Search results for: drug transport
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3848

Search results for: drug transport

2708 Dielectric Study of Ethanol Water Mixtures at Different Concentration Using Hollow Channel Cantilever Platform

Authors: Maryam S. Ghoraishi, John E. Hawk, Thomas Thundat

Abstract:

Understanding liquid properties in small scale has become important in recent decades as immerging new microelectromechanical systems (MEMS) devices have been widely used for micro pumps, drug delivery, and many other laboratory-on-microchips analysis. Often in microfluidic devices, fluids are transported electrokinetically. Therefore, extensive knowledge of fluid flow, heat transport, electrokinetics and electrochemistry are key to successful lab on a chip design. Among different microfluidic devices, recently developed hollow channel cantilever offers an ideal platform to study different fluid properties simultaneously without drastic decrease in quality factor which normally occurs when traditional cantilevers operate in the liquid phase. Using hollow channel cantilever, we monitor changes in density and viscosity of liquid while simultaneously investigating dielectric properties of alcohol water binary mixtures. Considerable research has been conducted on alcohol-water mixtures since such a mixture is a typical prototype for biomolecules, Micelle formation, and structural stability of proteins (to name a few). Here we show that hollow channel cantilever can be employed to investigate dielectric properties of ethanol/water mixtures in different concentrations. We study dynamic amplitude shifts of hollow channel cantilever oscillation at different concentrations of ethanol/water for different voltages. Our results show how interactions between solute and solvent, and possibly cluster formation, could change dielectric properties and dipole reorientation of the mixture, as well as the resulting force on the hollow cantilever. For comparison, we also examine higher conductivity ionic mixtures of sodium sulfate solution under the same conditions as low conductivity ethanol/water mixtures. We will show the results from systematic investigation of solvent effects on dielectric properties of the binary mixture. We will also address the question of resolution limits in dielectric study of analyte molecules imposed by solvent concentrations.

Keywords: dielectric constant, cantilever sensors, ethanol water mixtures, low frequency

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2707 Unknown Groundwater Pollution Source Characterization in Contaminated Mine Sites Using Optimal Monitoring Network Design

Authors: H. K. Esfahani, B. Datta

Abstract:

Groundwater is one of the most important natural resources in many parts of the world; however it is widely polluted due to human activities. Currently, effective and reliable groundwater management and remediation strategies are obtained using characterization of groundwater pollution sources, where the measured data in monitoring locations are utilized to estimate the unknown pollutant source location and magnitude. However, accurately identifying characteristics of contaminant sources is a challenging task due to uncertainties in terms of predicting source flux injection, hydro-geological and geo-chemical parameters, and the concentration field measurement. Reactive transport of chemical species in contaminated groundwater systems, especially with multiple species, is a complex and highly non-linear geochemical process. Although sufficient concentration measurement data is essential to accurately identify sources characteristics, available data are often sparse and limited in quantity. Therefore, this inverse problem-solving method for characterizing unknown groundwater pollution sources is often considered ill-posed, complex and non- unique. Different methods have been utilized to identify pollution sources; however, the linked simulation-optimization approach is one effective method to obtain acceptable results under uncertainties in complex real life scenarios. With this approach, the numerical flow and contaminant transport simulation models are externally linked to an optimization algorithm, with the objective of minimizing the difference between measured concentration and estimated pollutant concentration at observation locations. Concentration measurement data are very important to accurately estimate pollution source properties; therefore, optimal design of the monitoring network is essential to gather adequate measured data at desired times and locations. Due to budget and physical restrictions, an efficient and effective approach for groundwater pollutant source characterization is to design an optimal monitoring network, especially when only inadequate and arbitrary concentration measurement data are initially available. In this approach, preliminary concentration observation data are utilized for preliminary source location, magnitude and duration of source activity identification, and these results are utilized for monitoring network design. Further, feedback information from the monitoring network is used as inputs for sequential monitoring network design, to improve the identification of unknown source characteristics. To design an effective monitoring network of observation wells, optimization and interpolation techniques are used. A simulation model should be utilized to accurately describe the aquifer properties in terms of hydro-geochemical parameters and boundary conditions. However, the simulation of the transport processes becomes complex when the pollutants are chemically reactive. Three dimensional transient flow and reactive contaminant transport process is considered. The proposed methodology uses HYDROGEOCHEM 5.0 (HGCH) as the simulation model for flow and transport processes with chemically multiple reactive species. Adaptive Simulated Annealing (ASA) is used as optimization algorithm in linked simulation-optimization methodology to identify the unknown source characteristics. Therefore, the aim of the present study is to develop a methodology to optimally design an effective monitoring network for pollution source characterization with reactive species in polluted aquifers. The performance of the developed methodology will be evaluated for an illustrative polluted aquifer sites, for example an abandoned mine site in Queensland, Australia.

Keywords: monitoring network design, source characterization, chemical reactive transport process, contaminated mine site

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2706 An Investigation of the Operation and Performance of London Cycle Hire Scheme

Authors: Amer Ali, Jessica Cecchinelli, Antonis Charalambous

Abstract:

Cycling is one of the most environmentally friendly, economic and healthy modes of transport but it needs more efficient cycle infrastructure and more effective safety measures. This paper represents an investigation into the performance and operation of the London Cycle Hire Scheme which started to operate in July 2010 using 5,000 cycles and 315 docking stations and currently has more than 10,000 cycles and over 700 docking stations across London which are available 24/7, 365 days a year. The study, which was conducted during the second half of 2014, consists of two parts; namely, the longitudinal review of the hire scheme between its introduction in 2010 and November 2014, and a field survey in November 2014 in the form of face-face interviews of the users of the cycle scheme to ascertain the existing limitations and difficulties experienced by those users and how it could be improved in terms of capability and safety. The study also includes a correlation between the usage of the cycle scheme and the corresponding weather conditions. The main findings are that on average the number of users (hiring frequency) had increased from just over two millions hires in 2010 to just less than ten millions in 2014. The field survey showed that 80% of the users are satisfied with the performance of the scheme whilst 50% of the users raised concern about the safety level of using the available cycle routes and infrastructure. The study also revealed that a high percentage of the cycle trips were relatively short (less than 30 minutes). Although the weather condition had some effect on cycling, the cost of using the cycle scheme and the main events in London had more effect on the number of cycle hires. The key conclusions are that despite the safety concern and the lack of infrastructure for continuous routes there was an encouraging number of people who opted for cycling as a clean, affordable, and healthy mode of transport. There is a need to expand the scheme by providing more cycles and docking stations and to support that by more well-designed and maintained cycle routes. More details about the development of London Cycle Hire Scheme during the last five years, its performance and the key issues revealed by the surveyed users will be reported in the full version of the paper.

Keywords: cycling mode of transport, london cycle hire scheme, safety, environmental and health benefits, user satisfaction

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2705 Genotoxic Effect of Tricyclieandidepressant Drug “Clomipramine Hydrochloride’ on Somatic and Germ Cells of Male Mice

Authors: Samia A. El-Fiky, F. A. Abou-Zaid, Ibrahim M. Farag, Naira M. Efiky

Abstract:

Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: clomipramine, mice, chromosome aberrations, sperm abnormalities, histopathology

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2704 Effect of Installation of Long Cylindrical External Store on Performance, Stability, Control and Handling Qualities of Light Transport Aircraft

Authors: Ambuj Srivastava, Narender Singh

Abstract:

This paper presents the effect of installation of cylindrical external store on the performance, stability, control and handling qualities of light transport category aircraft. A pair of long cylindrical store was installed symmetrically on either side of the fuselage (port and starboard) ahead of the wing and below the fuselage bottom surface running below pilot and co-pilot window. The cylindrical store was installed as hanging from aircraft surface through specially designed brackets. The adjoining structure was sufficiently reinforced for bearing aerodynamic loads. The length to diameter ratio of long cylindrical store was ~20. Based on academic studies and flow simulation analysis, a considerable detrimental effect on single engine second segment climb performance was found which was later validated through extensive flight testing exercise. The methodology of progressive flight envelope opening was adopted. The certification was sought from Regional airworthiness authorities and for according approval.

Keywords: second segment climb, maximum operating speed, cruise performance (single engine and twin engine), minimum control speed, and additional trim required

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2703 Uncontrolled Urbanization Leads to Main Challenge for Sustainable Development of Mongolia

Authors: Davaanyam Surenjav, Chinzolboo Dandarbaatar, Ganbold Batkhuyag

Abstract:

Primate city induced rapid urbanization has been become one of the main challenges in sustainable development in Mongolia like other developing countries since transition to market economy in 1990. According due to statistical yearbook, population number of Ulaanbaatar city has increased from 0.5 million to 1.5 million for last 30 years and contains now almost half (47%) of total Mongolian population. Rural-Ulaanbaatar and local Cities-Ulaanbaatar city migration leads to social issues like uncontrolled urbanization, income inequality, poverty, overwork of public service, economic over cost for redevelopment and limitation of transport and environmental degradation including air, noise, water and soil pollution. Most thresholds of all of the sustainable urban development main and sub-indicators over exceeded from safety level to unsafety level in Ulaanbaatar. So, there is an urgent need to remove migration pull factors including some administrative and high education functions from Ulaanbaatar city to its satellite cities or secondary cities. Moreover, urban smart transport system and green and renewable energy technologies should be introduced to urban development master plan of Ulaanbaatar city.

Keywords: challenge for sustainable urban development, migration factors, primate city , urban safety thresholds

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2702 Binding Studies of Complexes of Anticancer Drugs with DNA and Enzymes Involved in DNA Replication Using Molecular Docking and Cell Culture Techniques

Authors: Fouzia Perveen, Rumana Qureshi

Abstract:

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

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

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2701 The Potential Impact of Big Data Analytics on Pharmaceutical Supply Chain Management

Authors: Maryam Ziaee, Himanshu Shee, Amrik Sohal

Abstract:

Big Data Analytics (BDA) in supply chain management has recently drawn the attention of academics and practitioners. Big data refers to a massive amount of data from different sources, in different formats, generated at high speed through transactions in business environments and supply chain networks. Traditional statistical tools and techniques find it difficult to analyse this massive data. BDA can assist organisations to capture, store, and analyse data specifically in the field of supply chain. Currently, there is a paucity of research on BDA in the pharmaceutical supply chain context. In this research, the Australian pharmaceutical supply chain was selected as the case study. This industry is highly significant since the right medicine must reach the right patients, at the right time, in right quantity, in good condition, and at the right price to save lives. However, drug shortages remain a substantial problem for hospitals across Australia with implications on patient care, staff resourcing, and expenditure. Furthermore, a massive volume and variety of data is generated at fast speed from multiple sources in pharmaceutical supply chain, which needs to be captured and analysed to benefit operational decisions at every stage of supply chain processes. As the pharmaceutical industry lags behind other industries in using BDA, it raises the question of whether the use of BDA can improve transparency among pharmaceutical supply chain by enabling the partners to make informed-decisions across their operational activities. This presentation explores the impacts of BDA on supply chain management. An exploratory qualitative approach was adopted to analyse data collected through interviews. This study also explores the BDA potential in the whole pharmaceutical supply chain rather than focusing on a single entity. Twenty semi-structured interviews were undertaken with top managers in fifteen organisations (five pharmaceutical manufacturers, five wholesalers/distributors, and five public hospital pharmacies) to investigate their views on the use of BDA. The findings revealed that BDA can enable pharmaceutical entities to have improved visibility over the whole supply chain and also the market; it enables entities, especially manufacturers, to monitor consumption and the demand rate in real-time and make accurate demand forecasts which reduce drug shortages. Timely and precise decision-making can allow the entities to source and manage their stocks more effectively. This can likely address the drug demand at hospitals and respond to unanticipated issues such as drug shortages. Earlier studies explore BDA in the context of clinical healthcare; however, this presentation investigates the benefits of BDA in the Australian pharmaceutical supply chain. Furthermore, this research enhances managers’ insight into the potentials of BDA at every stage of supply chain processes and helps to improve decision-making in their supply chain operations. The findings will turn the rhetoric of data-driven decision into a reality where the managers may opt for analytics for improved decision-making in the supply chain processes.

Keywords: big data analytics, data-driven decision, pharmaceutical industry, supply chain management

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2700 Effective Apixaban Clearance with Cytosorb Extracorporeal Hemoadsorption

Authors: Klazina T. Havinga, Hilde R. H. de Geus

Abstract:

Introduction: Pre-operative coagulation management of Apixaban prescribed patients, a new oral anticoagulant (a factor Xa inhibitor), is difficult, especially when chronic kidney disease (CKD) causes drug overdose. Apixaban is not dialyzable due to its high level of protein binding. An antidote, Andexanet α, is available but expensive and has an unfavorable short half-life. We report the successful extracorporeal removal of Apixaban prior to emergency surgery with the CytoSorb® Hemoadsorption device. Methods: A 89-year-old woman with CKD, with an Apixaban prescription for atrial fibrillation, was presented at the ER with traumatic rib fractures, a flail chest, and an unstable spinal fracture (T12) for which emergency surgery was indicated. However, due to very high Apixaban levels, this surgery had to be postponed. Based on the Apixaban-specific anti-factor Xa activity (AFXaA) measurements at admission and 10 hours later, complete clearance was expected after 48 hours. In order to enhance the Apixaban removal and reduce the time to operation, and therefore reduce pulmonary complications, CRRT with CytoSorb® cartridge was initiated. Apixaban-specific anti-factor Xa activity (AFXaA) was measured frequently as a substitute for Apixaban drug concentrations, pre- and post adsorber, in order to calculate the adsorber-related clearance. Results: The admission AFXaA concentration, as a substitute for Apixaban drug levels, was 218 ng/ml, which decreased to 157 ng/ml after ten hours. Due to sustained anticoagulation effects, surgery was again postponed. However, the AFXaA levels decreased quickly to sub-therapeutic levels after CRRT (Multifiltrate Pro, Fresenius Medical Care, Blood flow 200 ml/min, Dialysate Flow 4000 ml/h, Prescribed renal dose 51 ml-kg-h) with Cytosorb® connected in series into the circuit was initiated (within 5 hours). The adsorber-related (indirect) Apixaban clearance was calculated every half hour (Cl=Qe * (AFXaA pre- AFXaA post/ AFXaA pre) with Qe=plasma flow rate calculated with Ht=0.38 and system blood flow rate 200 ml-min): 100 ml/min, 72 ml/min and 57 ml/min. Although, as expected, the adsorber-related clearance decreased quickly due to saturation of the beads, still the reduction rate achieved resulted in a very rapid decrease in AFXaA levels. Surgery was ordered and possible within 5 hours after Cytosorb initiation. Conclusion: The CytoSorb® Hemoadsorption device enabled rapid correction of Apixaban associated anticoagulation.

Keywords: Apixaban, CytoSorb, emergency surgery, Hemoadsorption

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2699 The Optimization of Topical Antineoplastic Therapy Using Controlled Release Systems Based on Amino-functionalized Mesoporous Silica

Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

Abstract:

Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

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2698 Development of Peptide Inhibitors against Dengue Virus Infection by in Silico Design

Authors: Aussara Panya, Nunghathai Sawasdee, Mutita Junking, Chatchawan Srisawat, Kiattawee Choowongkomon, Pa-Thai Yenchitsomanus

Abstract:

Dengue virus (DENV) infection is a global public health problem with approximately 100 million infected cases a year. Presently, there is no approved vaccine or effective drug available; therefore, the development of anti-DENV drug is urgently needed. The clinical reports revealing the positive association between the disease severity and viral titer has been reported previously suggesting that the anti-DENV drug therapy can possibly ameliorate the disease severity. Although several anti-DENV agents showed inhibitory activities against DENV infection, to date none of them accomplishes clinical use in the patients. The surface envelope (E) protein of DENV is critical for the viral entry step, which includes attachment and membrane fusion; thus, the blocking of envelope protein is an attractive strategy for anti-DENV drug development. To search the safe anti-DENV agent, this study aimed to search for novel peptide inhibitors to counter DENV infection through the targeting of E protein using a structure-based in silico design. Two selected strategies has been used including to identify the peptide inhibitor which interfere the membrane fusion process whereby the hydrophobic pocket on the E protein was the target, the destabilization of virion structure organization through the disruption of the interaction between the envelope and membrane proteins, respectively. The molecular docking technique has been used in the first strategy to search for the peptide inhibitors that specifically bind to the hydrophobic pocket. The second strategy, the peptide inhibitor has been designed to mimic the ectodomain portion of membrane protein to disrupt the protein-protein interaction. The designed peptides were tested for the effects on cell viability to measure the toxic to peptide to the cells and their inhibitory assay to inhibit the DENV infection in Vero cells. Furthermore, their antiviral effects on viral replication, intracellular protein level and viral production have been observed by using the qPCR, cell-based flavivirus immunodetection and immunofluorescence assay. None of tested peptides showed the significant effect on cell viability. The small peptide inhibitors achieved from molecular docking, Glu-Phe (EF), effectively inhibited DENV infection in cell culture system. Its most potential effect was observed for DENV2 with a half maximal inhibition concentration (IC50) of 96 μM, but it partially inhibited other serotypes. Treatment of EF at 200 µM on infected cells also significantly reduced the viral genome and protein to 83.47% and 84.15%, respectively, corresponding to the reduction of infected cell numbers. An additional approach was carried out by using peptide mimicking membrane (M) protein, namely MLH40. Treatment of MLH40 caused the reduction of foci formation in four individual DENV serotype (DENV1-4) with IC50 of 24-31 μM. Further characterization suggested that the MLH40 specifically blocked viral attachment to host membrane, and treatment with 100 μM could diminish 80% of viral attachment. In summary, targeting the hydrophobic pocket and M-binding site on the E protein by using the peptide inhibitors could inhibit DENV infection. The results provide proof of-concept for the development of antiviral therapeutic peptide inhibitors to counter DENV infection through the use of a structure-based design targeting conserved viral protein.

Keywords: dengue virus, dengue virus infection, drug design, peptide inhibitor

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2697 Membrane Permeability of Middle Molecules: A Computational Chemistry Approach

Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

Abstract:

Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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2696 Antibiotic Susceptibility Profile and Horizontal Gene Transfer in Pseudomonas sp. Isolated from Clinical Specimens

Authors: Sadaf Ilyas, Saba Riaz

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The extensive use of antibiotics has led to increases emergence of antibiotic-resistant organisms. Pseudomonas is a notorious opportunistic pathogen involoved in nosocomial infections and exhibit innate resistance to many antibiotics. The present study was conducted to assess the prevalence, levels of antimicrobial susceptibility and resistance mechanisms of Pseudomonas. A total of thirty clinical strains of Pseudomonas were isolated from different clinical sites of infection. All clinical specimens were collected from Chughtais Lahore Lab. Jail road, during 8-07-2010 to 11-01-2011. Biochemical characterization was done using routine biochemical tests. Antimicrobial susceptibility was determined by Kirby-Baeur method. The plasmids were isolated from all the strains and digested with restriction enzyme PstI and EcoRI. Transfer of Multi-resistance plasmid was checked via transformation and conjugation to confirm the plasmid mediated resistance to antibiotics. The prevalence of Pseudomonas in clinical specimens was found out to be 14% of all bacterial infections. IPM has shown to be the most effective drug against Pseudomonas followed by CES, PTB and meropenem, wheareas most of the Pseudomonas strains have developed significant resistance against Penicillins and some Cephalasporins. Antibiotic resistance determinants were carried by plasmids, as they conferred resistance to transformed K1 strains. The isolates readily undergo conjugation, transferring the resistant genes to other strains, illustrating the high rates of cross infection and nosocomial infection in the immunocompromised patients.

Keywords: pseudomonas, antibiotics, drug resistance, horizontal gene transfer

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2695 Synthesis and Characterization of pH-Responsive Nanocarriers Based on POEOMA-b-PDPA Block Copolymers for RNA Delivery

Authors: Bruno Baptista, Andreia S. R. Oliveira, Patricia V. Mendonca, Jorge F. J. Coelho, Fani Sousa

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Drug delivery systems are designed to allow adequate protection and controlled delivery of drugs to specific locations. These systems aim to reduce side effects and control the biodistribution profile of drugs, thus improving therapeutic efficacy. This study involved the synthesis of polymeric nanoparticles, based on amphiphilic diblock copolymers, comprising a biocompatible, poly (oligo (ethylene oxide) methyl ether methacrylate (POEOMA) as hydrophilic segment and a pH-sensitive block, the poly (2-diisopropylamino)ethyl methacrylate) (PDPA). The objective of this work was the development of polymeric pH-responsive nanoparticles to encapsulate and carry small RNAs as a model to further develop non-coding RNAs delivery systems with therapeutic value. The responsiveness of PDPA to pH allows the electrostatic interaction of these copolymers with nucleic acids at acidic pH, as a result of the protonation of the tertiary amine groups of this polymer at pH values below its pKa (around 6.2). Initially, the molecular weight parameters and chemical structure of the block copolymers were determined by size exclusion chromatography (SEC) and nuclear magnetic resonance (1H-NMR) spectroscopy, respectively. Then, the complexation with small RNAs was verified, generating polyplexes with sizes ranging from 300 to 600 nm and with encapsulation efficiencies around 80%, depending on the molecular weight of the polymers, their composition, and concentration used. The effect of pH on the morphology of nanoparticles was evaluated by scanning electron microscopy (SEM) being verified that at higher pH values, particles tend to lose their spherical shape. Since this work aims to develop systems for the delivery of non-coding RNAs, studies on RNA protection (contact with RNase, FBS, and Trypsin) and cell viability were also carried out. It was found that they induce some protection against constituents of the cellular environment and have no cellular toxicity. In summary, this research work contributes to the development of pH-sensitive polymers, capable of protecting and encapsulating RNA, in a relatively simple and efficient manner, to further be applied on drug delivery to specific sites where pH may have a critical role, as it can occur in several cancer environments.

Keywords: drug delivery systems, pH-responsive polymers, POEOMA-b-PDPA, small RNAs

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2694 Optimization of Process Parameters and Modeling of Mass Transport during Hybrid Solar Drying of Paddy

Authors: Aprajeeta Jha, Punyadarshini P. Tripathy

Abstract:

Drying is one of the most critical unit operations for prolonging the shelf-life of food grains in order to ensure global food security. Photovoltaic integrated solar dryers can be a sustainable solution for replacing energy intensive thermal dryers as it is capable of drying in off-sunshine hours and provide better control over drying conditions. But, performance and reliability of PV based solar dryers depend hugely on climatic conditions thereby, drastically affecting process parameters. Therefore, to ensure quality and prolonged shelf-life of paddy, optimization of process parameters for solar dryers is critical. Proper moisture distribution within the grains is most detrimental factor to enhance the shelf-life of paddy therefore; modeling of mass transport can help in providing a better insight of moisture migration. Hence, present work aims at optimizing the process parameters and to develop a 3D finite element model (FEM) for predicting moisture profile in paddy during solar drying. Optimization of process parameters (power level, air velocity and moisture content) was done using box Behnken model in Design expert software. Furthermore, COMSOL Multiphysics was employed to develop a 3D finite element model for predicting moisture profile. Optimized model for drying paddy was found to be 700W, 2.75 m/s and 13% wb with optimum temperature, milling yield and drying time of 42˚C, 62%, 86 min respectively, having desirability of 0.905. Furthermore, 3D finite element model (FEM) for predicting moisture migration in single kernel for every time step has been developed. The mean absolute error (MAE), mean relative error (MRE) and standard error (SE) were found to be 0.003, 0.0531 and 0.0007, respectively, indicating close agreement of model with experimental results. Above optimized conditions can be successfully used to dry paddy in PV integrated solar dryer in order to attain maximum uniformity, quality and yield of product to achieve global food and energy security

Keywords: finite element modeling, hybrid solar drying, mass transport, paddy, process optimization

Procedia PDF Downloads 137
2693 Constraint-Based Computational Modelling of Bioenergetic Pathway Switching in Synaptic Mitochondria from Parkinson's Disease Patients

Authors: Diana C. El Assal, Fatima Monteiro, Caroline May, Peter Barbuti, Silvia Bolognin, Averina Nicolae, Hulda Haraldsdottir, Lemmer R. P. El Assal, Swagatika Sahoo, Longfei Mao, Jens Schwamborn, Rejko Kruger, Ines Thiele, Kathrin Marcus, Ronan M. T. Fleming

Abstract:

Degeneration of substantia nigra pars compacta dopaminergic neurons is one of the hallmarks of Parkinson's disease. These neurons have a highly complex axonal arborisation and a high energy demand, so any reduction in ATP synthesis could lead to an imbalance between supply and demand, thereby impeding normal neuronal bioenergetic requirements. Synaptic mitochondria exhibit increased vulnerability to dysfunction in Parkinson's disease. After biogenesis in and transport from the cell body, synaptic mitochondria become highly dependent upon oxidative phosphorylation. We applied a systems biochemistry approach to identify the metabolic pathways used by neuronal mitochondria for energy generation. The mitochondrial component of an existing manual reconstruction of human metabolism was extended with manual curation of the biochemical literature and specialised using omics data from Parkinson's disease patients and controls, to generate reconstructions of synaptic and somal mitochondrial metabolism. These reconstructions were converted into stoichiometrically- and fluxconsistent constraint-based computational models. These models predict that Parkinson's disease is accompanied by an increase in the rate of glycolysis and a decrease in the rate of oxidative phosphorylation within synaptic mitochondria. This is consistent with independent experimental reports of a compensatory switching of bioenergetic pathways in the putamen of post-mortem Parkinson's disease patients. Ongoing work, in the context of the SysMedPD project is aimed at computational prediction of mitochondrial drug targets to slow the progression of neurodegeneration in the subset of Parkinson's disease patients with overt mitochondrial dysfunction.

Keywords: bioenergetics, mitochondria, Parkinson's disease, systems biochemistry

Procedia PDF Downloads 293
2692 Travel Behavior Simulation of Bike-Sharing System Users in Kaoshiung City

Authors: Hong-Yi Lin, Feng-Tyan Lin

Abstract:

In a Bike-sharing system (BSS), users can easily rent bikes from any station in the city for mid-range or short-range trips. BSS can also be integrated with other types of transport system, especially Green Transportation system, such as rail transport, bus etc. Since BSS records time and place of each pickup and return, the operational data can reflect more authentic and dynamic state of user behaviors. Furthermore, land uses around docking stations are highly associated with origins and destinations for the BSS users. As urban researchers, what concerns us more is to take BSS into consideration during the urban planning process and enhance the quality of urban life. This research focuses on the simulation of travel behavior of BSS users in Kaohsiung. First, rules of users’ behavior were derived by analyzing operational data and land use patterns nearby docking stations. Then, integrating with Monte Carlo method, these rules were embedded into a travel behavior simulation model, which was implemented by NetLogo, an agent-based modeling tool. The simulation model allows us to foresee the rent-return behaviour of BSS in order to choose potential locations of the docking stations. Also, it can provide insights and recommendations about planning and policies for the future BSS.

Keywords: agent-based model, bike-sharing system, BSS operational data, simulation

Procedia PDF Downloads 330
2691 Silica Sulfuric Acid as an Efficient Catalyst One-Pot Three-Component Aza-Friedel-Crafts Reactions of 2-(thiophen-2-yl)-1H-Indole, Aldehydes, and N-Substituted Anilines

Authors: Nagwa Mourad Abdelazeem, Marwa El-hussieny

Abstract:

Multicomponent reactions (MCRs), one-pot reactions form products from more than two different starting compounds. (MCRs) are ideal reaction systems leading to high structural diversity and molecular complexity through a single transformation. (MCRs) have a lot of advantage such as higher yield, less waste generation, use of readily available starting materials and high atom. (MCRs) provide a rapid process for efficient synthesis of key structures in discovery of drug on the other hand silica sulfuric acid (SSA) has been used as an efficient heterogeneous catalyst for many organic transformations. (SSA) is low cost, ease of preparation, catalyst recycling, and ease of handling, so in this article we used 2-(thiophen-2-yl)-1H-indole, N-substituted anilines and aldehyde in the presence of silica sulfuric acid (SSA) as a catalyst in water as solvent at room temperature to prepare 3,3'-(phenylmethylene)bis(2-(thiophen-2-yl)-1H-indole) and N-methyl-4-(phenyl(2-(thiophen-2-yl)-1H-indol-3-yl)methyl)aniline derivatives Via one-pot reaction. Compound 2-(thiophen-2-yl)-1H-indole belongs to the ubiquitous class of indoles which enjoy broad synthetic, biological and industrial applications ]. Cancer is considered the first or second most common reason of death all through the world. So the synthesized compounds will be tested as anticancer. We expected the synthesized compounds will give good results comparison to the reference drug.

Keywords: aldehydes, aza-friedel-crafts reaction, indole, multicomponent reaction

Procedia PDF Downloads 94
2690 Genotoxic Effect of Tricyclic Antidepressant Drug “Clomipramine Hydrochloride’ on Somatic and Germ Cells of Male Mice

Authors: Samia A. El-Fiky, Fouad A. Abou-Zaid, Ibrahim M. Farag, Naira M. El-Fiky

Abstract:

Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: chromosome aberrations, clomipramine, mice, histopathology, sperm abnormalities

Procedia PDF Downloads 519
2689 Raman Spectroscopic Detection of the Diminishing Toxic Effect of Renal Waste Creatinine by Its in vitro Reaction with Drugs N-Acetylcysteine and Taurine

Authors: Debraj Gangopadhyay, Moumita Das, Ranjan K. Singh, Poonam Tandon

Abstract:

Creatinine is a toxic chemical waste generated from muscle metabolism. Abnormally high levels of creatinine in the body fluid indicate possible malfunction or failure of the kidneys. This leads to a condition termed as creatinine induced nephrotoxicity. N-acetylcysteine is an antioxidant drug which is capable of preventing creatinine induced nephrotoxicity and is helpful to treat renal failure in its early stages. Taurine is another antioxidant drug which serves similar purpose. The kidneys have a natural power that whenever reactive oxygen species radicals increase in the human body, the kidneys make an antioxidant shell so that these radicals cannot harm the kidney function. Taurine plays a vital role in increasing the power of that shell such that the glomerular filtration rate can remain in its normal level. Thus taurine protects the kidneys against several diseases. However, taurine also has some negative effects on the body as its chloramine derivative is a weak oxidant by nature. N-acetylcysteine is capable of inhibiting the residual oxidative property of taurine chloramine. Therefore, N-acetylcysteine is given to a patient along with taurine and this combination is capable of suppressing the negative effect of taurine. Both N-acetylcysteine and taurine being affordable, safe, and widely available medicines, knowledge of the mechanism of their combined effect on creatinine, the favored route of administration, and the proper dose may be highly useful in their use for treating renal patients. Raman spectroscopy is a precise technique to observe minor structural changes taking place when two or more molecules interact. The possibility of formation of a complex between a drug molecule and an analyte molecule in solution can be explored by analyzing the changes in the Raman spectra. The formation of a stable complex of creatinine with N-acetylcysteinein vitroin aqueous solution has been observed with the help of Raman spectroscopic technique. From the Raman spectra of the mixtures of aqueous solutions of creatinine and N-acetylcysteinein different molar ratios, it is observed that the most stable complex is formed at 1:1 ratio of creatinine andN-acetylcysteine. Upon drying, the complex obtained is gel-like in appearance and reddish yellow in color. The complex is hygroscopic and has much better water solubility compared to creatinine. This highlights that N-acetylcysteineplays an effective role in reducing the toxic effect of creatinine by forming this water soluble complex which can be removed through urine. Since the drug taurine is also known to be useful in reducing nephrotoxicity caused by creatinine, the aqueous solution of taurine with those of creatinine and N-acetylcysteinewere mixed in different molar ratios and were investigated by Raman spectroscopic technique. It is understood that taurine itself does not undergo complexation with creatinine as no additional changes are observed in the Raman spectra of creatinine when it is mixed with taurine. However, when creatinine, N-acetylcysteine and taurine are mixed in aqueous solution in molar ratio 1:1:3, several changes occurring in the Raman spectra of creatinine suggest the diminishing toxic effect of creatinine in the presence ofantioxidant drugs N-acetylcysteine and taurine.

Keywords: creatinine, creatinine induced nephrotoxicity, N-acetylcysteine, taurine

Procedia PDF Downloads 150
2688 Proposal of Commutation Protocol in Hybrid Sensors and Vehicular Networks for Intelligent Transport Systems

Authors: Taha Bensiradj, Samira Moussaoui

Abstract:

Hybrid Sensors and Vehicular Networks (HSVN), represent a hybrid network, which uses several generations of Ad-Hoc networks. It is used especially in Intelligent Transport Systems (ITS). The HSVN allows making collaboration between the Wireless Sensors Network (WSN) deployed on the border of the road and the Vehicular Network (VANET). This collaboration is defined by messages exchanged between the two networks for the purpose to inform the drivers about the state of the road, provide road safety information and more information about traffic on the road. Moreover, this collaboration created by HSVN, also allows the use of a network and the advantage of improving another network. For example, the dissemination of information between the sensors quickly decreases its energy, and therefore, we can use vehicles that do not have energy constraint to disseminate the information between sensors. On the other hand, to solve the disconnection problem in VANET, the sensors can be used as gateways that allow sending the messages received by one vehicle to another. However, because of the short communication range of the sensor and its low capacity of storage and processing of data, it is difficult to ensure the exchange of road messages between it and the vehicle, which can be moving at high speed at the time of exchange. This represents the time where the vehicle is in communication range with the sensor. This work is the proposition of a communication protocol between the sensors and the vehicle used in HSVN. The latter has as the purpose to ensure the exchange of road messages in the available time of exchange.

Keywords: HSVN, ITS, VANET, WSN

Procedia PDF Downloads 360
2687 3D Simulation and Modeling of Magnetic-Sensitive on n-type Double-Gate Metal-Oxide-Semiconductor Field-Effect Transistor (DGMOSFET)

Authors: M. Kessi

Abstract:

We investigated the effect of the magnetic field on carrier transport phenomena in the transistor channel region of Double-Gate Metal-Oxide-Semiconductor Field-Effect Transistor (MOSFET). This explores the Lorentz force and basic physical properties of solids exposed to a constant external magnetic field. The magnetic field modulates the electrons and potential distribution in the case of silicon Tunnel FETs. This modulation shows up in the device's external electrical characteristics such as ON current (ION), subthreshold leakage current (IOF), the threshold voltage (VTH), the magneto-transconductance (gm) and the output magneto-conductance (gDS) of Tunnel FET. Moreover, the channel doping concentration and potential distribution are obtained using the numerical method by solving Poisson’s transport equation in 3D modules semiconductor magnetic sensors available in Silvaco TCAD tools. The numerical simulations of the magnetic nano-sensors are relatively new. In this work, we present the results of numerical simulations based on 3D magnetic sensors. The results show excellent accuracy comportment and good agreement compared with that obtained in the experimental study of MOSFETs technology.

Keywords: single-gate MOSFET, magnetic field, hall field, Lorentz force

Procedia PDF Downloads 179
2686 The Ultimate Scaling Limit of Monolayer Material Field-Effect-Transistors

Authors: Y. Lu, L. Liu, J. Guo

Abstract:

Monolayer graphene and dichaclogenide semiconductor materials attract extensive research interest for potential nanoelectronics applications. The ultimate scaling limit of double gate MoS2 Field-Effect-Transistors (FETs) with a monolayer thin body is examined and compared with ultra-thin-body Si FETs by using self-consistent quantum transport simulation in the presence of phonon scattering. Modelling of phonon scattering, quantum mechanical effects, and self-consistent electrostatics allows us to accurately assess the performance potential of monolayer MoS2 FETs. The results revealed that monolayer MoS2 FETs show 52% smaller Drain Induced Barrier Lowering (DIBL) and 13% Smaller Sub-Threshold Swing (SS) than 3 nm-thick-body Si FETs at a channel length of 10 nm with the same gating. With a requirement of SS<100mV/dec, the scaling limit of monolayer MoS2 FETs is assessed to be 5 nm, comparing with 8nm of the ultra-thin-body Si counterparts due to the monolayer thin body and higher effective mass which reduces direct source-to-drain tunnelling. By comparing with the ITRS target for high performance logic devices of 2023; double gate monolayer MoS2 FETs can fulfil the ITRS requirements.

Keywords: nanotransistors, monolayer 2D materials, quantum transport, scaling limit

Procedia PDF Downloads 233
2685 Providing a Road Pricing and Toll Allocation Method for Toll Roads

Authors: Ali Babaei

Abstract:

There is a worldwide growing tendency toward construction of infrastructures with the possibility of private sector participation instead of free exploitation of public infrastructures. The construction and development of roads through private sector participation is performed by different countries because of appropriate results and benefits such as compensation of public budget deficit in road construction and maintenance and responding to traffic growth (demand). Toll is the most definite form of budget provision in road development. There are two issues in the toll rate assignment: A. costing of transport, B. Cost allocation and distribution of cost between different types of vehicles as each vehicle pay its own share. There can be different goals in toll collection and its extent is variable according to the strategy of toll collection. Costing principles in different countries are based on inclusion of the whole transport and not peculiar to the toll roads. For example, fuel tax policy functions where the road network users pay transportation cost (not just users of toll road). Whereas transportation infrastructures in Iran are free, these methods are not applicable. In Iran, different toll freeways have built by public investment and government provides participation in the road construction through encouragement of financial institutions. In this paper, the existing policies about the toll roads are studied and then the appropriate method of costing and cost allocation to different vehicles is introduced.

Keywords: toll allocation, road pricing, transportation, financial and industrial systems

Procedia PDF Downloads 362
2684 Separation of Copper(II) and Iron(III) by Solvent Extraction and Membrane Processes with Ionic Liquids as Carriers

Authors: Beata Pospiech

Abstract:

Separation of metal ions from aqueous solutions is important as well as difficult process in hydrometallurgical technology. This process is necessary for obtaining of clean metals. Solvent extraction and membrane processes are well known as separation methods. Recently, ionic liquids (ILs) are very often applied and studied as extractants and carriers of metal ions from aqueous solutions due to their good extractability properties for various metals. This work discusses a method to separate copper(II) and iron(III) from hydrochloric acid solutions by solvent extraction and transport across polymer inclusion membranes (PIM) with the selected ionic liquids as extractants/ion carriers. Cyphos IL 101 (trihexyl(tetradecyl)phosphonium chloride), Cyphos IL 104 (trihexyl(tetradecyl)phosphonium bis(2,4,4 trimethylpentyl)phosphi-nate), trioctylmethylammonium thiosalicylate [A336][TS] and trihexyl(tetradecyl)phosphonium thiosalicylate [PR4][TS] were used for the investigations. Effect of different parameters such as hydrochloric acid concentration in aqueous phase on iron(III) and copper(II) extraction has been investigated. Cellulose triacetate membranes with the selected ionic liquids as carriers have been prepared and applied for transport of iron(IIII) and copper(II) from hydrochloric acid solutions.

Keywords: copper, iron, ionic liquids, solvent extraction

Procedia PDF Downloads 277
2683 Antihypertensive Effect of Formulated Apium graveolens: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Authors: Maryam Shayani Rad, Seyed Ahmad Mohajeri, Mohsen Mouhebati, Seyed Danial Mousavi

Abstract:

High blood pressure is one of the most important and serious health-threatening because of no symptoms in most people, which can lead to sudden heart attack, heart failure, and stroke. Nowadays, herbal medicine is one of the best and safest strategies for treatment that have no adverse effects. Apium graveolens (celery) can be used as an alternative treatment for many health conditions such as hypertension. Natural compounds reduce blood pressure via different mechanisms in which Apium graveolens extract provides potent calcium channel blocking properties. A randomized, double-blind, placebo-controlled, cross-over clinical trial was done to evaluate the efficacy of formulated Apium graveolens extract with a maximum yield of 3-n-butylphthalide to reduce systolic and diastolic blood pressure in patients with hypertension. 54 hypertensive patients in the range of 20-68 years old were randomly assigned to the treatment group (26 cases) and the placebo control group (26 cases) and were crossed over after washout duration. The treatment group received at least 2 grams of formulated powder in hard capsules orally, before each meal, 2 times daily. The control group received 2 grams of placebo in hard capsules orally, exactly as the same as shape, time, and doses of treatment group. Treatment was administrated in 12 weeks with 4 weeks washout period at the middle of the study, meaning 4 weeks drug consumption for the treatment group, 4 weeks washout and 4 weeks placebo consumption, and vice versa for the placebo control group. The clinical assessment was done 4 times, including at the beginning and ending of the drug and placebo consumption period by 24-hour ambulatory blood pressure monitoring (ABPM) holter, which measured blood pressure every 15 minutes continuously. There was a statistically significant decrease in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the end of drug duration compared to baseline. The changes after 4 weeks on average was about 12.34 mm Hg for the SBP (P < 0.005) and 7.83 mm Hg for the DBP (P < 0.005). The results from this clinical trial study showed this Apium graveolens extract formulation in the mentioned dosage had a significant effect on blood pressure-lowering for hypertensive patients.

Keywords: Apium graveolens extract, clinical trial, cross-over, hypertension

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2682 The Toxicity of Doxorubicin Connected with Nanotransporters

Authors: Iva Blazkova, Amitava Moulick, Vedran Milosavljevic, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

Abstract:

Doxorubicin is one of the most commonly used and the most effective chemotherapeutic drugs. This antracycline drug isolated from the bacteria Streptomyces peuceticus var. caesius is sold under the trade name Adriamycin (hydroxydaunomycin, hydroxydaunorubicin). Doxorubicin is used in single therapy to treat hematological malignancies (blood cancers, leukaemia, lymphoma), many types of carcinoma (solid tumors) and soft tissue sarcomas. It has many serious side effects like nausea and vomiting, hair lost, myelosupression, oral mucositis, skin reactions and redness, but the most serious one is the cardiotoxicity. Because of the risk of heart attack and congestive heart failure, the total dose administered to patients has to be accurately monitored. With the aim to lower the side effects and to targeted delivery of doxorubicin into the tumor tissue, the different nanoparticles are studied. The drug can be bound on a surface of nanoparticle, encapsulated in the inner cavity, or incorporated into the structure of nanoparticle. Among others, carbon nanoparticles (graphene, carbon nanotubes, fullerenes) are highly studied. Besides the number of inorganic nanoparticles, a great potential exhibit also organic ones mainly lipid-based and polymeric nanoparticle. The aim of this work was to perform a toxicity study of free doxorubicin compared to doxorubicin conjugated with various nanotransporters. The effect of liposomes, fullerenes, graphene, and carbon nanotubes on the toxicity was analyzed. As a first step, the binding efficacy of between doxorubicin and the nanotransporter was determined. The highest efficacy was detected in case of liposomes (85% of applied drug was encapsulated) followed by graphene, carbon nanotubes and fullerenes. For the toxicological studies, the chicken embryos incubated under controlled conditions (37.5 °C, 45% rH, rotation every 2 hours) were used. In 7th developmental day of chicken embryos doxorubicin or doxorubicin-nanotransporter complex was applied on the chorioallantoic membrane of the eggs and the viability was analyzed every day till the 17th developmental day. Then the embryos were extracted from the shell and the distribution of doxorubicin in the body was analyzed by measurement of organs extracts using laser induce fluorescence detection. The chicken embryo mortality caused by free doxorubicin (30%) was significantly lowered by using the conjugation with nanomaterials. The highest accumulation of doxorubicin and doxorubicin nanotransporter complexes was observed in the liver tissue

Keywords: doxorubicin, chicken embryos, nanotransporters, toxicity

Procedia PDF Downloads 447
2681 The Disease That 'Has a Woman Face': Feminization of HIV/AIDS in Nagaland, North-East India

Authors: Kitoholi V. Zhimo

Abstract:

Unlike the cases of cases of homosexuals, haemophilic and or drug users in USA, France, Africa and other countries, in India the first case of HIV/AIDS was detected in heterosexual female sex workers (FSW) in Chennai in 1986. This image played an important role in understanding HIV/AIDS scenario in the country. Similar to popular and dominant metaphors on HIV/AIDS such as ‘gay plague’, ‘new cancer’, ‘lethal disease’, ‘slim disease’, ‘foreign disease’, ‘junkie disease’, etc. around the world, the social construction of the virus was largely attributed to women in India. It was established that women particularly sex workers are ‘carrier’ and ‘transmitter’ of virus and were categorised as High Risk Groups (HRG’s) alongside homosexuals, transgenders and injecting drug users. Recent literature reveals growing rate of HIV infection among housewives since 1997 which revolutionised public health scenario in India. This means shift from high risk group to general public through ‘bridge population’ encompassing long distance truckers and migrant labours who at the expense of their nature of work and mobility comes in contact with HRG’s and transmit the virus to the general public especially women who are confined to the domestic space. As HIV epidemic expands, married women in monogamous relationship/marriage stand highly susceptible to infection with limited control, right and access over their sexual and reproductive health and planning. In context of Nagaland, a small state in North-eastern part of India HIV/AIDS transmission through injecting drug use dominated the early scene of the epidemic. However, paradigm shift occurred with declining trend of HIV prevalence among injecting drug users (IDU’s) over the past years with the introduction of Opioid Substitution Therapy (OST) and easy access/availability of syringes and injecting needles. Reflection on statistical data reveals that out of 36 states and union territories in India, the position of Nagaland in HIV prevalence among IDU’s has significantly dropped down from 6th position in 2003 to 16th position in 2017. The present face of virus in Nagaland is defined by (hetero) sexual mode of transmission which accounts for about 91% of as reported by Nagaland state AIDS control society (NSACS) in 2016 wherein young and married woman were found to be most affected leading to feminization of HIV/AIDS epidemic in the state. Thus, not only is HIV epidemic feminised but emerged victim to domestic violence which is more often accepted as normal part of heterosexual relationship. In the backdrop of these understanding, the present paper based on ethnographic fieldwork explores the plight, lived experiences and images of HIV+ve women with regard to sexual and reproductive rights against the backdrop of patriarchal system in Nagaland.

Keywords: HIV/AIDS, monogamy, Nagaland, sex worker disease, women

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2680 Preparedness for Nurses to Adopt the Implementation of Inpatient Medication Order Entry (IPMOE) System at United Christian Hospital (UCH) in Hong Kong

Authors: Yiu K. C. Jacky, Tang S. K. Eric, W. Y. Tsang, C. Y. Li, C. K. Leung

Abstract:

Objectives : (1) To enhance the competence of nurses on using IPMOE for drug administration; (2) To ensure the transition on implementation of IPMOE in safer and smooth way hospital-wide. Methodology: (1) Well-structured Governance: To make provision for IPMOE implementation, multidisciplinary governance structure at Corporate and Local levels are well established. (2) Staff Engagement: A series of staff engagement events were conducted including Staff Forum, IPMOE Hospital Visit, Kick-off Ceremony and establishment of IPMOE Webpage for familiarizing the forthcoming implementation with frontline staff. (3) Well-organized training program: from Workshop to Workplace Two different IPMOE training programs were tailor-made which aimed at introducing the core features of administration module. Fifty-five identical training classes and six train-the-trainer workshops were organized at 2-3Q 2015. Lending Scheme on IPMOE hardware for hands-on practicing was launched and further extended the training from workshop to workplace. (4) Standard Guidelines and Workflow: the related workflow and guidelines are developed which facilitates users to acquire the competence towards IPMOE and fully familiarize with the standardized contingency plan. (5) Facilities and Equipment: The installations of IPMOE hardware were promptly arranged for rollout. Besides, IPMOE training venue was well-established for staff training. (6) Risk Management Strategy: UCH Medication Safety Forum is organized in December 2015 for sharing “Tricks & Tips” on IPMOE which further disseminate at webpage for arousal of medication safety. Hospital-wide annual audit on drug administration was planned to figure out the compliance and deliberate the rooms for improvement. Results: Through the comprehensive training plan, over 1,000 UCH nurses attended the training program with positive feedback. They agreed that their competence on using IPMOE was enhanced. By the end of November 2015, 28 wards (over 1,000 Inpatient-bed) involving departments of M&G, SUR, O&T and O&G have been successfully rolled out IPMOE in 5-month. A smooth and safe transition of implementation of IPMOE was achieved. Eventually, we all get prepared for embedding IPMOE into daily nursing and work altogether for medication safety at UCH.

Keywords: drug administration, inpatient medication order entry system, medication safety, nursing informatics

Procedia PDF Downloads 341
2679 Polymer Composites Containing Gold Nanoparticles for Biomedical Use

Authors: Bozena Tyliszczak, Anna Drabczyk, Sonia Kudlacik-Kramarczyk, Agnieszka Sobczak-Kupiec

Abstract:

Introduction: Nanomaterials become one of the leading materials in the synthesis of various compounds. This is a reason for the fact that nano-size materials exhibit other properties compared to their macroscopic equivalents. Such a change in size is reflected in a change in optical, electric or mechanical properties. Among nanomaterials, particular attention is currently directed into gold nanoparticles. They find application in a wide range of areas including cosmetology or pharmacy. Additionally, nanogold may be a component of modern wound dressings, which antibacterial activity is beneficial in the viewpoint of the wound healing process. Specific properties of this type of nanomaterials result in the fact that they may also be applied in cancer treatment. Studies on the development of new techniques of the delivery of drugs are currently an important research subject of many scientists. This is due to the fact that along with the development of such fields of science as medicine or pharmacy, the need for better and more effective methods of administering drugs is constantly growing. The solution may be the use of drug carriers. These are materials that combine with the active substance and lead it directly to the desired place. A role of such a carrier may be played by gold nanoparticles that are able to covalently bond with many organic substances. This allows the combination of nanoparticles with active substances. Therefore gold nanoparticles are widely used in the preparation of nanocomposites that may be used for medical purposes with special emphasis on drug delivery. Methodology: As part of the presented research, synthesis of composites was carried out. The mentioned composites consisted of the polymer matrix and gold nanoparticles that were introduced into the polymer network. The synthesis was conducted with the use of a crosslinking agent, and photoinitiator and the materials were obtained by means of the photopolymerization process. Next, incubation studies were conducted using selected liquids that simulated fluids are occurring in the human body. The study allows determining the biocompatibility of the tested composites in relation to selected environments. Next, the chemical structure of the composites was characterized as well as their sorption properties. Conclusions: Conducted research allowed for the preliminary characterization of prepared polymer composites containing gold nanoparticles in the viewpoint of their application for biomedical use. Tested materials were characterized by biocompatibility in tested environments. What is more, synthesized composites exhibited relatively high swelling capacity that is essential in the viewpoint of their potential application as drug carriers. During such an application, composite swells and at the same time releases from its interior introduced active substance; therefore, it is important to check the swelling ability of such material. Acknowledgements: The authors would like to thank The National Science Centre (Grant no: UMO - 2016/21/D/ST8/01697) for providing financial support to this project. This paper is based upon work from COST Action (CA18113), supported by COST (European Cooperation in Science and Technology).

Keywords: nanocomposites, gold nanoparticles, drug carriers, swelling properties

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