62 research outputs found

    Learning a Complete Image Indexing Pipeline

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    To work at scale, a complete image indexing system comprises two components: An inverted file index to restrict the actual search to only a subset that should contain most of the items relevant to the query; An approximate distance computation mechanism to rapidly scan these lists. While supervised deep learning has recently enabled improvements to the latter, the former continues to be based on unsupervised clustering in the literature. In this work, we propose a first system that learns both components within a unifying neural framework of structured binary encoding

    Phenylhexyl isothiocyanate has dual function as histone deacetylase inhibitor and hypomethylating agent and can inhibit myeloma cell growth by targeting critical pathways

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    Histone deacetylase (HDAC) inhibitors are a new class of chemotherapeutic agents. Our laboratory has recently reported that phenylhexyl isothiocyanate (PHI), a synthetic isothiocyanate, is an inhibitor of HDAC. In this study we examined whether PHI is a hypomethylating agent and its effects on myeloma cells. RPMI8226, a myeloma cell line, was treated with PHI. PHI inhibited the proliferation of the myeloma cells and induced apoptosis in a concentration as low as 0.5 ÎĽM. Cell proliferation was reduced to 50% of control with PHI concentration of 0.5 ÎĽM. Cell cycle analysis revealed that PHI caused G1-phase arrest of RPMI8226 cells. PHI induced p16 hypomethylation in a concentration- dependent manner. PHI was further shown to induce histone H3 hyperacetylation in a concentration-dependent manner. It was also demonstrated that PHI inhibited IL-6 receptor expression and VEGF production in the RPMI8226 cells, and reactivated p21 expression. It was found that PHI induced apoptosis through disruption of mitochondrial membrane potential. For the first time we show that PHI can induce both p16 hypomethylation and histone H3 hyperacetylation. We conclude that PHI has dual epigenetic effects on p16 hypomethylation and histone hyperacetylation in myeloma cells and targets several critical processes of myeloma proliferation

    Increased recruitment of endogenous stem cells and chondrogenic differentiation by a composite scaffold containing bone marrow homing peptide for cartilage regeneration

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    Even small cartilage defects could finally degenerate to osteoarthritis if left untreated, owing to the poor self-healing ability of articular cartilage. Stem cell transplantation has been well implemented as a common approach in cartilage tissue engineering but has technical complexity and safety concerns. The stem cell homing-based technique emerged as an alternative promising therapy for cartilage repair to overcome traditional limitations. In this study, we constructed a composite hydrogel scaffold by combining an oriented acellular cartilage matrix (ACM) with a bone marrow homing peptide (BMHP)-functionalized self-assembling peptide (SAP). We hypothesized that increased recruitment of endogenous stem cells by the composite scaffold could enhance cartilage regeneration. Methods: To test our hypothesis, in vitro proliferation, attachment and chondrogenic differentiation of rabbit mesenchymal stem cells (MSCs) were tested to confirm the bioactivities of the functionalized peptide hydrogel. The composite scaffold was then implanted into full-thickness cartilage defects on rabbit knee joints for cartilage repair, in comparison with microfracture or other sample groups. Stem cell recruitment was monitored by dual labeling with CD29 and CD90 under confocal microcopy at 1 week after implantation, followed by chondrogenic differentiation examined by qRT-PCR. Repaired tissue of the cartilage defects was evaluated by histological and immunohistochemistry staining, microcomputed tomography (micro-CT) and magnetic resonance imaging (MRI) at 3 and 6 months post-surgery. Macroscopic and histological scoring was done to evaluate the optimal in vivo repair outcomes of this composite scaffold. Results: The functionalized SAP hydrogels could stimulate rabbit MSC proliferation, attachment and chondrogenic differentiation during in vitro culture. At 7 days after implantation, increased recruitment of MSCs based on CD29(+)/CD90(+) double-positive cells was found in vivo in the composite hydrogel scaffold, as well as upregulation of cartilage-associated genes (aggrecan, Sox9 and type II collagen). After 3 and 6 months post-surgery, the articular cartilage defect in the composite scaffold-treated group was fully covered with cartilage-like tissue with a smooth surface, which was similar to the surrounding native cartilage, according to the results of histological and immunohistochemistry staining, micro-CT and MRI analysis. Macroscopic and histological scoring confirmed that the quality of cartilage repair was significantly improved with implantation of the composite scaffold at each timepoint, in comparison with microfracture or other sample groups. Conclusion: Our findings demonstrated that the composite scaffold could enhance endogenous stem cell homing and chondrogenic differentiation and significantly improve the therapeutic outcome of chondral defects. The present study provides a promising approach for in vivo cartilage repair without cell transplantation. Optimization of this strategy may offer great potential and benefits for clinical application in the future

    Research on Urban Public Green Space Planning Based on Taxi Data: A Case Study on Three Districts of Shenzhen, China

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    Urban public green space (UPGS) plays an important role in sustainable development. In China, the planning, classification, and management of green spaces are based on the Standard for Classification of Urban Green Space (SCUGS). However, limitations to the UPGS exist due to the over-emphasis on quantitative standards and insufficient consideration of the actual access mode of residents. Though the taxi trajectory data are widely selected to study public service facilities, its adoption in UPGSs research remains limited. Based on the case of UPGSs in the three districts of Shenzhen, we used the taxi (including cruise taxis and Didi cars, which are like Uber) trajectory data to investigate the spatial layout and the allocation of management resource of the UPGSs from the spatial interaction perspective. By rasterizing and visualizing the percentage of pick-up and drop-off points in the UPGSs’ buffer, the service scope of UPGSs was defined, which reflected the spatial distribution and activity intensity of the visitors. Then, an unsupervised classification method was introduced to reclassify the twenty two municipal parks in the three districts. Compared to the traditional planning method, the results show that the service scope of the same type of UPGS in the traditional classification is not the same as the one obtained by the study. Visitors to all UPGSs are distributed as a quadratic function and decay as the distance increases. In addition, the attenuation rates of the same type of UPGSs are similar. The findings of this study are expected to assist planners in improving the spatial layout of UPGSs and optimizing the allocation of UPGS management resources based on new classifications

    The compactness of spatial structure in Chinese cities: measurement, clustering patterns and influencing factors

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    Rapid urbanization in China has led to an excessive urban expansion of built-up areas, which makes quantitative research on compact city important. We adopted density and the degree of mixed land use to measure the compactness of 160 Chinese cities. Spatial autocorrelation analysis was performed to identify spatial clustering patterns, and the relationships between compactness and five variables were explored through regression models. The result shows that in nearly half of the cases, the calculated values of two indices are less than the average. The high or low values of density and the degree of mixed land use tend to be spatially clustered. The hot spot regions of density and the degree of mixed land use lie mainly in the south of China, while the north present as cold spots or the insignificant regions. Urban compactness can be affected by multifaceted factors and the relationships between compactness and five variables are not consistent throughout the areas of analysis. The GWR model can identify this phenomenon and provides a better fit than the OLS model. This study proposed a new approach to measure the compactness, and the results of GWR analysis can conducive to appropriate policy-making based on different local conditions

    Rituximab and new regimens for indolent lymphoma: a brief update from 2012 ASCO Annual Meeting

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    <p>Abstract</p> <p>Indolent lymphoma (IL), the second most common lymphoma, remains incurable with chemotherapy alone. While R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) remains the standard frontline regimen for diffuse Large B –cell lymphoma, the optimal chemotherapy regimen for frontline therapy of advanced IL remains uncertain. FCR (fludarabine, cyclophosphamide, rituximab) has been shown to be better than fludarabine alone and fludarabine plus cyclophosphamide for IL. In FOLL05 trial, R-CHOP was compared with R-CVP (cyclophosphamide, vincristine, prednisone) and R-FM (fludarabine, mitoxantrone). The study showed that R-CHOP appears to have the best risk-benefit ratio for IL. The StiL NHL1 trial showed that BR (bendamustine, rituximab) has longer progression free survival and is better tolerated than R-CHOP. Long-term complications with secondary malignancies between the two regimens appear to be comparable. In this review, new combination regimens reported at 2012 ASCO annual meeting were evaluated for frontline and salvage therapy of indolent lymphoma.</p

    Study on pharmacokinetics and tissue distribution of the isocorydine derivative (AICD) in rats by HPLC-DAD method

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    A simple and effective high-performance liquid chromatography with diode-array detection method coupled with a liquid-liquid extraction pretreatment has been developed for determining the pharmacokinetics and tissue distribution of a novel structurally modified derivative (8-acetamino-isocorydine) of isocorydine. According to the in vivo experiments data calculations by DAS 2.0 software, a two-compartment metabolic model was suitable for describing the pharmacokinetic of 8-acetamino-isocorydine in rats. 8-Acetamino-isocorydine was absorbed well after oral administration, and the absolute bioavailability was 76.5%. The half-life of 8-acetamino-isocorydine after intravenous and oral administration was 2.2 h and 2.0 h, respectively. In vivo, 8-acetamino-isocorydine was highly distributed in the lungs, kidney and liver; however, relatively little entered the brain, suggesting that 8-acetamino-isocorydine could not easily pass through the blood brain barrier. Our work describes the first characterization of the pharmacokinetic parameters and tissue distribution of 8-acetamino-isocorydine. The acquired data will provide useful information for the in vivo pharmacology of 8-acetamino-isocorydine, and can be applied to new drug research
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