Displaying publications 301 - 320 of 616 in total

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  1. Design and synthesis of new barbituric- and thiobarbituric acid derivatives as potent urease inhibitors: Structure activity relationship and molecular modeling studies
    Rauf A, Shahzad S, Bajda M, Yar M, Ahmed F, Hussain N, et al.
    Bioorg Med Chem, 2015 Sep 1;23(17):6049-58.
    PMID: 26081763 DOI: 10.1016/j.bmc.2015.05.038
    In this study 36 new compounds were synthesized by condensing barbituric acid or thiobarbituric acid and respective anilines (bearing different substituents) in the presence of triethyl orthoformate in good yields. In vitro urease inhibition studies against jack bean urease revealed that barbituric acid derived compounds (1-9 and 19-27) were found to exhibit low to moderate activity however thiobarbituric acid derived compounds (10-18 and 28-36) showed significant inhibition activity at low micro-molar concentrations. Among the synthesized compounds, compounds (15), (12), (10), (36), (16) and (35) showed excellent urease inhibition with IC50 values 8.53 ± 0.027, 8.93 ± 0.027, 12.96 ± 0.13, 15 ± 0.098, 18.9 ± 0.027 and 19.7 ± 0.63 μM, respectively, even better than the reference compound thiourea (IC50 = 21 ± 0.011). The compound (11) exhibited comparable activity to the standard with IC50 value 21.83 ± 0.19 μM. In silico molecular docking studies for most active compounds (10), (12), (15), (16), (35) and (36) and two inactive compounds (3) and (6) were performed to predict the binding patterns.
    Matched MeSH terms: Computer Simulation
  2. In silico deletion of PtsG gene in Escherichia coli genome-scale model predicts increased succinate production from glycerol
    Mienda BS, Shamsir MS
    J Biomol Struct Dyn, 2015;33(11):2380-9.
    PMID: 25921851 DOI: 10.1080/07391102.2015.1036461
    Systems metabolic engineering and in silico analyses are necessary to study gene knockout candidate for enhanced succinic acid production by Escherichia coli. Metabolically engineered E. coli has been reported to produce succinate from glucose and glycerol. However, investigation on in silico deletion of ptsG/b1101 gene in E. coli from glycerol using minimization of metabolic adjustment algorithm with the OptFlux software platform has not yet been elucidated. Herein we report what is to our knowledge the first direct predicted increase in succinate production following in silico deletion of the ptsG gene in E. coli GEM from glycerol with the OptFlux software platform. The result indicates that the deletion of this gene in E. coli GEM predicts increased succinate production that is 20% higher than the wild-type control model. Hence, the mutant model maintained a growth rate that is 77% of the wild-type parent model. It was established that knocking out of the ptsG/b1101 gene in E. coli using glucose as substrate enhanced succinate production, but the exact mechanism of this effect is still obscure. This study informs other studies that the deletion of ptsG/b1101 gene in E. coli GEM predicted increased succinate production, enabling a model-driven experimental inquiry and/or novel biological discovery on the underground metabolic role of this gene in E. coli central metabolism in relation to increasing succinate production when glycerol is the substrate.
    Matched MeSH terms: Computer Simulation
  3. Fulltext Analysis of human standing balance by largest lyapunov exponent
    Liu K, Wang H, Xiao J, Taha Z
    Comput Intell Neurosci, 2015;2015:158478.
    PMID: 25866500 DOI: 10.1155/2015/158478
    The purpose of this research is to analyse the relationship between nonlinear dynamic character and individuals' standing balance by the largest Lyapunov exponent, which is regarded as a metric for assessing standing balance. According to previous study, the largest Lyapunov exponent from centre of pressure time series could not well quantify the human balance ability. In this research, two improvements were made. Firstly, an external stimulus was applied to feet in the form of continuous horizontal sinusoidal motion by a moving platform. Secondly, a multiaccelerometer subsystem was adopted. Twenty healthy volunteers participated in this experiment. A new metric, coordinated largest Lyapunov exponent was proposed, which reflected the relationship of body segments by integrating multidimensional largest Lyapunov exponent values. By using this metric in actual standing performance under sinusoidal stimulus, an obvious relationship between the new metric and the actual balance ability was found in the majority of the subjects. These results show that the sinusoidal stimulus can make human balance characteristics more obvious, which is beneficial to assess balance, and balance is determined by the ability of coordinating all body segments.
    Matched MeSH terms: Computer Simulation
  4. Fulltext Preload-based starling-like control for rotary blood pumps: numerical comparison with pulsatility control and constant speed operation
    Mansouri M, Salamonsen RF, Lim E, Akmeliawati R, Lovell NH
    PLoS One, 2015;10(4):e0121413.
    PMID: 25849979 DOI: 10.1371/journal.pone.0121413
    In this study, we evaluate a preload-based Starling-like controller for implantable rotary blood pumps (IRBPs) using left ventricular end-diastolic pressure (PLVED) as the feedback variable. Simulations are conducted using a validated mathematical model. The controller emulates the response of the natural left ventricle (LV) to changes in PLVED. We report the performance of the preload-based Starling-like controller in comparison with our recently designed pulsatility controller and constant speed operation. In handling the transition from a baseline state to test states, which include vigorous exercise, blood loss and a major reduction in the LV contractility (LVC), the preload controller outperformed pulsatility control and constant speed operation in all three test scenarios. In exercise, preload-control achieved an increase of 54% in mean pump flow ([Formula: see text]) with minimum loading on the LV, while pulsatility control achieved only a 5% increase in flow and a decrease in mean pump speed. In a hemorrhage scenario, the preload control maintained the greatest safety margin against LV suction. PLVED for the preload controller was 4.9 mmHg, compared with 0.4 mmHg for the pulsatility controller and 0.2 mmHg for the constant speed mode. This was associated with an adequate mean arterial pressure (MAP) of 84 mmHg. In transition to low LVC, [Formula: see text] for preload control remained constant at 5.22 L/min with a PLVED of 8.0 mmHg. With regards to pulsatility control, [Formula: see text] fell to the nonviable level of 2.4 L/min with an associated PLVED of 16 mmHg and a MAP of 55 mmHg. Consequently, pulsatility control was deemed inferior to constant speed mode with a PLVED of 11 mmHg and a [Formula: see text] of 5.13 L/min in low LVC scenario. We conclude that pulsatility control imposes a danger to the patient in the severely reduced LVC scenario, which can be overcome by using a preload-based Starling-like control approach.
    Matched MeSH terms: Computer Simulation
  5. Management and control of pollution in Inner Johore Strait
    Koh HL, Lim PE, Midun Z
    Environ Monit Assess, 1991 Oct;19(1-3):349-59.
    PMID: 24233952 DOI: 10.1007/BF00401324
    Coastal waters in South Johore, Malaysia are polluted to various degrees. The major pollution sources are domestric wastes from human settlements, agro-based wastes from palm oil mills and rubber processing factories, industrial effluents from industrial estates and discharges from animal farms. These pollution problems have adversely affected resources such as fisheries, recreational potential as well as the general aesthetic quality of the coastal environment particularly the Inner Johore Strait. Hence proper management and control measures are urgently needed to protect and further enhance the water quality to ensure environmentally sustainable development. This study examines various management options to control the pollution in the Inner Johore Strait. The options involve partial opening as well as complete removal of the Causeway to improve the tidal flow for more effective dilution and dispersion of pollutants. Computer simulation models are used to assess the impacts of the proposed options.
    Matched MeSH terms: Computer Simulation
  6. Molecular dynamics study of the structure, flexibility and dynamics of thermostable l1 lipase at high temperatures
    Abedi Karjiban R, Abdul Rahman MB, Basri M, Salleh AB, Jacobs D, Abdul Wahab H
    Protein J, 2009 Jan;28(1):14-23.
    PMID: 19130194 DOI: 10.1007/s10930-008-9159-7
    Molecular Dynamics (MD) simulations have been used to understand how protein structure, dynamics, and flexibility are affected by adaptation to high temperature for several years. We report here the results of the high temperature MD simulations of Bacillus stearothermophilus L1 (L1 lipase). We found that the N-terminal moiety of the enzyme showed a high flexibility and dynamics during high temperature simulations which preceded and followed by clear structural changes in two specific regions; the small domain and the main catalytic domain or core domain of the enzyme. These two domains interact with each other through a Zn(2+)-binding coordination with Asp-61 and Asp-238 from the core domain and His-81 and His-87 from the small domain. Interestingly, the His-81 and His-87 were among the highly fluctuated and mobile residues at high temperatures. The results appear to suggest that tight interactions of Zn(2+)-binding coordination with specified residues became weak at high temperature which suggests the contribution of this region to the thermostability of the enzyme.
    Matched MeSH terms: Computer Simulation
  7. Fulltext A Low Cost and Portable Microwave Imaging System for Breast Tumor Detection Using UWB Directional Antenna array
    Islam MT, Mahmud MZ, Islam MT, Kibria S, Samsuzzaman M
    Sci Rep, 2019 10 29;9(1):15491.
    PMID: 31664056 DOI: 10.1038/s41598-019-51620-z
    Globally, breast cancer is a major reason for female mortality. Due to the limitations of current clinical imaging, the researchers are encouraged to explore alternative and complementary tools to available techniques to detect the breast tumor in an earlier stage. This article outlines a new, portable, and low-cost microwave imaging (MWI) system using an iterative enhancing technique for breast imaging. A compact side slotted tapered slot antenna is designed for microwave imaging. The radiating fins of tapered slot antenna are modified by etching nine rectangular side slots. The irregular slots on the radiating fins enhance the electrical length as well as produce strong directive radiation due to the suppression of induced surface currents that radiate vertically at the outer edges of the radiating arms with end-fire direction. It has remarkable effects on efficiency and gain. With the addition of slots, the side-lobe levels are reduced, the gain of the main-lobe is increased and corrects the squint effects simultaneously, thus improving the characteristics of the radiation. For experimental validation, a heterogeneous breast phantom was developed that contains dielectric properties identical to real breast tissues with the inclusion of tumors. An alternative PC controlled and microcontroller-based mechanical MWI system is designed and developed to collect the antenna scattering signal. The radiated backscattered signals from the targeted area of the human body are analyzed to reveal the changes in dielectric properties in tissues. The dielectric constants of tumorous cells are higher than that of normal tissues due to their higher water content. The remarkable deviation of the scattered field is processed by using newly proposed Iteratively Corrected Delay and Sum (IC-DAS) algorithm and the reconstruction of the image of the phantom interior is done. The developed UWB (Ultra-Wideband) antenna based MWI has been able to perform the detection of tumorous cells in breast phantom that can pave the way to saving lives.
    Matched MeSH terms: Computer Simulation
  8. Haloadaptation: insights from comparative modeling studies between halotolerant and non-halotolerant dehalogenases
    Edbeib MF, Aksoy HM, Kaya Y, Wahab RA, Huyop F
    J Biomol Struct Dyn, 2020 Aug;38(12):3452-3461.
    PMID: 31422756 DOI: 10.1080/07391102.2019.1657498
    Halophiles are extremophilic microorganisms that grow optimally at high salt concentrations by producing a myriad of equally halotolerant enzymes. Structural haloadaptation of these enzymes adept to thriving under high-salt environments, though are not fully understood. Herein, the study attempts an in silico investigation to identify and comprehend the evolutionary structural adaptation of a halotolerant dehalogenase, DehHX (GenBank accession number: KR297065) of the halotolerant Pseudomonas halophila, over its non-halotolerant counterpart, DehMX1 (GenBank accession number KY129692) produced by Pseudomonas aeruginosa. GC content of the halotolerant DehHX DNA sequence was distinctively higher (58.9%) than the non-halotolerant dehalogenases (55% average GC). Its acidic residues, Asp and Glu were 8.27% and 12.06%, respectively, compared to an average 5.5% Asp and 7% Glu, in the latter; but lower contents of basic and hydrophobic residues in the DehHX. The secondary structure of DehHX interestingly revealed a lower incidence of α-helix forming regions (29%) and a higher percentage of coils (57%), compared to 49% and 29% in the non-halotolerant homologues, respectively. Simulation models showed the DehHX is stable under a highly saline environment (25% w/v) by adopting a highly negative-charged surface with a concomitant weakly interacting hydrophobic core. The study thus, established that a halotolerant dehalogenase undergoes notable evolutionary structural changes related to GC content over its non-halotolerant counterpart, in order to adapt and thrive under highly saline environments.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Computer Simulation
  9. Impacts of dynamic degradation on the morphological and mechanical characterisation of porous magnesium scaffold
    Md Saad AP, Prakoso AT, Sulong MA, Basri H, Wahjuningrum DA, Syahrom A
    Biomech Model Mechanobiol, 2019 Jun;18(3):797-811.
    PMID: 30607641 DOI: 10.1007/s10237-018-01115-z
    This study employs a computational approach to analyse the impact of morphological changes on the structural properties of biodegradable porous Mg subjected to a dynamic immersion test for its application as a bone scaffold. Porous Mg was immersed in a dynamic immersion test for 24, 48, and 72 h. Twelve specimens were prepared and scanned using micro-CT and then reconstructed into a 3D model for finite element analysis. The structural properties from the numerical simulation were then compared to the experimental values. Correlations between morphological parameters, structural properties, and fracture type were then made. The relative losses were observed to be in agreement with relative mass loss done experimentally. The degradation rates determined using exact (degraded) surface area at particular immersion times were on average 20% higher than the degradation rates obtained using original surface area. The dynamic degradation has significantly impacted the morphological changes of porous Mg in volume fraction, surface area, and trabecular separation, which in turn affects its structural properties and increases the immersion time.
    Matched MeSH terms: Computer Simulation
  10. Estimation of an Instrument-Defined Minimally Important Difference in EQ-5D-5L Index Scores Based on Scoring Algorithms Derived Using the EQ-VT Version 2 Valuation Protocols
    Henry EB, Barry LE, Hobbins AP, McClure NS, O'Neill C
    Value Health, 2020 07;23(7):936-944.
    PMID: 32762996 DOI: 10.1016/j.jval.2020.03.003
    OBJECTIVES: To estimate and compare the minimally important difference (MID) in index score of country-specific EQ-5D-5L scoring algorithms developed using EuroQol Valuation Technology protocol version 2, including algorithms from Germany, Indonesia, Ireland, Malaysia, Poland, Portugal, Taiwan, and the United States.

    METHODS: A simulation-based approach contingent on all single-level transitions defined by the EQ-5D-5L descriptive system was used to estimate the MID for each algorithm.

    RESULTS: The resulting mean (and standard deviation) instrument-defined MID estimates were Germany, 0.083 (0.022); Indonesia, 0.093 (0.012); Ireland, 0.098 (0.023); Malaysia, 0.072 (0.010); Poland, 0.080 (0.030); Portugal, 0.080 (0.018); Taiwan, 0.101 (0.010); and the United States, 0.078 (0.014).

    CONCLUSIONS: These population preference-based MID estimates and accompanying evidence of how such values vary as a function of baseline index score can be used to aid interpretation of index score change. The marked consistency in the relationship between the calculated MID estimate and the range of the EQ-5D-5L index score, represented by a ratio of 1:20, might substantiate a rule of thumb allowing for MID approximation in EQ-5D-5L index score warranting further investigation.

    Matched MeSH terms: Computer Simulation
  11. Fulltext An Improved Fabrication Technique for the 3-D Frequency Selective Surface based on Water Transfer Printing Technology
    Harnois M, Himdi M, Yong WY, Rahim SKA, Tekkouk K, Cheval N
    Sci Rep, 2020 Feb 03;10(1):1714.
    PMID: 32015444 DOI: 10.1038/s41598-020-58657-5
    Manufacturing an array of high-quality metallic pattern layers on a dielectric substrate remains a major challenge in the development of flexible and 3-D frequency selective surfaces (FSS). This paper proposes an improved fabrication solution for the 3-D FSS based on water transfer printing (WTP) technology. The main advantages of the proposed solution are its ability to transform complicated 2-D planar FSS patterns into 3-D structures while improving both manufacturing quality and production costs. WTP technology makes use of water surface tension to keep the thin metallic patterns of the proposed FSS floating flat with the absence of a solid planar substrate. This feature enables these metallic FSS patterns to be transferred onto 3-D structures through a dipping process. To test the effectiveness of the proposed technique, the FSS was designed using computer simulation software Microwave Studio to obtain the numerical performance of the FSS structure. The WTP technology was then used to fabricate the proposed FSS prototype before its performance was tested experimentally. The measurement results agreed well with the numerical results, indicating the proposed manufacturing solution would support the development of complicated 3-D electronics devices, such as conformal antenna arrays and metamaterials.
    Matched MeSH terms: Computer Simulation
  12. An improved hybrid of particle swarm optimization and the gravitational search algorithm to produce a kinetic parameter estimation of aspartate biochemical pathways
    Ismail AM, Mohamad MS, Abdul Majid H, Abas KH, Deris S, Zaki N, et al.
    Biosystems, 2017 Dec;162:81-89.
    PMID: 28951204 DOI: 10.1016/j.biosystems.2017.09.013
    Mathematical modelling is fundamental to understand the dynamic behavior and regulation of the biochemical metabolisms and pathways that are found in biological systems. Pathways are used to describe complex processes that involve many parameters. It is important to have an accurate and complete set of parameters that describe the characteristics of a given model. However, measuring these parameters is typically difficult and even impossible in some cases. Furthermore, the experimental data are often incomplete and also suffer from experimental noise. These shortcomings make it challenging to identify the best-fit parameters that can represent the actual biological processes involved in biological systems. Computational approaches are required to estimate these parameters. The estimation is converted into multimodal optimization problems that require a global optimization algorithm that can avoid local solutions. These local solutions can lead to a bad fit when calibrating with a model. Although the model itself can potentially match a set of experimental data, a high-performance estimation algorithm is required to improve the quality of the solutions. This paper describes an improved hybrid of particle swarm optimization and the gravitational search algorithm (IPSOGSA) to improve the efficiency of a global optimum (the best set of kinetic parameter values) search. The findings suggest that the proposed algorithm is capable of narrowing down the search space by exploiting the feasible solution areas. Hence, the proposed algorithm is able to achieve a near-optimal set of parameters at a fast convergence speed. The proposed algorithm was tested and evaluated based on two aspartate pathways that were obtained from the BioModels Database. The results show that the proposed algorithm outperformed other standard optimization algorithms in terms of accuracy and near-optimal kinetic parameter estimation. Nevertheless, the proposed algorithm is only expected to work well in small scale systems. In addition, the results of this study can be used to estimate kinetic parameter values in the stage of model selection for different experimental conditions.
    Matched MeSH terms: Computer Simulation
  13. Fulltext An analysis of a nonlinear susceptible-exposed-infected-quarantine-recovered pandemic model of a novel coronavirus with delay effect
    Raza A, Ahmadian A, Rafiq M, Salahshour S, Ferrara M
    Results Phys, 2021 Feb;21:103771.
    PMID: 33391985 DOI: 10.1016/j.rinp.2020.103771
    In the present study, a nonlinear delayed coronavirus pandemic model is investigated in the human population. For study, we find the equilibria of susceptible-exposed-infected-quarantine-recovered model with delay term. The stability of the model is investigated using well-posedness, Routh Hurwitz criterion, Volterra Lyapunov function, and Lasalle invariance principle. The effect of the reproduction number on dynamics of disease is analyzed. If the reproduction number is less than one then the disease has been controlled. On the other hand, if the reproduction number is greater than one then the disease has become endemic in the population. The effect of the quarantine component on the reproduction number is also investigated. In the delayed analysis of the model, we investigated that transmission dynamics of the disease is dependent on delay terms which is also reflected in basic reproduction number. At the end, to depict the strength of the theoretical analysis of the model, computer simulations are presented.
    Matched MeSH terms: Computer Simulation
  14. Fulltext Finite element modelling and simulation for lower limb of human bone: a review
    Muhammad Hanif Ramlee
    Malaysian Journal of Medicine and Health Sciences, 2020;16(3):262-271.
    MyJurnal
    Most orthopaedic cases that involved with bone fracture are normally treated with medical implants. To be noticed that some precautions in terms of biomechanical and biomaterial properties are necessary for a successful post-sur- gery process. The biomechanical evaluation of implants could be carried out using computing and engineering technologies. However, in the computer simulation, some assumptions are needed as the limitations on computer resources and data input. This review focuses on the current method of developing the finite element model for patients with specific values of material properties for lower limb part such as hip, knee and ankle joint. Previous literature was reviewed from which keywords and search engines were identified. In this review, inclusion and exclusion criteria were used to limit the literature search. We reviewed the state-of-the-art in this area and provide recommendations for future research. In conclusion, the previous published reports illustrated different methods to develop numerical models.
    Matched MeSH terms: Computer Simulation
  15. Transcriptome-Guided Identification of Carbohydrate Active Enzymes (CAZy) from the Christmas Island Red Crab, Gecarcoidea natalis and a Vote for the Inclusion of Transcriptome-Derived Crustacean CAZys in Comparative Studies
    Gan HM, Austin C, Linton S
    Mar Biotechnol (NY), 2018 Oct;20(5):654-665.
    PMID: 29995174 DOI: 10.1007/s10126-018-9836-2
    The Christmas Island red crab, Gecarcoidea natalis, is an herbivorous land crab that consumes mostly fallen leaf litter. In order to subsist, G. natalis would need to have developed specialised digestive enzymes capable of supplying significant amounts of metabolisable sugars from this diet. To gain insights into the carbohydrate metabolism of G. natalis, a transcriptome assembly was performed, with a specific focus on identifying transcripts coding for carbohydrate active enzyme (CAZy) using in silico approaches. Transcriptome sequencing of the midgut gland identified 70 CAZy-coding transcripts with varying expression values. At least three newly discovered putative GH9 endo-β-1,4-glucanase ("classic cellulase") transcripts were highly expressed in the midgut gland in addition to the previously characterised GH9 and GH16 (β-1,3-glucanase) transcripts, and underscoring the utility of whole transcriptome in uncovering new CAZy-coding transcripts. A highly expressed transcript coding for GH5_10 previously missed by conventional screening of cellulase activity was inferred to be a novel endo-β-1,4-mannase in G. natalis with in silico support from homology modelling and amino acid alignment with other functionally validated GH5_10 proteins. Maximum likelihood tree reconstruction of the GH5_10 proteins demonstrates the phylogenetic affiliation of the G. natalis GH5_10 transcript to that of other decapods, supporting endogenous expression. Surprisingly, crustacean-derived GH5_10 transcripts were near absent in the current CAZy database and yet mining of the transcriptome shotgun assembly (TSA) recovered more than 100 crustacean GH5_10s in addition to several other biotechnological relevant CAZys, underscoring the unappreciated potential of the TSA database as a valuable resource for crustacean CAZys.
    Matched MeSH terms: Computer Simulation
  16. Fulltext Hypothetical Protein BPSL3393 of Burkholderia pseudomallei is Involved in Ethanolamine Catabolism
    Luan OG, Yam H, Samian R, Wajidi MFF, Mahadi NM, Mohamad S, et al.
    Trop Life Sci Res, 2017 Jul;28(2):57-74.
    PMID: 28890761 MyJurnal DOI: 10.21315/tlsr2017.28.2.5
    Burkholderia pseudomallei is a soil-dwelling bacterium that causes a globally emerging disease called melioidosis. Approximately one third of the in silico annotated genes in its genome are classified as hypothetical genes. This group of genes is difficult to be functionally characterised partly due to the absence of noticeable phenotypes under conventional laboratory settings. A bioinformatic survey of hypothetical genes revealed a gene designated as BPSL3393 that putatively encodes a small protein of 11 kDA with a CoA binding domain. BPSL3393 is conserved in all the B. pseudomallei genomes as well as various in other species within the genus Burkholderia. Taking into consideration that CoA plays a ubiquitous metabolic role in all life forms, characterisation of BPSL3393 may uncover a previously over-looked metabolic feature of B. pseudomallei. The gene was deleted from the genome using a double homologous recombination approach yielding a null mutant. The BPSL3393 mutant showed no difference in growth rate with the wild type under rich and minimal growth conditions. An extensive metabolic phenotyping test was performed involving 95 metabolic substrates. The deletion mutant of BPSL3393 was severely impaired in its ethanolamine metabolism. The growth rate of the mutant was attenuated when ethanolamine was used as the sole carbon source. A transcriptional analysis of the ethanolamine metabolism genes showed that they were down-regulated in the BPSL3393 mutant. This seemed to suggest that BPSL3393 functions as a positive regulator for ethanolamine metabolism.
    Matched MeSH terms: Computer Simulation
  17. Discovery of small molecule inhibitors against the NS3/4A serine protease of Hepatitis C virus genotype 3 via highthroughput virtual screening and in vitro evaluations
    Sakhor W, Teoh TC, Yusof R, Lim SK, Razif MFM
    Trop Biomed, 2020 Sep 01;37(3):609-625.
    PMID: 33612776 DOI: 10.47665/tb.37.3.609
    The hepatitis C virus (HCV) consists of eight genotypes and 90 subtypes, with genotype (GT) 3 being the second most common globally and is linked to higher incidences of steatosis and rapid development of fibrosis and cirrhosis. The NS3/4A serine protease, a heterodimer complex of two HCV non-structural proteins, is an effective target for pharmaceutical intervention due to its essential roles in processing HCV polyproteins and inhibiting innate immunity. This study combines structure-based virtual screening (SBVS) of predefined compound libraries, pharmacokinetic prediction (ADME/T) and in vitro evaluation to identify potential low molecular weight (<500 Dalton) inhibitors of the NS3/4A serine protease (GT3). In silico screening of ZINC and PubChem libraries yielded five selected compounds as potential candidates. Dose-dependent inhibition of the NS3/4A serine protease and HCV replication in HuH-7.5 cells revealed that compound A (PubChem ID No. 16672637) exhibited inhibition towards HCV GT3 with an IC50 of 106.7µM and EC50 of 25.8µM, respectively. Thus, compound A may be developed as a potent, low molecular weight drug against the HCV NS3/4A serine protease of GT3.
    Matched MeSH terms: Computer Simulation
  18. In silico analysis of nonsynonymous single nucleotide polymorphisms of the human adiponectin receptor 2 (ADIPOR2) gene
    Solayman M, Saleh MA, Paul S, Khalil MI, Gan SH
    Comput Biol Chem, 2017 Jun;68:175-185.
    PMID: 28359874 DOI: 10.1016/j.compbiolchem.2017.03.005
    Polymorphisms of the ADIPOR2 gene are frequently linked to a higher risk of developing diseases including obesity, type 2 diabetes and cardiovascular diseases. Though mutations of the ADIPOR2 gene are detrimental, there is a lack of comprehensive in silico analyses of the functional and structural impacts at the protein level. Considering the involvement of ADIPOR2 in glucose uptake and fatty acid oxidation, an in silico functional analysis was conducted to explore the possible association between genetic mutations and phenotypic variations. A genomic analysis of 82 nonsynonymous SNPs in ADIPOR2 was initiated using SIFT followed by the SNAP2, nsSNPAnalyzer, PolyPhen-2, SNPs&GO, FATHMM and PROVEAN servers. A total of 10 mutations (R126W, L160Q, L195P, F201S, L235R, L235P, L256R, Y328H, E334K and Q349H) were predicted to have deleterious effects on the ADIPOR2 protein and were therefore selected for further analysis. Theoretical models of the variants were generated by comparative modeling via MODELLER 9.16. A protein structural analysis of these amino acid variants was performed using SNPeffect, I-Mutant, ConSurf, Swiss-PDB Viewer and NetSurfP to explore their solvent accessibility, molecular dynamics and energy minimization calculations. In addition, FTSite was used to predict the ligand binding sites, while NetGlycate, NetPhos2.0, UbPerd and SUMOplot were used to predict post-translational modification sites. All of the variants showed increased free energy, though F201S exhibited the highest energy increase. The root mean square deviation values of the modeled mutants strongly indicated likely pathogenicity. Remarkably, three binding sites were detected on ADIPOR2, and two mutations at positions 328 and 201 were found in the first and second binding pockets, respectively. Interestingly, no mutations were found at the post-translational modification sites. These genetic variants can provide a better understanding of the wide range of disease susceptibility associated with ADIPOR2 and aid the development of new molecular diagnostic markers for these diseases. The findings may also facilitate the development of novel therapeutic elements for associated diseases.
    Matched MeSH terms: Computer Simulation
  19. Fulltext Compact circularly polarized truncated square ring slot antenna with suppressed higher resonances
    Sabran MI, Abdul Rahim SK, Leow CY, Soh PJ, Chew BW, Vandenbosch GA
    PLoS One, 2017;12(2):e0172162.
    PMID: 28192504 DOI: 10.1371/journal.pone.0172162
    This paper presents a compact circularly polarized (CP) antenna with an integrated higher order harmonic rejection filter. The proposed design operates within the ISM band of 2.32 GHz- 2.63 GHz and is suitable for example for wireless power transfer applications. Asymmetrical truncated edges on a square ring create a defected ground structure to excite the CP property, simultaneously realizing compactness. It offers a 50.5% reduced patch area compared to a conventional design. Novel stubs and slot shapes are integrated in the transmission line to reduce higher (up to the third) order harmonics. The proposed prototype yields a -10 dB reflection coefficient (S11) impedance bandwidth of 12.53%, a 3 dB axial ratio bandwidth of 3.27%, and a gain of 5.64 dBi. Measurements also show good agreement with simulations.
    Matched MeSH terms: Computer Simulation
  20. Fulltext Implications for Drug Characterization in Glucose Tolerance Tests Without Insulin: Simulation Study of Power and Predictions Using Model-Based Analysis
    Sheikh Ghadzi SM, Karlsson MO, Kjellsson MC
    CPT Pharmacometrics Syst Pharmacol, 2017 10;6(10):686-694.
    PMID: 28575547 DOI: 10.1002/psp4.12214
    In antihyperglycemic drug development, drug effects are usually characterized using glucose provocations. Analyzing provocation data using pharmacometrics has shown powerful, enabling small studies. In preclinical drug development, high power is attractive due to the experiment sizes; however, insulin is not always available, which potentially impacts power and predictive performance. This simulation study was performed to investigate the implications of performing model-based drug characterization without insulin. The integrated glucose-insulin model was used to simulate and re-estimated oral glucose tolerance tests using a crossover design of placebo and study compound. Drug effects were implemented on seven different mechanisms of action (MOA); one by one or in two-drug combinations. This study showed that exclusion of insulin may severely reduce the power to distinguish the correct from competing drug effect, and to detect a primary or secondary drug effect, however, it did not affect the predictive performance of the model.
    Matched MeSH terms: Computer Simulation
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