2,4-Diamino-5-(2'-arylpropargyl)pyrimidine derivatives as new nonclassical antifolates for human dihydrofolate reductase inhibition

Dihydrofolate reductase (DHFR) has been a well-recognized target for the development of therapeutics for human cancers for several decades. Classical inhibitors of DHFR use an active transport mechanism to gain access to the cell; disabling this mechanism creates a pathway for resistance. In response, recent research focuses on nonclassical lipid-soluble DHFR inhibitors that are designed to passively diffuse through the membrane. Here, a new series of propargyl-linked antifolates are investigated as potential nonclassical human DHFR inhibitors. Several of these compounds exhibit potent enzyme inhibition with 50% inhibition concentration values under 500 nM. Molecular docking investigations show that the compounds maintain conserved hydrogen bonds between the pyrimidine ring and the enzyme as well as form van der Waals interactions with critical residues in the active site. Interestingly, the most potent compound, 2,4-diamino-5-(3-(3,4,5-trimethoxyphenyl)prop-1-ynyl)-6-ethylpyrimidine (compound 35), is 3500-fold more potent than trimethoprim, a potent inhibitor of bacterial DHFR but weak inhibitor of human DHFR. The two structural differences between compound 35 and trimethoprim show that the propargyl linkage and the substitution at C6 of the pyrimidine ring are critical to the formation of contacts with Thr 56, Ser 59, Ile 60, Leu 22, Phe 31 and Phe 34 and hence, to enhancing potency. The propargyl-linked antifolates are efficient ligands with a high ratio of potency to the number of non-hydrogen atoms and represent a potentially fruitful avenue for future development of antineoplastic agents.     

Decentralized Coordination Control for a Network of Mobile Robotic Sensors

A decentralized control approach is presented for a network of robotic sensors to achieve the global coordination: group aggregation or consensus flocking. Each robotic sensor obeys three local interaction rules: group cohesion, collision avoidance and velocity alignment. Accordingly, the resultant control law for each robotic sensor is composed of three associated control components. The cohesion control component is based on geometry and additionally enables maintaining initial interconnection of network. The alignment control component ensures that all members in an interconnected network eventually reach to a common velocity. The control component for collision avoidance among members, as a passive role, is embedded in cohesion control. Simulation results demonstrate the capability of the proposed control approach in achieving the coordination behaviour with an initially interconnected network. However, we observed that an initially non-interconnected network may also achieve the coordination behaviour depending on the initial distribution and velocities. Initial interconnection of a network is only a sufficient but not essential condition for the network to achieve the coordination behaviour for our control approach.     

An artificial neural network model for the prediction of critical submergence for intake in a stratified fluid medium

Density differences may occur because of temperature differentials, suspended sediments, dissolved salts or other chemicals. Most of the large surface reservoirs are stably stratified throughout most, or all, of the year. One of the means of assisting the management is to allow a selective withdrawal from the reservoir. And while an intake is used for withdrawal (from the lower layer), a maximum discharge is required not allowing the uptake of the upper layer fluids. The value of the intake's vertical distance from the upper layer elevation (submergence) when the upper layer fluids begin to be drawn into the intake is known as ‘critical submergence’. In this study, the critical submergence for a circular intake pipe in a stratified body (which has different layer thickness) is investigated. Experiments were conducted on a vertically flowing downward intake pipe in a still-water reservoir. Artificial neural network (ANN) models and formulas, which are found by the theoretical analysis of critical spherical sink surface (CSSS), are used for the analysis of experimental results. The CSSS has the same centre and discharge as the intake. The ANN model and CSSS results are compared with the experimental results.     

Enzymatic polymerization of polythiophene by immobilized glucose oxidase

In this study ‘green’, environmentally friendly enzymatic reaction-based synthesis of conducting polymer polythiophene (PTP) is proposed. Glucose oxidase (GO_x) was shown as an effective catalyst, which, in the presence of glucose, produces hydrogen peroxide suitable for the oxidative polymerization of PTP under ambient conditions at neutral pH. Enzymatically induced formation of the PTP layer over GO_x-modified graphite rod electrode (GRE) was demonstrated and evaluated amperometrically and by attenuated total reflectance – Fourier transform infrared (ATR-FTIR) spectroscopy. Surface morphology of GO_x- and PTP-modified GR electrodes was characterized by atomic force microscopy. It was clearly shown that the apparent kinetic Michaelis constant (K_M(app.)) of GO_x/PTP-modified GRE increased by increasing the duration of polymerization reaction. Therefore, enzymatic polymerization could be applied in adjustment and/or tuning of K_M(app.) and other kinetic parameters of GO_x-based electrodes used in biosensor design.     

Dyeing of poly(lactic acid) fibres with synthesised novel heterocyclic disazo disperse dyes

Poly(lactic acid) (PLA) is the first melt‐processable, renewable, sustainable and biodegradable natural‐based synthetic fibre. It has a broad range of uses and combines ecological advantages with outstanding performance in textiles. PLA fibre, as an aliphatic polyester, can be dyed with disperse dyes. Apart from the limited number of commercial disperse dyes, disperse dye exhaustion on PLA is generally lower than that on  poly(ethylene terephthalate) (PET). In this study, new heterocyclic disazo disperse dyes, substituted with methyl, nitro and chloro groups at their ortho‐, meta‐ and para‐ positions, synthesised in our previous study, were applied to PLA and PET fibres to examine their dyeing performance, and colour fastness and dye exhaustion properties. Different shades of yellow, orange, reddish brown and brown were obtained. Most of the synthesised novel heterocyclic disazo disperse dyes exhibited good build‐up properties with high K/S levels on both fibres. Para‐ bonding substituent provided higher K/S values than meta‐ and ortho‐ positions for –NO₂ and –Cl substituents for both fibres. Overall, the most synthesised novel heterocyclic disazo disperse dyes in this study exhibited good build‐up properties with high K/S, exhaustion and wet fastness levels on both PLA and PET fibres.      

Effect of Ultrasonic Irradiation on the Treatment of Poly-Aromatic Substances (PAHs) from a Petrochemical Industry Wastewater

The effects of sonication time, nitrogen, N₂(g), increasing temperature, dissolved oxygen (DO) and titanium dioxide (TiO₂) concentrations on the sonodegradation of polyaromatic hydrocarbons (PAHs) in petrochemical wastewaters were investigated. Sonication alone without N₂(g), DO and TiO₂ provided 80% maximum PAH yields at 2 5°C after 150 min. This PAH yield increased to 89–95% at 60 °C after 150 min sonication. The contribution of DO, N₂(g) and TiO₂ on the PAH removal was not significant compared to the control. In the presence of HCO₃ ^?, the degradation of hydrophobic PAH dibenz[a,h]anthracene (DahA)was suppressed in the acceleration step of the sonication. Maximum acute toxicity removal was reached by 30 min N₂(g) sparging, 4 mg/L DO and by 0.1 mg/L TiO₂ after 150 min sonication.     

Recovery of metals from complexed solutions by electrodeposition

Electrolytic recovery of metals from aqueous solutions containing complexing chelating agents such as EDTA, NTA, and citrate was studied in a two-chamber cell separating with a commercial cation-exchange membrane (CEM). Equimolar solutions of metal and a chelating agent as a catholyte and NaNO₃ as an anolyte were used; the effect of current densities, initial catholyte and anolyte pH, metal concentration and the type of the CEM, chelating agent and metal on the recovery of metals was determined. The recovery of metal increased with higher initial anolyte pH, concentration and current density, whereas it decreased with lower initial catholyte pH. The results show that electrodeposition seems to be an applicable method for the recovery of metals under appropriate conditions.     

Robust quadratic stabilization applied to design of continuous-time and discrete-time observers

In this paper, an application of a robust quadratic stabilization algorithm (RQSA) to continuous-time and discrete-time observers is presented. The RQSA is based on checking end points of a bounding hyperpolyhedron. The RQSA applied to observers is introduced, and implemented for a simplified car model, in both continuous-time and discrete-time case. The paper concludes that the RQSA is feasible to estimate unavailable states, even though there are structured uncertainties in the system matrix and in the measurement matrix.     

2,4,6 Tri-Chlorophenol Containing Wastewater Treatment Using a Hybrid-Loop Bioreactor System

A hybrid-loop bioreactor system consisting of a packed column biofilm and an aerated tank bioreactor with an effluent recycle was used for biological treatment of 2,4,6 tri-chlorophenol (TCP) containing synthetic wastewater. The effects of sludge age (solids retention time) on chemical oxygen demand (COD), TCP, and toxicity removal performance of the system were investigated for sludge ages between 5 and 30?days, while the feed COD (2600±100?mg?L?1), TCP (370±10?mg?L?1), and the hydraulic residence time (25?h) were constant. Percent TCP, COD, and toxicity removals increased with increasing sludge age resulting in nearly complete COD, TCP, and toxicity removal at sludge ages above 20?days. Biomass concentrations in the packed column and in the aeration tank increased with increasing sludge age resulting in low reactor TCP concentrations, and therefore, high TCP, COD, and toxicity removals. More than 95% of COD, TCP, and toxicity removal took place in the packed column reactor. Volumetric rates of TCP and COD removal increased due to increasing biomass and decreasing effluent TCP and COD concentrations with increasing sludge age. The specific rate of TCP removal was maximum (120?mg?TCP?gX?1?day?1) at a sludge age of 20?days. TCP inhibition was eliminated by operation of the system at sludge age above 20?days to obtain nearly complete COD, TCP, and toxicity removal.