The search of new negative allosteric GABAB receptor modulators using in silico and in vitro approaches

γ-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the CNS. GABA exerts its function on both ionotropic ligand-gated GABAA receptors and metabotropic GABAB G-protein coupled receptors (GPCRs). Disruption in the GABAergic system has been associated with numerous neurological and psychiatric disorders in humans. These include developmental dysfunctions, epilepsy, sleep disorders, drug and alcohol dependence, schizophrenia, motor coordination disorders, anxiety, autism, inability to regulate emotions, Huntington's disease, and Parkinson's disease. Hence, developing drugs to act on such a remarkable system can attract much attention and be beneficial. In recent years, there has been colossal attention toward development of allosteric modulators of GPCRs. These compounds provide high selectivity, novel modes of action and may lead to unique therapeutic agents for the treatment of many neurological and psychiatric human disorders. Baclofen, a GABAB receptor agonist, is still the only GABAB receptor approved drug, and is used for the treatment of muscle spasticity associated with spinal cord injury and multiple sclerosis; however, numerous side effects hamper its clinical use. Allosteric modulators, on the other hand, are expected to have a much better side-effect profile than traditional orthosteric drugs. In the current study, in silico and in vitro methods were adopted to screen for potential negative allosteric modulators within the MolPort database. A sequential combination of ligand- and structure-based virtual screening was first performed to reduce the significant number of chemical compounds followed by the in vitro experimental testing. The virtual screening procedure facilitated the selection of 16 hit compounds that were purchased and tested experimentally using an in vitro functional assay. Only one compound, A-8, was tested in a dose-response cAMP assay, and results indicate that it is a negative allosteric modulator. In addition, analysis of the initial test results suggests that A-9 might be a negative allosteric modulator and that A-20 might be a positive allosteric modulator. Further accurate experimental tests are required for these compounds

Stability and Rupture of Liquid Film Flowing Down an Inclined Plane

Liquid film flowing down inclined or vertical planes find applications in thin film heat and mass transfer, wetted wall columns, liquid drainage in packed columns, surface coating operations, and the like. The film is modeled as a two-dimensional Newtonian liquid of constant density p and viscosity u flowing down an inclined plane. The liquid film of mean thickness ho is bounded above by a passive gas and laterally extends to infinity (two-dimensional model). Then such a flow can be represented by a two-dimensional Navier-Stokes equation coupled with continuity equation and associated boundary conditions. The body force term in the Navier-Stokes equation is modified by the inclusion of excess intermolecular interactions between fluid film and the solid surface owing to long-range van der Waals force, in addition to gravity force. The modified Navier-Stokes equation with associated boundary conditions is solved under long wave approximation method to obtain a nonlinear equation of evolution of the film interface. A nonlinear theory based upon the condition of infinitesimal perturbation on the film surface is derived to obtain the growth coefficient, dominant wavelength (i.e., wavelength corresponding to maximum growth coefficient of the surface instability) and the film rupture time. The nonlinear equation of evolution is solved numerically in conservative form as part of an initial-value problem for spatially periodic boundary condition on the fixed domain 0< x< 21t/k, where k is a wavenumber. Centered difference in space and the midpoint (Crank-Nicholson) rule in time are employed. The mesh size is taken sufficiently small so that space and time errors are negligible. The nonlinear algebraic equations obtained as a result of finite difference discretization are solved using efficient-numerical technique employing IMSL subroutine DNEQNJ. The nonlinear simulation shows that the dominant wavelengths (corresponding to minimum time) for film rupture are very close to the prediction of the linear theory for all types of films. There seems to be no influence of surface inclination on the instability of thin films. Inclination dose influence the growth of instability in thick films. The film rupture time increases with increasing film thickness for inclined planes. Increase in the amplitude of perturbation results into decreased time of rupture. The deviations between the predictions of nonlinear and linear theory results are minimum around dominant wavelength. The linear theory may overestimate or underestimates the time of rupture by several orders of magnitude depending upon thin film parameters. Hence linear theory is inadequate to describe the stability characteristics of inclined films and therefore, the need of a nonlinear approach to the study of inclined film dynamics

Synthesis, Characterization and Application of Carbon Nanotubes and Carbon Nanofibers

Well aligned multi wall carbon nanotubes (MWCNTs), carbon nanofibers (CNFs) and other type of carbon nanostructure materials have been synthesized by a fabricated floating catalyst chemical vapor deposition (FC-CVD) method. This involved the pyrolysis of benzene-ferrocene vapor mixture. The CVD parameters (Hydrogen flow rate, reaction time and reaction temperature) were studied to selectively synthesize nanotubes and nanofibers with required dimensions. Carbon nanotubes films with a diameter of 2-50 nm and nanofiber with a diameter range from 100-300 nm were synthesized in a benzenelhydrogen atmosphere. Furthermore vapor grown carbon fibers have been synthesized with different diameters and lengths. Iron clusters that were produced from the thermal decomposition of ferrocene films were used as catalyst for the synthesis of the carbon structures.The effects of different hydrogen flow rates (50-500 ml/min) on the morphology, quality and quantity of the product were investigated. Maximum yield and purity was obtained at 300 ml/min. The effect of the reaction time on the purity and yield of carbon nanotubes was studied from 1 minute to 60 minutes. There was no effect of the reaction time on the average diameter while maximum yield of carbon nanotubes was achieved at 45 minutes. The last variable was the reaction temperature, which was varied from 500 "C to 1200 "C. By controlling the growth temperature, carbon nanotubes (CNTs), carbon nanofibers (CNFs) and vapor grown carbon fiber with different structures were produced. Increasing the temperature has a remarkable effect on the size and shape of the catalyst and this in turn affected the diameter distribution and structure of the carbon materials. The carbon nanotubes were produced from 600 "C to 850 "C with maximum yield at 850 "C, while for the production of carbon nanofibers the reaction temperature was from 900 "C to 1000 "C with a maximum yield at 1000 "C. Vapor grown carbon fibers were produced at 1050 "C to 1200 "C with maximum yield at 1050 "C. The synthesised nanotubes/nanofibers were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) .The thermal degradation kinetics of CNTs was investigated by dynamic thermogravimetry, in an air atmosphere, over the temperature range 25 - 800 "C and at constant nominal heating rate 10 "C / min. The corresponding activation energies, frequency factors and reaction orders were determined. Homogenous distribution of MWCNTsICNFs in natural rubber (NR) was achieved by ultrasonic assisted solution-evaporating method. Addition of 1-10 wt% of CNFs and CNTs to natural rubber as nanocomposite increased the rubber mechanical properties significantly. The properties of the composites such as tensile strength, tensile modulus, and elongation at break were studied. In addition to mechanical testing, the dispersion state of the MWNTs into NR was studied by TEM in order to understand the morphology of the resulting system. The result indicated that, by increasing the amount of CNTs and CNFs into the natural rubber the ductility decreased and the material became stronger and tougher but at the same time more brittle. The results showed that by adding 1 wt% of CNTs and CNFs to NR the stress level were increased sharply to 0.56413 and 0.54 MPa respectively compared to NR which was 0.2839 MPa. At 10 wt% the stress level of CNTs with NR were increased sharply 9 times and reached to 2.55 MPa while for CNFs it increased 4.66 times and reached to 1.33 MPa

Development and Validation of a Kinetic Model for Enzymatic Hydrolysis Using \u3ci\u3eCandida rugosa\u3c/i\u3e Lipase

Biochemical processing involving enzymatic catalysis of hydrolysis reactions of oils and fats must overcome significant technological barriers before the full benefits of the technology can be realized. Owing to their selectivity and mild reaction conditions, lipases are becoming increasingly important as biocatalysts provided that their kinetics and optimum reaction conditions are well-understood. In this study we report on the development and validation of a kinetic model for the degradation of oils using Candida rugosa lipase, from which a better understanding of the influence of different reaction conditions on hydrolysis kinetics is elucidated. Variations of reaction temperature, mixing speed, enzyme loading and substrate concentrations yielded a maximum lipase activity of 25.67 lipase units (LU), and an activation energy of 4.32 Kcal/gmol. Significantly higher enzyme loading at 0.7 mg/ml was achieved, a 169% increase over most recently reported loading by other investigators. Optimum operating ranges for medium pH and substrate concentration were established to be 7.5 to 8.5, and 30 to 55%, respectively. Reported findings mark a significant improvements over previously reported much narrower ranges of 8.0 for pH and 30 to 43% for the substrate concentration under similar experimental conditions. Developed kinetics model closely predicted and matched experimental results, rendering it suitable for biochemical engineering design application

Multi-wall carbon nanotubes/styrene butadiene rubber (SBR) nanocomposite

A floating catalyst chemical vapor deposition (FC-CVD) method was designed and fabricated to produce high-quality and -quantity carbon nanotubes. The design parameters like the hydrogen flow rate; reaction time and reaction temperature were optimized to produce high yield and purity of Multi-Wall Carbon Nanotubes (MWCNTs). Multi-Walled Carbon Nanotubes (MWNTs) were used to prepare natural rubber (NR) nanocomposites. Our first efforts to achieve nanostructures in MWNTs/styrene butadiene rubber (SBR) nanocomposites were formed by incorporating carbon nanotubes in a polymer solution and subsequently evaporating the solvent. Using this technique, nanotubes can be dispersed homogeneously in the NR matrix in an attempt to increase the mechanical properties of these nanocomposites. The properties of the nanocomposites such as tensile strength, tensile modulus, elongation at break and hardness were studied. Using different percentages of carbon nanotubes from 1 wt% to 10 wt%, several nanocomposites samples were fabricated. Significant improvements in the mechanical properties of the resulting nanocomposites showed almost 10% increase in the Young’s modulus for 1 wt% of CNTs and up to around 200% increase for 10 wt% of CNTs

Fast Disinfection of Escherichia coli

Water disinfection has attracted the attention of scientists worldwide due to water scarcity. The most significant challenges are determining how to achieve proper disinfection without producing harmful byproducts obtained usually using conventional chemical disinfectants and developing new point-of-use methods for the removal and inactivation of waterborne pathogens. The removal of contaminants and reuse of the treated water would provide significant reductions in cost, time, liabilities, and labour to the industry and result in improved environmental stewardship. The present study demonstrates a new approach for the removal of Escherichia coli (E. coli) from water using as-produced and modified/functionalized carbon nanotubes (CNTs) with 1-octadecanol groups (C18) under the effect of microwave irradiation. Scanning/transmission electron microscopy, thermogravimetric analysis, and FTIR spectroscopy were used to characterise the morphological/structural and thermal properties of CNTs. The 1-octadecanol (C18) functional group was attached to the surface of CNTs via Fischer esterification. The produced CNTs were tested for their efficiency in destroying the pathogenic bacteria (E. coli) in water with and without the effect of microwave radiation. A low removal rate (3–5%) of (E. coli) bacteria was obtained when CNTs alone were used, indicating that CNTs did not cause bacterial cellular death. When combined with microwave radiation, the unmodified CNTs were able to remove up to 98% of bacteria from water, while a higher removal of bacteria (up to 100%) was achieved when CNTs-C18 was used under the same conditions

Performance of electrical discharge machining (EDM) with nickel added dielectric fluid

In this study, the effect of nickel powder mixed dielectric fluid on Electrical Discharge Machining (EDM) performance of mild steel has been carried out. Peak current, tool/electrode diameter and concentration of powder are the process parameters. The process performance is measured in terms of material removal rate (MRR), tool wear rate (TWR), and surface roughness (SR). The experiment has been designed using a Full Factorial in Design of Experiment (DOE) software. The research outcome is to identify the important process parameters that maximize MRR and minimize TWR and SR. The experiment has been carried out using 2 levels of current (3.5 A and 6.5 A), tool diameters (14 mm and 20 mm) and Nickel powder concentrations (0 g/l and 6 g/l). The weight of the mild steel work piece and copper electrode are measured before and after each run. Based on the results, current is the most significant parameter affecting MRR, TWR, and SR. It was also found that with added nickel powder in the dielectric fluid, the tool life is longer and surface roughness of the work piece is improved. Furthermore, it was shown that both MRR and TWR increased with the increase in tool diameter. However, SR was improved as tool diameter increased but its effect was not very significant

Effect of multi-wall carbon nanotubes on the mechanical properties of natural rubber

Multi-walled carbon nanotubes (MWNTs) were used to prepare natural rubber (NR) nanocomposites. Our first effort to achieve nanostructures in MWNTs/NR nanocomposites were formed by incorporating carbonnanotubes in a polymer solution and subsequently evaporating the solvent. Using this technique, nanotubess can be dispersed homogeneously in the NR matrix in an attempt to increase the mechanical properties of these nanocomposites. The properties of the nanocomposites such as tensile strength, tensile modulus, tear strength, elongation at break and hardness were studied. Mechanical test results show an increase in the initial modulus for up to 12 times in relation to pure NR. In addition to mechanical testing, the dispersion state of the MWNTs into NR was studied by transmission electron microscopy (TEM) in order to understand the morphology of the resulting system. According to the present study, application of the physical and mechanical properties of carbon nanotubes to NR can result in rubber products which have improved mechanical, physical and chemical properties, compared with existing rubber products reinforced with carbon black or silicone

Flexural behavior of open-cell aluminum foam sandwich under three-point bending

Aluminum foam sandwich (AFS) panels are one of an advanced material that has various advantages such as lightweight, excellent stiffness to weight ratio and high-energy absorption. Due to their advantages, many researchers’ shows an interest in aluminum foam material for expanding the use of foam structure. However, there is still a gap need to be filling in order to develop reliable data on mechanical behavior of AFS with different parameters and analysis method approach. There are two types of aluminum foam that is open-cell and closed-cell foam. Few researchers were focusing on open-cell aluminum foam. Moreover, open-cell metal foam had some advantages compared to closed-cell due to the cost and weight matters. Thus, this research is focusing on aluminum foam sandwich using open-cell aluminum foam core with grade 6101 attached to aluminum sheets skin tested under three point bending. The effect Skin to core ratio investigated on AFS specimens analyzed by constructing load-displacement curves and observing the failure modes of AFS. Design of experiment of three levels skin sheet thickness (0.2mm, 0.4mm, and 0.6mm) and two levels core thickness (3.2mm and 6.35mm). a full factorial of six runs were performed with three time repetition. The results show that when skin to core ratio increase, force that AFS panels can withstand also increase with increasing core thickness