Search results for: drug property prediction

Authors: Tamrat Balcha Balla

Abstract:

Background: Tablets are still the most preferred means of drug delivery. The search for new and improved direct compression tablet excipients is an area of research focus. Taro Boloso-I is a variety of Colocasia esculenta (L. Schott) yielding 67% more than the other varieties (Godare) in Ethiopia. This study aimed to enhance the flowability while keeping the compressibility and compactibility of the pregelatinized Taro Boloso-I starch. Methods: Central composite design was used for the optimization of two factors which were the temperature and duration of pregelatinization against 5 responses. The responses were angle of repose, Hausner ratio, Kawakita compressibility index, mean yield pressure and tablet breaking force. Results and Discussions: An increase in both temperature and time resulted in decrease in the angle of repose. The increase in temperature was shown to decrease the Hausner ratio and to decrease the Kawakita compressibility index. The mean yield pressure was observed to increase with increasing levels of both temperature and time. The pregelatinized (optimized) Taro Boloso-I starch could show desired flow property and compressibility. Conclusions: Pregelatinized Taro Boloso - I starch could be regarded as a potential direct compression excipient in terms of flowability, compressibility and compactibility.

Keywords: starch, compression, pregelatinization, Taro Boloso-I

Procedia PDF Downloads 113

Authors: Geetakshi Arora, Danish Malhotra

Abstract:

Diabetic wounds are serious health issues and often fail to heal, leading to limb amputation that makes the life of the patient miserable. Delayed wound healing has been characterized by an increase in matrix metalloproteinase-9 (MMP-9). Thus research throughout the world has been going on to develop selective MMP-9 inhibitors for aiding diabetic wound healing. Bioactive constituents from natural sources always served as potential leads in drug development with high rates of success. Considering the need for novel selective MMP-9 inhibitors and the importance of natural bioactive compounds in drug development, we have screened a library of bioactive constituents from plant sources that were effective in diabetic wound healing on human MMP-9 (hMMP-9) using molecular docking studies. Screened constituents are ranked according to their dock score, ∆G value (binding affinity), and Ligand efficiency evaluated from FleXX docking and Hyde scoring modules available with drug designing platform LeadIT. Rhamnocitrin showed the highest correlation between dock score, ∆G value (binding affinity), and Ligand efficiency was further explored for binding interactions with hMMP-9. The overall study suggest that Rhamnocitrin is sufficiently decorated with both hydrophilic and hydrophobic substitutions that perfectly block hMMP-9 and act as a potential lead in the design and development of selective hMMP-9 inhibitors.

Keywords: MMP-9, diabetic wound, molecular docking, phytoconstituents

Procedia PDF Downloads 126

Authors: Nihar Ranjan, Derrick Watkins, Dev P. Arya

Abstract:

Current methods in the study of antibiotic activity of ribosome targeted antibiotics are dependent on cell based bacterial inhibition assays or various forms of ribosomal binding assays. These assays are typically independent of each other and little direct correlation between the ribosomal binding and bacterial inhibition is established with the complementary assay. We have developed novel high-throughput capable assays for ribosome targeted drug discovery. One such assay examines the compounds ability to bind to a model ribosomal RNA A-site. We have also coupled this assay to other functional orthogonal assays. Such analysis can provide valuable understanding of the relationships between two complementary drug screening methods and could be used as standard analysis to correlate the affinity of a compound for its target and the effect the compound has on a cell.

Keywords: bacterial resistance, aminoglycosides, screening, drugs

Procedia PDF Downloads 370

Authors: Liang Zhao, Jili Zhang, Chongquan Zhong

Abstract:

Energy consumption data, in particular those involving public buildings, are impacted by many factors: the building structure, climate/environmental parameters, construction, system operating condition, and user behavior patterns. Traditional methods for data analysis are insufficient. This paper delves into the data mining technology to determine its application in the analysis of building energy consumption data including energy consumption prediction, fault diagnosis, and optimal operation. Recent literature are reviewed and summarized, the problems faced by data mining technology in the area of energy consumption data analysis are enumerated, and research points for future studies are given.

Keywords: data mining, data analysis, prediction, optimization, building operational performance

Procedia PDF Downloads 852

Authors: Matej Buzgo, Erico Himawan, Ksenija JašIna, Aiva Simaite

Abstract:

Electrospinning is a versatile and efficient technology for producing nanofibers for biomedical applications. One of the most common polymers used for the preparation of nanofibers for regenerative medicine and drug delivery applications is polycaprolactone (PCL). PCL is a biocompatible and bioabsorbable material that can be used to stimulate the regeneration of various tissues. It is also a common material used for the development of drug delivery systems by blending the polymer with small active molecules. However, for many drug delivery applications, e.g. cancer immunotherapy, PCL biodegradation rate that may exceed 9 months is too long, and faster nanofiber dissolution is needed. In this paper, we investigate the dissolution and small molecule release rates of PCL blends with two hydrophilic polymers: polyethylene oxide (PEO) or polyvinylpyrrolidone (PVP). We show that adding hydrophilic polymer to the PCL reduces the water contact angle, increases the dissolution rate, and strengthens the interactions between the hydrophilic drug and polymer matrix that further sustain its release. Finally using this method, we were also able to increase the nanofiber degradation rate when PCL-PEO and PCL-PVP were used as a shell in the electrospun core-shell nanofibers and spread up the release of active proteins from their core. Electrospinning can be used for the preparation of the core-shell nanofibers, where active ingredients are encapsulated in the core and their release rate is regulated by the shell. However, such fibers are usually prepared by coaxial electrospinning that is an extremely low-throughput technique. An alternative is emulsion electrospinning that could be upscaled using needleless blades. In this work, we investigate the possibility of using emulsion electrospinning for encapsulation and sustained release of the growth factors for the development of the organotypic skin models. The core-shell nanofibers were prepared using the optimized formulation and the release rate of proteins from the fibers was investigated for 2 weeks – typical cell culture conditions.

Keywords: electrospinning, polycaprolactone (PCL), polyethylene oxide (PEO), polyvinylpyrrolidone (PVP)

Procedia PDF Downloads 273

Authors: R. M. Noah, N. M. Nasir, M. R. Jais, M. S. S. Wahab, M. H. Abdullah, A. S. S. Raj

Abstract:

Infectious diseases are getting more difficult to treat due to the resistant strains of bacteria. Current generations of antibiotics are most likely ineffective against multi-drug resistant strains bacteria. Thus, there is an urgent need in search of natural antibiotics in particular from medicinal plants. One of the common medicinal plants, Melaleuca cajuputi, has been reported to possess antibacterial properties. The study was conducted to evaluate and justify the presence of antibacterial activity of Melaleuca cajuputi essential oil (EO) against the multi-drug resistant bacteria. Clinical isolates obtained from the teaching hospital were re-assessed to confirm the exact identity of the bacteria to be tested, namely methicillin-resistant staphylococcus aureus (MRSA), carbapenem-resistant enterobacteriaceae (CRE), and extended-spectrum beta-lactamases producer (ESBLs). A well diffusion method was done to observe the inhibition zones of the essential oil against the bacteria. Minimum inhibitory concentration (MIC) was determined using the microdilution method in 96-well flat microplate. The absorbance was measured using a microplate reader. Minimum bactericidal concentration (MBC) was performed using the agar medium method. The zones of inhibition produced by the EO against MRSA, CRE, and ESBL were comparable to that of generic antibiotics used, gentamicin and augmentin. The MIC and MBC results highlighted the antimicrobial efficacy of the EO. The outcome of this study indicated that the EO of Melaleuca cajuputi had antibacterial activity on the multi-drug resistant bacteria. This finding was eventually substantiated by electron microscopy work.

Keywords: melaleuca cajuputi, antibacterial, resistant bacteria, essential oil

Procedia PDF Downloads 122

Authors: Omar M. Elmabrouk., Roaa Y. Taha., Najat M. Ebrahim, Sabbreen A. Mohammed

Abstract:

Power transformers are the most crucial part of power electrical system, distribution and transmission grid. This part is maintained using predictive or condition-based maintenance approach. The diagnosis of power transformer condition is performed based on Dissolved Gas Analysis (DGA). There are five main methods utilized for analyzing these gases. These methods are International Electrotechnical Commission (IEC) gas ratio, Key Gas, Roger gas ratio, Doernenburg, and Duval Triangle. Moreover, due to the importance of the transformers, there is a need for an accurate technique to diagnose and hence predict the transformer condition. The main objective of this technique is to avoid the transformer faults and hence to maintain the power electrical system, distribution and transmission grid. In this paper, the DGA was utilized based on the data collected from the transformer records available in the General Electricity Company of Libya (GECOL) which is located in Benghazi-Libya. The Fuzzy Logic (FL) technique was implemented as a diagnostic approach based on IEC gas ratio method. The FL technique gave better results and approved to be used as an accurate prediction technique for power transformer faults. Also, this technique is approved to be a quite interesting for the readers and the concern researchers in the area of FL mathematics and power transformer.

Keywords: dissolved gas-in-oil analysis, fuzzy logic, power transformer, prediction

Procedia PDF Downloads 144

Authors: Eun-Taek Sin, Hyun-Ju Jang, Chang Geun Song, Yong-Sik Han

Abstract:

Due to the climate change, the coastal urban area repeatedly suffers from the loss of property and life by flooding. There are three main causes of inland submergence. First, when heavy rain with high intensity occurs, the water quantity in inland cannot be drained into rivers by increase in impervious surface of the land development and defect of the pump, storm sewer. Second, river inundation occurs then water surface level surpasses the top of levee. Finally, Coastal inundation occurs due to rising sea water. However, previous studies ignored the complex mechanism of flooding, and showed discrepancy and inadequacy due to linear summation of each analysis result. In this study, inland flooding and river inundation were analyzed together by HDM-2D model. Petrov-Galerkin stabilizing method and flux-blocking algorithm were applied to simulate the inland flooding. In addition, sink/source terms with exponentially growth rate attribute were added to the shallow water equations to include the inland flooding analysis module. The applications of developed model gave satisfactory results, and provided accurate prediction in comprehensive flooding analysis. The applications of developed model gave satisfactory results, and provided accurate prediction in comprehensive flooding analysis. To consider the coastal surge, another module was developed by adding seawater to the existing Inland Flooding-River Inundation binding module for comprehensive flooding analysis. Based on the combined modules, the Coastal Inundation – Inland & River Flow Interface was simulated by inputting the flow rate and depth data in artificial flume. Accordingly, it was able to analyze the flood patterns of coastal cities over time. This study is expected to help identify the complex causes of flooding in coastal areas where complex flooding occurs, and assist in analyzing damage to coastal cities. Acknowledgements—This research was supported by a grant ‘Development of the Evaluation Technology for Complex Causes of Inundation Vulnerability and the Response Plans in Coastal Urban Areas for Adaptation to Climate Change’ [MPSS-NH-2015-77] from the Natural Hazard Mitigation Research Group, Ministry of Public Safety and Security of Korea.

Keywords: flooding analysis, river inundation, inland flooding, 2D hydrodynamic model

Procedia PDF Downloads 362

Authors: Smruti Mahapatra, Dipankar Biswas, Richard Um, Michael Meggyesy, Riccardo Serra, Noah Gorelick, Steven Marra, Amir Manbachi, Mark G. Luciano

Abstract:

Intracranial pressure (ICP) is profoundly regulated by the effects of cardiac pulsation and the volume of the incoming blood. Furthermore, these effects on ICP are incremented by the presence of a rigid skull that does not allow for changes in total volume during the cardiac cycle. These factors play a pivotal role in cerebrospinal fluid (CSF) dynamics and distribution, with consequences that are not well understood to this date and that may have a deep effect on the Central Nervous System (CNS) functioning. We designed this study with two specific aims: (a) To study how pulsatility influences local CSF flow, and (b) To study how modulating intracranial pressure affects drug distribution throughout the SAS globally. In order to achieve these aims, we built an elaborate in-vitro model of the SAS closely mimicking the dimensions and flow rates of physiological systems. To modulate intracranial pressure, we used an intracranially implanted, cardiac-gated, volume-oscillating balloon (CADENCE device). Commercially available dye was used to visualize changes in CSF flow. We first implemented two control cases, seeing how the tracer behaves in the presence of pulsations from the brain phantom and the balloon individually. After establishing the controls, we tested 2 cases, having the brain and the balloon pulsate together in sync and out of sync. We then analyzed the distribution area using image processing software. The in-sync case produced a significant increase, 5x times, in the tracer distribution area relative to the out-of-sync case. Assuming that the tracer fluid would mimic blood flow movement, a drug introduced in the SAS with such a system in place would enhance drug distribution and increase the bioavailability of therapeutic drugs to a wider spectrum of brain tissue.

Keywords: blood-brain barrier, cardiac-gated, cerebrospinal fluid, drug delivery, neurosurgery

Procedia PDF Downloads 183

Authors: Peter Yamoah, Frasia Oosthuizen

Abstract:

Introduction: Reporting of Adverse Events Following Immunization continues to be a challenge. Pharmacovigilance centers throughout the world are mandated by the WHO to submit AEFI reports from various countries to a large pool of adverse drug reaction electronic database called Vigibase. Despite the relevant information of AEFI in Vigibase, it is unavailable to the general public. However, the WHO has an alternative website called VigiAccess which is an open access website serving as a repository of reported adverse drug reactions and AEFIs. The aim of the study was to ascertain the reporting pattern of a number of commonly used vaccines in VigiAccess. Methods: VigiAccess was thoroughly searched on the 5th of February 2018 for AEFI reports of measles vaccine, oral polio vaccine (OPV), yellow fever vaccine, pneumococcal vaccine, rotavirus vaccine, meningococcal vaccine, tetanus vaccine and tuberculosis (BCG) vaccine. These were reports from all pharmacovigilance centers in the world from the time they joined the WHO drug monitoring program. Results: After a thorough search in VigiAccess, there were 9,062 measles vaccine AEFIs, 185,829 OPV AEFIs, 24,577 yellow fever vaccine AEFIs, 317,208 pneumococcal vaccine AEFIs, 73,513 rotavirus vaccine AEFIs, 145,447 meningococcal vaccine AEFIs, 22,781 tetanus vaccine AEFIs and 35,556 BCG vaccine AEFIs. Conclusion: The study revealed that out of the eight vaccines studied, pneumococcal vaccines are associated with the highest number of AEFIs whilst measles vaccines were associated with the least AEFIs.

Keywords: vaccines, adverse reactions, VigiAccess, adverse event reporting

Procedia PDF Downloads 155

Authors: Prozorkevitch D., Mishurov A., Sokolov K., Karsakov L., Pestrikova L.

Abstract:

The current body of knowledge about the marine environment and the dynamics of marine ecosystems includes a huge amount of heterogeneous data collected over decades. It generally includes a wide range of hydrological, biological and fishery data. Marine researchers collect these data and analyze how and why the ecosystem changes from past to present. Based on these historical records and linkages between the processes it is possible to predict future changes. Multivariate analysis of trends and their interconnection in the marine ecosystem may be used as an instrument for predicting further ecosystem evolution. A wide range of information about the components of the marine ecosystem for more than 50 years needs to be used to investigate how these arrays can help to predict the future.

Keywords: barents sea ecosystem, abiotic, biotic, data sets, trends, prediction

Procedia PDF Downloads 116

Authors: Yasir E. Mohieldeen

Abstract:

Qatar is one of the most water scarce countries in the World. In 2014, the average per capita rainfall was less than 29 m3/y/ca, while the global average is 6,000 m3/y/ca. However, the per capita water consumption in Qatar is among the highest in the World: more than 500 liters per person per day, whereas the global average is 160 liters per person per day. Since the early 2000s, Qatar has been relying heavily on desalinated water from the Arabian Gulf as the main source of fresh water. In 2009, about 99.9% of the total potable water produced was desalinated. Reliance on desalinated water makes Qatar very vulnerable to water related natural disasters, such as the red-tide phenomenon. Qatar’s strategic water reserve lasts for only 7 days. In case of red-tide outbreak, the country would not be able to desalinate water for days, let alone the months that this disaster would bring about (as it clogs the desalination equipment). The 2008-09 red-tide outbreak, for instance, lasted for more than eight months and forced the closure of desalination plants in the region for weeks. This study aims at identifying favorite conditions for red-tide outbreaks, using satellite data along with in-situ measurements. This identification would allow the prediction of these outbreaks and their hotspots. Prediction and monitoring of outbreaks are crucial to water security in the country, as different measures could be put in place in advance to prevent an outbreak and mitigate its impact if it happened. Red-tide outbreaks are detected using different algorithms for chlorophyll concentration in the Gulf waters. Vegetation indices, such as Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) were used along with Surface Algae Bloom Index (SABI) to detect known outbreaks. MODIS (or Moderate Resolution Imaging Spectroradiometer) bands are used to calculate these indices. A red-tide outbreaks atlas in the Arabian Gulf is being produced. Prediction of red-tide outbreaks ahead of their occurrences would give critical information on possible water-shortage in the country. Detecting known outbreaks in the past few decades and related parameters (e.g. water salinity, water surface temperature, nutrition, sandstorms, … etc) enables the identification of favorite conditions of red-tide outbreak that are key to the prediction of these outbreaks.

Keywords: Arabian Gulf, MODIS, red-tide detection, strategic water reserve, water desalination

Procedia PDF Downloads 107

Authors: Noora Al Muftah, Reda Rawi, Richard Thompson, Halima Bensmail

Abstract:

Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. There is an urgent need to identify biomarkers that predict which patients with are most likely to respond to treatment. Systematic efforts to correlate tumor mutational data with biologic dependencies may facilitate the translation of somatic mutation catalogs into meaningful biomarkers for patient stratification. To identify genomic features associated with drug sensitivity and uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we have screened and integrated a panel of several hundred cancer cell lines from different databases, mutation, DNA copy number, and gene expression data for hundreds of cell lines with their responses to targeted and cytotoxic therapies with drugs under clinical and preclinical investigation. We found mutated cancer genes were associated with cellular response to most currently available Glioma cancer drugs and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Keywords: cancer, gene network, Lasso, penalized regression, P-values, unbiased estimator

Procedia PDF Downloads 409

Authors: Dariush Jafari, S. Mostafa Nowee

Abstract:

In this study a ternary system containing sodium chloride as solute, water as primary solvent and ethanol as the antisolvent was considered to investigate the application of artificial neural network (ANN) in prediction of sodium solubility in the mixture of water as the solvent and ethanol as the antisolvent. The system was previously studied using by Extended UNIQUAC model by the authors of this study. The comparison between the results of the two models shows an excellent agreement between them (R2=0.99), and also approves the capability of ANN to predict the thermodynamic behavior of ternary electrolyte systems which are difficult to model.

Keywords: thermodynamic modeling, ANN, solubility, ternary electrolyte system

Procedia PDF Downloads 385

Authors: Yujiang Wu

Abstract:

As electrical machine (e-machine) power density re-querulents become more stringent in vehicle electrification, mounting a temperature sensor for e-machine stator windings becomes increasingly difficult. This can lead to higher manufacturing costs, complicated harnesses, and reduced reliability. In this paper, we propose a deep-learning method for predicting electric machine winding temperature, which can either replace the sensor entirely or serve as a backup to the existing sensor. We compare the performance of our method, the stateful long short-term memory networks (LSTM) with truncated backpropagation through time (TBTT), with that of linear regression, as well as stateless LSTM with/without residual connection. Our results demonstrate the strength of combining stateful LSTM and TBTT in tackling nonlinear time series prediction problems with long sequence lengths. Additionally, in industrial applications, high-temperature region prediction accuracy is more important because winding temperature sensing is typically used for derating machine power when the temperature is high. To evaluate the performance of our algorithm, we developed a temperature-stratified MSE. We propose a simple but effective data preprocessing trick to improve the high-temperature region prediction accuracy. Our experimental results demonstrate the effectiveness of our proposed method in accurately predicting winding temperature, particularly in high-temperature regions, while also reducing manufacturing costs and improving reliability.

Keywords: deep learning, electrical machine, functional safety, long short-term memory networks (LSTM), thermal management, time series prediction

Procedia PDF Downloads 99

Authors: A. J. Regan, F. J. Lidgey, M. Betteridge, P. Georgiou, C. Toumazou, K. Hayatleh, J. R. Dibble

Abstract:

Our goal is development of an algorithm capable of predicting the directional trend of the Standard and Poor’s 500 index (S&P 500). Extensive research has been published attempting to predict different financial markets using historical data testing on an in-sample and trend basis, with many authors employing excessively complex mathematical techniques. In reviewing and evaluating these in-sample methodologies, it became evident that this approach was unable to achieve sufficiently reliable prediction performance for commercial exploitation. For these reasons, we moved to an out-of-sample strategy based on linear regression analysis of an extensive set of financial data correlated with historical closing prices of the S&P 500. We are pleased to report a directional trend accuracy of greater than 55% for tomorrow (t+1) in predicting the S&P 500.

Keywords: financial algorithm, GPU, S&P 500, stock market prediction

Procedia PDF Downloads 350

Authors: Rajesh S. Mony, Vaidyaratnam Oushadhasala

Abstract:

An attempt is made in this study to evolve a drug development modality based on classical Ayurvedic knowledge base as well as on modern scientific methodology. The present study involves (a) identification of a specific ailment condition, (b) the selection of a polyherbal formulation, (c) deciding suitable extraction procedure, (d) confirming the efficacy of the combination by in-vitro trials and (e) fixing up the recommended dose. The ailment segment selected is arthritic condition. The selected herbal combination is Kunturushka, Vibhitaki, Guggulu, Haridra, Maricha and Nirgundi. They were selected as per Classical Ayurvedic references, Authentified as per API (Ayurvedic Pharmacopeia of India), Extraction of each drug was done by different ratios of Hydroalcoholic menstrums, Invitro assessment of each extract after removing residual solvent for anti-Inflammatory, anti-arthritic activities (by UV-Vis. Spectrophotometer with positive control), Invitro assessment of each extract for COX enzyme inhibition (by UV-Vis. Spectrophotometer with positive control), Selection of the extracts was made having good in-vitro activity, Performed the QC testing of each selected extract including HPTLC, that is the in process QC specifications, h. Decision of the single dose with mixtures of selected extracts was made as per the level of in-vitro activity and available toxicology data, Quantification of major groups like Phenolics, Flavonoids, Alkaloids and Bitters was done with both standard Spectrophotometric and Gravimetric methods, Method for Marker assay was developed and validated by HPTLC and a good resolved HPTLC finger print was developed for the single dosage API (Active Pharmaceutical Ingredient mixture of extracts), Three batches was prepared to fix the in process and API (Active Pharmaceutical Ingredient) QC specifications.

Keywords: drug development, antiinflammatory, quality stardardisation, planar chromatography

Procedia PDF Downloads 99

Authors: Tomilola J. Ajayi

Abstract:

A category of nanovalves system containing the α-cyclodextrin (α-CD) ring on a stalk tethered to the pores of mesoporous silica nanoparticles (MSN) is theoretically and computationally modelled. This functions to control opening and blocking of the MSN pores for efficient targeted drug release system. Modeling of the nanovalves is based on the interaction between α-CD and the stalk (p-anisidine) in relation to pH variation. Conformational analysis was carried out prior to the formation of the inclusion complex, to find the global minimum of both neutral and protonated stalk. B3LYP/6-311G**(d, p) basis set was employed to attain all theoretically possible conformers of the stalk. Six conformers were taken into considerations, and the dihedral angle (θ) around the reference atom (N17) of the p-anisidine stalk was scanned from 0° to 360° at 5° intervals. The most stable conformer was obtained at a dihedral angle of 85.3° and was fully optimized at B3LYP/6-311G**(d, p) level of theory. The most stable conformer obtained from conformational analysis was used as the starting structure to create the inclusion complexes. 9 complexes were formed by moving the neutral guest into the α-CD cavity along the Z-axis in 1 Å stepwise while keeping the distance between dummy atom and OMe oxygen atom on the stalk restricted. The dummy atom and the carbon atoms on α-CD structure were equally restricted for orientation A (see Scheme 1). The generated structures at each step were optimized with B3LYP/6-311G**(d, p) methods to determine their energy minima. Protonation of the nitrogen atom on the stalk occurs at acidic pH, leading to unsatisfactory host-guest interaction in the nanogate; hence there is dethreading. High required interaction energy and conformational change are theoretically established to drive the release of α-CD at a certain pH. The release was found to occur between pH 5-7 which agreed with reported experimental results. In this study, we applied the theoretical model for the prediction of the experimentally observed pH-responsive nanovalves which enables blocking, and opening of mesoporous silica nanoparticles pores for targeted drug release system. Our results show that two major factors are responsible for the cargo release at acidic pH. The higher interaction energy needed for the complex/nanovalve formation to exist after protonation as well as conformational change upon protonation are driving the release due to slight pH change from 5 to 7.

Keywords: nanovalves, nanogate, mesoporous silica nanoparticles, cargo

Procedia PDF Downloads 123

Authors: Sandeep Pandey, Nimra Habib, Ranjana Singh, Abbas Ali Mahdi

Abstract:

Leukemia is a malignancy of blood that mainly affects children and young adults; while advancement in the early diagnosis will have the potential to improve the outcome of diseases. A wide range of disease including leukemia shows inflammatory signals in their pathogenesis. In a pilot study conducted in our laboratory, 52 people were screened, of which 26 had leukemia and 26 were free from any kind of malignancy. We performed the estimation of the inflammatory cytokine Interleukin-8 and it was found significantly raised in all the leukemia patients concerning healthy volunteers who participated in the study. Flow cytometry had been performed for the confirmation of leukemia and further genomic, and proteomic, analyses of the sample revealed that IL-8 levels showed a positive correlation in patients with leukemia. The results had shown constitutive secretion of interleukin-8 by leukemia cells. So, our finding demonstrated that IL-8 is considered to have a role in the pathogenesis of leukemia, and quantification of IL-8 levels in leukemia conditions might be more useful and feasible in the clinical setting for the prediction of drug responses where it may represent a putative target for innovative diagnostic toward effective therapeutic approaches. However, further research explorations in this area are needed that include a greater number of patients with all different forms of leukemia, and estimating their IL-8 levels may hold the key for the additional predictive values on the recurrence of leukemia and its prognosis.

Keywords: T-ALL, IL-8, leukemia pathogenesis, cancer therapeutics

Procedia PDF Downloads 72

Authors: Tsegay Giday Woldu, Haibin Zhang, Xin Zhang, Yemane Hailu Fissuh

Abstract:

It is well known that nonlinear conjugate gradient method is one of the widely used first order methods to solve large scale unconstrained smooth optimization problems. Because of the low memory requirement, attractive theoretical features, practical computational efficiency and nice convergence properties, nonlinear conjugate gradient methods have a special role for solving large scale unconstrained optimization problems. Large scale optimization problems are with important applications in practical and scientific world. However, nonlinear conjugate gradient methods have restricted information about the curvature of the objective function and they are likely less efficient and robust compared to some second order algorithms. To overcome these drawbacks, the new modified nonlinear conjugate gradient method is presented. The noticeable features of our work are that the new search direction possesses the sufficient descent property independent of any line search and it belongs to a trust region. Under mild assumptions and standard Wolfe line search technique, the global convergence property of the proposed algorithm is established. Furthermore, to test the practical computational performance of our new algorithm, numerical experiments are provided and implemented on the set of some large dimensional unconstrained problems. The numerical results show that the proposed algorithm is an efficient and robust compared with other similar algorithms.

Keywords: conjugate gradient method, global convergence, large scale optimization, sufficient descent property

Procedia PDF Downloads 205

Authors: Husham Bayazed

Abstract:

A growing number of studies indicate that atherosclerotic coronary artery disease (CAD) has a complex pathogenesis that extends beyond cholesterol intimal infiltration. The atherosclerosis process may involve an immune micro-environmental condition driven by local activation of the adaptive and innate immunity arrays, resulting in the formation of atherosclerotic plaques. Therefore, despite the wide usage of lipid-lowering agents, these devastating coronary diseases are not averted either at primary or secondary prevention levels. Many trials have recently shown an interest in the immune targeting of the inflammatory process of atherosclerotic plaques, with the promised improvement in atherosclerotic cardiovascular disease outcomes. This recently includes the immune-modulatory drug “Canakinumab” as an anti-interleukin-1 beta monoclonal antibody in addition to "Colchicine,” which's established as a broad-effect drug in the management of other inflammatory conditions. Recent trials and studies highlight the importance of inflammation and immune reactions in the pathogenesis of atherosclerosis and plaque formation. This provides an insight to discuss and extend the therapies from old lipid-lowering drugs (statins) to anti-inflammatory drugs (colchicine) and new targeted immune-modulatory therapies like inhibitors of IL-1 beta (canakinumab) currently under investigation.

Keywords: atherosclerotic plagues, immune microenvironment, lipid-lowering agents, and immunomodulatory drugs

Procedia PDF Downloads 69

Authors: Vera Sovkova, Andrea Mickova, Matej Buzgo, Karolina Vocetkova, Eva Filova, Evzen Amler

Abstract:

PCL (poly-ε-caprolactone) nanofibrous scaffolds with adhered liposomes were prepared and tested as a possible drug delivery system for various synthetic growth factors. TGFβ, bFGF, and IGF-I have been shown to increase hMSC (human mesenchymal stem cells) proliferation and to induce hMSC differentiation. Functionalized PCL nanofibers were prepared with synthetic growth factors encapsulated in liposomes adhered to them in three different concentrations. Other samples contained PCL nanofibers with adhered, free synthetic growth factors. The synthetic growth factors free medium served as a control. The interaction of liposomes with the PCL nanofibers was visualized by SEM, and the release kinetics were determined by ELISA testing. The potential of liposomes, immobilized on the biodegradable scaffolds, as a delivery system for synthetic growth factors, and as a suitable system for MSCs adhesion, proliferation and differentiation in vitro was evaluated by MTS assay, dsDNA amount determination, confocal microscopy, flow cytometry and real-time PCR. The results showed that the growth factors adhered to the PCL nanofibers stimulated cell proliferation mainly up to day 11 and that subsequently their effect was lower. By contrast, the release of the lowest concentration of growth factors from liposomes resulted in gradual proliferation of MSCs throughout the experiment. Moreover, liposomes, as well as free growth factors, stimulated type II collagen production, which was confirmed by immunohistochemical staining using monoclonal antibody against type II collagen. The results of this study indicate that growth factors enriched liposomes adhered to surface of PCL nanofibers could be useful as a drug delivery instrument for application in short timescales, be combined with nanofiber scaffolds to promote local and persistent delivery while mimicking the local microenvironment. This work was supported by project LO1508 from the Ministry of Education, Youth and Sports of the Czech Republic

Keywords: drug delivery, growth factors, hMSC, liposomes, nanofibres

Procedia PDF Downloads 289

Authors: Jonas Pedro Fabris, Alberth Almeida Amorim Souza, Maria Emilia Camargo, Suzana Leitão Russo

Abstract:

With the law Nº. 9279, of May 14, 1996, the Brazilian government regulates rights and obligations relating to industrial property considering the economic development of the country as granting patents, trademark registration, registration of industrial designs and other forms of protection copyright. In this study, we show the application of the methodology of Box and Jenkins in the series of deposits of industrial design at the National Institute of Industrial Property for the period from May 1996 to April 2013. First, a graphical analysis of the data was done by observing the behavior of the data and the autocorrelation function. The best model found, based on the analysis of charts and statistical tests suggested by Box and Jenkins methodology, it was possible to determine the model number for the deposit of industrial design, SARIMA (2,1,0)(2,0,0), with an equal to 9.88% MAPE.

Keywords: ARIMA models, autocorrelation, Box and Jenkins Models, industrial design, MAPE, time series

Procedia PDF Downloads 544

Authors: Jong Won, Park, Sung Hyun, Kim

Abstract:

The kinetic energy to pass subjected to shock and chisel reciprocating piston hydraulic power supplied by the excavator using for the purpose of crushing the rock, and roads, buildings, etc., hydraulic breakers blow. Impact frequency, efficiency measurement of the impact energy, hydraulic breakers, to demonstrate the ability of hydraulic breaker manufacturers and users to a very important item. And difficult in order to confirm the initial performance degradation in the life of the hydraulic breaker has been thought to be a problem.In this study, we measure the efficiency of hydraulic breaker, Impact energy and Impact frequency, the degradation analysis of research to predict the life.

Keywords: impact energy, impact frequency, hydraulic breaker, life prediction

Procedia PDF Downloads 441

Authors: Deepak Raj Bhat, Ryuichi Yatabe

Abstract:

In this study, a residual-state creep failure model was developed based on the residual-state creep test results of clayey soils. To develop the proposed model, the regression analyses were done by using the R. The model results of the failure time (tf) and critical displacement (δc) were compared with experimental results and found in close agreements to each others. It is expected that the proposed regression model for residual-state creep failure will be more useful for the prediction of displacement of different clayey soils in the future.

Keywords: regression model, residual-state creep failure, displacement prediction, clayey soils

Procedia PDF Downloads 408

Authors: Temesgen Sidamo, Prakruti S. Rao, Eleni Akllilu, Workineh Shibeshi, Yumi Park, Yong-Soon Cho, Jae-Gook Shin, Scott K. Heysell, Stellah G. Mpagama, Ephrem Engidawork

Abstract:

The fluoroquinolones (FQs) are used off-label for the treatment of multidrug-resistant tuberculosis (MDR-TB), and for evaluation in shortening the duration of drug-susceptible TB in recently prioritized regimens. Within the class, levofloxacin (LFX) and moxifloxacin (MXF) play a substantial role in ensuring success in treatment outcomes. However, sub-therapeutic plasma concentrations of either LFX or MXF may drive unfavorable treatment outcomes. To the best of our knowledge, the pharmacokinetics of LFX and MXF in Ethiopian patients with MDR-TB have not yet been investigated. Therefore, the aim of this study was to develop a population pharmacokinetic (PopPK) model of levofloxacin (LFX) and moxifloxacin (MXF) and assess the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24-h (AUC0-24) and the in vitro minimum inhibitory concentration (MIC) (AUC0-24/MIC) in Ethiopian MDR-TB patients. Steady-state plasma was collected from 39 MDR-TB patients enrolled in the programmatic treatment course and the drug concentrations were determined using optimized liquid chromatography-tandem mass spectrometry. In addition, the in vitro MIC of the patients' pretreatment clinical isolates was determined. PopPK and simulations were run at various doses, and PK parameters were estimated. The effect of covariates on the PK parameters and the PTA for maximum mycobacterial kill and resistance prevention was also investigated. LFX and MXF both fit in a one-compartment model with adjustments. The apparent volume of distribution (V) and clearance (CL) of LFX were influenced by serum creatinine (Scr), whereas the absorption constant (Ka) and V of MXF were influenced by Scr and BMI, respectively. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L was 29%, 62%, and 95% with the simulated 750 mg, 1000 mg, and 1500 mg doses, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no difference in the PTA (94.4%) for maximum bacterial kill among the simulated doses of MXF (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention improved proportionately with dose. Standard LFX and MXF doses may not provide adequate drug exposure. LFX PopPK is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Scr and BMI are likely to be important covariates in dose optimization or therapeutic drug monitoring (TDM) studies in Ethiopian patients.

Keywords: population PK, PTA, moxifloxacin, levofloxacin, MDR-TB patients, ethiopia

Procedia PDF Downloads 120

Authors: Nuwan Kuruwitaarachchi, M. K. M. Peiris, C. N. Madawala, K. M. A. R. Perera, V. U. N Perera

Abstract:

Dealing with businesses with the foreign market always took a special place in a country’s economy. Political and social factors came into play making currency rate changes fluctuate rapidly. Currency rate prediction has become an important factor for larger international businesses since large amounts of money exchanged between countries. This research focuses on comparing the accuracy of mainly three models; Autoregressive Integrated Moving Average (ARIMA), Artificial Neural Networks(ANN) and Support Vector Machines(SVM). series of data import, export, USD currency exchange rate respect to LKR has been selected for training using above mentioned algorithms. After training the data set and comparing each algorithm, it was able to see that prediction in SVM performed better than other models. It was improved more by combining SVM and SVR models together.

Keywords: ARIMA, ANN, FFNN, RMSE, SVM, SVR

Procedia PDF Downloads 212

Authors: Hassan Baji, Chun-Qing Li, Wei Yang

Abstract:

Water seepage is one of the most common causes of damage in tunnel structures, which can cause direct and indirect e.g. reinforcement corrosion and calcium leaching damages. Estimation of water seepage or inflow is one of the main challenges in probabilistic assessment of tunnels. The methodology proposed in this study is an attempt for mathematically modeling the water seepage in tunnel structures and further predicting its service life. Using the time-dependent reliability, water seepage is formulated as a failure mode, which can be used for prediction of service life. Application of the formulated seepage failure mode to a case study tunnel is presented.

Keywords: water seepage, tunnels, time-dependent reliability, service life

Procedia PDF Downloads 482

Authors: Maryamsadat Habibi

Abstract:

Objective: pharmaceutical errors are avoidable occurrences that can result in inappropriate pharmaceutical use, patient harm, treatment failure, increased hospital costs and length of stay, and other outcomes that affect both the individual receiving treatment and the healthcare provider. This study aimed to perform a reconciliation of medications in the cardiovascular ward of Imam Reza Hospital in Mashhad, Iran, and evaluate the prevalence of medication discrepancies between the best medication list created for the patient by the pharmacist and the medication order of the treating physician there. Materials & Methods: The 97 patients in the cardiovascular ward of the Imam Reza Hospital in Mashhad were the subject of a cross-sectional study from June to September of 2021. After giving their informed consent and being admitted to the ward, all patients with at least one underlying condition and at least two medications being taken at home were included in the study. A medical reconciliation form was used to record patient demographics and medical histories during the first 24 hours of admission, and the information was contrasted with the doctors' orders. The doctor then discovered medication inconsistencies between the two lists and double-checked them to separate the intentional from the accidental anomalies. Finally, using SPSS software version 22, it was determined how common medical discrepancies are and how different sorts of discrepancies relate to various variables. Results: The average age of the participants in this study was 57.6915.84 years, with 57.7% of men and 42.3% of women. 95.9% of the patients among these people encountered at least one medication discrepancy, and 58.9% of them suffered at least one unintentional drug cessation. Out of the 659 medications registered in the study, 399 cases (60.54%) had inconsistencies, of which 161 cases (40.35%) involved the intentional stopping of a medication, 123 cases (30.82%) involved the stopping of a medication unintentionally, and 115 cases (28.82%) involved the continued use of a medication by adjusting the dose. Additionally, the category of cardiovascular pharmaceuticals and the category of gastrointestinal medications were found to have the highest medical inconsistencies in the current study. Furthermore, there was no correlation between the frequency of medical discrepancies and the following variables: age, ward, date of visit, type, and number of underlying diseases (P=0.13), P=0.61, P=0.72, P=0.82, P=0.44, and so forth. On the other hand, there was a statistically significant correlation between the number of medications taken at home (P=0.037) and the prevalence of medical discrepancies with gender (P=0.029). The results of this study revealed that 96% of patients admitted to the cardiovascular unit at Imam Reza Hospital had at least one medication error, which was typically an intentional drug discontinuance. According to the study's findings, patients admitted to Imam Reza Hospital's cardiovascular ward have a great potential for identifying and correcting various medication discrepancies as well as for avoiding prescription errors when the medication reconciliation method is used. As a result, it is essential to carry out a precise assessment to achieve the best treatment outcomes and avoid unintended medication discontinuation, unwanted drug-related events, and drug interactions between the patient's home medications and those prescribed in the hospital.

Keywords: drug combination, drug side effects, drug incompatibility, cardiovascular department

Procedia PDF Downloads 88

Authors: Fitri CaturLestari

Abstract:

According to National Population and Family Planning Board (BKKBN), demographic bonus will occur in 2025-2035, when the number of people within the productive age bracket is higher than the number of elderly people and children. This time will be a gold moment for Indonesia to achieve maximum productivity and prosperity. But it will be a demographic bomb if it isn’t balanced by economic and social aspect considerations. Therefore it is important to make a prediction mapping of all provinces in Indonesia whether in demographic bomb or bonus condition after 100 years Indonesian independence. The purpose of this research were to make the demographic mapping based on the economic and social aspects of the provinces in Indonesia and categorizing them into demographic bomb and bonus condition. The research data are gained from Statistics Indonesia (BPS) as the secondary data. The multiregional component method, regression and quadrant analysis were used to predict the number of people, economic growth, Human Development Index (HDI), and gender equality in education and employment. There were different characteristic of provinces in Indonesia from economic aspect and social aspect. The west Indonesia was already better developed than the east one. The prediction result, many provinces in Indonesia will get demographic bonus but the others will get demographic bomb. It is important to prepare particular strategy to particular provinces with all of their characteristic based on the prediction result so the demographic bomb can be minimalized.

Keywords: demography, economic growth, gender, HDI

Procedia PDF Downloads 335