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Lignin is an eco-friendly, low-cost, and abundant natural biopolymer. However, few studies have explored the potential application of lignin as electrolyte matrix for lithium-ion batteries or obtained excellent cell performance using lignin-based electrolyte. In this paper, lignin and poly(N-vinylimidazole)-co-poly(poly(ethylene glycol) methyl ether methacrylate) are mixed thoroughly in water, then a free-standing lignin-based film is obtained by casting and drying. The resulting film shows obviously higher mechanical strength (over 10 times) than that of the pure lignin film due to the construction of internal physical cross-linking network. Through activation of the prepared film by organic electrolyte, the membrane exhibits superior electrochemical performances (such as outstanding lithium-ion transfer number (0.63) and the ability to inhibit the growth of lithium dendrites). As a result, the LiFePO4/lignin-based electrolyte/Li cell presents excellent long cycle performance (∼150 mAh g–1 at 1 C more th...

Traffic jam has become a severe urban problem to most metropolises in the world. How to understand and resolve these traffic problems has become a global issue. In the new era of big data, visualization and analysis with traffic-related data are increasingly appreciated. This paper presents DiffusionInsighter, a web-based visual traffic analysis system, that allows users to explore the traffic flow and diffusion patterns with different spatial and temporal granularity. The DiffusionInsighter first applies a visual data cleaning and filtering component to remove dirty data and remain available ones for further analysis. A set of carefully designed interaction and visualization tools including geographical view, pixel map view, chord diagram and network diffusion view is proposed in the DiffusionInsighter to support level-of-detail exploration of diffusion patterns of the traffic flow. Different views are collaborated together and are integrated into geographic map. A series of real-life case studies are conducted using a large GPS trajectory dataset of taxis in Hangzhou.

All-solid-state polymer electrolytes (SPEs) have aroused great interests as one of the most promising alternatives for liquid electrolyte in the next-generation high-safety, and flexible lithium-ion batteries. However, some disadvantages of SPEs such as inefficient ion transmission capacity and poor interface stability result in unsatisfactory cyclic performance of the assembled batteries. Especially, the solid cell is hard to be run at room temperature. Herein, a novel and flexible discotic liquid-crystal (DLC)-based cross-linked solid polymer electrolyte (DLCCSPE) with controlled ion-conducting channels is fabricated via a one-pot photopolymerization of oriented reactive discogen, poly(ethylene glycol)diacrylate, and lithium salt. The experimental results indicate that the macroscopic alignment of self-assembled columns in the DLCCSPEs is successfully obtained under annealing and effectively immobilized via the UV photopolymerization. Because of the existence of unique oriented structure in the electrolytes, the prepared DLCCSPE films exhibit higher ionic conductivities and better comprehensive electrochemical properties than the DLCCSPEs without controlled ion-conductive pathways. Especially, the assembled LiFePO

It is important to help researchers find valuable papers from a large literature collection. To this end, many graph-based ranking algorithms have been proposed. However, most of these algorithms suffer from the problem of ranking bias. Ranking bias hurts the usefulness of a ranking algorithm because it returns a ranking list with an undesirable time distribution. This paper is a focused study on how to alleviate ranking bias by leveraging the heterogeneous network structure of the literature collection. We propose a new graph-based ranking algorithm, MutualRank, that integrates mutual reinforcement relationships among networks of papers, researchers, and venues to achieve a more synthetic, accurate, and less-biased ranking than previous methods. MutualRank provides a unified model that involves both intra- and inter-network information for ranking papers, researchers, and venues simultaneously. We use the ACL Anthology Network as the benchmark data set and construct the gold standard from computer linguistics course websites of well-known universities and two well-known textbooks. The experimental results show that MutualRank greatly outperforms the state-of-the-art competitors, including PageRank, HITS, CoRank, Future Rank, and P-Rank, in ranking papers in both improving ranking effectiveness and alleviating ranking bias. Rankings of researchers and venues by MutualRank are also quite reasonable.

It is very useful to understand metropolitan human movement patterns for better city planning and traffic management. As the most accessible and wide-coverage data source for probing the laws behind city pulse and human movement, taxi O/D data have been receiving more and more attention from road traffic administration offices. In this paper, we design a visual analysis system for big taxis O/D data for assisting understanding the spatio-temporal patterns of human mobility. The system first helps users determine the regions of interest for further investigation by the global heat map view of O/D distributions; visually encodes the spatio-temporal patterns of the O/D data of the to-be-analyzed regions chosen by lasso or rectangle region selection tools; and provides a multi-dimensidoneonal analysis of the latent spatio-temporal patterns of taxis O/D data through interactions between multiple coordinated views of visualizations including circular pixel graph, spatio-temporal stacked graph and nested pixel bar. The proposed system of taxis O/D data visual analysis gets interesting findings about the metropolitan residents’ movement behavior when applied to large-scale real taxis GPS data in Hangzhou and receives good user feedbacks.

Retinoid X receptor (RXR) and Histone deacetylase (HDAC) are considered important targets for cancer therapy due to their crucial roles in genetic or epigenetic regulations of cancer development and progression. Here, we evaluated the potential of dual targeting of RXR and HDAC using DW22 as a novel therapeutic approach to cancer treatment. We found that the co-expression of RXR-α and HDAC1 was frequently appeared in lung cancer and breast cancer tissues and cell lines. RXR was activated by DW22 in RXRα and HDAC1 overexpressed A549 and MDA-MB-435 cell lines. Meanwhile, DW22 inhibited the activity of HDAC by decreasing its expression in A549 and MDA-MB-435 cell lines, but not in RXRα and HDAC1 deficient cell lines. Moreover, DW22 suppressed cell growth, induced cell differentiation, prompted cell apoptosis and arrested cell cycle in A549, MDA-MB-435 or HL60 cell lines. Treatment human umbilical vascular endothelial cells (HUVECs) with DW22 suppressed migration, invasion and tube formation through decreasing VEGF expression. The up-regulation of Ac-H3 and p21, and down-regulation of VEGF caused by DW22 was markedly attenuated by silencing of HDAC1. Furthermore, knockdown of RXRα by siRNA completely blocked DW22-induced cell differentiation, but partially attenuated DW22-caused inhibition of cell proliferation, induction of cell apoptosis, and suppression of cell migration, invasion and tube formation. Moreover, intravenous administration of DW22 significantly retarded tumor growth of A549 and MDA-MB-435 xenograft mice models, and induced no substantial weight loss and gross toxicity. In addition, DW22 also reduced cell proliferation, angiogenesis, and induced cell apoptosis in vivo. Collectively, our data demonstrates that dual targeting of RXR and HDAC using DW22 possesses pleiotropic antitumor activities both in vitro and in vivo, providing a novel therapeutic approach for cancer treatment.

A novel series of chalcone derivatives were synthesized and their biological activities against HIF-1 were evaluated. Among these compounds, 5d exhibited clearly inhibitory effects on HIF-1 by downregulating the expression of HIF-1α under hypoxic conditions. Meanwhile, it also significantly suppressed VEGF-induced migration and invasion of Hep3B and HUVEC cells in nontoxic concentrations. Additionally, tube formation assay demonstrated its anti-angiogenesis activity. Moreover, the in vivo study indicated that compound 5d could retard tumor growth of Hep3B xenograft models and reduced CD31 and MMP-2 expression in tumor tissues. Finally, in acute intravenous toxicity, 5d was well tolerated and was found to be non-toxic up to 200 mg/kg in Swiss mice. These findings support the further investigation on the anti-invasive and anti-angiogenic potential of this class of compounds as HIF-1 inhibitor.

The demineralized bone matrix (DBM) putty is a traditional bone graft utilized to facilitate the repair and reconstruction of bone. Recent studies indicated the DBM putties with the various carriers were different in bone repairing ability. In order to prepare a kind of DBM putty with a good biocompatibility and bioactivity, the DBM gel was processed from the DBM and the feasibility as a carrier for the DBM putty was evaluated. After the bovine DBM gel was prepared, the BMPs content as well as the ability to promote osteogenic differentiation of MC3T3-E1 cells in vitro were investigated. Then the DBM putty was prepared and filled into the rat calvarial defect model to evaluate the bone repairing ability by micro-CT and histology. The result showed there was 2.953 ± 0.054 ng BMP contained in per gram of the DBM gel. And the ALP production of MC3T3-E1 cells in the DBM gels group increased with prolonged culturing, the mineralized nodules formed in MC3T3-E1 cells on 14th day after co-culture. The putty prepared by DBM gel was easy to handle without loss of DBM particles at room temperature. In the rat calvarial bone defect experiment, histological observation showed more mature bone formed in the DBM putty group than that in the type I collagen group at 12 weeks, which indicated the bone putty prepared by DBM gel exhibited a better bone repair capability.

This study aims to investigate the repair of bone defects with prefabricated vascularized bone grafts and double-labeled bone marrow-derived mesenchymal stem cells (BMSCs) in a rat model. BMSCs were separated from rat bone marrow. LTR-CMVpro-RFP and LTR-CMVpro-GFP were transfected into the BMSCs for in vitro and in vivo tracking. BMSCs-RFP and BMSCs-GFP were induced into endothelial progenitor cells (EPCs) and osteoblasts (OBs). Rats were divided into five groups: Group A: in vitro prefabrication with EPCs-RFP + in vivo prefabrication with arteriovenous vascular bundle + secondary OBs-GFP implantation; Group B: in vitro prefabrication with EPCs-RFP + secondary OBs-GFP implantation; Group C: in vivo prefabrication with arteriovenous vascular bundle + secondary OBs-GFP implantation; Group D: implantation of EPCs-RFP + implantation of with arteriovenous vascular bundle + simultaneous OBs-GFP implantation; Group E: demineralized bone matrix (DBM) grafts (blank control). Among five groups, Group A had the fastest bone regeneration and repair, and the regenerated bone highly resembled normal bone tissues; Group D also had fast bone repair, but the repair was slightly slower than Group A. Therefore, in vitro prefabrication with EPCs-RFP plus in vivo prefabrication with arteriovenous vascular bundle and secondary OBs-GFP implantation could be the best treatment for bone defect.

Graphs are becoming increasingly dominant in modeling real-life networked data including social and biological networks, the WWW and the Semantic Web, etc. Graph pattern queries are useful for gathering information with expressive semantics from these graph-structured data. Current methods for graph pattern query processing have performance deficiency caused by inefficiencies of the underlying reachability index and costly merge-join operations on huge amounts of tuple-formatted intermediate results. To overcome the above problems, this paper contributes in the following aspects to boost graph pattern query evaluation. First, we propose an improved hop-based reachability indexing scheme 3-Hop* which gains faster reachability query evaluation, less indexing costs and better scalabilities than state-of-the-art hop-based methods. Second, we propose a two-stage node filtering algorithm based on 3-Hop* to answer tree pattern queries more efficiently. Tree pattern queries serve as the underlying facility for graph pattern query evaluation. Furthermore, we use a graph representation of the intermediate results during node filtering and final results enumeration. Experiments on real-life and synthetic datasets demonstrate the effectiveness of the proposed methods.

Main path analysis is a popular method for extracting the backbone of scientific evolution from a (paper) citation network. The first and core step of main path analysis, called search path counting, is to weight citation arcs by the number of scientific influence paths from old to new papers. Search path counting shows high potential in scientific impact evaluation due to its semantic similarity to the meaning of scientific impact indicator, i.e. how many papers are influenced to what extent. In addition, the algorithmic idea of search path counting also resembles many known indirect citation impact indicators. Inspired by the above observations, this paper presents the FSPC (Forward Search Path Count) framework as an alternative scientific impact indicator based on indirect citations. Two critical assumptions are made to ensure the effectiveness of FSPC. First, knowledge decay is introduced to weight scientific influence paths in decreasing order of length. Second, path capping is introduced to mimic human literature search and citing behavior. By experiments on two well-studied datasets against two carefully created gold standard sets of papers, we have demonstrated that FSPC is able to achieve surprisingly good performance in not only recognizing high-impact papers but also identifying undercited papers.

Baicalein has been used for many years as a popular antiviral and antibacterial in China. Recent investigations revealed that baicalein also has anti-inflammatory activities. Our results indicated that baicalein increases ERE-luciferase activity in an estrogen receptor (ER)-dependent manner when either ERα or ERβ were coexpressed in Hela cells. This study examined whether baicalein exerts an anti-inflammatory effect in RAW264.7 cells through an estrogen receptor-dependent pathway and through regulation of NF-ĸB activation. In lipopolysaccharide (LPS)-induced RAW264.7 cells, baicalein exerts anti-inflammatory effects by inhibiting iNOS, COX-2, and TNF-α mRNA expression; NO production; as well as inflammatory cytokine (IL-1β, PGE2, and TNF-α) production through an ER-dependent pathway. These effects are accompanied with the inhibition of the transcription factor NF-ĸB activation and IκBα phosphorylation. We therefore conclude that baicalein inhibits LPS-induced inflammatory cytokine production via regulation of the NF-ĸB pathway and estrogen-like activity, suggesting that it may be useful for preventing inflammation-related diseases.

Scientific importance ranking has long been an important research topic in scientometrics. Many indices based on citation counts have been proposed. In recent years, several graph-based ranking algorithms have been studied and claimed to be reasonable and effective. However, most current researches fall short of a concrete view of what these graph-based ranking algorithms bring to bibliometric analysis. In this paper, we make a comparative study of state-of-the-art graph-based algorithms using the APS (American Physical Society) dataset. We focus on ranking researchers. Some interesting findings are made. Firstly, simple citation-based indices like citation count can return surprisingly better results than many cutting-edge graph-based ranking algorithms. Secondly, how we define researcher importance may have tremendous impacts on ranking performance. Thirdly, some ranking methods which at the first glance are totally different have high rank correlations. Finally, the data of which time period are chosen for ranking greatly influence ranking performance but still remains open for further study. We also try to give explanations to a large part of the above findings. The results of this study open a third eye on the current research status of bibliometric analysis.

SL4, a chalcone-based compound, has been shown to retard tumor invasion and angiogenesis by suppressing HIF1 activity and to induce apoptosis by promoting ROS release. Here, we report that SL4 is able to inhibit the proliferation of different types of breast cancer cell in vitro and in vivo by inducing G2/M cell cycle arrest. Our results showed that SL4 exhibited strong anti-proliferative activity in several human breast cancer cell lines, with IC50 values lower than 1.3 μM. Further studies indicated that SL4 induced G2/M arrest in these cell lines. Mechanistically, SL4 reduces the expression of cyclin A2 and cdc25C and decreases the activity of the cdc2/cyclin B1 complex. Notably, SL4 treatment resulted in an obvious increase in p21 mRNA and protein levels through activation of MAPK signaling pathways, but not the TGF-β pathway. SP600125 and PD98059, specific inhibitors of JNK kinase and ERK kinase, significantly blocked the SL4-induced G2/M phase arrest and upregulation of p21. Furthermore, SL4 suppressed the growth of established breast tumors in nude mice through upregulation of p21 and downregulation of cdc25C, and displayed a good safety profile. Taken together, these findings demonstrate the potential value of SL4 as a novel multi-target anti-tumor drug candidate.

Scientific ranking has long been a hot and important topic in both computer science and scientometrics. A lot of statistics-based and graph-based methods have been proposed for calculating a prestige value as the assessment of each paper's scientific influence. However, being ignorant of the dynamic nature of scientific publication and science evolution, all these methods present a biased point of view of scientific influence. Besides, the ranking results of these methods are not accessible to users because of lack of an explainable model. As an alternative to the state-of-the-art, this paper proposes a cognitively explainable model by integrating three factors in scientific development including knowledge accumulation by individual papers, knowledge diffusion through citation behaviour and knowledge decay with time elapse. Evaluated on ACL Anthology Network using the reference lists of four textbooks or handbooks as the gold standard, the proposed model is proved to be effective in scientific ranking and potential for new insights into the definition and measurement of scientific influence.

Hypoxia-inducible factor-1 (HIF-1) plays an essential role in carcinogenesis. The overexpression of HIF-1 induced by hypoxia is closely associated with metastasis, poor prognosis and high mortality. In this study, a novel HIF-1 inhibitor SYP-5 was first observed by the luciferase reporter assay. Western blots results showed SYP-5 inhibited hypoxia-induced upregulation of HIF-1. Moreover, the proteins of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP)-2 that are targets of HIF-1, were down-regulated by SYP-5. Furthermore, in the tube formation assay, SYP-5 suppressed angiogenesis induced by hypoxia and VEGF in vitro. Additionally, using Transwell and RTCA assays, we found that SYP-5 also retarded the Hep3B and Bcap37 cells migration and invasion induced by hypoxia and FBS. Last, we also detected the upstream pathways related to HIF-1 and found both PI3K/AKT and MAPK/ERK were involved in the SYP-5 mediated invasive inhibition of Bcap37 cells. These results indicates that SYP-5 inhibits tumor cell migration and invasion, as well as tumor angiogenesis, which are mediated by suppressing PI3K/AKT- and MAPK/ERK-dependent HIF-1 pathway. It suggests that SYP-5 might be a potential HIF-1 inhibitor as an anticancer agent.

Host genetic, environmental and viral factors are classified as three categories that determine clinical outcomes of hepatitis B virus (HBV) infection. The objective of this study was to detect the associations between polymorphisms rs346473 and rs346482 in Rho GTPase-activating protein 24 (ARHGAP24) gene and disease progression of HBV infection in Han Chinese population. These two SNPs were found by our DNA pooling using Affymetrix Genome-Wide Human Mapping SNP6.0 Array in HBV carriers, and verified by using TaqMan 7900HT Sequence Detection System with 758 progressed HBV carriers versus 300 asymptomatic HBV carriers (AsC) in a discovery phase and 971 progressed HBV carriers versus 328 AsC in a replication phase. Multivariable logistic regression revealed that individuals with genotype TT at variant rs346473 displayed remarkable correlations with disease progression of HBV infection both in the discovery phase (OR, 2.693; 95% CI, 1.928-3.760; P=6.2×10(-9); additive model) and the replication phase (OR, 1.490; 95% CI, 1.104-2.012; P=9.0×10(-3); additive model). These two SNPs were in strong linkage disequilibrium with D'=0.99 and r (2)=0.951, and haplotype TT disclosed an increased susceptibility to HBV progression (OR, 1.980; 95% CI, 1.538-2.545; P=8.1×10(-8)). These findings suggest that polymorphism rs346473 in the ARHGAP24 gene might be a part of the genetic variants underlying the susceptibility of HBV carriers to disease progression.

Inflammation is a physiological response to infection or injury and involves the innate and adaptive immune system. Tanshinone IIA (Tan IIA) is a well-known flavonoid that elicits an important therapeutic effect by inhibiting inflammatory response. In this study, we examined whether Tan IIA exerts anti-inflammatory activity and investigated the possible mechanisms, including Toll-like receptor 4 (TLR4)-MyD88-nuclear factor kappa B (NF-κB) signaling pathway and microRNA expression in lipopolysaccharide (LPS)-induced RAW264.7 cells. Tan IIA could attenuate the inflammatory reaction via decreasing cytokine, chemokine, and acute-phase protein production, including GM-CSF, sICAM-1, cxcl-1, MIP-1α, and tumor necrosis factor alpha (TNF-α), analyzed by Proteome profile array in LPS-induced RAW264.7 cells. Concurrently, the messenger RNA (mRNA) expressions of IL-1β, TNF-α, and COX-2 were also significantly reduced by Tan IIA. Additionally, Tan IIA decreased LPS-induced NF-κB activation and downregulated TLR4 and MyD88 protein expression levels. We also observed reduced microRNA-155, miR-147, miR-184, miR-29b, and miR-34c expression levels, while LPS-induced microRNA-105, miR-145a, miR-194, miR-383, miR-132, and miR-451a expression levels were upregulated using microRNA (miRNA) qPCR array. Our results indicate that Tan IIA could exert an anti-inflammatory effect on LPS-induced RAW264.7 cells by decreasing TLR4-MyD88-NF-κB signaling pathway and regulating a series of cytokine production and miRNA expression.

Chemotherapy paclitaxel yields significant reductions in tumor burden in the majority of advanced non-small cell lung cancer (NSCLC) patients. However, acquired resistance limits its clinical use. Here we demonstrated that the histone deacetylase (HDAC) was activated in paclitaxel-resistant NSCLC cells, and its activation promoted proliferation and tumorigenesis of paclitaxel-resistant NSCLC cells in vitro and in vivo. By contrast, knockdown of HDAC1, a primary isoform of HDAC, sensitized resistant cells to paclitaxel in vitro. Furthermore, we observed that overexpression of HDAC1 was associated with the downregulation of p21, a known HDAC target, in advanced NSCLC patients with paclitaxel treatment, and predicted chemotherapy resistance and bad outcome. In addition, we also identified a novel HDACs inhibitor, SNOH-3, which inhibited HDAC expression and activity, induced cell apoptosis, and suppressed cell migration, invasion and angiogenesis. Notably, co-treatment with SNOH-3 and paclitaxel overcome paclitaxel resistance through inhibiting HDAC activity, leading to the induction of apoptosis and suppression of angiogenesis in vitro and in preclinical model. In summary, our data demonstrate a role of HDAC in paclitaxel-resistant NSCLC and provide a promising therapeutic strategy to overcome paclitaxel-acquired resistance.

Artificial Intelligence development is stepping into a new era due to the recent exciting achievements from neural network and statistical machine learning research communities. Statistic neural-computing based machine learning has been deemed as one of promising roads towards realizing the ideal of Artificial Intelligence promoted since last century. Learning is the key in making progress. Statistic machine learning is to obtain a probability distribution or a function from a set of training samples according to a certain optimization target over the training cost based on a predefined model. While there are many significant improvements in image, sound and text recognition and analyzing using neural network based learning strategies, a new open question emerges, that is, what is the next? To ask this question is to mean that the neural network solution is not an ultimate solution, and there will be more challenges to meet in coming future. We discussed these aspects of deep neural network research work in this paper and focused on semantics in deep neural-network computing models. We try to browse how semantics or knowledge are to be involved in deep neural network models and how the semantics and knowledge will be a key factor towards making more intelligent machines. We argue that priori semantics and knowledge in modelling a neural network is important, which could be the key for researchers to design intelligent machine models to perform complex tasks.

Due to the explosion of scientific literature, the need for an efficient scientific ranking algorithm has become more important than ever before to assess the importance of scientific articles. The state-of-the-art graph-based algorithms employ the structure of the heterogeneous academic network by mapping the multidimensional relationships between papers, authors and venues into a set of binary relationships. To avoid information loss, this paper proposes a novel mutual ranking algorithm HOMR based on a tensor-based representation of the ternary relationships between academic entities. HOMR is demonstrated effective for ranking scientific publications compared to PageRank, HITS, CoRank and P-Rank by experiments performed on the dataset and gold standard built on the ACL Anthology Network.

Spinal cord injury (SCI) refers to the damage of spinal cord’s structure and function due to a variety of causes. At present, many scholars have confirmed that apoptosis is the main method of secondary injury in spinal cord injury. In view of understanding the function of PI3K/Akt pathway on spinal cord injury, this study observed the temporal variation of key molecules (PI3K, Akt, p-Akt) in the PI3K/Akt pathway after spinal cord injury by immunohistochemistry and Western-blot. The results showed that the expression of PI3K, Akt and p-Akt display a sharp increase one day after the spinal cord injury, and then it decreased gradually with the time passing by, but the absolute expression was certainly higher than the normal group. These results indicate that the PI3K/Akt signaling pathway is involved in the spinal cord injury and the mechanism may be related to apoptosis.

Objectives SL4, a chalcone-based compound, exhibits clearly inhibitory effects on HIF-1 and has been shown to effectively suppress tumour invasion and angiogenesis in vitro and in vivo. Here, studies were conducted to determine SL4's anti-apoptotic effects and its underlying mechanisms, in human cancer cells. Materials and methods Cytotoxicity, apoptotic induction and its involved mechanisms of SL4 were investigated using normal cells, cancer cells and mouse xenograft models. The role of reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) signalling in SL4-induced apoptosis was explored by manipulating specific scavenger or signalling inhibitors, in cultured cells. Results SL4 significantly inhibited cell population growth of human cancer cell lines but exhibited lower cytotoxicity against normal cells. In addition, SL4 effectively induced apoptosis of Hep3B and MDA-MB-435 cells by activating procaspase-8, -9 and -3, and down-regulating expression levels of XIAP, but did not affect HIF-1 apoptosis-related targets, Survivin and Bcl-XL. Further study showed that SL4 also reduced mitochondrial membrane potential and promoted generation of ROS. ROS generation and apoptotic induction by SL4 were blocked by NAC, a scavenger of ROS, suggesting SL4-induced apoptosis via ROS accumulation. We also found that MAPKs, JNK and p38, but not ERK1/2, to be critical mediators in SL4-induced apoptosis. SP600125 and SB203580, specific inhibitors of JNK kinase and p38 kinase, significantly retarded apoptosis induced by SL4. Moreover, anti-oxidant NAC blocked activation of JNK and p38 induced by SL4, indicating that ROS may act as upstream signalling of JNK and p38 activation. It is noteworthy that animal studies revealed dramatic reduction (49%) in tumour volume after 11 days SL4 treatment. Conclusions These data demonstrate that SL4 induced apoptosis in human cancer cells through activation of the ROS/MAPK signalling pathway, suggesting that it may be a novel lead compound, as a cancer drug candidate, with polypharmacological characteristics.

Analogous layered double hydroxides (LDHs) with the Cu 2+ /Ni 2+ /Cr 3+ molar ratio of 1/2/1 on the brucite-like layers and interlayer anions (viz sulfate, nitrate and carbonate, respectively) were synthesized by a coprecipitation method. For the first time, the effects of interlayer anions on the structural properties of as-synthesized LDHs and resulting calcined products at 773 K were investigated by means of powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), simultaneous thermogravimetric and differential thermal analysis (TG-DTA), X-ray photoelectron spectroscopy (XPS) and temperature programmed reduction (TPR). The results indicate that the nature of interlayer anions involved within the hydrotalcite (HT)-like structure has a larger influence on the thermal stability of LDHs precursors. Calcination of well-crystallized LDHs leads to the formation of mixed metal oxides including CuO, NiO and Cu 2+ -, Ni 2+ - and Cr 3+ -containing spinel phases, the composition distributions of which obtained from LDHs precursors depend on the nature of interlayer anions, thus resulting in the difference of the reducibility of reducible metal species in the calcined LDHs. Moreover, the surface basicity of the calcined material, which is related to the different behaviour of LDHs precursors during the thermal decomposition depending on the interlayer anions, increases progressively following the order of calcined LDHs from sulfate to nitrate and carbonate.

This paper presents the synthesis of mesoporous materials from hydrotalcite-like layered double hydroxides (LDHs) with the Mg2 +/(Al3 + + In3 +) molar ratio of 3.0 on the brucite-like lattice and the interlayer carbonate anions, using a novel separate nucleation and aging steps method developed in our laboratory. The physicochemical properties of as-synthesized LDHs and resulting calcined products at 500∘C were investigated by powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), simultaneous thermogravimetric and differential thermal analysis (TG-DTA), 27Al nuclear magnetic resonance (NMR) and low-temperature nitrogen adsorption-desorption experiments. The results indicate calcination of LDHs with a well-crystallized single phase and nanoscale crystallites leads to the formation of the type MgO-like phase, and the pore size distributions of uncalcined and calcined LDHs are mostly in the range of mesopores. Furthermore, calcined materials have higher surface areas, pore volumes, pore diameters and surface basicities than corresponding precursors. When used as solid base catalysts for the Knoevenagel condensation of ethyl cyanoacetate with benzaldehyde, the material with higher density of base sites on the surface also exhibited a higher catalytic activity. Particularly, calcined MgAlIn-LDH has highest density of base sites resulting in a highest catalytic activity, as points to an important role of indium as a modifier of the surface properties of solid base catalysts.

To study the effect of Schwann cells (SCs) promoting the function of nitric oxide (NO) secretion of bone marrow mesenchymal stem cells (BMSCs) derived endothelial cells so as to lay the experimental foundation for research of the effect of nerves on vessels during the process of tissue engineering bone formation.SCs were collected from 1-day-old Sprague Dawley (SD) rats, and identified through S100 immunohistochemistry (IHC). BMSCs were collected from 2-week-old SD rats and induced into endothelial cells (IECs), which were identified through von Willebrand factor (vWF) and CD31 immunofluorescence (IF). Transwell system was used for co-culture of SCs and IECs without contact as the experimental group, and simple culture of IECs served as the control group. The NO concentration in the medium was measured at 1, 3, 5, and 7 days after culture; the mRNA expressions of nitric oxide synthetase 2 (NOS2) and NOS3 were detected by real-time fluorescence quantitative PCR (RT -qPCR) at 1, 3, 7, and 10 days.SCs and IECs were identified through morphology and immunology indexes of S100 IHC, vWF and CD31 IF. Significant differences were found in the NO concentration among different time points in 2 groups (P0.05); the NO concentration of the experimental group was significantly higher than that of the control group at the other time points (P0.05) except at 3 days. NOS2 mRNA expression of the experimental group was significantly higher than that of the control group (P0.05); difference was significant in the NOS2 mRNA expression among different time points in 2 groups (P0.05). NOS3 mRNA expression of the experimental group was significantly higher than that of the control group at the other time points (P0.05) except at 10 days. No significant difference was found in NOS3 mRNA expression among different time points in the experimental group (F = 6.673, P = 0.062), but it showed significant differences in the control group (F = 36.581, P = 0.000).SCs can promote NO secretion of BMSCs derived endothelial cells, which is due to promoting the activity of NOS.

A reachability query is to ask whether there exists a path between two nodes in a directed graph. To build a compact index for efficiently handling reachability queries, most existing approaches label the nodes of a small induced subgraph as the base index to cover a portion of transitive information and then either explicitly store or encode the remaining transitive information into a complementary index. Although hop-based methods have the most compact index size, they inevitably suffer from big index construction costs in terms of long indexing time and huge memory consumption. This paper proposes a new hop-based indexing scheme 3-Hop that greatly reduces index construction costs than state-of-the-art hop-based indices. 3-Hop first extracts a planar induces subgraph which consists of a spanning tree and the set of short non-tree edges to label graph nodes for covering more reachability information in the base index as well as providing more hop choices for building the complementary index. Then, an efficient labeling algorithm is proposed for encoding the remaining transitive information with a smaller index size based on the up-per-bound density heuristic and early-stop hop selection strategy. Extensive experiments over real and synthetic datasets show that 3-Hop* is the most efficient and effective hop-based reachability indexing method scalable for large sparse graphs.

Background Study on viruses has greatly benefited from visualization of viruses tagged with green fluorescent protein (GFP) in living cells. But GFP tag, as a large inserted fragment, is not suitable for labelling Hepatitis B virus (HBV) that is a compact virion with limited internal space. Aim To visualize HBV in living cells, we constructed several recombinant HBV fluorescently labelled with biarsenical dye to track the behaviour of HBV in the cytoplasm of infected cells. Methods By mutagenesis, a smaller size tetracysteine (TC) tag (C-C-P-G-C-C) that could be bound with a biarsenical fluorescent dye was genetically inserted at different cell epitopes of HBV core protein expressed in transfected cells. Result Confocal microscopy and transmission electron microscopy (TEM) observations showed that TC-tagged core proteins bound with biarsenical dye could specifically fluoresce in cells and be incorporated into nucleocapsid to form fluorescent virions. The recombinant fluorescent HBV virions retained their infectivity as wild-type ones. Moreover, tracking of fluorescent HBV particles in living cells reveals microtubule-dependent motility of the intracellular particles. Conclusion To the best of our knowledge, this is the first time to generate fluorescent HBV virions with biarsenical labelling and to visualize their trafficking in living cells. The fluorescent HBV may become one highly valuable tool for further studying detailed dynamic processes of HBV life cycle and interaction of HBV with host in live-imaging approach.

It is important to help researchers find valuable scientific papers from a large literature collection containing information of authors, papers and venues. Graph-based algorithms have been proposed to rank papers based on networks formed by citation and co-author relationships. This paper proposes a new graph-based ranking framework MutualRank that integrates mutual reinforcement relationships among networks of papers, researchers and venues to achieve a more synthetic, accurate and fair ranking result than previous graph-based methods. MutualRank leverages the network structure information among papers, authors, and their venues available from a literature collection dataset and sets up a unified mutual reinforcement model that involves both intra- and inter-network information for ranking papers, authors and venues simultaneously. To evaluate, we collect a set of recommended papers from websites of graduate-level computational linguistics courses of 15 top universities as the benchmark and apply different methods to estimate paper importance. The results show that MutualRank greatly outperforms the competitors including Pag-eRank, HITS and CoRank in ranking papers as well as researchers. The experimental results also demonstrate that venues ranked by MutualRank are reasonable.

With tremendous research progress in biomedical sensors and sensor networks, there is an increasingly need for employing new data processing technologies that are capable of online analysis of the streaming medical sensor data, which is a typical health monitoring scenario. This paper describes using the data stream management system (DSMS) in developing ubiquitous health monitoring application. We propose the system architecture suitable for simultaneously processing streaming data from heterogeneous sources and performing different monitoring tasks planned by clinicians. A pilot heart rate variability (HRV) monitor with a graphical user interface is developed based on Borealis and several tasks are implemented, including monitoring Rmssd, MeanHR (mean heart rate), and pNN50. Results of the test runs in the lab environment show the usefulness and potential of DSMS in performing intelligent realtime medical data processing.

BackgroundHuman leukocyte antigen DP (HLA-DP) locus has been reported to be associated with hepatitis B virus (HBV) infection in populations of Japan and Thailand. We aimed to examine whether the association can be replicated in Han Chinese populations.Methodology/principal findingsTwo HLA-DP variants rs2395309 and rs9277535 (the most strongly associated SNPs from each HLA-DP locus) were genotyped in three independent Han cohorts consisting of 2 805 cases and 1 796 controls. By using logistic regression analysis, these two SNPs in the HLA-DPA1 and HLA-DPB1 genes were significantly associated with HBV infection in Han Chinese populations (P = 0.021∼3.36×10(-8) at rs2395309; P = 8.37×10(-3)∼2.68×10(-10) at rs9277535). In addition, the genotype distributions of both sites (rs2395309 and rs9277535) were clearly different between southern and northern Chinese population (P = 8.95×10(-5) at rs2395309; P = 1.64×10(-9) at rs9277535). By using asymptomatic HBV carrier as control group, our study showed that there were no associations of two HLA-DP variants with HBV progression (P = 0.305∼0.822 and 0.163∼0.881 in southern Chinese population, respectively; P = 0.097∼0.697 and 0.198∼0.615 in northern Chinese population, respectively).ConclusionsOur results confirmed that two SNPs (rs2395309 and rs9277535) in the HLA-DP loci were strongly associated with HBV infection in southern and northern Han Chinese populations, but not with HBV progression.

To study the feasibility of preparation of the poly-D, L-lactide acid (PDLLA) scaffolds treated by ammonia plasma and subsequent conjugation of Gly-Arg-Gly-Asp-Ser (GRGDS) peptides via amide linkage formation.PDLLA scaffolds (8 mm diameter, 1 mm thickness) were prepared by solvent casting/particulate leaching procedure and then treated by ammonia plasma. The consequent scaffolds were labeled as aminated PDLLA (A/PDLLA). The pore size, porosity, and surface water contact angle of groups 0 (un-treated control), 5, 10, and 20 minutes A/PDLLA were measured. A/PDLLA scaffolds in groups above were immersed into the FITC labelled GRGDS aqueous solution which contain 1-[3-(dimethylamino) propyl]-3-ethylcarbodiimide hydrochloride (EDC-HCl) and N-hydroxysuccinimide (NHS), the molar ratio of peptides/EDC*HCL/NHS was 1.5 : 1.5 : 1.0, then brachytely slashed for 24 hours in room temperature. The consequent scaffolds were labelled as peptides conjugated A/PDLLA (PA/PDLLA). The scaffolds in groups 0, 5, 10, and 20 minutes A/PDLLA and groups correspondingly conjugation of peptides were detected using X-ray photoelectron spectroscopy (XPS). The scaffolds in groups of conjugation of peptides were measured by confocal laser scanning microscope and high performance liquid chromatography (HPLC), un-treated and un-conjugated scaffolds employed as control. Bone marrow mesenchymal stem cells (BMSCs) from SD rats were isolated and cultured by whole bone marrow adherent culture method. BMSCs at the 3rd-6th passages were seeded to the scaffolds as follows: 20 minutes ammonia plasma treatment (group A/PDLLA), 20 minutes ammonia plasma treatment and conjugation of GRGDS (group PA/PDLLA), and untreated PDLLA control (group PDLLA). After 16 hours of culture, the adhesive cells on scaffolds and the adhesive rate were calculated. After 4 and 8 days of culture, the BMSCs/scaffold composites was observed by scanning electron microscope (SEM).No significant difference in pore size and porosity of PDLLA were observed between before and after ammonia plasma treatments (P0.05). With increased time of ammonia plasma treatment, the water contact angle of A/PDLLA scaffolds surface was decreased, and the hydrophilicity in the treated scaffolds was improved gradually, showing significant differences when these groups were compared with each other (P0.001). XPS results indicated that element nitrogen appeared on the surface of PDLLA treated by ammonia plasma. With time passing, the peak N1s became more visible, and the ratio of N/C increased more obviously. After PDLLA scaffolds treated for 0, 5, 10, and 20 minutes with ammonia plasma and subsequent conjugation of peptides, the ratio of N/C increased and the peak of S2p appeared on the surface. The confocal laser scanning microscope observation showed that the fluorescence intensity of PA/PDLLA scaffolds increased obviously with treatment time. The amount of peptides conjugated for 10 minutes and 20 minutes PA/PDLLA was detected by HPLC successfully, showing significant differences between 10 minutes and 20 minutes groups (P0.001). However, the amount of peptides conjugated in un-treated control and 0, 5 minutes PA/PDLLA scaffolds was too small to detect. After 16 hours co-culture of BMSCs/scaffolds, the adhesive cells and the adhesive rates of A/PDLLA and PA/PDLLA scaffolds were higher than those of PDLLA scaffolds, showing significant difference between every 2 groups (P0.01). Also, SEM observation confirmed that BMSCs proliferation in A/PDLLA and PA/PDLLA groups was more detectable than that in PDLLA group, especially in PA/PDLLA group.Ammonia plasma treatment will significantly increase the amount of FITC-GRGDS peptides conjugated to surface of PDLLA via amide linkage formation. This new type of biomimetic bone has stabilized bioactivities and has proved to promote the adhesion and proliferation of BMSCs in PDLLA.

As data are increasingly modeled as graphs for expressing complex relationships, the tree pattern query on graph-structured data becomes an important type of queries in real-world applications. Most practical query languages, such as XQuery and SPARQL, support logical expressions using logical-AND/OR/NOT operators to define structural constraints of tree patterns. In this paper, (1) we propose generalized tree pattern queries (GTPQs) over graph-structured data, which fully support propositional logic of structural constraints. (2) We make a thorough study of fundamental problems including satisfiability, containment and minimization, and analyze the computational complexity and the decision procedures of these problems. (3) We propose a compact graph representation of intermediate results and a pruning approach to reduce the size of intermediate results and the number of join operations -- two factors that often impair the efficiency of traditional algorithms for evaluating tree pattern queries. (4) We present an efficient algorithm for evaluating GTPQs using 3-hop as the underlying reachability index. (5) Experiments on both real-life and synthetic data sets demonstrate the effectiveness and efficiency of our algorithm, from several times to orders of magnitude faster than state-of-the-art algorithms in terms of evaluation time, even for traditional tree pattern queries with only conjunctive operations., Comment: 16 pages

Data space is a semi-structural data model for the management of large-scale heterogeneous data objects. In a data space, each data object consists of a set of attribute-value pairs to describe the internal properties of the object and their relationships to other objects. The data space model provides a flexible query language that supports attribute queries and semantic link queries. In this paper we introduce a Resource Space Model that extends the concepts of data space to make it more flexible by incorporating classification semantics. We model a data space as a set of Resource Spaces (RS) with each RS representing a kind of resources that share common attributes and can be put into the same category, either according to a user’s knowledge of the world or his query preferences. Our model is suitable for designing a user-tailored semantic view of a data space while at the same time without losing the schema-later data-centric nature. A practical query language is introduced to implement flexible query operations on the resource spaces of the data space. Examples show how the proposed model and language support both the schema query and the data query.

In traditional Chinese pulse diagnosis (TCPD), diseases of internal organs can be detected by recognizing pulse waveform patterns of wrist radial arterial. However pulse waveform analysis, for which Doppler diagnosis is a powerful tool, is limited to cardiovascular diseases. This paper tries to fill the gap between TCPD and Doppler diagnosis by applying signal analysis and pattern recognition technologies to Doppler blood flow signals (DBFS's) of wrist radial arterial, which are recorded from both hands of healthy people, gastritis and cholecystitis patients. DBFS's are classified using the features proposed by an L2-soft margin support vector machine (L2-SVM): five clinical Doppler parameters (DP), wavelet energies (WE), wavelet packet energies (WPE), and piecewise axially integrated bispectra (PAIB). 5-fold cross validation is used for performance evaluation. The sick are differentiated from the healthy with an accuracy of about 80% using DP, WE and WPE, while the classification rate between gastritis and cholecystitis reaches 100%. Using PAIB, ether two groups of subjects are classified with accuracy greater than 93%. Gastritis is more accurately recognized than cholecystitis, while the latter is recognized with a higher accuracy on data from the left hand than right. Though the sample size is relatively small, we still argue that the methods proposed here are effective and could serve as an assisstive tool for TCPD.

This paper tries to fill the gap between Traditional Chinese Pulse Diagnosis (TCPD) and Doppler diagnosis by applying digital signal analysis and pattern classification techniques to wrist radial arterial Doppler blood flow signals. Doppler blood flows signals (DBFS) of patients with cholecystitis, gastritis and healthy people are classified by L2-soft margin SVM and 5 linear classifiers using the proposed feature - piecewise axially integrated bispectra (PAIB). A 5-fold cross validation is used for performance evaluation. The classification accuracies between either two groups of subjects are greater than 93%. Gastritis can be recognized with higher accuracy than cholecystitis. Cholecystitis can be recognized with higher accuracy on left hand data than right. The findings in this paper partly conform to the theory of TCPD. Though the sample size is relatively small, we could still argue that the methods proposed here are effective and could serve as an assistive tool for TCPD.

OBJECTIVE To explore the cytotoxicity, labeled time, marking rate, and effect on adhesion of quantum dot 655 (QD655) labeled rat bone marrow mesenchymal stem cells (BMSCs) in vitro, and to confirm its feasibility for stem cell labeling and tracer means for rat.BMSCs were collected from the femur and tibia bone marrow cavity of a 2-week-old SD rat, cultured and identified. The 3rd passage of BMSCs were incubated with QD655 as the experimental group according to the recommended concentration of the markers. The cells were not labeled by QD655 as control group. The cell survival rate after QD655 labeling was detected by trypan-blue exclusion. The effect of QD655 on cell proliferation was observed by MTT. The osteogenic differentiation potential was identified by Alizarin red staining, alkaline phosphatase (ALP) staining, and real-time fluorogenic quantitative PCR. At immediately, 1, 2, 4, and 6 weeks, fluorescent microscopy was used to observe the labeled rate and scanning electron microscope was used to observe the cell adhesion to scaffold (bioglass/collagen composite).The cell survival rates were more than 90% in both experimental group and control group, showing no significant difference (P0.05). There was no significant difference in the cell proliferation between 2 groups (P0.05). Alizarin red staining and ALP staining showed positive results. Real-time fluorogenic quantitative PCR result showed that the mRNA expression levels of osteopontin, osteocalcin, collagen type I, ALP, and BMP-2 in the experimental group was significantly higher than those in the control group. The labeled rates were 96.50% +/- 1.59%, 93.30% +/- 1.51%, 72.40% +/- 2.90%, 40.10% + 3.60%, and 10.00% +/- 1.70% immediately, 1, 2, 4, and 6 weeks after labeling, respectively. The labeled rate in the control group was 0. Scanning electron microscope showed a good distribution of fusiform or polygonal cells in the pores of scaffold.QD655 can be used as a labeling marker for BMSCs. Rat BMSCs labeled with QD655 is of high efficiency and safety.

Ranking is an important way of retrieving authoritative papers from a large scientific literature database. Current state-of-the-art exploits the flat structure of the heterogeneous academic network to achieve a better ranking of scientific articles, however, ignores the multinomial nature of the multidimensional relationships between different types of academic entities. This paper proposes a novel mutual ranking algorithm based on the multinomial heterogeneous academic hypernetwork, which serves as a generalized model of a scientific literature database. The proposed algorithm is demonstrated effective through extensive evaluation against well-known IR metrics on a well-established benchmarking environment based on the ACL Anthology Network.