Search results for: molecular dynamic

Authors: Rozhgar A. Khailany, Mehri Igci, Emine Bayraktar, Sakip Erturhan, Metin Karakok, Ahmet Arslan

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Kidney cancer is the most lethal urological cancer accounting for 3% of adult malignancies. VHL, a tumor-suppressor gene, is best known to be associated with renal cell carcinoma (RCC). The VHL functions as negative regulator of hypoxia inducible factors. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC (clear cell RCC) including PBRM1 and SETD2. The PBRM1 gene encodes the BAF180 protein, which involved in transcriptional activation and repression of selected genes. SETD2 encodes a histone methyltransferase, which may play a role in suppressing tumor development. In this study, RNAs of 30 paired tumor and normal samples that were grouped according to the types of kidney cancer and clinical characteristics of patients, including gender and average age were examined by RT-PCR, SSCP and sequencing techniques. VHL, PBRM1 and SETD2 expressions were relatively down-regulated. However, statistically no significance was found (Wilcoxon signed rank test, p > 0.05). Interestingly, no mutation was observed on the contrary of previous studies. Understanding the molecular mechanisms involved in the pathogenesis of RCC has aided the development of molecular-targeted drugs for kidney cancer. Further analysis is required to identify the responsible genes rather than VHL, PBRM1 and SETD2 in kidney cancer.

Keywords: kidney cancer, molecular biomarker, expression analysis, mutation screening

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Authors: Alok Shiomurti Tripathi, Ajay Kumar Timiri, Papiya Mitra Mazumder, Anil Chandewar

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The present study evaluates the possible drug interaction between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ) induced in diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction by molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg/kg, ip) and confirms it by assessing the blood and urine biochemical parameters on 28th day of its induction. Selected DN animals were used for the drug interaction between GLIM (0.5mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) after 29th and 70th day of protocol. Drug interaction were assessed by evaluating the plasma drug concentration using HPLC-UV and also determine the change in the biochemical parameter in blood and urine. Mechanism of the interaction was postulated by molecular modeling study using Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in the blood and urine biochemical parameter in STZ treated groups. The concentration of SIL increased significantly (p<0.001) in rat plasma when co administered with GLIM after 70th day of protocol. Molecular modelling study revealed few important interactions with rat serum albumin and CYP2C9.GLIM has strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL. Whereas, for CYP2C9, GLIM has strong hydrogen bond with polar contacts and hydrophobic interactions than SIL. Present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals and mechanism has been supported by molecular modeling studies.

Keywords: diabetic nephropathy, glimepiride, sildenafil citrate, pharmacokinetics, homology modeling, schrodinger

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Authors: Evgeniia V. Mekhonoshina, Vladimir Ya. Modorskii, Vasilii Yu. Petrov

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At present, vibrations of rotors of gas transmittal unit evade sustainable forecasting. This paper describes elastic oscillation modes in resilient supports and rotor impellers modeled during computational experiments with regard to interference in the system of gas-dynamic flow and compressor rotor. Verification of aeroelastic approach was done on model problem of interaction between supersonic jet in shock tube with deformed plate. ANSYS 15.0 engineering analysis system was used as a modeling tool of numerical simulation in this paper. Finite volume method for gas dynamics and finite elements method for assessment of the strain stress state (SSS) components were used as research methods. Rotation speed and material’s elasticity modulus varied during calculations, and SSS components and gas-dynamic parameters in the dynamic system of gas-dynamic flow and compressor rotor were evaluated. The analysis of time dependence demonstrated that gas-dynamic parameters near the rotor blades oscillate at 200 Hz, and SSS parameters at the upper blade edge oscillate four times higher, i.e. with blade frequency. It has been detected that vibration amplitudes correction in the test points at magnetic bearings by aeroelasticity may correspond up to 50%, and about -π/4 for phases.

Keywords: Centrifugal compressor, aeroelasticity, interdisciplinary calculation, oscillation phase displacement, vibration, nonstationarity

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Authors: Mohammad Reza Ameri, Ali Massumi, Mohammad Haghbin

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Non-linear static analysis, commonly referred to as pushover analysis, is a powerful tool for assessing the seismic response of structures. A suitable lateral load pattern for pushover analysis can bring the results of this simple, quick and low-cost analysis close to the realistic results of nonlinear dynamic analyses. In this research, four samples of 10- and 15 story (two- and four-bay) reinforced concrete frames were studied. The lateral load distribution patterns recommended in FEMA 273/356 guidelines were applied to the sample models in order to perform pushover analyses. The results were then compared to the results obtained from several nonlinear incremental dynamic analyses for a range of earthquakes. Finally, a lateral load distribution pattern was proposed for pushover analysis of medium-rise reinforced concrete buildings based on the results of nonlinear static and dynamic analyses.

Keywords: lateral load pattern, nonlinear static analysis, incremental dynamic analysis, medium-rise reinforced concrete frames, performance based design

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Authors: Ajish Sreedharan

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Security in transmission and storage of digital images has its importance in today’s image communications and confidential video conferencing. Due to the increasing use of images in industrial process, it is essential to protect the confidential image data from unauthorized access. Advanced Encryption Standard (AES) is a well known block cipher that has several advantages in data encryption. However, it is not suitable for real-time applications. This paper presents modifications to the Advanced Encryption Standard to reflect a high level security and better image encryption. The modifications are done by adjusting the ShiftRow Transformation and using On Dynamic chaotic S-BOX. In AES the Substitute bytes, Shift row and Mix columns by themselves would provide no security because they do not use the key. In Dynamic chaotic S-BOX Based AES the Substitute bytes provide security because the S-Box is constructed from the key. Experimental results verify and prove that the proposed modification to image cryptosystem is highly secure from the cryptographic viewpoint. The results also prove that with a comparison to original AES encryption algorithm the modified algorithm gives better encryption results in terms of security against statistical attacks.

Keywords: advanced encryption standard (AES), on dynamic chaotic S-BOX, image encryption, security analysis, ShiftRow transformation

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Authors: Nahush Modak, Meena Pangarkar, Anand Pathak, Ankita Tamhane

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Background: Breast cancer is the prominent cause of cancer and mortality among women. This study was done to show the statistical analysis of a cohort of over 250 patients detected with breast cancer diagnosed by oncologists using Immunohistochemistry (IHC). IHC was performed by using ER; PR; HER2; Ki-67 antibodies. Materials and methods: Formalin fixed Paraffin embedded tissue samples were obtained by surgical manner and standard protocol was followed for fixation, grossing, tissue processing, embedding, cutting and IHC. The Ventana Benchmark XT machine was used for automated IHC of the samples. Antibodies used were supplied by F. Hoffmann-La Roche Ltd. Statistical analysis was performed by using SPSS for windows. Statistical tests performed were chi-squared test and Correlation tests with p<.01. The raw data was collected and provided by National Cancer Insitute, Jamtha, India. Result: Luminal B was the most prevailing molecular subtype of Breast cancer at our institute. Chi squared test of homogeneity was performed to find equality in distribution and Luminal B was the most prevalent molecular subtype. The worse prognostic indicator for breast cancer depends upon expression of Ki-67 and her2 protein in cancerous cells. Our study was done at p <.01 and significant dependence was observed. There exists no dependence of age on molecular subtype of breast cancer. Similarly, age is an independent variable while considering Ki-67 expression. Chi square test performed on Human epidermal growth factor receptor 2 (HER2) statuses of patients and strong dependence was observed in percentage of Ki-67 expression and Her2 (+/-) character which shows that, value of Ki depends upon Her2 expression in cancerous cells (p<.01). Surprisingly, dependence was observed in case of Ki-67 and Pr, at p <.01. This shows that Progesterone receptor proteins (PR) are over-expressed when there is an elevation in expression of Ki-67 protein. Conclusion: We conclude from that Luminal B is the most prevalent molecular subtype at National Cancer Institute, Jamtha, India. There was found no significant correlation between age and Ki-67 expression in any molecular subtype. And no dependence or correlation exists between patients’ age and molecular subtype. We also found that, when the diagnosis is Luminal A, out of the cohort of 257 patients, no patient shows >14% Ki-67 value. Statistically, extremely significant values were observed for dependence of PR+Her2- and PR-Her2+ scores on Ki-67 expression. (p<.01). Her2 is an important prognostic factor in breast cancer. Chi squared test for Her2 and Ki-67 shows that the expression of Ki depends upon Her2 statuses. Moreover, Ki-67 cannot be used as a standalone prognostic factor for determining breast cancer.

Keywords: breast cancer molecular subtypes , correlation, immunohistochemistry, Ki-67 and HR, statistical analysis

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Authors: Nurullah Buker, Ezgi Karagoz, Yesim Salik Sengul, Sevay Alsen Guney, Gokhan Yoyler, Aylin Ozbek

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Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders with heterogeneous clinical features such as inattention, hyperactivity, and impulsivity. Many different types of exercise interventions were employed for children with ADHD. However, previous studies have usually examined the effects of non-specific exercise programs or short-term effects of exercise. The aim of this study is to investigate the effect of the Neurocognitive Exercise Program (NEP), which is a structured exercise program derived from Life Kinetik, and a relatively new for children with ADHD, on symptoms, attention, and dynamic balance in medication-naïve children with ADHD. Fourteen medication-naive children (7-12 years) with ADHD were included in the intervention group. NEP was performed once a week for ten weeks. The intervention group also performed a structured home exercise program for another six days, for ten weeks. The children in the intervention group were assessed at baseline, in the third month, in the sixth month, and in the twelfth month regarding ADHD-related symptoms, attention, and dynamic balance. Fifteen age-matched typically developing children were assessed once for establishing normative values. Hyperactivity-Impulsivity score and dynamic balance were found to improve after NEP in the ADHD group in the 3rd month (p<0.05). In addition, these results were similar for both groups after NEP and at the end of the 12th month (p>0.05). The NEP may provide beneficial effects on hyperactivity-impulsivity, oppositional defiant, and dynamic balance in children with ADHD, and the improvements may be maintained in the long term.

Keywords: ADHD, attention problems, dynamic balance, neurocognitive exercise

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Authors: Jui-Pui Hung, Yu-Sheng Lai, Tzuo-Liang Luo, Kung-Da Wu, Yun-Ji Zhan

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This study presented the investigation of the influence of the tool holder interface stiffness on the dynamic characteristics of a spindle tool system. The interface stiffness was produced by drawbar force on the tool holder, which tends to affect the spindle dynamics. In order to assess the influence of interface stiffness on the vibration characteristic of spindle unit, we first created a three dimensional finite element model of a high speed spindle system integrated with tool holder. The key point for the creation of FEM model is the modeling of the rolling interface within the angular contact bearings and the tool holder interface. The former can be simulated by a introducing a series of spring elements between inner and outer rings. The contact stiffness was calculated according to Hertz contact theory and the preload applied on the bearings. The interface stiffness of the tool holder was identified through the experimental measurement and finite element modal analysis. Current results show that the dynamic stiffness was greatly influenced by the tool holder system. In addition, variations of modal damping, static stiffness and dynamic stiffness of the spindle tool system were greatly determined by the interface stiffness of the tool holder which was in turn dependent on the draw bar force applied on the tool holder. Overall, this study demonstrates that identification of the interface characteristics of spindle tool holder is of very importance for the refinement of the spindle tooling system to achieve the optimum machining performance.

Keywords: dynamic stiffness, spindle-tool holder, interface stiffness, drawbar force

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Authors: Fabrizio Iezzi, Claudio Valente

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The viscous damping in dynamic systems can be proportional or non-proportional. In the first case, the mode shapes are real whereas in the second case they are complex. From an engineering point of view, the complexity of the mode shapes is important in order to quantify the non-proportional damping. Different indices exist to provide estimates of the modal complexity. These indices are or not zero, depending whether the mode shapes are not or are complex. The modal density problem arises in the experimental identification when the dynamic systems have close modal frequencies. Depending on the entity of this closeness, the mode shapes can hold fictitious imaginary quantities that affect the values of the modal complexity indices. The results are the failing in the identification of the real or complex mode shapes and then of the proportional or non-proportional damping. The paper aims to show the influence of the modal density on the values of these indices in case of both proportional and non-proportional damping. Theoretical and pseudo-experimental solutions are compared to analyze the problem according to an appropriate mechanical system.

Keywords: complex mode shapes, dynamic systems identification, modal density, non-proportional damping

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Authors: Rizwan H. Khan, Saima Nusrat

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Despite the fact that amyloid associated neurodegenerative diseases and non-neuropathic systemic amyloidosis have allured the research endeavors, as no curative drugs have been proclaimed up till now except for symptomatic cure. Therapeutic compounds which can diminish or disaggregate such toxic oligomers and fibrillar species have been examined and more are on its way. In the present study, we had reported an extensive biophysical, microscopic and computational study, revealing that L-3, 4-dihydroxyphenylalanine (L-Dopa) possess undeniable potency to inhibit heat induced human lysozyme (HL) amyloid fibrillation and also retain the fibril disaggregating potential. L-Dopa interferes in the amyloid fibrillogenesis process by interacting hydrophobically and also by forming hydrogen bonds with the amino acid residues found in amyloid fibril forming prone region of HL as elucidated by molecular docking results. L-Dopa also disaggregates the mature amyloid fibrils into some unorganised species. Thus, L-Dopa and related compounds can work as a promising inhibitor for the therapeutic advancement prospective against systemic amyloidosis.

Keywords: amyloids, disaggregation, human lysozyme, molecular docking

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Authors: A. Bogdanovic, M. Vitanova, J. Bojadjieva, Z. Rakicevic, V. Sesov, K. Edip, N. Naumovski, F. Manojlovski, A.Popovska, A. Shoklarovski, T. Kitanovski, D. Ivanovski, I. Markovski, D. Filipovski

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The conditions of existing structures change in the course of time and can hardly be characterized particularly if a bridge has long been in function and there is no design documentation related to it. To define the real conditions of a structure, detailed static and dynamic analysis of the structure has to be carried out and its modal parameters have to be defined accurately. Modal analysis enables a quite accurate identification of the natural frequencies and mode shapes. Presented in this paper are the results from the performed detailed analyses of a steel truss bridge that has been in use for more than 7 decades by the military services of R.N. Macedonia and for which there is no documentation at all. Static and dynamic investigations and ambient vibration measurements were performed. The acquired data were used to identify the mode shapes that were used for comparison with the numerical model. Dynamic tests were performed to define the bridge behaviour and the damping index. Finally, based on all the conducted detailed analyses and investigations, conclusions on the conditions of the bridge structure were drawn.

Keywords: ambient vibrations, dynamic identification, in-situ measurement, steel truss bridge

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Authors: M. Cangi, T. Dolar, C. Ersoy, Y. E. Aydogdu, A. I. Aydeniz, A. Mugan

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The drum is one of the critical parts in a washing machine in which the clothes are washed and spin by the rotational movement. It is activated by the drum shaft which is attached to an electric motor and subjected to dynamic loading. Being one of the critical components, failures of the drum require costly repairs of dynamic components. In this study, tolerance bands between the drum shaft and its two bearings were examined to develop a relationship between the fatigue life of the shaft and the interaction tolerances. Optimization of tolerance bands was completed in consideration of the fatigue life of the shaft as the cost function. The following methodology is followed: multibody dynamic model of a washing machine was constructed and used to calculate dynamic loading on the components. Then, these forces were used in finite element analyses to calculate the stress field in critical components which was used for fatigue life predictions. The factors affecting the fatigue life were examined to find optimum tolerance grade for a given test condition. Numerical results were verified by experimental observations.

Keywords: fatigue life, finite element analysis, tolerance analysis, optimization

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Authors: Shokofeh Ebrtahimi

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Let G be the chemical graph of a molecule. The matrix D = [dij ] is called the detour matrix of G, if dij is the length of longest path between atoms i and j. The sum of all entries above the main diagonal of D is called the detour index of G.Chemical graph theory is the topology branch of mathematical chemistry which applies graph theory to mathematical modelling of chemical phenomena.[1] The pioneers of the chemical graph theory are Alexandru Balaban, Ante Graovac, Ivan Gutman, Haruo Hosoya, Milan Randić and Nenad TrinajstićLet G be the chemical graph of a molecule. The matrix D = [dij ] is called the detour matrix of G, if dij is the length of longest path between atoms i and j. The sum of all entries above the main diagonal of D is called the detour index of G. In this paper, a new program for computing the detour index of molecular graphs of nanotubes by heptagons is determineded. Some Conjectures about detour index of Molecular graphs of nanotubes is included.

Keywords: chemical graph, detour matrix, Detour index, carbon nanotube

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Authors: Abdulrahman M. Hamid

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Dynamic Cone Penetration Test (DCPT) is widely used for field quality assessment of soils. Its application to predict the engineering properties of soil is globally promoted by the fact that it is difficult to obtain undisturbed soil samples, especially when loose or submerged sandy soil is encountered. Detailed discussion will be presented on the current development of DCPT correlations with resilient modulus, relative density, California Bearing Ratio (CBR), unconfined compressive strength and shear strength that have been developed for different materials in both the laboratory and field, as well as on the usage of DCPT in quality control of compaction of earth fills and performance evaluation of pavement layers. In addition, the relationship of the DCPT with other instruments such as falling weight deflectometer, nuclear gauge, soil stiffens gauge, and plate load test will be reported. Lastely, the application of DCPT in Saudi Arabia in recent years will be addressed in this manuscript.

Keywords: dynamic cone penetration test, falling weight deflectometer, nuclear gauge, soil stiffens gauge, plate load test, automated dynamic cone penetration

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Authors: Abdul Hakim Abdullah, Mohamad Syafiq Abdul Khadir

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In present investigations, thermal behaviours of Arenga pinnata fibres prior and after alkaline treatment were studied. The alkaline treatments were applied on the Arenga pinnata fibres by immersing in the alkaline solution, 6% sodium hydroxide (NaOH). Using hand lay-out technique, composites were fabricated at 20% and 40% by Arenga pinnata fibres weight contents. The thermal behaviours of both untreated and treated composites were determined by employing Dynamic Mechanical Analysis (DMA). The results show that the TAP owned better results of Storage Modulus (E’), Loss Modulus (E”) and Tan Delta temperatures ranges from 0°C to 60°C.

Keywords: composites, Arenga pinnata fibre, alkaline treatment, dynamic mechanical properties

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Authors: A. Didaoui, N. Benhalima, M. Elkeurti, A. Chouaih, F. Hamzaoui

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The monomer and dimer structures of the title molecule have been obtained from density functional theory (DFT) B3LYP method with 6-31G (d,p) as basis set calculations. The optimized geometrical parameters obtained by B3LYP/6-31G (d,p) method show good agreement with xperimental X-ray data. The polarizability and first order hyperpolarizabilty of the title molecule were calculated and interpreted. the intermolecular N–H•••O hydrogen bonds are discussed in dimer structure of the molecule. The vibrational wave numbers and their assignments were examined theoretically using the Gaussian 03 set of quantum chemistry codes. The predicted frontier molecular orbital energies at B3LYP/6-31G(d,p) method set show that charge transfer occurs within the molecule. The frontier molecular orbital calculations clearly show the inverse relationship of HOMO–LUMO gap with the total static hyperpolarizability. The results also show that N-(2-Methylphenyl)-2-nitrobenzenesulfonamide molecule may have nonlinear optical (NLO) comportment with non-zero values.

Keywords: DFT, Gaussian 03, NLO, N-(2-Methylphenyl)-2-nitrobenzenesulfonamide

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Authors: N. Khelloul, N. Benhalima, A. Chouaih, F. Hamzaoui

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The monomer and dimer structures of the title molecule have been obtained from density functional theory (DFT) B3LYP method with 6-31G (d,p) as basis set calculations. The optimized geometrical parameters obtained by B3LYP/6-31G (d,p) method shows good agreement with experimental X-ray data. The polarizability and first order hyperpolarizabilty of the title molecule were calculated and interpreted. The intermolecular N–H•••O hydrogen bonds are discussed in dimer structure of the molecule. The vibrational wave numbers and their assignments were examined theoretically using the Gaussian 09 set of quantum chemistry codes. The predicted frontier molecular orbital energies at B3LYP/6-31G(d,p) method set show that charge transfer occurs within the molecule. The frontier molecular orbital calculations clearly show the inverse relationship of HOMO–LUMO gap with the total static hyperpolarizability. The results also show that 2-Chloro-N-(2-methylphenyl) benzamide 2 molecule may have nonlinear optical (NLO) comportment with non-zero values.

Keywords: DFT, HOMO, LUMO, NLO

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Authors: Martynova Alina, Lyubov Buzoleva

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Streptococcus pneumoniae is the causative agent of pneumonias and meningitids throught all the world. Having high genetic diversity, this microorganism can cause different clinical forms of pneumococcal infections and microbiologically it is really difficult diagnosed by routine methods. Also, epidemiological surveillance requires more developed methods of molecular typing because the recent method of serotyping doesn't allow to distinguish invasive and non-invasive isolates properly. Non-coding genome of bacteria seems to be the interesting source for seeking of highly distinguishable markers to discriminate the subspecies of such a variable bacteria as Streptococcus pneumoniae. Technically, we proposed scheme of discrimination of S.pneumoniae strains with amplification of non-coding region (SP_1932) with the following restriction with 2 types of enzymes of Alu1 and Mn1. Aim: This research aimed to compare different methods of typing and their application for molecular epidemiology purposes. Methods: we analyzed population of 100 strains of S.pneumoniae isolated from different patients by different molecular epidemiology methods such as pulse-field gel electophoresis (PFGE), restriction polymorphism analysis (RFLP) and multilolocus sequence typing (MLST), and all of them were compared with classic typing method as serotyping. The discriminative power was estimated with Simpson Index (SI). Results: We revealed that the most discriminative typing method is RFLP (SI=0,97, there were distinguished 42 genotypes).PFGE was slightly less discriminative (SI=0,95, we identified 35 genotypes). MLST is still the best reference method (SI=1.0). Classic method of serotyping showed quite weak discriminative power (SI=0,93, 24 genotypes). In addition, sensivity of RFLP was 100%, specificity was 97,09%. Conclusion: the most appropriate method for routine epidemiology surveillance is RFLP with non-coding region of Streptococcsu pneumoniae, then PFGE, though in some cases these results should be obligatory confirmed by MLST.

Keywords: molecular epidemiology typing, non-coding genome, Streptococcus pneumoniae, MLST

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Authors: Ewelina Nowak, Anna Wisla-Swider, Gohar Khachatryan, Krzysztof Danel

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Complexes of ionic liquids with different heterocyclic-rings were synthesized by ion exchange reactions with pure salmon DNA. Ionic liquids (ILs) like 1-hexyl-3-methylimidazolium chloride, 1-butyl-4-methylpyridinium chloride and 1-ethyl-1-methylpyrrolidinium bromide were used. The ILs were built into helical state and confirmed by IR spectrometric techniques. Patterns of UV-Vis, photoluminescence, IR, and CD spectra indicated inclusion of small molecules into DNA structure. Molecular weight and radii of gyrations values of ILs-DNA complexes chains were established by HPSEC–MALLS–RI method. Modification DNA with 1-ethyl-1-methylpyrrolidinium bromide gives more uniform material and leads to elimination of high molecular weight chains. Thus, the incorporation DNA double helical structure with both 1-hexyl-3-methylimidazolium chloride and 1-butyl-4-methylpyridinium chloride exhibited higher molecular weight values. Scanning electron microscopy images indicate formation of nanofibre structures in all DNA complexes. Fluorescence depends strongly on the environment in which the chromophores are inserted and simultaneously on the molecular interactions with the biopolymer matrix. The most intensive emission was observed for DNA-imidazole ring complex. Decrease in intensity UV-Vis peak absorption is a consequence of a reduction in the spatial order of polynucleotide strands and provides different π–π stacking structure. Changes in optical properties confirmed by spectroscopy methods make DNA-ILs complexes potential biosensor applications.

Keywords: biopolymers, biosensors, cationic surfactant, DNA, DNA-gels

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Authors: Amir Zeb, Shailima Rampogu, Minky Son, Ayoung Baek, Sang H. Yoon, Keun W. Lee

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Neurotoxic insults activate calpain, which in turn produces truncated p25 from p35. p25 forms hyperactivated Cdk5/p25 complex, and thereby induces severe neuropathological aberrations including hyperphosphorylated tau, neuroinflammation, apoptosis, and neuronal death. Inhibition of Cdk5/p25 complex alleviates aberrant phosphorylation of tau to mitigate AD pathology. PHA-793887 and Roscovitine have been investigated as selective inhibitors of Cdk5/p25 with IC50 values 5nM and 160nM, respectively, but their mechanistic studies remain unknown. Herein, computational simulations have explored the binding mode and interaction mechanism of PHA-793887 and Roscovitine with Cdk5/p25. Docking results suggested that PHA-793887 and Rsocovitine have occupied the ATP-binding site of Cdk5 and obtained highest docking (GOLD) score of 66.54 and 84.03, respectively. Furthermore, molecular dynamics (MD) simulation demonstrated that PHA-793887 and Roscovitine established stable RMSD of 1.09 Å and 1.48 Å with Cdk5/p25, respectively. Profiling of polar interactions suggested that each inhibitor formed hydrogen bonds (H-bond) with catalytic residues of Cdk5 and could remain stable throughout the molecular dynamics simulation. Additionally, binding free energy calculation by molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) suggested that PHA-793887 and Roscovitine had lowest binding free energies of -150.05 kJ/mol and -113.14 kJ/mol, respectively with Cdk5/p25. Free energy decomposition demonstrated that polar energy by H-bond between the Glu81 of Cdk5 and PHA-793887 is the essential factor to make PHA-793887 highly selective towards Cdk5/p25. Overall, this study provided substantial evidences to explore mechanistic interactions of the selective inhibitors of Cdk5/p25 and could be used as fundamental considerations in the development of structure-based selective inhibitors of Cdk5/p25.

Keywords: Cdk5/p25 inhibition, molecular modeling of Cdk5/p25, PHA-793887 and roscovitine, selective inhibition of Cdk5/p25

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Authors: Najib Belhadj Messaoud, Slim Souissi

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The non-linear dynamic behavior of a single stage spur gear reducer is studied in this paper in transient regime. Driving and driver rotors are, respectively, powered by a motor torque Cm and loaded by a resistive torque Cr. They are supported by two identical Active Magnetic Bearings (AMBs). Gear excitation is induced by the motor torque and load variation in addition to the fluctuation of meshing stiff-ness due to the variation of input rotational speed. Three models of AMBs were used with four, six and eight magnets. They are operated by P.D controller and powered by control and bias currents. The dynamic parameters of the AMBs are modeled by stiffness and damping matrices computed by the derivation of the electromagnetic forces. The equations of motion are solved iteratively using Newmark time integration method. In the first part of the study, the model is powered by an electric motor and by a four strokes four cylinders diesel engine in the second part. The numerical results of the dynamic responses of the system come to confirm the significant effect of the transient regime on the dynamic behavior of a gear set, particularly in the case of engine acyclism condition. Results also confirm the influence of the magnet number by AMBs on the dynamic behavior of the system. Indeed, vibrations were more important in the case of gear reducer supported by AMBs with four magnets.

Keywords: motor, stiffness, gear, acyclism, fluctuation, torque

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Authors: Palwinder Singh

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Beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, herein, an alternate substrate of cyclooxygenase-2 was developed. Proline centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Remarkably, COX-2 metabolized the pentapeptide into small fragments consisting mainly of di- and tri-peptides that ensured the safe breakdown of the peptide under in-vivo conditions. The kinetic parameter Kcat/Km for COX-2 mediated metabolism of peptide 6.3 x 105 M-1 s-1 was quite similar to 9.5 x 105 M-1 s-1 for arachidonic acid. Evidenced by the dynamic molecular studies and the use of Y385F COX-2, it was observed that the breakage of the pentapeptide has probably taken place through H-bond activation of the peptide bond by the side chains of Y385 and S530.

Keywords: small peptides, anti-inflammatory agents, cyclooxygenase-2, unnatural substrates

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Authors: Fouzia Perveen, Rumana Qureshi

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The presently studied twelve anticancer drugs are the cytotoxic agents which inhibit the replication of DNA and activity of enzymes involved in DNA replication namely topoisomerase-II, polymerase and helicase and have shown remarkable anticancer activity in clinical trials. In this study, we performed molecular docking studies of twelve antitumor drugs against DNA and DNA enzymes in the presence and absence of ascorbic acid (AA) and developed the quantitative structure-activity relationship (QSAR) model for anticancer activity screening. A number of electronic and steric descriptors were calculated using MOE software package. QSAR was established showing a correlation of binding strength with various physicochemical descriptors. Out of these twelve, eight cytotoxic drugs were tested on Non-Small Cell Lung Cancer cell lines (H-157 and H-1299) in the absence and presence of ascorbic acid and experimental IC50 values were calculated. From the docking studies, binding constants were calculated indicating the strength of drug-DNA and drug-enzyme complex formation and it was correlated to the IC50 values (both experimental and theoretical). These results can offer useful references for directing the molecular design of DNA enzyme inhibitor with improved anticancer activity.

Keywords: ascorbic acid, binding constant, cytotoxic agents, cell culture, DNA, DNA enzymes, molecular docking

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Authors: Igor B. Sivaev

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Design of molecular machines is an extraordinary growing and very important area of research that it was recognized by awarding Sauvage, Stoddart and Feringa the Nobel Prize in Chemistry in 2016 'for the design and synthesis of molecular machines'. Based on the type of motion being performed, molecular machines can be divided into two main types: molecular motors and molecular switches. Molecular switches are molecules or supramolecular complexes having bistability, i.e., the ability to exist in two or more stable forms, among which may be reversible transitions under external influence (heating, lighting, changing the medium acidity, the action of chemicals, exposure to magnetic or electric field). Molecular switches are the main structural element of any molecular electronics devices. Therefore, the design and the study of molecules and supramolecular systems capable of performing mechanical movement is an important and urgent problem of modern chemistry. There is growing interest in molecular switches and other devices of molecular electronics based on transition metal complexes; therefore choice of suitable stable organometallic unit is of great importance. An example of such unit is bis(dicarbollide) complexes of transition metals [3,3’-M(1,2-C₂B₉H₁₁)₂]ⁿ⁻. The control on the ligand rotation in such complexes can be reached by introducing substituents which could provide stabilization of certain rotamers due to specific interactions between the ligands, on the one hand, and which can participate as Lewis bases in complex formation with external metals resulting in a change in the rotation angle of the ligands, on the other hand. A series of isomeric methyl sulfide derivatives of cobalt bis(dicarbollide) complexes containing methyl sulfide substituents at boron atoms in different positions of the pentagonal face of the dicarbollide ligands [8,8’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻, rac-[4,4’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻ and meso-[4,7’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻ were synthesized by the reaction of CoCl₂ with the corresponding methyl sulfide carborane derivatives [10-MeS-7,8-C₂B₉H₁₁)₂]⁻ and [10-MeS-7,8-C₂B₉H₁₁)₂]⁻. In the case of asymmetrically substituted cobalt bis(dicarbollide) complexes the corresponding rac- and meso-isomers were successfully separated by column chromatography as the tetrabutylammonium salts. The compounds obtained were studied by the methods of ¹H, ¹³C, and ¹¹B NMR spectroscopy, single crystal X-ray diffraction, cyclic voltammetry, controlled potential coulometry and quantum chemical calculations. It was found that in the solid state, the transoid- and gauche-conformations of the 8,8’- and 4,4’-isomers are stabilized by four intramolecular CH···S(Me)B hydrogen bonds each one (2.683-2.712 Å and 2.709-2.752 Å, respectively), whereas gauche-conformation of the 4,7’-isomer is stabilized by two intramolecular CH···S hydrogen bonds (2.699-2.711 Å). The existence of the intramolecular CH·S(Me)B hydrogen bonding in solutions was supported by the 1H NMR spectroscopy. These data are in a good agreement with results of the quantum chemical calculations. The corresponding iron and nickel complexes were synthesized as well. The reaction of the methyl sulfide derivatives of cobalt bis(dicarbollide) with various labile transition metal complexes results in rupture of intramolecular hydrogen bonds and complexation of the methyl sulfide groups with external metal. This results in stabilization of other rotational conformation of cobalt bis(dicarbollide) and can be used in design of molecular switches. This work was supported by the Russian Science Foundation (16-13-10331).

Keywords: molecular switches, NMR spectroscopy, single crystal X-ray diffraction, transition metal bis(dicarbollide) complexes, quantum chemical calculations

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Authors: Ali M. EL-Soll

Abstract:

Physical properties of Sarir waxy crude oil was investigated, pour-point was determined using ASTM D-79 procedure, paraffin content and carbon number distribution of the paraffin was determined using gas liquid Chromatography(GLC), polymeric additives were prepared and their structures were confirmed using IR spectrophotometer. The molecular weight and molecular weigh distribution of these additives were determined by gel permeation chromatography (GPC). the performance of the synthesized additives as pour-point depressants was evaluated, for the mentioned crude oil.

Keywords: sarir, waxy, crude, pour point, depressants

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Authors: A. Didaoui, N. Benhalima, M. Elkeurti, A. Chouaih, F. Hamzaoui

Abstract:

The monomer and dimer structures of the title molecule have been obtained from density functional theory (DFT) B3LYP method with 6-31G(d,p) as basis set calculations. The optimized geometrical parameters obtained by B3LYP/6-31G(d,p) method show good agreement with experimental X-ray data. The polarizability and first order hyperpolarizability of the title molecule were calculated and interpreted. The intermolecular N–H•••O hydrogen bonds are discussed in dimer structure of the molecule. The vibrational wave numbers and their assignments were examined theoretically using the Gaussian 03 set of quantum chemistry codes. The predicted frontier molecular orbital energies at B3LYP/6-31G(d,p) method set show that charge transfer occurs within the molecule. The frontier molecular orbital calculations clearly show the inverse relationship of HOMO–LUMO gap with the total static hyperpolarizability. The results also show that N-(2-Methylphenyl)-2-nitrobenzenesulfonamide molecule may have nonlinear optical (NLO) comportment with non-zero values.

Keywords: DFT, Gaussian 03, NLO, N-(2-Methylphenyl)-2-nitrobenzenesulfonamide, polarizability

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Authors: Strahinja Kovačević, Sanja Podunavac-Kuzmanović, Lidija Jevrić, Milica Karadžić

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The present study is based on the quantitative structure-activity relationship (QSAR) analysis of eighteen compounds with anti-prion activity. The structures and anti-prion activities (expressed in response units, RU%) of the analyzed compounds are taken from CHEMBL database. In the first step of analysis 85 molecular descriptors were calculated and based on them the hierarchical cluster analysis (HCA) and principal component analysis (PCA) were carried out in order to detect potential significant similarities or dissimilarities among the studied compounds. The calculated molecular descriptors were physicochemical, lipophilicity and ADMET (absorption, distribution, metabolism, excretion and toxicity) descriptors. The first stage of the QSAR analysis was simple linear regression modeling. It resulted in one acceptable model that correlates Henry's law constant with RU% units. The obtained 2D-QSAR model was validated by cross-validation as an internal validation method. The validation procedure confirmed the model’s quality and therefore it can be used for prediction of anti-prion activity. The next stage of the analysis of anti-prion activity will include 3D-QSAR and molecular docking approaches in order to select the most promising compounds in treatment of prion diseases. These results are the part of the project No. 114-451-268/2016-02 financially supported by the Provincial Secretariat for Science and Technological Development of AP Vojvodina.

Keywords: anti-prion activity, chemometrics, molecular modeling, QSAR

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Authors: Weirong Wang, Shenghong Huang, Xisheng Luo, Zhenyu Li

Abstract:

Material mixing process and related dynamic issues at extreme compressing conditions have gained more and more concerns in last ten years because of the engineering appealings in inertial confinement fusion (ICF) and hypervelocity aircraft developments. However, there lacks models and methods that can handle fully coupled turbulent material mixing and complex fluid evolution under conditions of high energy density regime up to now. In aspects of macro hydrodynamics, three numerical methods such as direct numerical simulation (DNS), large eddy simulation (LES) and Reynolds-averaged Navier–Stokes equations (RANS) has obtained relative acceptable consensus under the conditions of low energy density regime. However, under the conditions of high energy density regime, they can not be applied directly due to occurrence of dissociation, ionization, dramatic change of equation of state, thermodynamic properties etc., which may make the governing equations invalid in some coupled situations. However, in view of micro/meso scale regime, the methods based on Molecular Dynamics (MD) as well as Monte Carlo (MC) model are proved to be promising and effective ways to investigate such issues. In this study, both classical MD and first-principle based electron force field MD (eFF-MD) methods are applied to investigate Richtmyer-Meshkov Instability of metal Lithium and gas Hydrogen (Li-H2) interface mixing at different shock loading speed ranging from 3 km/s to 30 km/s. It is found that: 1) Classical MD method based on predefined potential functions has some limits in application to extreme conditions, since it cannot simulate the ionization process and its potential functions are not suitable to all conditions, while the eFF-MD method can correctly simulate the ionization process due to its ‘ab initio’ feature; 2) Due to computational cost, the eFF-MD results are also influenced by simulation domain dimensions, boundary conditions and relaxation time choices, etc., in computations. Series of tests have been conducted to determine the optimized parameters. 3) Ionization induced by strong shock compression has important effects on Li-H2 interface evolutions of RMI, indicating a new micromechanism of RMI under conditions of high energy density regime.

Keywords: first-principle, ionization, molecular dynamics, material mixture, Richtmyer-Meshkov instability

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Authors: Bergun Meric Bingul, Yezdan Cinel, Murat Son, Cigdem Bulgan, Mensure Aydin

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The aim of this study was to determination of the effects of knee and hip isokinetic performance during the training with the special designed roller-shoes. 30 soccer players participated as subjects and these subjects were divided into 3 groups randomly. Training groups were; with the dynamic training shoes group, without the dynamic training shoes group and control group. Subjects were trained speed strength trainings during 8 weeks (3 days a week and 1 hour a day). 6 exercises were focused on the knee flexors and extensors, also hip adductor and abductor muscles were chosen and performed in 3x30secs at each sets. Control group was not paticipated to the training program. Before and after the training programs knee flexor and extensor muscles and hip abductor and adductor muscles’ peak torques were measured by Biodex III isokinetic dynamometer. Isokinetic strength data were analyzed by using SPSS program. A repeated measures analysis of variance (ANOVA) was used to determine differences among the peak torque values for three groups. The results indicated that soccer players’ peak torque values that the group of using the dynamic training shoes, were found higher. Also, hip adductor and abductor peak torques that the group of using the dynamic training shoes, were obtained better than the other groups. In conclusion, the ground friction forces are an important role of increasing strength. With these shoes, using rollers, soccer players were able to move easily because of the friction forces were reduced and created more range of motion. So, exercises were performed faster than before and strength movements in all angles, it ensured that the active state. This was resulted in a better use of force.

Keywords: isokinetic, soccer, dynamic training shoes, training

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Authors: M. F. Elzarei, A. M. Alseaf

Abstract:

Hundred uncorrelated animal and thirty six markers were used in this study to study the molecular characterization of Saudi native Ardi goat (BM18189, ILSTS030, INRA005, OarFCB48, BM2113, ILSTS033, INRA023, RM088, CSRD247, ILSTS034, INRA063, SRCRSP1, ILSTS002, ILSTS044, INRA172, SRCRSP5, ILSTS005, ILSTS049, MAF70, SRCRSP8, ILSTS011, ILSTS058, OarAE54, SRCRSP9, ILSTS019, ILSTS059, OARCP34, TGLA53, ILSTS022, ILSTS082, OARE129, TGLA73, ILSTS029, ILSTS087, OARE193, and RM004). Ardi goat showed high variability. The mean number of alleles per locus ranged from 5 in SRCRSP1 locus to 13.5 in CSRD247 locus. Gene diversities varied within a wide range, from 0.53 in ILSTS002 locus to 0.86 in RM088 locus. Hardy-Weinberg equilibrium was tested in order to evaluate the significance of inbreeding occurring in each locus in Ardi population. Only SRCRSP9, INRA005, ILSTS030 loci showed significance in this way.

Keywords: molecular characterization, microsatellite markers, Ardi goats, Hardy-Weinberg equilibrium

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