Identification of 3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine Derivatives as Novel Selective Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase

Plasmodium falciparum’s resistance to available antimalarial drugs highlights the need for the development of novel drugs. Pyrimidine de novo biosynthesis is a validated drug target for the prevention and treatment of malaria infection. P. falciparum dihydroorotate dehydrogenase (PfDHODH) catalyzes the oxidation of dihydroorotate to orotate and utilize ubiquinone as an electron acceptor in the fourth step of pyrimidine de novo biosynthesis. PfDHODH is targeted by the inhibitor DSM265, which binds to a hydrophobic pocket located at the N-terminus where ubiquinone binds, which is known to be structurally divergent from the mammalian orthologue. In this study, we screened 40,400 compounds from the Kyoto University chemical library against recombinant PfDHODH. These studies led to the identification of 3,4-dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine and its derivatives as a new class of PfDHODH inhibitor. Moreover, the hit compounds identified in this study are selective for PfDHODH without inhibition of the human enzymes. Finally, this new scaffold of PfDHODH inhibitors showed growth inhibition activity against P. falciparum 3D7 with low toxicity to three human cell lines, providing a new starting point for antimalarial drug development.     

Numerical evaluation of laminar heat transfer enhancement in nanofluid flow in coiled square tubes

Convective heat transfer can be enhanced by changing flow geometry and/or by enhancing thermal conductivity of the fluid. This study proposes simultaneous passive heat transfer enhancement by combining the geometry effect utilizing nanofluids inflow in coils. The two nanofluid suspensions examined in this study are: water-Al2O3 and water-CuO. The flow behavior and heat transfer performance of these nanofluid suspensions in various configurations of coiled square tubes, e.g., conical spiral, in-plane spiral, and helical spiral, are investigated and compared with those for water flowing in a straight tube. Laminar flow of a Newtonian nanofluid in coils made of square cross section tubes is simulated using computational fluid dynamics (CFD)approach, where the nanofluid properties are treated as functions of particle volumetric concentration and temperature. The results indicate that addition of small amounts of nanoparticles up to 1% improves significantly the heat transfer performance; however, further addition tends to deteriorate heat transfer performance.     

Plasma-activated immobilization of biomolecules onto graphite-encapsulated magnetic nanoparticles

We describe the amino group surface functionalisation of graphite-encapsulated iron compound nanoparticles by radio frequency (RF) plasma processing followed by oxidized dextran immobilization. We have found that surface treatment using plasma represents an important step before biomolecules immobilization. After plasma treatment, the dispersion property of nanoparticles in dextran solution in water was significantly improved. The successful dextran immobilization was confirmed by X-ray photoelectron spectroscopy (XPS) and high resolution-transmission electron microscopy (HR-TEM) analyses followed by amino group derivatization using 4-(trifluoromethyl)-benzaldehyde (TFBA). As an evidence for covalent bonding between nanoparticles and dextran, the area percentage of deconvoluted CN peak at ～389.6 eV increased from 0% to 10.53 ± 1.30% with increasing the dextran concentration. The result is consistent with the evidenced decreasing of the free amino group percentage from 68.09 ± 5.10% to 14.73 ± 5.89% on the nanoparticle surface after dextran immobilization.     

Thermal Performance of Coiled Square Tubes at Large Temperature Differences for Heat Exchanger Application

In many heat exchanger applications, working fluid inside the tubes is subjected to considerable temperature changes. Coiled tubes are used widely in heat exchanger applications due to the enhanced heat transfer rate caused by secondary flows. This study examines the thermal performance of three configurations of coiled tubes of square cross-section, namely, in-plane, helical, and conical coiled tubes, subjected to a large temperature difference between the fluid and the wall and compares it with that of a straight tube of identical cross-section area and length. The concept of figure of merit (FoM) is introduced to compare the heat transfer performance of the various configurations tested. The results indicate that FoM increases as the wall temperature is increased. In addition, the combination of temperature-induced buoyant flow and curvature-induced secondary flow significantly affects the flow behavior and heat transfer performance inside the tubes. The coil pitch in helical and conical tubes has an adverse effect on the heat transfer performance due to shift in vortices generation. The in-plane spiral tube operates at a higher wall temperature and lower Reynolds number, which gives rise to a higher FoM. The highest Nusselt number is obtained for the in-plane spiral tube at higher wall temperature and higher Reynolds number, which shows potential for practical applications.     

Energy-efficient thermal drying using impinging-jets with time-varying heat input – A computational study

This study investigates the performance of impinging-jet drying at various configurations. The computational fluid dynamic (CFD) approach was used for solving the conjugated heat/mass transfer problem during drying with impinging-jets. In short, the model considers slab material with drying chamber, and solve for conservation equations of mass, momentum, species and energy with associated turbulence model. To ensure the validity of the mathematical model, validation with the experimental data is carried out. The effect of jet velocity, pulsation and intermittency on the jet inlet, slab geometry and slab thickness are then investigated. The results are then examined to obtain optimum conditions for impinging-jet drying of model materials in the form of a thin slab. Finally, it is noted that lower energy consumption of impinging-jet with pulsating and/or intermittent flow offers comparable drying kinetics as compared to that with that of a steady jet, which shows potential for energy saving.     

Analysis of lard in meatball broth using Fourier transform infrared spectroscopy and chemometrics

Meatball is one of the favorite foods in Indonesia. For the economic reason (due to the price difference), the substitution of beef meat with pork can occur. In this study, FTIR spectroscopy in combination with chemometrics of partial least square (PLS) and principal component analysis (PCA) was used for analysis of pork fat (lard) in meatball broth. Lard in meatball broth was quantitatively determined at wavenumber region of 1018–1284 cm^− 1. The coefficient of determination (R²) and root mean square error of calibration (RMSEC) values obtained were 0.9975 and 1.34% (v/v), respectively. Furthermore, the classification of lard and beef fat in meatball broth as well as in commercial samples was performed at wavenumber region of 1200–1000 cm^− 1. The results showed that FTIR spectroscopy coupled with chemometrics can be used for quantitative analysis and classification of lard in meatball broth for Halal verification studies. The developed method is simple in operation, rapid and not involving extensive sample preparation.     

Finite deformation of fast-response thermo-sensitive hydrogels – A computational study

This computational study investigates three-dimensional, finite deformation of four common shapes – rod, disc, cube, and sphere – for fast-response, thermo-sensitive hydrogels. These hydrogels have an inherent advantage in their fast-response to stimuli, making them attractive components for a wide range of applications. Here, two basic hydrogels with varying compositions are considered: semi-interpenetrating-networked and macroporous poly(N-isopropylacrylamide). The predicted equilibrium swelling and deformation kinetics are calibrated and validated with their experimental counterparts. In short, the results suggest that the deformation kinetics of a hydrogel is significantly influenced by its geometry; however, the equilibrium swelling ratio of the hydrogels is found to be independent of their geometries. Within the mathematical framework one can also explore the stress distribution within the hydrogels as well as other related parameters. In addition, the model can be extended to account for other stimuli, such as glucose and alcohol.     

Air quality monitoring and analysis with dynamic training using deep learning

The Journal of Supercomputing - Time series prediction is a challenging predictive modeling case. It is essential to have a prediction model that can adapt to dynamic data. Air quality data show a...     

Cyberattack detection model using deep learning in a network log system with data visualization

The Journal of Supercomputing - Network log data is significant for network administrators, since it contains information on every event that occurs in a network, including system errors, alerts,...