Search results for: binding site

Authors: Mohammad Hossein Modarressi, Mozhgan Mondeali, Khabat Barkhordari, Ali Etemadi

Abstract:

The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant concerns worldwide due to its catastrophic effects on public health. The SARS-CoV-2 infection is initiated with the binding of the receptor-binding domain (RBD) in its spike protein to the ACE2 receptor in the host cell membrane. Due to the error-prone entity of the viral RNA-dependent polymerase complex, the virus genome, including the coding region for the RBD, acquires new mutations, leading to the appearance of multiple variants. These variants can potentially impact transmission, virulence, antigenicity and evasive immune properties. S477N mutation located in the RBD has been observed in the SARS-CoV-2 omicron (B.1.1. 529) variant. In this study, we investigated the consequences of S477N mutation at the molecular level using computational approaches such as molecular dynamics simulation, protein-protein interaction analysis, immunoinformatics and free energy computation. We showed that displacement of Ser with Asn increases the stability of the spike protein and its affinity to ACE2 and thus increases the transmission potential of the virus. This mutation changes the folding and secondary structure of the spike protein. Also, it reduces antibody neutralization, raising concern about re-infection, vaccine breakthrough and therapeutic values.

Keywords: S477N, COVID-19, molecular dynamic, SARS-COV2 mutations

Procedia PDF Downloads 177

Authors: Sumeyra Sevim, Gulsum Gizem Topal, Mercan Merve Tengilimoglu-Metin, Mevlude Kizil

Abstract:

Aflatoxin M1 (AFM1) is a major toxic and carcinogenic molecule in milk and milk products. Therefore, it poses a risk for public health. Probiotics can be biological agent to remove AFM1. The aim of this study is to evaluate the effect of probiotic bacteria on AFM1 detoxification in phosphate buffer saline. The PBS samples artificially contaminated with AFM1 at concentration 100 pg/ml were prepared with probiotics bacteria that including monoculture (L. plantarum, B. bifidum ATCC, B. animalis ATCC 27672) and binary culture (L. bulgaricus + S. thermophiles, B. bifidum ATCC + B. animalis ATCC 27672, L. plantarum+B. bifidum ATCC, L. plantarum+ B. animalis ATCC 27672). The samples were incubated at 37°C for 4 hours and stored for 1, 5 and 10 days. The toxin was measured by the ELISA. The highest levels of AFM1 binding ability (63.6%) in PBS were detected yoghurt starter bacteria, while L. plantarum had the lowest levels of AFM1 binding ability (35.5%) in PBS. In addition, it was found that there was significant effect of storage on AFM1 binding ability in all groups except the one including B. animalis (p < 0.05). Consequently, results demonstrate that AFM1 detoxification by probiotic bacteria has a potential application to reduce toxin concentrations in yoghurt. Moreover, probiotic strains can react with itself as synergic or antagonist.

Keywords: aflatoxin M1, ELISA, probiotics, storage

Procedia PDF Downloads 331

Authors: Connor Dunlop, Bassim Abbassi, Richard G. Zytner

Abstract:

Life cycle assessment (LCA) is a powerful tool established by the International Organization for Standardization (ISO) that can be used to assess the environmental impacts of a product or process from cradle to grave. Many studies utilize the LCA methodology within the site remediation field to compare various decontamination methods, including bioremediation, soil vapor extraction or excavation, and off-site disposal. However, with the authors' best knowledge, limited information is available in the literature on a sustainability tool that could be used to help with the selection of the optimal remediation technology. This tool, based on the LCA methodology, would consider site conditions like environmental, economic, and social impacts. Accordingly, this project was undertaken to develop a tool to assist with the selection of optimal sustainable technology. Developing a proper tool requires a large amount of data. As such, data was collected from previous LCA studies looking at site remediation technologies. This step identified knowledge gaps or limitations within project data. Next, utilizing the data obtained from the literature review and other organizations, an extensive LCA study is being completed following the ISO 14040 requirements. Initial technologies being compared include bioremediation, excavation with off-site disposal, and a no-remediation option for a generic gasoline-contaminated site. To complete the LCA study, the modelling software SimaPro is being utilized. A sensitivity analysis of the LCA results will also be incorporated to evaluate the impact on the overall results. Finally, the economic and social impacts associated with each option will then be reviewed to understand how they fluctuate at different sites. All the results will then be summarized, and an interactive tool using Excel will be developed to help select the best sustainable site remediation technology. Preliminary LCA results show improved sustainability for the decontamination of a gasoline-contaminated site for each technology compared to the no-remediation option. Sensitivity analyses are now being completed on on-site parameters to determine how the environmental impacts fluctuate at other contaminated gasoline locations as the parameters vary, including soil type and transportation distances. Additionally, the social improvements and overall economic costs associated with each technology are being reviewed. Utilizing these results, the sustainability tool created to assist in the selection of the overall best option will be refined.

Keywords: life cycle assessment, site remediation, sustainability tool, contaminated sites

Procedia PDF Downloads 59

Authors: Mao-Sheng Su, Santhanamoorthi Nachimuthu, Jyh-Chiang Jiang

Abstract:

Climate change is widely recognized as a global crisis, with anthropogenic CO₂ emissions from fossil fuel combustion and industrial processes being major contributors. To address this challenge, carbon capture and sequestration (CCS) technology has emerged as a key strategy for selectively capturing CO₂ from flue gas streams. Among the various solid adsorbents, metal–organic frameworks (MOFs) are notable for their extensive surface area and controllable pore chemistry. The porous MOF structure is comprised of metal ions or clusters coordinated to organic linker compounds. In particular, the pore parameters of MOFs are readily tunable, making them promising materials for CO₂ capture applications. Among these, amine-functionalized MOFs have demonstrated exceptional CO₂ capture abilities because their high uptake capacity and selectivity. In this study, we have investigated the CO₂ capture abilities and adsorption mechanisms of the diamine-appended framework N-Ethylethylenediamine-Mg₂(4,4’-dioxidobiphenyl-3,3’-dicarboxylate) (e-2-Mg₂(dobpdc)) using density functional theory (DFT) calculations. Previous studies have suggested that CO₂ can be captured via both outer- and inner-amine binding sites. Our findings reveal that CO₂ adsorption at the outer amine site is kinetically more favorable compared to the inner amine site, with a lower energy barrier of 1.34 eV for CO₂ physisorption to chemisorption compared to the inner amine, which has an activation barrier of 1.60 eV. Furthermore, we find that CO₂ adsorption is significantly enhanced in an alkaline environment, as deprotonation of the diamine molecule reduces the energy barrier to 0.24 eV. This theoretical study provides detailed insights into CO₂ adsorption in diamine-appended e-2-Mg₂(dobpdc) MOF, offering a deeper understanding of CO₂ capture mechanisms and valuable information for the advancement of effective CO₂ sequestration technologies.

Keywords: DFT, MOFs, CO₂ capture, catalyst

Procedia PDF Downloads 40

Authors: Mustafa Ali Abugila, Basma Nuri Kajruba, Hanan Elhadi, Rehab Ramadan Wali

Abstract:

Iron deficiency anemia is characterized by a decrease of Hb (hemoglobin), serum iron, ferritin, and RBC (red blood cells) (shape and size). Also, it is characterized by an increase in total iron binding capacity (TIBC). Red blood cells become microctytic and hypochromic due to a decrease in iron content. This study was conducted in the north west of Libya and included 210 women in childbearing age (18-45 years) who were visiting women clinic. After filling the questionnaire, blood samples were taken and analyzed for hematological and biochemical profiles. Biochemical tests included measurement of serum iron, ferritin, and total iron binding capacity (TIBC). Among the total sample (210 women), there were 87 (41.42%) pregnant and 123 (58.57%) non-pregnant women (includes married and single). Pregnant women (87) were classified according to the gestational age into first, second, and third trimesters. The means of biochemical and hematological parameters in the studied samples were: Hb = 10.37± 2.02 g/dl, RBC = 3.78± 1.037 m/m3, serum iron 61.86± 40.28 µg/dl, and TIBC = 386.01 ± 94.91 µg/dl. In this study, we considered that any women have hemoglobin below 11.5 g/dl is anemic. 89.1%, 69.5%, and 47.8% of pregnant women who belong to third trimester had low (below normal value) Hb, serum iron, and ferritin, i.e. iron deficiency anemia was more common in third trimester among the first and the second trimesters. Third trimester pregnant women also had high TIBC more than first and second trimesters.

Keywords: red blood cells, hemoglobin, total iron binding capacity, ferritin

Procedia PDF Downloads 531

Authors: Anika Chebrolu

Abstract:

Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

Procedia PDF Downloads 99

Authors: Hari Bezwada, Michelle Cheon, Ryan Divan, Hannah Escritor, Michelle Kagramian, Isha Korgaonkar, Maya MacAdams, Udgita Pamidigantam, Richard Pilny, Eleanor Race, Angadh Singh, Nathan Zhang, LeeAnn Nguyen, Fina Liotta

Abstract:

Malaria is a deadly disease caused by the Plasmodium parasite, which continues to develop resistance to current antimalarial drugs. In this research project, the effectiveness of numerous thiazole derivatives was explored in inhibiting the PfPKG, a crucial part of the Plasmodium life cycle. This study involved the synthesis of six thiazole-derived amides to inhibit the PfPKG pathway. Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy were used to characterize these compounds. Furthermore, AutoDocking software was used to predict binding affinities of these thiazole-derived amides in silico. In silico, compound 6 exhibited the highest predicted binding affinity to PfPKG, while compound 5 had the lowest affinity. Compounds 1-4 displayed varying degrees of predicted binding affinity. In-vitro, it was found that compound 4 had the best percent inhibition, while compound 5 had the worst percent inhibition. Overall, all six compounds had weak inhibition (approximately 30-39% at 10 μM), but these results provide a foundation for future drug discovery experiments.

Keywords: Medicinal Chemistry, Malaria, drug discovery, PfPKG, Thiazole, Plasmodium

Procedia PDF Downloads 98

Authors: Chinmayee Choudhury

Abstract:

Human Melanocortin 4 Receptor (HMC4R) is one of the most potential drug targets for the treatment of obesity which controls the appetite. A deletion of the residues 88-92 in HMC4R is sometimes the cause of severe obesity in the humans. In this study, two homology models are constructed for the normal as well as mutated HMC4Rs and some phytochemicals present in Green Tea, Honey and Cinnamon have been docked to them to study their differential binding to the normal and mutated HMC4R as compared to the natural agonist α- MSH. Two homology models have been constructed for the normal as well as mutated HMC4Rs using the Modeller9v7. Some of the phytochemicals present in Green Tea, Honey, and Cinnamon, which have appetite suppressant activities are constructed, minimized and docked to these normal and mutated HMC4R models using ArgusLab 4.0.1. The mode of binding of the phytochemicals with the Normal and Mutated HMC4Rs have been compared. Further, the mode of binding of these phytochemicals with that of the natural agonist α- Melanocyte Stimulating Hormone(α-MSH) to both normal and mutated HMC4Rs have also been studied. It is observed that the phytochemicals Kaempherol, Epigallocatechin-3-gallate (EGCG) present in Green Tea and Honey, Isorhamnetin, Chlorogenic acid, Chrysin, Galangin, Pinocambrin present in Honey, Cinnamaldehyde, Cinnamyl acetate and Cinnamyl alcohol present in Cinnamon have capacity to form more stable complexes with the Mutated HMC4R as compared to α- MSH. So they may be potential agonists of HMC4R to suppress the appetite.

Keywords: HMC4R, α-MSH, docking, photochemical, appetite suppressant, homology modelling

Procedia PDF Downloads 196

Authors: H. Abu-Ali, A. Nabok, T. Smith

Abstract:

Aptamers are single-strand of DNA or RNA nucleotides sequence which is designed in vitro using selection process known as SELEX (systematic evolution of ligands by exponential enrichment) were developed for the selective detection of many toxic materials. In this work, we have developed an electrochemical biosensor for highly selective and sensitive detection of Hg2+ and Pb2+ using a specific aptamer probe (SAP) labelled with ferrocene (or methylene blue) in (5′) end and the thiol group at its (3′) termini, respectively. The SAP has a specific coil structure that matching with G-G for Pb2+ and T-T for Hg2+ interaction binding nucleotides ions, respectively. Aptamers were immobilized onto surface of screen-printed gold electrodes via SH groups; then the cyclic voltammograms were recorded in binding buffer with the addition of the above metal salts in different concentrations. The resulted values of anode current increase upon binding heavy metal ions to aptamers and analyte due to the presence of electrochemically active probe, i.e. ferrocene or methylene blue group. The correlation between the anodic current values and the concentrations of Hg2+ and Pb2+ ions has been established in this work. To the best of our knowledge, this is the first example of using a specific DNA aptamers for electrochemical detection of heavy metals. Each increase in concentration of 0.1 μM results in an increase in the anode current value by simple DC electrochemical test i.e (Cyclic Voltammetry), thus providing an easy way of determining Hg2+ and Pb2+concentration.

Keywords: aptamer, based, biosensor, DNA, electrochemical, highly, specific

Procedia PDF Downloads 162

Authors: Mohd Farooq Naqshbandi

Abstract:

The four fractions of aqueous extract of Sesame Seeds (Sesamum indicum L.) were studied for invitro DNA fragmentation, cell migration, and cellular apoptosis on SW480 and HTC116 human colorectal cancer cell lines. The seeds of Sesamum indicum were extracted with six solvents, including Methanol, Ethanol, Aqueous, Chloroform, Acetonitrile, and Hexane. The aqueous extract (IC₅₀ value 154 µg/ml) was found to be the most active in terms of cytotoxicity with SW480 human colorectal cancer cell lines. Further fractionation of this aqueous extract on flash chromatography gave four fractions. These four fractions were studied for anticancer and DNA binding studies. Cell viability was assessed by colorimetric assay (MTT). IC₅₀ values for all these four fractions ranged from 137 to 548 µg/mL for the HTC116 cancer cell line and 141 to 402 µg/mL for the SW480 cancer cell line. The four fractions showed good anticancer and DNA binding properties. The DNA binding constants ranged from 10.4 ×10⁴ 5 to 28.7 ×10⁴, showing good interactions with DNA. The DNA binding interactions were due to intercalative and π-π electron forces. The results indicate that aqueous extract fractions of sesame showed inhibition of cell migration of SW480 and HTC116 human colorectal cancer cell lines and induced DNA fragmentation and apoptosis. This was demonstrated by calculating the low wound closure percentage in cells treated with these fractions as compared to the control (80%). Morphological features of nuclei of cells treated with fractions revealed chromatin compression, nuclear shrinkage, and apoptotic body formation, which indicate cell death by apoptosis. The flow cytometer of fraction-treated cells of SW480 and HTC116 human colorectal cancer cell lines revealed death due to apoptosis. The results of the study indicate that aqueous extract of sesame seeds may be used to treat colorectal cancer.

Keywords: Sesamum indicum, cell migration inhibition, apoptosis induction, anticancer activity, colorectal cancer

Procedia PDF Downloads 88

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: Giovanni Forte, Melania De Falco, Antonio Santo

Abstract:

On 24th August 2016, central Italy was affected by a Mw 6.0 earthquake, representing the main shock of a long seismic sequence, which had a second shock Mw 6.6 on 26th October and lasts still nowadays. After the event, several field survey were carried out in the affected areas, which is made of historical masonry buildings. The post event reconnaissance missions were aimed at collecting information on the damage states of the buildings, the triggering of the landslides and the relationships with site effects. In this paper, the data collected after the event are analyzed considering the role of the geological and geomorphological setting and the ground motion scenario. The buildings displayed an uneven damage distribution, which was affected by both topographic and stratigraphic amplification. As pertains the landslides, which were the most recurrent among the ground failures, consisted mainly of rock falls and subordinately of translational slides. Finally, the collected knowledge showed a strong contribution of the local geological and geomorphological site condition on the resulting damage.

Keywords: Amatrice earthquake, damage states, landslides, site effects

Procedia PDF Downloads 324

Authors: Suzan Salem, Heba Moustafa, Abd El-Aziz Abd El-Aal

Abstract:

Seismic micro hazard zonation for urban areas is the first step towards a seismic risk analysis and mitigation strategy. Essential here is to obtain a proper understanding of the local subsurface conditions and to evaluate ground-shaking effects. In the present study, an attempt has been made to evaluate the seismic hazard considering local site effects by carrying out detailed geotechnical and geophysical site characterization in El-Fayoum New City. Seismic hazard analysis and microzonation of El-Fayoum New City are addressed in three parts: in the first part, estimation of seismic hazard is done using seismotectonic and geological information. The second part deals with site characterization using geotechnical and shallow geophysical techniques. In the last part, local site effects are assessed by carrying out one-dimensional (1-D) ground response analysis using the equivalent linear method by program SHAKE 2000. Finally, microzonation maps have been prepared. The detailed methodology, along with experimental details, collected data, results and maps are presented in this paper.

Keywords: El-Fayoum, microzonation, seismotectonic, Egypt

Procedia PDF Downloads 383

Authors: Arzu Baloglu, Ugur Kaplancali

Abstract:

This paper focuses on Background Check Systems and Pre-Employment Screening. In our study, we attempted to make an online background checking site that will help employers when hiring employees. Our site has two types of users which are free and powered user. Free users are the employees and powered users are the employers which will hire employers. The database of the site will contain all the information about the employees and employers which are registered in the system so the employers can make a search based on their searching criteria to find the suitable employee for the job. The web site also has a comments and points system. The current employer can make comments to his/her employees and can also give them points. The comments will be shown on employee’s profile, so; when an employer searches for an employee he/she can check the points and comments of the employee to see whether he or she is capable of the job or not. The employers can also follow some employees if they desire. This paper has been designed and implemented with using ASP.NET, C# and JavaScript. The outputs have a user friendly interface. The interface also aimed to provide the useful information for Turkish Technology Companies.

Keywords: background, checking, verification, human resources, online

Procedia PDF Downloads 198

Authors: Priyanka Tamta, Sukanya Sharma

Abstract:

The Kamakhya Temple in Assam plays a very important role in the development of Assam as not only a historical place but also as an archaeologically important site. Temple building activity on the site began in 5th century AD when a cave temple dedicated to Lord Balabhadraswami was constructed here by King Maharajadhiraja Sri Surendra Varman. In the history of Assam, the name of this king is not found and neither the name of this form of Vishnu is known in this region. But this inscription sanctified the place as it recorded the first ever temple building activity in this region. The fifteen hundred years habitation history of the Kamakhya temple sites shows a gradual progression of the site from a religious site to an archaeological site and finally as a historical landmark. Here, in this paper, our main objective is to understand the evolution of Kamakhya temple site as a historical landscape and as an important landmark in the history of Assam. The central theme of the paper is the gradual development of the religious site to a historical landmark. From epigraphical records, it is known that the site received patronage from all ruling dynasties of Assam and its adjoining regions. Royal households of Kashmir, Nepal, Bengal, Orissa, Bihar, etc. have left their footprints on the site. According to records they donated wealth, constructed or renovated temples and participated in the overall maintenance of the deity. This made Kamakhya temple a ground of interaction of faiths, communities, and royalties of the region. Since the 5th century AD, there was a continuous struggle between different beliefs, faiths, and power on the site to become the dominant authority of the site. In the process, powerful beliefs system subsumed minor ones into a larger doctrine of beliefs. This can be seen in the case of the evolution of the Kamakhya temple site as one of the important Shakta temples in India. Today, it is cultural identity marker of the state of Assam within which it is located. Its diverse faiths and beliefs have been appropriated by powerful legends to the dominant faith of the land. The temple has evolved from a cave temple to a complex of seventeen temples. The faith has evolved from the worship of water, an element of nature to the worship of the ten different forms of the goddess with their five male consorts or Bhairavas. Today, it represents and symbolizes the relationship of power and control out of which it has emerged. During different periods of occupation certain architectural and iconographical characters developed which indicated diffusion and cultural adaptation. Using this as sources and the epigraphical records this paper will analyze the interactive and dynamic processes which operated in the building of this cultural marker, the archaeological site of Kamakhya.

Keywords: cultural adaptation and diffusion, cultural and historical landscape, Kamakhya, Saktism, temple art and architecture, historiography

Procedia PDF Downloads 251

Authors: Zahid Manzoor, Shaukat Hussain Munawar, Zahid Iqbal, Imran Ahmad Khan, Abdul Aziz, Hafiz Muhammad Qasim

Abstract:

The present study was aimed to investigate the pharmacokinetics behavior and optimal dosage regimen of danofloxacin in 8 adult healthy buffaloes of local breed (Nili Ravi) following single intravenous administration at the dose of 2.5 mg/kg body weight. Plasma drug concentrations at various time intervals were measured by HPLC method. In vitro plasma protein binding was determined employing the ultrafiltration technique. The distribution and elimination of danofloxacin was rapid, as indicated by the values (Mean±SD) of distribution half-life (t1/2α = 0.25±0.09 hours) and elimination half life (t1/2β = 3.26±0.43 hours), respectively. Volume of distribution at steady state (Vss) was 1.14±0.12 L/kg, displaying its extensive distribution into various body fluids and tissues. The high value of AUC (9.80±2.14 µg/ml.hr) reflected the vast area of the body covered by drug concentration. The mean residence time was noted to be 4.78±0.52 hours. On the basis of pharmacokinetic parameters, a suitable intravenous regimen for danofloxacin in adult buffaloes would be 6.5 mg/kg to be repeated after 12 hours intervals. The present study is the foremost pharmacokinetic study of danofloxacin in the local species which would provide the valueable contribution in the local manufacturing of danofloxacin in Pakistan in future.

Keywords: danofloxacin, pharmacokinetics, plasma protein binding, buffaloes, dosage regimen

Procedia PDF Downloads 612

Authors: Sherif A. Abu El-Magd, Ahmed M. Sefelnasr, Ahmed M. Masoud

Abstract:

Groundwater modeling is the way and tool for assessing and managing groundwater resources efficiently. The present work was carried out in the ancient Egyptian archeological site (Abydos) fromDynastyIandII.Theareaislocated about 13km west of the River Nilecourse, Upper Egypt. The main problem in this context is that the ground water level rise threatens and damages fragile carvings and paintings of the ancient buildings. The main objective of the present work is to identify the sources of the groundwater recharge in the site, further more, equally important there is to control the ground water level rise. Numerical modeling combined with field water level measurements was implemented to understand the ground water recharge sources. However, building a conceptual model was an important step in the groundwater modeling to phase to satisfy the modeling objectives. Therefore, boreholes, crosssections, and a high-resolution digital elevation model were used to construct the conceptual model. To understand the hydrological system in the site, the model was run under both steady state and transient conditions. Then, the model was calibrated agains the observation of the water level measurements. Finally, the results based on the modeling indicated that the groundwater recharge is originating from an indirect flow path mainly from the southeast. Besides, there is a hydraulic connection between the surface water and groundwater in the study site. The decision-makers and archeologyists could consider the present work to understand the behavior of groundwater recharge and water table level rise.

Keywords: numerical modeling, archeological site, groundwater recharge, egypt

Procedia PDF Downloads 124

Authors: Kakali Bhadra

Abstract:

Harmalol administration caused remarkable reduction in proliferation of HepG₂ cells with GI₅₀ of 14.2 mM, without showing much cytotoxicity in embryonic liver cell line, WRL-68. Data from circular dichroism and differential scanning calorimetric analysis of harmalol-CT DNA complex shows conformational changes with prominent CD perturbation and stabilization of CT DNA by 8 ^oC. Binding constant and stoichiometry was also calculated using the above biophysical techniques. Further, dose dependent apoptotic induction ability of harmalol was studied in HepG₂ cells using different biochemical assays. Generation of ROS, DNA damage, changes in cellular external and ultramorphology, alteration of membrane, formation of comet tail, decreased mitochondrial membrane potential and a significant increase in Sub G_o/G₁ population made the cancer cell, HepG₂, prone to apoptosis. Up regulation of p53 and caspase 3 further indicated the apoptotic role of harmalol.

Keywords: apoptosis, beta carboline alkaloid, comet assay, cytotoxicity, ROS

Procedia PDF Downloads 209

Authors: Hamidrza Joodaki

Abstract:

The most complex issue in urban land use planning is site selection that needs to assess the verity of elements and factors. Multi Criteria Decision Making (MCDM) methods are the best approach to deal with complex problems. In this paper, combination of the analytical hierarchy process (AHP) model and FUZZY logic was used as MCDM methods to select the best site for gas station in the 4th gas zone of Tehran. The first and the most important step in FUZZY-AHP model is selection of criteria and sub-criteria. Population, accessibility, proximity and natural disasters were considered as the main criteria in this study. After choosing the criteria, they were weighted based on AHP by EXPERT CHOICE software, and FUZZY logic was used to enhance accuracy and to approach the reality. After these steps, criteria layers were produced and weighted based on FUZZY-AHP model in GIS. Finally, through ARC GIS software, the layers were integrated and the 4th gas zone in TEHRAN was selected as the best site to locate gas station.

Keywords: multiple criteria decision making (MCDM), analytic hierarchy process (AHP), FUZZY logic, geographic information system (GIS)

Procedia PDF Downloads 363

Authors: Fatima Chaudhary, Rehan Ul Haq

Abstract:

Spatial and anthropogenic factors influencing nest-site selection in birds need to be identified for effective conservative practices. Environmental attributes such as food availability, predator density, previous reproductive success, etc., provide information regarding the site's quality. An artificial nest box experiment was carried out to evaluate the effect of various factors on nest-site selection, as it is hard to assess the natural cavities. The experiment was conducted whereby half of the boxes were filled with old nest material. Artificial nest boxes created with different materials and different sizes and colors were installed at different heights. A total of 14 out of 60 nest boxes were occupied and four of them faced predation. The birds explored a total of 32 out of 60 nests, whereas anthropogenic factors destroyed 25 out of 60 nests. Birds chose empty nest boxes at higher rates however, there was no obvious avoidance of sites having high ectoparasites load due to old nest material. It is also possible that the preference towards the artificial nest boxes may differ from year to year because of several climatic factors and the age of old nest material affecting the parasite's survival. These variables may fluctuate from one season to another. Considering these factors, nest-site selection experiments concerning the effectiveness of artificial nest boxes should be carried out over several successive seasons. This topic may stimulate further studies, which could lead to a fully understanding the birds' evolutionary ecology. Precise information on these factors influencing nest-site selection can be essential from an economic point of view as well.

Keywords: artificial nesting, nest box, old nest material, birds

Procedia PDF Downloads 96

Authors: A. M. Naraghi, V. Gonzalez, M. O'Sullivan, C. G. Walker, M. Poshdar, F. Ying, M. Abdelmegid

Abstract:

Discrete Event Simulation (DES) and Agent Based Simulation (ABS) are two simulation approaches that have been proposed to support decision-making in the construction industry. Despite the wide use of these simulation approaches in the construction field, their applications for production and material planning is still limited. This is largely due to the dynamic and complex nature of construction material supply chain systems. Moreover, managing the flow of construction material is not well integrated with site logistics in traditional construction planning methods. This paper presents a hybrid of DES and ABS to simulate on-site and off-site material supply processes. DES is applied to determine the best production scenarios with information of on-site production systems, while ABS is used to optimize the supply chain network. A case study of a construction piling project in New Zealand is presented illustrating the potential benefits of using the proposed hybrid simulation model in construction material flow planning. The hybrid model presented can be used to evaluate the impact of different decisions on construction supply chain management.

Keywords: construction supply-chain management, simulation modeling, decision-support tools, hybrid simulation

Procedia PDF Downloads 207

Authors: Bongmun Kang, Kagnari Yamakawa, Yoshihisa Hagihara, Yuji Ito, Michimasa Kishimoto, Yoichi Kumada

Abstract:

The PMMA-tag was genetically fused with the C-terminal region of VHH molecules. This antibody, VHH, is known as a single-chain domain, which is devoid of light chains. The PMMA-tag, which could affect the isoelectric point (pI) changeable with a charge of amino acid in VHHs were closely related to the solubility of VHH molecules during refolding. The genetic fusion of PMMA-tag to C-terminal region of VHHs significantly affects the recovery of their soluble protein during refolding by 50 mM TAPS at pH 8.5. It could be refolded with a recovery of more than 95% by dialysis at pH 8.5. A marked difference in the antigen-binding activities in the adsorption state was significantly high in VHH-PM compared to the wild type of VHH. There are approximately 8-fold differences in the antigen-binding activities in the adsorption state between VHH-PM and VHH.

Keywords: VHH, PMMA-tag, isoelectric point, pH, Solubility, refolding, immobilization, ELISA

Procedia PDF Downloads 419

Authors: V. Sulakatko, F. U. Vogdt, I. Lill

Abstract:

Construction technology and on-site construction activities have a direct influence on the life cycle costs of energy efficiently renovated apartment buildings. The systematic inadequacies of the External Thermal Insulation Composite System (ETICS) which occur during the construction phase increase the risk for all stakeholders, reduce mechanical durability and increase the life cycle costs of the building. The economic effect of these shortcomings can be minimised if the risk of the most significant on-site activities is recognised. The objective of the presented ETICS economic assessment concept is to evaluate the economic influence of on-site shortcomings and reveal their significance to the foreseeable future repair costs. The model assembles repair techniques, discusses their direct cost calculation methods, argues over the proper usage of net present value over the life cycle of the building, and proposes a simulation tool to evaluate the risk of on-site activities. As the technique is dependent on the selected real interest rate, a sensitivity analysis is anticipated to determine the validity of the recommendations. After the verification of the model on the sample buildings by the industry, it is expected to increase economic rationality of resource allocation and reduce high-risk systematic shortcomings during the construction process of ETICS.

Keywords: activity-based cost estimating, cost estimation, ETICS, life cycle costing

Procedia PDF Downloads 297

Authors: Ziyda Abunada

Abstract:

In-situ remediation of contaminated land with deep mixing can deliver a multi-technique remedial strategy. A field trail includes permeable reactive barrier (PRB) took place at a severely contaminated site in Yorkshire to the north of the UK through the SMiRT (Soil Mix Remediation Technology) project in May 2011. SMiRT involved the execution of the largest research field trials in the UK to provide field validation. Innovative modified bentonite materials in combination with zeolite and organoclay were used to construct six different walls of a hexagonal PRB. Field monitoring, testing and site cores were collected from the PRB twice: once 2 months after the construction and again in March 2014 (almost 34 months later).This paper presents an overview of the results of the PRB materials’ relative performance with some initial 3-year time-related assessment. Results from the monitoring program and the site cores are presented. Some good correlations are seen together with some clear difference among the materials’ efficiency. These preliminary observations represent a potential for further investigations and highlighted the main lessons learned in a filed scale.

Keywords: in-situ remediation, groundwater, permeable reactive barrier, site cores

Procedia PDF Downloads 205

Authors: Yousef S. Al-Othman

Abstract:

The growth and expansion of the industrial facilities comes proportional to the market increasing demand of products and services. Furthermore, raw material producers such as oil companies usually undergo massive revamping projects to maintain a synchronized supply. These revamping projects are usually delivered through challenging construction projects held and associated with daily site risks related to the construction process. Henceforth, a case study related to these risks and corresponding on-spot corrective measurements has been made on a certain number of construction project contractors at Kuwait Oil Company (KOC) to derive the benefits and overall effectiveness of the on-spot corrective measurements during the construction phase of a project, and how would the same help in avoiding major incidents, ensuring a smooth, cost effective and on time delivery of the project. Findings of this case study shall have an added value to the overall risk management process by minimizing the daily site risks that may affect the project lead time, resulting in an undisturbed on-site construction process.

Keywords: oil and gas, risk management, construction projects, project lead time

Procedia PDF Downloads 107

Authors: Marie-Elise Beydon, Daniel Sacristan, Isabel Ruppen

Abstract:

MB02 (Alymsys®) is a candidate biosimilar to bevacizumab, which was developed against the reference product (RP) Avastin® sourced from both the European Union (EU) and United States (US). MB02 has been extensively characterized comparatively to Avastin® at a physicochemical and biological level using sensitive orthogonal state-of-the-art analytical methods. MB02 has been demonstrated similar to the RP with regard to its primary and higher-order structure, post- and co-translational profiles such as glycosylation, charge, and size variants. Specific focus has been put on the characterization of Fab-related activities, such as binding to VEGF A 165, which directly reflect the bevacizumab mechanism of action. Fc-related functionality was also investigated, including binding to FcRn, which is indicative of antibodies' half-life. The data generated during the analytical similarity assessment demonstrate the high analytical similarity of MB02 to its RP.

Keywords: analytical similarity, bevacizumab, biosimilar, MB02

Procedia PDF Downloads 289

Authors: Claudiu Marcu, Cristina Paul, Adelina Andelescu, Corneliu Mircea Davidescu, Francisc Péter

Abstract:

Heavy metal pollution has become a more serious environmental problem in the last several decades as a result of its toxicity and insusceptibility to the environment. Methods for removing metal ions from aqueous solution mainly consist of physical, chemical and biochemical procedures. Biosorption is defined as the removal of metal or metalloid species, compounds and particulates from solution by a biological material. Biosorption represents a very attractive method for the removal of toxic metal ions from aqueous effluents because it uses the ability of various biomass to bind the metal ions without the risk of releasing other toxic chemical compounds into the environment. The problem with using biomass or living cells as biosorbents is that their regeneration/reuse is often either impossible or very laborious. One of the most common chelating group found in biosorbents is the thiol group in cysteine. Therefore, we immobilized cysteine using covalent binding using glutaraldehyde as a linker on a synthetic sol-gel support obtained using 3-amino-propyl-trimetoxysilane and trimetoxysilane as precursors. The obtained adsorbents were used for removal of cadmium from aqueous solutions and the removal capacity was investigated in relation to the composition of the sol-gel hybrid composite, the loading of the biomolecule and the physical parameters of the biosorption process. In the same conditions, the bare sol-gel support without cysteine had no Cd removal effect, while the adsorbent with cysteine had an adsorption capacity up to 25.8 mg Cd/g adsorbent at pH 2.0 and 119 mg Cd/g adsorbent at pH 6.6, depending on cadmium concentration and adsorption conditions. We used atomic adsorption spectrometry to assess the cadmium concentration in the samples after the biosorbtion process. The parameters for the Freundlich and Langmuir adsorption isotherms where calculated from plotting the results of the adsorption experiments. The results for cysteine immobilization show a good loading capacity of the sol-gel support which indicates it could be used to immobilize metal binding proteins and by doing so boosting the heavy metal adsorption capacity of the biosorbent.

Keywords: biosorbtion, cadmium, cysteine covalent binding, sol-gel

Procedia PDF Downloads 294

Authors: Sakshi Piplani, Ajit Kumar

Abstract:

Valproic acid (VPA) is the first synthetic therapeutic agent used to treat epileptic disorders, which account for affecting nearly 1% world population. Teratogenicity caused by VPA has prompted the search for next generation drug with better efficacy and lower side effects. Recent studies have posed HDAC8 as direct target of VPA that causes the teratogenic effect in foetus. We have employed molecular dynamics (MD) and docking simulations to understand the binding mode of VPA and their analogues onto HDAC8. A total of twenty 3D-structures of human HDAC8 isoforms were selected using BLAST-P search against PDB. Multiple sequence alignment was carried out using ClustalW and PDB-3F07 having least missing and mutated regions was selected for study. The missing residues of loop region were constructed using MODELLER and energy was minimized. A set of 216 structural analogues (>90% identity) of VPA were obtained from Pubchem and ZINC database and their energy was optimized with Chemsketch software using 3-D CHARMM-type force field. Four major neurotransmitters (GABAt, SSADH, α-KGDH, GAD) involved in anticonvulsant activity were docked with VPA and its analogues. Out of 216 analogues, 75 were selected on the basis of lower binding energy and inhibition constant as compared to VPA, thus predicted to have anti-convulsant activity. Selected hHDAC8 structure was then subjected to MD Simulation using licenced version YASARA with AMBER99SB force field. The structure was solvated in rectangular box of TIP3P. The simulation was carried out with periodic boundary conditions and electrostatic interactions and treated with Particle mesh Ewald algorithm. pH of system was set to 7.4, temperature 323K and pressure 1atm respectively. Simulation snapshots were stored every 25ps. The MD simulation was carried out for 20ns and pdb file of HDAC8 structure was saved every 2ns. The structures were analysed using castP and UCSF Chimera and most stabilized structure (20ns) was used for docking study. Molecular docking of 75 selected VPA-analogues with PDB-3F07 was performed using AUTODOCK4.2.6. Lamarckian Genetic Algorithm was used to generate conformations of docked ligand and structure. The docking study revealed that VPA and its analogues have more affinity towards ‘hydrophobic active site channel’, due to its hydrophobic properties and allows VPA and their analogues to take part in van der Waal interactions with TYR24, HIS42, VAL41, TYR20, SER138, TRP137 while TRP137 and SER138 showed hydrogen bonding interaction with VPA-analogues. 14 analogues showed better binding affinity than VPA. ADMET SAR server was used to predict the ADMET properties of selected VPA analogues for predicting their druggability. On the basis of ADMET screening, 09 molecules were selected and are being used for in-vivo evaluation using Danio rerio model.

Keywords: HDAC8, docking, molecular dynamics simulation, valproic acid

Procedia PDF Downloads 255

Authors: Jessica A. Soto-Bear, Virginia González-Vélez, Norma Castañeda-Villa, Amparo Gil

Abstract:

Glutamate release of the cochlear inner hair cell (IHC) ribbon synapse is a fundamental step in transferring sound information in the auditory pathway. Otoferlin is the calcium sensor in the IHC and its activity has been related to many auditory disorders. In order to simulate secretion dynamics occurring in the IHC in a few milliseconds timescale and with high spatial resolution, we proposed an active-zone model solved with Monte Carlo algorithms. We included models for calcium buffered diffusion, calcium-binding schemes for vesicle fusion, and L-type voltage-gated calcium channels. Our results indicate that calcium influx and calcium binding is managing IHC secretion as a function of voltage depolarization, which in turn mean that IHC response depends on sound intensity.

Keywords: inner hair cells, Monte Carlo algorithm, Otoferlin, secretion

Procedia PDF Downloads 221

Authors: Udaya Kumar

Abstract:

The aim of this paper is to discuss recent research conducted in experimental studies related to the process of the iron smelting. The paper will discuss issues related to the selection of iron ore, structure of furnace, making of tuyeres, fashioning of blowers and firing temperatures through experiments conducted recently and scientific analyses of experimental work. Experiments were conducted in order to investigate iron smelting techniques used at the Early Historic site of Nathara-Ki-Pal. (73°47’E; 24°16N is located about 70 km south-east of Udaipur city). Geographically, Nathara-Ki-Pal has located the foot hills of Aravalli’s. Iron ore and iron slag can be seen on the surface of the site. The remains of 4 broken furnaces were recovered during excavations (2007 and 2008) and the site was excavated by Prof. Pandey from the Department of Archaeology of the Institute of Rajasthan studies, Rajasthan Vidyapeeth University. This shows that the site of Nathara-Ki-Pal was a center of iron smelting. Results of experiments performed both in the field reconstruction of a bloomery furnace and in the laboratory are discussed.

Keywords: experimental studies, furnace, smelting techniques, making of tuyeres

Procedia PDF Downloads 189