Search results for: drug loading
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3479

Search results for: drug loading

2879 Response of Full-Scale Room Building Against Blast Loading

Authors: Eid Badshah, Amjad Naseer, Muhammad Ashraf

Abstract:

In this paper full-scale brick masonry room along with the veranda of a typical school building was subjected to eight successive blast tests with increasing charge weights ranging from 0.5kg to 16.02kg at 3.66m fixed stand-off distance. Pressure-time histories were obtained by data acquisition system from pressure sensors, installed on different points of room as well as veranda columns. The resulting damage pattern of different locations was observed during each test. Weak zones of masonry room were identified. Scaled distances for different damage levels in masonry room were experimentally obtained. The results provided a basis for determining the response of masonry room building against blast loading in a specific threat scenario.

Keywords: peak pressure, composition-B, TNT, pressure sensor, scaled distance, masonry

Procedia PDF Downloads 126
2878 Evaluation on Effective Size and Hysteresis Characteristics of CHS Damper

Authors: Daniel Y. Abebe, Jaehyouk Choi

Abstract:

This study aims to evaluate the effective size and hysteresis characteristics of Circular Hollow Steel (CHS) damper. CHS damper is among steel dampers which are used widely for seismic energy dissipation because they are easy to install, maintain and are low cost. CHS damper dissipates seismic energy through metallic deformation due to the geometrical elasticity of circular shape and fatigue resistance around connection part. After calculating the effective size, which is found to be height to diameter ratio of √ ("3”), nonlinear FE analyses were conducted to evaluate the hysteresis characteristics. To verify the analysis simulation quasi static loading was carried out and the result was compared and satisfactory result was obtained.

Keywords: SS400 steel, circular hollow steel damper, effective size, quasi static loading, FE analysis

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2877 Profile of Cortisol in Bali's Crossbreed Cows for 120 Hours Shipping Using Traditional Vessel

Authors: Hindar Panguji, Nichlah Rifqiyah, Irkham Widiono, Pudji Astuti

Abstract:

Many transportations of livestock in Indonesia is still managed traditionally. Transportation involves several things that may cause stress, from a certain treatment or other factors, either externally or internally, that act as stressors. This study aimed to determine the profile of cortisol and IL-6 in female Bali breeding cattle transported for 120 hours using 100 GT traditional vessels with two floors and a capacity of 300-400 heads. Before transportation, all of the animals have got the vaccination. Blood samples from thirty cows were taken before transportation, during loading, during docking, and after transportation. ELISA method was used to analyze the concentration of cortisol and IL6. The averages of cortisol concentration before transportation, during loading, docking, and after transportation were 78.21±27.96 ng/mL, 90.78±30.91 ng/mL, 69.90±53.92 ng/mL and 69.34±32.03 ng/mL respectively. The average concentration of IL-6 before, during, docking and after transportation were 259.86±70.16 pg/mL, 315.41±64.21 pg/mL, 410.13±247.43 pg/mL dan 424.81±98.86 pg/mL. It was concluded there were no differences in cortisol concentrations and level of IL6 of each cow at different stages of transportation (p > 0.05) It would be possible that vaccination could reduce the fluctuation of cortisol.

Keywords: shipping, Bali's breed cows, vessel, cortisol, IL6

Procedia PDF Downloads 223
2876 Engineering Optimization Using Two-Stage Differential Evolution

Authors: K. Y. Tseng, C. Y. Wu

Abstract:

This paper employs a heuristic algorithm to solve engineering problems including truss structure optimization and optimal chiller loading (OCL) problems. Two different type algorithms, real-valued differential evolution (DE) and modified binary differential evolution (MBDE), are successfully integrated and then can obtain better performance in solving engineering problems. In order to demonstrate the performance of the proposed algorithm, this study adopts each one testing case of truss structure optimization and OCL problems to compare the results of other heuristic optimization methods. The result indicates that the proposed algorithm can obtain similar or better solution in comparing with previous studies.

Keywords: differential evolution, Truss structure optimization, optimal chiller loading, modified binary differential evolution

Procedia PDF Downloads 168
2875 Virtual Screening of Potential Inhibitors against Efflux Pumps of Mycobacterium tuberculosis

Authors: Gagan Dhawan

Abstract:

Mycobacterium tuberculosis was described as ‘captain of death’ with an inherent property of multiple drug resistance majorly caused by the competent mechanism of efflux pumps. In this study, various open source tools combining chemo-informatics with bioinformatics were used for efficient in-silico drug designing. The efflux pump, Rv1218c, belonging to the ABC transporter superfamily, which is predicted to be a tetronasin-transporter in M. tuberculosis was targeted. Recent studies have shown that Rv1218c forms a complex with two more efflux pumps (Rv1219c and Rv1217c) to provide multidrug resistance to the bacterium. The 3D structure of the protein was modeled (as the structure was unavailable in the previously collected databases on this gene). The TMHMM analysis of this protein in TubercuList has shown that this protein is present in the outer membrane of the bacterium. Virtual screening of compounds from various publically available chemical libraries was performed on the M. tuberculosis protein using various open source tools. These ligands were further assessed where various physicochemical properties were evaluated and analyzed. On comparison of different physicochemical properties, toxicity and docking, the ligand 2-(hydroxymethyl)-6-[4, 5, 6-trihydroxy-2-(hydroxymethyl) tetrahydropyran-3-yl] oxy-tetrahydropyran-3, 4, 5-triol was found to be best suited for further studies.

Keywords: drug resistance, efflux pump, molecular docking, virtual screening

Procedia PDF Downloads 369
2874 Computational Approach to Identify Novel Chemotherapeutic Agents against Multiple Sclerosis

Authors: Syed Asif Hassan, Tabrej Khan

Abstract:

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

Procedia PDF Downloads 256
2873 Structural Property and Mechanical Behavior of Polypropylene–Elemental Sulfur (S8) Composites: Effect of Sulfur Loading

Authors: S. Vijay Kumar, Kishore K. Jena, Saeed M. Alhassan

Abstract:

Elemental sulfur is currently produced on the level of 70 million tons annually by petroleum refining, majority of which is used in the production of sulfuric acid, fertilizer and other chemicals. Still, over 6 million tons of elemental sulfur is generated in excess, which creates exciting opportunities to develop new chemistry to utilize sulfur as a feedstock for polymers. Development of new polymer composite materials using sulfur is not widely explored and remains an important challenge in the field. Polymer nanocomposites prepared by carbon nanotube, graphene, silica and other nanomaterials were well established. However, utilization of sulfur as filler in the polymer matrix could be an interesting study. This work is to presents the possibility of utilizing elemental sulfur as reinforcing fillers in the polymer matrix. In this study we attempted to prepare polypropylene/sulfur nanocomposite. The physical, mechanical and morphological properties of the newly developed composites were studied according to the sulfur loading. In the sample preparation, four levels of elemental sulfur loading (5, 10, 20 and 30 wt. %) were designed. Composites were prepared by the melt mixing process by using laboratory scale mini twin screw extruder at 180°C for 15 min. The reaction time and temperature were maintained constant for all prepared composites. The structure and crystallization behavior of composites was investigated by Raman, FTIR, XRD and DSC analysis. It was observed that sulfur interfere with the crystalline arrangement of polypropylene and depresses the crystallization, which affects the melting point, mechanical and thermal stability. In the tensile test, one level of test temperature (room temperature) and crosshead speed (10 mm/min) was designed. Tensile strengths and tensile modulus of the composites were slightly decreased with increasing in filler loading, however, percentage of elongation improved by more than 350% compared to neat polypropylene. The effect of sulfur on the morphology of polypropylene was studied with TEM and SEM techniques. Microscope analysis revels that sulfur is homogeneously dispersed in polymer matrix and behaves as single phase arrangement in the polymer. The maximum elongation for the polypropylene can be achieved by adjusting the sulfur loading in the polymer. This study reviles the possibility of using elemental sulfur as a solid plasticizer in the polypropylene matrix.

Keywords: crystallization, elemental sulfur, morphology, thermo-mechanical properties, polypropylene, polymer nanocomposites

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2872 Spatial Analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) Patients in Lagos, Nigeria

Authors: Akinsola Oluwatosin, Udofia Samuel, Odofin Mayowa

Abstract:

The study is aimed at assessing the Geographic Information System (GIS)-based spatial analysis of Survival Pattern and Treatment Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) cases for Lagos, Nigeria, with an objective to inform priority areas for public health planning and resource allocation. Multi-drug resistant tuberculosis (MDR-TB) develops due to problems such as irregular drug supply, poor drug quality, inappropriate prescription, and poor adherence to treatment. The shapefile(s) for this study were already georeferenced to Minna datum. The patient’s information was acquired on MS Excel and later converted to . CSV file for easy processing to ArcMap from various hospitals. To superimpose the patient’s information the spatial data, the addresses was geocoded to generate the longitude and latitude of the patients. The database was used for the SQL query to the various pattern of the treatment. To show the pattern of disease spread, spatial autocorrelation analysis was used. The result was displayed in a graphical format showing the areas of dispersing, random and clustered of patients in the study area. Hot and cold spot analysis was analyzed to show high-density areas. The distance between these patients and the closest health facility was examined using the buffer analysis. The result shows that 22% of the points were successfully matched, while 15% were tied. However, the result table shows that a greater percentage of it was unmatched; this is evident in the fact that most of the streets within the State are unnamed, and then again, most of the patients are likely to supply the wrong addresses. MDR-TB patients of all age groups are concentrated within Lagos-Mainland, Shomolu, Mushin, Surulere, Oshodi-Isolo, and Ifelodun LGAs. MDR-TB patients between the age group of 30-47 years had the highest number and were identified to be about 184 in number. The outcome of patients on ART treatment revealed that a high number of patients (300) were not ART treatment while a paltry 45 patients were on ART treatment. The result shows the Z-score of the distribution is greater than 1 (>2.58), which means that the distribution is highly clustered at a significance level of 0.01.

Keywords: tuberculosis, patients, treatment, GIS, MDR-TB

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2871 Failure Criterion for Mixed Mode Fracture of Cracked Wood Specimens

Authors: Mahdi Fakoor, Seyed Mohammad Navid Ghoreishi

Abstract:

Investigation of fracture of wood components can prevent from catastrophic failures. Created fracture process zone (FPZ) in crack tip vicinity has important effect on failure of cracked composite materials. In this paper, a failure criterion for fracture investigation of cracked wood specimens under mixed mode I/II loading is presented. This criterion is based on maximum strain energy release rate and material nonlinearity in the vicinity of crack tip due to presence of microcracks. Verification of results with available experimental data proves the coincidence of the proposed criterion with the nature of fracture of wood. To simplify the estimation of nonlinear properties of FPZ, a damage factor is also introduced for engineering and application purposes.

Keywords: fracture criterion, mixed mode loading, damage zone, micro cracks

Procedia PDF Downloads 298
2870 An Investigation of Wind Loading Effects on the Design of Elevated Steel Tanks with Lattice Tower Supporting Structures

Authors: J. van Vuuren, D. J. van Vuuren, R. Muigai

Abstract:

In recent times, South Africa has experienced extensive droughts that created the need for reliable small water reservoirs. These reservoirs have comparatively quick fabrication and installation times compared to market alternatives. An elevated water tank has inherent potential energy, resulting in that no additional water pumps are required to sustain water pressure at the outlet point – thus ensuring that, without electricity, a water source is available. The initial construction formwork and the complex geometric shape of concrete towers that requires casting can become time-consuming, rendering steel towers preferable. Reinforced concrete foundations, cast in advance, are required to be of sufficient strength. Thereafter, the prefabricated steel supporting structure and tank, which consist of steel panels, can be assembled and erected on site within a couple of days. Due to the time effectiveness of this system, it has become a popular solution to aid drought-stricken areas. These sites are normally in rural, schools or farmland areas. As these tanks can contain up to 2000kL (approximately 19.62MN) of water, combined with supporting lattice steel structures ranging between 5m and 30m in height, failure of one of the supporting members will result in system failure. Thus, there is a need to gain a comprehensive understanding of the operation conditions because of wind loadings on both the tank and the supporting structure. The aim of the research is to investigate the relationship between the theoretical wind loading on a lattice steel tower in combination with an elevated sectional steel tank, and the current wind loading codes, as applicable to South Africa. The research compares the respective design parameters (both theoretical and wind loading codes) whereby FEA analyses are conducted on the various design solutions. The currently available wind loading codes are not sufficient to design slender cantilever latticed steel towers that support elevated water storage tanks. Numerous factors in the design codes are not comprehensively considered when designing the system as these codes are dependent on various assumptions. Factors that require investigation for the study are; the wind loading angle to the face of the structure that will result in maximum load; the internal structural effects on models with different bracing patterns; the loading influence of the aspect ratio of the tank; and the clearance height of the tank on the structural members. Wind loads, as the variable that results in the highest failure rate of cantilevered lattice steel tower structures, require greater understanding. This study aims to contribute towards the design process of elevated steel tanks with lattice tower supporting structures.

Keywords: aspect ratio, bracing patterns, clearance height, elevated steel tanks, lattice steel tower, wind loads

Procedia PDF Downloads 150
2869 Investigation into the Optimum Hydraulic Loading Rate for Selected Filter Media Packed in a Continuous Upflow Filter

Authors: A. Alzeyadi, E. Loffill, R. Alkhaddar

Abstract:

Continuous upflow filters can combine the nutrient (nitrogen and phosphate) and suspended solid removal in one unit process. The contaminant removal could be achieved chemically or biologically; in both processes the filter removal efficiency depends on the interaction between the packed filter media and the influent. In this paper a residence time distribution (RTD) study was carried out to understand and compare the transfer behaviour of contaminants through a selected filter media packed in a laboratory-scale continuous up flow filter; the selected filter media are limestone and white dolomite. The experimental work was conducted by injecting a tracer (red drain dye tracer –RDD) into the filtration system and then measuring the tracer concentration at the outflow as a function of time; the tracer injection was applied at hydraulic loading rates (HLRs) (3.8 to 15.2 m h-1). The results were analysed according to the cumulative distribution function F(t) to estimate the residence time of the tracer molecules inside the filter media. The mean residence time (MRT) and variance σ2 are two moments of RTD that were calculated to compare the RTD characteristics of limestone with white dolomite. The results showed that the exit-age distribution of the tracer looks better at HLRs (3.8 to 7.6 m h-1) and (3.8 m h-1) for limestone and white dolomite respectively. At these HLRs the cumulative distribution function F(t) revealed that the residence time of the tracer inside the limestone was longer than in the white dolomite; whereas all the tracer took 8 minutes to leave the white dolomite at 3.8 m h-1. On the other hand, the same amount of the tracer took 10 minutes to leave the limestone at the same HLR. In conclusion, the determination of the optimal level of hydraulic loading rate, which achieved the better influent distribution over the filtration system, helps to identify the applicability of the material as filter media. Further work will be applied to examine the efficiency of the limestone and white dolomite for phosphate removal by pumping a phosphate solution into the filter at HLRs (3.8 to 7.6 m h-1).

Keywords: filter media, hydraulic loading rate, residence time distribution, tracer

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2868 Rapid and Easy Fabrication of Collagen-Based Biocomposite Scaffolds for 3D Cell Culture

Authors: Esra Turker, Umit Hakan Yildiz, Ahu Arslan Yildiz

Abstract:

The key of regenerative medicine is mimicking natural three dimensional (3D) microenvironment of tissues by utilizing appropriate biomaterials. In this study, a synthetic biodegradable polymer; poly (L-lactide-co-ε-caprolactone) (PLLCL) and a natural polymer; collagen was used to mimic the biochemical structure of the natural extracellular matrix (ECM), and by means of electrospinning technique the real physical structure of ECM has mimicked. PLLCL/Collagen biocomposite scaffolds enables cell attachment, proliferation and nutrient transport through fabrication of micro to nanometer scale nanofibers. Biocomposite materials are commonly preferred due to limitations of physical and biocompatible properties of natural and synthetic materials. Combination of both materials improves the strength, degradation and biocompatibility of scaffold. Literature studies have shown that collagen is mostly solved with heavy chemicals, which is not suitable for cell culturing. To overcome this problem, a new approach has been developed in this study where polyvinylpyrrolidone (PVP) is used as co-electrospinning agent. PVP is preferred due to its water solubility, so PLLCL/collagen biocomposite scaffold can be easily and rapidly produced. Hydrolytic and enzymatic biodegradation as well as mechanical strength of scaffolds were examined in vitro. Cell adhesion, proliferation and cell morphology characterization studies have been performed as well. Further, on-chip drug screening analysis has been performed over 3D tumor models. Overall, the developed biocomposite scaffold was used for 3D tumor model formation and obtained results confirmed that developed model could be used for drug screening studies to predict clinical efficacy of a drug.

Keywords: biomaterials, 3D cell culture, drug screening, electrospinning, lab-on-a-chip, tissue engineering

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2867 Nanopharmaceutical: A Comprehensive Appearance of Drug Delivery System

Authors: Mahsa Fathollahzadeh

Abstract:

The various nanoparticles employed in drug delivery applications include micelles, liposomes, solid lipid nanoparticles, polymeric nanoparticles, functionalized nanoparticles, nanocrystals, cyclodextrins, dendrimers, and nanotubes. Micelles, composed of amphiphilic block copolymers, can encapsulate hydrophobic molecules, allowing for targeted delivery. Liposomes, vesicular structures made up of phospholipids, can encapsulate both hydrophobic and hydrophilic molecules, providing a flexible platform for delivering therapeutic agents. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are designed to improve the stability and bioavailability of lipophilic drugs. Polymeric nanoparticles, such as poly(lactic-co-glycolic acid) (PLGA), are biodegradable and can be engineered to release drugs in a controlled manner. Functionalized nanoparticles, coated with targeting ligands or antibodies, can specifically target diseased cells or tissues. Nanocrystals, engineered to have specific surface properties, can enhance the solubility and bioavailability of poorly soluble drugs. Cyclodextrins, doughnut-shaped molecules with hydrophobic cavities, can be complex with hydrophobic molecules, allowing for improved solubility and bioavailability. Dendrimers, branched polymers with a central core, can be designed to deliver multiple therapeutic agents simultaneously. Nanotubes and metallic nanoparticles, such as gold nanoparticles, offer real-time tracking capabilities and can be used to detect biomolecular interactions. The use of these nanoparticles has revolutionized the field of drug delivery, enabling targeted and controlled release of therapeutic agents, reduced toxicity, and improved patient outcomes.

Keywords: nanotechnology, nanopharmaceuticals, drug-delivery, proteins, ligands, nanoparticles, chemistry

Procedia PDF Downloads 51
2866 Innovative Preparation Techniques: Boosting Oral Bioavailability of Phenylbutyric Acid Through Choline Salt-Based API-Ionic Liquids and Therapeutic Deep Eutectic Systems

Authors: Lin Po-Hsi, Sheu Ming-Thau

Abstract:

Urea cycle disorders (UCD) are rare genetic metabolic disorders that compromise the body's urea cycle. Sodium phenylbutyrate (SPB) is a medication commonly administered in tablet or powder form to lower ammonia levels. Nonetheless, its high sodium content poses risks to sodium-sensitive UCD patients. This necessitates the creation of an alternative drug formulation to mitigate sodium load and optimize drug delivery for UCD patients. This study focused on crafting a novel oral drug formulation for UCD, leveraging choline bicarbonate and phenylbutyric acid. The active pharmaceutical ingredient-ionic liquids (API-ILs) and therapeutic deep eutectic systems (THEDES) were formed by combining these with choline chloride. These systems display characteristics like maintaining a liquid state at room temperature and exhibiting enhanced solubility. This in turn amplifies drug dissolution rate, permeability, and ultimately oral bioavailability. Incorporating choline-based phenylbutyric acid as a substitute for traditional SPB can effectively curtail the sodium load in UCD patients. Our in vitro dissolution experiments revealed that the ILs and DESs, synthesized using choline bicarbonate and choline chloride with phenylbutyric acid, surpassed commercial tablets in dissolution speed. Pharmacokinetic evaluations in SD rats indicated a notable uptick in the oral bioavailability of phenylbutyric acid, underscoring the efficacy of choline salt ILs in augmenting its bioavailability. Additional in vitro intestinal permeability tests on SD rats authenticated that the ILs, formulated with choline bicarbonate and phenylbutyric acid, demonstrate superior permeability compared to their sodium and acid counterparts. To conclude, choline salt ILs developed from choline bicarbonate and phenylbutyric acid present a promising avenue for UCD treatment, with the added benefit of reduced sodium load. They also hold merit in formulation engineering. The sustained-release capabilities of DESs position them favorably for drug delivery, while the low toxicity and cost-effectiveness of choline chloride signal potential in formulation engineering. Overall, this drug formulation heralds a prospective therapeutic avenue for UCD patients.

Keywords: phenylbutyric acid, sodium phenylbutyrate, choline salt, ionic liquids, deep eutectic systems, oral bioavailability

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2865 Design, Synthesis and Pharmacological Investigation of Novel 2-Phenazinamine Derivatives as a Mutant BCR-ABL (T315I) Inhibitor

Authors: Gajanan M. Sonwane

Abstract:

Nowadays, the entire pharmaceutical industry is facing the challenge of increasing efficiency and innovation. The major hurdles are the growing cost of research and development and a concurrent stagnating number of new chemical entities (NCEs). Hence, the challenge is to select the most druggable targets and to search the equivalent drug-like compounds, which also possess specific pharmacokinetic and toxicological properties that allow them to be developed as drugs. The present research work includes the studies of developing new anticancer heterocycles by using molecular modeling techniques. The heterocycles synthesized through such methodology are much effective as various physicochemical parameters have been already studied and the structure has been optimized for its best fit in the receptor. Hence, on the basis of the literature survey and considering the need to develop newer anticancer agents, new phenazinamine derivatives were designed by subjecting the nucleus to molecular modeling, viz., GQSAR analysis and docking studies. Simultaneously, these designed derivatives were subjected to in silico prediction of biological activity through PASS studies and then in silico toxicity risk assessment studies. In PASS studies, it was found that all the derivatives exhibited a good spectrum of biological activities confirming its anticancer potential. The toxicity risk assessment studies revealed that all the derivatives obey Lipinski’s rule. Amongst these series, compounds 4c, 5b and 6c were found to possess logP and drug-likeness values comparable with the standard Imatinib (used for anticancer activity studies) and also with the standard drug methotrexate (used for antimitotic activity studies). One of the most notable mutations is the threonine to isoleucine mutation at codon 315 (T315I), which is known to be resistant to all currently available TKI. Enzyme assay planned for confirmation of target selective activity.

Keywords: drug design, tyrosine kinases, anticancer, Phenazinamine

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2864 Increased Retention of Nanoparticle by Small Molecule Inhibitor in Cancer Cells

Authors: Neha Singh

Abstract:

Background: Nowadays, the nanoparticle is gaining unexceptional attention in targeted drug delivery. But before proceeding to this episode of accomplishment, the journey and closure of these nanoparticles inside the cells should be disentangle. Being foreign for the cells, nanoparticles will easily getcleared off without any effective outcome. As the cancer cells withhold these nanoparticles for a longer period of time, more will be the drug’s effect. Chlorpromazine is a cationic amphiphilic drug which is believed to inhibit clathrin-coated pit formation by a reversible translocation of clathrin and its adapter proteins from the plasma membrane to intracellular vesicles. Chlorpromazine has a role in increasing the retention of nanoparticles in cancer cells. The mechanism of action how this small molecule increases the retention of nanoparticles is still uncovered. Method: Polymeric nanoparticle (PLGA) with Cyanine3.5 dye were synthesized by solvent evaporation method and characterized for size and zeta potential. FTIR was also done. Pulse and chase studies with and without inhibitor were done to check the retention of nanoparticle using fluorescence microscopy. Mean fluorescence intensity was measured by ImageJ software. Results: Increased retention of nanoparticle with inhibitor was observed in both pulse and chase studies. Conclusion: Our results demonstrate that by repurposing these small molecule inhibitor, we can increase the retention of nanoparticle at the targeted site.

Keywords: nanoparticle, endocytosis, clathrin inhibitor, cancer cell

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2863 Delivery of Positively Charged Proteins Using Hyaluronic Acid Microgels

Authors: Elaheh Jooybar, Mohammad J. Abdekhodaie, Marcel Karperien, Pieter J. Dijkstra

Abstract:

In this study, hyaluronic acid (HA) microgels were developed for the goal of protein delivery. First, a hyaluronic acid-tyramine conjugate (HA-TA) was synthesized with a degree of substitution of 13 TA moieties per 100 disaccharide units. Then, HA-TA microdroplets were produced using a water in oil emulsion method and crosslinked in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). Loading capacity and the release kinetics of lysozyme and BSA, as model proteins, were investigated. It was shown that lysozyme, a cationic protein, can be incorporated efficiently in the HA microgels, while the loading efficiency for BSA, as a negatively charged protein, is low. The release profile of lysozyme showed a sustained release over a period of one month. The results demonstrated that the HA-TA microgels are a good carrier for spatial delivery of cationic proteins for biomedical applications.

Keywords: microgel, inverse emulsion, protein delivery, hyaluronic acid, crosslinking

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2862 Radiofrequency and Near-Infrared Responsive Core-Shell Multifunctional Nanostructures Using Lipid Templates for Cancer Theranostics

Authors: Animesh Pan, Geoffrey D. Bothun

Abstract:

With the development of nanotechnology, research in multifunctional delivery systems has a new pace and dimension. An incipient challenge is to design an all-in-one delivery system that can be used for multiple purposes, including tumor targeting therapy, radio-frequency (RF-), near-infrared (NIR-), light-, or pH-induced controlled release, photothermal therapy (PTT), photodynamic therapy (PDT), and medical diagnosis. In this regard, various inorganic nanoparticles (NPs) are known to show great potential as the 'functional components' because of their fascinating and tunable physicochemical properties and the possibility of multiple theranostic modalities from individual NPs. Magnetic, luminescent, and plasmonic properties are the three most extensively studied and, more importantly biomedically exploitable properties of inorganic NPs. Although successful attempts of combining any two of them above mentioned functionalities have been made, integrating them in one system has remained challenge. Keeping those in mind, controlled designs of complex colloidal nanoparticle system are one of the most significant challenges in nanoscience and nanotechnology. Therefore, systematic and planned studies providing better revelation are demanded. We report a multifunctional delivery platform-based liposome loaded with drug, iron-oxide magnetic nanoparticles (MNPs), and a gold shell on the surface of liposomes, were synthesized using a lipid with polyelectrolyte (layersomes) templating technique. MNPs and the anti-cancer drug doxorubicin (DOX) were co-encapsulated inside liposomes composed by zwitterionic phophatidylcholine and anionic phosphatidylglycerol using reverse phase evaporation (REV) method. The liposomes were coated with positively charge polyelectrolyte (poly-L-lysine) to enrich the interface with gold anion, exposed to a reducing agent to form a gold nanoshell, and then capped with thio-terminated polyethylene glycol (SH-PEG2000). The core-shell nanostructures were characterized by different techniques like; UV-Vis/NIR scanning spectrophotometer, dynamic light scattering (DLS), transmission electron microscope (TEM). This multifunctional system achieves a variety of functions, such as radiofrequency (RF)-triggered release, chemo-hyperthermia, and NIR laser-triggered for photothermal therapy. Herein, we highlight some of the remaining major design challenges in combination with preliminary studies assessing therapeutic objectives. We demonstrate an efficient loading and delivery system to significant cell death of human cancer cells (A549) with therapeutic capabilities. Coupled with RF and NIR excitation to the doxorubicin-loaded core-shell nanostructure helped in securing targeted and controlled drug release to the cancer cells. The present core-shell multifunctional system with their multimodal imaging and therapeutic capabilities would be eminent candidates for cancer theranostics.

Keywords: cancer thernostics, multifunctional nanostructure, photothermal therapy, radiofrequency targeting

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2861 Prussian Blue/Chitosan Mixed-Matrix Membranes with Improved Separation Performance of Ethanol/Water Mixtures

Authors: Ting-YuLiu, Yi-Feng Lin

Abstract:

Porous Prussian Blue (PB) nanoparticles were successfully incorporated into chitosan (CS) membranes to form PB/CS mixed-matrix membranes (MMMs) and the as-prepared PB/CS MMMs were used to dehydration of ethanol at 25 oC in the pervaporation process. The effect of PB loading in CS matrix on pervaporation performance was investigated. The FESEM, EDS, FTIR and XRD measurements were also used for the characterization of the PB/CS MMMs. The PB/CS membranes with 30 wt% PB loading show the best performance with the permeate flux of 614 g/m2h and the separation factor of 1472. The pervaporation using the PB/CS membranes exhibits outstanding performance as compared with the previously reported CS based membranes and MMMs. The present work demonstrates good pervaporation performance of the PB/CS MMMs for the separation of 90wt% ethanol aqueous solution, moreover, it has an opportunity for dehydration of bioethanol in this system of pervaporation.

Keywords: pervaporation, chitosan, Prussian blue, mixed-matrix membrane

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2860 Efficient Moment Frame Structure

Authors: Mircea I. Pastrav, Cornelia Baera, Florea Dinu

Abstract:

A different concept for designing and detailing of reinforced concrete precast frame structures is analyzed in this paper. The new detailing of the joints derives from the special hybrid moment frame joints. The special reinforcements of this alternative detailing, named modified special hybrid joint, are bondless with respect to both column and beams. Full scale tests were performed on a plan model, which represents a part of 5 story structure, cropped in the middle of the beams and columns spans. Theoretical approach was developed, based on testing results on twice repaired model, subjected to lateral seismic type loading. Discussion regarding the modified special hybrid joint behavior and further on widening research needed concludes the presentation.

Keywords: modified hybrid joint, repair, seismic loading type, acceptance criteria

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2859 Enhanced Thermal Properties of Rigid PVC Foams Using Fly Ash

Authors: Nidal H. Abu-Zahra, Parisa Khoshnoud, Murtatha Jamel, Subhashini Gunashekar

Abstract:

PVC foam-fly ash composites (PVC-FA) are characterized for their structural, morphological, mechanical and thermal properties. The tensile strength of the composites increased modestly with higher fly ash loading, while there was a significant increase in the elastic modulus for the same composites. On the other hand, a decrease in elongation at UTS was observed upon increasing fly ash content due to increased rigidity of the composites. Similarly, the flexural modulus increased as the fly ash loading increased, where the composites containing 25 phr fly ash showed the highest flexural strength. Thermal properties of PVC-fly ash composites were determined by Thermo Gravimetric Analysis (TGA). The micro structural properties were studied by Scanning Electron Microscopy (SEM). SEM results confirm that fly ash particles were mechanically interlocked in PVC matrix with good inter facial interaction with the matrix. Particle agglomeration and debonding was observed in samples containing higher amounts of fly ash.

Keywords: PVC foam, polyvinyl chloride, rigid PVC, fly ash composites, polymer composites

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2858 Structural Performance of Mechanically Connected Stone Panels under Cyclic Loading: Application to Aesthetic and Environmental Building Skin Design

Authors: Michel Soto Chalhoub

Abstract:

Building designers in the Mediterranean region and other parts of the world utilize natural stone panels on the exterior façades as skin cover. This type of finishing is not only intended for aesthetic reasons but also environmental. The stone, since the earliest ages of civilization, has been used in construction and to-date some of the most appealing buildings owe their beauty to stone finishing. The stone also provides warmth in winter and freshness in summer as it moderates heat transfer and absorbs radiation. However, as structural codes became increasingly stringent about the dynamic performance of buildings, it became essential to study the performance of stone panels under cyclic loading – a condition that arises under the building is subjected to wind or earthquakes. The present paper studies the performance of stone panels using mechanical connectors when subjected to load reversal. In this paper, we present a theoretical model that addresses modes of failure in the steel connectors, by yield, and modes of failure in the stone, by fracture. Then we provide an experimental set-up and test results for rectangular stone panels of varying thickness. When the building is subjected to an earthquake, its rectangular panels within the structural system are subjected to shear deformations, which in turn impart stress into the stone cover. Rectangular stone panels, which typically range from 40cmx80cm to 60cmx120cm, need to be designed to withstand transverse loading from the direct application of lateral loads, and to withstand simultaneously in-plane loading (membrane stress) caused by inter-story drift and overall building lateral deflection. Results show correlation between the theoretical model which we derive from solid mechanics fundamentals and the experimental results, and lead to practical design recommendations. We find that for panel thickness below a certain threshold, it is more advantageous to utilize structural adhesive materials to connect stone panels to the main structural system of the building. For larger panel thicknesses, it is recommended to utilize mechanical connectors with special detailing to ensure a minimum level of ductility and energy dissipation.

Keywords: solid mechanics, cyclic loading, mechanical connectors, natural stone, seismic, wind, building skin

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2857 Full-Field Estimation of Cyclic Threshold Shear Strain

Authors: E. E. S. Uy, T. Noda, K. Nakai, J. R. Dungca

Abstract:

Cyclic threshold shear strain is the cyclic shear strain amplitude that serves as the indicator of the development of pore water pressure. The parameter can be obtained by performing either cyclic triaxial test, shaking table test, cyclic simple shear or resonant column. In a cyclic triaxial test, other researchers install measuring devices in close proximity of the soil to measure the parameter. In this study, an attempt was made to estimate the cyclic threshold shear strain parameter using full-field measurement technique. The technique uses a camera to monitor and measure the movement of the soil. For this study, the technique was incorporated in a strain-controlled consolidated undrained cyclic triaxial test. Calibration of the camera was first performed to ensure that the camera can properly measure the deformation under cyclic loading. Its capacity to measure deformation was also investigated using a cylindrical rubber dummy. Two-dimensional image processing was implemented. Lucas and Kanade optical flow algorithm was applied to track the movement of the soil particles. Results from the full-field measurement technique were compared with the results from the linear variable displacement transducer. A range of values was determined from the estimation. This was due to the nonhomogeneous deformation of the soil observed during the cyclic loading. The minimum values were in the order of 10-2% in some areas of the specimen.

Keywords: cyclic loading, cyclic threshold shear strain, full-field measurement, optical flow

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2856 Alumina Supported Copper-Manganese Catalysts for Combustion of Exhaust Gases: Effect of Preparation Method

Authors: Krasimir Ivanov, Elitsa Kolentsova, Dimitar Dimitrov

Abstract:

The development of active and stable catalysts without noble metals for low temperature oxidation of exhaust gases remains a significant challenge. The purpose of this study is to determine the influence of the preparation method on the catalytic activity of the supported copper-manganese mixed oxides in terms of VOCs oxidation. The catalysts were prepared by impregnation of γ-Al2O3 with copper and manganese nitrates and acetates and the possibilities for CO, CH3OH and dimethyl ether (DME) oxidation were evaluated using continuous flow equipment with a four-channel isothermal stainless steel reactor. Effect of the support, Cu/Mn mole ratio, heat treatment of the precursor and active component loading were investigated. Highly active alumina supported Cu-Mn catalysts for CO and VOCs oxidation were synthesized. The effect of preparation conditions on the activity behavior of the catalysts was discussed. The synergetic interaction between copper and manganese species increases the activity for complete oxidation over mixed catalysts. Type of support, calcination temperature and active component loading along with catalyst composition are important factors, determining catalytic activity. Cu/Mn molar ratio of 1:5, heat treatment at 450oC and 20 % active component loading are the best compromise for production of active catalyst for simultaneous combustion of CO, CH3OH and DME.

Keywords: copper-manganese catalysts, CO, VOCs oxidation, exhaust gases

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2855 Oral Betahistine Versus Intravenous Diazepam in Acute Peripheral Vertigo: A Randomized, Double-Blind Controlled Trial

Authors: Saeed Abbasi, Davood Farsi, Soudabeh Shafiee Ardestani, Neda Valizadeh

Abstract:

Objectives: Peripheral vertigo is a common complaint of patients who are visited in emergency departments. In our study, we wanted to evaluate the effect of betahistine as an oral drug vs. intravenous diazepam for the treatment of acute peripheral vertigo. We also wanted to see the possibility of substitution of parenteral drug with an oral one with fewer side effects. Materials and Methods: In this randomized, double-blind study, 101 patients were enrolled in the study. The patients were divided in two groups in a double-blind randomized manner. Group A took oral placebo and 10 mg of intravenous diazepam. Group B received 8mg of oral betahistine and intravenous placebo. Patients’ symptoms and signs (Vertigo severity, Nausea, Vomiting, Nistagmus and Gate) were evaluated after 0, 2, 4, 6 hours by emergency physicians and data were collected by a questionnaire. Results: In both groups, there was significant improvement in vertigo (betahistine group P=0.02 and Diazepam group P=0.03). Analysis showed more improvement in vertigo severity after 4 hours of treatment in betahistine group comparing to diazepam group (P=0.02). Nausea and vomiting were significantly lower in patients receiving diazepam after 2 and 6 hours (P=0.02 & P=0.03).No statistically significant differences were found between the groups in nistagmus, equilibrium & vertigo duration. Conclusion: The results of this randomized trial showed that both drugs had acceptable therapeutic effects in peripheral vertigo, although betahistine was significantly more efficacious after 4 hours of drug intake. As for higher nausea and vomiting in betahistine group, physician should consider these side effects before drug prescription.

Keywords: acute peripheral vertigo, betahistine, diazepam, emergency department

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2854 Investigation of Crack Formation in Ordinary Reinforced Concrete Beams and in Beams Strengthened with Carbon Fiber Sheet: Theory and Experiment

Authors: Anton A. Bykov, Irina O. Glot, Igor N. Shardakov, Alexey P. Shestakov

Abstract:

This paper presents the results of experimental and theoretical investigations of the mechanisms of crack formation in reinforced concrete beams subjected to quasi-static bending. The boundary-value problem has been formulated in the framework of brittle fracture mechanics and has been solved by using the finite-element method. Numerical simulation of the vibrations of an uncracked beam and a beam with cracks of different size serves to determine the pattern of changes in the spectrum of eigenfrequencies observed during crack evolution. Experiments were performed on the sequential quasistatic four-point bending of the beam leading to the formation of cracks in concrete. At each loading stage, the beam was subjected to an impulse load to induce vibrations. Two stages of cracking were detected. At the first stage the conservative process of deformation is realized. The second stage is an active cracking, which is marked by a sharp change in eingenfrequencies. The boundary of a transition from one stage to another is well registered. The vibration behavior was examined for the beams strengthened by carbon-fiber sheet before loading and at the intermediate stage of loading after the grouting of initial cracks. The obtained results show that the vibrodiagnostic approach is an effective tool for monitoring of cracking and for assessing the quality of measures aimed at strengthening concrete structures.

Keywords: crack formation, experiment, mathematical modeling, reinforced concrete, vibrodiagnostics

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2853 Prediction of the Behavior of 304L Stainless Steel under Uniaxial and Biaxial Cyclic Loading

Authors: Aboussalih Amira, Zarza Tahar, Fedaoui Kamel, Hammoudi Saleh

Abstract:

This work focuses on the simulation of the prediction of the behaviour of austenitic stainless steel (SS) 304L under complex loading in stress and imposed strain. The Chaboche model is a cable to describe the response of the material by the combination of two isotropic and nonlinear kinematic work hardening, the model is implemented in the ZébuLon computer code. First, we represent the evolution of the axial stress as a function of the plastic strain through hysteresis loops revealing a hardening behaviour caused by the increase in stress by stress in the direction of tension/compression. In a second step, the study of the ratcheting phenomenon takes a key place in this work by the appearance of the average stress. In addition to the solicitation of the material in the biaxial direction in traction / torsion.

Keywords: damage, 304L, Ratcheting, plastic strain

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2852 Formulation and Evaluation of Mouth Dissolving Tablet of Ketorolac Tromethamine by Using Natural Superdisintegrants

Authors: J. P. Lavande, A. V.Chandewar

Abstract:

Mouth dissolving tablet is the speedily growing and highly accepted drug delivery system. This study was aimed at development of Ketorolac Tromethamine mouth dissolving tablet (MDTs), which can disintegrate or dissolve rapidly once placed in the mouth. Conventional Ketorolac tromethamine tablet requires water to swallow it and has limitation like low disintegration rate, low solubility etc. Ketorolac Tromethamine mouth dissolving tablets (formulation) consist of super-disintegrate like Heat Modified Karaya Gum, Co-treated Heat Modified Agar & Filler microcrystalline cellulose (MCC). The tablets were evaluated for weight variation, friability, hardness, in vitro disintegration time, wetting time, in vitro drug release profile, content uniformity. The obtained results showed that low weight variation, good hardness, acceptable friability, fast wetting time. Tablets in all batches disintegrated within 15-50 sec. The formulation containing superdisintegrants namely heat modified karaya gum and heat modified agar showed better performance in disintegration and drug release profile.

Keywords: mouth dissolving tablet, Ketorolac tromethamine, disintegration time, heat modified karaya gum, co-treated heat modified agar

Procedia PDF Downloads 281
2851 The Impact of Combined Loading on Lateral Capacity and Group Efficiency of Helical Piles

Authors: Hesham Hamdy Abdulmohsen, Ahmed Shawky Abdel Aziz, Mona Fawzy Aldaghma

Abstract:

Helical piles have gained significant attention as efficient alternatives for deep foundations due to their rapid installation process and dual functionality in compression and tension. They experience various combinations of axial and lateral loads. While extensive research has explored helical pile behavior under individual axial or lateral loads, the effects of combined axial compression and lateral loads still need further study. This paper compares experimental and numerical (PLAXIS-3D) results for vertical helical-pile groups under combined loads. The study aims to clarify the impact of key factors, including helix location and lateral load direction, on the lateral capacity of helical-pile groups and, consequently, their overall efficiency. The study concludes that the lateral capacity of the helical-pile group significantly depends on the helix location within the pile shaft length. Optimal lateral performance occurs when helices are positioned at a depth ratio of H/L = 0.4. Furthermore, rectangular plan distribution groups exhibit greater lateral capacity when subjected to lateral loads aligned with their long axis. The presence of vertical compression loading enhances the lateral capacity of the group, with the specific enhancement depending on the value of the vertical compression load, lateral load direction, and helix location.

Keywords: experimental, numerical model, lateral loading, group efficiency, helical piles

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2850 Investigating the Dynamic Plantar Pressure Distribution in Individuals with Multiple Sclerosis

Authors: Hilal Keklicek, Baris Cetin, Yeliz Salci, Ayla Fil, Umut Altinkaynak, Kadriye Armutlu

Abstract:

Objectives and Goals: Spasticity is a common symptom characterized with a velocity dependent increase in tonic stretch reflexes (muscle tone) in patient with multiple sclerosis (MS). Hypertonic muscles affect the normal plantigrade contact by disturbing accommodation of foot to the ground while walking. It is important to know the differences between healthy and neurologic foot features for management of spasticity related deformities and/or determination of rehabilitation purposes and contents. This study was planned with the aim of investigating the dynamic plantar pressure distribution in individuals with MS and determining the differences between healthy individuals (HI). Methods: Fifty-five individuals with MS (108 foot with spasticity according to Modified Ashworth Scale) and 20 HI (40 foot) were the participants of the study. The dynamic pedobarograph was utilized for evaluation of dynamic loading parameters. Participants were informed to walk at their self-selected speed for seven times to eliminate learning effect. The parameters were divided into 2 categories including; maximum loading pressure (N/cm2) and time of maximum pressure (ms) were collected from heal medial, heal lateral, mid foot, heads of first, second, third, fourth and fifth metatarsal bones. Results: There were differences between the groups in maximum loading pressure of heal medial (p < .001), heal lateral (p < .001), midfoot (p=.041) and 5th metatarsal areas (p=.036). Also, there were differences between the groups the time of maximum pressure of all metatarsal areas, midfoot, heal medial and heal lateral (p < .001) in favor of HI. Conclusions: The study provided basic data about foot pressure distribution in individuals with MS. Results of the study primarily showed that spasticity of lower extremity muscle disrupted the posteromedial foot loading. Secondarily, according to the study result, spasticity lead to inappropriate timing during load transfer from hind foot to forefoot.

Keywords: multiple sclerosis, plantar pressure distribution, gait, norm values

Procedia PDF Downloads 320