Search results for: drug release

Authors: Norma Rodrigues Gomes

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This paper presents initiatives of Knowledge Management (KM) applied to Forensic Sciences field, especially developed at the Forensic Science Institute of the Brazilian Federal Police. Successful projects, related to knowledge sharing, drugs analysis and environmental crimes, are reported in the KM perspective. The described results are related to: a) the importance of having an information repository, like a digital library, in such a multidisciplinary organization; b) the fight against drug dealing and environmental crimes, enabling the possibility to map the evolution of crimes, drug trafficking flows, and the advance of deforestation in Amazon rain forest. Perspectives of new KM projects under development and studies are also presented, tracing an evolution line of the KM view at the Forensic Science Institute.

Keywords: Business Intelligence, Digital Library, Forensic Science, Knowledge Management

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Authors: J. Zambujal-Oliveira

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The relation between taxation states and foreign direct investment has been studied for several perspectives and with states of different levels of development. Usually it's only considered the impact of tax level on the foreign direct investment volume. This paper enhances this view by assuming that multinationals companies (MNC) can use transfer prices systems and have got investment timing flexibility. Thus, it evaluates the impact of the use of international transfer pricing systems on the states- policy and on the investment timing of the multinational companies. In uncertain business environments (with periodical release of news), the investment can increase if MNC detain investment delay options. This paper shows how tax differentials can attract foreign direct investments (FDI) and influence MNC behavior. The equilibrium is set in a global environment where MNC can shift their profits between states depending on the corporate tax rates. Assuming the use of transfer pricing schemes, this paper confirms the relationship between MNC behavior and the release of new business news.

Keywords: Corporate Taxation, International Profit Shifting, Real Options

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Authors: Farhad Asgari Mehrabadi, Mohammad Reza Khoshravan

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In the present study, fracture behavior of woven fabric-reinforced glass/epoxy composite laminates under mode III crack growth was experimentally investigated and numerically modeled. Two methods were used for the calculation of the strain energy release rate: the experimental compliance calibration (CC) method and the Virtual Crack Closure Technique (VCCT). To achieve this aim ECT (Edge Crack Torsion) was used to evaluate fracture toughness in mode III loading (out of plane-shear) at different crack lengths. Load–displacement and associated energy release rates were obtained for various case of interest. To calculate fracture toughness JIII, two criteria were considered including non-linearity and maximum points in load-displacement curve and it is observed that JIII increases with the crack length increase. Both the experimental compliance method and the virtual crack closure technique proved applicable for the interpretation of the fracture mechanics data of woven glass/epoxy laminates in mode III.

Keywords: Mode III, Fracture, Composite, Crack growth Finite Element.

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Authors: Nélio Veiga, Paula Ferreira, Tiago Correia, Maria J. Correia, Carlos Pereira, Odete Amaral, Ilídio J. Correia

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Introduction: The application of fissure sealants is considered to be an important primary prevention method used in dental medicine. However, the formation of microleakage gaps between tooth enamel and the fissure sealant applied is one of the most common reasons of dental caries development in teeth with fissure sealants. The association between various dental biomaterials may limit the major disadvantages and limitations of biomaterials functioning in a complementary manner. The present study consists in the incorporation of a cariostatic agent – silver diamine fluoride (SDF) – in a resin-based fissure sealant followed by the study of release kinetics by spectrophotometry analysis of the association between both biomaterials and assessment of the inhibitory effect on the growth of the reference bacterial strain Streptococcus mutans (S. mutans) in an in vitro study. Materials and Methods: An experimental in vitro study was designed consisting in the entrapment of SDF (Cariestop^® 12% and 30%) into a commercially available fissure sealant (Fissurit^®), by photopolymerization and photocrosslinking. The same sealant, without SDF was used as a negative control. The effect of the sealants on the growth of S. mutans was determined by the presence of bacterial inhibitory halos in the cultures at the end of the incubation period. In order to confirm the absence of bacteria in the surface of the materials, Scanning Electron Microscopy (SEM) characterization was performed. Also, to analyze the release profile of SDF along time, spectrophotometry technique was applied. Results: The obtained results indicate that the association of SDF to a resin-based fissure sealant may be able to increase the inhibition of S. mutans growth. However, no SDF release was noticed during the in vitro release studies and no statistical significant difference was verified when comparing the inhibitory halo sizes obtained for test and control group.  Conclusions: In this study, the entrapment of SDF in the resin-based fissure sealant did not potentiate the antibacterial effect of the fissure sealant or avoid the immediate development of dental caries. The development of more laboratorial research and, afterwards, long-term clinical data are necessary in order to verify if this association between these biomaterials is effective and can be considered for being used in oral health management. Also, other methodologies for associating cariostatic agents and sealant should be addressed.

Keywords: Biomaterial, fissure sealant, primary prevention, silver diamine fluoride, S. mutans.

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Authors: Yang Fu, Jaime Rodrigo Navarro, Jose F. Monserrat, Faiza Bouchmal, Oscar Carrasco Quilis

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Cellular Vehicle to Everything (C-V2X) is considered a promising solution for future autonomous driving. From Release 16 to Release 17, the Third Generation Partnership Project (3GPP) has introduced the definitions and services for 5G New Radio (NR) V2X. Since establishing a simulator for C-V2X communications is an essential preliminary step to achieve reliable and stable communication links, this paper proposes a complete framework of a link-level simulator based on the 3GPP specifications for the Physical Sidelink Share Channel (PSSCH) of the 5G NR Physical Layer (PHY). In this framework, several algorithms in the receiver part, i.e., sliding window in channel estimation and Minimum Mean Square Error (MMSE)-based equalization, are developed. Finally, the performance of the developed PSSCH receiver is validated through extensive simulations under different assumptions.

Keywords: Yang Fu, Jaime Rodrigo Navarro, Jose F. Monserrat, Faiza Bouchmal, Oscar Carrasco Quilis

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Authors: Mohammad Sadeghi, Behrouz Heidari, Korush Montazeri

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In this article, we synthesize a novel chitosan -based superabsorbent hydrogel via graft copolymerization of mixtures acrylic acid (AA) and N-vinyl pyrollidon onto chitosan backbones. The polymerization reaction was carried out in an aqueous medium and in the presence of ammonium persulfate (APS) as an initiator and N,N'-methylene bisacrylamide (MBA) as a crosslinker.The hydrogel structures were confirmed by FTIR spectroscopy. The swelling behavior of these absorbent polymers was also investigated in various salt solutions. Results indicated that the swelling capacity decreased with an increase in the ionic strength of the swelling medium. Furthermore, the swelling of superabsorbing hydrogels was examined in solutions with pH values ranging between 1.0 and 13.0. It showed a reversible pH-responsive behavior at pHs 2.0 and 8.0. This on-off switching behavior makes the synthesized hydrogels as an excellent candidate for controlled delivery of bioactive agents.

Keywords: chitosan, acrylic acid, N-vinyl pyrollidon, hydrogel, Ibuprofen's drug delivery

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Authors: Avdhesh K. Sharma

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Formulation for drying and pyrolysis process in packed beds at slow heating rates is presented. Drying of biomass particles bed is described by mass diffusion equation and local moisture-vapour-equilibrium relations. In gasifiers, volatilization rate during pyrolysis of biomass is modeled by using apparent kinetic rate expression, while product compositions at slow heating rates is modeled using empirical fitted mass ratios (i.e., CO/CO₂, ME/CO₂, H₂O/CO₂) in terms of pyrolysis temperature. The drying module is validated fairly with available chemical kinetics scheme and found that the testing zone in gasifier bed constituted of relatively smaller particles having high airflow with high isothermal temperature expedite the drying process. Further, volatile releases more quickly within the shorter zone height at high temperatures (isothermal). Both, moisture loss and volatile release profiles are found to be sensitive to temperature, although the influence of initial moisture content on volatile release profile is not so sensitive.

Keywords: Modeling downdraft gasifier, drying, pyrolysis, moist woody biomass.

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Authors: Muhammad Waseem Ashraf, Shahzadi Tayyaba, Nitin Afzulpurkar, Asim Nisar, Adisorn Tuantranont, Erik L J Bohez

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In this paper, design, fabrication and coupled multifield analysis of hollow out-of-plane silicon microneedle array with piezoelectrically actuated microfluidic device for transdermal drug delivery (TDD) applications is presented. The fabrication process of silicon microneedle array is first done by series of combined isotropic and anisotropic etching processes using inductively coupled plasma (ICP) etching technology. Then coupled multifield analysis of MEMS based piezoelectrically actuated device with integrated 2×2 silicon microneedle array is presented. To predict the stress distribution and model fluid flow in coupled field analysis, finite element (FE) and computational fluid dynamic (CFD) analysis using ANSYS rather than analytical systems has been performed. Static analysis and transient CFD analysis were performed to predict the fluid flow through the microneedle array. The inlet pressure from 10 kPa to 150 kPa was considered for static CFD analysis. In the lumen region fluid flow rate 3.2946 μL/min is obtained at 150 V for 2×2 microneedle array. In the present study the authors have performed simulation of structural, piezoelectric and CFD analysis on three dimensional model of the piezoelectrically actuated mcirofluidic device integrated with 2×2 microneedle array.

Keywords: Coupled multifield, finite element analysis, hollow silicon microneedle, transdermal drug delivery.

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Authors: M. Saravanan

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Antimicrobial resistant is becoming a major factor in virtually all hospital acquired infection may soon untreatable is a serious public health problem. These concerns have led to major research effort to discover alternative strategies for the treatment of bacterial infection. Nanobiotehnology is an upcoming and fast developing field with potential application for human welfare. An important area of nanotechnology for development of reliable and environmental friendly process for synthesis of nanoscale particles through biological systems In the present studies are reported on the use of fungal strain Aspergillus species for the extracellular synthesis of bionanoparticles from 1 mM silver nitrate (AgNO3) solution. The report would be focused on the synthesis of metallic bionanoparticles of silver using a reduction of aqueous Ag+ ion with the culture supernatants of Microorganisms. The bio-reduction of the Ag+ ions in the solution would be monitored in the aqueous component and the spectrum of the solution would measure through UV-visible spectrophotometer The bionanoscale particles were further characterized by Atomic Force Microscopy (AFM), Fourier Transform Infrared Spectroscopy (FTIR) and Thin layer chromatography. The synthesized bionanoscale particle showed a maximum absorption at 385 nm in the visible region. Atomic Force Microscopy investigation of silver bionanoparticles identified that they ranged in the size of 250 nm - 680 nm; the work analyzed the antimicrobial efficacy of the silver bionanoparticles against various multi drug resistant clinical isolates. The present Study would be emphasizing on the applicability to synthesize the metallic nanostructures and to understand the biochemical and molecular mechanism of nanoparticles formation by the cell filtrate in order to achieve better control over size and polydispersity of the nanoparticles. This would help to develop nanomedicine against various multi drug resistant human pathogens.

Keywords: Bionanoparticles, UV-visible spectroscopy, AtomicForce Microscopy, Extracellular synthesis, Multi drug resistant, antimicrobial activity, Nanomedicine

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Authors: Q. Wei, D. G. Hwang, Z. Mohy-Udin, D. H. Shin, J. H. Park, M. Y. Kang, J. H. Cho

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This study presents design of a carbon silicon electrode for iontophorsis treatment towards alopecia. The alopecia is a medical description means loss of hair from the body. For solving this problem, the drug need to be delivered into the scalp, therefore, the iontophoresis was chosen to use in this treatment. However, almost common electrodes of iontophoresis device are made with metal material, the electrodes could give patients hurt when they using it, and it is hard to avoid the hair for attaching the hair. For this reason, an electrode is made with silicon material to decrease the hurt from the electrodes, and the carbon material is mixed in it for increasing conductance. The several cones with stainless material on the electrode make the electrode is able to void hair to attach the affected part. According to the results of a vivo-experiment, the carbon silicon electrode showed a good performance and in treatment comfortably.

Keywords: Carbon silicon, drug delivery system, iontophoresis

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Authors: Wudhichai Assawinchaichote

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This paper examines the problem of designing robust H controllers for for HIV/AIDS infection system with dual drug dosages described by a Takagi-Sugeno (S) fuzzy model. Based on a linear matrix inequality (LMI) approach, we develop an H controller which guarantees the L2-gain of the mapping from the exogenous input noise to the regulated output to be less than some prescribed value for the system. A sufficient condition of the controller for this system is given in term of Linear Matrix Inequalities (LMIs). The effectiveness of the proposed controller design methodology is finally demonstrated through simulation results. It has been shown that the anti-HIV vaccines are critically important in reducing the infected cells.

Keywords: H∞ Fuzzy control; Takagi-Sugeno (TS) fuzzy model; Linear Matrix Inequalities (LMIs); HIV/AIDS infection system

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Authors: Marjan Omranpour, Saeed Abbasi, Sohbat Bahraminejad

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White rust, caused by Albugo candida, is the most destructive foliar diseases of persian cress, Lepidium sativum in Iran. Application of fungicide is the most common method for the disease control. However, regarding the problems created by synthetic pesticides application, environmentally safe methods are needed to replace chemical pesticides. In this study, the antifungal activity of plant natural extracts was investigated for their ability to inhibit zoospore release from sporangia of A. candida. The crude extract of 46 plants was obtained using methanol. The inhibitory effect of the extracts was examined by mixing the plant extracts with a zoosporangial suspension of A. candida (1×106 spore/ml) at three concentrations, 250, 100 and 50 ppm. The experiments were conducted in a completely randomized design, with three replicates. The results of the experiment showed that three out of 46 plants species, including, Rhus coriaria, Anagallis arvensis and Mespilus germanica were completely inhibit zoospore release from zoosporangia of Albugo candida at concentration of 50 ppm.

Keywords: white rust, plant extract, Rhus coriaria, Anagallis arvensis and Mespilus germanica

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Authors: Asad Ullah Madni, Mahmood Ahmad, Naveed Akhtar, Muhammad Usman

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A new and cost effective RP-HPLC method was developed and validated for simultaneous analysis of non steroidal anti inflammatory dugs Diclofenac sodium (DFS), Flurbiprofen (FLP) and an opioid analgesic Tramadol (TMD) in advanced drug delivery systems (Liposome and Microcapsules), marketed brands and human plasma. Isocratic system was employed for the flow of mobile phase consisting of 10 mM sodium dihydrogen phosphate buffer and acetonitrile in molar ratio of 67: 33 with adjusted pH of 3.2. The stationary phase was hypersil ODS column (C18, 250×4.6 mm i.d., 5 μm) with controlled temperature of 30 C°. DFS in liposomes, microcapsules and marketed drug products was determined in range of 99.76-99.84%. FLP and TMD in microcapsules and brands formulation were 99.78 - 99.94 % and 99.80 - 99.82 %, respectively. Single step liquid-liquid extraction procedure using combination of acetonitrile and trichloroacetic acid (TCA) as protein precipitating agent was employed. The detection limits (at S/N ratio 3) of quality control solutions and plasma samples were 10, 20, and 20 ng/ml for DFS, FLP and TMD, respectively. The Assay was acceptable in linear dynamic range. All other validation parameters were found in limits of FDA and ICH method validation guidelines. The proposed method is sensitive, accurate and precise and could be applicable for routine analysis in pharmaceutical industry as well as in human plasma samples for bioequivalence and pharmacokinetics studies.

Keywords: Diclofenac Sodium, Flurbiprofen, Tramadol, HPLCUV detection, Validation.

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Authors: Sankar Chandrasekar, Rana Niranchan V.S., Joseph Sidharth Leon

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As the demand and prices of various petroleum products have been on the rise in recent years, there is a growing need for alternative fuels. Biodiesel, which consists of alkyl monoesters of fatty acids from vegetable oils and animal fats, is considered as an alternative to petroleum diesel. Biodiesel has comparable performance with that of diesel and has lower brake specific fuel consumption than diesel with significant reduction in emissions of CO, hydrocarbons (HC) and smoke with however, a slight increase in NOx emissions. This paper analyzes the effect of cooled exhaust gas recirculation in the combustion characteristics of a direct injection compression ignition engine using biodiesel blended fuel as opposed to the conventional system. The combustion parameters such as cylinder pressure, heat release rate, delay period and peak pressure were analyzed at various loads. The maximum cylinder pressure reduces as the fraction of biodiesel increases in the blend the maximum rate of pressure rise was found to be higher for diesel at higher engine loads.

Keywords: Cylinder pressure, delay period, EGR, heat release.

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Authors: Raniah Al-Shalabi, Omaima Al- Gohary, Samar Afify, Eram Eltahir

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Acetaminophen (Paracetamol) tablets are popular OTC products among patients as analgesics and antipyretics. Paracetamol is marketed by a lot of suppliers around the world. The aim of the present investigation was to compare between many types of paracetamol tablets obtained from different suppliers (six brands produced by different pharmaceutical companies in middle east countries, and Panadol® manufactured in Ireland), by different quality control tests according to USP pharmacopeia.Using Non official tests-hardness and friability; official tests- disintegration, dissolution, and drug content. Additionally, evaluate the influence of temperatures 4°C, 25°C and 40°C at 75% relative humidity on the stability of the same brands in their original packaging has been conducted for two months. The results revealed that all paracetamol tablet brands complied with the official USP specifications. In conclusion, paracetamol tablets preferred to be stored at 25°C. All the tested brands being biopharmaceutically and chemically equivalent.

Keywords: Non official tests-hardness and friability, official tests –disintegration, dissolution, and drug content.

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Authors: Hind Bouami, Patrick Millot

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Medication dispensing system is a life-critical system whose failure may result in preventable adverse events leading to longer patient stays in hospitals or patient death. Automation has led to great improvements in life-critical systems as it increased safety, efficiency, and comfort. However, critical risks related to medical organization complexity and automated solutions integration can threaten drug dispensing security and performance. Knowledge about the system’s complexity aspects and human machine parameters to control for automated equipment’s security and performance will help operators to secure their automation process and to optimize their system’s reliability. In this context, this study aims to document the operator’s situation awareness about automation risks and parameters involved in automation security and performance. Our risk management approach has been deployed in the North Luxembourg hospital center’s pharmacy, which is equipped with automated drug dispensing systems since 2009. With more than 4 million euros of gains generated, North Luxembourg hospital center’s success story was enabled by the management commitment, pharmacy’s involvement in the implementation and improvement of the automation project, and the close collaboration between the pharmacy and Sinteco’s firm to implement the necessary innovation and organizational actions for automated solutions integration security and performance. An analysis of the actions implemented by the hospital and the parameters involved in automated equipment’s integration security and performance has been made. The parameters to control for automated equipment’s integration security and performance are human aspects (6.25%), technical aspects (50%), and human-machine interaction (43.75%). The implementation of an anthropocentric analysis system before automation would have prevented and optimized the control of risks related to automation.

Keywords: Automated drug delivery systems, hospitals, human-centered automated system, risk management.

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Authors: Anurag Gaur, Nidhi, Shashi Sharma

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Targeted drug delivery is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. Targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of the medication in the remaining tissues. This improves efficacy of the while reducing side effects. In the present work, we investigate the effect of magnetic field, flow rate and particle concentration on the capturing of magnetic particles transported in a stent implanted fluidic channel. Iron oxide magnetic nanoparticles (Fe3O4) nanoparticles were synthesized via co-precipitation method. The synthesized Fe3O4 nanoparticles were added in the de-ionized (DI) water to prepare the Fe3O4 magnetic particle suspended fluid. This fluid is transported in a cylindrical tube of diameter 8 mm with help of a peristaltic pump at different flow rate (25-40 ml/min). A ferromagnetic coil of SS 430 has been implanted inside the cylindrical tube to enhance the capturing of magnetic nanoparticles under magnetic field. The capturing of magnetic nanoparticles was observed at different magnetic magnetic field, flow rate and particle concentration. It is observed that capture efficiency increases from 47-67% at magnetic field 2-5kG, respectively at particle concentration 0.6mg/ml and at flow rate 30 ml/min. However, the capture efficiency decreases from 65 to 44% by increasing the flow rate from 25 to 40 ml/min, respectively. Furthermore, it is observed that capture efficiency increases from 51 to 67% by increasing the particle concentration from 0.3 to 0.6 mg/ml, respectively.

Keywords: Capture efficiency, Implant assisted-Magnetic drug targeting (IA-MDT), Magnetic nanoparticles, in vitro study.

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Authors: Dong-Jae Kang, Nam-Woo Kim, Duk-Joo Son, Sung-In Jung

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According to dramatic growth of internet services, an easy and prompt service deployment has been important for internet service providers to successfully maintain time-to-market. Before global service deployment, they have to pay the big cost for service evaluation to make a decision of the proper system location, system scale, service delay and so on. But, intra-Lab evaluation tends to have big gaps in the measured data compared with the realistic situation, because it is very difficult to accurately expect the local service environment, network congestion, service delay, network bandwidth and other factors. Therefore, to resolve or ease the upper problems, we propose multiple cloud based GPES Broker system and use case that helps internet service providers to alleviate the above problems in beta release phase and to make a prompt decision for their service launching. By supporting more realistic and reliable evaluation information, the proposed GPES Broker system saves the service release cost and enables internet service provider to make a prompt decision about their service launching to various remote regions.

Keywords: GPES Broker system, Cloud Service Broker, Multiple Cloud, Global performance evaluation service (GPES), Service provisioning

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Authors: Jayashree Ramana

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An alarming emergence of multidrug-resistant strains of the tuberculosis pathogen Mycobacterium tuberculosis and continuing high worldwide incidence of tuberculosis has invigorated the search for novel drug targets. The enzyme glutamate racemase (MurI) in bacteria catalyzes the stereoconversion of L-glutamate to D-glutamate which is a component of the peptidoglycan cell wall of the bacterium. The inhibitors targeted against MurI from several bacterial species have been patented and are advocated as promising antibacterial agents. However there are none available against MurI from Mycobacterium tuberculosis, due to the lack of its threedimensional structure. This work accomplished two major objectives. First, the tertiary structure of MtMurI was deduced computationally through homology modeling using the templates from bacterial homologues. It is speculated that like in other Gram-positive bacteria, MtMurI exists as a dimer and many of the protein interactions at the dimer interface are also conserved. Second, potent candidate inhibitors against MtMurI were identified through docking against already known inhibitors in other organisms.

Keywords: Glutamate racemase, homology modeling, docking, drug resistance.

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Authors: Omid Adibi, Nategheh Najafpour, Bijan Farhanieh, Hossein Afshin

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Gas release from the pipelines is one of the main factors in the gas industry accidents. Released gas ejects from the pipeline as a free jet and in the growth process, the fuel gets mixed with the ambient air. Accordingly, an accidental spark will release the chemical energy of the mixture with an explosion. Gas explosion damages the equipment and endangers the life of staffs. So due to importance of safety in gas industries, prevision of accident can reduce the number of the casualties. In this paper, natural gas leakages from the low pressure pipelines are studied in two steps: 1) the simulation of mixing process and identification of flammable zones and 2) the simulation of wind effects on the mixing process. The numerical simulations were performed by using the finite volume method and the pressure-based algorithm. Also, for the grid generation the structured method was used. The results show that, in just 6.4 s after accident, released natural gas could penetrate to 40 m in vertical and 20 m in horizontal direction. Moreover, the results show that the wind speed is a key factor in dispersion process. In fact, the wind transports the flammable zones into the downstream. Hence, to improve the safety of the people and human property, it is preferable to construct gas facilities and buildings in the opposite side of prevailing wind direction.

Keywords: Flammable zones, gas pipelines, numerical simulation, wind effects.

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Authors: Simone Galati, Adriano Troia

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Ultrasound (US) is widely used in medical field for a variety diagnostic techniques but, in recent years, it has also been creating great interest for therapeutic aims. Regarding drug delivery, the use of US as an activation source provides better spatial delivery confinement and limits the undesired side effects. However, at present there is no complete characterization at a fundamental level of the different signals produced by sono-activated nanocarriers. Therefore, the aim of this study is to obtain a metrological characterization of the cavitation phenomena induced by US through three parallel investigation approaches. US was focused into a channel of a customized phantom in which a solution with oxygen-loaded nanodroplets (OLNDs) was led to flow and the cavitation activity was monitored. Both quantitative and qualitative real-time analysis were performed giving information about the dynamics of bubble formation, oscillation and final implosion with respect to the working acoustic pressure and the type of nanodroplets, compared with pure water. From this analysis a possible interpretation of the observed results is proposed.

Keywords: Cavitation, Drug Delivery, Nanodroplets, Ultrasound.

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Authors: Khalid Pervaiz Akhter, Mahmood Ahmad, Ghulam Murtaza, Ishrat Shafi, Zafar Javed

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The objective of this manuscript is to find area under the plasma concentration- time curve (AUC) for multiple doses of salbutamol sulphate sustained release tablets (Ventolin® oral tablets SR 8 mg, GSK, Pakistan) in the group of 18 healthy adults by using computational mathematics techniques. Following the administration of 4 doses of Ventolin® tablets 12 hourly to 24 healthy human subjects and bioanalysis of obtained plasma samples, plasma drug concentration-time profile was constructed. AUC, an important pharmacokinetic parameter, was measured using integrated equation of multiple oral dose regimens. The approximated AUC was also calculated by using computational mathematics techniques such as repeated rectangular, repeated trapezium and repeated Simpson's rule and compared with exact value of AUC calculated by using integrated equation of multiple oral dose regimens to find best computational mathematics method that gives AUC values closest to exact. The exact values of AUC for four consecutive doses of Ventolin® oral tablets were 150.5819473, 157.8131756, 164.4178231 and 162.78 ng.h/ml while the closest values approximated AUC values were 149.245962, 157.336171, 164.2585768 and 162.289224 ng.h/ml, respectively as found by repeated rectangular rule. The errors in the approximated values of AUC were negligible. It is concluded that all computational tools approximated values of AUC accurately but the repeated rectangular rule gives slightly better approximated values of AUC as compared to repeated trapezium and repeated Simpson's rules.

Keywords: Salbutamol sulphate, Area under curve (AUC), repeated rectangular rule, repeated trapezium rule, repeated Simpson's rule.

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Authors: Marios M. Hadjiandreou, Raul Conejeros, Ian Wilson

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This study presents a mathematical modeling approach to the planning of HIV therapies on an individual basis. The model replicates clinical data from typical-progressors to AIDS for all stages of the disease with good agreement. Clinical data from rapid-progressors and long-term non-progressors is also matched by estimation of immune system parameters only. The ability of the model to reproduce these phenomena validates the formulation, a fact which is exploited in the investigation of effective therapies. The therapy investigation suggests that, unlike continuous therapy, structured treatment interruptions (STIs) are able to control the increase in both the drug-sensitive and drug-resistant virus population and, hence, prevent the ultimate progression from HIV to AIDS. The optimization results further suggest that even patients characterised by the same progression type can respond very differently to the same treatment and that the latter should be designed on a case-by-case basis. Such a methodology is presented here.

Keywords: AIDS, chemotherapy, mathematical modeling, optimal control, progression.

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Authors: B.Rajendra Prasath, P.Tamilporai, Mohd.F.Shabir

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An effort has been taken to simulate the combustion and performance characteristics of biodiesel fuel in direct injection (D.I) low heat rejection (LHR) diesel engine. Comprehensive analyses on combustion characteristics such as cylinder pressure, peak cylinder pressure, heat release and performance characteristics such as specific fuel consumption and brake thermal efficiency are carried out. Compression ignition (C.I) engine cycle simulation was developed and modified in to LHR engine for both diesel and biodiesel fuel. On the basis of first law of thermodynamics the properties at each degree crank angle was calculated. Preparation and reaction rate model was used to calculate the instantaneous heat release rate. A gas-wall heat transfer calculations are based on the ANNAND-s combined heat transfer model with instantaneous wall temperature to analyze the effect of coating on heat transfer. The simulated results are validated by conducting the experiments on the test engine under identical operating condition on a turbocharged D.I diesel engine. In this analysis 20% of biodiesel (derived from Jatropha oil) blended with diesel and used in both conventional and LHR engine. The simulated combustion and performance characteristics results are found satisfactory with the experimental value.

Keywords: Biodiesel, Direct injection, Low heat rejection, Turbocharged engine

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Authors: Pamita Awasthi, Kirna, Shilpa Dogra, Manu Vatsal, Ritu Barthwal

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Doxorubicin, also known as Adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemia, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, antiinflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilinoethyl) benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 μM whereas for doxorubicin is 7.2 μM.

Keywords: Anticancer, Auto Dock, Doxorubicin, Sulfonamide.

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Authors: Ponshano Kaselekela, Simooya O. Oscar, Lunshano Boyd

Abstract:

The Copperbelt University Health Services (CBUHS) was designated by the Zambia Medicines Regulatory Authority (ZAMRA), formally the Pharmaceutical Regulatory Authority (PRA) as a regional pharmacovigilance centre to carryout activities of drug safety monitoring in four provinces in Zambia. CBUHS’s mandate included stimulating the reporting of adverse drug reactions (ADRs), as well as collecting and collating ADR reports from health institutions in the four provinces. This report covers the researchers’ experiences from May 2008 to September, 2016. The main objectives are 1) to monitor ADRs in the Zambian population, 2) to disseminate information to all health professionals in the region advising that the CBU health was a centre for reporting ADRs in the region, 3) to monitor polypharmacy as well as the benefit-risk profile of medicines, 4) to generate independent, evidence based recommendations on the safety of medicines, 5) to support ZAMRA in formulating safety related regulatory decisions for medicines, and 6) to communicate findings with all key stakeholders. The methodology involved monthly visits, beginning in early May 2008 to September, 2016, by the CBUHS to health institutions in the programme areas. Activities included holding discussions with health workers, distribution of ADR forms and collection of ADRs reports. These reports, once collected, were documented and assessed at the CBUHS. A report was then prepared for ZAMRA on quarterly basis. At ZAMRA, serious ADRs were noted and recommendations made to the Ministry of Health of the Republic of Zambia. The results show that 2,600 ADRs reports were received at the pharmacovigilance regional centre. Most of the ADRs reports that received were due to antiretroviral drugs, as well as a few from anti-malarial drugs like Artemether/Lumefantrine – Coartem®. Three hundred and twelve ADRs were entered in the Uppsala Monitoring Centre WHO Vigiflow for further analysis. It was concluded that in general, 2008-16 were exciting years for the pharmacovigilance group at CBUHS. From a very tentative beginning, a lot of strides were made and contacts established with healthcare facilities in the region. The researchers were encouraged by the support received from the Copperbelt University management, the motivation provided by ZAMRA and most importantly the enthusiasm of health workers in all the health care facilities visited. As a centre for drug safety in Zambia, the results show it achieves its objectives for monitoring ADRs, Pharmacovigilance (drug safety monitoring), and activities of monitoring ADRs as well as preventing them. However, the centre faces critical challenges caused by erratic funding that prevents the smooth running of the programme.

Keywords: Assessments, evaluation, monitoring, pharmacovigilance.

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Authors: M. Sreedhar Babu, Vishal Garg, S. B. Akella, Shibu Clement, N. K. S Rajan

Abstract:

Producer gas is a biomass derived gaseous fuel which is extensively used in internal combustion engines for power generation application. Unlike the conventional hydrocarbon fuels (Gasoline and Natural gas), the combustion properties of producer gas fuel are much different. Therefore, setting of optimal spark time for efficient engine operation is required. Owing to the fluctuating tendency of producer gas composition during gasification process, the heat release patterns (dictating the power output and emissions) obtained are quite different from conventional fuels. It was found that, valve lift timing is yet another factor which influences the burn rate of producer gas fuel, and thus, the heat release rate of the engine. Therefore, the present study was motivated to estimate the influence of valve lift timing analytically (Wiebe model) on the burn rate of producer gas through curve fitting against experimentally obtained mass fraction burn curves of several producer gas compositions. Furthermore, Wiebe models are widely used in zero-dimensional codes for engine parametric studies and are quite popular. This study also addresses the influence of hydrogen and methane concentration of producer gas on combustion trends, which are known to cause dynamics in engine combustion.

Keywords: Combustion Duration, crank angle, mass fraction burnt, producer gas, wiebe combustion model, wide open throttle.

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Authors: Hong Yi Huang, Wei Ti Kuo, Yi You Huang

Abstract:

Non-viral gene carriers composed of biodegradable polymers or lipids have been considered as a safer alternative for gene carriers over viral vectors. We have developed multi-functional nano-micelles for both drug and gene delivery application. Polyethyleneimine (PEI) was modified by grafting stearic acid (SA) and formulated to polymeric micelles (PEI-SA) with positive surface charge for gene and drug delivery. Our results showed that PEI-SA micelles provided high siRNA binding efficiency. In addition, siRNA delivered by PEI-SA carriers also demonstrated significantly high cellular uptake even in the presence of serum proteins. The post-transcriptional gene silencing efficiency was greatly improved by the polyplex formulated by 10k PEI-SA/siRNA. The amphiphilic structure of PEI-SA micelles provided advantages for multifunctional tasks; where the hydrophilic shell modified with cationic charges can electrostatically interact with DNA or siRNA, and the hydrophobic core can serve as payloads for hydrophobic drugs, making it a promising multifunctional vehicle for both genetic and chemotherapy application.

Keywords: polyethyleneimine, gene delivery, micelles, siRNA

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Authors: Chanin Park, Sundarapandian Thangapandian, Yuno Lee, Minky Son, Shalini John, Young-sik Sohn, Keun Woo Lee

Abstract:

Hypertension is characterized with stress on the heart and blood vessels thus increasing the risk of heart attack and renal diseases. The Renin angiotensin system (RAS) plays a major role in blood pressure control. Renin is the enzyme that controls the RAS at the rate-limiting step. Our aim is to develop new drug-like leads which can inhibit renin and thereby emerge as therapeutics for hypertension. To achieve this, molecular dynamics (MD) simulation and receptor-based pharmacophore modeling were implemented, and three rennin-inhibitor complex structures were selected based on IC50 value and scaffolds of inhibitors. Three pharmacophore models were generated considering conformations induced by inhibitor. The compounds mapped to these models were selected and subjected to drug-like screening. The identified hits were docked into the active site of renin. Finally, hit1 satisfying the binding mode and interaction energy was selected as possible lead candidate to be used in novel renin inhibitors.

Keywords: Renin inhibitor, Molecular dynamics simulation, Structure-based pharmacophore modeling

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Authors: Benjawan Saengwichian, Alasdair E. Charles, Philip J. Hyde

Abstract:

Magnetically controlled growing rods (MCGRs) have been used to stabilise and correct spinal curvature in children to support non-invasive scoliosis adjustment. Although the encapsulated driving components are intended to be isolated from body fluid contact, in vivo corrosion was observed on these components due to sealing mechanism damage. Consequently, a corrosion circuit is created with the body fluids, resulting in malfunction of the lengthening mechanism. Particularly, the chloride ions in blood plasma or cerebrospinal fluid (CSF) may corrode the MCGR alloys, possibly resulting in metal ion release in long-term use. However, there is no data available on the corrosion resistance of spinal implant alloys in CSF. In this study, an in vitro immersion configuration was designed to simulate in vivo corrosion of 440C SS-Ti6Al4V couples. The 440C stainless steel (SS) was heat-treated to investigate the effect of tempering temperature on intergranular corrosion (IGC), while crevice and galvanic corrosion were studied by limiting the clearance of dissimilar couples. Tests were carried out in a neutral artificial cerebrospinal fluid (ACSF) and phosphate-buffered saline (PBS) under aeration and deaeration for 2 months. The composition of the passive films and metal ion release were analysed. The effect of galvanic coupling, pH, dissolved oxygen and anion species on corrosion rates and corrosion mechanisms are discussed based on quantitative and qualitative measurements. The results suggest that ACSF is more aggressive than PBS due to the combination of aggressive chlorides and sulphate anions, while phosphate in PBS acts as an inhibitor to delay corrosion. The presence of Vivianite on the SS surface in PBS lowered the corrosion rate (CR) more than 5 times for aeration and nearly 2 times for deaeration, compared with ACSF. The CR of 440C is dependent on passive film properties varied by tempering temperature and anion species. Although the CR of Ti6Al4V is insignificant, it tends to release more Ti ions in deaerated ACSF than under aeration, about 6 µg/L. It seems the crevice-like design has more effect on macroscopic corrosion than combining the dissimilar couple, whereas IGC is dominantly observed on sensitized microstructure.

Keywords: Cerebrospinal fluid, crevice corrosion, intergranular corrosion, magnetically controlled growing rods.

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