Search results for: drug transport
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3846

Search results for: drug transport

2136 Effectiveness, Safety, and Tolerability Profile of Stribild® in HIV-1-infected Patients in the Clinical Setting

Authors: Heiko Jessen, Laura Tanus, Slobodan Ruzicic

Abstract:

Objectives: The efficacy of Stribild®, an integrase strand transfer inhibitor (INSTI) -based STR, has been evaluated in randomized clinical trials and it has demonstrated durable capability in terms of achieving sustained suppression of HIV-1 RNA-levels. However, differences in monitoring frequency, existing selection bias and profile of patients enrolled in the trials, may all result in divergent efficacy of this regimen in routine clinical settings. The aim of this study was to assess the virologic outcomes, safety and tolerability profile of Stribild® in a routine clinical setting. Methods: This was a retrospective monocentric analysis on HIV-1-infected patients, who started with or were switched to Stribild®. Virological failure (VF) was defined as confirmed HIV-RNA>50 copies/ml. The minimum time of follow-up was 24 weeks. The percentage of patients remaining free of therapeutic failure was estimated using the time-to-loss-of-virologic-response (TLOVR) algorithm, by intent-to-treat analysis. Results: We analyzed the data of 197 patients (56 ART-naïve and 141 treatment-experienced patients), who fulfilled the inclusion criteria. Majority (95.9%) of patients were male. The median time of HIV-infection at baseline was 2 months in treatment-naïve and 70 months in treatment-experienced patients. Median time [IQR] under ART in treatment-experienced patients was 37 months. Among the treatment-experienced patients 27.0% had already been treated with a regimen consisting of two NRTIs and one INSTI, whereas 18.4% of them experienced a VF. The median time [IQR] of virological suppression prior to therapy with Stribild® in the treatment-experienced patients was 10 months [0-27]. At the end of follow-up (median 33 months), 87.3% (95% CI, 83.5-91.2) of treatment-naïve and 80.3% (95% CI, 75.8-84.8) of treatment-experienced patients remained free of therapeutic failure. Considering only treatment-experienced patients with baseline VL<50 copies/ml, 83.0% (95% CI, 78.5-87.5) remained free of therapeutic failure. A total of 17 patients stopped treatment with Stribild®, 5.4% (3/56) of them were treatment-naïve and 9.9% (14/141) were treatment-experienced patients. The Stribild® therapy was discontinued in 2 (1.0%) because of VF, loss to follow-up in 4 (2.0%), and drug-drug interactions in 2 (1.0%) patients. Adverse events were in 7 (3.6%) patients the reason to switch from therapy with Stribild® and further 2 (1.0%) patients decided personally to switch. The most frequently observed adverse events were gastrointestinal side effects (20.0%), headache (8%), rash events (7%) and dizziness (6%). In two patients we observed an emergence of novel resistances in integrase-gene. The N155H evolved in one patient and resulted in VF. In another patient S119R evolved either during or shortly upon switch from therapy with Stribild®. In one further patient with VF two novel mutations in the RT-gene were observed when compared to historical genotypic test result (V106I/M and M184V), whereby it is not clear whether they evolved during or already before the switch to Stribild®. Conclusions: Effectiveness of Stribild® for treatment-naïve patients was consistent with data obtained in clinical trials. The safety and tolerability profile as well as resistance development confirmed clinical efficacy of Stribild® in a daily practice setting.

Keywords: ART, HIV, integrase inhibitor, stribild

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2135 Linear Study of Electrostatic Ion Temperature Gradient Mode with Entropy Gradient Drift and Sheared Ion Flows

Authors: M. Yaqub Khan, Usman Shabbir

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History of plasma reveals that continuous struggle of experimentalists and theorists are not fruitful for confinement up to now. It needs a change to bring the research through entropy. Approximately, all the quantities like number density, temperature, electrostatic potential, etc. are connected to entropy. Therefore, it is better to change the way of research. In ion temperature gradient mode with the help of Braginskii model, Boltzmannian electrons, effect of velocity shear is studied inculcating entropy in the magnetoplasma. New dispersion relation is derived for ion temperature gradient mode, and dependence on entropy gradient drift is seen. It is also seen velocity shear enhances the instability but in anomalous transport, its role is not seen significantly but entropy. This work will be helpful to the next step of tokamak and space plasmas.

Keywords: entropy, velocity shear, ion temperature gradient mode, drift

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2134 Quality Assessment of the Given First Aid on the Spot Events in the Opinion of Members of the Teams of the Medical Rescue in Warsaw in Poland

Authors: Aneta Binkowska, Artur Kamecki

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The ability to provide first aid should be one of the basic skills of each of us. First aid by the Law on National Medical Emergency dated 8 September 2006 as amended, is a set of actions undertaken to save a person at the scene of an accident. In Poland, on the basis of Article 162 of the Criminal Code, we are obliged to provide first aid to the victim. In addition, according to a large part of society, unselfishness towards others in need of help is our moral obligation. The aim of the study was to learn the opinion of the members of Medical Rescue Teams (MRT) of the ‘Meditrans’ Provincial Ambulance and Sanitary Transport Service (PA and STS ‘Meditrans’) in Warsaw on how people react in real situations threatening life or health of the injured person. The study was conducted in the third quarter of 2015 on 335 members of medical rescue teams, including 77 W and 258 M, who provided medical services in the ‘Meditrans’ Provincial Ambulance and Sanitary Transport Service MRT in Warsaw. The research tool was an anonymous questionnaire survey of own design, which consisted of 12 questions: closed, half open and one open question. Respondents were divided into 3 age groups and by individual medical professions (doctor, paramedic, nurse). The straight majority of respondents encountered granting the first aid the event on the spot. However, the frequency of appearing in such proceedings isn’t too high. The first aid has most often been given in the street and in houses. The final audited fairly important element is the reason not to provide first aid by bystanders in the opinion of members of the medical teams. Respondents to this question, which was an open question were asked to name the reason for not taking any action while waiting for an ambulance. Over 50% of respondents could not answer. The most common answers were: fear, lack of knowledge and skills, reluctance, indifference, lack of training, lack of experience and fear that harm. Conclusion: The majority of respondents have encountered instances of first aid provision, but respondents assessed the frequency of such situations as low. Placing the victim in the recovery position is the simplest and most common form of first aid. Therefore, training should be introduced not only on CPR but also in the scope of helping persons in sudden health emergency, who do not have a sudden cardiac arrest. A statement can be formulated, as a main conclusion of the analysis, that only continuous education and in particular practical training will help people to overcome the barrier of their limitations in order to help others. Among the largest group of witnesses providing first aid are the elderly and youth, who are subjected to various forms of education related to first aid provision.

Keywords: BLS, first aid, medical rescue, resuscitation

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2133 Analyzing Transit Network Design versus Urban Dispersion

Authors: Hugo Badia

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This research answers which is the most suitable transit network structure to serve specific demand requirements in an increasing urban dispersion process. Two main approaches of network design are found in the literature. On the one hand, a traditional answer, widespread in our cities, that develops a high number of lines to connect most of origin-destination pairs by direct trips; an approach based on the idea that users averse to transfers. On the other hand, some authors advocate an alternative design characterized by simple networks where transfer is essential to complete most of trips. To answer which of them is the best option, we use a two-step methodology. First, by means of an analytical model, three basic network structures are compared: a radial scheme, starting point for the other two structures, a direct trip-based network, and a transfer-based one, which represent the two alternative transit network designs. The model optimizes the network configuration with regard to the total cost for each structure. For a scenario of dispersion, the best alternative is the structure with the minimum cost. This dispersion degree is defined in a simple way considering that only a central area attracts all trips. If this area is small, we have a high concentrated mobility pattern; if this area is too large, the city is highly decentralized. In this first step, we can determine the area of applicability for each structure in function to that urban dispersion degree. The analytical results show that a radial structure is suitable when the demand is so centralized, however, when this demand starts to scatter, new transit lines should be implemented to avoid transfers. If the urban dispersion advances, the introduction of more lines is no longer a good alternative, in this case, the best solution is a change of structure, from direct trips to a network based on transfers. The area of applicability of each network strategy is not constant, it depends on the characteristics of demand, city and transport technology. In the second step, we translate analytical results to a real case study by the relationship between the parameters of dispersion of the model and direct measures of dispersion in a real city. Two dimensions of the urban sprawl process are considered: concentration, defined by Gini coefficient, and centralization by area based centralization index. Once it is estimated the real dispersion degree, we are able to identify in which area of applicability the city is located. In summary, from a strategic point of view, we can obtain with this methodology which is the best network design approach for a city, comparing the theoretical results with the real dispersion degree.

Keywords: analytical network design model, network structure, public transport, urban dispersion

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2132 Amino Acid Based Biodegradable Amphiphilic Polymers and Micelles as Drug Delivery Systems: Synthesis and Study

Authors: Sophio Kobauri, Vladimir P. Torchilin, David Tugushi, Ramaz Katsarava

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Nanotherapy is an actual newest mode of treatment numerous diseases using nanoparticles (NPs) loading with different pharmaceuticals. NPs of biodegradable polymeric micelles (PMs) are gaining increased attention for their numerous and attractive abilities to be used in a variety of applications in the various fields of medicine. The present paper deals with the synthesis of a class of biodegradable micelle-forming polymers, namely ABA triblock-copolymer in which A-blocks represent amino-poly(ethylene glycol) (H2N-PEG) and B-block is biodegradable amino acid-based poly(ester amide) constituted of α-amino acid – L-phenylalanine. The obtained copolymer formed micelles of 70±4 nm size at 10 mg/mL concentration.

Keywords: amino acids, biodegradable poly (ester amide), amphiphilic triblock-copolymer, micelles

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2131 Choice of Sleeper and Rail Fastening Using Linear Programming Technique

Authors: Luciano Oliveira, Elsa Vásquez-Alvarez

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The increase in rail freight transport in Brazil in recent years requires new railway lines and the maintenance of existing ones, which generates high costs for concessionaires. It is in this context that this work is inserted, whose objective is to propose a method that uses Binary Linear Programming for the choice of sleeper and rail fastening, from various options, including the way to apply these materials, with focus to minimize costs. Unit value information, the life cycle each of material type, and service expenses are considered. The model was implemented in commercial software using real data for its validation. The formulated model can be replicated to support decision-making for other railway projects in the choice of sleepers and rail fastening with lowest cost.

Keywords: linear programming, rail fastening, rail sleeper, railway

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2130 Data Mining Techniques for Anti-Money Laundering

Authors: M. Sai Veerendra

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Today, money laundering (ML) poses a serious threat not only to financial institutions but also to the nation. This criminal activity is becoming more and more sophisticated and seems to have moved from the cliché of drug trafficking to financing terrorism and surely not forgetting personal gain. Most of the financial institutions internationally have been implementing anti-money laundering solutions (AML) to fight investment fraud activities. However, traditional investigative techniques consume numerous man-hours. Recently, data mining approaches have been developed and are considered as well-suited techniques for detecting ML activities. Within the scope of a collaboration project on developing a new data mining solution for AML Units in an international investment bank in Ireland, we survey recent data mining approaches for AML. In this paper, we present not only these approaches but also give an overview on the important factors in building data mining solutions for AML activities.

Keywords: data mining, clustering, money laundering, anti-money laundering solutions

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2129 Traditional Phytotherapy among Tribes of Madhya Pradesh, India Used in the Treatment of Ear, Nose and Throat Disorders

Authors: Sumeet Dwivedi, Shweta Shriwas, Raghvendra Dubey

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Madhya Pradesh, a Central State of India is rich in natural heritage due to tribal impact. Herbal harmony present either cultivated or by naturally being used by the tribes of the state in the treatment of several human and animal disorders. Diseases of ear, nose and throat (ENT) often have serious consequences including hearing impairment, and emotional strain that lower the quality of life of patients. Traditional phytotherapy have now been found to be instrumental in improving chances of discovering plants with antimicrobial activity in new drug development. The present paper enumerates the uses of ten herbs viz., garlic, eucalyptus, marigold, tulsi, euphorbia, lemon grass, haldi, bhringraj, ginger and ajwain. An attempt has also been made to reveal the method of preparation, dose, duration possible MOA of these herbs used for ENT disorders.

Keywords: ENT, traditional phytotherapy, herbs, Madhya Pradesh

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2128 Self-Tuning Robot Control Based on Subspace Identification

Authors: Mathias Marquardt, Peter Dünow, Sandra Baßler

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The paper describes the use of subspace based identification methods for auto tuning of a state space control system. The plant is an unstable but self balancing transport robot. Because of the unstable character of the process it has to be identified from closed loop input-output data. Based on the identified model a state space controller combined with an observer is calculated. The subspace identification algorithm and the controller design procedure is combined to a auto tuning method. The capability of the approach was verified in a simulation experiments under different process conditions.

Keywords: auto tuning, balanced robot, closed loop identification, subspace identification

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2127 Prediction of CO2 Concentration in the Korea Train Express (KTX) Cabins

Authors: Yong-Il Lee, Do-Yeon Hwang, Won-Seog Jeong, Duckshin Park

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Recently, because of the high-speed trains forced ventilation, it is important to control the ventilation. The ventilation is for controlling various contaminants, temperature, and humidity. The high-speed train route is straight to a destination having a high speed. And there are many mountainous areas in Korea. So, tunnel rate is higher then other country. KTX HVAC block off the outdoor air, when entering tunnel. So the high tunnel rate is an effect of ventilation in the KTX cabin. It is important to reduction rate in CO2 concentration prediction. To meet the air quality of the public transport vehicles recommend standards, the KTX cabin of CO2 concentration should be managed. In this study, the concentration change was predicted by CO2 prediction simulation in route to be opened.

Keywords: CO2 prediction, KTX, ventilation, infrastructure and transportation engineering

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2126 Electrodeposition of Nickel-Zinc Alloy on Stainless Steel in a Magnetic Field in a Chloride Environment

Authors: Naima Benachour, Sabiha Chouchane, J. Paul Chopart

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The objective of this work is to determine the appropriate conditions for a Ni-Zn deposit with good nickel content. The electrodeposition of zinc-nickel on a stainless steel is carried out in a chlorinated bath NiCl2.6H2O, ZnCl2, and H3BO3), whose composition is 1.1 M; 1.8 M; 0.1 M respectively. Studies show the effect of the concentration of NH4Cl, which reveals a significant effect on the reduction and ion transport in the electrolyte. In order to highlight the influence of magnetic field on the chemical composition and morphology of the deposit, chronopotentiometry tests were conducted, the curves obtained inform us that the application of a magnetic field promotes stability of the deposit. Characterization developed deposits was performed by scanning electron microscopy coupled with EDX and specified by the X-ray diffraction.

Keywords: Zn-Ni alloys, electroplating, magnetic field, chronopotentiometry

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2125 Oblique Wing: Future Generation Transonic Aircraft

Authors: Mushfiqul Alam, Kashyapa Narenathreyas

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The demand for efficient transonic transport has been growing every day and may turn out to be the most pressed innovation in coming years. Oblique wing configuration was proposed as an alternative to conventional wing configuration for supersonic and transonic passenger aircraft due to its aerodynamic advantages. This paper re-demonstrates the aerodynamic advantages of oblique wing configuration using open source CFD code. The aerodynamic data were generated using Panel Method. Results show that Oblique Wing concept with elliptical wing planform offers a significant reduction in drag at transonic and supersonic speeds and approximately twice the lift distribution compared to conventional operating aircrafts. The paper also presents a preliminary conceptual aircraft sizing which can be used for further experimental analysis.

Keywords: aerodynamics, asymmetric sweep, oblique wing, swing wing

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2124 Analysis of Magnesium Alloy Wheel Forming Technologies for Light Vehicles

Authors: Anna Dziubinska

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The applications of magnesium alloys in transport include all kinds of vehicle wheels for cars, motorcycles, bicycles, trolleys, etc. Modern technologies of manufacturing products from these materials have been noticeably improved recently, creating new possibilities for their application. Continuously developed technologies for forming Mg alloys must not be overlooked, which make it possible to manufacture products with better properties compared to those obtained by casting only. The article reviews the specialized literature on magnesium wheel forming and presents a concept of technology for forging magnesium wheels for light vehicles from cast preforms. The research leading to these results has received funding from the Norway Grants 2014-2021 via the National Centre for Research and Development.

Keywords: forming, forging, magnesium alloy, wheels, vehicles

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2123 A Spin and Valley Modulating Device in Grapheme heterostructure: Controlling Valley and Spin Current

Authors: Adel Belayadi

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The investigation of two-dimensional (2D) heterostructures, whether in the presence or the absence of magnetic substrates that sustain several induced spin-orbit couplings, has shown a promising/essential application for advancing the emerging fields of spintronics and valleytronics. In this contribution, we study spin/valley transport in graphene-like substrates in the presence of one or several locally induced spin-orbit coupling (SOC) terms resulting from graphene-based heterostructures. The models we proposed are based on the tight-binding approach, and our findings imply an alternative approach for conducting valley-polarized currents and suggest a corresponding mechanism for valley-dependent electron optics and optoelectronic devices.

Keywords: graphene-heterostructures, tight binding pproch, Spintronics, Valleytronics

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2122 Effect of Hemicellulase on Extraction of Essential Oil from Algerian Artemisia campestris

Authors: Khalida Boutemak, Nasssima Benali, Nadji Moulai-Mostefa

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Effect of enzyme on the yield and chemical composition of Artemisia campestris essential oil is reported in the present study. It was demonstrated that enzyme facilitated the extraction of essential oil with increase in oil yield and did not affect any noticeable change in flavour profile of the volatile oil. Essential oil was tested for antibacterial activity using Escherichia coli; which was extremely sensitive against control with the largest inhibition (29mm), whereas Staphylococcus aureus was the most sensitive against essential oil obtained from enzymatic pre-treatment with the largest inhibition zone (25mm). The antioxidant activity of the essential oil with hemicellulase pre-treatment (EO2) and control sample (EO1) was determined through reducing power. It was significantly lower than the standard drug (vitamin C) in this order: vitamin C˃EO2˃EO1.

Keywords: Artemisia campestris, enzyme pre-treatment, hemicellulase, antibacterial activity, antioxidant activity

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2121 Enhanced Thermal and Electrical Properties of Terbium Manganate-Polyvinyl Alcohol Nanocomposite Film

Authors: Monalisa Halder, Amit K. Das, Ajit K. Meikap

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Polymer nanocomposites are very significant materials both in academia and industry for diverse potential applicability in electronics. Polymer plays the role of matrix element which has low density, flexibility, good mechanical strength and electrical properties. Use of nanosized multiferroic filler in the polymer matrix is suitable to achieve nanocomposites with enhanced magneto-dielectric effect and good mechanical properties both at the same time. Multiferroic terbium manganate (TbMnO₃) nanoparticles have been synthesized by sol-gel method using chloride precursors. Terbium manganate-polyvinyl alcohol (TbMnO₃-PVA) nanocomposite film has been prepared by solution casting method. Crystallite size of TbMnO₃ nanoparticle has been calculated to be ~ 40 nm from XRD analysis. Morphological study of the samples has been done by scanning electron microscopy and a well dispersion of the nanoparticles in the PVA matrix has been found. Thermogravimetric analysis (TGA) exhibits enhancement of thermal stability of the nanocomposite film with the inclusion of TbMnO₃ nanofiller in PVA matrix. The electrical transport properties of the nanocomposite film sample have been studied in the frequency range 20Hz - 2MHz at and above room temperature. The frequency dependent variation of ac conductivity follows universal dielectric response (UDR) obeying Jhonscher’s sublinear power law. Correlated barrier hopping (CBH) mechanism is the dominant charge transport mechanism with maximum barrier height 19 meV above room temperature. The variation of dielectric constant of the sample with frequency has been studied at different temperatures. Real part of dielectric constant at 1 KHz frequency at room temperature of the sample is found to be ~ 8 which is higher than that of the pure PVA film sample (~ 6). Dielectric constant decreases with the increase in frequency. Relaxation peaks have been observed in the variation of imaginary part of electric modulus with frequency. The relaxation peaks shift towards higher frequency as temperature increases probably due to the existence of interfacial polarization in the sample in presence of applied electric field. The current-voltage (I-V) characteristics of the nanocomposite film have been studied under ±40 V applied at different temperatures. I-V characteristic exhibits temperature dependent rectifying nature indicating the formation of Schottky barrier diode (SBD) with barrier height 23 meV. In conclusion, using multiferroic TbMnO₃ nanofiller in PVA matrix, enhanced thermal stability and electrical properties can be achieved.

Keywords: correlated barrier hopping, nanocomposite, schottky diode, TbMnO₃, TGA

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2120 Use of Satellite Altimetry and Moderate Resolution Imaging Technology of Flood Extent to Support Seasonal Outlooks of Nuisance Flood Risk along United States Coastlines and Managed Areas

Authors: Varis Ransibrahmanakul, Doug Pirhalla, Scott Sheridan, Cameron Lee

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U.S. coastal areas and ecosystems are facing multiple sea level rise threats and effects: heavy rain events, cyclones, and changing wind and weather patterns all influence coastal flooding, sedimentation, and erosion along critical barrier islands and can strongly impact habitat resiliency and water quality in protected habitats. These impacts are increasing over time and have accelerated the need for new tracking techniques, models and tools of flood risk to support enhanced preparedness for coastal management and mitigation. To address this issue, NOAA National Ocean Service (NOS) evaluated new metrics from satellite altimetry AVISO/Copernicus and MODIS IR flood extents to isolate nodes atmospheric variability indicative of elevated sea level and nuisance flood events. Using de-trended time series of cross-shelf sea surface heights (SSH), we identified specific Self Organizing Maps (SOM) nodes and transitions having a strongest regional association with oceanic spatial patterns (e.g., heightened downwelling favorable wind-stress and enhanced southward coastal transport) indicative of elevated coastal sea levels. Results show the impacts of the inverted barometer effect as well as the effects of surface wind forcing; Ekman-induced transport along broad expanses of the U.S. eastern coastline. Higher sea levels and corresponding localized flooding are associated with either pattern indicative of enhanced on-shore flow, deepening cyclones, or local- scale winds, generally coupled with an increased local to regional precipitation. These findings will support an integration of satellite products and will inform seasonal outlook model development supported through NOAAs Climate Program Office and NOS office of Center for Operational Oceanographic Products and Services (CO-OPS). Overall results will prioritize ecological areas and coastal lab facilities at risk based on numbers of nuisance flood projected and inform coastal management of flood risk around low lying areas subjected to bank erosion.

Keywords: AVISO satellite altimetry SSHA, MODIS IR flood map, nuisance flood, remote sensing of flood

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2119 Particle Separation Using Individually-Controlled Magnetic Soft Artificial Cilia

Authors: Yau-Luen Ng, Nathan Banka, Santosh Devasia

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In this paper, a method based on soft artificial cilia is introduced to separate particles based on size and mass. In nature, cilia are used for fluid propulsion in the mammalian circulatory system, as well as for swimming and size-selective particle entrainment for feeding in microorganisms. Inspired by biological cilia, an array of artificial cilia was fabricated using Polydimethylsiloxane (PDMS) to simulate the actual motion. A row of four individually-controlled magnetic artificial cilia in a semi-circular channel are actuated by the magnetic fields from four permanent magnets. Each cilium is a slender rectangular cantilever approximately 13mm long made from a composite of PDMS and carbonyl iron particles. A time-varying magnetic force is achieved by periodically varying the out-of-plane distance from the permanent magnets to the cilia, resulting in large-amplitude deflections of the cilia that can be used to drive fluid motion. Previous results have shown that this system of individually-controlled magnetic cilia can generate effective mixing flows; the purpose of the present work is to apply the individual cilia control to a particle separation task. Based on the observed beating patterns of cilia arrays in nature, the experimental beating patterns were selected as a metachronal wave, in which a fixed phase lead or lag is imposed between adjacent cilia. Additionally, the beating frequency was varied. For each set of experimental parameters, the channel was filled with water and polyethylene microspheres introduced at the center of the cilia array. Two types of particles were used: large red microspheres with density 0.9971 g/cm³ and 850-1000 μm avg. diameter, and small blue microspheres with density 1.06 g/cm³ and diameter 30 μm. At low beating frequencies, all particles were propelled in the mean flow direction. However, the large particles were observed to reverse directions above about 4.8 Hz, whereas reversal of the small particle transport direction did not occur until 6 Hz. Between these two transition frequencies, the large and small particles can be separated as they move in opposite directions. The experimental results show that selecting an appropriate cilia beating pattern can lead to selective transport of neutrally-buoyant particles based on their size. Importantly, the separation threshold can be chosen dynamically by adjusting the actuation frequency. However, further study is required to determine the range of particle sizes that can be effectively separated for a given system geometry.

Keywords: magnetic cilia, particle separation, tunable separation, soft actutors

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2118 Impact of Simulated Brain Interstitial Fluid Flow on the Chemokine CXC-Chemokine-Ligand-12 Release From an Alginate-Based Hydrogel

Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon

Abstract:

The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.

Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling

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2117 Policy Initiatives That Increase Mass-Market Participation of Fuel Cell Electric Vehicles

Authors: Usman Asif, Klaus Schmidt

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In recent years, the development of alternate fuel vehicles has helped to reduce carbon emissions worldwide. As the number of vehicles will continue to increase in the future, the energy demand will also increase. Therefore, we must consider automotive technologies that are efficient and less harmful to the environment in the long run. Battery Electric Vehicles (BEVs) have gained popularity in recent years because of their lower maintenance, lower fuel costs, and lower carbon emissions. Nevertheless, BEVs show several disadvantages, such as slow charging times and lower range than traditional combustion-powered vehicles. These factors keep many people from switching to BEVs. The authors of this research believe that these limitations can be overcome by using fuel cell technology. Fuel cell technology converts chemical energy into electrical energy from hydrogen power and therefore serves as fuel to power the motor and thus replacing heavy lithium batteries that are expensive and hard to recycle. Also, in contrast to battery-powered electric vehicle technology, Fuel Cell Electric Vehicles (FCEVs) offer higher ranges and lower fuel-up times and therefore are more competitive with electric vehicles. However, FCEVs have not gained the same popularity as electric vehicles due to stringent legal frameworks, underdeveloped infrastructure, high fuel transport, and storage costs plus the expense of fuel cell technology itself. This research will focus on the legal frameworks for hydrogen-powered vehicles, and how a change in these policies may affect and improve hydrogen fueling infrastructure and lower hydrogen transport and storage costs. These policies may also facilitate reductions in fuel cell technology costs. In order to attain a better framework, a number of countries have developed conceptual roadmaps. These roadmaps have set out a series of objectives to increase the access of FCEVs to their respective markets. This research will specifically focus on policies in Japan, Europe, and the USA in their attempt to shape the automotive industry of the future. The researchers also suggest additional policies that may help to accelerate the advancement of FCEVs to mass-markets. The approach was to provide a solid literature review using resources from around the globe. After a subsequent analysis and synthesis of this review, the authors concluded that in spite of existing legal challenges that have hindered the advancement of fuel-cell technology in the automobile industry in the past, new initiatives that enhance and advance the very same technology in the future are underway.

Keywords: fuel cell electric vehicles, fuel cell technology, legal frameworks, policies and regulations

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2116 Association between G2677T/A MDR1 Polymorphism with the Clinical Response to Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis

Authors: Alan Ruiz-Padilla, Brando Villalobos-Villalobos, Yeniley Ruiz-Noa, Claudia Mendoza-Macías, Claudia Palafox-Sánchez, Miguel Marín-Rosales, Álvaro Cruz, Rubén Rangel-Salazar

Abstract:

Introduction: In patients with rheumatoid arthritis, resistance or poor response to disease modifying antirheumatic drugs (DMARD) may be a reflection of the increase in g-P. The expression of g-P may be important in mediating the effluence of DMARD from the cell. In addition, P-glycoprotein is involved in the transport of cytokines, IL-1, IL-2 and IL-4, from normal lymphocytes activated to the surrounding extracellular matrix, thus influencing the activity of RA. The involvement of P-glycoprotein in the transmembrane transport of cytokines can serve as a modulator of the efficacy of DMARD. It was shown that a number of lymphocytes with glycoprotein P activity is increased in patients with RA; therefore, P-glycoprotein expression could be related to the activity of RA and could be a predictor of poor response to therapy. Objective: To evaluate in RA patients, if the G2677T/A MDR1 polymorphisms is associated with differences in the rate of therapeutic response to disease-modifying antirheumatic agents in patients with rheumatoid arthritis. Material and Methods: A prospective cohort study was conducted. Fifty seven patients with RA were included. They had an active disease according to DAS-28 (score >3.2). We excluded patients receiving biological agents. All the patients were followed during 6 months in order to identify the rate of therapeutic response according to the American College of Rheumatology (ACR) criteria. At the baseline peripheral blood samples were taken in order to identify the G2677T/A MDR1 polymorphisms using PCR- Specific allele. The fragment was identified by electrophoresis in polyacrylamide gels stained with ethidium bromide. For statistical analysis, the genotypic and allelic frequencies of MDR1 gene polymorphism between responders and non-responders were determined. Chi-square tests as well as, relative risks with 95% confidence intervals (95%CI) were computed to identify differences in the risk for achieving therapeutic response. Results: RA patients had a mean age of 47.33 ± 12.52 years, 87.7% were women with a mean for DAS-28 score of 6.45 ± 1.12. At the 6 months, the rate of therapeutic response was 68.7 %. The observed genotype frequencies were: for G/G 40%, T/T 32%, A/A 19%, G/T 7% and for A/A genotype 2%. Patients with G allele developed at 6 months of treatment, higher rate for therapeutic response assessed by ACR20 compared to patients with others alleles (p=0.039). Conclusions: Patients with G allele of the - G2677T/A MDR1 polymorphisms had a higher rate of therapeutic response at 6 months with DMARD. These preliminary data support the requirement for a deep evaluation of these and other genotypes as factors that may influence the therapeutic response in RA.

Keywords: pharmacogenetics, MDR1, P-glycoprotein, therapeutic response, rheumatoid arthritis

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2115 Automated Resin Transfer Moulding of Carbon Phenolic Composites

Authors: Zhenyu Du, Ed Collings, James Meredith

Abstract:

The high cost of composite materials versus conventional materials remains a major barrier to uptake in the transport sector. This is exacerbated by a shortage of skilled labour which makes the labour content of a hand laid composite component (~40 % of total cost) an obvious target for reduction. Automation is a method to remove labour cost and improve quality. This work focuses on the challenges and benefits to automating the manufacturing process from raw fibre to trimmed component. It will detail the experimental work required to complete an automation cell, the control strategy used to integrate all machines and the final benefits in terms of throughput and cost.

Keywords: automation, low cost technologies, processing and manufacturing technologies, resin transfer moulding

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2114 Two Layer Photo-Thermal Deflection Model to Investigate the Electronic Properties in BGaAs/GaAs Alloys

Authors: S. Ilahi, M. Baira, F. Saidi, N. Yacoubi, L. Auvray, H. Maaref

Abstract:

Photo-thermal deflection technique (PTD) is used to study the nonradiative recombination process in BGaAs/GaAs alloy with boron composition of 3% and 8% grown by metal organic chemical vapor deposition (MOCVD). A two layer theoretical model has been developed taking into account both thermal and electronic contribution in the photothermal signal allowing to extract the electronic parameters namely electronic diffusivity, surface and interface recombination. It is found that the increase of boron composition alters the BGaAs epilayers transport properties.

Keywords: photothermal defelction technique, two layer model, BGaAs/GaAs alloys, boron composition

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2113 The Therapeutic Potential, Functions, and Use of Ibogaine

Authors: João Pedro Zanella, Michel J. O. Fagundes

Abstract:

Introduction: Drug use has been practised by humans universally for millennia, not excluding any population from these habits, however, the rampant drug use is a global concern due to the harm that affects the health of the world population. In this sense, it is observed the reduction of lasting and effective public policies for the resolution, increasing the demand for treatment services. With this comes ibogaine, an alkaloid derived from the root of an African bush (Tabernanthe Iboga), found mostly in Gabon and used widely by the native Bwiti population in rituals, and also other social groups, which demonstrates efficacy against chemical dependence, psychic and emotional disorders, opioid withdrawal was first confirmed by a study in rats done by Michailo Dzoljic and associates in 1988 and again in 1994. Methods: A brief description of the plant, its neurohumoral potential and the effects caused by ingested doses, in a simplified and objective way, will be discussed in the course of this abstract. Results: Ibogaine is not registered or passed by Anvisa, regarding safety and efficacy, and cannot be sold in Brazil. Its illegal trade reaches R$ 5 thousand for a session with the proceeds of the root, and its effect can last up to 72 hours, attributing Iboga's psychoactive effects to the alkaloid called ibogaine. The shrub where Ibogaine is located has pink and yellow flowers, and its fruit produced does not have psychoactive substances, but its root bark contains 6 to 7% indolic alkaloids. Besides extraction from the iboga plant, ibogaine hydrochloride can be semisynthesized from voacangine, another plant alkaloid that acts as a precursor. Its potential has the ability to perform multiple interactions with the neurotransmitter system, which are closely associated with addiction, including nicotinic, opioid and serotoninergic systems. Studies carried out by Edwards found that the doses administered of Iboga should be determined by a health professional when its purpose is to treat individuals for dependence on other drugs. Its use in small doses may cause an increase in sensibility, impaired vision and motor alterations; in moderate quantities, hallucinations, motor and neurological alterations and impaired vision; in high quantities it may cause hallucinations with personal events at a deeper level lasting up to 24 hours or more, followed by motor and visual alterations. Conclusion: The product extracted from the Iboga plant is of great importance in controlling addiction, reducing the need for the use of narcotics by patients, thus gaining a space of extreme importance in the treatment of users of psychoactive substances. It is remarkable the progress of the latest’s research about the usefulness of Ibogaine, and its benefits for certain treatments, even with the restriction of its sale in Brazil. Besides this, Ibogaine has an additional benefit of helping the patient to gain self-control over their destructive behaviours.

Keywords: alkaloids, dependence, Gabon, ibogaine

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2112 Ethno-Medical Potentials of Tacazzea apiculata Oliv. (Periplocaceae)

Authors: Abubakar Ahmed, Zainab Mohammed, Hadiza D. Nuhu, Hamisu Ibrahim

Abstract:

Introduction: The plant Tacazzea apiculata Oliv (Periplocaceae) is widely distributed in tropical West Africa. It is claimed to have multiple uses in traditional medicine among which are its use to treat hemorrhoids, inflammations and cancers. Methods: Ethno-botanical survey through interview and using show-and-tell method of data collection were conducted among Hausa and Fulani tribes of northern Nigeria with the view to document useful information on the numerous claims by the local people on the plant. Results: The results revealed that the plant T. apiculata has relative popularity among the herbalist (38.2 %), nomads (14.8 %) and fishermen (16.0%). The most important uses of the plant in traditional medicine are inflammation (Fedelity level: 25.7 %) and Haemorrhoids (Fedelity level: 17.1 %) Conclusion: These results suggest the relevance of T. apiculata in traditional medicine and as a good candidate for drug Development.

Keywords: ethno-botany, periplocaceae, Tacazzea apiculata, traditional medicine

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2111 Blood Clot Emulsification via Ultrasonic Thrombolysis Device

Authors: Sun Tao, Lou Liang, Tan Xing Haw Marvin, Gu Yuandong Alex

Abstract:

Patients with blood clots in their brains can experience problems with their vision or speech, seizures and general weakness. To treat blood clots, clinicians presently have two options. The first involves drug therapy to thin the blood and thus reduce the clot. The second choice is to invasively remove the clot using a plastic tube called a catheter. Both approaches carry a high risk of bleeding, and invasive procedures, such as catheter intervention, can also damage the blood vessel wall and cause infection. Ultrasonic treatment as a potential alternative therapy to break down clots is attracting growing interests due to the reduced adverse effects. To demonstrate the concept, in this investigation a microfabricated ultrasonic device was electrically packaged with printed circuit board to treat healthy human blood. The red blood cells could be broken down after 3-hour ultrasonic treatment.

Keywords: microfabrication, blood clot, ultrasonic thrombolysis device, ultrasonic device

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2110 A Strategic Sustainability Analysis of Electric Vehicles in EU Today and Towards 2050

Authors: Sven Borén, Henrik Ny

Abstract:

Ambitions within the EU for moving towards sustainable transport include major emission reductions for fossil fuel road vehicles, especially for buses, trucks, and cars. The electric driveline seems to be an attractive solution for such development. This study first applied the Framework for Strategic Sustainable Development to compare sustainability effects of today’s fossil fuel vehicles with electric vehicles that have batteries or hydrogen fuel cells. The study then addressed a scenario were electric vehicles might be in majority in Europe by 2050. The methodology called Strategic Lifecycle Assessment was first used, were each life cycle phase was assessed for violations against sustainability principles. This indicates where further analysis could be done in order to quantify the magnitude of each violation, and later to create alternative strategies and actions that lead towards sustainability. A Life Cycle Assessment of combustion engine cars, plug-in hybrid cars, battery electric cars and hydrogen fuel cell cars was then conducted to compare and quantify environmental impacts. The authors found major violations of sustainability principles like use of fossil fuels, which contribute to the increase of emission related impacts such as climate change, acidification, eutrophication, ozone depletion, and particulate matters. Other violations were found, such as use of scarce materials for batteries and fuel cells, and also for most life cycle phases for all vehicles when using fossil fuel vehicles for mining, production and transport. Still, the studied current battery and hydrogen fuel cell cars have less severe violations than fossil fuel cars. The life cycle assessment revealed that fossil fuel cars have overall considerably higher environmental impacts compared to electric cars as long as the latter are powered by renewable electricity. By 2050, there will likely be even more sustainable alternatives than the studied electric vehicles when the EU electricity mix mainly should stem from renewable sources, batteries should be recycled, fuel cells should be a mature technology for use in vehicles (containing no scarce materials), and electric drivelines should have replaced combustion engines in other sectors. An uncertainty for fuel cells in 2050 is whether the production of hydrogen will have had time to switch to renewable resources. If so, that would contribute even more to a sustainable development. Except for being adopted in the GreenCharge roadmap, the authors suggest that the results can contribute to planning in the upcoming decades for a sustainable increase of EVs in Europe, and potentially serve as an inspiration for other smaller or larger regions. Further studies could map the environmental effects in LCA further, and include other road vehicles to get a more precise perception of how much they could affect sustainable development.

Keywords: strategic, electric vehicles, sustainability, LCA

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2109 Numerical Study of Fire Propagation in Confined and Open Area

Authors: Hadj Miloua, Abbes Azzi

Abstract:

The objective of the present paper is to understand, predict and modeled the fire behavior in confined and open area in different conditions and diverse fuels such as liquid pool fire and the vegetative materials. The distinctive problems are a ventilated road tunnel used for urban transport, by the characterization installations of ventilation and his influence in the mode of smoke dispersion and the flame shape. A general investigation is relatively traditional, based on the modeling and simulation the scenario of the pool fire interacted with wind ventilation by the use of numerical software fire dynamic simulator FDS ver.5 to simulate the fire in ventilated tunnel. The second simulation by WFDS.5 is Wildland fire which is always occurs in forest and rangeland fire environments and will thus have an impact on people, property and resources.

Keywords: fire, road tunnel, simulation, vegetation, wildland

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2108 Characterization of an Ecological Mortar Lightweight With Polystyrene

Authors: Aidoud Assia, Bencheikh Messaouda, Boukour Salima

Abstract:

Polystyrene is often seen in the ocean and on Algerian beaches, mainly as food containers. It's one of the top 10 most common items found there. This happens because it's light and easily carried away from its original source, like packaging or transport, into the environment. Unfortunately, it's not recycled much because it's not very profitable to do so. Hence, turning this waste into a resource can turn challenges into opportunities for a territory's economic and environmental development, which is the focus of this study. the goal is to analyze the physical and mechanical properties of a new type of mortar made from dune sand mixed with recycled polystyrene. it also aim to assess its potential for use in various construction applications. The mixtures were prepared by replacing portions of dune sand with polystyrene waste at varying volumes (10%, 20%, and 30%), while keeping the amount of cement constant. The results indicate a noticeable impact on both the physical and mechanical properties because of incorporating polystyrene waste.

Keywords: polystyrène, eco-mortier, sable de dune, résistance

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2107 Influence of Natural Gum on Curcumin Supersaturationin Gastrointestinal Fluids

Authors: Patcharawalai Jaisamut, Kamonthip Wiwattanawongsa, Ruedeekorn Wiwattanapatapee

Abstract:

Supersaturation of drugs in the gastrointestinal tract is one approach to increase the absorption of poorly water-soluble drugs. The stabilization of a supersaturated state was achieved by adding precipitation inhibitors that may act through a variety of mechanisms.In this study, the effect of the natural gums, acacia, gelatin, pectin and tragacanth on curcumin supersaturation in simulated gastric fluid (SGF) (pH 1.2), fasted state simulated gastric fluid (FaSSGF) (pH 1.6), and simulated intestinal fluid (SIF) (pH 6.8)was investigated. The results indicated that all natural gums significantly increased the curcum insolubility (about 1.2-6-fold)when compared to the absence of gum, and assisted in maintaining the supersaturated drug solution. Among the tested gums, pectin at 3% w/w was the best precipitation inhibitor with a significant increase in the degree of supersaturation about 3-fold in SGF, 2.4-fold in FaSSGF and 2-fold in SIF.

Keywords: curcumin, solubility, supersaturation, precipitation inhibitor

Procedia PDF Downloads 348