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Open AccessFeature PaperArticle
Synthesis and Biological Evaluation of Novel Triple-Modified Colchicine Derivatives as Potent Tubulin-Targeting Anticancer Agents
Cells 2018, 7(11), 216; https://doi.org/10.3390/cells7110216 (registering DOI) -
Abstract
Specific modifications of colchicine followed by synthesis of its analogues have been tested in vitro with the objective of lowering colchicine toxicity. Our previous studies have clearly shown the anticancer potential of double-modified colchicine derivatives in C-7 and C-10 positions. Here, a series
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Specific modifications of colchicine followed by synthesis of its analogues have been tested in vitro with the objective of lowering colchicine toxicity. Our previous studies have clearly shown the anticancer potential of double-modified colchicine derivatives in C-7 and C-10 positions. Here, a series of novel triple-modified colchicine derivatives is reported. They have been obtained following a four-step strategy. In vitro cytotoxicity of these compounds has been evaluated against four human tumor cell lines (A549, MCF-7, LoVo, and LoVo/DX). Additionally, the mode of binding of the synthesized compounds was evaluated in silico using molecular docking to a 3D structure of β-tubulin based on crystallographic data from the Protein Data Bank and homology methodology. Binding free energy estimates, binding poses, and MlogP values of the compounds were obtained. All triple-modified colchicine derivatives were shown to be active at nanomolar concentrations against three of the investigated cancer cell lines (A549, MCF-7, LoVo). Four of them also showed higher potency against tumor cells over normal cells as confirmed by their high selectivity index values. A vast majority of the synthesized derivatives exhibited several times higher cytotoxicity than colchicine, doxorubicin, and cisplatin. Full article
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Open AccessFeature PaperArticle
Scaling Criteria for Axial Piston Machines Based on Thermo-Elastohydrodynamic Effects in the Tribological Interfaces
Energies 2018, 11(11), 3210; https://doi.org/10.3390/en11113210 (registering DOI) -
Abstract
In lieu of reliable scaling rules, hydraulic pump and motor manufacturers pay a high monetary and temporal price for attempting to expand their production lines by scaling their existing units to other sizes. The challenge is that the lubricating interfaces, which are the
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In lieu of reliable scaling rules, hydraulic pump and motor manufacturers pay a high monetary and temporal price for attempting to expand their production lines by scaling their existing units to other sizes. The challenge is that the lubricating interfaces, which are the key elements in determining the performance of a positive displacement machine, are not easily scalable. This article includes an analysis of the size-dependence of these units with regard to the significant physical phenomena describing the behavior of their three most critical lubricating interfaces. These phenomena include the non-isothermal elastohydrodynamic effects in the fluid domain, and the heat transfer and thermal elastic deflection in the solid domain. The performance change due to size variation is found to be unavoidable and explained through fundamental physics. The results are demonstrated using a numerical fluid–structure–thermal interaction model over a wide range of unit sizes. Based on the findings, a guide to scaling swashplate-type axial piston machines such as to uphold their efficiency is proposed. Full article
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Open AccessArticle
A New Class of Hermite-Apostol Type Frobenius-Euler Polynomials and Its Applications
Symmetry 2018, 10(11), 652; https://doi.org/10.3390/sym10110652 (registering DOI) -
Abstract
The article is written with the objectives to introduce a multi-variable hybrid class, namely the Hermite–Apostol-type Frobenius–Euler polynomials, and to characterize their properties via different generating function techniques. Several explicit relations involving Hurwitz–Lerch Zeta functions and some summation formulae related to these polynomials
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The article is written with the objectives to introduce a multi-variable hybrid class, namely the Hermite–Apostol-type Frobenius–Euler polynomials, and to characterize their properties via different generating function techniques. Several explicit relations involving Hurwitz–Lerch Zeta functions and some summation formulae related to these polynomials are derived. Further, we establish certain symmetry identities involving generalized power sums and Hurwitz–Lerch Zeta functions. An operational view for these polynomials is presented, and corresponding applications are given. The illustrative special cases are also mentioned along with their generating equations. Full article
Open AccessEditorial
Bainite and Martensite: Developments and Challenges
Metals 2018, 8(11), 966; https://doi.org/10.3390/met8110966 (registering DOI) -
Abstract
Both microstructures, martensite and bainite, although share some common features, when studied in further detail depict a plethora of subtle differences that make them unique. [...] Full article
Open AccessReview
Revisiting Rab7 Functions in Mammalian Autophagy: Rab7 Knockout Studies
Cells 2018, 7(11), 215; https://doi.org/10.3390/cells7110215 (registering DOI) -
Abstract
Rab7 (or Ypt7 in yeast) is one of the well-characterized members of the Rab family small GTPases, which serve as master regulators of membrane trafficking in eukaryotes. It localizes to late endosomes and lysosomes and has multiple functions in the autophagic pathway as
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Rab7 (or Ypt7 in yeast) is one of the well-characterized members of the Rab family small GTPases, which serve as master regulators of membrane trafficking in eukaryotes. It localizes to late endosomes and lysosomes and has multiple functions in the autophagic pathway as well as in the endocytic pathway. Because Rab7/Ypt7 has previously been shown to regulate the autophagosome-lysosome fusion step in yeast and fruit flies (i.e., autophagosome accumulation has been observed in both Ypt7-knockout [KO] yeast and Rab7-knockdown fruit flies), it is widely assumed that Rab7 regulates the autophagosome-lysosome fusion step in mammals. A recent analysis of Rab7-KO mammalian cultured cells, however, has revealed that Rab7 is essential for autolysosome maturation (i.e., autolysosome accumulation has been observed in Rab7-KO cells), but not for autophagosome-lysosome fusion, under nutrient-rich conditions. Thus, although Rab7/Ypt7 itself is essential for the proper progression of autophagy in eukaryotes, the function of Rab7/Ypt7 in autophagy in yeast/fruit flies and mammals must be different. In this review article, we describe novel roles of Rab7 in mammalian autophagy and discuss its functional diversification during evolution. Full article
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Open AccessArticle
Synthesis and Anticancer Activity Evaluation of Hydrolyzed Derivatives of Panaxnotoginseng Saponins
Molecules 2018, 23(11), 3021; https://doi.org/10.3390/molecules23113021 (registering DOI) -
Abstract
To increase the antitumor activity of ginsenosides and acetylsalicylic acid, acid hydrolysis products of Panaxnotoginseng saponin were used as raw materials to be combined with salicylic acid to obtain ginsenoside salicylic acid derivatives. All derivatives were assessed for anti-cancer activity. A total of
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To increase the antitumor activity of ginsenosides and acetylsalicylic acid, acid hydrolysis products of Panaxnotoginseng saponin were used as raw materials to be combined with salicylic acid to obtain ginsenoside salicylic acid derivatives. All derivatives were assessed for anti-cancer activity. A total of 20 target compounds were designed and synthesized. The cytotoxic activity on five cancer cell lines, including human colon cancer (HT-29), gastric cancer (BGC-823), cervical cancer (Hela), human breast cancer (MCF-7), human lung cancer cells (A549), and two normal cancer cell lines (human gastric epithelial cells (GES-1), and human ovarian epithelial cells (IOSE144)) was evaluated following treatment with the compounds. The results showed that all compounds inhibited the growth of cancer cells. Compounds 1a, 3a, 7a, 1b, 2b, 3b and 8b showed strong anticancer activity. For MCF-7 cells, compound 3b showed the strongest inhibitory activity, IC50 = 2.56 ± 0.09 μM. In the cytotoxicity test, all compounds showed low toxicity or no toxicity (IC50 > 100 μM). In addition, a cell cycle distribution assay and wound healing assay demonstrated that compound 3b specifically inhibited MCF-7 proliferation and migration ability. Our results indicate that compound 3b represents a promising compound for further cancer studies. Full article
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Open AccessArticle
Impact of Hydrological Modellers’ Decisions and Attitude on the Performance of a Calibrated Conceptual Catchment Model: Results from a ‘Modelling Contest’
Hydrology 2018, 5(4), 64; https://doi.org/10.3390/hydrology5040064 (registering DOI) -
Abstract
In this study, 17 hydrologists with different experience in hydrological modelling applied the same conceptual catchment model (HBV) to a Greek catchment, using identical data and model code. Calibration was performed manually. Subsequently, the modellers were asked for their experience, their calibration strategy,
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In this study, 17 hydrologists with different experience in hydrological modelling applied the same conceptual catchment model (HBV) to a Greek catchment, using identical data and model code. Calibration was performed manually. Subsequently, the modellers were asked for their experience, their calibration strategy, and whether they enjoyed the exercise. The exercise revealed that there is considerable modellers’ uncertainty even among the experienced modellers. It seemed to be equally important whether the modellers followed a good calibration strategy, and whether they enjoyed modelling. The exercise confirmed previous studies about the benefit of model ensembles: Different combinations of the simulation results (median, mean) outperformed the individual model simulations, while filtering the simulations even improved the quality of the model ensembles. Modellers’ experience, decisions, and attitude, therefore, have an impact on the hydrological model application and should be considered as part of hydrological modelling uncertainty. Full article
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Open AccessArticle
Capital Adequacy, Deposit Insurance, and the Effect of Their Interaction on Bank Risk
J. Risk Financial Manag. 2018, 11(4), 79; https://doi.org/10.3390/jrfm11040079 (registering DOI) -
Abstract
This paper investigates how deposit insurance and capital adequacy affect bank risk for five developed and nine emerging markets over the period of 1992–2015. Although full coverage of deposit insurance induces moral hazard by banks, deposit insurance is still an effective tool, especially
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This paper investigates how deposit insurance and capital adequacy affect bank risk for five developed and nine emerging markets over the period of 1992–2015. Although full coverage of deposit insurance induces moral hazard by banks, deposit insurance is still an effective tool, especially during the time of crisis. On the contrary, capital adequacy by itself does not effectively perform the monitoring role and leads to the asset substitution problem. Implementing the safety nets of both deposit insurance and capital adequacy together could be a sustainable financial architecture. Immediate-effect analysis reveals that the interplay between deposit insurance and capital adequacy is indispensable for banking system stability. Full article
Open AccessArticle
The Application of Improved Random Forest Algorithm on the Prediction of Electric Vehicle Charging Load
Energies 2018, 11(11), 3207; https://doi.org/10.3390/en11113207 (registering DOI) -
Abstract
To cope with the increasing charging demand of electric vehicle (EV), this paper presents a forecasting method of EV charging load based on random forest algorithm (RF) and the load data of a single charging station. This method is completed by the classification
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To cope with the increasing charging demand of electric vehicle (EV), this paper presents a forecasting method of EV charging load based on random forest algorithm (RF) and the load data of a single charging station. This method is completed by the classification and regression tree (CART) algorithm to realize short-term forecast for the station. At the same time, the prediction algorithm of the daily charging capacity of charging stations with different scales and locations is proposed. By combining the regression and classification algorithms, the effective learning of a large amount of historical charging data is completed. The characteristic data is divided from different aspects, realizing the establishment of RF and the effective prediction of fluctuate charging load. By analyzing the data of each charging station in Shenzhen from the aspect of time and space, the algorithm is put into practice. The application form of current data in the algorithm is determined, and the accuracy of the prediction algorithm is verified to be reliable and practical. It can provide a reference for both power suppliers and users through the prediction of charging load. Full article
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