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Open AccessArticle A Novel Fluoroimmunoassay for Detecting Ruscogenin with Monoclonal Antibodies Conjugated with CdSe/ZnS Quantum Dots
Molecules 2017, 22(8), 1250; doi:10.3390/molecules22081250
Received: 27 June 2017 / Revised: 20 July 2017 / Accepted: 23 July 2017 / Published: 26 July 2017
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Abstract
Ruscogenin (RUS) is a steroidal sapogenin found in Ruscus aculeatus and Ophiopogon japonicus with several pharmacological activities. In the work reported herein, a novel method termed competitive fluorescence-linked immunosorbent assay (cFLISA) based on monoclonal antibodies (mAbs) coupled with quantum dots (QDs) was developed
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Ruscogenin (RUS) is a steroidal sapogenin found in Ruscus aculeatus and Ophiopogon japonicus with several pharmacological activities. In the work reported herein, a novel method termed competitive fluorescence-linked immunosorbent assay (cFLISA) based on monoclonal antibodies (mAbs) coupled with quantum dots (QDs) was developed for the quick and sensitive determination of RUS in biological samples. The mAbs against RUS were conjugated with CdSe/ZnS QDs by the crossing-linking reagents and an indirect cFLISA method was developed. There was a good linear relationship between inhibition efficiency and logarithm concentration of RUS which was varied from 0.1 to 1000 ng/mL. The IC50 and limit of detection (LOD) were 9.59 ng/mL and 0.016 ng/mL respectively, which much lower than the enzyme-linked immunosorbent assay (ELISA) method. The recoveries in plasma and tissues were ranged from 82.3% to 107.0% and the intra- and inter-day precision values were below 15%. The developed cFLISA has been successfully applied to the measurement of the concentrations of RUS in biological samples of rats, and showed great potential for the tissue distribution study of RUS. The cFLISA method may provide a valuable tool for the analysis of small molecules in biological samples and such an approach could be applied to other natural products. Full article
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Open AccessArticle Mathematical Modeling and Accuracy Testing of WorldView-2 Level-1B Stereo Pairs without Ground Control Points
Remote Sens. 2017, 9(7), 737; doi:10.3390/rs9070737
Received: 23 June 2017 / Revised: 23 June 2017 / Accepted: 13 July 2017 / Published: 17 July 2017
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Abstract
With very high resolution satellite (VHRS) imagery of 0.5 m, WorldView-2 (WV02) satellite images have been widely used in the field of surveying and mapping. However, for the specific WV02 satellite image geometric orientation model, there is a lack of detailed research and
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With very high resolution satellite (VHRS) imagery of 0.5 m, WorldView-2 (WV02) satellite images have been widely used in the field of surveying and mapping. However, for the specific WV02 satellite image geometric orientation model, there is a lack of detailed research and explanation. This paper elaborates the construction process of the WV02 satellite rigorous sensor model (RSM), which considers the velocity aberration, the optical path delay and the atmospheric refraction. We create a new physical inverse model based on a double-iterative method. Through this inverse method, we establish the virtual control grid in the object space to calculate the rational function model (RFM) coefficients. In the RFM coefficient calculation process, we apply the correcting characteristic value method (CCVM) and least squares (LS) method to compare the two experiments’ accuracies. We apply two stereo pairs of WV02 Level 1B products in Qinghai, China to verify the algorithm and test image positioning accuracy. Under the no-control conditions, the monolithic horizontal mean square error (RMSE) of the rational polynomial coefficient (RPC) is 3.8 m. This result is 13.7% higher than the original RPC positioning accuracy provided by commercial vendors. The stereo pair horizontal positioning accuracy of both the physical and RPC models is 5.0 m circular error 90% (CE90). This result is in accordance with the WV02 satellite images nominal positioning accuracy. This paper provides a new method to improve the positioning accuracy of the WV02 satellite image RPC model without GCPs. Full article
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Open AccessArticle Income Diversification and Rural Consumption—Evidence from Chinese Provincial Panel Data
Sustainability 2017, 9(6), 1014; doi:10.3390/su9061014
Received: 24 April 2017 / Revised: 6 June 2017 / Accepted: 9 June 2017 / Published: 12 June 2017
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Abstract
In China, income diversification has become a useful method for the rural households to smooth their income and maintain a sustainable mode of consumption. Additionally, income diversification affects rural consumption differently in regions with different income levels. In this paper, I have analyzed
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In China, income diversification has become a useful method for the rural households to smooth their income and maintain a sustainable mode of consumption. Additionally, income diversification affects rural consumption differently in regions with different income levels. In this paper, I have analyzed the impacts of income diversification on the peasants’ consumption in the Chinese rural areas with the provincial level panel data from 1998 to 2015. The findings indicate that income diversification can increase the Chinese peasants’ consumption, but the consumption of the peasants from the low- and the high- income subsamples of provinces are more sensitive to income diversification while the peasants from the middle-income provinces are not so sensitive to income diversification. Moreover, there is a significant ratchet effect and demonstration effect in the peasants’ consumption, as is stated by the traditional literature. This paper contributes to the research by testing the impact of peasants’ income sources diversification on the rural consumption and investigating its mechanism against the changing social background in China with the latest panel data. Full article
(This article belongs to the Section Sustainable Urban and Rural Development)
Open AccessArticle Preparation of Porous Poly(Styrene-Divinylbenzene) Microspheres and Their Modification with Diazoresin for Mix-Mode HPLC Separations
Materials 2017, 10(4), 440; doi:10.3390/ma10040440
Received: 8 February 2017 / Revised: 15 April 2017 / Accepted: 20 April 2017 / Published: 22 April 2017
Viewed by 582 | PDF Full-text (4808 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
By using the two-step activated swelling method, monodisperse porous poly(styrene-divinylbenzene) (P(S-DVB)) microparticles were successfully synthesized. The influence of porogens, swelling temperatures and crosslinking agents on the porosity of porous microparticles was carefully investigated. Porous P(S-DVB) microparticles were used as a packing material for
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By using the two-step activated swelling method, monodisperse porous poly(styrene-divinylbenzene) (P(S-DVB)) microparticles were successfully synthesized. The influence of porogens, swelling temperatures and crosslinking agents on the porosity of porous microparticles was carefully investigated. Porous P(S-DVB) microparticles were used as a packing material for high performance liquid chromatography (HPLC). Several benzene analogues were effectively separated in a stainless-steel column as short as 75 mm due to the high specific surface area of the porous microparticles. Porous P(S-DVB) microparticles were further sulfonated and subsequently modified with diazoresin (DR) via electrostatic self-assembly and UV (ultraviolet) radiation. After treatment with UV light, the ionic bonding between sulfonated P(S-DVB) and DR was converted into covalent bonding through a unique photochemistry reaction of DR. Depending on the chemical structure of DR and mobile phase composition, the DR-modified P(S-DVB) stationary phase performed different separation mechanisms, including reversed phase (RP) and hydrophilic interactions. Therefore, baseline separations of benzene analogues and organic acids were achieved by using the DR-modified P(S-DVB) particles as packing materials in HPLC. According to the π–π interactional difference between carbon rings of fullerenes and benzene rings of DR, C60 and C70 were also well separated in the HPLC column packed with DR-modified P(S-DVB) particles. Full article
(This article belongs to the Section Porous Materials)
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Open AccessArticle An Entropy-Based Approach for Evaluating Travel Time Predictability Based on Vehicle Trajectory Data
Entropy 2017, 19(4), 165; doi:10.3390/e19040165
Received: 29 January 2017 / Revised: 24 March 2017 / Accepted: 7 April 2017 / Published: 11 April 2017
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Abstract
With the great development of intelligent transportation systems (ITS), travel time prediction has attracted the interest of many researchers, and a large number of prediction methods have been developed. However, as an unavoidable topic, the predictability of travel time series is the basic
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With the great development of intelligent transportation systems (ITS), travel time prediction has attracted the interest of many researchers, and a large number of prediction methods have been developed. However, as an unavoidable topic, the predictability of travel time series is the basic premise for travel time prediction, which has received less attention than the methodology. Based on the analysis of the complexity of the travel time series, this paper defines travel time predictability to express the probability of correct travel time prediction, and proposes an entropy-based method to measure the upper bound of travel time predictability. Multiscale entropy is employed to quantify the complexity of the travel time series, and the relationships between entropy and the upper bound of travel time predictability are presented. Empirical studies are made with vehicle trajectory data in an express road section to shape the features of travel time predictability. The effectiveness of time scales, tolerance, and series length to entropy and travel time predictability are analyzed, and some valuable suggestions about the accuracy of travel time predictability are discussed. Finally, comparisons between travel time predictability and actual prediction results from two prediction models, ARIMA and BPNN, are made. Experimental results demonstrate the validity and reliability of the proposed travel time predictability. Full article
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Open AccessArticle An Optimized Energy Management Strategy for Preheating Vehicle-Mounted Li-ion Batteries at Subzero Temperatures
Energies 2017, 10(2), 243; doi:10.3390/en10020243
Received: 5 December 2016 / Revised: 14 February 2017 / Accepted: 15 February 2017 / Published: 17 February 2017
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Abstract
This paper presents an optimized energy management strategy for Li-ion power batteries used on electric vehicles (EVs) at low temperatures. In low-temperature environments, EVs suffer a sharp driving range loss resulting from the energy and power capability reduction of the battery. Simultaneously, because
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This paper presents an optimized energy management strategy for Li-ion power batteries used on electric vehicles (EVs) at low temperatures. In low-temperature environments, EVs suffer a sharp driving range loss resulting from the energy and power capability reduction of the battery. Simultaneously, because of Li plating, battery degradation becomes an increasing concern as the temperature drops. All these factors could greatly increase the total vehicle operation cost. Prior to battery charging and vehicle operating, preheating the battery to a battery-friendly temperature is an approach to promote energy utilization and reduce total cost. Based on the proposed LiFePO4 battery model, the total vehicle operation cost under certain driving cycles is quantified in the present paper. Then, given a certain ambient temperature, a target preheating temperature is optimized under the principle of minimizing total cost. As for the preheating method, a liquid heating system is also implemented on an electric bus. Simulation results show that the preheating process becomes increasingly necessary with decreasing ambient temperature, however, the preheating demand declines as driving range grows. Vehicle tests verify that the preheating management strategy proposed in this paper is able to save on total vehicle operation costs. Full article
(This article belongs to the collection Electric and Hybrid Vehicles Collection)
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Open AccessArticle Experimental and Numerical Investigation on Non-Newtonian Nanofluids Flowing in Shell Side of Helical Baffled Heat Exchanger Combined with Elliptic Tubes
Appl. Sci. 2017, 7(1), 48; doi:10.3390/app7010048
Received: 25 October 2016 / Revised: 26 December 2016 / Accepted: 28 December 2016 / Published: 4 January 2017
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Abstract
In this paper, an aqueous solution of xanthan gum (XG) at a weight fraction as high as 0.2% was elected as the non-Newtonian base liquid, the multi-walled carbon nanotubes (MWCNTs) dispersed into non-Newtonian XG aqueous at different weight factions of MWCNTs was prepared.
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In this paper, an aqueous solution of xanthan gum (XG) at a weight fraction as high as 0.2% was elected as the non-Newtonian base liquid, the multi-walled carbon nanotubes (MWCNTs) dispersed into non-Newtonian XG aqueous at different weight factions of MWCNTs was prepared. Convection heat transfer of non-Newtonian nanofluids in the shell side of helical baffled heat exchanger combined with elliptic tubes has been investigated experimentally and numerically using single-phase flow model. Results showed that the enhancement of the convective heat transfer coefficient increases with an increase in the Reynolds number and the nanoparticle concentration. For nanofluids with 0.2 wt %, 0.5 wt % and 1.0 wt % MWCNTs, the Nusselt number, respectively, increases by 11%, 21% and 35% on average at the same Reynolds number, while the comprehensive thermal performance factors are 3%–5%, 15%–17% and 24%–26% higher than that of base fluid at the same volume rate. A remarkable heat transfer enhancement can be obtained by adding MWCNTs into XG aqueous solution based on thermal resistance analysis. Correlations have been suggested for the shell-side Nusselt number and friction factor of non-Newtonian nanofluids in the helical baffled heat exchanger with elliptic tubes. Good agreements existed between corrections and experimental data. Full article
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Open AccessArticle Simulating Microwave Scattering for Wetland Vegetation in Poyang Lake, Southeast China, Using a Coherent Scattering Model
Remote Sens. 2015, 7(8), 9796-9821; doi:10.3390/rs70809796
Received: 27 March 2015 / Revised: 23 July 2015 / Accepted: 27 July 2015 / Published: 31 July 2015
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Abstract
We developed a polarimetric coherent electromagnetic scattering model for Poyang Lake wetland vegetation. Realistic canopy structures including curved leaves and the lodging situation of the vegetation were taken into account, and the situation at the ground surface was established using an Advanced Integral
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We developed a polarimetric coherent electromagnetic scattering model for Poyang Lake wetland vegetation. Realistic canopy structures including curved leaves and the lodging situation of the vegetation were taken into account, and the situation at the ground surface was established using an Advanced Integral Equation Model combined with Oh’s 2002 model. This new model can reasonably describe the coherence effect caused by the phase differences of the electromagnetic fields scattered from different particles by different scattering mechanisms. We obtained good agreement between the modeling results and C-band data from the Radarsat-2 satellite. A simulation of scattering from the vegetation in Poyang Lake showed that direct vegetation scattering and the single-ground-bounce mechanism are the dominant scattering mechanisms in the C-band and L-band, while the effects of the double-ground-bounce mechanism are very small. We note that the curvature of the leaves and the lodging characteristics of the vegetation cannot be ignored in the modeling process. Monitoring soil moisture in the Poyang Lake wetland with the C-band data was not feasible because of the density and depth of Poyang Lake vegetation. When the density of Poyang Lake Carex increases, the backscattering coefficient either decreases or remains stable. Full article
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Open AccessArticle Highly Active Non-PGM Catalysts Prepared from Metal Organic Frameworks
Catalysts 2015, 5(2), 955-965; doi:10.3390/catal5020955
Received: 11 May 2015 / Revised: 5 June 2015 / Accepted: 5 June 2015 / Published: 11 June 2015
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Abstract
Finding inexpensive alternatives to platinum group metals (PGMs) is essential for reducing the cost of proton exchange membrane fuel cells (PEMFCs). Numerous materials have been investigated as potential replacements of Pt, of which the transition metal and nitrogen-doped carbon composites (TM/Nx/C)
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Finding inexpensive alternatives to platinum group metals (PGMs) is essential for reducing the cost of proton exchange membrane fuel cells (PEMFCs). Numerous materials have been investigated as potential replacements of Pt, of which the transition metal and nitrogen-doped carbon composites (TM/Nx/C) prepared from iron doped zeolitic imidazolate frameworks (ZIFs) are among the most active ones in catalyzing the oxygen reduction reaction based on recent studies. In this report, we demonstrate that the catalytic activity of ZIF-based TM/Nx/C composites can be substantially improved through optimization of synthesis and post-treatment processing conditions. Ultimately, oxygen reduction reaction (ORR) electrocatalytic activity must be demonstrated in membrane-electrode assemblies (MEAs) of fuel cells. The process of preparing MEAs using ZIF-based non-PGM electrocatalysts involves many additional factors which may influence the overall catalytic activity at the fuel cell level. Evaluation of parameters such as catalyst loading and perfluorosulfonic acid ionomer to catalyst ratio were optimized. Our overall efforts to optimize both the catalyst and MEA construction process have yielded impressive ORR activity when tested in a fuel cell system. Full article
(This article belongs to the Special Issue Electrocatalysis in Fuel Cells) Printed Edition available
Open AccessArticle Nighttime Light Derived Assessment of Regional Inequality of Socioeconomic Development in China
Remote Sens. 2015, 7(2), 1242-1262; doi:10.3390/rs70201242
Received: 24 June 2014 / Accepted: 15 January 2015 / Published: 23 January 2015
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Abstract
Satellite-derived nighttime light (NTL) data have been extensively used as an efficient proxy measure for monitoring urbanization dynamics and socioeconomic activity. This is because remotely sensed NTL signals can be quantitatively connected to demographic and socioeconomic variables at regional and global scales. The
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Satellite-derived nighttime light (NTL) data have been extensively used as an efficient proxy measure for monitoring urbanization dynamics and socioeconomic activity. This is because remotely sensed NTL signals can be quantitatively connected to demographic and socioeconomic variables at regional and global scales. The recently composited cloud-free NTL imagery derived from the Visible Infrared Imaging Radiometer Suite (VIIRS) aboard the Suomi National Polar-orbiting Partnership (Suomi-NPP) satellite provides spatially detailed observations of human settlements. We quantitatively estimated socioeconomic development inequalities across 30 provinces and municipalities in mainland China using VIIRS NTL data associated with both regional gross domestic product (GDP) and population census data. We quantitatively investigated relations between NTL, GDP, and population using a linear regression model. Our results suggest that NTL radiances have significant positive correlations with GDP and population at different levels. Several inequality coefficients, commonly used in economics, were derived from VIIRS NTL data and statistical data at multiple spatial scales. Compared with the statistical data, NTL-derived inequality coefficients enabled us to elicit more detailed information on differences in regional development at multiple levels. Our study of provinces and municipalities revealed that county-level inequality was more significant than city-level inequality. The results of population-weighted NTL inequality indicate an obvious regional disparity with NTL distribution being more unequal in China’s undeveloped western regions compared with more developed eastern regions. Our findings suggest that given the timely and spatially explicit advantages of VIIRS, NTL data are capable of providing comprehensive information regarding inequality at multiple levels, which is not possible through the use of traditional statistical sources. Full article
(This article belongs to the Special Issue Remote Sensing with Nighttime Lights)
Open AccessArticle Evaluating the Role of PTH in Promotion of Chondrosarcoma Cell Proliferation and Invasion by Inhibiting Primary Cilia Expression
Int. J. Mol. Sci. 2014, 15(11), 19816-19831; doi:10.3390/ijms151119816
Received: 2 September 2014 / Revised: 15 October 2014 / Accepted: 23 October 2014 / Published: 31 October 2014
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Abstract
Chondrosarcoma is characterized by secretion of a cartilage-like matrix, with high proliferation ability and metastatic potential. Previous studies have shown that parathyroid hormone-related protein (PTHrP) has a close relationship with various tumor types. The objectives of this study were to research the function
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Chondrosarcoma is characterized by secretion of a cartilage-like matrix, with high proliferation ability and metastatic potential. Previous studies have shown that parathyroid hormone-related protein (PTHrP) has a close relationship with various tumor types. The objectives of this study were to research the function played by PTHrP in human chondrosarcoma, especially targeting cell proliferation and invasion, and to search for the potential interaction between PTHrP and primary cilia in tumorigenesis. Surgical resection tissues and the human chondrosarcoma cell line SW1353 were used in the scientific research. Cells were stimulated with an optimum concentration of recombinant PTH (1-84), and siRNA was used to interfere with internal PTHrP. Cell proliferation and invasion assays were applied, including MTS-8 cell proliferation assay, Western blot, RT-PCR, Transwell invasion assay, and immunohistochemistry and immunofluorescence assays. A high level of PTHrP expression was found in human chondrosarcoma tissues, and recombinant PTH exhibited positive promotion in tumor cell proliferation and invasion. In the meantime, PTHrP could inhibit the assembly of primary cilia and regulate downstream gene expression. These findings indicate that PTHrP can regulate tumor cell proliferation and invasion ability, possibly through suppression of primary cilia assembly. Thus, restricting PTHrP over-expression is a feasible potential therapeutic method for chondrosarcoma. Full article
(This article belongs to the Special Issue Advances in Molecular Oncology 2014)
Open AccessArticle Comparative Estimation of Urban Development in China’s Cities Using Socioeconomic and DMSP/OLS Night Light Data
Remote Sens. 2014, 6(8), 7840-7856; doi:10.3390/rs6087840
Received: 24 June 2014 / Revised: 29 July 2014 / Accepted: 12 August 2014 / Published: 22 August 2014
Cited by 11 | Viewed by 1975 | PDF Full-text (5321 KB) | HTML Full-text | XML Full-text
Abstract
China has been undergoing a remarkably rapid urbanization process in the last several decades. Urbanization is a complicated phenomenon involving imbalanced transformation processes, such as population migrations, economic advancements and human activity dynamics. It is important to evaluate the imbalances between transformation processes
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China has been undergoing a remarkably rapid urbanization process in the last several decades. Urbanization is a complicated phenomenon involving imbalanced transformation processes, such as population migrations, economic advancements and human activity dynamics. It is important to evaluate the imbalances between transformation processes to support policy making in the realms of environmental management and urban planning. The Defense Meteorological Satellite Program’s Operational Linescan System (DMSP/OLS) nighttime lights time series imagery provides a consistent and timely measure to estimate socioeconomic dynamics and changes in human activity. In this study, we jointly compared the annual ranks of three variables: the population, the gross domestic product (GDP) and the sum of weighted DMSP/OLS nighttime lights to estimate spatial and temporal imbalances in the urbanization processes of 226 cities in China between 1994 and 2011. We used ternary plots and a Euclidean distance-based method to quantitatively estimate the spatial and temporal imbalances between cities and to classify diverse urban development patterns in China. Our results suggest that, from 1994 to 2011, the imbalances of urbanization processes observed in the eastern, western and middle cities decreased, respectively, by 35.26%, 29.04% and 25.84%; however, imbalances in the northeast increased by 33.29%. The average decrement in imbalances across all urbanization processes in the 226 cities was 17.58%. Cities in the eastern region displayed relatively strong attractions to population, more rapid economic development processes and lower imbalances between socioeconomic and anthropogenic dynamics than cities in other regions. Several types of urban development patterns can be identified by comparing the morphological characteristics of temporal ternary plots of the 226 cities in China. More than one third (35.40%) of the 226 cities presented balanced states during the period studied; however, the remainder showed alternative urban development patterns. Full article
(This article belongs to the Special Issue Remote Sensing with Nighttime Lights)
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Open AccessArticle Characterizing Spatio-Temporal Dynamics of Urbanization in China Using Time Series of DMSP/OLS Night Light Data
Remote Sens. 2014, 6(8), 7708-7731; doi:10.3390/rs6087708
Received: 24 June 2014 / Revised: 21 July 2014 / Accepted: 12 August 2014 / Published: 20 August 2014
Cited by 10 | Viewed by 1954 | PDF Full-text (10606 KB) | HTML Full-text | XML Full-text
Abstract
Stable nighttime light (NTL) data, derived from the Defense Meteorological Satellite Program’s Operational Linescan System (DMSP/OLS), are typically considered a proxy measure of the dynamics of human settlements and have been extensively used to quantitative estimates of demographic variables, economic activity, and land-use
[...] Read more.
Stable nighttime light (NTL) data, derived from the Defense Meteorological Satellite Program’s Operational Linescan System (DMSP/OLS), are typically considered a proxy measure of the dynamics of human settlements and have been extensively used to quantitative estimates of demographic variables, economic activity, and land-use change in previous studies at both regional and global scales. The utility of DMSP data for characterizing spatio-temporal trends in urban development at a local scale, however, has received less attention. In this study, we utilize a time series of DMSP data to examine the spatio-temporal characteristics of urban development in 285 Chinese cities from 1992 to 2009, at both the local and national levels. We compare linear models and piecewise linear models to identify the turning points of nighttime lights and calculate the trends in nighttime light growth at the pixel level. An unsupervised classification is applied to identify the patterns in the nighttime light time series quantitatively. Our results indicate that nighttime light brightness in most areas of China exhibit a positive, multi-stage process over the last two decades; however, the average trends in nighttime light growth differ significantly. Through the piecewise linear model, we identify the saturation of nighttime light brightness in the urban center and significant increases in suburban areas. The maps of turning points indicate the greater the distance to the city center or sub-center, the later the turning point occurs. Six patterns derived from the classification illustrate the various characteristics of the nighttime light time series from the local to the national level. The results portray spatially explicit patterns and conspicuous temporal trends of urbanization dynamics for individual Chinese cities from 1992 to 2009. Full article
(This article belongs to the Special Issue Remote Sensing with Nighttime Lights)
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Open AccessArticle A 3D QSAR Study of Betulinic Acid Derivatives as Anti-Tumor Agents Using Topomer CoMFA: Model Building Studies and Experimental Verification
Molecules 2013, 18(9), 10228-10241; doi:10.3390/molecules180910228
Received: 2 July 2013 / Revised: 13 August 2013 / Accepted: 13 August 2013 / Published: 22 August 2013
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Abstract
Betulinic acid (BA) is a natural product that exerts its cytotoxicity against various malignant carcinomas without side effects by triggering the mitochondrial pathway to apoptosis. Betulin (BE), the 28-hydroxyl analog of BA, is present in large amounts (up to 30% dry weight) in
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Betulinic acid (BA) is a natural product that exerts its cytotoxicity against various malignant carcinomas without side effects by triggering the mitochondrial pathway to apoptosis. Betulin (BE), the 28-hydroxyl analog of BA, is present in large amounts (up to 30% dry weight) in the outer bark of birch trees, and shares the same pentacyclic triterpenoid core as BA, yet exhibits no significant cytotoxicity. Topomer CoMFA studies were performed on 37 BA and BE derivatives and their in vitro anti-cancer activity results (reported as IC50 values) against HT29 human colon cancer cells in the present study. All derivatives share a common pentacyclic triterpenoid core and the molecules were split into three pieces by cutting at the C-3 and C-28 sites with a consideration toward structural diversity. The analysis gave a leave-one-out cross-validation q2 value of 0.722 and a non-cross-validation r2 value of 0.974, which suggested that the model has good predictive ability (q2 > 0.2). The contour maps illustrated that bulky and electron-donating groups would be favorable for activity at the C-28 site, and a moderately bulky and electron-withdrawing group near the C-3 site would improve this activity. BE derivatives were designed and synthesized according to the modeling result, whereby bulky electronegative groups (maleyl, phthalyl, and hexahydrophthalyl groups) were directly introduced at the C-28 position of BE. The in vitro cytotoxicity values of the given analogs against HT29 cells were consistent with the predicted values, proving that the present topomer CoMFA model is successful and that it could potentially guide the synthesis of new betulinic acid derivatives with high anti-cancer activity. The IC50 values of these three new compounds were also assayed in five other tumor cell lines. 28-O-hexahydrophthalyl BE exhibited the greatest anti-cancer activities and its IC50 values were lower than those of BA in all cell lines, excluding DU145 cells. Full article
(This article belongs to the Section Medicinal Chemistry)

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