Search results for: drug stability

Authors: Meryl Abigail Lucasan

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The purpose of this research paper is to present a Single Country Comparative Contextual Description Study of the Executive Authorities in Austria, focusing with the Federal President, Cabinet members (Federal Chancellor, the Vice-Chancellor and the other Federal Ministers) and the State Government. In this paper, the roles and powers of the executive authorities of Austria will be enumerated and explained; and the behavior of the executive authorities of Austria will be described in detail. In addition, the researcher will provide a survey that was answered by an Austrian citizen through electronic mail to gain more concrete information about the current political condition in Austria. Based on research, Austria has a remarkable political stability. This paper will develop a conceptual framework or a sample paradigm to represent the political system in Austria, focusing on its states and Executive Authorities in achieving political stability.

Keywords: Austrian politics, executive branch of the government, federal government, political stability

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Authors: Antonis Constantinides, Christos Yiallouras, Christakis Damianou

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The application of today's semiconductor transistors in high power UHF DVB-T linear amplifiers has evolved significantly by utilizing LDMOS technology. This fact provides engineers with the option to design a single transistor signal amplifier which enables output power and linearity that was unobtainable previously using bipolar junction transistors or later type first generation MOSFETS. The quiescent current stability in terms of thermal variations of the LDMOS guarantees a robust operation in any topology of DVB-T signal amplifiers. Otherwise, progressively uncontrolled heat dissipation enhancement on the LDMOS case can degrade the amplifier’s crucial parameters in regards to the gain, linearity, and RF stability, resulting in dysfunctional operation or a total destruction of the unit. This paper presents one more sophisticated approach from the traditional biasing circuits used so far in LDMOS DVB-T amplifiers. It utilizes a microprocessor control technology, providing stability in topologies where IDQ must be perfectly accurate.

Keywords: LDMOS, amplifier, back-off, bias circuit

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Authors: Mubarek Alpkiray, Tan Nguyen, Arild Saasen

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Geothermal drilling operations contain numerous challenges that are encountered to increase the well cost and nonproductive time. Fluid loss is one of the most undesirable troublesome that can cause well abandonment in geothermal drilling. Lost circulation can be seen due to natural fractures, high mud weight, and extremely high formation temperatures. This challenge may cause wellbore stability problems and lead to expensive drilling operations. Wellbore stability is the main domain that should be considered to mitigate or prevent fluid loss into the formation. This paper describes the causes of fluid loss in the Pamukoren geothermal field in Turkey. A geomechanics approach integration and assessment is applied to help the understanding of fluid loss problems. In geothermal drillings, geomechanics is primarily based on rock properties, in-situ stress characterization, the temperature of the rock, determination of stresses around the wellbore, and rock failure criteria. Since a high-temperature difference between the wellbore wall and drilling fluid is presented, temperature distribution through the wellbore is estimated and implemented to the wellbore stability approach. This study reviewed geothermal drilling data to analyze temperature estimation along the wellbore, the cause of fluid loss and stored electric capacity of the reservoir. Our observation demonstrates the geomechanical approach's significant role in understanding safe drilling operations on high-temperature wells. Fluid loss is encountered due to thermal stress effects around the borehole. This paper provides a wellbore stability analysis for a geothermal drilling operation to discuss the causes of lost circulation resulting in nonproductive time and cost.

Keywords: geothermal wells, drilling, wellbore stresses, drilling fluid loss, thermal stress

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Authors: Felipe Riveros, Ricardo Alvarez, Claudia Rahmann, Rodrigo Moreno

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Around the world, many countries have committed to a decarbonization of their electricity system. Under this global drive, converter-interfaced generators (CIG) such as wind and photovoltaic generation appear as cornerstones to achieve these energy targets. Despite its benefits, an increasing use of CIG brings several technical challenges in power systems, especially from a stability viewpoint. Among the key differences are limited short circuit current capacity, inertia-less characteristic of CIG, and response times within the electromagnetic timescale. Along with the integration of CIG into the power system, one enabling technology for the energy transition towards low-carbon power systems is battery energy storage systems (BESS). Because of the flexibility that BESS provides in power system operation, its integration allows for mitigating the variability and uncertainty of renewable energies, thus optimizing the use of existing assets and reducing operational costs. Another characteristic of BESS is that they can also support power system stability by injecting reactive power during the fault, providing short circuit currents, and delivering fast frequency response. However, most methodologies for sizing and allocating BESS in power systems are based on economic aspects and do not exploit the benefits that BESSs can offer to system stability. In this context, this paper presents a methodology for determining the optimal allocation of battery energy storage systems (BESS) in weak power systems with high levels of CIG. Unlike traditional economic approaches, this methodology incorporates stability constraints to allocate BESS, aiming to mitigate instability issues arising from weak grid conditions with low short-circuit levels. The proposed methodology offers valuable insights for power system engineers and planners seeking to maintain grid stability while harnessing the benefits of renewable energy integration. The methodology is validated in the reduced Chilean electrical system. The results show that integrating BESS into a power system with high levels of CIG with stability criteria contributes to decarbonizing and strengthening the network in a cost-effective way while sustaining system stability. This paper potentially lays the foundation for understanding the benefits of integrating BESS in electrical power systems and coordinating their placements in future converter-dominated power systems.

Keywords: battery energy storage, power system stability, system strength, weak power system

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Authors: Babatunde James Falaye, Shi Hai Dong, Kayode John Oyewumi

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We study the effects of oblateness up to J4 of the primaries and power-law density profile (PDP) on the linear stability of libration location of an innitesimal mass within the framework of restricted three body problem (R3BP), by using a more realistic model in which a disc with PDP is rotating around the common center of the system mass with perturbed mean motion. The existence and stability of triangular equilibrium points have been explored. It has been shown that triangular equilibrium points are stable for 0 < μ < μc and unstable for μc ≤ μ ≤ 1/2, where c denotes the critical mass parameter. We find that, the oblateness up to J2 of the primaries and the radiation reduces the stability range while the oblateness up to J4 of the primaries increases the size of stability both in the context where PDP is considered and ignored. The PDP has an eect of about ≈0:01 reduction on the application of c to Earth-Moon and Jupiter-Moons systems. We find that the comprehensive effects of the perturbations have a stabilizing proclivity. However, the oblateness up to J2 of the primaries and the radiation of the primaries have tendency for instability, while coecients up to J4 of the primaries have stability predisposition. In the limiting case c = 0, and also by setting appropriate parameter(s) to zero, our results are in excellent agreement with the ones obtained previously. Libration points play a very important role in space mission and as a consequence, our results have a practical application in space dynamics and related areas. The model may be applied to study the navigation and station-keeping operations of spacecraft (innitesimal mass) around the Jupiter (more massive) -Callisto (less massive) system, where PDP accounts for the circumsolar ring of asteroidal dust, which has a cloud of dust permanently in its wake.

Keywords: libration points, oblateness, power-law density profile, restricted three-body problem

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Authors: Salah Belaidi

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We have carried out extensive and in-depth research to search for bioactive compounds based on Algerian plants. A selection of 50 ligands from Algerian medicinal plants. Several compounds used in herbal medicine have been drawn using Marvin Sketch software. We determined the three-dimensional structures of the ligands with the MMFF94 force field in order to prepare these ligands for molecular docking. The 3D protein structure of the SARS-CoV-2 main protease was taken from the Protein Data Bank. We used AutoDockVina software to apply molecular docking. The hydrogen atoms were added during the molecular docking process, and all the twist bonds of the ligands were added using the (ligand) module in the AutoDock software. The COVID-19 main protease (Mpro) is a key enzyme that plays a vital role in viral transcription and mediating replication, so it is a very attractive drug target for SARS-CoV-2. In this work, an evaluation was carried out on the biologically active compounds present in these selected medicinal plants as effective inhibitors of the protease enzyme of COVID-19, with an in-depth computational calculation of the molecular docking using the Autodock Vina software. The top 7 ligands: Phloroglucinol, Afzelin, Myricetin-3-O- rutinosidTricin 7-neohesperidoside, Silybin, Silychristinthat and Kaempferol are selected among the 50 molecules studied which are Algerian medicinal plants, whose selection is based on the best binding energy which is relatively low compared to the reference molecule with binding affinities of -9.3, -9.3, -9, -8.9, -8 .5, 8.3 and -8.3 kcal mol-1 respectively. Then, we analyzed the ADME properties of the best7 ligands using the web server SwissADME. Two ligands (Silybin, Silychristin) were found to be potential candidates for the discovery and design of novel drug inhibitors of the protease enzyme of SARS-CoV-2. The stability of the two ligands in complexing with the Mpro protease was validated by molecular dynamics simulation; they revealed a stable trajectory in both techniques, RMSD and RMSF, by showing molecular properties with coherent interactions in molecular dynamics simulations. Finally, we conclude that the Silybin ligand forms a more stable complex with the Mpro protease compared to the Silychristin ligand.

Keywords: COVID-19, medicinal plants, molecular docking, ADME properties, molecular dynamics

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Authors: Vijayakameswara Rao Neralla, Jueun Jeon, Jae Hyung Park

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To develop a potential nanocarrier for diagnosis and treatment of rheumatoid arthritis (RA), we prepared a hyaluronic acid (HA)-5β-cholanic acid (CA) conjugate with an acid-labile ketal linker. This conjugate could self-assemble in aqueous conditions to produce pH-responsive HA-CA nanoparticles as potential carriers of the anti-inflammatory drug methotrexate (MTX). MTX was rapidly released from nanoparticles under inflamed synovial tissue in RA. In vitro cytotoxicity data showed that pH-responsive HA-CA nanoparticles were non-toxic to RAW 264.7 cells. In vivo biodistribution results confirmed that, after their systemic administration, pH-responsive HA-CA nanoparticles selectively accumulated in the inflamed joints of collagen-induced arthritis mice. These results indicate that pH-responsive HA-CA nanoparticles represent a promising candidate as a drug carrier for RA therapy.

Keywords: rheumatoid arthritis, hyaluronic acid, nanocarrier, self-assembly, MTX

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Authors: Shashi Sharma, V. K. Katiyar, Uaday Singh

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The ability to manipulate magnetic particles in fluid flows by means of inhomogeneous magnetic fields is used in a wide range of biomedical applications including magnetic drug targeting (MDT). In MDT, magnetic carrier particles bounded with drug molecules are injected into the vascular system up-stream from the malignant tissue and attracted or retained at the specific region in the body with the help of an external magnetic field. Although the concept of MDT has been around for many years, however, wide spread acceptance of the technique is still looming despite the fact that it has shown some promise in both in vivo and clinical studies. This is because traditional MDT has some inherent limitations. Typically, the magnetic force is not very strong and it is also very short ranged. Since the magnetic force must overcome rather large hydrodynamic forces in the body, MDT applications have been limited to sites located close to the surface of the skin. Even in this most favorable situation, studies have shown that it is difficult to collect appreciable amounts of the MDCPs at the target site. To overcome these limitations of the traditional MDT approach, Ritter and co-workers reported the implant assisted magnetic drug targeting (IA-MDT). In IA-MDT, the magnetic implants are placed strategically at the target site to greatly and locally increase the magnetic force on MDCPs and help to attract and retain the MDCPs at the targeted region. In the present work, we develop a mathematical model to study the capturing of magnetic nanoparticles flowing in a fluid in an implant assisted cylindrical channel under the magnetic field. A coil of ferromagnetic SS 430 has been implanted inside the cylindrical channel to enhance the capturing of magnetic nanoparticles under the magnetic field. The dominant magnetic and drag forces, which significantly affect the capturing of nanoparticles, are incorporated in the model. It is observed through model results that capture efficiency increases from 23 to 51 % as we increase the magnetic field from 0.1 to 0.5 T, respectively. The increase in capture efficiency by increase in magnetic field is because as the magnetic field increases, the magnetization force, which is attractive in nature and responsible to attract or capture the magnetic particles, increases and results the capturing of large number of magnetic particles due to high strength of attractive magnetic force.

Keywords: capture efficiency, implant assisted-magnetic drug targeting (IA-MDT), magnetic nanoparticles, modelling

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Authors: Mihika Shivkumar, Krishna Kumar, C. Perisamy

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3D printing is a method of manufacturing wherein materials, such as plastic or metal, are deposited in layers one on top of the other to produce a three dimensional object. 3D printing is most commonly associated with creating engineering prototypes. However, its applications in the field of human health care have been frequently disregarded. Medical applications for 3D printing are expanding rapidly and are envisaged to revolutionize health care. Medical applications for 3D printing, both present and its potential, can be categorized broadly, including: creation of customized prosthetics tissue and organ fabrication; creation of implants, and anatomical models and pharmaceutical research regarding drug dosage forms. This piece breaks down bioprinting in the healthcare sector. It focuses on the better subtle elements of every particular point, including how 3D printing functions in the present, its impediments, and future applications in the health care sector.

Keywords: bio-printing, prototype, drug delivery, organ regeneration

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Authors: Marzieh Zarei

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Well instability is one of the most fundamental challenges faced by the oil and gas industry. Well wall stability analysis is a gap to be filled in the oil industry. The collection of static data such as well logging leads to the construction of a geomechanical numerical model, which will help in assessing the probable risks in future drilling. In this paper, geomechanical model was designed, and mechanical properties of the rock was determined at all points of the model. It was found the safe mud window was determined and the minimum and maximum mud pressures were determined in the ranges of 70-60 MPa and 110-100 MPa, respectively.

Keywords: geomechanics, numerical model, well stability, in-situ stress, underbalanced drilling

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Authors: Huafeng Wei

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Dementia in Alzheimer’s Disease (AD) is the number one cause of dementia internationally, without effective treatments. Increasing evidence suggest that disruption of intracellular calcium homeostasis, primarily pathological elevation of cytosol and mitochondria but reduction of endoplasmic reticulum (ER) calcium concentrations, play critical upstream roles on multiple pathologies and associated neurodegeneration, impaired neurogenesis, synapse, and cognitive dysfunction in various AD preclinical studies. The last federal drug agency (FDA) approved drug for AD dementia treatment, memantine, exert its therapeutic effects by ameliorating N-methyl-D-aspartate (NMDA) glutamate receptor overactivation and subsequent calcium dysregulation. More research works are needed to develop other drugs targeting calcium dysregulation at multiple pharmacological acting sites for future effective AD dementia treatment. Particularly, calcium channel blockers for the treatment of hypertension and dantrolene for the treatment of muscle spasm and malignant hyperthermia can be repurposed for this purpose. In our own research work, intranasal administration of dantrolene significantly increased its brain concentrations and durations, rendering it a more effective therapeutic drug with less side effects for chronic AD dementia treatment. This review summarizesthe progress of various studies repurposing drugs targeting calcium dysregulation for future effective AD dementia treatment as potentially disease-modifying drugs.

Keywords: alzheimer, calcium, cognitive dysfunction, dementia, neurodegeneration, neurogenesis

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Authors: Rachmat Mauludin, Nurmazidah

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Background and purpose: Famotidine is an H2 receptor blocker. Absorption orally is rapid enough, but famotidine can be degraded by stomach acid causing dose reduction until 35.8% after 50 minutes. This drug also undergoes first-pass metabolism which reduced its bio availability only until 40-50%. To overcome these problems, Solid Lipid Nano particles (SLNs) as alternative delivery systems can be formulated. SLNs is a lipid-based drug delivery technology with 50-1000 nm particle size, where the drug incorporated into the bio compatible lipids and the lipid particles are stabilized using appropriate stabilizers. When the particle size is 200 nm or below, lipid containing famotidine can be absorbed through the lymphatic vessels to the subclavian vein, so first-pass metabolism can be avoided. Method: Famotidine SLNs with various compositions of stabilizer was prepared using a high-speed homogenization and sonication method. Then, the particle size distribution, zeta potential, entrapment efficiency, particle morphology and in vitro release profiles were evaluated. Optimization of sonication time also carried out. Result: Particle size of SLN by Particle Size Analyzer was in range 114.6 up to 455.267 nm. Ultrasonicated SLNs within 5 minutes generated smaller particle size than SLNs which was ultrasonicated for 10 and 15 minutes. Entrapment efficiency of SLNs were 74.17 up to 79.45%. Particle morphology of the SLNs was spherical and distributed individually. Release study of Famotidine revealed that in acid medium, 28.89 up to 80.55% of famotidine could be released after 2 hours. Nevertheless in basic medium, famotidine was released 40.5 up to 86.88% in the same period. Conclusion: The best formula was SLNs which stabilized by 4% Poloxamer 188 and 1 % Span 20, that had particle size 114.6 nm in diameter, 77.14% famotidine entrapped, and the particle morphology was spherical and distributed individually. SLNs with the best drug release profile was SLNs which stabilized by 4% Eudragit L 100-55 and 1% Tween 80 which had released 36.34 % in pH 1.2 solution, and 74.13% in pH 7.4 solution after 2 hours. The optimum sonication time was 5 minutes.

Keywords: famotodine, SLN, high speed homogenization, particle size, release study

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Authors: E. G. Karvelas, C. Liosis, A. Theodorakakos, T. E. Karakasidis

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Magnetic navigation of the drug inside the human vessels is a very important concept since the drug is delivered to the desired area. Consequently, the quantity of the drug required to reach therapeutic levels is being reduced while the drug concentration at targeted sites is increased. Magnetic navigation of drug agents can be achieved with the use of magnetic nanoparticles where anti-tumor agents are loaded on the surface of the nanoparticles. The magnetic field that is required to navigate the particles inside the human arteries is produced by a magnetic resonance imaging (MRI) device. The main factors which influence the efficiency of the usage of magnetic nanoparticles for biomedical applications in magnetic driving are the size and the magnetization of the biocompatible nanoparticles. In this study, a computational platform for the simulation of the optimal gradient magnetic fields for the navigation of magnetic nanoparticles inside a carotid artery is presented. For the propulsion model of the particles, seven major forces are considered, i.e., the magnetic force from MRIs main magnet static field as well as the magnetic field gradient force from the special propulsion gradient coils. The static field is responsible for the aggregation of nanoparticles, while the magnetic gradient contributes to the navigation of the agglomerates that are formed. Moreover, the contact forces among the aggregated nanoparticles and the wall and the Stokes drag force for each particle are considered, while only spherical particles are used in this study. In addition, gravitational forces due to gravity and the force due to buoyancy are included. Finally, Van der Walls force and Brownian motion are taken into account in the simulation. The OpenFoam platform is used for the calculation of the flow field and the uncoupled equations of particles' motion. To verify the optimal gradient magnetic fields, a covariance matrix adaptation evolution strategy (CMAES) is used in order to navigate the particles into the desired area. A desired trajectory is inserted into the computational geometry, which the particles are going to be navigated in. Initially, the CMAES optimization strategy provides the OpenFOAM program with random values of the gradient magnetic field. At the end of each simulation, the computational platform evaluates the distance between the particles and the desired trajectory. The present model can simulate the motion of particles when they are navigated by the magnetic field that is produced by the MRI device. Under the influence of fluid flow, the model investigates the effect of different gradient magnetic fields in order to minimize the distance of particles from the desired trajectory. In addition, the platform can navigate the particles into the desired trajectory with an efficiency between 80-90%. On the other hand, a small number of particles are stuck to the walls and remains there for the rest of the simulation.

Keywords: artery, drug, nanoparticles, navigation

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Authors: Helena M. Wilhelm, Paulo O. Fernandes, Laís P. Dill, Kethlyn G. Moscon

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The use of vegetable oil (or natural ester) as an insulating fluid in electrical transformers is a trend that aims to contribute to environmental preservation since it is biodegradable and non-toxic. Besides, vegetable oil has high flash and combustion points, being considered a fire safety fluid. However, vegetable oil is usually less stable towards oxidation than mineral oil. Both insulating fluids, mineral and vegetable oils, need to be tested periodically according to specific standards. Oxidation stability can be determined by the induction period measured by conductivity method (Rancimat) by monitoring the effectivity of oil’s antioxidant additives, a methodology already developed for food application and biodiesel but still not standardized for insulating fluids. Besides adequate oxidation stability, fluids must be compatible with transformer's construction materials under normal operating conditions to ensure that damage to the oil and parts of the transformer does not occur. ASTM standard and Brazilian normative differ in parameters evaluated, which reveals the need to regulate tests for each oil type. The aim of this study was to assess oxidation stability and compatibility of vegetable oils to suggest the best way to assure a viable performance of vegetable oil as transformer insulating fluid. The determination of the induction period for several vegetable insulating oils from the local market by using Rancimat was carried out according to BS EN 14112 standard, at different temperatures (110, 120, and 130 °C). Also, the compatibility of vegetable oil was assessed according to ASTM and ABNT NBR standards. The main results showed that the best temperature for use in the Rancimat test is 130 °C, which allows a better observation of conductivity change. The compatibility test results presented differences between vegetable and mineral oil standards that should be taken into account in oil testing since materials compatibility and oxidation stability are essential for equipment reliability.

Keywords: compatibility, Rancimat, natural ester, vegetable oil

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Authors: S. Chandrasekaran, P. A. Kiran

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Increasing demand for large-sized Floating, Storage and Regasification Units (FSRUs) for oil and gas industries led to the development of novel geometric form of Buoyant Leg Storage and Regasification Platform (BLSRP). BLSRP consists of a circular deck supported by six buoyant legs placed symmetrically with respect to wave direction. Circular deck is connected to buoyant legs using hinged joints, which restrain transfer of rotational response from the legs to deck and vice-versa. Buoyant legs are connected to seabed using taut moored system with high initial pretension, enabling rigid body motion in vertical plane. Encountered environmental loads induce dynamic tether tension variations, which in turn affect stability of the platform. The present study investigates Mathieu stability of BLSRP under the postulated tether pullout cases by inducing additional tension in the tethers. From the numerical studies carried out, it is seen that postulated tether pullout on any one of the buoyant legs does not result in Mathieu type instability even under excessive tether tension. This is due to the presence of hinged joints, which are capable of dissipating the unbalanced loads to other legs. However, under tether pullout of consecutive buoyant legs, Mathieu-type instability is observed.

Keywords: offshore platforms, stability, postulated failure, dynamic tether tension

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Authors: Sarwar Beg, Gajanand Sharma, O. P. Katare, Bhupinder Singh

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The current studies entail development of self-nano emulsifying drug delivery systems (SNEDDS) of rosuvastatin, employing rational QbD-based approach for enhancing its oral bioavailability. SNEDDS were prepared using the blend of lipidic and emulsifying excipients, i.e., Peceol, Tween 80, and Transcutol HP. The prepared formulations evaluated for in vitro drug release, ex vivo permeation, in situ perfusion studies and in vivo pharmacokinetic studies in rats, which demonstrated 3-4 fold improvement in biopharmaceutical performance of the developed formulations. Cytotoxicity studies using MTT assay and histopathological studies in intestinal cells revealed the lack of cytotoxicity and thereby safety and efficacy of the developed formulations.

Keywords: SNEDDS, bioavailability, solubility, Quality by Design (QbD)

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Authors: Eliska Oberhofnerova, Milos Panek, Stepan Hysek, Martin Lexa

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Nowadays the use of wood, both indoors and outdoors, is constantly increasing. However wood is a natural organic material and in the exterior is subjected to a degradation process caused by abiotic factors (solar radiation, rain, moisture, wind, dust etc.). This process affects only surface layers of wood but neglecting some of the basic rules of wood protection leads to increased possibility of biological agents attack and thereby influences a function of the wood element. The process of wood degradation can be decreased by proper surface treatment, especially in the case of less naturally durable wood species, as spruce. Modern coating systems are subjected to many requirements such as colour stability, hydrophobicity, low volatile organic compound (VOC) content, long service life or easy maintenance. The aim of this study is to evaluate the colour stability of spruce wood (Picea abies), as the basic parameter indicating the coating durability, treated with two layers of transparent natural oil wood stain and exposed to outdoor conditions. The test specimens were exposed for 2 years to natural weathering and 2000 hours to artificial weathering in UV-chamber. The colour parameters were measured before and during exposure to weathering by the spectrophotometer according to CIELab colour space. The comparison between untreated and treated wood and both testing procedures was carried out. The results showed a significant effect of coating on the colour stability of wood, as expected. Nevertheless, increasing colour changes of wood observed during the exposure to weathering differed according to applied testing procedure - natural and artificial.

Keywords: colour stability, natural and artificial weathering, spruce wood, transparent coating

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Authors: D. Dixon, J. Nicol, J. A. Coulter, E. Harrison

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The ease with which they can be functionalized, combined with their excellent biocompatibility, make gold nanoparticles (AuNPs) ideal candidates for various applications in nanomedicine. Indeed several promising treatments are currently undergoing human clinical trials (CYT-6091 and Auroshell). A successful nanoparticle treatment must first evade the immune system, then accumulate within the target tissue, before enter the diseased cells and delivering the payload. In order to create a clinically relevant drug delivery system, contrast agent or radiosensitizer, it is generally necessary to functionalize the AuNP surface with multiple groups; e.g. Polyethylene Glycol (PEG) for enhanced stability, targeting groups such as antibodies, peptides for enhanced internalization, and therapeutic agents. Creating and characterizing the biological response of such complex systems remains a challenge. The two commonly used methods to attach multiple groups to the surface of AuNPs are the creation of a mixed monolayer, or by binding groups to the AuNP surface using a bi-functional PEG linker. While some excellent in-vitro and animal results have been reported for both approaches further work is necessary to directly compare the two methods. In this study AuNPs capped with both PEG and a Receptor Mediated Endocytosis (RME) peptide were prepared using both mixed monolayer and PEG linker approaches. The PEG linker used was SH-PEG-SGA which has a thiol at one end for AuNP attachment, and an NHS ester at the other to bind to the peptide. The work builds upon previous studies carried out at the University of Ulster which have investigated AuNP synthesis, the influence of PEG on stability in a range of media and investigated intracellular payload release. 18-19nm citrate capped AuNPs were prepared using the Turkevich method via the sodium citrate reduction of boiling 0.01wt% Chloroauric acid. To produce PEG capped AuNPs, the required amount of PEG-SH (5000Mw) or SH-PEG-SGA (3000Mw Jenkem Technologies) was added, and the solution stirred overnight at room temperature. The RME (sequence: CKKKKKKSEDEYPYVPN, Biomatik) co-functionalised samples were prepared by adding the required amount of peptide to the PEG capped samples and stirring overnight. The appropriate amounts of PEG-SH and RME peptide were added to the AuNP to produce a mixed monolayer consisting of approximately 50% PEG and 50% RME. The PEG linker samples were first fully capped with bi-functional PEG before being capped with RME peptide. An increase in diameter from 18-19mm for the ‘as synthesized’ AuNPs to 40-42nm after PEG capping was observed via DLS. The presence of PEG and RME peptide on both the mixed monolayer and PEG linker co-functionalized samples was confirmed by both FTIR and TGA. Bi-functional PEG linkers allow the entire AuNP surface to be capped with PEG, enabling in-vitro stability to be achieved using a lower molecular weight PEG. The approach also allows the entire outer surface to be coated with peptide or other biologically active groups, whilst also offering the promise of enhanced biological availability. The effect of mixed monolayer versus PEG linker attachment on both stability and non-specific protein corona interactions was also studied.

Keywords: nanomedicine, gold nanoparticles, PEG, biocompatibility

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Authors: Amir A. Beltagi, Ahmed R. Abdelbaki

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Background: Core stability training has recently attracted attention for optimizing performance and improving muscle balance for healthy and unhealthy individuals. The purpose of this study was to investigate the effect of beginner’s core stability exercises on the trunk flexors’/extensors’ peak torque ratio and trunk flexors’ and extensors’ peak torques. Methods: Thirty five healthy individuals, randomly assigned into two groups; experimental (group I) and control (group II), participated in the study. Group I involved 20 participants (10 male & 10 female) with mean ±SD age, weight, and height of 20.7±2.4 years, 66.5±12.1 kg and 166.7±7.8 cm respectively. Group II involved 15 participants (6 male & 9 female) with mean ±SD age, weight, and height of 20.3±0.61 years, 68.57±12.2 kg and 164.28 ±7.59 cm respectively. Data were collected using the Biodex Isokinetic system. The participants were tested twice; before and after a 6-week period during which the experimental group performed a core stability training program. Findings: Statistical analysis using the 2x2 Mixed Design ANOVA revealed that there were no significant differences in the trunk flexors’/extensors’ peak torque ratio between the ‘pre’ and ‘post’ tests for either group (p > 0.025). Moreover, there were no significant differences in the trunk flexors’/extensors’ ratios between both groups at either test (p > 0.025). Meanwhile, the 2x2 Mixed Design MANOVA revealed that there were significant differences in the trunk flexors’ and extensors’ peak torques between the ‘pre’ and ‘post’ tests for group I (p < 0.025), while there were no significant differences inbetween for group II (p > 0.025). Moreover, there were no significant differences between both groups for the tested muscles’ peak torques at either test except for that of the trunk flexors at the ‘post’ test only (p < 0.025). Interpretation: The improvement in muscle performance indicated by the increase in the trunk flexors’ and extensors’ peak torques in the experimental group recommends including core stability training in the exercise programs that aim to improve muscle performance.

Keywords: core stability, isokinetic, trunk muscles, muscle balance

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Authors: Moez ul Hassan, Bushra Noman, Sarmad Hameed, Shahab Mehmood, Asma Bashir

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The importance of Noble prize winning “Patch Clamp Technique” is well documented. However, Patch Clamp Technique is very expensive and hence hinders research in developing countries. In this paper, detection, processing and recording of ultra low current from induced cells by using transimpedence amplifier is described. The sensitivity of the proposed amplifier is in the range of femto amperes (fA). Capacitive-feedback is used with active load to obtain a 20MΩ transimpedance gain. The challenging task in designing includes achieving adequate performance in gain, noise immunity and stability. The circuit designed by the authors was able to measure current in the rangeof 300fA to 100pA. Adequate performance shown by the amplifier with different input current and outcome result was found to be within the acceptable error range. Results were recorded using LabVIEW 8.5®for further research.

Keywords: drug discovery, ionic current, operational amplifier, patch clamp

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Authors: Gail Louw, Helena Boshoff, Taeksun Song, Clifton Barry

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Drug resistance in Mycobacterium tuberculosis is primarily attributed to mutations in target genes. These mutations incur a fitness cost and result in bacterial generations that are less fit, which subsequently acquire compensatory mutations to restore fitness. We hypothesize that mutations in specific drug target genes influence bacterial metabolism and cellular function, which affects its ability to develop subsequent resistance to additional agents. We aim to determine whether the sequential acquisition of drug resistance and specific mutations in a well-defined clinical M. tuberculosis strain promotes or limits the development of additional resistance. In vitro mutants resistant to pretomanid, linezolid, moxifloxacin, rifampicin and kanamycin were generated from a pan-susceptible clinical strain from the Beijing lineage. The resistant phenotypes to the anti-TB agents were confirmed by the broth microdilution assay and genetic mutations were identified by targeted gene sequencing. Growth of mono-resistant mutants was done in enriched medium for 14 days to assess in vitro fitness. Double resistant mutants were generated against anti-TB drug combinations at concentrations 5x and 10x the minimum inhibitory concentration. Subsequently, mutation frequencies for these anti-TB drugs in the different mono-resistant backgrounds were determined. The initial level of resistance and the mutation frequencies observed for the mono-resistant mutants were comparable to those previously reported. Targeted gene sequencing revealed the presence of known and clinically relevant mutations in the mutants resistant to linezolid, rifampicin, kanamycin and moxifloxacin. Significant growth defects were observed for mutants grown under in vitro conditions compared to the sensitive progenitor. Mutation frequencies determination in the mono-resistant mutants revealed a significant increase in mutation frequency against rifampicin and kanamycin, but a significant decrease in mutation frequency against linezolid and sutezolid. This suggests that these mono-resistant mutants are more prone to develop resistance to rifampicin and kanamycin, but less prone to develop resistance against linezolid and sutezolid. Even though kanamycin and linezolid both inhibit protein synthesis, these compounds target different subunits of the ribosome, thereby leading to different outcomes in terms of fitness in the mutants with impaired cellular function. These observations showed that oxazolidinone treatment is instrumental in limiting the development of multi-drug resistance in M. tuberculosis in vitro.

Keywords: oxazolidinones, mutations, resistance, tuberculosis

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Authors: Bhumika Wadhwa, Fayaz Malik

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The serine/threonine protein kinase B (PKB) also known as Akt, is one of the multifaceted kinase in human kinome, existing in three isoforms. Akt plays a vital role in phosphoinositide 3-kinase (PI3K) mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. The functional significance of an individual isoform of Akt is not redundant in cancer cell proliferation and metastasis instead Akt isoforms play distinct roles during metastasis; thereby regulating EMT. This study aims to determine isoform specific functions of Akt in cancer. The results obtained suggest that Akt1 restrict tumor invasion, whereas Akt2 promotes cell migration and invasion by various techniques like MTT, wound healing and invasion assay. Similarly, qRT-PCR also revealed that Akt3 has shown promising results in promoting cancer cell migration. Contrary to pro-oncogenic properties attributed to Akt, it is to be understood how various isoforms of Akt compensates each other in the regulation of common pathways during cancer progression and drug resistance. In conclusion, this study aims to target selective isoforms which is essential to inhibit cancer. However, the question now is whether, and how much, Akt inhibition will be tolerated in the clinic remains to be answered and the experiments will have to address the question of which combinations of newly devised Akt isoform specific inhibitors exert a favourable therapeutic effect in in vivo models of cancer to provide the therapeutic window with minimal toxicity.

Keywords: Akt isoforms, cancer, drug resistance, epithelial mesenchymal transition

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Authors: Melkamu Tadesse Getachew

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Intelligent control systems have revolutionized biomedical engineering, advancing research and enhancing medical practice. This review paper examines the impact of intelligent control on various aspects of biomedical engineering. It analyzes how these systems enhance precision and accuracy in biomedical instrumentation, improving diagnostics, monitoring, and treatment. Integration challenges are addressed, and potential solutions are proposed. The paper also investigates the optimization of drug delivery systems through intelligent control. It explores how intelligent systems contribute to precise dosing, targeted drug release, and personalized medicine. Challenges related to controlled drug release and patient variability are discussed, along with potential avenues for overcoming them. The comparison of algorithms used in intelligent control systems in biomedical control is also reviewed. The implications of intelligent control in computational and systems biology are explored, showcasing how these systems enable enhanced analysis and prediction of complex biological processes. Challenges such as interpretability, human-machine interaction, and machine reliability are examined, along with potential solutions. Intelligent control in biomedical engineering also plays a crucial role in risk management during surgical operations. This section demonstrates how intelligent systems improve patient safety and surgical outcomes when integrated into surgical robots, augmented reality, and preoperative planning. The challenges associated with these implementations and potential solutions are discussed in detail. In summary, this review paper comprehensively explores the widespread impact of intelligent control on biomedical engineering, showing the future of human health issues promising. It discusses application areas, challenges, and potential solutions, highlighting the transformative potential of these systems in advancing research and improving medical practice.

Keywords: Intelligent control systems, biomedical instrumentation, drug delivery systems, robotic surgical instruments, Computational monitoring and modeling

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Authors: Somyoung Shin, Donghun Jeong, Yeoil Yun

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South Korea continuously installed tunnels in consideration of the safety and operation efficiency, and the number of installed tunnels has doubled over the past ten years. The tunnel section is designed based on the guidelines, but the tunnel entrance becomes narrow due to dark adaptation and pressure. In fact, around 13% of traffic in expressways of Japan happens at the entrance, leading to congestion and rear-ends collision accidents. Therefore, this study aims to analyze the stability from the expansion of the shoulder width in the tunnel entrance by applying a virtual reality driving simulator in order to reduce the accidents that happen in the tunnel entrance. To compare the driving stability based on the changes in the width of the right shoulder under the same condition, a virtual reality driving simulator is used to conduct an experiment on 30 subjects in their 20s to 60s and to provide a more practical virtual reality driving environment, and an experiment map is designed based on actual roads as the background to conduct the experiment. The right shoulder is classified into 2.5m and 3.0m based on the design guidelines of the expressways and the road structure installation regulations. The experimenters' experiment order is decided randomly. As a result of analyzing the average speed, it was displayed as 100.73km/h when the shoulder width was 2.5m and 101.69km/h when the shoulder width was 3.0m and as a result of conducting t-test analysis, the p-value appeared as more than 0.05 in the significance level of 95%, so it was statistically insignificant. Also, as a result of analyzing the speed deviation between the average driving speed of the analyzed interval and the average driving speed upon entering the tunnel, it was displayed as 3.06km/h when the shoulder width was 2.5m and 1.87km/h when the shoulder width was 3.0m and as a result of conducting t-test analysis, the p-value appeared as less than 0.05 in the significance level of 95%, so it was statistically significant. This means that when the shoulder width is 3.0m, there is stability in terms of the driving stability compared to when it is 2.5m. Therefore, it is considered that when new roads are constructed in Korea, the right shoulder width should be installed as 3.0m to enhance the driving stability.

Keywords: driving stability, shoulder width, tunnel, virtual reality driving simulator

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Authors: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant

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Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.

Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment

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Authors: Larifah Mohd Sidik, Anuar Kasa

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In recent years, the demands for raw water are increasing along with the growth of the economy and population. Hence, the need for the construction and operation of dams is one of the solutions for the management of water resources problems. The stability of the embankment should be taken into consideration to evaluate the safety of retaining water. The safety of the dam is mostly based on numerous measurable components, for instance, seepage flowrate, pore water pressure and deformation of the embankment. Seepage and slope stability is the primary and most important reason to ascertain the overall safety behavior of the dams. This research study was conducted to evaluate static condition seepage and slope stability performances of Batu dam which is located in Kuala Lumpur capital city. The numerical solution Geostudio-2012 software was employed to analyse the seepage using finite element method, SEEP/W and slope stability using limit equilibrium method, SLOPE/W for three different cases of reservoir level operations; normal and flooded condition. Results of seepage analysis using SEEP/W were utilized as parental input for the analysis of SLOPE/W. Sensitivity analysis on hydraulic conductivity of material was done and calibrated to minimize the relative error of simulation SEEP/W, where the comparison observed field data and predicted value were also carried out. In seepage analysis, such as leakage flow rate, pore water distribution and location of a phreatic line are determined using the SEEP/W. The result of seepage analysis shows the clay core effectively lowered the phreatic surface and no piping failure is shown in the result. Hence, the total seepage flux was acceptable and within the permissible limit.

Keywords: earth dam, dam safety, seepage, slope stability, pore water pressure

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Authors: Garzon V., Bustos R., Salvador J. P., Marco M. P., Pinacho D. G.

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Bacterial resistance to antimicrobial treatment has increased significantly in recent years, making it a public health problem. Large numbers of bacteria are resistant to all or nearly all known antimicrobials, creating the need for the development of new types of antimicrobials or the use of “last line” antimicrobial drug therapies for the treatment of multi-resistant bacteria. Some of the chemical groups of antimicrobials most used for the treatment of infections caused by multiresistant bacteria in the clinic are Glycopeptide (Vancomycin), Polymyxin (Colistin), Lipopeptide (Daptomycin) and Carbapenem (Meropenem). Molecules that require therapeutic drug monitoring (TDM). Due to the above, a methodology based on nanobiotechnology based on an optical and electrochemical biosensor is being developed, which allows the evaluation of the plasmatic levels of some antimicrobials such as glycopeptide, polymyxin, lipopeptide and carbapenem quickly, at a low cost, with a high specificity and sensitivity and that can be implemented in the future in public and private health hospitals. For this, the project was divided into five steps i) Design of specific anti-drug antibodies, produced in rabbits for each of the types of antimicrobials, evaluating the results by means of an immunoassay analysis (ELISA); ii) quantification by means of an electrochemical biosensor that allows quantification with high sensitivity and selectivity of the reference antimicrobials; iii) Comparison of antimicrobial quantification with an optical type biosensor; iv) Validation of the methodologies used with biosensor by means of an immunoassay. Finding as a result that it is possible to quantify antibiotics by means of the optical and electrochemical biosensor at concentrations on average of 1,000ng/mL, the antibodies being sensitive and specific for each of the antibiotic molecules, results that were compared with immunoassays and HPLC chromatography. Thus, contributing to the safe use of these drugs commonly used in clinical practice and new antimicrobial drugs.

Keywords: antibiotics, electrochemical biosensor, optical biosensor, therapeutic drug monitoring

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Authors: Akwu N. A., Naidoo Y., Salau V. F., Olofinsan K. A.

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Grewia lasiocarpa E. Mey. ex Harv. (Malvaceae) is a Southern African medicinal plant indigenously used with other plants for birthing problems. The anti-diabetic properties of the hexane, chloroform, and methanol extracts of Grewia lasiocarpa stem bark were assessed using in vitro α-glucosidase enzyme inhibition assay. The predictive in silico drug-likeness and toxicity properties of the phytocompounds were conducted using the pKCSM, ADMElab, and SwissADME computer-aided online tools. The highest α-glucosidase percentage inhibition was observed in the hexane extract (86.76%, IC50= 0.24 mg/mL), followed by chloroform (63.08%, IC50= 4.87 mg/mL) and methanol (53.22%, IC50= 9.41 mg/mL); while acarbose, the standard anti-diabetic drug was (84.54%, IC50= 1.96 mg/mL). The α-glucosidase assay revealed that the hexane extract exhibited the strongest carbohydrate inhibiting capacity and is a better inhibitor than the standard reference drug-acarbose. The computational studies also affirm the results observed in the in vitroα-glucosidaseassay. Thus, the extracts of G. lasiocarpa may be considered a potential plant-sourced compound for treating type 2 diabetes mellitus. This is the first study on the anti-diabetic properties of Grewia lasiocarpa hexane, chloroform, and methanol extracts using in vitro and in silico models.

Keywords: grewia lasiocarpa, α-glucosidase inhibition, anti-diabetes, ADMET

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Authors: Ilaria Manca, Ilaria Manca, Francesca Pettinau, Ignazia Mocci, Elisabetta M. Usai, Barbara Pittau

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Lamotrigine is a phenyltriazine used in the treatment of epilepsy and bipolar disorder type I. The purpose of this study was to test and compare various solid forms of immediate release (IR) lamotrigine products, at different strenghts, in order to study their disaggregation and dissolution behavior. IR products are designed to release their active substance promptly after administration. Concentration of hydrochloric acid in gastric juice is about 0.1-0.001 M, so FDA (Food and Drug Administration) recommends, for lamotrigine regular tablets, dissolution tests in HCl 0.1 M.Toinvestigate the pH dependency of drug release in the entire gastrointestinal tract, we worked at two additional media with different pH values (4.5 and 6.8), that reflect conditions in it. To afford acceptable dissolution rates, tablets must disintegrate. Disaggregation of constituent particles increases the surface area and substantially increases the dissolution rate. For this reason availability of an active substance from tablets depends on its ability to disintegrate fast in dissolution media. pH of gastrointestinal fluid affects drug absorption by conditioning its solubility and dissolution, but also tablet disintegration may be influenced by it. To obtain information about the quantitative relationship between different mixture components, Nuclear Magnetic Resonance (NMR) spectroscopy was used. We also investigate tablet hardness. The investigation carried out confirms pH 1.2 as the ideal environment for the immediate availability of the active substance.

Keywords: dissolution, disaggregation, Lamotrigine, bioequivalence

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Authors: Guillaume Lemahieu, Matthias Sentis, Giovanni Brambilla, Gérard Meunier

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Static Multiple Light Scattering (SMLS) has been shown to be a straightforward technique for the characterization of colloidal dispersions without dilution, as multiply scattered light in backscattered and transmitted mode is directly related to the concentration and size of scatterers present in the sample. In this view, the use of SMLS for stability measurement of various dispersion types has already been widely described in the literature. Indeed, starting from a homogeneous dispersion, the variation of backscattered or transmitted light can be attributed to destabilization phenomena, such as migration (sedimentation, creaming) or particle size variation (flocculation, aggregation). In a view to investigating more on the dispersibility of colloidal suspensions, an experimental set-up for “at the line” SMLS experiment has been developed to understand the impact of the formulation parameters on particle size and dispersibility. The SMLS experiment is performed with a high acquisition rate (up to 10 measurements per second), without dilution, and under direct agitation. Using such experimental device, SMLS detection can be combined with the Hansen approach to optimize the dispersing and stabilizing properties of TiO₂ particles. It appears that the dispersibility and the stability spheres generated are clearly separated, arguing that lower stability is not necessarily a consequence of poor dispersibility. Beyond this clarification, this combined SMLS-Hansen approach is a major step toward the optimization of dispersibility and stability of colloidal formulations by finding solvents having the best compromise between dispersing and stabilizing properties. Such study can be intended to find better dispersion media, greener and cheaper solvents to optimize particles suspensions, reduce the content of costly stabilizing additives or satisfy product regulatory requirements evolution in various industrial fields using suspensions (paints & inks, coatings, cosmetics, energy).

Keywords: dispersibility, stability, Hansen parameters, particles, solvents

Procedia PDF Downloads 99