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  • 1
    In: Designing the Digital Transformation, DESRIST, International Conference on Design Science Research in Information Systems and Technology, 12, 2017, Vol.10243, p.218
    Subject(s): Informationstechnologie
    ISSN: 0302-9743
    Source: wiso Wirtschaftswissenschaften (GBI-Genios Deutsche Wirtschaftsdatenbank GmbH) 〈img src="http://exlibris-pub.s3.amazonaws.com/wiso_logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: STEM CELLS, August 2013, Vol.31(8), pp.1574-1583
    Description: Itch, a HECT family E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of target proteins. However, the role of Itch in osteoblasts has not been investigated. We report that mice have significantly increased bone volume, osteoblast numbers, and bone formation rate. Using bone marrow stromal cells from mice and wild‐type (WT) littermates as bone marrow mesenchymal precursor cells (BM‐MPCs), we found that BM‐MPCs from mice have compatible numbers of cells expressing mesenchymal stem cell markers. However, BM‐MPCs grew faster in an in vitro culture, formed more CFU‐F mesenchymal colonies, and exhibited increased osteoblast differentiation and decreased adipogenesis. Importantly, mesenchymal colony cells formed significantly more new bone in a tibial defect of recipient mice compared with WT cells. The expression levels of JunB, an AP‐1 transcription factor that positively regulate osteoblast differentiation, were significantly increased in BM‐MPCs when proteasome function is intact. In contrast, the amount of ubiquitinated JunB protein was markedly decreased in cells when proteasome function was blocked. Overexpression of WT Itch, but not an Itch ligase‐inactive mutant, rescued differentiation defects of BM‐MPCs. BM‐MPCs had a similar role in immune modulation as WT cells. Thus, Itch negatively controls osteoblast differentiation from BM‐MPCs through the regulation of proteasomal degradation of positive osteoblast regulator JunB protein. Itch is a potential new target for bone anabolic drug development to treat patients with bone loss.
    Subject(s): Itch ; E3 Ligase ; Mesenchymal Progenitor Cells ; Osteoblasts ; Bone Formation
    ISSN: 1066-5099
    E-ISSN: 1549-4918
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  • 3
    In: FASEB Journal, June 2018, Vol.32(6), pp.3174-3183
    Description: Thy1 (CD90), a glycosylated, glycophosphatidylinositol‐anchored membrane protein highly expressed by subsets of mesenchymal stem cells and fibroblasts, inhibits adipogenesis. The role of Thy1 on bone structure and function has been poorly studied and represents a major knowledge gap. Therefore, we analyzed the long bones of wild‐type (WT) and Thy1 knockout (KO) mice with micro‐computed tomography (micro‐CT) and histomorphometry to compare changes in bone architecture and overall bone structure. micro‐CT analysis of long bones revealed Thy1 KO and WT mice fed a high‐fat diet demonstrated bone structural parameters at 4 mo that differed significantly between WT and KO mice. A significant reduction in trabecular bone volume was noted in Thy1 KO mice. The most prominent differences were observed in trabecular bone volume ratio and trabecular bone connectivity density. Consistent with micro‐CT measurements, histomorphometric analysis also showed decreased bone volume in the obese Thy1 KO mice...
    Subject(s): Adipocytes ; Cd90 ; Mesenchymal Stem Cells ; Osteoblastogenesis ; Trabecular Bone Volume
    ISSN: 0892-6638
    E-ISSN: 1530-6860
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  • 4
    Language: English
    In: The Journal of clinical investigation, July 2014, Vol.124(7), pp.3200-14
    Description: NOTCH-dependent signaling pathways are critical for normal bone remodeling; however, it is unclear if dysfunctional NOTCH activation contributes to inflammation-mediated bone loss, as observed in rheumatoid arthritis (RA) patients. We performed RNA sequencing and pathway analyses in mesenchymal stem cells (MSCs) isolated from transgenic TNF-expressing mice, a model of RA, to identify pathways responsible for decreased osteoblast differentiation. 53 pathways were dysregulated in MSCs from RA mice, among which expression of genes encoding NOTCH pathway members and members of the noncanonical NF-κB pathway were markedly elevated. Administration of NOTCH inhibitors to RA mice prevented bone loss and osteoblast inhibition, and CFU-fibroblasts from RA mice treated with NOTCH inhibitors formed more new bone in recipient mice with tibial defects. Overexpression of the noncanonical NF-κB subunit p52 and RELB in a murine pluripotent stem cell line increased NOTCH intracellular domain-dependent (NICD-dependent)...
    Subject(s): Arthritis, Rheumatoid -- Metabolism ; Nf-Kappa B -- Metabolism ; Osteoblasts -- Metabolism ; Receptors, Notch -- Metabolism
    ISSN: 0021-9738
    E-ISSN: 1558-8238
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  • 5
    Language: English
    In: IEEE Access, 2018, Vol.6, pp.39621-39634
    Description: While network attack and defense are experiencing a rapid change, the current research achievements of network security based on traditional game theory fail to characterize the real-time performance of the actual network attack-defense process accurately. Furthermore, all kinds of disturbance and accidental factors would affect the evolution of the network security state. Therefore, to tackle with the randomness of network security state and the high dynamic of network defense decision making, we analyzed the attack-defense behaviors from the perspectives of dynamic and real-time confrontation. Then we constructed the Markov attack-defense differential game model for the dynamic analysis to predict multi-stage continuous attack-defense process by combining differential game models and the Markov decision-making method. In addition, according to the discounted total payoffs of attack-defense game, we designed the objective function of the game. Based on previous statements, we proposed the multistage game equilibrium solution and designed the optimal defense strategy selection algorithm. Finally, we conducted simulations to demonstrate that the proposed model and method could shed some light to the real-time interplay of decision making between attack and defense.
    Subject(s): Games ; Markov Processes ; Decision Making ; Security ; Analytical Models ; Communication Networks ; Real-Time Systems ; Network Security ; Network Attack and Defense ; Differential Game ; Markov Decision-Making ; Optimal Strategies Selection ; Engineering
    E-ISSN: 2169-3536
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  • 6
    Language: English
    In: Multimedia Tools and Applications, 2018, Vol.77(4), pp.4355-4378
    Description: As one of the most widely used algorithms in recommendation field, collaborative filtering (CF) predicts the unknown rating of items based on similar neighbors. Although many CF-based recommendation methods have been proposed, there still be room for improvement. Firstly, the data sparsity problem still remains a big challenge for CF algorithms to find similar neighbors. Secondly, there are many redundant similar items in the recommendation list generated by traditional CF algorithms, which cannot meet the user wide interest. Therefore, we propose a diversified recommendation method combining topic model and random walk. A weighted random walk model is presented to find all direct and indirect similar neighbors on the sparse data, improving the accuracy of rating prediction. By taking both users’ behavior data and items’ lags into account, we give a diversity measurement method based on the topic distribution of items discovered by Linked-LDA model. Furthermore, a diversified ranking algorithm is developed to balance the accuracy and diversity of recommendation results. We compare our method with six other recommendation methods on a real-world dataset. Experimental results show that our method outperforms the other methods and achieves the best personalized recommendation effect.
    Subject(s): Collaborative filtering ; Data sparsity ; Topic model ; Random walk ; Recommendation diversity
    ISSN: 1380-7501
    E-ISSN: 1573-7721
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  • 7
    Language: English
    In: Drying Technology, 26 April 2017, Vol.35(6), pp.680-688
    Description: Due to the limited penetration of infrared, it is very difficult to develop an infrared drying model of rice kernels. In this study, two kinds of simplified drying models, which assumed the penetration depth is infinity and zero, were developed to investigate the effects of penetration on drying...
    Subject(s): Drying Model ; Infrared Drying ; Moisture Gradient ; Rice Kernel ; Stress ; Engineering ; Chemistry
    ISSN: 0737-3937
    E-ISSN: 1532-2300
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  • 8
    Language: English
    In: IEEE Access, 2017, Vol.5, pp.19505-19516
    Description: Since the characteristics of opposite objectives, non-cooperation relationship, and dependent strategies of network attack and defense are highly consistent with game theory, researching the decision-making methods of network defense and applying the game models to analyze the network attack-defense behaviors has been of concern in recent years. However, most of the research achievements regarding to the game models are based on the hypothesis that both the two sides' players are completely rational, which is hard to meet. Therefore, we combined the evolutionary game theory and Markov decisionmaking process to construct a multi-stage Markov evolutionary game model for network attack-defense analysis, in view of the bounded rationality constraint. The model, based on the non-cooperative evolutionary game theory, could accomplish dynamic analysis and deduction for the multi-stage and multi-state network attack-defense process. In addition, an objective function with discounted total payoffs was designed by analyzing payoff characteristics of the multi-stage evolutionary game, which is more consistent with the reality of network attack and defense. Besides, the solving method for multi-stage game equilibrium was proposed on the basis of calculating the single-stage evolutionary game equilibrium. In addition, an algorithm for optimal defense strategy of the multi-stage evolutionary games was given. Finally, the experiments showed the high effectiveness and validity of the model and method that has a guiding significance for the network attack and defense.
    Subject(s): Games ; Analytical Models ; Markov Processes ; Game Theory ; Biological System Modeling ; Security ; Network Attack and Defense ; Bounded Rationality ; Evolutionary Games ; Markov Decision-Making Process ; Multi-Stage Game Equilibrium ; Engineering
    E-ISSN: 2169-3536
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  • 9
    In: Journal of Bone and Mineral Research, September 2013, Vol.28(9), pp.1925-1935
    Description: Byline: , , Brendan F Boyce, Lianping Xing ABSTRACT Ubiquitin E3 ligase-mediated protein degradation promotes proteasomal degradation of key positive regulators of osteoblast functions. For example, the E3 ligases-SMAD-specific E3 ubiquitin protein ligase 1 (Smurf1), Itch, and WW domain-containing E3 ubiquitin protein ligase 1 (Wwp1)-promote degradation of Runt-related transcription factor 2 (Runx2), transcription factor jun-B (JunB), and chemokine (C-X-C) receptor type 4 (CXCR-4) proteins to inhibit their functions. However, the role of E3 ligases in age-associated bone loss is unknown. We found that the expression level of Wwp1, but not Smurf1 or Itch, was significantly increased in CD45-negative (CD45.sub.-) bone marrow-derived mesenchymal stem cells from 6-month-old and 12-month-old wild-type (WT) mice. Wwp1 knockout (Wwp1.sub.-/-) mice developed increased bone mass as they aged, associated with increased bone formation rates and normal bone resorption parameters. Bone marrow stromal cells (BMSCs) from Wwp1.sub.-/- mice formed increased numbers and areas of alkaline phosphatase.sub.+ and Alizarin red.sub.+ nodules and had increased migration potential toward chemokine (C-X-C motif) ligand 12 (CXCL12) gradients. Runx2, JunB, and CXCR-4 protein levels were significantly increased in Wwp1.sub.-/- BMSCs. Wwp1.sub.-/- BMSCs had increased amount of ubiquitinated JunB protein, but Runx2 ubiquitination was no change. Knocking down JunB in Wwp1.sub.-/- BMSCs returned Runx2 protein levels to that in WT cells. Thus, Wwp1 negatively regulates osteoblast functions by affecting both their migration and differentiation. Mechanisms designed to decrease Wwp1 levels in BMSCs may represent a new approach to prevent the decrease in osteoblastic bone formation associated with aging. Article Note: LS and HZ contributed equally to this work.
    Subject(s): Wwp1 ; Mesenchymal Stem Cells ; Osteoblasts ; Bone Formation
    ISSN: 0884-0431
    E-ISSN: 1523-4681
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  • 10
    Language: English
    In: Journal of experimental & clinical cancer research : CR, 12 February 2015, Vol.34, pp.16
    Description: To detect genetic expression profile alterations after papillary thyroid carcinoma (PTC) cells transfected with chemokine receptor CXCR7 gene by gene microarray, and gain insights into molecular mechanisms of how CXCR7 regulating PTC growth and metastasis. The Human OneArray microarray was used for a complete genome-wide transcript profiling of CXCR7 transfected PTCs (K1-CXCR7 cells), defined as experimental group. Non CXCR7 transfected PTCs (K1 cells) were used as control group. Differential analysis for per gene was performed with a random variance model and t test, p values were adjusted to control the false discovery rate. Gene ontology (GO) on differentially expressed genes to identify the biological processes in modulating the progression of papillary thyroid carcinoma. Pathway analysis was used to evaluate the signaling pathway that differentially expressed genes were involved in. In addition, quantitative real-time polymerase chain reaction (q-PCR) and Western blot were used to verify the top differentially expression genes. Comparative analysis revealed that the expression level of 1149 genes was changed in response to CXCR7 transfection. After unsupervised hierarchical clustering analysis, 270 differentially expressed genes were filtered, of them 156 genes were up-regulated whereas 114 genes were down-regulated in K1-CXCR7 cells. GO enrichment analysis revealed the differentially expressed genes were mainly involved in biopolymer metabolic process, signal transduction and protein metabolism. Pathway enrichment analysis revealed differentially expressed genes were mainly involved in ECM-receptor interaction, Focal adhesion, MAPK signaling pathway and Cytokine-cytokine receptor interaction pathway. More importantly, the expression level of genes closely associated with tumor growth and metastasis was altered significantly in K1-CXCR7 cells, including up-regulated genes FN1, COL1A1, COL4A1, PDGFRB, LTB, CXCL12, MMP-11, MT1-MMP and down-regulated genes ITGA7, and Notch-1. Gene expression profiling analysis of papillary thyroid carcinoma can further delineate the mechanistic insights on how CXCR7 regulating papillary thyroid carcinoma growth and metastasis. CXCR7 may regulate growth and metastasis of papillary thyroid carcinoma via the activation of PI3K/AKT pathway and its downstream NF-κB signaling, as well as the down-regulation of Notch signaling.
    Subject(s): Gene Expression Profiling ; Transcriptome ; Carcinoma -- Genetics ; Receptors, Cxcr -- Metabolism ; Thyroid Neoplasms -- Genetics
    ISSN: 0392-9078
    E-ISSN: 1756-9966
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