In Silico/In Vitro Hit-to-Lead Methodology Yields SMYD3 Inhibitor That Eliminates Unrestrained Proliferation of Breast Carcinoma Cells

SMYD3 is a lysine methyltransferase that regulates the expression of over 80 genes and is required for the uncontrolled proliferation of most breast, colorectal, and hepatocellular carcinomas. The elimination of SMYD3 restores normal expression patterns of these genes and halts aberrant cell proliferation, making it a promising target for small molecule inhibition. In this study, we sought to establish a proof of concept for our in silico/in vitro hit-to-lead enzyme inhibitor development platform and to identify a lead small molecule candidate for SMYD3 inhibition. We used Schrodinger^® software to screen libraries of small molecules in silico and the five compounds with the greatest predicted binding affinity within the SMYD3 binding pocket were purchased and assessed in vitro in direct binding assays and in breast cancer cell lines. We have confirmed the ability of one of these inhibitors, Inhibitor-4, to restore normal rates of cell proliferation, arrest the cell cycle, and induce apoptosis in breast cancer cells without affecting wildtype cell behavior. Our results provide a proof of concept for this fast and affordable small molecule hit-to-lead methodology as well as a promising candidate small molecule SMYD3 inhibitor for the treatment of human cancer.     

Synthesis of Novel Series of Benzothieno [2,3-d] Pyrimidine Derivatives, Promising Anticancer Agents

An extension of the authors＇ previous discovery of in vitro antitumor activity of substituted thino [2,3-d] prymidine derivatives is reported. The synthesis of some new spirothino [2,3-d] prymidine （4a-f）, imidazolidin, substituted prymidinyl and substituted thiazolidine thino [2,3-d] prymidine derivatives have been described. Thirteen of the obtained compounds were selected by the NCI and evaluated for their in vitro anticancer activity. Seven of the investigated compounds, 4a, 8a, 9a, （12a, b）, 14a and 15a, displayed high anticancer activity in the primary assay. These compounds have been selected for a full anticancer screening against a 60-cell panel assay where they showed non-selective broad spectrum and promising activity against all cancer cell lines. Compounds 12a and 12b proved to be the active members in this study compared to 5-fluorouracil and cyclophosphamide as reference drugs, respectively. Compounds 12a and 12b were identified as promising lead compounds, evaluated for their in-vitro antitumor activity.     

Transition metal nanoparticles doped carbon paper as a cost-effective anode in a microbial fuel cell powered by pure and mixed biocatalyst cultures

The poor wettability and high cost of the carbonaceous electrodes materials prohibited the practical applications of microbial fuel cells (MFCs) on large scale. Here, a novel nanoparticles of metal sheathed with metal oxide is electrodeposited on carbon paper (CP) to introduce as high-performance anodes of microbial fuel cell (MFC). This thin layer of metal/metal oxide significantly enhance the microbial adhesion, the wettability of the anode surface and decrease the electron transfer resistance. The investigation of the modified CP anodes in an air-cathode MFCs fed by various biocatalyst cultures shows a significant improving in the MFC performance. Where, the generated power and current density was 140% and 210% higher as compared to the pristine CP. Mixed culture of exoelectrogenic microorganism in wastewater exhibited good performance and generated higher power and current density compared to yeast as pure culture. The excellent capacitance with a distinctive nanostructure morphology of the modified-CP open an avenues for practical applications of MFCs.     

Assessment of grape skin hardness by a puncture test

BACKGROUND: The release of grape components during wine making might be related to the mechanical properties of the skin, in particular its hardness. Samples from three varieties collected during the 2005 vintage season in Piedmont, Italy, were tested for their skin hardness using a texture analyser. The goal was to understand the statistical interactions between three factors—variety, cluster position and puncture point—and their influence on the grape skin hardness. A discussion on the relationship between the size of the sample used and the confidence level is also provided. RESULTS: Results of the ANOVA test showed that there is an interaction between the variety and the puncture point when measuring the skin hardness with the break energy. The position of the berry on the cluster does not affect the berry skin break energy. We also show that a sample size depend on the variety tested. CONCLUSION: The break energy is more useful in understanding the effect of the three factors on the skin hardness. Other factors that might affect the puncture test applied to grapes need to be studied in the future and the usefulness of the test in winemaking will need to be further developed. Copyright © 2008 Society of Chemical Industry     

Diglycidyl ether of bisphenol A/chitosan‐graft‐polyaniline composites with electromagnetic interference shielding properties: Synthesis,characterization, and curing kinetics

Conducting filler based on chitosan and grafted polyaniline (Ch‐g‐PANI) was prepared with different grafting ratios and used as fillers for polyester powder coating system. Differential scanning calorimetry is applied to study the effect of Ch‐g‐PANI on the curing of the polyester powder coating. The activation energy calculated by isoconversional Kissinger method was increased by either increasing the Ch‐g‐PANI content or the content of polyaniline in the filler, suggesting the contribution of the filler in the curing reactions. The cured samples were characterized using FTIR and TG analyses. Thermogravimetric analysis showed that the total thermal stability was enhanced upon the filler addition as detected from the values of integral procedural decomposition temperature. Furthermore, a dielectric study showed that the dielectric constant and loss were increased upon increasing of the filler. Vogel–Fulcher–Tammann equation was well‐fitted when used to examine the dependence of α‐relaxation on the temperature and the dielectrically calculated T_g values were comparable to that measured by DSC. The shielding effectiveness toward microwaves was enhanced by increasing the filler content. POLYM. ENG. SCI., 59:372–381, 2019. © 2018 Society of Plastics Engineers     

2D/3D Shaped Radiation Patterns of Sunflower and Conformal Antenna Arrays Using Phase Synthesis

2D and 3D beam synthesis from different antenna array arrangements are investigated in this paper. Planar sunflower, conformal cylinderical and spherical helical array arrangements are studied. The particle swarm optimization (PSO) technique is used to predict the phase distribution on the array elements. The beam synthesis is achieved by comparing the array factor with a predetermined mask with both upper and lower limits according to the intented application requirements. Different 2D and 3D masks are used in beam synthesis as pencil, flat-top, and cosecant single beam are predicted. The planar sunflower antenna array is investigated due to its high gain, low side-lobe level (SLL) below ??20 dB and its compact size. The phase distribution of sunflower array is estimated using PSO to radiate dual-beams in different planes. Dual-beam with pencil, flat-top, and cosecant beams are obtained with different half-power beam widths. 3D conformal antenna arrays of cylindrical and spherical helical arrangements are studied. Each 3D conformal array consists of four arms shifted in position by 90° orintation angle. Each arm is designed to radiate single beam in a specific direction. Four-beams are considered to radiate in the directions of θ_1,2,3,4?=?30°, and ?₁?=?0°, ?₂?=?90°, ?₃?=?180°, and ?₄?=?270° with SLL optimized below ??17 dB. The array arrangements analysis is based on the array theory formulation, through the implemention of the estimiated equation using a home programmed MATLAB code.

     

Selective Recovery of Cadmium,Cobalt, and Nickel from Spent Ni–Cd Batteries Using Adogen® 464 and Mesoporous Silica Derivatives

Spent Ni–Cd batteries are now considered an important source for many valuable metals. The recovery of cadmium, cobalt, and nickel from spent Ni–Cd Batteries has been performed in this study. The optimum leaching process was achieved using 20% H₂SO₄, solid/liquid (S/L) 1/5 at 80 °C for 6 h. The leaching efficiency of Fe, Cd, and Co was nearly 100%, whereas the leaching efficiency of Ni was 95%. The recovery of the concerned elements was attained using successive different separation techniques. Cd(II) ions were extracted by a solvent, namely, Adogen^® 464, and precipitated as CdS with 0.5% Na₂S solution at pH of 1.25 and room temperature. The extraction process corresponded to pseudo-2nd-order. The prepared PTU-MS silica was applied for adsorption of Co(II) ions from aqueous solution, while the desorption process was performed using 0.3 M H₂SO₄. Cobalt was precipitated at pH 9.0 as Co(OH)₂ using NH₄OH. The kinetic and thermodynamic parameters were also investigated. Nickel was directly precipitated at pH 8.25 using a 10% NaOH solution at ambient temperature. FTIR, SEM, and EDX confirm the structure of the products.     

Octafilar Helical Antenna for Circular Polarization Wireless Capsule Endoscopy Applications

Wireless Personal Communications - This paper introduces a proposed design of a circularly polarized quadfilar or octafilar helical antenna (QFHA or OFHA) dedicated for wireless...     

Revisiting the accessibility of Saudi Arabia government websites

Universal Access in the Information Society - With the significant inclusion of the Internet in nearly all aspects of our daily lives, achieving accessible e-government services that enable...     

Identification of injection and extraction wells from overspecified boundary data

In this paper, we focus on the identification of wells’ positions and fluxes/flows from the knowledge of overspecified data: hydraulic head and flux, on a part of the domain boundary. The used method is based on minimizing a constitutive law gap functional. We consider two inverse problems: in the first one overspecified conditions are available throughout the entire domain boundary; in the second inverse problem, in addition to the wells, boundary condition are also unknown on an inaccessible part of the domain boundary.