Search results for: entry inhibitors

Authors: A. R. Diniz, P. Borrego, I. Bártolo, N. Taveira

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Cell-to-cell transmission plays a critical role in the spread of HIV-1 infection in vitro and in vivo. Inhibition of HIV-1 cell-associated infection by antiretroviral drugs and neutralizing antibodies (NAbs) is more difficult compared to cell-free infection. Limited data exists on cell-associated infection by HIV-2 and its inhibition. In this work, we determined the ability of entry inhibitors to inhibit HIV-1 and HIV-2 cell-to cell fusion as a proxy to cell-associated infection. We developed a method in which Hela-CD4-cells are first transfected with a Tat expressing plasmid (pcDNA3.1+/Tat101) and infected with recombinant vaccinia viruses expressing either the HIV-1 (vPE16: from isolate HTLV-IIIB, clone BH8, X4 tropism) or HIV-2 (vSC50: from HIV-2SBL/ISY, R5 and X4 tropism) envelope glycoproteins (M.O.I.=1 PFU/cell).These cells are added to TZM-bl cells. When cell-to-cell fusion (syncytia) occurs the Tat protein diffuses to the TZM-bl cells activating the expression of a reporter gene (luciferase). We tested several entry inhibitors including the fusion inhibitors T1249, T20 and P3, the CCR5 antagonists MVC and TAK-779, the CXCR4 antagonist AMD3100 and several HIV-2 neutralizing antibodies (Nabs). All compounds inhibited HIV-1 and HIV-2 cell fusion albeit to different levels. Maximum percentage of HIV-2 inhibition (MPI) was higher for fusion inhibitors (T1249- 99.8%; P3- 95%, T20-90%) followed by co-receptor antagonists (MVC- 63%; TAK-779- 55%; AMD3100- 45%). NAbs from HIV-2 infected patients did not prevent cell fusion up to the tested concentration of 4μg/ml. As for HIV-1, MPI reached 100% with TAK-779 and T1249. For the other antivirals, MPIs were: P3-79%; T20-75%; AMD3100-61%; MVC-65%.These results are consistent with published data. Maraviroc had the lowest IC50 both for HIV-2 and HIV-1 (IC50 HIV-2= 0.06 μM; HIV-1=0.0076μM). Highest IC50 were observed with T20 for HIV-2 (3.86μM) and with TAK-779 for HIV-1 (12.64μM). Overall, our results show that entry inhibitors in clinical use are less effective at preventing Env mediated cell-to-cell-fusion in HIV-2 than in HIV-1 which suggests that cell-associated HIV-2 infection will be more difficult to inhibit compared to HIV-1. The method described here will be useful to screen for new HIV entry inhibitors.

Keywords: cell-to-cell fusion, entry inhibitors, HIV, NAbs, vaccinia virus

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Authors: Samira Ghizellaoui, Manel Boumagoura

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The municipality of Constantine in eastern Algeria draws water from the Hamma groundwater source. The high fouling capacity is due to the high content of bicarbonate (442 mg/L) and calcium (136 mg/L). This work focuses on the use of three new green inhibitors for reducing calcium carbonate scale formation: gallic acid, quercetin and alginate, and on the comparison between them. These inhibitors have proven to be green antiscalants because they have no impact on the environment. Electrochemical methods (chronoamperometry and impedancemetry) were used to evaluate their performance. According to the study, these inhibitors are excellent green chemical inhibitors of scaling, and the best inhibitor is quercetin because it gave a good result with a lower concentration (2mg/L) compared to others inhibitors.

Keywords: scaling, green inhibitor, chronoamperometry, impedancemetry

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Authors: Jianxin Zhu, Na Liu

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Entry strategies play a vital role in the development of new enterprises in the catering industry. Different entry strategies will have different effects on the development of new enterprise. Based on the research of scholars at home and abroad, and combining the characteristics of the catering industry, the entry strategies are divided into low-price entry strategies and high-quality entry strategies. Facing the entry of new enterprise, the strategies of incumbent enterprises are divided into response strategies and non-response strategies. This paper uses evolutionary game theory to study the strategic interaction mechanism between incumbent companies and new enterprises. When different initial values and parameter values are set, which strategy will the two-game subjects choose, respectively? Using matlab2016 for numerical simulation, the results show that the choice of strategies for new enterprise and incumbent enterprise is influenced by more than one factor, and the system has different evolution trends under different circumstances. When the parameters were set, the choice of two subjects' strategies mainly depends on the net profit between the strategies.

Keywords: catering industry, entry strategy, evolutionary game, strategic interaction mechanism

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Authors: Lin Lu, Qiang Li, Tao Cai, Pengjun Zhang

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In this study, a detailed analysis of trajectory stability and flow characteristics of a high-speed projectile during the water-entry and water-exit process has been investigated numerically. The Zwart-Gerber-Belamri (Z-G-B) cavitation model and the SST k-ω turbulence model based on the Reynolds Averaged Navier-Stokes (RANS) method are employed. The numerical methodology is validated by comparing the experimental photograph of cavitation shape and the experimental underwater velocity with the numerical simulation results. Based on the numerical methodology, the influences of rotational speed, water-entry and water-exit angle of the projectile on the trajectory stability and flow characteristics have been carried out in detail. The variation features of projectile trajectory and total resistance have been conducted, respectively. In addition, the cavitation characteristics of water-entry and water-exit have been presented and analyzed. Results show that it may not be applicable for the water-entry and water-exit to achieve the projectile stability through the rotation of projectile. Furthermore, there ought to be a critical water-entry angle for the water-entry stability of practical projectile. The impact of water-exit angle on the trajectory stability and cavity phenomenon is not as remarkable as that of the water-entry angle.

Keywords: cavitation characteristics, high-speed projectile, numerical predictions, trajectory stability, water-entry, water-exit

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Authors: Go Woon Kwak, Siyoung Jun, Soyun Maeng, Haeyoung Lee

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Entry is an education platform used in South Korea, created to help students learn to program, in which they can learn to code while playing. Using the online version of the entry, teachers can easily assign programming homework to the student and the students can make programs simply by linking programming blocks. However, the programs may be made by others, so that the authors of the programs should be identified. In this paper, as the first step toward author identification of entry programs, we present an artificial neural network based classification approach to identify genders of authors of a program written in an entry. A neural network has been trained from labeled training data that we have collected. Our result in progress, although preliminary, shows that the proposed approach could be feasible to be applied to the online version of entry for gender identification of authors. As future work, we will first use a machine learning technique for age identification of entry programs, which would be the second step toward the author identification.

Keywords: artificial intelligence, author identification, deep neural network, gender identification, machine learning

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Authors: Khalid Ahmed Eldwaib

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In this study, Al-Mg alloy 5052 was used as the testing material. Corrosion fatigue life was studied for the alloy in 3.5% NaCl (pH=1, 3, 5, 7, 9, and 11), and 3.5% NaCl (pH=1) with inhibitors. The compound inhibitors were composed mainly of phosphate (PO4³-), adding a certain proportion of other nontoxic inhibitors so as to select alternatives to environmentally hazardous chromate (Cr2O7²-). The inhibitors were sodium dichromate Na2Cr2O7, sodium phosphate Na3PO4, sodium molybdate Na2MoO4, and sodium citrate Na3C6H5O7. The total amount of inhibiting pigments was at different concentrations (250,500,750, and 1000 ppm) in the solutions. Corrosion fatigue behavior was studied by using plane-bending corrosion fatigue machine with stress ratio R=0.5 and under the constant frequency of 13.3 Hz. Results show that in 3.5% NaCl the highest fatigue life (number of cycles to failure Nf) is obtained at pH=5 where the oxide film on aluminum has very low solubility, and the lowest number of cycles is obtained at pH=1, where the media is too aggressive (extremely acidic). When the concentration of inhibitor increases the cycles to failure increase. The surface morphology and fracture section of the specimens had been characterized through scanning electron microscope (SEM).

Keywords: Al-Mg alloy 5052, corrosion, fatigue, inhibitors

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Authors: K. D. Mroczek

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In the study presented institutional context is discussed in terms of companies’ entry mode choice. In contrary to many previous analyses, instead of using one or two aggregated variables, a set of eleven determinants is used to establish equity and non-equity internationalization friendly conditions. Based on secondary data, 140 countries are analysed and grouped into clusters revealing similar framework. The range of the economies explored is wide as it covers all regions distinguished by The World Bank. The results can prove a useful alternative for operationalization of institutional variables in further research concerning entry modes or strategic management in international markets.

Keywords: clustering, entry mode choice, institutional environment, transaction costs

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Authors: Driss Cherqaoui, Nouhaila Ait Lahcen, Ismail Hdoufane, Mehdi Oubahmane, Wissal Liman, Christelle Delaite, Mohammed M. Alanazi

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The Ebola virus is a highly contagious and deadly pathogen that causes Ebola virus disease. The Ebola virus glycoprotein (EBOV-GP) is a key factor in viral entry into host cells, making it a critical target for therapeutic intervention. Using a combination of computational approaches, this study focuses on the identification of natural compounds that could serve as potent inhibitors of EBOV-GP. The 3D structure of EBOV-GP was selected, with missing residues modeled, and this structure was minimized and equilibrated. Two large natural compound databases, COCONUT and NPASS, were chosen and filtered based on toxicity risks and Lipinski’s Rule of Five to ensure drug-likeness. Following this, a pharmacophore model, built from 22 reported active inhibitors, was employed to refine the selection of compounds with a focus on structural relevance to known Ebola inhibitors. The filtered compounds were subjected to virtual screening via molecular docking, which identified ten promising candidates (five from each database) with strong binding affinities to EBOV-GP. These compounds were then validated through molecular dynamics simulations to evaluate their binding stability and interactions with the target. The top three compounds from each database were further analyzed using ADMET profiling, confirming their favorable pharmacokinetic properties, stability, and safety. These results suggest that the selected compounds have the potential to inhibit EBOV-GP, offering new avenues for antiviral drug development against the Ebola virus.

Keywords: EBOV-GP, Ebola virus glycoprotein, high-throughput drug screening, molecular docking, molecular dynamics, natural compounds, pharmacophore modeling, virtual screening

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Authors: Gabriel S. De Oliveira, Patricia P. Adriani, Christophe Moriseau, Bruce D. Hammock, Felipe S. Chambergo

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Epoxide hydrolases (EHs) are enzymes that are present in all living organisms and catalyze the hydrolysis of epoxides to the corresponding vicinal diols. EHs have high biotechnological interest for the drug design and chemistry transformation for industries. In this study, we describe the identification of substrates and inhibitors of epoxide hydrolase enzyme from the filamentous fungus Trichoderma reesei (TrEH), and these inhibitors showed the fungal growth inhibitory activity. We have used the cloned enzyme and expressed in E. coli to develop the screening in the library of fluorescent substrates with the objective of finding the best substrate to be used in the identification of good inhibitors for the enzyme TrEH. The substrate (3-phenyloxiranyl)-acetic acid cyano-(6-methoxy-naphthalen-2-yl)-methyl ester showed the highest specific activity and was chosen for the next steps of the study. The inhibitors screening was performed in the library with more than three thousand molecules and we could identify the 6 best inhibitors. The IC50 of these molecules were determined in nM and all the best inhibitors have urea or amide in their structure, because It has been recognized that these groups fit well in the hydrolase catalytic pocket of the epoxide hydrolases. Then the growth of T. reesei in PDA medium containing these TrEH inhibitors was tested, and fungal growth inhibition activity was demonstrated with more than 60% of inhibition of fungus growth in the assay with the TrEH inhibitor with the lowest IC50. Understanding how this EH enzyme from T. reesei responds to inhibitors may contribute for the study of fungal metabolism and drug design against pathogenic fungi.

Keywords: epoxide hydrolases, fungal growth inhibition, inhibitor, Trichoderma reesei

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Authors: C. M. Mat Isa, H. Mohd Saman, S. R. Mohd Nasir, A. Jaapar

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International market expansion involves a strategic process of market entry decision through which a firm expands its operation from domestic to the international domain. Hence, entry timing choices require the needs to balance the early entry risks and the problems in losing opportunities as a result of late entry into a new market. Questionnaire surveys administered to 115 Malaysian construction firms operating in 51 countries worldwide have resulted in 39.1 percent response rate. Factor analysis was used to determine the most significant factors affecting entry timing choices of the firms to penetrate the international market. A logistic regression analysis used to examine the firms’ entry timing choices, indicates that the model has correctly classified 89.5 per cent of cases as late movers. The findings reveal that the most significant factor influencing the construction firms’ choices as late movers was the firm factor related to the firm’s international experience, resources, competencies and financing capacity. The study also offers valuable information to construction firms with intention to internationalize their businesses.

Keywords: factors, early movers, entry timing choices, late movers, logistic regression model, principal axis factorial analysis, Malaysian construction firms

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Authors: Jiyaul Haque, Vandana Srivastava, M. A. Quraishi

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The amino acids based corrosion inhibitors 2-(3-(carboxymethyl)-1H-imidazol-3-ium-1-yl) acetate (Z-1),2-(3-(1-carboxyethyl)-1H-imidazol-3-ium-1-yl) propanoate (Z-2) and 2-(3-(1-carboxy-2-phenylethyl)-1H-imidazol-3-ium-1-yl)-3- phenylpropanoate (Z-3) were synthesized by the reaction of amino acids, glyoxal and formaldehyde, and characterized by the FTIR and NMR spectroscopy. The corrosion inhibition performance of synthesized inhibitors was studied by electrochemical (EIS and PDP), surface and DFT methods. The results show, the studied Z-1, Z-2 and Z-3 are effective inhibitors, showed the maximum inhibition efficiency of 88.52 %, 89.48 and 96.08% at concentration 200ppm, respectively. The results of potentiodynamic polarization (PDP) study showed that Z-1 act as a cathodic inhibitor, while Z-2 and Z-3 act as mixed type inhibitors. The results of electrochemical impedance spectroscopy (EIS) studies showed that zwitterions inhibit the corrosion through adsorption mechanism. The adsorption of synthesized zwitterions on the mild steel surface was followed the Langmuir adsorption isotherm. The formation of zwitterions film on mild steel surface was confirmed by the scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDX). The quantum chemical parameters were used to study the reactivity of inhibitors and supported the experimental results. An inhibitor adsorption model is proposed.

Keywords: electrochemical impedance spectroscopy, green corrosion inhibitors, mild steel, SEM, quantum chemical calculation, zwitterions

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Authors: Abrar Al-Mutairi, Talal Al-Bazali

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In this study, changes in capillary entry pressure of shale, as it interacts with CO₂, under different temperatures (25 °C to 250 °C) have been investigated. The combined impact of temperature and petrophysical properties (water content, water activity, permeability and porosity) of shale was also addressed. Results showed that the capillary entry pressure of shale when it interacted with CO₂ was highly affected by temperature. In general, increasing the temperature decreased capillary entry pressure of shale. We believe that pore dilation, where pore throat size expands due to the application of heat, may have caused this decrease in capillary entry pressure of shale. However, in some cases we found that at higher temperature some shale samples showed that the temperature activated clay swelling may have caused an apparent decrease in pore throat radii of shale which translates into higher capillary entry pressure of shale. Also, our results showed that there is no distinct relationship between shale’s water content, water activity, permeability, and porosity on the capillary entry pressure of shale samples as it interacted with CO₂ at different temperatures.

Keywords: heat, threshold pressure, CO₂ sequestration, shale

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Authors: Shazia Anwer Bukhari, Waseem Akhtar Shamshari, Mahmood-Ur-Rahman, Muhammad Zia-Ul-Haq, Hawa Z. E. Jaafar

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Diabetes mellitus is a life threatening disease and scientists are doing their best to find a cost effective and permanent treatment of this malady. The recent trend is to control the disease by target base inhibiting of enzymes or proteins. Secreted frizzled-related protein 4 (SFRP4) is found to cause five times more risk of diabetes when expressed above average levels. This study was therefore designed to analyze the SFRP4 and to find its potential inhibitors. SFRP4 was analyzed by bio-informatics tools of sequence tool and structure tool. A total of three potential inhibitors of SFRP4 were found, namely cyclothiazide, clopamide and perindopril. These inhibitors showed significant interactions with SFRP4 as compared to other inhibitors as well as control (acetohexamide). The findings suggest the possible treatment of diabetes mellitus type 2 by inhibiting the SFRP4 using the inhibitors cyclothiazide, clopamide and perindopril.

Keywords: bioscreening, clopamide, cyclothiazide, diabetes mellitus, perindopril, SFRP4

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Authors: T. Ferreira, A. Kulkarni, C. Bretscher, K. Richter, M. Ehrlich, A. Marchini

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H-1 protoparvovirus (H-1PV) is a virus with inherent oncolytic and oncosuppressive activities while remaining non-pathogenic in humans. H-1PV was the first oncolytic parvovirus to undergo clinical testing. Results from trials in patients with glioblastoma or pancreatic carcinoma showed an excellent safety profile and first signs of efficacy. H-1PV infection is vastly dependent on cellular factors, from cell attachment and entry to viral replication and egress. Hence, we believe that the characterisation of the parvovirus life cycle would ultimately help further improve H-1PV clinical outcome. In the present study, we explored the entry pathway of H-1PV in cervical HeLa and glioma NCH125 cancer cell lines. Electron and confocal microscopy showed viral particles associated with clathrin-coated pits and vesicles, providing the first evidence that H-1PV cell entry occurs through clathrin-mediated endocytosis. Accordingly, we observed that by blocking clathrin-mediated endocytosis with hypertonic sucrose, chlorpromazine, or pitstop 2, H-1PV transduction was markedly decreased. Accordingly, siRNA-mediated knockdown of AP2M1, which retains a crucial role in clathrin-mediated endocytosis, verified the reliance of H-1PV on this route to enter HeLa and NCH125 cancer cells. By contrast, we found no evidence of viral entry through caveolae-mediated endocytosis. Indeed, pre-treatment of cells with nystatin or methyl-β-cyclodextrin, both inhibitors of caveolae-mediated endocytosis, did not affect viral transduction levels. Unexpectedly, siRNA-mediated knockdown of caveolin-1, the main driver of caveolae-mediated endocytosis, increased H-1PV transduction, suggesting caveolin-1 is a negative modulator of H-1PV infection. We also show that H-1PV entry is dependent on dynamin, a protein responsible for mediating the scission of vesicle neck and promoting further internalisation. Furthermore, since dynamin inhibition almost completely abolished H-1PV infection, makes it unlikely that H-1PV uses macropinocytosis as an alternative pathway to enter cells. After viral internalisation, H-1PV passes through early to late endosomes as observed by confocal microscopy. Inside these endocytic compartments, the acidic environment proved to be crucial for a productive infection. Inhibition of acidification of pH dramatically reduced H-1PV transduction. Besides, a fraction of H-1PV particles was observed inside LAMP1-positive lysosomes, most likely following a non-infectious route. To the author's best knowledge, this is the first study to characterise the cell entry pathways of H-1PV. Along these lines, this work will further contribute to understand H-1PV oncolytic properties as well as to improve its clinical potential in cancer virotherapy.

Keywords: clathrin-mediated endocytosis, H-1 parvovirus, oncolytic virus, virus entry

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Authors: Harish Rajak, Kamlesh Raghuwanshi

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Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

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Authors: Pritika Ramharack, Mahmoud E. S. Soliman

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The re-emerging Zika virus is an arthropod-borne virus that has been described to have explosive potential as a worldwide pandemic. The initial transmission of the virus was through a mosquito vector, however, evolving modes of transmission has allowed the spread of the disease over continents. The virus already been linked to irreversible chronic central nervous system (CNS) conditions. The concerns of the scientific and clinical community are the consequences of Zika viral mutations, thus suggesting the urgent need for viral inhibitors. There have been large strides in vaccine development against the virus but there are still no FDA-approved drugs available. Rapid rational drug design and discovery research is fundamental in the production of potent inhibitors against the virus that will not just mask the virus, but destroy it completely. In silico drug design allows for this prompt screening of potential leads, thus decreasing the consumption of precious time and resources. This study demonstrates an optimized and proven screening technique in the discovery of two potential small molecule inhibitors of Zika virus Methyltransferase and RNA-dependent RNA polymerase. This in silico “per-residue energy decomposition pharmacophore” virtual screening approach will be critical in aiding scientists in the discovery of not only effective inhibitors of Zika viral targets, but also a wide range of anti-viral agents.

Keywords: NS5 protein inhibitors, per-residue decomposition, pharmacophore model, virtual screening, Zika virus

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Authors: Naoual Boussoualim, Hayat Trabsa, Iman Krache, Lekhmici Arrar, Abderrahmane Baghiani

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Resistance to antibiotics has emerged following their widespread use; the important mechanism of beta-lactam resistance in bacteria is the production of beta-lactamase. In order to find new bioactive beta-lactamase inhibitors, this study investigated the inhibition effect of the extracts of Anchusa azurea (AA) on a beta-lactamase from Bacillus cereus. The extracts exerted inhibitory effects on beta-lactamase in a dose-dependent manner, the results showed that the crude extract (BrE) and the ethyl acetate extract (AcE) of Anchusa azurea showed a very high inhibitory activity at a concentration of 10 mg, the percentage of inhibition was between 58% and 68%. Not all extracts were as potent as the original inhibitors such as clavulanic acid, the isolation and the structural elucidation of the active constituents in these extracts will provide useful means in the development of beta -lactamase inhibitors.

Keywords: Anchusa azurea, natural product, resistance, antibiotics, beta-lactamase, inhibitors

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Authors: Ahmed A. Farag, M. A. Hgazy

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The influence of three Schiff bases (SB-I, SB-II, and SB-III) on the corrosion of carbon steel in 0.5 M H2SO4 solution was studied by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) techniques. The inhibition efficiency increases with the concentration of the Schiff bases and follow the trend: SB-III > SB-II > SB-I. Tafel polarization measurements revealed that the three tested inhibitors function as anodic inhibitors. The thermodynamic parameters Kads and ΔGºads are calculated and discussed. The Langmuir isotherm equation was found to provide an accurate description of the adsorption behaviour of the investigated Schiff bases. Depending on the results, the inhibitive mechanism was proposed.

Keywords: Schiff bases, corrosion inhibitors, EIS, adsorption

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Authors: Saeeda Nadir Ali, Najma Sultana, Muhammad Saeed Arayne, Amtul Qayoom

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Present study describes a simple and a fast liquid chromatographic method using ultraviolet detector for simultaneous determination of anxiety relief medicine alprazolam with ACE inhibitors i.e; lisinopril, captopril and enalapril employing purospher star C18 (25 cm, 0.46 cm, 5 µm). Separation was achieved within 5 min at ambient temperature via methanol: water (8:2 v/v) with pH adjusted to 2.9, monitoring the detector response at 220 nm. Optimum parameters were set up as per ICH (2006) guidelines. Calibration range was found out to be 0.312-10 µg mL-1 for alprazolam and 0.625-20 µg mL-1 for all the ACE inhibitors with correlation coefficients > 0.998 and detection limits 85, 37, 68 and 32 ng mL-1 for lisinopril, captopril, enalapril and alprazolam respectively. Intra-day, inter-day precision and accuracy of the assay were in acceptable range of 0.05-1.62% RSD and 98.85-100.76% recovery. Method was determined to be robust and effectively useful for the estimation of studied drugs in dosage formulations and human serum without obstruction of excipients or serum components.

Keywords: alprazolam, ACE inhibitors, RP HPLC, serum

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Authors: Ismail Bin Mohd Saaid, Abubakar Abubakar Umar

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Despite the successes recorded by Alkaline/Surfactant/Polymer (ASP) flooding as an effective chemical EOR technique, the combination CEOR is not unassociated with stern glitches, one of which is the scaling of downhole equipment. One of the major issues inside the oil industry is how to control scale formation, regardless of whether it is in the wellhead equipment, down-hole pipelines or even the actual field formation. The best approach to handle the challenge associated with oilfield scale formation is the application of scale inhibitors to avert the scale formation. Chemical inhibitors have been employed in doing such. But due to environmental regulations, the industry have focused on using green scale inhibitors to mitigate the formation of scales. This paper compares the scale inhibition performance of Polyaspartic acid and sodium polyacrylic acid, both commercial green scale inhibitors, in mitigating silicate scales formed during Alkaline/Surfactant/polymer flooding under static conditions. Both PASP and TH5000 are non-threshold inhibitors, therefore their efficiency was only seeing in delaying the deposition of the silicate scales.

Keywords: alkaline/surfactant/polymer flooding (ASP), polyaspartic acid (PASP), sodium polyacrylate (SPA)

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Authors: Hung-Yi Chen, Shih-Jye Wu

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The existing literature provides little discussion on why a public monopolist gives up its market dominant position and allows private firms entering the market. We argue that the privatization of a public monopolist under a vertically related market may induce the entry of private firms. We develop a model of a mixed oligopoly with vertically related markets to explain the change in the market from a public monopolist to a mixed oligopoly and examine issues on privatizing the downstream public enterprise both in the short run and long run in the vertically related markets. We first show that the welfare-maximizing public monopoly firm is suboptimal in the vertically related markets. This is due to the fact that the privatization will reduce the input price charged by the upstream foreign monopolist. Further, the privatization will induce the entry of private firms since input price will decrease after privatization. Third, we demonstrate that the complete privatizing the public firm becomes a possible solution if the entry cost of private firm is low. Finally, we indicate that the public firm should partially privatize if the free-entry of private firms is allowed. JEL classification: F12, F14, L32, L33

Keywords: free entry, mixed oligopoly, public monopoly, the initiation of privatization, vertically related markets, mixed oligopoly

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Authors: Eda Orhun

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Turkey stayed as a closed economy until the beginning of 1980s. This changed with the de-regulation and the liberalization program that was adopted by the government at that time. This re-structuring program also affected the Turkish banking system by triggering more foreign bank entry. While the number of foreign banks have been increasing, the number of (local) private banks have been decreasing especially after the currency crisis of 2001. This outcome is largely due to increased acquisitions of (local) private banks by foreign entrants.

Keywords: acquisitions, de-regulation, foreign bank entry, globalization

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Authors: Ali Bhayani

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The article analyses determinants of the market entry modes used by corporate firms to expand internationally and explore whether higher education institutions uses the same determinants to decide on mode adopted to enter the market. Determinants like transaction costs, location advantage, idiosyncratic capabilities, isomorphic pressure to mimic, psychic distance, uncertainty, risks, the control over academic process, previous internationalisation experience and entry to homogenous markets are considered with regards to universities. A sample consisting of 40+ branch campuses from United Arab Emirates (UAE), host to highest number of branch campuses, is selected to study the determinants of the entry modes adopted. The aim of this article is not to prescribe or offer a solution for the best-available model of market entry that can be adopted by universities but rather to act as a trigger for a critical check up on universities planning to internationalize their offering. Determinants like idiosyncratic capabilities, isomorphic pressure and control over the academic process were found to be most prevalent. However, determinants like transaction cost efficiency, internationalisation experience, psychic distance, uncertainty and risks are not significant factors.

Keywords: higher education, UAE, internationalisation, market entry, international branch campuses

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Authors: Ghazala Yaqub, Zubi Sadiq, Almas Hamid, Saira Iqbal

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This paper is the very first report of three dual action hybrids synthesized by covalent linkage of carbazole based novel antibacterial compounds with efflux pump inhibitors i.e., indole acetic acid/gallic acid. Novel carbazole based antibacterial compounds were prepared first and then these were covalently linked with efflux pump inhibitors which leads to the successful formation of hybrids. All prepared compounds were evaluated for their bacterial cell killing capability against Escherichia coli, Staphylococcus aureus, Pasteurella multocida and Bacillus subtilis. Compound were effective against all tested bacterial strains at different concentrations. But when these compounds were linked with efflux pump inhibitors they showed dramatic enhancement in their bacterial cell killing potential and minimum inhibitory concentration of all hybrids ranges from 7.250 µg/mL to 0.0283 µg/mL.

Keywords: antimicrobial assay, carbazole, dual action hybrids, efflux pump inhibitors

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Authors: Tang Wei, Yang Xiaofeng, Gui Yewei, Du Yanxia

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Complex lifting entry was selected for precise landing performance during the Mars Science Laboratory entry. This study aims to develop the three-dimensional numerical method for precise computation and the surface panel method for rapid engineering prediction. Detailed flow field analysis for Mars exploration mission was performed by carrying on a series of fully three-dimensional Navier-Stokes computations. The static aerodynamic performance was then discussed, including the surface pressure, lift and drag coefficient, lift-to-drag ratio with the numerical and engineering method. Computation results shown that the shock layer is thin because of lower effective specific heat ratio, and that calculated results from both methods agree well with each other, and is consistent with the reference data. Aerodynamic performance analysis shows that CG location determines trim characteristics and pitch stability, and certain radially and axially shift of the CG location can alter the capsule lifting entry performance, which is of vital significance for the aerodynamic configuration des0ign and inner instrument layout of the Mars entry capsule.

Keywords: Mars entry capsule, static aerodynamics, computational fluid dynamics, hypersonic

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Authors: Rahma Tibigui, Ikram Hadj Said, Rachid Belkada, Dalila Hammoutene

Abstract:

The vulnerability of industrial facilities is highly concerned with multiple risks from corrosion. The commonly adopted solution is based on the use of organic inhibitors, which are gradually being replaced by environmentally friendly organic inhibitors. In our work, we carried out a quantum chemical study based on the Density Functional Theory (DFT) method at the B3LYP/6-311G (d,p) level of theory. The inhibitory performance of a derivative of the tetrazole molecule has been investigated and reported as a carbon steel-friendly corrosion inhibitor in hydrochloric acid (HCl) medium. The relationship is likely to exist between the molecular structure of this compound as well as its various global reactivity descriptors, and its corrosion inhibition efficiency, which was examined and then discussed. The results show low values of ΔE, which represent strong adsorption of the inhibitor on the steel surface. Moreover, the flat adsorption orientation confirmed the great ability to donate (accept) electrons to (from) steel, fabricating an anchored barrier to prevent steel from corrosion.

Keywords: eco-friendly, corrosion inhibitors, tetrazole, DFT

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Authors: Boukli Hacene Faiza, Soufi Wassila, Ghalem Said

Abstract:

The oral antidiabetics drugs such as alpha glucosidase inhibitors present undesirable effects like acarbose. Flavonoids are class of molecules widely distributed in plants, for this reason we are interested in our work to study the inhibition in silico of alpha glucosidase by natural ligands ( flavonoids analogues) using molecular modeling methods using MOE (Molecular Operating Environment) software to predict their interaction with this enzyme with score energy, ADME /T tests and druglikeness properties experiments. Two flavonoids Beicalein and Apigenin have high binding affinity with alpha glucosidase with lower IC50 supposed potent inhibitors.

Keywords: alpha glucosidase, flavonoides analogues, drug research, molecular modeling

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Authors: Elham Rezaee, Sayyed Abbas Tabatabai

Abstract:

Dual inhibition of COX-2 and sEH enzymes represents one of the distinct pharmaceutical approaches for the treatment of inflammation, pain, cancers, and other diseases. The discovery of these inhibitors for treatment is a great deal of attention because of some advantages such as increased efficacy, a promising safety profile, ease of formulation, and better target engagement. In this research, based on the structure-activity relationship of COX-2 and sEH inhibitors, some amide derivatives with oxadiazole and dihydropyrimidinone rings against sEH and COX-2 enzymes were developed. The designed compounds showed high affinity to the active site of both enzymes in docking studies and were synthesized in good yield and characterized by IR, Mass, 1HNMR, and 13CNMR. All of the novel compounds exhibited considerable in-vitro sEH and COX-2 inhibitory activities in comparison with 12-(3-Adamantan-1-yl-ureido)- dodecanoic acid and celecoxib (a potent urea-based sEH inhibitor and selective nonsteroidal anti-inflammatory drug, respectively). Ethyl 6-methyl-4-(4-(4-(methylsulfonyl)benzamido)phenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate was found to be the most selective COX-2 inhibitor (COX-2/COX-1 ratio: 683) with IC50 value of 2.1 nM targeting sEH enzyme.

Keywords: COX-2, dual inhibitors, sEH, synthesis

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Authors: Ambrish Singh

Abstract:

The corrosion inhibition performance of pyran derivatives (AP) on mild steel in 15% HCl was investigated by electrochemical impedance spectroscopy (EIS), potentiodynamic polarization, weight loss, contact angle, and scanning electron microscopy (SEM) measurements, DFT and molecular dynamic simulation. The adsorption of APs on the surface of mild steel obeyed Langmuir isotherm. The potentiodynamic polarization study confirmed that inhibitors are mixed type with cathodic predominance. Molecular dynamic simulation was applied to search for the most stable configuration and adsorption energies for the interaction of the inhibitors with Fe (110) surface. The theoretical data obtained are, in most cases, in agreement with experimental results.

Keywords: acidizing inhibitor, pyran derivatives, DFT, molecular simulation, mild steel, EIS

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Authors: Christolyn Raj, Lewis Levitz

Abstract:

Introduction: Two cases of late presentation ( > five years ) of bilateral pseudophakic macula edema related to oral tyrosine kinase inhibitors are described. These cases are the first of their type in the published literature. A review of ocular inflammatory complications of tyrosine kinase inhibitors in the current literature is explored. Case Presentations(s): Case 1 is an 83-year-old female who has been stable on Ibrutinib (Imbruvica ®) for chronic lymphocytic leukemia (CLL). She presented with bilateral blurred vision from severe cystoid macula edema seven years following routine cataract surgery. She was treated with intravitreal steroids with complete resolution without relapse. Case 2 is a 76-year-old female who was on therapy for polycythemia vera with Ruxolitinib (Jakafi®). She presented with bilateral blurred vision from mild cystoid macula edema six years following routine cataract surgery. She responded well to topical steroids without relapse. In both cases, oral tyrosine kinase inhibitor agents were presumed to be the underlying cause and were ceased. Over the last five years, there have been increasing reports in the literature of the inflammatory effects of tyrosine kinase inhibitors on the retina, uvea and optic nerve. Conclusion: Late presentation of pseudophakic macula edema following routine cataract surgery is rare. Such presentations should prompt investigation of the chronic use of systemic medications, especially oral kinase inhibitors. Patients who must remain on these agents require ongoing ophthalmologic assessment in view of their long-term inflammatory side effects.

Keywords: macula edema, oral kinase inhibitors, retinal toxicity, pseudo-phakia

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