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Summary: Anaplastic lymphoma kinase (ALK), which belongs to the insulin receptor tyrosine kinase superfamily, plays an important role in nervous system development. Due to chromosomal translocations, point mutations, and gene amplification, constitutively activated ALK has been implicated in a variety of human cancers, including anaplastic large-cell lymphoma (ALCL), non-small cell lung cancer, and neuroblastoma. We evaluated the anti-cancer activity of the ALK inhibitor KRCA-0008 using ALCL cell lines that express NPM (nucleophosmin)-ALK. KRCA-0008 strongly suppressed the proliferation and survival of NPM-ALK-positive ALCL cells. Additionally, it induced G0/G1 cell cycle arrest and apoptosis by blocking downstream signals including STAT3, Akt, and ERK1/2. Tumor growth was strongly suppressed in mice inoculated with Karpas-299 tumor xenografts and orally treated with KRCA-0008 (50 mg/kg, BID) for 2 weeks. Our results suggest that KRCA-0008 will be useful in further investigations of ALK signaling, and may provide therapeutic opportunities for NPM-ALK-positive ALCL patients. [ABSTRACT FROM AUTHOR]

Researchers and donors consider informal recyclers as an important part of improving waste management in developing countries. This study investigates data relating to the recycling rate of waste pickers in Bantar Gebang, Republic of Indonesia. The study estimates the net weight of soft plastic and hard plastic recycling achieved by these waste pickers. Data were obtained from qualitative and quantitative field surveys conducted over a total of 808 days, from February 2010 to January 2018. Based on 78 households with a total of 156 individuals, the average monthly weight of collected recyclables was 126.7 kg per household. The average monthly weight of collected recyclables on an individual basis varied between 81.0 and 63.3 kg, depending on the number of informal recyclers in the household. The estimated total weight of collected recyclables was 3617.6 tons per month. Bosses sold these collected recyclables to different recycling factories depending on the expected profit. It was estimated that the activities of the waste pickers produced at least 725.4 tons of recycled pellets of soft plastic and 280.8 tons of recycled pellets and flakes of hard plastic. The informal recycling rate for all waste and non-organic waste on the site was 1.6% and 9.3%, respectively. [ABSTRACT FROM AUTHOR]

An extensive phytochemical investigation on the roots of Glycyrrhiza uralensis led to the isolation of two new minor chalcone acetylglycosides, i.e., 6″- O-acetylisoliquiritin ( 1) and 6″- O-acetylneoisoliquiritin ( 2), including 16 kinds of known constituents ( 3-18) of flavonoids, chalcones and triterpene saponins. The chemical structures of 1 and 2 were established by spectroscopic analyses of them, particularly by the aid of two-dimensional NMR experiments, COSY, DEPT, HSQC and HMBC. Some isolated components except 1 and 2 exhibited significant inhibitory effects on the proliferation of cultured tumor cell lines, such as A549, SK-OV-3, A-498, and HCD15, in vitro. [ABSTRACT FROM AUTHOR]

Synthesis of reusable biomimetic enzymes was generated with the goal of cost-effective production of the enzyme for the application in bioconversion of lignocellulosic biomass. The current report describes the preparation and characterization of a biomimetic magnetic nanoenzyme (BMNE), functionalized with a carboxylic acid group that hydrolyzes β-1,4-glycosidic bonds with high catalytic efficiency. The nanometer scale of a BMNE allows it to structurally mimic the active sites of biomass-degrading enzymes. The BMNE functioned optimally at pH 3. The combination of BMNE with natural enzymes had a synergistic action on rice straw, increasing sugar release by 29.7 % and reducing hydrolysis time relative to the natural enzyme alone. The BMNE retained significant activity after five consecutive reaction cycles. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Syntheses of various bis- ortho-alkoxy- para-piperazineanilino-pyrimidines and -triazines of KRCA-0008 analogs are described and their structure-activity-relationship to anaplastic lymphoma kinase (ALK) is discussed. 5-trifluoromethyl-2,4-pyrimidine analog (2) seems to be most potent in both biochemical and cellular assay in this study, however it shows inferior mice xenograft activity to Crizotinib presumably due to its sub-optimal PK parameters. 4,6-disubstituted pyrimidine and 2,4-disubstituted triazine derivatives of KRCA-0008 are less potent or inactive to ALK wt., and this observation is explained with their molecular modeling compared to KRCA-0008. [ABSTRACT FROM AUTHOR]

A new series of 2,4-dianilino-5-fluoropyrimidine derivatives were designed and synthesized and their anaplastic lymphoma kinase (ALK) inhibitory activities were evaluated by biochemical and cell-based assays in order to discover a new ALK inhibitor. Most compounds synthesized showed good inhibitory activities against ALK and good cytotoxic activities in H3122 cell line. The best compound 6f showed good activity against wild-type ALK along with crizotinib-resistant mutant ALK, and it showed 6 times better activity in cell-based assay than crizotinib. Some SAR studies were performed by the comparisons of the activities between 6 and the designed-synthesized compounds. [ABSTRACT FROM AUTHOR]

Various carbon-based particles such as graphite, carbon black, graphite nanofibers and carbon nanotubes were dispersed in mineral oil to systematically examine the effect of the size and shape of particles on the properties of friction performance. As the results of friction tests using a disc-on-disc tribotester, the friction coefficient of a disc specimen was significantly reduced when nano-sized spherical particles were suspended in mineral oil. This was attributed to the presence of spherical nanoparticles, which prevented direct contact between frictional surfaces. However, the fibrous nanoparticles with high aspect ratios deteriorated the lubrication performance between friction surfaces due to a higher degree of agglomeration. [ABSTRACT FROM AUTHOR]

The heating performance of a water-to-refrigerant type ground source heat pump system is represented in this paper under the actual working conditions of the GSHP (ground source heat pump) system during the winter season of 2008. Ten heat pump equipments with the capacity of 10 HP each and a closed vertical typed-ground heat exchanger with 24 boreholes of 175 m in depth were constructed. We investigated a variety of working conditions, including the outdoor temperature, the ground temperature, and the water temperature of inlet and outlet of the ground heat exchanger in order to examine the heating performance of the GSHP system. Subsequently, the heating capacity and the input power were investigated to determine the heating performance of the GSHP system. The average heating coefficient of performance (COP) of the heat pump was noted to be 5.1 at partial load of 47%, while the overall system COP was found to be 4.2. Also, performance of the GSHP system was compared with that of air source heat pump. [ABSTRACT FROM AUTHOR]

The Viscoelastic Continuum Damage (VECD) model has been implemented into a finite element package (FEP++) to predict the fatigue performance of asphalt concrete (AC) mixtures tested at the Federal Highway Administration Accelerated Load Facility (FHWA ALF) and the Korea Expressway Corporation (KEC) test road project sites. Both the VECD model and the FEP++ were developed at North Carolina State University. The conceptual approach taken for this research is to separate the characteristics of the pavement system that are related to the material from those related to the boundary conditions. It is believed that this study is the first application of an integrated structural/material mechanistic model for the fatigue performance prediction of AC pavements where damage in the asphalt layers is considered for the full time history and where the change in stiffness due to damage evolution is captured in the subsequent calculation of damage. The VECD model accounts for the viscoelastic nature of AC mixtures with growing damage, whereas the finite element model accounts for other important characteristics, such as temperature, layer thickness, stiffness gradient, etc. The controlled FHWA ALF experiment allows a direct comparison between observed and modeled fatigue performance. Because the KEC test road experiment is subjected to real and variable traffic and environmental factors, the finite element simulation results are used to examine the effects of specific parameters in the pavement system on fatigue performance. In this regard, the model is found to effectively capture the effects of changes in layer thickness, layer material, and layer type. The need to develop transfer functions for true field performance prediction is also shown, and a simple example function is developed as proof of this concept. [ABSTRACT FROM AUTHOR]

An alumina ball milling method was applied to enhance the adhesiveness and smoothness of the diaphragm-to-housing (D-H) junction. The impact produced by the three rotating alumina balls along the meshed junction made the surface of the junction uniform and smooth. The quality of the D-H junction was evaluated by various methods, such as inspection using an optical microscope and a scanning electron microscope, smoothness examination by an atomic force microscope, and measurement of the tensile strength. All the evaluations revealed marked improvements, and the platelet adhesion test revealed that the alumina ball milling method plays an important role in the blood compatibility enhancement of the D-H junction. [ABSTRACT FROM AUTHOR]

Transcriptional variation in histologically- and genetically- identical cells is a widespread phenomenon in tissues, yet the processes conferring this heterogeneity are not well understood. To identify contributing factors, we analyzed epigenetic profiles associated with the in vivo transcriptional gradient of the mouse lactase gene (Lct), which occurs in enterocytes along the proximal-to-distal axis of the small intestine. We found that epigenetic signatures at enhancer and promoter elements aligns with transcriptional variation of Lct in enterocytes. Age and phenotype-specific environmental cues (lactose exposure after weaning) induced changes to epigenetic modifications and CTCF binding at select regulatory elements, which corresponded to the alterations in the intestinal Lct mRNA gradient. Thus, epigenetic modifications in combination with CTCF binding at regulatory elements account for the transcriptional gradient in Lct in cells of the same type. Epigenetic divergence within enterocytes may contribute to the functional specialization of intestinal subregions. [ABSTRACT FROM AUTHOR]