Search results for: drug transport

Authors: Nidhi Prabha

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Transportation as a sector is one of the most significant infrastructural elements of the ‘urban.' The distinctness of an urban life in a city is marked by the dynamic movements that it enables within the city-space. Therefore it is important to study the public-transport systems that enable and foster mobility which characterizes the urban. It is also crucial to underscore the way one is examining the urban transport systems - either as an infrastructural unit in a strict physical-structural sense or as a structural unit which acts as a prism refracting multiple experiences depending on the location of the ‘commuter.' In the proposed paper, the attempt is to uncover and investigate the assumption of the neuter-commuter by looking at urban transportation in the secondary sense i.e. as a structural unit which is experienced differently by different kinds of commuters, thus making transportation deeply distributed with various social structures and locations like class or gender which map onto the transport systems. To this end, the public-transit systems operating in Urban Delhi i.e. the Delhi Metros and the Delhi Transport Corporation run public-buses are looked at as case studies. The study is premised on the knowledge and data gained from both primary and secondary sources. Primary sources include data and knowledge collected from fieldwork, the methodology for which has ranged from adopting ‘mixed-methods’ which is ‘Qualitative-then-Quantitative’ as well as borrowing ethnographic techniques. Apart from fieldwork, other primary sources looked at including Annual Reports and policy documents of the Delhi Metro Rail Corporation (DMRC) and the Delhi Transport Corporation (DTC), Union and Delhi budgets, Economic Survey of Delhi, press releases, etc. Secondary sources include the vast array of literature available on the critical nodes that inform the research like gender, transport geographies, urban-space, etc. The study indicates a deeply-distributed urban transport system wherein the various social-structural locations or different kinds of commuters map onto the way these different commuters experience mobility or movement within the city space. Mobility or movement, therefore, becomes gendered or has class-based ramifications. The neuter-commuter assumption is thus challenged. Such an understanding enables us to challenge the anonymity which the ‘urban’ otherwise claims it provides over the rural. The rural is opposed to the urban wherein urban ushers a modern way of life, breaking ties of traditional social identities. A careful study of the transport systems through the traveling patterns and choices of the commuters, however, indicate that this does not hold true as even the same ‘public-space’ of the transport systems allocates different places to different kinds of commuters. The central argument made though the research done is therefore that infrastructure like urban-transport-systems has to be studied and examined as seen beyond just a physical structure. The various experiences of daily mobility of different kinds of commuters have to be taken into account in order to design and plan more inclusive transport systems.

Keywords: gender, infrastructure, mobility, urban-transport-systems

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Authors: Sunil Kamboj, Suman Bala, Vipin Saini

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Niosomes were formulated with an aim of enhancing the oral bioavailability of losartan potassium and formulated in different molar ratios of surfactant, cholesterol and dicetyl phosphate. The formulated niosomes were found in range of 54.98 µm to 107.85 µm in size. Formulations with 1:1 ratio of surfactant and cholesterol have shown maximum entrapment efficiencies. Niosomes with sorbitan monostearate showed maximum drug release and zero order release kinetics, at the end of 24 hours. The in vivo study has shown the significant enhancement in oral bioavailability of losartan potassium in rats, after a dose of 10 mg/kg. The average relative bioavailability in relation with pure drug solution was found 2.56, indicates more than two fold increase in oral bioavailability. A significant increment in MRT reflects the release retarding ability of the vesicles. In conclusion, niosomes could be a promising delivery of losartan potassium with improved oral bioavailability and prolonged release profiles.

Keywords: non-ionic surfactant vesicles, losartan potassium, oral bioavailability, controlled release

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Authors: Owonikoko Abayomi Dele

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Epilepsy is an unresolved disease that needs urgent attention. It is a brain disorder that affects over sixty-five (65) million people around the globe. Despite the availability of commercial anti-epileptic drugs, the war against this unmet condition is yet to be resolved. Most epilepsy patients are resistant to available anti-epileptic medications thus the need for affordable novel therapy against epilepsy is a necessity. Numerous phytochemicals have been reported for their potency, efficacy and safety as therapeutic agents against many diseases. This study investigated 99 isolated phytochemicals from Chasmanthera dependens and Carissa edulis against carbonic anhydrase (ii) drug target. The absorption, distribution, metabolism, excretion and toxicity (ADMET) of the isolated compounds were examined using admet SAR-2 web server while Swiss ADME was used to analyze the oral bioavailability, drug-likeness and lead-likeness properties of the selected leads. PASS web server was used to predict the biological activities of selected leads while other important physicochemical properties and interactions of the selected leads with the active site of the target after successful molecular docking simulation with the pyrx virtual screening tool were also examined. The results of these study identified seven lead compounds; C49- alpha-carissanol (-7.6 kcal/mol), C13- Catechin (-7.4 kcal/mol), C45- Salicin (-7.4 kcal/mol), C6- Bisnorargemonine (-7.3 kcal/mol), C36- Pallidine (-7.1 kcal/mol), S4- Lacosamide (-7.1 kcal/mol), and S7- Acetazolamide (-6.4 kcal/mol) for CA II (3HS4 receptor). These leads compounds are probable inhibitors of this drug target due to the observed good binding affinities and favourable interactions with the active site of the drug target, excellent ADMET profiles, PASS Properties, drug-likeness, lead-likeness and oral bioavailability properties. The identified leads have better binding energies as compared to the binding energies of the two standards. Thus, seven identified lead compounds can be developed further towards the development of new anti-epileptic medications.

Keywords: drug-likeness, phytochemicals, carbonic anhydrases, metalloeazymes, active site, ADMET

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Authors: Eman M. Sarhan, Doaa A. Ghareeb, Gabriella Ortore, Amr A. Amara, Mohamed M. El-Sayed

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Drug salting and nanoparticle-based drug delivery formulations are considered to be an effective means for rendering the hydrophobic drugs’ nano-scale dispersion in aqueous media, and thus circumventing the pitfalls of their poor solubility as well as enhancing their membrane permeability. The current study aims to increase the bioavailability of quaternary ammonium berberine through acid salting and biodegradable bovine serum albumin (BSA)-based nanoparticulate drug formulation. Berberine hydroxide (BBR-OH) that was chemically synthesized by alkalization of the commercially available berberine hydrochloride (BBR-HCl) was then acidified to get Di-berberine sulfate (BBR)₂SO₄. The purified crystals were spectrally characterized. The desolvation technique was optimized for the preparation of size-controlled BSA-BBR-HCl, BSA-BBR-OH, and BSA-(BBR)₂SO₄ nanoparticles. Particle size, zeta potential, drug release, encapsulation efficiency, Fourier transform infrared spectroscopy (FTIR), tandem MS-MS spectroscopy, energy-dispersive X-ray spectroscopy (EDX), scanning and transmitting electron microscopic examination (SEM, TEM), in vitro bioactivity, and in silico drug-polymer interaction were determined. BSA (PDB ID; 4OR0) protonation state at different pH values was predicted using Amber12 molecular dynamic simulation. Then blind docking was performed using Lamarkian genetic algorithm (LGA) through AutoDock4.2 software. Results proved the purity and the size-controlled synthesis of berberine-BSA-nanoparticles. The possible binding poses, hydrophobic and hydrophilic interactions of berberine on BSA at different pH values were predicted. Antioxidant, anti-hemolytic, and cell differentiated ability of tested drugs and their nano-formulations were evaluated. Thus, drug salting and the potentially effective albumin berberine nanoparticle formulations can be successfully developed using a well-optimized desolvation technique and exhibiting better in vitro cellular bioavailability.

Keywords: berberine, BSA, BBR-OH, BBR-HCl, BSA-BBR-HCl, BSA-BBR-OH, (BBR)₂SO₄, BSA-(BBR)₂SO₄, FTIR, AutoDock4.2 Software, Lamarkian genetic algorithm, SEM, TEM, EDX

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Authors: Shasline Gedeon, Tiffany W. Ardley, Ying Wang, Nathan J. Gesmundo, Katarina A. Sarris, Ana L. Aguirre

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Drug discovery and delivery involve drug targeting, an approach that helps find a drug against a chosen target through high throughput screening and other methods by way of identifying the physical properties of the potential lead compound. Physical properties of potential drug candidates have been an imperative focus since the unveiling of Lipinski's Rule of 5 for oral drugs. Throughout a compound's journey from discovery, clinical phase trials, then becoming a classified drug on the market, the desirable properties are optimized while minimizing/eliminating toxicity and undesirable properties. In the pharmaceutical industry, the ability to generate molecules in parallel with maximum efficiency is a substantial factor achieved through sp²-sp² carbon coupling reactions, e.g., Suzuki Coupling reactions. These reaction types allow for the increase of aromatic fragments onto a compound. More recent literature has found benefits to decreasing aromaticity, calling for more sp³-sp² carbon coupling reactions instead. The objective of this project is to provide a comparison between various sp³-sp² carbon coupling methods and reaction conditions, collecting data on production of the desired product. There were four different coupling methods being tested amongst three cores and 4-5 installation groups per method; each method ran under three distinct reaction conditions. The tested methods include the Photoredox Decarboxylative Coupling, the Photoredox Potassium Alkyl Trifluoroborate (BF3K) Coupling, the Photoredox Cross-Electrophile (PCE) Coupling, and the Weix Cross-Electrophile (WCE) Coupling. The results concluded that the Decarboxylative method was very difficult in yielding product despite the several literature conditions chosen. The BF3K and PCE methods produced competitive results. Amongst the two Cross-Electrophile coupling methods, the Photoredox method surpassed the Weix method on numerous accounts. The results will be used to build future libraries.

Keywords: drug discovery, high throughput chemistry, photoredox chemistry, sp³-sp² carbon coupling methods

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Authors: Ravi Sheshala, Annie Lee, Ai Lin Ong, Ling Ling Cheu, Thiagarajan Madheswaran, Thankur R. R. Singh

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The objectives of the present research work were to develop and characterize biodegradable controlled release photo cross-linked implants of Triamcinolone Acetonide (TA) for the treatment of chronic ocular diseases. The photo cross-linked implants were prepared using film casting technique by mixing TA (2.5%) polyethylene glycol diacrylate (PEGDA 700), pore formers (mannitol, maltose, and gelatin) and the photoinitiator (Irgacure 2959). The resulting mixture was injected into moulds using 21 G and subjected to photocrosslinking at 365 nm. Scanning electron microscopy results demonstrated that more pores were formed in the films with the increase in the concentration of pore formers from 2%-10%. The maximum force required to break the films containing 2-10% of pore formers were determined in both dry and wet conditions using texture analyzer and found that films in a dry condition required a higher force to break compared to wet condition and blank films. In vitro drug release from photo cross-linked films were determined by incubating samples in 50 ml PBS pH 7.4 at 37 C and the samples were analyzed for drug release by HPLC. The films demonstrated a biphasic release profile i.e. an initial burst release (<20%) on the first day followed by a constant and continuous drug release in a controlled manner for 42 days. The drug release from all formulations followed the first-order release pattern and the combination of diffusion and erosion release mechanism. In conclusion, the developed formulations were able to provide controlled drug delivery to treat the chronic ocular diseases.

Keywords: controlled release, ophthalmic, PEGDA, photocrosslinking, pore formers

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Authors: Swapna Begum, Higano Yoshiro

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Dhaka is the capital city of Bangladesh. It is considered as one of the traffic congested cities in the world. The growth of the population of this city is increasing day by day. The land use pattern and the increased socio-economic characteristics increase the motor vehicle ownership of this city. The rapid unplanned urbanization and poor transportation planning have deteriorated the transport environment of this city. Also, the huge travel demand with non-motorized traffics on streets is accounted for enormous traffic congestion in this city. The land transport sector in Dhaka is mainly dependent on road transport comprised of both motorized and non-motorized modes of travel. This improper modal mix and the un-integrated system have resulted in huge traffic congestion in this city. Moreover, this city has no well-organized public transport system and any Mass Transit System to cope with this ever increasing demand. Traffic congestion causes serious air pollution and adverse impact on the economy by deteriorating the accessibility, level of service, safety, comfort and operational efficiency. Therefore, there is an imperative need to introduce a well-organized, properly scheduled mass transit system like (Bus Rapid Transit) BRT minimizing the existing problems.

Keywords: air pollution, BRT, mass transit, traffic congestion

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Authors: Lichung Jen, Yi Chun Liu, Kuan-Wei Lee

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Fruitful data has been accumulated in database nowadays and is commonly used as support for decision-making. In the healthcare industry, hospital, for instance, ordering pharmacy inventory is one of the key decision. With large drug inventory, the current cost increases and its expiration dates might lead to future issue, such as drug disposal and recycle. In contrast, underestimating demand of the pharmacy inventory, particularly standing drugs, affects the medical treatment and possibly hospital reputation. Prescription behaviour of hospital physicians is one of the critical factor influencing this decision, particularly irregular prescription behaviour. If a drug’s usage amount in the month is irregular and less than the regular usage, it may cause the trend of subsequent stockpiling. On the contrary, if a drug has been prescribed often than expected, it may result in insufficient inventory. We proposed a hierarchical Bayesian mixture model with two components to identify physicians’ regular/irregular prescription patterns with probabilities. Heterogeneity of hospital is considered in our proposed hierarchical Bayes model. The result suggested that modeling the prescription patterns of physician is beneficial for estimating the order quantity of medication and pharmacy inventory management of the hospital. Managerial implication and future research are discussed.

Keywords: hierarchical Bayesian model, poission mixture model, medicines prescription behavior, irregular behavior

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Authors: Francesca Fermi, Paola Astegiano, Angelo Martino, Stephanie Heitel, Michael Krail

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In order to achieve the targeted emission reductions for the decarbonisation of the European economy by 2050, fundamental contributions are required from both energy and transport sectors. The objective of this paper is to analyse the impacts of a largescale diffusion of e-vehicles, either battery-based or fuel cells, together with the implementation of transport policies aiming at decreasing the use of motorised private modes in order to achieve greenhouse gas emission reduction goals, in the context of a future high share of renewable energy. The analysis of the impacts and challenges of future scenarios on transport sector is performed with the ASTRA (ASsessment of TRAnsport Strategies) model. ASTRA is a strategic system-dynamic model at European scale (EU28 countries, Switzerland and Norway), consisting of different sub-modules related to specific aspects: the transport system (e.g. passenger trips, tonnes moved), the vehicle fleet (composition and evolution of technologies), the demographic system, the economic system, the environmental system (energy consumption, emissions). A key feature of ASTRA is that the modules are linked together: changes in one system are transmitted to other systems and can feed-back to the original source of variation. Thanks to its multidimensional structure, ASTRA is capable to simulate a wide range of impacts stemming from the application of transport policy measures: the model addresses direct impacts as well as second-level and third-level impacts. The simulation of the different scenarios is performed within the REFLEX project, where the ASTRA model is employed in combination with several energy models in a comprehensive Modelling System. From the transport sector perspective, some of the impacts are driven by the trend of electricity price estimated from the energy modelling system. Nevertheless, the major drivers to a low carbon transport sector are policies related to increased fuel efficiency of conventional drivetrain technologies, improvement of demand management (e.g. increase of public transport and car sharing services/usage) and diffusion of environmentally friendly vehicles (e.g. electric vehicles). The final modelling results of the REFLEX project will be available from October 2018. The analysis of the impacts and challenges of future scenarios is performed in terms of transport, environmental and social indicators. The diffusion of e-vehicles produces a consistent reduction of future greenhouse gas emissions, although the decarbonisation target can be achieved only with the contribution of complementary transport policies on demand management and supporting the deployment of low-emission alternative energy for non-road transport modes. The paper explores the implications through time of transport policy measures on mobility and environment, underlying to what extent they can contribute to a decarbonisation of the transport sector. Acknowledgements: The results refer to the REFLEX project which has received grants from the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. 691685.

Keywords: decarbonisation, greenhouse gas emissions, e-mobility, transport policies, energy

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Authors: Amanda C. Q. M. Vieira, Cybelly M. Melo, Camila B. M. Figueirêdo, Giovanna C. R. M. Schver, Salvana P. M. Costa, Magaly A. M. de Lyra, Ping I. Lee, José L. Soares-Sobrinho, Pedro J. Rolim-Neto, Mônica F. R. Soares

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Epiisopiloturine (EPI) is a drug candidate that is extracted from Pilocarpus microphyllus and isolated from the waste of Pilocarpine. EPI has demonstrated promising schistosomicidal, leishmanicide, anti-inflammatory and antinociceptive activities, according to in vitro studies that have been carried out since 2009. However, this molecule shows poor aqueous solubility, which represents a problem for the release of the drug candidate and its absorption by the organism. The purpose of the present study is to investigate the extent of enhancement of kinetic solubility of a solid solution (SS) of EPI in hipromellose phthalate HP-55 (HPMCP), an enteric polymer carrier. SS was obtained by the solvent evaporation methodology, using acetone/methanol (60:40) as solvent system. Both EPI and polymer (drug loading 10%) were dissolved in this solvent until a clear solution was obtained, and then dried in oven at 60ºC during 12 hours, followed by drying in a vacuum oven for 4 h. The results show a considerable modification in the crystalline structure of the drug candidate. For instance, X-ray diffraction (XRD) shows a crystalline behavior for the EPI, which becomes amorphous for the SS. Polarized light microscopy, a more sensitive technique than XRD, also shows completely absence of crystals in SS sample. Differential Scanning Calorimetric (DSC) curves show no signal of EPI melting point in SS curve, indicating, once more, no presence of crystal in this system. Interaction between the drug candidate and the polymer were found in Infrared microscopy, which shows a carbonyl 43.3 cm-1 band shift, indicating a moderate-strong interaction between them, probably one of the reasons to the SS formation. Under sink conditions (pH 6.8), EPI SS had its dissolution performance increased in 2.8 times when compared with the isolated drug candidate. EPI SS sample provided a release of more than 95% of the drug candidate in 15 min, whereas only 45% of EPI (alone) could be dissolved in 15 min and 70% in 90 min. Thus, HPMCP demonstrates to have a good potential to enhance the kinetic solubility profile of EPI. Future studies to evaluate the stability of SS are required to conclude the benefits of this system.

Keywords: epiisopiloturine, hipromellose phthalate HP-55, pharmaceuticaltechnology, solubility

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Authors: Chinedu Ejike

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The United States is now energy self-sufficient due to the production of shale oil reserves. With more than half of it being tapped daily in the United States, these unconventional reserves are massive and provide immense potential for future energy demands. Drilling horizontal wells and fracking are the primary methods for developing these reserves. Regrettably, recovery efficiency is rarely greater than 10%. As a result, optimizing recuperation offers a significant benefit. Huff and puff gas flooding and cyclic gas injection have all been demonstrated to be more successful than tapping the remaining oil in place. Methane, nitrogen, and carbon (IV) oxide, among other high-pressure gases, can be injected. Operators use Darcy's law to assess a reservoir's productive capacity, but they are unaware that the law may not apply to shale oil reserves. This is due to the fact that, unlike pressure differences alone, diffusion, concentration, and gas selection all play a role in the flow of gas injected into the wellbore. The reservoir drainage and oil sweep efficiency rates are determined by the transport method. This research assesses the parameters that influence the gas injection transport mechanism. Understanding the process causing these factors could accelerate recovery by two to three times, according to peer-reviewed studies and effective field testing.

Keywords: enhanced oil recovery, gas injection, shale oil, transport mechanism, unconventional reserve

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Authors: Tadesse Melaku Abegaz

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Background: there was paucity of data on the self-reported adverse drug reactions (ADRs), level of adherence and clinical outcomes with antidepressants among major depressive disorder (MDD) patients in Ethiopia. Hence, the present study sought to determine the level of adherence for and clinical outcome with antidepressants and the magnitude of ADRs. Methods: A prospective cross-sectional study was employed on MDD patients from September 2016 to January 2017 at Gondar university hospital psychiatry clinic. All patients who were available during the study period were included under the study population. The Naranjo adverse drug reaction probability scale was employed to assess the adverse drug reaction. The rate of medication adherence was determined using morisky medication adherence measurement scale eight. Clinical Outcome of patients was measured by using patient health questionnaire. Multivariable logistic carried out to determine factors for adherence and patient outcome. Results: two hundred seventy patients were participated in the study. More than half of the respondents were males 122(56.2%). The mean age of the participants was 30.94 ± 8.853. More than one-half of the subjects had low adherence to their medications 124(57.1%). About 186(85.7%) of patients encountered ADR. The most common ADR was weight gain 29(13.2). Around 198(92.2%) ADRs were probable and 19(8.8%) were possible. Patients with long standing MDD had high risk of non-adherence COR: 2.458[4.413-4.227], AOR: 2.424[1.185-4.961]. More than one-half 125(57.6) of respondents showed improved outcome. Optimal level of medication adherence was found to be associated with reduced risk of progression of the diseases COR: 0.37[0.110-5.379] and AOR: 0.432[0.201-0.909]. Conclusion: Patient reported adverse drug reactions were more prevalent in major depressive disorder patients. Adherence to medications was very poor in the setup. However, the clinical outcome was relatively higher. Long standing depression was associated with non-adherence. In addition, clinical outcome of patients were affected by non-adherence. Therefore, adherence enhancing interventions should be provided to improve medication adherence and patient outcome.

Keywords: adverse drug reactions, clinical outcomes, Ethiopia, prospective study, medication adherence

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Authors: Jinfeng Zhang, Chun-Sing Lee

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Pure nanodrugs (PNDs) – nanoparticles consisting entirely of drug molecules, have been considered as promising candidates for the next-generation nanodrugs. However, the traditional preparation method via reprecipitation faces critical challenges including low production rates, relatively large particle sizes and batch-to-batch variations. Here, for the first time, we successfully developed a novel, versatile and controllable strategy for preparing PNDs via an anodized aluminium oxide (AAO) template-assisted method. With this approach, we prepared PNDs of an anti-cancer drug (VM-26) with precisely controlled sizes reaching the sub-20 nm range. This template-assisted approach has much higher feasibility for mass production comparing to the conventional reprecipitation method and is beneficial for future clinical translation. The present method is further demonstrated to be easily applicable for a wide range of hydrophobic biomolecules without the need of custom molecular modifications and can be extended for preparing all-in-one nanostructures with different functional agents.

Keywords: drug delivery, pure nanodrugs, size control, template

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Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, C. V. Rao

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Elvitegravir is the mainstay of anti-HIV combination therapy in most endemic countries presently. However, it cannot be used alone owing to its long onset time of action. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one (Quercetin: QU) is a polyphenolic compound obtained from Argeria speciosa Linn (Family: Convolvulaceae), an anti-HIV candidate. In the present study, a sensitive, simple and rapid high-performance liquid chromatography coupled with positive ion electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the simultaneous determination elvitegravir and Quercetin, in rat plasma. The method was linear over a range of 0.2–500 ng/ml. All validation parameters met the acceptance criteria according to regulatory guidelines. LC–MS/MS method for determination of Elvitegravir and Quercetin was developed and validated. Results show the potential of drug–drug interaction upon co-administration this marketed drugs and plant derived secondary metabolite.

Keywords: anti-HIV resistance, extraction, HPLC-ESI-MS-MS, validation

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Authors: Ramin Mirzada, Takuya Maruyama

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Kabul is the heart of political, commercial, cultural, educational and social life in Afghanistan and the fifth fastest growing city in the world. Minimum income inclined most of Kabul residents to use public transport, especially buses, although there is no proper bus system, beside that there is no proper fare exist in Kabul city Due to wars. From 1992 to 2001 during civil wars, Kabul suffered damage and destruction of its transportation facilities including pavements, sidewalks, traffic circles, drainage systems, traffic signs and signals, trolleybuses and almost all of the public transport system (e.g. Millie bus). This research is mainly focused on Kabul city’s transportation system. In this research, the data used have been gathered by Japan International Cooperation Agency (JICA) in 2008 and this data will be used to find demand and fare structure, additionally a survey was done in 2016 to find satisfaction level of Kabul residents for fare structure. Aim of this research is to observe the demand for Large Buses, compare to the actual supply from the government, analyze the current fare structure and compare it with the proposed fare (distance based fare) structure which has already been analyzed. Outcome of this research shows that the demand of Kabul city residents for the public transport (Large Buses) exceeds from the current supply, so that current public transportation (Large Buses) is not sufficient to serve public transport in Kabul city, worth to be mentioned, that in order to overcome this problem, there is no need to build new roads or exclusive way for buses. This research proposes government to change the fare from fixed fare to distance based fare, invest on public transportation and increase the number of large buses so that the current demand for public transport is met.

Keywords: transportation, planning, public transport, large buses, Kabul, Afghanistan

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Authors: U. Farooq, A. Samson, V. Thangadurai, R. Edwards

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In recent years, an impressive research has been conducted to introduce the solid-state electrolytes for the future energy storage devices like Li-ion batteries more specifically. In this work we tried to prepare a ceramic electrolyte (Li6.5 La2.5 Ba0.5 Nb Zr O12(LLBNZO)) and sintered the pallets of as-prepared material at elevated temperature like 1050, 1100, 1150 and 1200 °C. The objective to carry out this research was to observe the effect of temperature on porosity, density and transport properties of materials. Preliminary results suggest that the material sintered at higher temperature could show enhanced performance in terms of fast ionic transport. This enhancement in performance can be attributed to low porosity of materials which is result of high temperature sintering.

Keywords: solid state battery, electrolyte, garnet structures, Li-ion battery

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Authors: Walter Vera-Ortega, Idoia Busnadiego, Sam J. Wilson

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Introduction: Human Immunodeficiency Virus type 1 (HIV-1) is responsible for the acquired immunodeficiency syndrome (AIDS), a leading cause of death worldwide infecting millions of people each year. Despite intensive research in vaccine development, therapies against HIV-1 infection are not curative, and the huge genetic variability of HIV-1 challenges to drug development. Current animal models for HIV-1 research present important limitations, impairing the progress of in vivo approaches. Macaques require a CD8+ depletion to progress to AIDS, and the maintenance cost is high. Mice are a cheaper alternative but need to be 'humanized,' and breeding is not possible. The development of an HIV-1 clone able to replicate in mice is a challenging proposal. The lack of human co-factors in mice impedes the function of the HIV-1 accessory proteins, Tat and Rev, hampering HIV-1 replication. However, Tat and Rev function can be replaced by constitutive/chimeric promoters, codon-optimized proteins and the constitutive transport element (CTE), generating a novel HIV-1 clone able to replicate in mice without disrupting the amino acid sequence of the virus. By minimally manipulating the genomic 'identity' of the virus, we propose the generation of an HIV-1 clone able to replicate in mice to assist in antiviral drug development. Methods: i) Plasmid construction: The chimeric promoters and CTE copies were cloned by PCR using lentiviral vectors as templates (pCGSW and pSIV-MPCG). Tat mutants were generated from replication competent HIV-1 plasmids (NHG and NL4-3). ii) Infectivity assays: Retroviral vectors were generated by transfection of human 293T cells and murine NIH 3T3 cells. Virus titre was determined by flow cytometry measuring GFP expression. Human B-cells (AA-2) and Hela cells (TZMbl) were used for infectivity assays. iii) Protein analysis: Tat protein expression was determined by TZMbl assay and HIV-1 capsid by western blot. Results: We have determined that NIH 3T3 cells are able to generate HIV-1 particles. However, they are not infectious, and further analysis needs to be performed. Codon-optimized HIV-1 constructs are efficiently made in 293T cells in a Tat and Rev independent manner and capable of packaging a competent genome in trans. CSGW is capable of generating infectious particles in the absence of Tat and Rev in human cells when 4 copies of the CTE are placed preceding the 3’LTR. HIV-1 Tat mutant clones encoding different promoters are functional during the first cycle of replication when Tat is added in trans. Conclusion: Our findings suggest that the development of an HIV-1 Tat-Rev independent clone is challenging but achievable aim. However, further investigations need to be developed prior presenting our HIV-1 clone as a candidate model for research.

Keywords: codon-optimized, constitutive transport element, HIV-1, long terminal repeats, research model

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

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Authors: Ahmad Samim Ranjbar, Shoshi Mizokami

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Kabul is the heart of political, commercial, cultural, educational and social life in Afghanistan and the Kabul fifth fastest growing city in the world, since 2001 with the establishment of new government Lack of adequate employment opportunities and basic utility services in remote provinces have prompted people to move to Kabul and other urban areas. From 2001 to the present, a rapid increase in population, and also less income of the people most of residence tend to use public transport, especially buses, however there is no proper bus system exist in Kabul city, because of wars, from 1992 to 2001 Kabul suffered damage and destruction of its transportation facilities including pavements, sidewalks, traffic circles, drainage systems, traffic signs and signals, trolleybuses and almost all of the public transit buses (e.g. Millie bus). This research is a primary and very important phase into Kabul city transportation and especially an initial and important step toward using large bus in Kabul city, which the main purpose of this research is to find the demand of Kabul city residence for public transport (Large Bus) and compare it with the actual supply from government. Finding of this research shows that the demand of Kabul city residence for the public transport (Large Bus) exceed the supply from the government, means that current public transportation (Large Bus) is not sufficient to serve people of Kabul city, it is mentionable that according to this research there is no need to build a new road or exclusive way for bus, this research propose to government for investment on the public transportation and exceed the number of large buses to can handle the current demand for public transport.

Keywords: transportation, planning, public transport, large bus, Kabul, Afghanistan

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Authors: Congping Lin

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Intracellular transport in fungi has a number of important roles in, e.g., filamentous fungal growth and cellular metabolism. Two basic mechanisms for intracellular transport are motor-driven trafficking along microtubules (MTs) and diffusion. Mathematical modelling has been actively developed to understand such intracellular transport and provide unique insight into cellular complexity. Based on live-cell imaging data in Ustilago hyphal cells, probabilistic models have been developed to study mechanism underlying spatial organization of molecular motors and organelles. In particular, anther mechanism - stochastic motility of dynein motors along MTs has been found to contribute to half of its accumulation at hyphal tip in order to support early endosome (EE) recycling. The EE trafficking not only facilitates the directed motion of peroxisomes but also enhances their diffusive motion. Considering the importance of spatial organization of early endosomes in supporting peroxisome movement, computational and experimental approaches have been combined to a whole-cell level. Results from this interdisciplinary study promise insights into requirements for other membrane trafficking systems (e.g., in neurons), but also may inform future 'synthetic biology' studies.

Keywords: intracellular transport, stochastic process, molecular motors, spatial organization

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Authors: Huafeng Wei

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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: Zhi Hao Chow, Cian Mulligan, Jack Walsh, Antonio Garzon Vico, Dimitar Krastev

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Drug development is resource-intensive, time-consuming, and increasingly expensive with each developmental stage. The success rates of drug development are also relatively low, and the resources committed are wasted with each failed candidate. As such, a reliable method of predicting the success of drug development is in demand. The hypothesis was that some examples of failed drug candidates are pushed through developmental pipelines based on false confidence and may possess common linguistic features identifiable through sentiment analysis. Here, the concept of using text analysis to discover such features in research publications and investor reports as predictors of success was explored. R studios were used to perform text mining and lexicon-based sentiment analysis to identify affective phrases and determine their frequency in each document, then using SPSS to determine the relationship between our defined variables and the accuracy of predicting outcomes. A total of 161 publications were collected and categorised into 4 groups: (i) Cancer treatment, (ii) Neurodegenerative disease treatment, (iii) Vaccines, and (iv) Others (containing all other drugs that do not fit into the 3 categories). Text analysis was then performed on each document using 2 separate datasets (BING and AFINN) in R within the category of drugs to determine the frequency of positive or negative phrases in each document. A relative positivity and negativity value were then calculated by dividing the frequency of phrases with the word count of each document. Regression analysis was then performed with SPSS statistical software on each dataset (values from using BING or AFINN dataset during text analysis) using a random selection of 61 documents to construct a model. The remaining documents were then used to determine the predictive power of the models. Model constructed from BING predicts the outcome of drug performance in clinical trials with an overall percentage of 65.3%. AFINN model had a lower accuracy at predicting outcomes compared to the BING model at 62.5% but was not effective at predicting the failure of drugs in clinical trials. Overall, the study did not show significant efficacy of the model at predicting outcomes of drugs in development. Many improvements may need to be made to later iterations of the model to sufficiently increase the accuracy.

Keywords: data analysis, drug development, sentiment analysis, text-mining

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Authors: X. King, E. Nazarzadeh, J. Reboud, J. Cooper

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Pulmonary diseases, such as asthma, are generally treated by the inhalation of aerosols that has the advantage of reducing the off-target (e.g., toxicity) effects associated with systemic delivery in blood. Effective respiratory drug delivery requires a droplet size distribution between 1 and 5 µm. Inhalation of aerosols with wide droplet size distribution, out of this range, results in deposition of drug in not-targeted area of the respiratory tract, introducing undesired side effects on the patient. In order to solely deliver the drug in the lower branches of the lungs and release it in a targeted manner, a control mechanism to produce the aerosolized droplets is required. To regulate the drug release and to facilitate the uptake from cells, drugs are often encapsulated into protective liposomes. However, a multistep process is required for their formation, often performed at the formulation step, therefore limiting the range of available drugs or their shelf life. Using surface acoustic waves (SAWs), a pulmonary drug delivery platform was produced, which enabled the formation of defined size aerosols and the formation of liposomes in situ. SAWs are mechanical waves, propagating along the surface of a piezoelectric substrate. They were generated using an interdigital transducer on lithium niobate with an excitation frequency of 9.6 MHz at a power of 1W. Disposable silicon superstrates were etched using photolithography and dry etch processes to create an array of cylindrical through-holes with different diameters and pitches. Superstrates were coupled with the SAW substrate through water-based gel. As the SAW propagates on the superstrate, it enables nebulisation of a lipid solution deposited onto it. The cylindrical cavities restricted the formation of large drops in the aerosol, while at the same time unilamellar liposomes were created. SAW formed liposomes showed a higher monodispersity compared to the control sample, as well as displayed, a faster production rate. To test the aerosol’s size, dynamic light scattering and laser diffraction methods were used, both showing the size control of the aerosolised particles. The use of silicon superstate with cavity size of 100-200 µm, produced an aerosol with a mean droplet size within the optimum range for pulmonary drug delivery, containing the liposomes in which the medicine could be loaded. Additionally, analysis of liposomes with Cryo-TEM showed formation of vesicles with narrow size distribution between 80-100 nm and optimal morphology in order to be used for drug delivery. Encapsulation of nucleic acids in liposomes through the developed SAW platform was also investigated. In vitro delivery of siRNA and DNA Luciferase were achieved using A549 cell line, lung carcinoma from human. In conclusion, SAW pulmonary drug delivery platform was engineered, in order to combine multiple time consuming steps (formation of liposomes, drug loading, nebulisation) into a unique platform with the aim of specifically delivering the medicament in a targeted area, reducing the drug’s side effects.

Keywords: acoustics, drug delivery, liposomes, surface acoustic waves

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Authors: Jerzy Merkisz, Piotr Lijewski, Pawel Fuc, Maciej Siedlecki, Andrzej Ziolkowski, Sylwester Weymann

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The paper discusses the problem of load transport using farm tractors and road tractor units. This type of carriage of goods is often done with farm vehicles. The tests were performed with the PEMS equipment (Portable Emission Measurement System) under actual traffic conditions. The vehicles carried a load of 20000 kg. This research method is one of the most desired because it provides reliable information on the actual vehicle emissions and fuel consumption (carbon balance method). For the tests, a route was selected that simulated a trip from a small town to a food-processing facility located in a city. The analysis of the obtained results gave a clear answer as to what vehicles need to be used for the carriage of this type of cargo in terms of exhaust emissions and fuel consumption.

Keywords: emission, transport, fuel consumption, PEMS

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Authors: Jaeun Park, Daekyoung Kim, Ho Kyoon Chung, Heeyeop Chae

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Quantum dots light-emitting diodes (QD-LEDs) have been considered as the next generation display and lighting devices due to their excellent color purity, photo-stability solution process possibility and good device stability. Currently typical quantum dot light emitting diodes contain organic layers such as PEDOT:PSS and PVK for charge transport layers. To make quantum dot light emitting diodes (QD-LED) more stable, it is required to replace those acidic and relatively unstable organic charge transport layers with inorganic materials. Therefore all inorganic and solution processed quantum dot light emitting diodes can potentially be a solution to stable and cost-effective display devices. We studied solution processed NiO films to replace organic charge transport layers that are required for stable all-inorganic based light emitting diodes. The transition metal oxides can be made by various vacuum and solution processes, but the solution processes are considered more cost-effective than vacuum processes. In this work we investigated solution processed NiOx for a hole transport layer (HTL). NiOx, has valence band energy levels of 5.3eV and they are easy to make sol-gel solutions. Water vapor oxidation process was developed and applied to solution processed all-inorganic QD-LED. Turn-on voltage, luminance and current efficiency of QD in this work were 5V, 1800Cd/m2 and 0.5Cd/A, respectively.

Keywords: QD-LED, metal oxide solution, NiO, all-inorganic QD-LED device

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Authors: Minh-Phuong Ngoc Bui, Abdennour Abbas

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Microbial spoilage of food/drug has been a constant nuisance and an unavoidable problem throughout history that affects food/drug quality and safety in a variety of ways. A simple and rapid test of fungi and bacteria in food/drugs and environmental clinical samples is essential for proper management of contamination. A number of different techniques have been developed for detection and enumeration of foodborne microorganism including plate counting, enzyme-linked immunosorbent assay (ELISA), polymer chain reaction (PCR), nucleic acid sensor, electrical and microscopy methods. However, the significant drawbacks of these techniques are highly demand of operation skills and the time and cost involved. In this report, we introduce a rapid method for detection of bacteria and fungi in food/drug products using a specific interaction between a reducing agent (tris(2-carboxylethyl)phosphine (TCEP)) and the microbial surface proteins. The chemical reaction was transferred to a transduction system using gold nanoplates-enhanced chemiluminescence. We have optimized our nanoplates synthetic conditions, characterized the chemiluminescence parameters and optimized conditions for the microbial assay. The new detection method was applied for rapid detection of bacteria (E.coli sp. and Lactobacillus sp.) and fungi (Mucor sp.), with limit of detection as low as single digit cells per mL within 10 min using a portable luminometer. We expect our simple and rapid detection method to be a powerful alternative to the conventional plate counting and immunoassay methods for rapid screening of microorganisms in food/drug products.

Keywords: microorganism testing, gold nanoplates, chemiluminescence, reducing agents, luminol

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Authors: Hamida Hamed Said Al Harthi

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Background: Illegal drug use is a rising problem that affects Omani youth. This research aimed to study a group of young Omani men who were imprisoned more than once for illegal drug use, focusing on exploring their lifestyle experiences inside and outside the prison and whether these contributed to their early relapse and re-imprisonment. This is the first study of its kind from Oman conducted in a prison setting. Methods: 19 Omani males aged 18–35 years imprisoned in Oman Central Prison were recruited using purposive sampling. Focused ethnography was conducted over 8 months to explore the drug-related experiences outside the prison and during imprisonment. Face-to-face semi-structured interviews with the participants yielded detailed transcripts and field notes. These were thematically analyzed, and the results were compared with the existing literature. Results: The participants’ voices yielded new insights into the lives of young Omani men imprisoned for illegal drug use, including their sufferings and challenges in prison. These included: entry shock, timing and boredom, drug trafficking in prison, as well as physical and psychological health issues. Overall, imprisonment was reported to have negatively impacted the participants’ health, personality, self-concept, emotions, attitudes, behavior and life expectations. The participants reported how their efforts to reintegrate into the Omani community after release from prison were rebuffed due to stigmatization and rejection from society and family. They also experienced frequent unemployment, police surveillance, accommodation problems and a lack of rehabilitation facilities. The immensity of the accumulated psychophysiological trauma contributed to their early relapse and re-imprisonment. Conclusion: This thesis concludes that imprisonment is largely ineffective in controlling drug use in Oman. Urgent action is required across multiple sectors to improve the lives and prospects of users of illegal drugs within and outside the prison to minimize factors contributing to early relapse. Key Words: illegal drugs, drug users, Oman, addiction, Omani culture, prisoners, relapse, re-imprisonment, qualitative research, ethnography.

Keywords: illigal drugs, Prison, Omani culture lifestyle, post prison life

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Authors: Amit Kumar Jain, Surbhi Jain

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The urban freight in a city constitutes 10 to 18 per cent of all city road traffic, and 40 per cent of air pollution and noise emissions, are directly related to commercial transport. The policy measures implemented by urban planners have sought to restrict rather than assist goods-vehicle operations. This approach has temporarily controlled the urban transport demand during peak hours of traffic but has not effectively solved transport congestion. The solution discussed in the paper envisages the development of a comprehensive network of Urban Freight Stations (UFS) connected through underground conveyor belts in the city in line with baggage segregation and distribution in any of the major airports. The transportation of freight shall be done in standard size containers/cars through rail borne carts. The freight can be despatched or received from any of the UFS. Once freight is booked for a destination from any of the UFS, it would be stuffed in the container and digitally tagged for the destination. The container would reach the destination UFS through a network of rail borne carts. The container would be de-stuffed at the destination UFS and sent for further delivery, or the consignee may be asked to collect the consignment from urban freight station. The obvious benefits would be decongestion of roads, reduction in air and noise pollution, saving in manpower used for freight transportation.

Keywords: congestion, urban freight, intelligent transport system, pollution

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Authors: M. Imran Hossen Khan, M. Mahiuddin, M. A. Karim

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Drying is a food processing technique where simultaneous heat and mass transfer take place from surface to the center of the sample. Deformation of food materials during drying is a common physical phenomenon which affects the textural quality and taste of the dried product. Most of the plant-based food materials are porous and hygroscopic in nature that contains about 80-90% water in different cellular environments: intercellular environment and intracellular environment. Transport of this cellular water has a significant effect on material deformation during drying. However, understanding of the scale of deformation is very complex due to diverse nature and structural heterogeneity of food material. Knowledge about the effect of transport of cellular water on deformation of material during drying is crucial for increasing the energy efficiency and obtaining better quality dried foods. Therefore, the primary aim of this work is to investigate the effect of intracellular water transport on material deformation during drying. In this study, apple tissue was taken for the investigation. The experiment was carried out using 1H-NMR T2 relaxometry with a conventional dryer. The experimental results are consistent with the understanding that transport of intracellular water causes cellular shrinkage associated with the anisotropic deformation of whole apple tissue. Interestingly, it is found that the deformation of apple tissue takes place at different stages of drying rather than deforming at one time. Moreover, it is found that the penetration rate of heat energy together with the pressure gradient between intracellular and intercellular environments is the responsible force to rupture the cell membrane.

Keywords: heat and mass transfer, food material, intracellular water, cell rupture, deformation

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Authors: Abhay Asthana, Gyati Shilakari Asthana

Abstract:

It’s the patient compliance and stability in combination with controlled drug delivery and biocompatibility that forms the core feature in present research and development of sustained biodegradable patch formulation intended for wound healing. The aim was to impart sustained degradation, sterile formulation, significant folding endurance, elasticity, biodegradability, bio-acceptability and strength. The optimized formulation was developed using component including polymers including Hydroxypropyl methyl cellulose, Ethylcellulose, and Gelatin, and Citric Acid PEG Citric acid (CPEGC) triblock dendrimers and active Curcumin. Polymeric mixture dissolved in geometric order in suitable medium through continuous stirring under ambient conditions. With continued stirring Curcumin was added with aid of DCM and Methanol in optimized ratio to get homogenous dispersion. The dispersion was sonicated with optimum frequency and for given time and later casted to form a patch form. All steps were carried out under under strict aseptic conditions. The formulations obtained in the acceptable working range were decided based on thickness, uniformity of drug content, smooth texture and flexibility and brittleness. The patch kept on stability using butter paper in sterile pack displayed folding endurance in range of 20 to 23 times without any evidence of crack in an optimized formulation at room temperature (RT) (24 ± 2°C). The patch displayed acceptable parameters after stability study conducted in refrigerated conditions (8±0.2°C) and at RT (24 ± 2°C) upto 90 days. Further, no significant changes were observed in critical parameters such as elasticity, biodegradability, drug release and drug content during stability study conducted at RT 24±2°C for 45 and 90 days. The drug content was in range 95 to 102%, moisture content didn’t exceeded 19.2% and patch passed the content uniformity test. Percentage cumulative drug release was found to be 80% in 12h and matched the biodegradation rate as drug release with correlation factor R2>0.9. The biodegradable patch based formulation developed shows promising results in terms of stability and release profiles.

Keywords: sustained biodegradation, wound healing, polymers, stability

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