Search results for: drug loading

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

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

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

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Authors: A. Y. Purnama, N. Yasufuku

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The bridge structure is a building that has to be maintained, especially for the elastomeric bearing. The girder of the bridge needs to be lifted upward to maintain this elastomeric bearing, that needs high cost. Nowadays, integral abutment bridges are becoming popular. The integral abutment bridge is less costly because the elastomeric bearings are eliminated, which reduces the construction cost and maintenance costs. However, when this elastomeric bearing removed, the girder movement due to environmental thermal forces directly support by pile foundation, and it needs to be considered in the design. In case of pile foundation in a stiff soil, in the top area of the pile cannot move freely due to the fixed condition by soil stiffness. Pre-bored pile system can be used to increase the flexibility of pile foundation using a pre-bored hole that filled with elastic materials, but the behavior of soil-pile interaction and soil response due to this system is still rarely explained. In this paper, an experimental study using small-scale laboratory model test conducted in a half size model. Single flexible pile model embedded in sandy soil with the pre-bored ring, which filled with the filler material. The testing box made from an acrylic glass panel as observation area of the pile shaft to monitor the displacement of the pile during the lateral loading. The failure behavior of the soil inside the pre-bored ring and around the pile shaft was investigated to determine the point of pile rotation and the movement of this point due to the pre-bored ring system along the pile shaft. Digital images were used to capture the deformations of the soil and pile foundation during the loading from the acrylic glass on the side of the testing box. The results were presented in the form of lateral load resistance charts against the pile shaft displacement. The failure pattern result also established due to the cyclic lateral loading. The movement of the rotational point was measured due to the pre-bored system filled with appropriate filler material. Based on the findings, design considerations for pre-bored pile system due to cyclic lateral loading can be introduced.

Keywords: failure behavior, pre-bored pile system, cyclic lateral loading, sandy soil

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Authors: Abdul Rochim, Didier Marot, Luc Sibille

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This paper studies the characterization of soil sensibility due to suffusion process by carrying out a series of one-dimensional downward seepage flow tests realized with an erodimeter. Tests were performed under controlled hydraulic gradient in sandy gravel soils. We propose the analysis based on energy induced by the seepage flow to characterize the hydraulic loading and the cumulative eroded dry mass to characterize the soil response. With this approach, the effect of hydraulic loading histories and initial fines contents to soil sensibility are presented. It is found that for given soils, erosion coefficients are different if tests are performed under different hydraulic loading histories. For given initial fines fraction contents, the sensibility may be grouped in the same classification. The lower fines content soils tend to require larger flow energy to the onset of erosion. These results demonstrate that this approach is effective to characterize suffusion sensibility for granular soils.

Keywords: erodimeter, sandy gravel, suffusion, water seepage energy

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Authors: Eugene Y. C. Wong, Daniel Y. W. Mo, Cosmo T. Y. Ng, Jessica K. Y. Chan, Leith K. Y. Chan, Henry Y. K. Lau

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The real-time planning visualisation, precise allocation and loading optimisation in air cargo load planning operations are increasingly important as more considerations are needed on dangerous cargo loading, locations of lithium batteries, weight declaration and limited aircraft capacity. The planning of the unit load devices (ULD) can often be carried out only in a limited number of hours before flight departure. A dynamic air cargo load planning system is proposed with the optimisation of cargo load plan and visualisation of planning results in virtual reality systems. The system aims to optimise the cargo load planning and visualise the simulated loading planning decision on air cargo terminal operations. Adopting simulation tools, Cave Automatic Virtual Environment (CAVE) and virtual reality technologies, the results of planning with reference to weight and balance, Unit Load Device (ULD) dimensions, gateway, cargo nature and aircraft capacity are optimised and presented. The virtual reality system facilities planning, operations, education and training. Staff in terminals are usually trained in a traditional push-approach demonstration with enormous manual paperwork. With the support of newly customized immersive visualization environment, users can master the complex air cargo load planning techniques in a problem based training with the instant result being immersively visualised. The virtual reality system is developed with three-dimensional (3D) projectors, screens, workstations, truss system, 3D glasses, and demonstration platform and software. The content will be focused on the cargo planning and loading operations in an air cargo terminal. The system can assist decision-making process during cargo load planning in the complex operations of air cargo terminal operations. The processes of cargo loading, cargo build-up, security screening, and system monitoring can be further visualised. Scenarios are designed to support and demonstrate the daily operations of the air cargo terminal, including dangerous goods, pets and animals, and some special cargos.

Keywords: air cargo load planning, optimisation, virtual reality, weight and balance, unit load device

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Authors: Sumit Roy, A. Uddin

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One of the significant reasons that increase the delay time in the intersections at heterogeneous traffic condition is a sudden reduction of the capacity of the roads. In this study, the delay for this sudden capacity reduction is estimated. Two intersections at Dhaka city were brought in to thestudy, i.e., Kakrail intersection, and SAARC Foara intersection. At Kakrail intersection, the sudden reduction of capacity in the roads is seen at three downstream legs of the intersection, which are because of slowing down or stopping of buses for loading and unloading of passengers. At SAARC Foara intersection, sudden reduction of capacity was seen at two downstream legs. At one leg, it was due to loading and unloading of buses, and at another leg, it was for both loading and unloading of buses and reduction of the number of lanes. With these considerations, the delay due to intentional stoppage or slowing down of buses and reduction of the number of lanes for these two intersections are estimated. Here the delay was calculated by two approaches. The first approach came from the concept of shock waves in traffic streams. Here the delay was calculated by determining the flow, density, and speed before and after the sudden capacity reduction. The second approach came from the deterministic analysis of queues. Here the delay is calculated by determining the volume, capacity and reduced capacity of the road. After determining the delay from these two approaches, the results were compared. For this study, the video of each of the two intersections was recorded for one hour at the evening peak. Necessary geometric data were also taken to determine speed, flow, and density, etc. parameters. The delay was calculated for one hour with one-hour data at both intersections. In case of Kakrail intersection, the per hour delay for Kakrail circle leg was 5.79, and 7.15 minutes, for Shantinagar cross intersection leg they were 13.02 and 15.65 minutes, and for Paltan T intersection leg, they were 3 and 1.3 minutes for 1st and 2nd approaches respectively. In the case of SAARC Foara intersection, the delay at Shahbag leg was only due to intentional stopping or slowing down of busses, which were 3.2 and 3 minutes respectively for both approaches. For the Karwan Bazar leg, the delays for buses by both approaches were 5 and 7.5 minutes respectively, and for reduction of the number of lanes, the delays for both approaches were 2 and 1.78 minutes respectively. Measuring the delay per hour for the Kakrail leg at Kakrail circle, it is seen that, with consideration of the first approach of delay estimation, the intentional stoppage and lowering of speed by buses contribute to 26.24% of total delay at Kakrail circle. If the loading and unloading of buses at intersection is made forbidden near intersection, and any other measures for loading and unloading of passengers are established far enough from the intersections, then the delay at intersections can be reduced at significant scale, and the performance of the intersections can be enhanced.

Keywords: delay, deterministic queue analysis, shock wave, passenger loading-unloading

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Authors: A. B. M. Rezaul Islam, Ernur Karadogan

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Shape memory alloys (SMAs) are known for their shape memory effect and pseudoelasticity behavior. Their thermomechanical behaviors are modeled by numerous researchers using microscopic thermodynamic and macroscopic phenomenological point of view. Tanaka, Liang-Rogers and Ivshin-Pence models are some of the most popular SMA macroscopic phenomenological constitutive models. They describe SMA behavior in terms of stress, strain and temperature. These models involve material parameters and they have associated uncertainty present in them. At different operating temperatures, the uncertainty propagates to the output when the material is subjected to loading followed by unloading. The propagation of uncertainty while utilizing these models in real-life application can result in performance discrepancies or failure at extreme conditions. To resolve this, we used probabilistic approach to perform the sensitivity and uncertainty analysis of Tanaka, Liang-Rogers, and Ivshin-Pence models. Sobol and extended Fourier Amplitude Sensitivity Testing (eFAST) methods have been used to perform the sensitivity analysis for simulated isothermal loading/unloading at various operating temperatures. As per the results, it is evident that the models vary due to the change in operating temperature and loading condition. The average and stress-dependent sensitivity indices present the most significant parameters at several temperatures. This work highlights the sensitivity and uncertainty analysis results and shows comparison of them at different temperatures and loading conditions for all these models. The analysis presented will aid in designing engineering applications by eliminating the probability of model failure due to the uncertainty in the input parameters. Thus, it is recommended to have a proper understanding of sensitive parameters and the uncertainty propagation at several operating temperatures and loading conditions as per Tanaka, Liang-Rogers, and Ivshin-Pence model.

Keywords: constitutive models, FAST sensitivity analysis, sensitivity analysis, sobol, shape memory alloy, uncertainty analysis

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Authors: Badr M. Alshammari, T. Guesmi

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In recent years, the combined economic and emission power dispatch is one of the main problems of electrical power system. It aims to schedule the power generation of generators in order to minimize cost production and emission of harmful gases caused by fossil-fueled thermal units such as CO, CO₂, NO_x, and SO₂. To solve this complicated multi-objective problem, an improved version of the particle swarm optimization technique that includes non-dominated sorting concept has been proposed. Valve point loading effects and system losses have been considered. The three-unit and ten-unit benchmark systems have been used to show the effectiveness of the suggested optimization technique for solving this kind of nonconvex problem. The simulation results have been compared with those obtained using genetic algorithm based method. Comparison results show that the proposed approach can provide a higher quality solution with better performance.

Keywords: power dispatch, valve point loading effects, multiobjective optimization, Pareto solutions

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Authors: Mogens Saberi

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The following article focuses on a new seismic design approach for Denmark. Denmark is located in a low seismic zone and up till now a general and very simplified approach has been used to accommodate the effect of seismic loading. The current used method is presented and it is found that the approach is on the unsafe side for many building types in Denmark. The damages during time due to earth quake is presented and a seismic map for Denmark is developed and presented. Furthermore, a new design approach is suggested and compared to the existing one. The new approach is relatively simple but captures the effect of seismic loading more realistic than the existing one. The new approach is believed to the incorporated in the Danish Deign Code for building structures.

Keywords: low seismicity, new design approach, earthquakes, Denmark

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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

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

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Authors: Huafeng Wei

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

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

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Authors: Leila Baghaarabani, Parvin Razzaghi, Mennatolla Magdy Mostafa, Ahmad Albaqsami, Al Warith Al Rushaidi, Masoud Al Rawahi

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Predicting the interaction between drugs and their molecular targets is pivotal for advancing drug development processes. Due to the time and cost limitations, computational approaches have emerged as an effective approach to drug-target interaction (DTI) prediction. Most of the introduced computational based approaches utilize the drug molecule and protein sequence as input. This study does not only utilize these inputs, it also introduces a protein representation developed using a masked protein language model. In this representation, for every individual amino acid residue within the protein sequence, there exists a corresponding probability distribution that indicates the likelihood of each amino acid being present at that particular position. Then, the similarity between each pair of amino acids is computed to create a similarity matrix. To encode the knowledge of the similarity matrix, Bi-Level Routing Attention (BiFormer) is utilized, which combines aspects of transformer-based models with protein sequence analysis and represents a significant advancement in the field of drug-protein interaction prediction. BiFormer has the ability to pinpoint the most effective regions of the protein sequence that are responsible for facilitating interactions between the protein and drugs, thereby enhancing the understanding of these critical interactions. Thus, it appears promising in its ability to capture the local structural relationship of the proteins by enhancing the understanding of how it contributes to drugprotein interactions, thereby facilitating more accurate predictions. To evaluate the proposed method, it was tested on two widely recognized datasets: Davis and KIBA. A comprehensive series of experiments was conducted to illustrate its effectiveness in comparison to cutting edge techniques.

Keywords: BiFormer, transformer, protein language processing, self-attention mechanism, binding affinity, drug target interaction, similarity matrix, protein masked representation, protein language model

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

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

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

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Authors: Minh-Phuong Ngoc Bui, Abdennour Abbas

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

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

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Authors: Hamida Hamed Said Al Harthi

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

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

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Authors: Abhay Asthana, Gyati Shilakari Asthana

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

Keywords: sustained biodegradation, wound healing, polymers, stability

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Authors: Yuvraj Singh Dangi, Kamta Prasad Namdeo, Surendra Bodhake

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The purpose of this research was to develop and evaluate mucoadhesive films for buccal administration of itraconazole using film-forming and mucoashesive polymers. Buccal films of chitosan bearing Itraconazole were prepared by solvent casting technique. The films have been evaluated in terms of film weight, thickness, density, surface pH, FTIR, X-ray diffraction analysis, bioadhesion, swelling properties, and in vitro drug release studies. It was found that film formulations of 2 cm2 size having weight in the range of 204 ± 0.76 to 223 ± 2.09 mg and film thickness were in the range of 0.44 ± 0.11 to 0.57 ± 0.19 mm. Density of the films was found to be 0.102 to 0.126 g/ml. Drug content was found to be uniform in the range of 8.23 ± 0.07 to 8.73 ± 0.09 mg/cm2 for formulation A1 to A4. Maximum bioadhesion force was recorded for HPMC buccal films (A2) i.e. 0.57 ± 0.47 as compared to other films. In vitro residence time was in range of 1.7 ± 0.12 to 7.65 ± 0.15 h. The drug release studies show that formulations follow non-fickian diffusion. These mucoadhesive formulations could offer many advantages in comparison to traditional treatments.

Keywords: biovariability, buccal patches, itraconazole, Mucoadhesion

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Authors: Alok Shiomurti Tripathi, Ajay Kumar Timiri, Papiya Mitra Mazumder, Anil Chandewar

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The present study evaluates the possible drug interaction between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ) induced in diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction by molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg/kg, ip) and confirms it by assessing the blood and urine biochemical parameters on 28th day of its induction. Selected DN animals were used for the drug interaction between GLIM (0.5mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) after 29th and 70th day of protocol. Drug interaction were assessed by evaluating the plasma drug concentration using HPLC-UV and also determine the change in the biochemical parameter in blood and urine. Mechanism of the interaction was postulated by molecular modeling study using Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in the blood and urine biochemical parameter in STZ treated groups. The concentration of SIL increased significantly (p<0.001) in rat plasma when co administered with GLIM after 70th day of protocol. Molecular modelling study revealed few important interactions with rat serum albumin and CYP2C9.GLIM has strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL. Whereas, for CYP2C9, GLIM has strong hydrogen bond with polar contacts and hydrophobic interactions than SIL. Present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals and mechanism has been supported by molecular modeling studies.

Keywords: diabetic nephropathy, glimepiride, sildenafil citrate, pharmacokinetics, homology modeling, schrodinger

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Authors: Deepika Sudevan, Patrick Rozycki, Laurent Gornet

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This paper presents the experimental identification of the fatigue limit for pristine and impacted Carbon Fiber Reinforced Epoxy polymer (CFRP) woven composites based on the relatively new self-heating methodology for composites. CFRP composites of [0/90]8 and quasi isotropic configurations prepared using hand-layup technique are subjected to low energy impacts (20 J energy) simulating a barely visible impact damage (BVID). Runway debris strike, tool drop or hailstone impact can cause a BVID on an aircraft fuselage made of carbon composites and hence understanding the post-impact fatigue response of CFRP laminates is of immense importance to the aerospace community. The BVID zone on the specimens is characterized using X-ray Tomography technique. Both pristine and impacted specimens are subjected to several blocks of constant amplitude (CA) fatigue loading keeping R-ratio a constant but with increments in the mean loading stress after each block. The number of loading cycles in each block is a subjective parameter and it varies for pristine and impacted CFRP specimens. To monitor the temperature evolution during fatigue loading, thermocouples are pasted on the CFRP specimens at specific locations. The fatigue limit is determined by two strategies, first is by considering the stabilized temperature in every block and second is by considering the change in the temperature slope per block. The results show that both strategies can be adopted to determine the fatigue limit in both pristine and impacted CFRP composites.

Keywords: CFRP, fatigue limit, low energy impact, self-heating, WRM

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Authors: Erfan Rahimi, Hadi Bahari Far, Mojgan Shikhpour

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Background: Urinary tract infection is one of the most common nosocomial infections, especially among women. E. coli is one of the main causes of urinary tract infections and one of the most common antibiotics to fight this bacterium is ampicillin. As conventional antibiotics led to bacterial antibiotic resistance, modification of the pure drugs can address this issue. The aim of this study was to prepare nanofluids containing carbon nanotubes conjugated with ampicillin to improve drug performance and reduce antibiotic resistance. Methods: Multi-walled carbon nanotubes (MWCNTs) were activated with thionyl chloride by reflux system and nanofluids containing antibiotics were prepared by ultrasonic method. The properties of the prepared nano-drug were investigated by general element analysis, infrared spectroscopy, Raman spectroscopy, scanning electron microscopy and transmission electron microscopy. After the treatment of the desired strain with nanofluid, microbial studies were performed to evaluate the antibacterial effects and molecular studies were carried out to measure the expression of the resistance gene AcrAB. Result: We have shown that the antimicrobial effect of ampicillin-functionalized MWCNTs at low concentrations performed better than that of the conventional drug in both resistant and ATCC strains. Also, a decrease in antibiotic resistance of bacteria treated with ampicillin-functionalized MWCNTs compared to the pure drug was observed. Also, ampicillin-functionalized MWCNTs downregulated the expression of AcrAB in treated bacteria. Conclusion: Because carbon nanotubes are capable of destroying the bacterial wall, which provides antibiotic resistance features in bacteria, their usage in the form of nanofluids can make lower dosages (about three times less) than that of the pure drug more effective. Additionally, the expression of the bacterial resistance gene AcrAB decreased, thereby reducing antibiotic resistance and improving drug performance against bacteria.

Keywords: urinary tract infection, antibiotic resistance, carbon nanotube, nanofluid

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Authors: Anthony George Armiger II

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This paper focuses on the counternarcotic strategies of US government agencies in Afghanistan from 2001-2014. Despite a heavy US presence in the country, Afghanistan currently accounts for 80% of opium production worldwide and remains a key contributor to the global drug market. This paper argues that the divergent counternarcotic strategies of various US government agencies on the ground in Afghanistan are a product of the organizational differences amongst those agencies and that those differences can challenge the implementation of counternarcotics policies in Afghanistan. To gain a more in-depth perspective, this paper analyzes the counternarcotic strategies of two US government agencies in Afghanistan; the United States Department of Defense (DoD) and the Drug Enforcement Administration (DEA). Utilizing the framework of the organizational behavior model of organizational theory, this paper will highlight the varying organizational interests, opinions, standard operating procedures, and routines of both of the government agencies. The paper concludes with implications on counternarcotics, as well as the counterinsurgency in Afghanistan and provides recommendations for future research on foreign policy and counternarcotics.

Keywords: Afghanistan, drug policy, organizational theory, United States foreign policy

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Authors: E. H. N. Gashti, M. Zarrini, M. Irannezhad, J. R. Langroudi

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Using ETABS software, this study analyzed 23 buildings to evaluate effects of mistakes during construction phase on buildings structural behavior. For modelling, two different loadings were assumed: 1) design loading and 2) loading due to the effects of mistakes in construction phase. Research results determined that considering traditional construction methods for buildings resulted in a significant increase in dead loads and consequently intensified the displacements and base-shears of buildings under seismic loads.

Keywords: reinforced-concrete buildings, construction mistakes, base-shear, displacements, failure

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Authors: Kwak, Hyo-Gyung, Gang, Han Gul

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In the context of an increasing need for reliability and safety in concrete structures under blast and impact loading condition, the behavior of concrete under high strain rate condition has been an important issue. Since concrete subjected to impact loading associated with high strain rate shows quite different material behavior from that in the static state, several material models are proposed and used to describe the high strain rate behavior under blast and impact loading. In the process of modelling, in advance, mesh dependency in the used finite element (FE) is the key problem because simulation results under high strain-rate condition are quite sensitive to applied FE mesh size. It means that the accuracy of simulation results may deeply be dependent on FE mesh size in simulations. This paper introduces an improved criterion which can minimize the mesh-dependency of simulation results on the basis of the fracture energy concept, and HJC (Holmquist Johnson Cook), CSC (Continuous Surface Cap) and K&C (Karagozian & Case) models are examined to trace their relative sensitivity to the used FE mesh size. To coincide with the purpose of the penetration test with a concrete plate under a projectile (bullet), the residual velocities of projectile after penetration are compared. The correlation studies between analytical results and the parametric studies associated with them show that the variation of residual velocity with the used FE mesh size is quite reduced by applying a unique failure strain value determined according to the proposed criterion.

Keywords: high strain rate concrete, penetration simulation, failure strain, mesh-dependency, fracture energy

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Authors: Nadjet Mekaouche, Hanane Zitouni, Fatma Boudia, Habiba Fetati, A. Saleh, A. Lardjam, H. Geniaux, A. Coubret, H. Toumi

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Medicines have undeniably played a major role in prolonging shelf life and improving quality. The absolute efficacy of the drug remains a lever for innovation, its benefit/risk balance is not always assured and it does not always have the expected effects. Prior to marketing, knowledge about adverse drug reactions is incomplete. Once on the market, phase IV drug studies begin. For years, the drug was prescribed with less care to a large number of very heterogeneous patients and often in combination with other drugs. It is at this point that previously unknown adverse effects may appear, hence the need for the implementation of a pharmacovigilance system. Pharmacovigilance represents all methods for detecting, evaluating, informing and preventing the risks of adverse drug reactions. The most severe adverse events occur frequently in hospital and that a significant proportion of adverse events result in hospitalizations. In addition, the consequences of hospital adverse events in terms of length of stay, mortality and costs are considerable. It, therefore, appears necessary to develop ‘hospital pharmacovigilance’ aimed at reducing the incidence of adverse reactions in hospitals. The most widely used monitoring method in pharmacovigilance is spontaneous notification. However, underreporting of adverse drug reactions is common in many countries and is a major obstacle to pharmacovigilance assessment. It is in this context that this study aims to describe the experience of the pharmacovigilance service at the University Hospital of Oran (EHUO). This is a retrospective study extending from 2011 to 2017, carried out on archived records of declarations collected at the level of the EHUO Pharmacovigilance Department. Reporting was collected by two methods: ‘spontaneous notification’ and ‘active pharmacovigilance’ targeting certain clinical services. We counted 217 statements. It involved 56% female patients and 46% male patients. Age ranged from 5 to 78 years with an average of 46 years. The most common adverse reaction was drug toxidermy. For the drugs in question, they were essentially according to the ATC classification of anti-infectives followed by anticancer drugs. As regards the evolution of declarations by year, a low rate of notification was noted in 2011. That is why we decided to set up an active approach at the level of some services where a resident of reference attended the staffs every week. This has resulted in an increase in the number of reports. The declarations came essentially from the services where the active approach was installed. This highlights the need for ongoing communication between all relevant health actors to stimulate reporting and secure drug treatments.

Keywords: adverse drug reactions, hospital, pharmacovigilance, spontaneous notification

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Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu

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In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.

Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles

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Authors: Shashank Tiwari

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The most common method of drug delivery is the oral solid dosage form, of which tablets and capsules are predominant. The tablet is more widely accepted and used compared to capsules for a number of reasons, such as cost/price, tamper resistance, ease of handling and packaging, ease of identification, and manufacturing efficiency. Over the past several years, the issue of tamper resistance has resulted in the conversion of most over-the-counter (OTC) drugs from capsules to predominantly all tablets.

Keywords: capsule, drug delivery, dosages, solid, tablet

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Authors: Poteet Frances, Glovinski Ira

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INTRODUCTION: The interoceptive nervous system continuously senses chemical and anatomical changes and helps you recognize, understand, and feel what’s going on inside your body so it is important for energy regulation, memory, affect, and sense of self. A newborn needs predictable routines rather than confusion/chaos to make connections between internal experiences and emotions. AIM: Current legal protocols of removing babies from drug-addicted mothers impact the critical window of bonding. The newborn’s brain is social and the attachment process influences a child’s development which begins immediately after birth through nourishment, comfort, and protection. DESCRIPTION: Our project aims to educate drug-addicted mothers, and medical, nursing, and social work professionals on interoceptive concepts and practices to sustain the mother/newborn relationship. A mother’s interoceptive knowledge predicts children’s emotion regulation and social skills in middle childhood. CONCLUSION: When mothers develop an awareness of their inner bodily sensations, they can self-regulate and be emotionally available to co-regulate (support their newborn during distressing emotions and sensations). Our project has enhanced relationship preservation (mothers understand how their presence matters) and the overall mother/newborn connection.

Keywords: drug-addiction, interoception, legal, mothers, newborn, self-regulation

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Authors: Hamid Ahmadi, Neda Azari-Dodaran

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A total of 270 nonlinear steady-state finite element (FE) analyses were performed on 54 FE models of two-planar circular hollow section (CHS) KK-joints subjected to axial loading at five different temperatures (20 ºC, 200 ºC, 400 ºC, 550 ºC, and 700 ºC). The primary goal was to investigate the effects of temperature and geometrical characteristics on the ultimate strength, modes of failure, and initial stiffness of the KK-joints. Results indicated that on an average basis, the ultimate load of a two-planar tubular KK-joint at 200 ºC, 400 ºC, 550 ºC, and 700 ºC is 90%, 75%, 45%, and 16% of the joint’s ultimate load at ambient temperature, respectively. Outcomes of the parametric study showed that replacing the yield stress at ambient temperature with the corresponding value at elevated temperature to apply the EN 1993-1-8 equations for the calculation of the joint’s ultimate load at elevated temperatures may lead to highly unconservative results that might endanger the safety of the structure. Results of the parametric study were then used to develop a set of design formulas, through nonlinear regression analyses, to calculate the ultimate load of two-planar tubular KK-joints subjected to axial loading at elevated temperatures.

Keywords: ultimate load, two-planar tubular KK-joint, axial loading, elevated temperature, parametric equation

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Authors: Chayanon Hansapinyo

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This paper presents experimental investigation and finite element analysis on buckling behavior of irregular section cold-formed steel columns under axially concentric loading. For the experimental study, four different sections of columns were tested to investigate effect of stiffening and width-to-thickness ratio on buckling behavior. For each of the section, three lengths of 230, 950 and 1900 mm. were studied representing short, intermediate long and long columns, respectively. Then, nonlinear finite element analyses of the tested columns were performed. The comparisons in terms of load-deformation response and buckling mode show good agreement and hence the FEM models were validated. Parametric study of stiffening element and thickness of 1.0, 1.15, 1.2, 1.5, 1.6 and 2.0 mm. were analyzed. The test results showed that stiffening effect pays a large contribution to prevent distortional mode. The increase in wall thickness enhanced buckling stress beyond the yielding strength in short and intermediate columns, but not for the long columns.

Keywords: buckling behavior, irregular section, cold-formed steel, concentric loading

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Authors: Trunal Bhujangrao, Catherine Froustey, Fernando Veiga, Philippe Darnis, Franck Girot Mata

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The understanding of the material behavior under shear loading has great importance for a researcher in manufacturing processes like cutting, machining, milling, turning, friction stir welding, etc. where the material experiences large deformation at high temperature. For such material behavior analysis, hot shear tests provide a useful means to investigate the evolution of the microstructure at a wide range of temperature and to improve the material behavior model. Shear tests can be performed by direct shear loading (e.g. torsion of thin-walled tubular samples), or appropriate specimen design to convert a tensile or compressive load into shear (e.g. simple shear tests). The simple shear tests are straightforward and designed to obtained very large deformation. However, many of these shear tests are concerned only with the elastic response of the material. It is becoming increasingly important to capture a plastic response of the material. Plastic deformation is significantly more complex and is known to depend more heavily on the strain rate, temperature, deformation, etc. Besides, there is not enough work is done on high-temperature shear loading, because of geometrical instability occurred during the plastic deformation. The aim of this study is to design a new shear tensile specimen geometry to convert the tensile load into dominant shear loading under plastic deformation. Design of the specimen geometry is based on FEM. The material used in this paper is AA7075 alloy, tested quasi statically under elevated temperature. Finally, the microstructural changes taking place during

Keywords: AA7075 alloy, dynamic recrystallization, edge effect, large strain, shear tensile test

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Authors: B. Daee, H. M. El Naggar

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This paper presents an experimental study on structural performance of an innovative noise barrier consisting of poly-block, light polyurethane foam (LPF) and polyurea. This wall system (flexi-wall) is intended to be employed as a vertical extension to existing sound barriers in an accelerated construction method. To aid in the wall design, several mechanical tests were conducted on LPF specimens and two full-scale walls were then fabricated employing the same LPF material. The full-scale walls were subjected to lateral loading in order to establish their lateral resistance. A cyclic fatigue test was also performed on a full-scale flexi-wall in order to evaluate the performance of the wall under a repetitive loading condition. The result of the experiments indicated the suitability of flexi-wall in accelerated construction and confirmed that the structural performance of the wall system under lateral loading is satisfactory for the sound barrier application. The experimental results were discussed and a preliminary design procedure for application of flexi-wall in sound barrier applications was also developed.

Keywords: noise barrier, polyurethane foam, accelerated construction, full-scale experiment

Procedia PDF Downloads 291