miR-101 predicted a worse disease-free survival (DFS, P<0.05). In an animal model of HCC, we demonstrated that systemic delivery of lentivirus-mediated miR-101 abrogated HCC growth in the liver, intrahepatic metastasis and distant metastasis to the lung and to the mediastinum, resulting in a dramatic suppression of HCC development and metastasis in mice without toxicity and extending life expectancy. Furthermore, enforced overexpression of miR-101 in HCC cells not only decreased EZH2, COX2 and STMN1, but also directly down-regulated a novel target ROCK2, inhibited Rho/Rac GTPase activation, and blocked HCC cells epithelial-mesenchymal transition (EMT) and angiogenesis, inducing a strong abrogation of HCC tumorigenesis and aggressiveness both in vitro and in vivo. These results provide proof-of-concept support for systemic delivery of lentivirus-mediated miR-101 as a powerful anti-HCC therapeutic modality by repressing multiple molecular targets. © 2015 Zheng et al.published_or_final_versio

    EZH2 protein: A promising immunomarker for the detection of hepatocellular carcinomas in liver needle biopsies

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    Background and aims: A previous study of ours indicated that enhancer of zeste homologue 2 (EZH2) plays an important role in hepatocellular carcinoma (HCC) tumorigenesis. The aim of the present study was to investigate the potential diagnostic utility of EZH2 in HCC. Methods: Immunohistochemistry was performed to examine the expression dynamics of EZH2 in two independent surgical cohorts of HCC and non-malignant liver tissues to develop a diagnostic yield of EZH2, HSP70 and GPC3 for HCC detection. The diagnostic performances of EZH2 and a three-marker panel in HCC were re-evaluated by using an additional biopsy cohort. Results: Immunohistochemistry analysis demonstrated that the sensitivity and specificity of EZH2 for HCC detection was 95.8% and 97.8% in the testing cohort. Similar results were confirmed in the validation cohort. For diagnosis of well-differentiated HCCs, the sensitivity and specificity were 68.9% and 91.5% for EZH2, 62.5% and 98.5% for HSP70, 50.0% and 92.1% for GPC3, and 75.0% and 100% for a three-marker panel. In biopsies, positive cases for at least one marker increased from large regenerative nodule and hepatocellular adenoma (0/12) to focal nodular hyperplasia (2/20), dysplastic nodule (7/25), well-differentiated HCC (16/18) and moderately and poorly differentiated HCC (54/54). When at least two positive markers were considered, regardless of their identity, the positive cases were detected in 0/12 large regenerative nodules and hepatocellular adenomas, 0/20 focal nodular hyperplasias, 0/25 dysplastic nodules, 11/18 well-differentiated HCCs, 32/37 moderately differentiated HCCs and 15/17 poorly differentiated HCCs. Conclusion: Our findings suggest that EZH2 protein, as examined by immunohistochemistry, may serve as a promising diagnostic biomarker of HCCs, and the use of a three-marker panel (EZH2, HSP70 and GPC3) can improve the rate of detection of HCCs in liver biopsy tissues.published_or_final_versio

    Synergistic Antibacterial Effects of Metallic Nanoparticle Combinations

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    © The Author(s) 2019.Metallic nanoparticles have unique antimicrobial properties that make them suitable for use within medical and pharmaceutical devices to prevent the spread of infection in healthcare. The use of nanoparticles in healthcare is on the increase with silver being used in many devices. However, not all metallic nanoparticles can target and kill all disease-causing bacteria. To overcome this, a combination of several different metallic nanoparticles were used in this study to compare effects of multiple metallic nanoparticles when in combination than when used singly, as single elemental nanoparticles (SENPs), against two common hospital acquired pathogens (Staphylococcus aureus and Pseudomonas. aeruginosa). Flow cytometry LIVE/DEAD assay was used to determine rates of cell death within a bacterial population when exposed to the nanoparticles. Results were analysed using linear models to compare effectiveness of three different metallic nanoparticles, tungsten carbide (WC), silver (Ag) and copper (Cu), in combination and separately. Results show that when the nanoparticles are placed in combination (NPCs), antimicrobial effects significantly increase than when compared with SENPs (P < 0.01). This study demonstrates that certain metallic nanoparticles can be used in combination to improve the antimicrobial efficiency in destroying morphologically distinct pathogens within the healthcare and pharmaceutical industry.Peer reviewe

    A Wide-angle Multi-Octave Broadband Waveplate Based on Field Transformation Approach

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    J.Z. acknowledge the support from the National Nature Science Foundation of China (61571218, 61571216, 61301017, 61371034, 61101011), and the Ph.D. Programs Foundation of Ministry of Education of China (20120091110032, 20110091120052). Y. H. acknowledge the support from the UK EPSRC under the QUEST Programme Grant (EP/I034548/1)

    Insight into the Stability of Cross-β Amyloid Fibril from VEALYL Short Peptide with Molecular Dynamics Simulation

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    Amyloid fibrils are found in many fatal neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, type II diabetes, and prion disease. The VEALYL short peptide from insulin has been confirmed to aggregate amyloid-like fibrils. However, the aggregation mechanism of amyloid fibril is poorly understood. Here, we utilized molecular dynamics simulation to analyse the stability of VEALYL hexamer. The statistical results indicate that hydrophobic residues play key roles in stabilizing VEALYL hexamer. Single point and two linkage mutants confirmed that Val1, Leu4, and Tyr5 of VEALYL are key residues. The consistency of the results for the VEALYL oligomer suggests that the intermediate states might be trimer (3-0) and pentamer(3-2). These results can help us to obtain an insight into the aggregation mechanism of amyloid fibril. These methods can be used to study the stability of amyloid fibril from other short peptides

    Preferential Paths of Air-water Two-phase Flow in Porous Structures with Special Consideration of Channel Thickness Effects.

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    Accurate understanding and predicting the flow paths of immiscible two-phase flow in rocky porous structures are of critical importance for the evaluation of oil or gas recovery and prediction of rock slides caused by gas-liquid flow. A 2D phase field model was established for compressible air-water two-phase flow in heterogenous porous structures. The dynamic characteristics of air-water two-phase interface and preferential paths in porous structures were simulated. The factors affecting the path selection of two-phase flow in porous structures were analyzed. Transparent physical models of complex porous structures were prepared using 3D printing technology. Tracer dye was used to visually observe the flow characteristics and path selection in air-water two-phase displacement experiments. The experimental observations agree with the numerical results used to validate the accuracy of phase field model. The effects of channel thickness on the air-water two-phase flow behavior and paths in porous structures were also analyzed. The results indicate that thick channels can induce secondary air flow paths due to the increase in flow resistance; consequently, the flow distribution is different from that in narrow channels. This study provides a new reference for quantitatively analyzing multi-phase flow and predicting the preferential paths of immiscible fluids in porous structures

    Electronic data safes as an infrastructure for transformational government? A case study

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    This article introduces and explores the potential of an active electronic data safe (AEDS) serving as an infrastructure to achieve transformational government. An AEDS connects individuals and organizations from the private and the public sector to exchange information items related to business processes following the user-managed access paradigm. To realize the transformational government’s vision of user-centricity, fundamental changes in the service provision and collaboration of public and private sector organizations are needed. Findings of a user study with a prototype of an AEDS are used to identify four barriers for the adoption of an AEDS in the light of transformational government: (1.) offering citizens unfamiliar services having the character of experience-goods; (2.) failing to fulfill common service expectations of the customers; (3.) failing to establish contextual integrity for data sharing, and, (4.) failing to establish and run an AEDS as a multi-sided platform providing an attractive business model
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