A theory of mode of action of azolylalkylquinolines as DNA binding agents using automated flexible ligand docking

Azolylalkylquinolines (AAQs) are a family of quinolines with varying degrees of cytotoxic activity (comparable or moderately superior to adriamycin in some cases) developed in the past decade in our group where their exact mode of action is still unclear. In this study the most probable DNA binding mode of AAQs was investigated employing a novel flexible ligand docking approach by using AutoDock 3.0. Forty-nine AAQs with known experimental inhibitory activity were docked onto d(CGCAAATTTGCG)(2), d(CGATCG)(2) and d(CGCG)(2) oligonucleotides retrieved from the Protein Data Bank (PDB IDs: 102D, 1D12 and 1D32, respectively) as the representatives of the three plausible models of interactions between chemotherapeutic agents and DNA (groove binding, groove binding plus intercalation and bisintercalation, respectively). Good correlation (r(2)=0.64) between calculated binding energies and experimental inhibitory activities was obtained using groove binding plus intercalation model for phenyl-azolylalkylquinoline (PAAQ) series. Our findings show that the most probable mode of action of PAAQs as DNA binding agents is via intercalation of quinolinic moiety between CG base pairs with linker chain and azole moiety binding to the minor groove.     

Non-parametric estimate of the system function of a time-varying system

The task of identifying an unknown dynamic system is made easier with prior knowledge on its behaviour. Using a frequency domain approach, the non-parametric maximum likelihood estimator of the system function, associated with the time-dependent impulse response of a time-varying system, is constructed. This is accomplished by the use of a simple linear least squares fitting algorithm, applied to the spectral response of the system to a multisine excitation. The noise variance on the system function is estimated simultaneously, and modelling errors can be detected, as illustrated on a simulation example.     

The Plasminogen–Activator Plasmin System in Physiological and Pathophysiological Angiogenesis

Angiogenesis is a process associated with the migration and proliferation of endothelial cells (EC) to form new blood vessels. It is involved in various physiological and pathophysiological conditions and is controlled by a wide range of proangiogenic and antiangiogenic molecules. The plasminogen activator–plasmin system plays a major role in the extracellular matrix remodeling process necessary for angiogenesis. Urokinase/tissue-type plasminogen activators (uPA/tPA) convert plasminogen into the active enzyme plasmin, which in turn activates matrix metalloproteinases and degrades the extracellular matrix releasing growth factors and proangiogenic molecules such as the vascular endothelial growth factor (VEGF-A). The plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of uPA and tPA, thereby an inhibitor of pericellular proteolysis and intravascular fibrinolysis, respectively. Paradoxically, PAI-1, which is expressed by EC during angiogenesis, is elevated in several cancers and is found to promote angiogenesis by regulating plasmin-mediated proteolysis and by promoting cellular migration through vitronectin. The urokinase-type plasminogen activator receptor (uPAR) also induces EC cellular migration during angiogenesis via interacting with signaling partners. Understanding the molecular functions of the plasminogen activator plasmin system and targeting angiogenesis via blocking serine proteases or their interactions with other molecules is one of the major therapeutic strategies scientists have been attracted to in controlling tumor growth and other pathological conditions characterized by neovascularization.     

Benchmarking large-scale data management for Internet of Things

The Journal of Supercomputing - In the current era of the Internet of Things (IoT), massive number of sensors are used in our daily lives. Sensors are everywhere around us. They exist in our homes,...     

High Productive Ethylene Trimerization Catalyst Based on CrCl<Subscript>3</Subscript>/SNS Ligands

Abstract  

Methylaluminoxane (MAO)-activated chromium (III) complexes of tridentate SNS ligands of the form (RSCH₂–CH₂)₂NH (R = alkyl, aryl) have been prepared and tested for the trimerization of ethylene to 1-hexene. The effect of ethylene pressure, Al/Cr ratio and S donor substitution on 1-C6 selectivity and productivity has been examined. It is shown that when the substitution on S is pentyl group it will lead to the highest productivity, 174200 g 1-C6/g Cr h, due to the synergistic effect of this group.     

Effect of Atmospheric Ageing on the Properties of Organosilicon (Pp-HMDSO) Thin Films

Silicon - This study reports the effect of ageing on plasma polymerized hexamethyldisiloxane (pp-HMDSO) thin films properties during 90&nbsp;days storage in the atmosphere. The monitoring of...     

Effect of cellulose acetate/cellulose triacetate ratio on reverse osmosis blend membrane performance

Surface functionalization and modification including the grafting process are effective approaches to improve and enhance the reverse osmosis (RO) membrane performance. This work is aimed to synthesize grafted/crosslinked cellulose acetate (CA)/cellulose triacetate (CTA) blend RO membranes using N-isopropylacrylamide (N-IPAAm) as a monomer and N,N-methylene bisacrylamide (MBAAm) as a crosslinker. The morphology of these membranes was analyzed by scanning electron microscopy and their surface roughness was characterized by atomic force microscopy. The performance of these membranes was evaluated through measuring two major parameters of salt rejection and water flux using RO unit at variable operating pressures. It was noted that the surface average roughness obviously decreased from 148 nm for the pure CA/CTA blend membrane with 2.5% CTA to 110 nm and 87 nm for the grafted N-IPAAm and grafted/crosslinked N-IPAAM/MBAAm/CA/CTA-RO membranes, respectively. Moreover, the contact angle decreased from 51.98° to 47.6° and 43.8° after the grafting and crosslinking process. The salt rejection of the grafted CA/CTA-RO membrane by 0.1% N-IPAAm produced the highest value of 98.12% and the water flux was 3.29 L/m²h at 10 bar.     

Highly transparent antibacterial hydrogel-polymeric contact lenses doped with silver nanoparticles

Biocompatible polymers such as poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) are used to prepare hydrogels for biomedical applications, including optical applications such as the manufacture of sensing devices, cosmetic and smart, and medical contact lenses, among others. In this study, three contact lenses were prepared by doping PVP-PVA supportive hydrogel with 0.1, 0.5, and 1 wt% of laboratory-manufactured Ag NPs. The work demonstrates the evaluation of vision correction through each lens and the effect of changing the concentration of silver on its refractive index. The simulation involved the design and simulation of an aberrated human eye based on the Liou and Brennan model (LBM), and the insertion of the contact lenses for vision correction using the ZEMAX optical design program. This work also included a study of the antimicrobial properties of the resulting hydrogel contact lenses doped with Ag NPs. The resulting refractive index of one PVP-PVA-Ag lens was relatively high at 532 nm = 1.604, which made the lens provide the highest image contrast (the lowest MTF curve degradation) of 0.883 ± 0.027 at 20 cycles/mm and an RMS nearly the Airy disc diameter of 3.983 μm. PVA was used in combination with PVP for stabilizing Ag NPs to give the contact lenses an antibacterial property. Finally, the optimum contact lens with a 1 wt% Ag NPs concentration showed the highest inhibition activity.     

Influence of monovalent cations and CuO nanoparticles on X-nanozeolite in uranium anionic species separation from contaminated drinking water

The main purpose of this work was the modification of NaX nanozeolite using copper oxide nanoparticles and various monovalent cations such as K~+, Cs~+, and Ag~+in order to make the negatively charged zeolite surface accessible for anionic forms of uranium which are the most dominant species of uranium in the contaminated radioactive waters at natural p H. Various methods such as the X-ray fluorescence(XRF), X-ray powder diffraction(XRD), field emission scanning electron microscopy(FE-SEM), transmission electron microscopy(TEM), Fourier transform infrared spectroscopy(FT-IR), and atomic absorption spectroscopy(AAS) were used to characterize the final synthesized absorbents. Batch technique was used to study the adsorption behavior of uranium ions from polluted drinking water by Na X nanozeolite and its modified forms. In order to better understand the performance of them, the results were compared with those that were obtained for synthesizing bulk NaX zeolite and Na-form of clinoptilolite natural zeolite. Preliminary results indicated that uranium sorption increased as the loading level of CuO nanoparticles on NaX nanozeolite increased from 2.1 wt% to 11.2 wt%. In addition,from the obtained data, an increase in uranium removal efficiency resulted as charge/ionic radius ratio of exchanged cation decreased. Also, the effect of contact time, solid–liquid ratio, initial concentration and temperature on the adsorption process was studied. It is worth mentioning that, in this study, the sorption of uranium was performed under natural conditions of pH and the presence of competing cations and anions which are available in drinking waters.