Experimental and numerical studies on seismic behaviour of exterior beam-column joints

P. Asha,R. Sundararajan 사단법인 한국계산역학회 2014 Computers and Concrete, An International Journal Vol.13 No.2

A nonlinear finite element analysis using ANSYS is used to evaluate the seismic behavior of reinforced concrete exterior beam-column joints. The behavior of the finite element models under cyclic loading is compared with the experimental results. Two beam-column joint specimens (SH and SHD) with square hoop confinement in joint and throughout the column with detailing as per IS 13920 are studied. The specimen SHD was provided with additional diagonal bars from column to beam to relocate the plastic hinge formation from beam-column interface. The load-displacement relationship, joint shear stress and strain in beam obtained from numerical study showed good agreement with the experimental results. This investigation proves that seismic behaviour of reinforced concrete beam-column joints under reversed cyclic loading can be evaluated successfully using finite element modeling and analysis.

In silico QSAR studies of anilinoquinolines as EGFR inhibitors.

Pasha, Farhan Ahmad,Muddassar, Muhammad,Srivastava, Anil Kumar,Cho, Seung Joo Springer 2010 JOURNAL OF MOLECULAR MODELING Vol.16 No.2

<P>Members of the epidermal growth factor receptor (EGFR) family of proteins are frequently overactive in solid tumors. A relatively new therapeutic approach to inhibit the kinase activity is the use of ATP-competitive small molecules. In silico techniques were employed to identify the key interactions between inhibitors and their protein receptors. A series of EGFR inhibitory anilinoquinolines was studied within the framework of hologram quantitative structure activity relationship (HQSAR), density functional theory (DFT)-based QSAR, and three-dimensional (3D) QSAR (CoMFA/CoMSIA). The HQSAR analysis implied that substitutions at certain sites on the inhibitors play an important role in EGFR inhibition. DFT-based QSAR results suggested that steric and electronic interactions contributed significantly to the activity. Ligand-based 3D-QSAR and receptor-guided 3D-QSAR analyses such as CoMFA and CoMSIA techniques were carried out, and the results corroborated the previous two approaches. The 3D QSAR models indicated that steric and hydrophobic interactions are dominant, and that substitution patterns are an important factor in determining activity. Molecular docking was helpful in identifying a bioactive conformer as well as a plausible binding mode. The docked geometry-based CoMFA model with steric and electrostatic fields effect gave q(2) = 0.66, r(2) = 0.94 with r(2) (predictive) = 0.72. Similarly, CoMSIA with hydrophobic field gave q(2) = 0.59, r(2) = 0.85 with r(2) (predictive) = 0.63. Bulky groups around site 3 of ring 'C', and hydrophilic and bulky groups at position 6 of ring 'A' are desirable, with a hydrophobic and electron-donating group at site 7 of ring 'A' being helpful. Accordingly, potential EGFR inhibitors may be designed by modification of known inhibitors.</P>

WEIGHTED POSSIBILISTIC VARIANCE AND MOMENTS OF FUZZY NUMBERS

Pasha, E.,Asady, B.,Saeidifar, A. Korean Society of Computational and Applied Mathem 2008 Journal of applied mathematics & informatics Vol.26 No.5

In this paper, a method to find the weighted possibilistic variance and moments about the mean value of fuzzy numbers via applying a difuzzification using minimizer of the weighted distance between two fuzzy numbers is introduced. In this way, we obtain the nearest weighted point with respect to a fuzzy number, this main result is a new and interesting alternative justification to define of weighted mean of a fuzzy number. Considering this point and the weighted distance quantity, we introduce the weighted possibilistic mean (WPM) value and the weighted possibilistic variance(WPV) of fuzzy numbers. This paper shows that WPM is the nearest weighted point to fuzzy number and the WPV of fuzzy number is preserved more properties of variance in probability theory so that it can simply introduce the possibilistic moments about the mean of fuzzy numbers without problem. The moments of fuzzy numbers play an important role to estimate of parameters, skewness, kurtosis in many of fuzzy times series models.

Molecular Docking and 3D QSAR Studies of Chk2 Inhibitors

Pasha, Fahran Ahmad,Muddassar, Muhammad,Joo Cho, Seung Blackwell Publishing Ltd 2009 Chemical biology & drug design Vol.73 No.3

<P>Isothiazole-carboxamidines are potent ATP competitive checkpoint kinases (Chk2) inhibitors. Three-dimensional quantitative structure–activity relationship models were developed using comparative molecular field analysis and comparative molecular similarity indices analysis. The study was performed using three different geometrical methods. In geometrical method-1, molecules were fully optimized by PM3 Hamiltonian and aligned using common substructure. This alignment was subsequently used for Ligand-based comparative molecular field analysis and comparative molecular similarity indices analysis. In receptor-guided analyses, the receptor coordinates were obtained from public domine (PDB 2cn8). The molecule-7 was docked into receptor protein using FlexX and two plausible binding modes were identified. These modes were used as templates for geometrical method-2 and 3. These methods were used for 3D QSAR. The geometrical method-3-based comparative molecular field analysis (<I>q</I><SUP> 2</SUP> = 0.75, <I>r</I><SUP> <I>2</I></SUP> = 0.87 and <I>r </I><SUP><I>2</I></SUP><SUB>predict</SUB> = 0.81) and comparative molecular similarity indices analysis (<I>q </I><SUP><I>2</I></SUP> = 0.90, <I>r</I><SUP> <I>2</I></SUP> = 0.96 and <I>r</I><SUP> <I>2</I></SUP><SUB>predict</SUB> = 0.75) gave better result. The steric, hydrophobic and hydrogen bond donor fields effects significantly contribute to activity. In this way, the receptor-guided study presents a more detailed understanding about chk2 active site interactions. The study indicated some modifications to the active molecule which might be valuable to improve the activity.</P>

CoMFA Based Quantitative Structure Toxicity Relationship of Azo Dyes

Pasha, F.A.,Nam, Kee-Dal,Cho, Seung-Joo The Korean Society of Toxicogenomics and Toxicopro 2007 Molecular & cellular toxicology Vol.3 No.2

Studies of relationship between structure and toxicity of azo dyes have been performed with comparative molecular field analysis (CoMFA) techniques. 3D QSTR analyses indicate that the steric and electrostatic interactions are important. The steric field based model gives strong correlation ($q^2$=0.57, $r^2$= 0.92). The steric field in conjunction with electrostatic field give more strong correlation ($q^2$=0.57, $r^2$=0.95). All study indicates that a bulky and electronegative group at benzene ring and a small group at position 3 of aniline ring might be significant to reduce the mutagenicity.

DFT‐based <i>de novo</i> QSAR of Phenoloxidase Inhibitors

Pasha, Farhan Ahmad,Muddassar, Muhhammad,Beg, Yakub,Cho, Seung Joo Blackwell Publishing Ltd 2008 Chemical biology & drug design Vol.71 No.5

<P>The phenoloxidase or tyrosinase is a key enzyme in insects, which is responsible for hydroxylation of tyrosine into <I>o</I>‐quinones via <I>o</I>‐diphenols. A series of benzaldehyde thiosemicarbazone, benzaldehyde and benzoic acid families were taken with their pragmatic pIC<SUB>50</SUB> values against phenoloxidase from pieris rapae (Lepidoptera) larvae. Density functional theory‐based quantitative structure–activity relationship (QSAR) analyses were performed to speculate the key interaction. The most fitted four different QSAR models were identified and discussed. The softness, electrophilicity index, molar refractivity and log <I>P</I> were identified as best descriptors; however, the atomic values of softness and philicity obtained from Fukui function are more significant than global values. The study reveals that electrostatic and steric fields jointly contribute to activity. To gain further insight, the three‐dimensional quantitative structure–activity relationship (3D‐QSAR) analyses were performed using two molecular field techniques: comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The successful 3D‐QSAR models were obtained from CoMFA (<I>q</I><SUP>2<I> </I></SUP>= 0.94, <I>r</I><SUP>2<I> </I></SUP>= 0.99, <SUP><I> </I></SUP>= 0.92) and CoMSIA (<I>q</I><SUP>2<I> </I></SUP>= 0.94, <I>r</I><SUP>2<I> </I></SUP>= 0.98, = 0/95). The CoMFA and CoMSIA results indicate that, a bulky and negative group around sulfur atom but a small and positive group around nitrogen atom might have good effects on activity. The <I>ortho</I> and <I>meta</I> positions of ring are favorable for small group. These QSAR models might be helpful to design the novel and potent inhibitors.</P>

QM and Pharmacophore based 3D-QSAR of MK886 Analogues against mPGES-1

Pasha, F.A.,Muddassar, M.,Jung, Hwan-Won,Yang, Beom-Seok,Lee, Cheol-Ju,Oh, Jung-Soo,Cho, Seung-Joo,Cho, Hoon Korean Chemical Society 2008 Bulletin of the Korean Chemical Society Vol.29 No.3

Microsomal prostaglandin E2 synthase (mPGES-1) is a potent target for pain and inflammation. Various QSAR (quantitative structure activity relationship) analyses used to understand the factors affecting inhibitory potency for a series of MK886 analogues. We derived four QSAR models utilizing various quantum mechanical (QM) descriptors. These QM models indicate that steric, electrostatic and hydrophobic interaction can be important factors. Common pharmacophore hypotheses (CPHs) also have studied. The QSAR model derived by best-fitted CPHs considering hydrophobic, negative group and ring effect gave a reasonable result (q2 = 0.77, r2 = 0.97 and Rtestset = 0.90). The pharmacophore-derived molecular alignment subsequently used for 3D-QSAR. The CoMFA (Comparative Molecular Field Analysis) and CoMSIA (Comparative Molecular Similarity Indices Analysis) techniques employed on same series of mPGES-1 inhibitors which gives a statistically reasonable result (CoMFA; q2 = 0.90, r2 = 0.99. CoMSIA; q2 = 0.93, r2 = 1.00). All modeling results (QM-based QSAR, pharmacophore modeling and 3D-QSAR) imply steric, electrostatic and hydrophobic contribution to the inhibitory activity. CoMFA and CoMSIA models suggest the introduction of bulky group around ring B may enhance the inhibitory activity.

GOODNESS OF FIT TESTS BASED ON DIVERGENCE MEASURES

Pasha, Eynollah,Kokabi, Mohsen,Mohtashami, Gholam Reza Korean Society of Computational and Applied Mathem 2008 Journal of applied mathematics & informatics Vol.26 No.1

In this paper, we have considered an investigation on goodness of fit tests based on divergence measures. In the case of categorical data, under certain regularity conditions, we obtained asymptotic distribution of these tests. Also, we have proposed a modified test that improves the rate of convergence. In continuous case, we used our modified entropy estimator [10], for Kullback-Leibler information estimation. A comparative study based on simulation results is discussed also.

Effect of Storage Time on the Rancidity and Metabolizable Energy of Rice Polishing in Poultry

Pasha, T.N.,Khattak, F.M.,Khan, D.R.,Jabbar, M.A. Asian Australasian Association of Animal Productio 2008 Animal Bioscience Vol.21 No.3

The storage of rice polishing (RP) with and without addition of antioxidant for sixteen weeks and its effect on rancidity and metabolizable energy values during the summer season was determined. Fifteen Single Comb White Leghorn cockerels of approximately uniform age and weight were procured and kept in metabolic cages under standard feeding and management practices. Five force feeding trials were conducted. In the first trial, fresh RP with 0 weeks of storage (diet 1 and 2) was used followed by four feeding trials with 4 (diet 3, 4), 8 (diet 5, 6), 12 (diet 7, 8), and 16 (diet 9, 10) weeks of storage of RP. The same birds were used in all trails. The birds were fasted for a period of 21 h, followed by force feeding of 20 g of RP with and without antioxidant for all storage periods. The control/fasting group was also maintained to measure endogenous fecal losses. Excreta were collected after 48 h for the determination of AME and TME values of RP. Along with the biological trials, laboratory assay of the RP stored with and without antioxidant was conducted to measure the extent of rancidity in terms of Thiobarbituric acid value (TBA). The TBA values were affected (p<0.05) by storage period and the values increased when the storage period increased from 4 to 16 weeks. However, the TBA values were significantly reduced (p<0.05) when RP was stored after addition of antioxidant when compared with the values obtained from RP stored without antioxidant (diet 3 vs. 4, 5 vs. 6, 7 vs. 8, and 9 vs. 10). The AME MJ/kg and TME MJ/kg values of RP were neither affected by increase in storage period nor addition of antioxidant. The findings of this study revealed that there was no effect of rancidity and storage time on the nutritive value, AME or TME of RP in poultry. However, TBA values were increased with the increase in storage period.

Mechanism based QSAR studies of N-phenylbenzamides as antimicrobial agents

Pasha, F.A.,Muddassar, M.,Lee, C.,Cho, S.J. Elsevier Science B.V 2008 Environmental toxicology and pharmacology Vol.26 No.2

N-Phenyl benzamides are potent antibacterial agents. They are active against both Gram-positive and Gram-negative bacteria. The Gram-positive bacteria have strong and thick cell wall while the Gram-negative bacterial have thin and permeable cell wall. The DFT based QSAR reveals that molecular weight and total energy significantly contribute to activity against both kinds of target. The electrophilicity index involved in QSAR models derived with anti-Gram-positive activity indicates the dominance of electrostatic interaction. The molar refractivity and logP is involved in QSAR model derived with anti-Gram-negative activity shows steric and hydrophobic interaction. The CoMFA and CoMSIA results also indicate that anti-Gram-positive bacterial activity is a function of electrostatic field effect but the anti-Gram-negative activity depends on hydrophobicity and steric field effect. The CoMFA and CoMSIA contour maps give an indication, the electropositive group around benzene ''X'' and an electronegative group around carbonyl oxygen is desirable for better anti-Gram-positive bacterial activity. A hydrophobic group around meta position of ring ''X'' with bulky group at ortho position and a small group at para position are desirable for better activity against Gram-negative target. The findings are reasonable and the mechanism might be different due to difference in composition of cell wall. The cell wall of Gram-positive target does not allow the permeability and only external electrostatic interaction is possible while the cell wall of Gram-negative target allows the permeability of molecules inside the cell for possible hydrophobic and steric bulk interaction.