SOKNL: A novel way of integrating K-nearest neighbours with adaptive random forest regression for data streams

Data Mining and Knowledge Discovery - Most research in machine learning for data streams has focused on classification algorithms, whereas regression methods have received a lot less attention....     

Active Transport of Hepatotoxic Pyrrolizidine Alkaloids in HepaRG Cells

1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the beginning of being recognized as a key determinant of PA toxicity. Therefore, this study concentrated on assessing the general mode of action of PA transport in the human hepatoma cell line HepaRG using seven structurally different PAs. Furthermore, several hepatic uptake and efflux transporters were targeted with pharmacological inhibitors to identify their role in the uptake of the PAs retrorsine and senecionine and in the disposition of their N-oxides (PANO). For this purpose, PA and PANO content was measured in the supernatant using LC-MS/MS. Also, PA-mediated cytotoxicity was analyzed after transport inhibition. It was found that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner. This pattern correlates with other experimental endpoints such as cytotoxicity. Pharmacological inhibition of the influx transporters Na⁺/taurocholate co-transporting polypeptide (SLC10A1) and organic cation transporter 1 (SLC22A1) led to a reduced uptake of retrorsine and senecionine into HepaRG cells, emphasizing the relevance of these transporters for PA toxicokinetics.     

Design,Synthesis, Radiosynthesis and Biological Evaluation of Fenretinide Analogues as Anticancer and Metabolic Syndrome-Preventive Agents

Fenretinide (4-HPR) is a synthetic derivative of all-trans-retinoic acid (ATRA) characterised by improved therapeutic properties and toxicological profile relative to ATRA. 4-HPR has been mostly investigated as an anti-cancer agent, but recent studies showed its promising therapeutic potential for preventing metabolic syndrome. Several biological targets are involved in 4-HPR's activity, leading to the potential use of this molecule for treating different pathologies. However, although 4-HPR displays quite well-understood multitarget promiscuity with regards to pharmacology, interpreting its precise physiological role remains challenging. In addition, despite promising results in vitro, the clinical efficacy of 4-HPR as a chemotherapeutic agent has not been satisfactory so far. Herein, we describe the preparation of a library of 4-HPR analogues, followed by the biological evaluation of their anti-cancer and anti-obesity/diabetic properties. The click-type analogue 3 b showed good capacity to reduce the amount of lipid accumulation in 3T3-L1 adipocytes during differentiation. Furthermore, it showed an IC₅₀ of 0.53±0.8 μM in cell viability tests on breast cancer cell line MCF-7, together with a good selectivity (SI=121) over noncancerous HEK293 cells. Thus, 3 b was selected as a potential PET tracer to study retinoids in vivo, and the radiosynthesis of [¹⁸F] 3b was successfully developed. Unfortunately, the stability of [¹⁸F] 3b turned out to be insufficient to pursue imaging studies.     

Trans-differentiation of human adipose-derived mesenchymal stem cells into cardiomyocyte-like cells on decellularized bovine myocardial extracellular matrix-based films

In this study, we aimed at fabricating decellularized bovine myocardial extracellular matrix-based films (dMEbF) for cardiac tissue engineering (CTE). The decellularization process was carried out utilizing four consecutive stages including hypotonic treatment, detergent treatment, enzymatic digestion and decontamination, respectively. In order to fabricate the dMEbF, dBM were digested with pepsin and gelation process was conducted. dMEbF were then crosslinked with N-hydroxysuccinimide/1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (NHS/EDC) to increase their durability. Nuclear contents of native BM and decellularized BM (dBM) tissues were determined with DNA content analysis and agarose-gel electrophoresis. Cell viability on dMEbF for 3rd, 7th, and 14th days was assessed by MTT assay. Cell attachment on dMEbF was also studied by scanning electron microscopy. Trans-differentiation capacity of human adipose-derived mesenchymal stem cells (hAMSCs) into cardiomyocyte-like cells on dMEbF were also evaluated by histochemical and immunohistochemical analyses. DNA contents for native and dBM were, respectively, found as 886.11?±?164.85 and 47.66?±?0.09?ng/mg dry weight, indicating a successful decellularization process. The results of glycosaminoglycan and hydroxyproline assay, and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), performed in order to characterize the extracellular matrix (ECM) composition of native and dBM tissue, showed that the BM matrix was not damaged during the proposed method. Lastly, regarding the histological study, dMEbF not only mimics native ECM, but also induces the stem cells into cardiomyocyte-like cells phenotype which brings it the potential of use in CTE.     

Thermodynamic performance analysis of three solid oxide fuel cell and gas microturbine hybrid systems for application in auxiliary power units

In this study, three different configurations of a solid oxide fuel cell and gas microturbine hybrid system are evaluated for application in auxiliary power units. The first configuration is a common hybrid system in auxiliary power units, utilizing a fuel cell stack in the structure of the gas turbine cycle. The other configurations use two series and parallel fuel cell stacks in the structure of the gas turbine cycle. The main purpose of this research is thermodynamic analysis, evaluation of the performance of the proposed hybrid systems in similar conditions, and selection of an appropriate system in terms of efficiency, power generation, and entropy generation rate. In this study, the utilized fuel cells were subjected to electrochemical, thermodynamic, and thermal analyses and their working temperatures were calculated under various working conditions. Results indicate that the hybrid system with two series stacks had maximum power generation and efficiency compared with the other two cases. Moreover, the simple hybrid system and the system with two parallel stacks had relatively equal pure power generation and efficiency. According to the investigations, hybrid system with two series fuel cell stacks, which had 3424 and 1712 cells, respectively, can achieve the electrical efficiency of over 48%. A hybrid system with two parallel fuel cell stacks, in which each stack had 2568 cells, had the electrical efficiency of 46.3%. Findings suggested that maximum electrical efficiency occurred between the pressure ratios of 5–6 in the proposed hybrid systems.     

Effect of sand and clay fouling on the shear strength of railway ballast for different ballast gradations

Ballast contamination by fine materials such as sand and clay in railway track at arid regions is an important issue that causes track instability problems and settlement due to reduction of shear strength of ballast. In this paper, the results of direct shear box test conducted on clean ballast, sand-fouled ballast and clay-fouled ballast for different ballast gradations are reported and discussed. For this purpose, three different fouling amounts according to fouling index are added to clean ballast. Test results show that by increasing the fouling percentage, the ballast shear strength always decreases both for sand and clay fouled ballast. However, the amount of shear strength reduction is low at high normal stresses. Clay contamination has more adverse effect on the shear strength of ballast compared with sand contamination. Also, the results of tests for evaluation of gradation effect on shear strength of fouled ballast which are conducted on various gradations according to American Railway Engineering and Maintenance-of-Way Association, show that the maximum particle size as well as uniformity coefficient affect the shear strength of ballast. Also, an empirical equation is presented to observe the effect of ballast gradation on reduction of shear strength with regard to amount of fouling material and normal stress.     

Pressure Management in Water Distribution Systems Using a Self-Tuning Controller to Distribute the Available Potable Water with Equality

The rapid population growth of cities in developing countries (DC) make difficult to distribute the available potable water (PW) with equality. The distribution problem arises from an insufficient amount of PW and because cities water distribution systems (WDS) are not efficient. The novelty of this paper is a self-tuning controller (STC) proposed to manage, along the day, the pressure of water through the nodes of a WDS. It means, pressure management (PM) is proposed to control water levels (WLs) in householders tanks (HTs). The objective is to satisfy with equality the PW demand at different zones of a city forcing the flow of water by managing the pressure. The proposed STC performance is tested on the digital simulator developed to characterize the hydraulic operation of a WDS. The dynamic behaviour of the WDS is determined by the variation of the WL in the tanks of the WDS when water is supplied or extracted from them. The WDS of Mexico City is analysed and the proposed STC is applied to a simplified WDS. The results allow to conclude that the proposed STC could become a supporting tool for the decision making of WDS operators.     

Imaging of two-dimensional unsaturated moisture flows in uncracked and cracked cement-based materials using electrical capacitance tomography

The development of visualizing tools to monitor unsaturated moisture flow in cement-based materials is of great importance, as most degradation processes in cement-based materials are connected to and take place in the presence moisture. This paper investigates the ability of electrical capacitance tomography (ECT) to image two-dimensional (2D) unsaturated moisture flow in cement-based materials. In ECT, the electrical permittivity distribution within an object is reconstructed based on measured capacitances between electrodes attached on the object’s surface. In a series of experiments, mortar specimens with and without discrete cracks were imaged with ECT during a 2D moisture ingress. The results show that ECT is able to monitor the evolution of the moisture flow, and to approximate the shape and position of the moisture front. These findings indicate that ECT is a viable method for monitoring and visualizing 2D unsaturated moisture flow in cement-based materials in the presence and absence of discrete cracks.