Search results for: binding site
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3162

Search results for: binding site

2862 Study on Safety Management of Deep Foundation Pit Construction Site Based on Building Information Modeling

Authors: Xuewei Li, Jingfeng Yuan, Jianliang Zhou

Abstract:

The 21st century has been called the century of human exploitation of underground space. Due to the characteristics of large quantity, tight schedule, low safety reserve and high uncertainty of deep foundation pit engineering, accidents frequently occur in deep foundation pit engineering, causing huge economic losses and casualties. With the successful application of information technology in the construction industry, building information modeling has become a research hotspot in the field of architectural engineering. Therefore, the application of building information modeling (BIM) and other information communication technologies (ICTs) in construction safety management is of great significance to improve the level of safety management. This research summed up the mechanism of the deep foundation pit engineering accident through the fault tree analysis to find the control factors of deep foundation pit engineering safety management, the deficiency existing in the traditional deep foundation pit construction site safety management. According to the accident cause mechanism and the specific process of deep foundation pit construction, the hazard information of deep foundation pit engineering construction site was identified, and the hazard list was obtained, including early warning information. After that, the system framework was constructed by analyzing the early warning information demand and early warning function demand of the safety management system of deep foundation pit. Finally, the safety management system of deep foundation pit construction site based on BIM through combing the database and Web-BIM technology was developed, so as to realize the three functions of real-time positioning of construction site personnel, automatic warning of entering a dangerous area, real-time monitoring of deep foundation pit structure deformation and automatic warning. This study can initially improve the current situation of safety management in the construction site of deep foundation pit. Additionally, the active control before the occurrence of deep foundation pit accidents and the whole process dynamic control in the construction process can be realized so as to prevent and control the occurrence of safety accidents in the construction of deep foundation pit engineering.

Keywords: Web-BIM, safety management, deep foundation pit, construction

Procedia PDF Downloads 154
2861 Effects of Palm Waste Ash Residues on Acidic Soil in Relation to Physiological Responses of Habanero Chili Pepper (Capsicum chinense jacq.)

Authors: Kalu Samuel Ukanwa, Kumar Patchigolla, Ruben Sakrabani

Abstract:

The use of biosolids from thermal conversion of palm waste for soil fertility enhancement was tested in acidic soil of Southern Nigeria for the growing of Habanero chili pepper (Capsicum chinense jacq.). Soil samples from the two sites, showed pH 4.8 and 4.8 for site A and B respectively, below 5.6-6.8 optimum range and other fertility parameters indicating a low threshold for pepper growth. Nursery planting was done at different weeks to determine the optimum planting period. Ash analysis showed that it contains 26% of total K, 20% of total Ca, 0.27% of total P, and pH 11. The two sites were laid for an experiment in randomized complete block design and setup with three replications side by side. Each plot measured 3 x 2 m and a total of 15 plots for each site, four treatments, and one control. Outlined as control, 2, 4, 6 and 8 tonnes/hectare of palm waste ash, the combined average for both sites with correspondent yield after six harvests in one season are; 0, 5.8, 6, 6, 14.5 tonnes/hectare respectively to treatments. Optimum nursery survival rate was high in July; the crop yield was linear to the ash application. Site A had 6% yield higher than site B. Fruit development, weight, and total yield in relation to the control plot showed that palm waste ash is effective for soil amendment, nutrient delivery, and exchange.

Keywords: ash, palm waste, pepper, soil amendment

Procedia PDF Downloads 133
2860 Identification and Characterization of Nuclear Envelope Protein Interactions

Authors: Mohammed Hakim Jafferali, Balaje Vijayaraghavan, Ricardo A. Figueroa, Ellinor Crafoord, Veronica J. Larsson, Einar Hallberg, Santhosh Gudise

Abstract:

The nuclear envelope which surrounds the chromatin of eukaryotic cells contains more than a hundred transmembrane proteins. Mutations in some genes encoding nuclear envelope proteins give rise to human diseases including neurological disorders. The function of many nuclear envelope proteins is not well established. This is partly because nuclear envelope proteins and their interactions are difficult to study due to the inherent resistance to extraction of nuclear envelope proteins. We have developed a novel method called MCLIP, to identify interacting partners of nuclear envelope proteins in live cells. Using MCLIP, we found three new binding partners of the inner nuclear membrane protein Samp1: the intermediate filament protein Lamin B1, the LINC complex protein Sun1 and the G-protein Ran. Furthermore, using in vitro studies, we show that Samp1 binds both Emerin and Ran directly. We have also studied the interaction between Samp1 and Ran in detail. The results show that the Samp1 binds stronger to RanGTP than RanGDP. Samp1 is the first transmembrane protein known to bind Ran and it is tempting to speculate that Samp1 may provide local binding sites for RanGTP at membranes.

Keywords: MCLIP, nuclear envelope, ran, Samp1

Procedia PDF Downloads 353
2859 Experimental Investigations on Setting Behavior and Compreesive Strength of Flyash Based Geopolymer

Authors: Ishan Tank, Ashmita Rupal, Sanjay Kumar Sharma

Abstract:

Concrete, a widely used building material, has cement as its main constituent. An excessive amount of emissions are released into the atmosphere during the manufacture of cement, which is detrimental to the environment. To minimize this problem, innovative materials like geopolymer mortar (GPM) seem to be a better alternative. By using fly ash-based geopolymer instead of standard cement mortar as a binding ingredient, this concept has been successfully applied to the building sector. The advancement of this technology significantly reduces greenhouse gas emissions and helps in source reduction, thereby minimizing pollution of the environment. In order to produce mortar and use this geopolymer mortar in the development of building materials, the current investigation is properly introducing this geopolymeric material, namely fly ash, as a binder in place of standard cement. In the domain of the building material industry, fly ash based geopolymer is a new and optimistic replacement for traditional binding materials because it is both environmentally sustainable and has good durability. The setting behaviour and strength characteristics of fly ash, when mixed with alkaline activator solution with varied concentration of sodium hydroxide solution, alkaline liquids mix ratio, and curing temperature, must be investigated, though, in order to determine its suitability and application in comparison with the traditional binding material, by activating the raw materials, which include various elements of silica and alumina, finer material known as geopolymer mortar is created. The concentration of the activator solution has an impact on the compressive strength of the geopolymer concrete formed. An experimental examination of compressive strength after 7, 14, and 28 days of fly ash-based geopolymer concrete is presented in this paper. Furthermore, the process of geopolymerization largely relies on the curing temperature. So, the setting time of Geopolymer mortar due to different curing temperatures has been studied and discussed in this paper.

Keywords: geopolymer mortar, setting time, flyash, compressive strength, binder material

Procedia PDF Downloads 72
2858 A Comprehensive Study on Freshwater Aquatic Life Health Quality Assessment Using Physicochemical Parameters and Planktons as Bio Indicator in a Selected Region of Mahaweli River in Kandy District, Sri Lanka

Authors: S. M. D. Y. S. A. Wijayarathna, A. C. A. Jayasundera

Abstract:

Mahaweli River is the longest and largest river in Sri Lanka and it is the major drinking water source for a large portion of 2.5 million inhabitants in the Central Province. The aim of this study was to the determination of water quality and aquatic life health quality in a selected region of Mahaweli River. Six sampling locations (Site 1: 7° 16' 50" N, 80° 40' 00" E; Site 2: 7° 16' 34" N, 80° 40' 27" E; Site 3: 7° 16' 15" N, 80° 41' 28" E; Site 4: 7° 14' 06" N, 80° 44' 36" E; Site 5: 7° 14' 18" N, 80° 44' 39" E; Site 6: 7° 13' 32" N, 80° 46' 11" E) with various anthropogenic activities at bank of the river were selected for a period of three months from Tennekumbura Bridge to Victoria Reservoir. Temperature, pH, Electrical Conductivity (EC), Total Dissolved Solids (TDS), Dissolved Oxygen (DO), 5-day Biological Oxygen Demand (BOD5), Total Suspended Solids (TSS), hardness, the concentration of anions, and metal concentration were measured according to the standard methods, as physicochemical parameters. Planktons were considered as biological parameters. Using a plankton net (20 µm mesh size), surface water samples were collected into acid washed dried vials and were stored in an ice box during transportation. Diversity and abundance of planktons were identified within 4 days of sample collection using standard manuals of plankton identification under the light microscope. Almost all the measured physicochemical parameters were within the CEA standards limits for aquatic life, Sri Lanka Standards (SLS) or World Health Organization’s Guideline for drinking water. Concentration of orthophosphate ranged between 0.232 to 0.708 mg L-1, and it has exceeded the standard limit of aquatic life according to CEA guidelines (0.400 mg L-1) at Site 1 and Site 2, where there is high disturbance by cultivations and close households. According to the Pearson correlation (significant correlation at p < 0.05), it is obvious that some physicochemical parameters (temperature, DO, TDS, TSS, phosphate, sulphate, chloride fluoride, and sodium) were significantly correlated to the distribution of some plankton species such as Aulocoseira, Navicula, Synedra, Pediastrum, Fragilaria, Selenastrum, Oscillataria, Tribonema and Microcystis. Furthermore, species that appear in blooms (Aulocoseira), organic pollutants (Navicula), and phosphate high eutrophic water (Microcystis) were found, indicating deteriorated water quality in Mahaweli River due to agricultural activities, solid waste disposal, and release of domestic effluents. Therefore, it is necessary to improve environmental monitoring and management to control the further deterioration of water quality of the river.

Keywords: bio indicator, environmental variables, planktons, physicochemical parameters, water quality

Procedia PDF Downloads 106
2857 Noise Measurement and Awareness at Construction Site: A Case Study

Authors: Feiruz Ab'lah, Zarini Ismail, Mohamad Zaki Hassan, Siti Nadia Mohd Bakhori, Mohamad Azlan Suhot, Mohd Yusof Md. Daud, Shamsul Sarip

Abstract:

The construction industry is one of the major sectors in Malaysia. Apart from providing facilities, services, and goods it also offers employment opportunities to local and foreign workers. In fact, the construction workers are exposed to a hazardous level of noises that generated from various sources including excavators, bulldozers, concrete mixer, and piling machines. Previous studies indicated that the piling and concrete work was recorded as the main source that contributed to the highest level of noise among the others. Therefore, the aim of this study is to obtain the noise exposure during piling process and to determine the awareness of workers against noise pollution at the construction site. Initially, the reading of noise was obtained at construction site by using a digital sound level meter (SLM), and noise exposure to the workers was mapped. Readings were taken from four different distances; 5, 10, 15 and 20 meters from the piling machine. Furthermore, a set of questionnaire was also distributed to assess the knowledge regarding noise pollution at the construction site. The result showed that the mean noise level at 5m distance was more than 90 dB which exceeded the recommended level. Although the level of awareness regarding the effect of noise pollution is satisfactory, majority of workers (90%) still did not wear ear protecting device during work period. Therefore, the safety module guidelines related to noise pollution controls should be implemented to provide a safe working environment and prevent initial occupational hearing loss.

Keywords: construction, noise awareness, noise pollution, piling machine

Procedia PDF Downloads 388
2856 Allometric Models for Biomass Estimation in Savanna Woodland Area, Niger State, Nigeria

Authors: Abdullahi Jibrin, Aishetu Abdulkadir

Abstract:

The development of allometric models is crucial to accurate forest biomass/carbon stock assessment. The aim of this study was to develop a set of biomass prediction models that will enable the determination of total tree aboveground biomass for savannah woodland area in Niger State, Nigeria. Based on the data collected through biometric measurements of 1816 trees and destructive sampling of 36 trees, five species specific and one site specific models were developed. The sample size was distributed equally between the five most dominant species in the study site (Vitellaria paradoxa, Irvingia gabonensis, Parkia biglobosa, Anogeissus leiocarpus, Pterocarpus erinaceous). Firstly, the equations were developed for five individual species. Secondly these five species were mixed and were used to develop an allometric equation of mixed species. Overall, there was a strong positive relationship between total tree biomass and the stem diameter. The coefficient of determination (R2 values) ranging from 0.93 to 0.99 P < 0.001 were realised for the models; with considerable low standard error of the estimates (SEE) which confirms that the total tree above ground biomass has a significant relationship with the dbh. The F-test value for the biomass prediction models were also significant at p < 0.001 which indicates that the biomass prediction models are valid. This study recommends that for improved biomass estimates in the study site, the site specific biomass models should preferably be used instead of using generic models.

Keywords: allometriy, biomass, carbon stock , model, regression equation, woodland, inventory

Procedia PDF Downloads 448
2855 Qsar Studies of Certain Novel Heterocycles Derived From bis-1, 2, 4 Triazoles as Anti-Tumor Agents

Authors: Madhusudan Purohit, Stephen Philip, Bharathkumar Inturi

Abstract:

In this paper we report the quantitative structure activity relationship of novel bis-triazole derivatives for predicting the activity profile. The full model encompassed a dataset of 46 Bis- triazoles. Tripos Sybyl X 2.0 program was used to conduct CoMSIA QSAR modeling. The Partial Least-Squares (PLS) analysis method was used to conduct statistical analysis and to derive a QSAR model based on the field values of CoMSIA descriptor. The compounds were divided into test and training set. The compounds were evaluated by various CoMSIA parameters to predict the best QSAR model. An optimum numbers of components were first determined separately by cross-validation regression for CoMSIA model, which were then applied in the final analysis. A series of parameters were used for the study and the best fit model was obtained using donor, partition coefficient and steric parameters. The CoMSIA models demonstrated good statistical results with regression coefficient (r2) and the cross-validated coefficient (q2) of 0.575 and 0.830 respectively. The standard error for the predicted model was 0.16322. In the CoMSIA model, the steric descriptors make a marginally larger contribution than the electrostatic descriptors. The finding that the steric descriptor is the largest contributor for the CoMSIA QSAR models is consistent with the observation that more than half of the binding site area is occupied by steric regions.

Keywords: 3D QSAR, CoMSIA, triazoles, novel heterocycles

Procedia PDF Downloads 444
2854 Leveraging Remote Assessments and Central Raters to Optimize Data Quality in Rare Neurodevelopmental Disorders Clinical Trials

Authors: Pamela Ventola, Laurel Bales, Sara Florczyk

Abstract:

Background: Fully remote or hybrid administration of clinical outcome measures in rare neurodevelopmental disorders trials is increasing due to the ongoing pandemic and recognition that remote assessments reduce the burden on families. Many assessments in rare neurodevelopmental disorders trials are complex; however, remote/hybrid trials readily allow for the use of centralized raters to administer and score the scales. The use of centralized raters has many benefits, including reducing site burden; however, a specific impact on data quality has not yet been determined. Purpose: The current study has two aims: a) evaluate differences in data quality between administration of a standardized clinical interview completed by centralized raters compared to those completed by site raters and b) evaluate improvement in accuracy of scoring standardized developmental assessments when scored centrally compared to when scored by site raters. Methods: For aim 1, the Vineland-3, a widely used measure of adaptive functioning, was administered by site raters (n= 52) participating in one of four rare disease trials. The measure was also administered as part of two additional trials that utilized central raters (n=7). Each rater completed a comprehensive training program on the assessment. Following completion of the training, each clinician completed a Vineland-3 with a mock caregiver. Administrations were recorded and reviewed by a neuropsychologist for administration and scoring accuracy. Raters were able to certify for the trials after demonstrating an accurate administration of the scale. For site raters, 25% of each rater’s in-study administrations were reviewed by a neuropsychologist for accuracy of administration and scoring. For central raters, the first two administrations and every 10th administration were reviewed. Aim 2 evaluated the added benefit of centralized scoring on the accuracy of scoring of the Bayley-3, a comprehensive developmental assessment widely used in rare neurodevelopmental disorders trials. Bayley-3 administrations across four rare disease trials were centrally scored. For all administrations, the site rater who administered the Bayley-3 scored the scale, and a centralized rater reviewed the video recordings of the administrations and also scored the scales to confirm accuracy. Results: For aim 1, site raters completed 138 Vineland-3 administrations. Of the138 administrations, 53 administrations were reviewed by a neuropsychologist. Four of the administrations had errors that compromised the validity of the assessment. The central raters completed 180 Vineland-3 administrations, 38 administrations were reviewed, and none had significant errors. For aim 2, 68 administrations of the Bayley-3 were reviewed and scored by both a site rater and a centralized rater. Of these administrations, 25 had errors in scoring that were corrected by the central rater. Conclusion: In rare neurodevelopmental disorders trials, sample sizes are often small, so data quality is critical. The use of central raters inherently decreases site burden, but it also decreases rater variance, as illustrated by the small team of central raters (n=7) needed to conduct all of the assessments (n=180) in these trials compared to the number of site raters (n=53) required for even fewer assessments (n=138). In addition, the use of central raters dramatically improves the quality of scoring the assessments.

Keywords: neurodevelopmental disorders, clinical trials, rare disease, central raters, remote trials, decentralized trials

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2853 Building Information Modelling: A Review to Indian Scenario

Authors: P. Agnivesh, P. V. Ponambala Moorthi

Abstract:

Evolution of information modelling leads to the visualisation of well-organized built environment. Building Information Modelling (BIM) is considered as evolution in the off-site construction which essentially enhances and controls the present scenario of on-site construction paradigms. Promptness, sustainability and security are considered as the important characteristics of the building information modelling. Projects that uses BIM are tied firmly by technology but distributed organizationally. This allows different team members in the project to associate and integrate the works and work flows. This will in turn improve the efficiency of work breakdown structure. Internationally BIM had been accepted as modern computer aided way of information sharing by construction industry for efficient way of manipulation in order to avoid the on-site misperceptions. Even though, in developing countries like India BIM is in the phase of start and requires lot of mandates and policies to be brought about by the government for its widespread implementations. This paper reviews the current scenario of BIM worldwide and in India and suggests for the improved implementation of building modelling for Indian policy condition.

Keywords: building information modelling, Indian polity, information modelling, information sharing, mandates and policies, sustainability.

Procedia PDF Downloads 377
2852 Evaluation of Antioxidant Activity as a Function of the Genetic Diversity of Canna indica Complex

Authors: A. Rattanapittayapron, O. Vanijajiva

Abstract:

Canna indica is a prominent species complex in tropical and subtropical areas. They become indigenous in Southeast Asia where they have been introduced. At present, C. indica complex comprises over hundred hybrids, are cultivated as commercial horticulture. The species complex contains starchy rhizome having economic value in terms of food and herbal medicine. In addition, bright color of the flowers makes it a valuable ornamental plant and potential source for natural colorant. This study aims to assess genetic diversity of four varieties of C. indica complex based on SRAP (sequence-related amplified polymorphism) and iPBS (inter primer binding site) markers. We also examined phytochemical characteristics and antioxidant properties of the flower extracts from four different color varieties. Results showed that despite of the genetic variation, there were no significant differences in phytochemical characteristics and antioxidant properties of flowers. The SRAP and iPBS results agree with the more primitive traits showed by morphological information and phytochemical and antioxidant characteristics from the flowers. Since Canna flowers has long been used as natural colorants together with the antioxidant activities from the ethanol extracts in this study, there are likely to be good source for cosmetics additives.

Keywords: Canna indica, antioxidant activity, genetic diversity, SRAP, iPBS

Procedia PDF Downloads 313
2851 Environmental Impact Assessment of OMI Irrigation Scheme, Nigeria

Authors: Olumuyiwa I. Ojo, Kola Amao, Josiah A. Adeyemo, Fred A. O. Otieno

Abstract:

A study was carried out to assess the environmental impact of Kampe (Omi) irrigation scheme with respect to public health hazards, the rising water table, salinity and alkalinity problems on the project site. A structured questionnaire was used as the main tool to gather information on the effect of the irrigation project on the various communities around the project site. The different sections of the questionnaire enabled the gathering of information ranging from general to more specific information. The results obtained from the study showed that the two effects are obvious: the 'positive effects' which include increasing the socioeconomic development of the entire communities, resulting in an increase in employment opportunities and better lifestyle and the 'negative effects' in which malaria (100% occurrence) and schistosomiasis (66.7%) were found to be active diseases caused by irrigation activities. Increase in height of water table and salinity is eminent in the irrigation site unless adequate drainage is provided. The collection and experimental analyses of representation soil and water samples from each scheme were used to assess the current status of each receptor. Results obtained indicate the absence of soil with sodium adsorption ration (SAR) values ranging from 3.0 to 3.89, exchangeable sodium percentage (ESP) ranged from 3.8% to 5.5% while pH values ranged from 6.60 to 7.00. Drainage facilities of the project site are inadequate, therefore making it difficult to leach the soil and flood history is occasional.

Keywords: irrigation, impact, soil analysis, Nigeria

Procedia PDF Downloads 297
2850 Analysis of Brownfield Soil Contamination Using Local Government Planning Data

Authors: Emma E. Hellawell, Susan J. Hughes

Abstract:

BBrownfield sites are currently being redeveloped for residential use. Information on soil contamination on these former industrial sites is collected as part of the planning process by the local government. This research project analyses this untapped resource of environmental data, using site investigation data submitted to a local Borough Council, in Surrey, UK. Over 150 site investigation reports were collected and interrogated to extract relevant information. This study involved three phases. Phase 1 was the development of a database for soil contamination information from local government reports. This database contained information on the source, history, and quality of the data together with the chemical information on the soil that was sampled. Phase 2 involved obtaining site investigation reports for development within the study area and extracting the required information for the database. Phase 3 was the data analysis and interpretation of key contaminants to evaluate typical levels of contaminants, their distribution within the study area, and relating these results to current guideline levels of risk for future site users. Preliminary results for a pilot study using a sample of the dataset have been obtained. This pilot study showed there is some inconsistency in the quality of the reports and measured data, and careful interpretation of the data is required. Analysis of the information has found high levels of lead in shallow soil samples, with mean and median levels exceeding the current guidance for residential use. The data also showed elevated (but below guidance) levels of potentially carcinogenic polyaromatic hydrocarbons. Of particular concern from the data was the high detection rate for asbestos fibers. These were found at low concentrations in 25% of the soil samples tested (however, the sample set was small). Contamination levels of the remaining chemicals tested were all below the guidance level for residential site use. These preliminary pilot study results will be expanded, and results for the whole local government area will be presented at the conference. The pilot study has demonstrated the potential for this extensive dataset to provide greater information on local contamination levels. This can help inform regulators and developers and lead to more targeted site investigations, improving risk assessments, and brownfield development.

Keywords: Brownfield development, contaminated land, local government planning data, site investigation

Procedia PDF Downloads 140
2849 Vision Aided INS for Soft Landing

Authors: R. Sri Karthi Krishna, A. Saravana Kumar, Kesava Brahmaji, V. S. Vinoj

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The lunar surface may contain rough and non-uniform terrain with dips and peaks. Soft-landing is a method of landing the lander on the lunar surface without any damage to the vehicle. This project focuses on finding a safe landing site for the vehicle by developing a method for the lateral velocity determination of the lunar lander. This is done by processing the real time images obtained by means of an on-board vision sensor. The hazard avoidance phase of the soft-landing starts when the vehicle is about 200 m above the lunar surface. Here, the lander has a very low velocity of about 10 cm/s:vertical and 5 m/s:horizontal. On the detection of a hazard the lander is navigated by controlling the vertical and lateral velocity. In order to find an appropriate landing site and to accordingly navigate, the lander image processing is performed continuously. The images are taken continuously until the landing site is determined, and the lander safely lands on the lunar surface. By integrating this vision-based navigation with the INS a better accuracy for the soft-landing of the lunar lander can be obtained.

Keywords: vision aided INS, image processing, lateral velocity estimation, materials engineering

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2848 A Computational Investigation of Potential Drugs for Cholesterol Regulation to Treat Alzheimer’s Disease

Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

Abstract:

Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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2847 A Small-Molecular Inhibitor of Influenza Virus via Disrupting the PA and PB1 Interaction of the Viral Polymerase

Authors: Shuofeng Yuan, Bojian Zheng

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Assembly of the heterotrimeric polymerase complex of influenza virus from the individual subunits PB1, PA, and PB2 is a prerequisite for viral replication, in which the interaction between the N-terminal of PB1 (PB1N) and the C terminal of PA (PAC) may be a desired target for antiviral development. In this study, we first compared the feasibility of high throughput screening by enzyme-linked immunosorbent assay (ELISA) and fluorescence polarization (FP) assay. Among the two, ELISA was demonstrated to own broader dynamic range so that it was used for screening inhibitors, which blocked PA and PB1 interaction. Several binding inhibitors of PAC-PB1N were identified and subsequently tested for the antiviral efficacy. Apparently, 3-(2-chlorophenyl)-6-ethyl-7-methyl[1,2,4]triazolo[4,3-a]pyrimidin-5-ol, designated ANA-1, was found to be a strong inhibitor of PAC-PB1N interaction and act as a potent antiviral agent against the infections of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2 subtypes, in cell cultures. Intranasal administration of ANA-1 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted that ANA-1 bound to an allosteric site of PAC, which would cause conformational changes thereby disrupting the PAC-PB1N interaction. Overall, our study has identified a novel compound with potential to be developed as an anti-influenza drug.

Keywords: influenza, antiviral, viral polymerase, compounds

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2846 Geochemical and Spatial Distribution of Minerals in the Tailings of IFE/IJESA Gold Mine Zone, Nigeria

Authors: Oladejo S. O, Tomori W. B, Adebayo A. O

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The main objective of this research is to identify the geochemical and mineralogical characteristics potential of unexplored tailings around the gold deposit region using spatial statistics and map modeling. Some physicochemical parameters such as pH, redox potential, electrical conductivity, cation exchange capacity, total organic carbon, total organic matter, residual humidity, Cation exchange capacity, and particle size were determined from both the mine drains and tailing samples using standard methods. The physicochemical parameters of tailings ranges obtained were pH (6.0 – 7.3), Eh (−16 - 95 Mev), EC (49 - 156 µS/cm), RH (0.20-2.60%), CEC (3.64-6.45 cmol/kg), TOC (3.57-18.62%), TOM (6.15-22.93%). The geochemical oxide composition were identified using Proton Induced X-ray emission and the results indicated that SiO2>Al2O3>Fe2O3>TiO2>K2O>MgO>CaO>Na2O> P2O5>MnO>Cr2O3>SrO>K2O>P2O5. The major mineralogical components in the tailing samples were determined by quantitative X-ray diffraction techniques using the Rietveld method. Geostatistical relationships among the known points were determined using ArcGIS 10.2 software to interpolate mineral concentration with respect to the study area. The Rietveld method gave a general Quartz value of 73.73-92.76%, IImenite as 0.38-4.77%, Kaolinite group as 3.19-20.83%, Muscovite as 0.77-11.70% with a trace of other minerals. The high percentage of quartz is an indication of a sandy environment with a loose binding site.

Keywords: tailings, geochemical, mineralogy, spatial

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2845 Comparison of Mean Monthly Soil Temperature at (5 and 30 cm) Depths at Compton Experimental Site, West Midlands (UK), between 1976-2008

Authors: Aminu Mansur

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A comparison of soil temperature at (5 and 30 cm) depths at a research site over the period (1976-2008) was analyzed. Based on the statistical analysis of the database of (12,045) days of individual soil temperature measurements in sandy-loam of the (salwick series) soils, the mean soil temperature revealed a statistically significant increase of about -1.1 to 10.9°C at 5 cm depth in 1976 compared to 2008. Similarly, soil temperature at 30 cm depth increased by -0.1 to 2.1°C in 2008 compared to 1976. Although, rapid increase in soil temperature at all depths was observed during that period, but a thorough assessment of these conditions suggested that the soil temperature at 5 cm depth are progressively increasing over time. A typical example of those increases in soil temperature was provided for agriculture where Miscanthus (elephant) plant that grows within the study area is adversely affected by the mean soil temperature increase. The study concluded that these observations contribute to the growing mass of evidence of global warming and knowledge on secular trends. Therefore, there was statistically significant increase in soil temperature at Compton Experimental Site between 1976-2008.

Keywords: soil temperature, warming trend, environment science, climate and atmospheric sciences

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2844 Safety Management on Construction Sites

Authors: Jonathan Doku

Abstract:

The study's goal was to evaluate construction site safety management in Ghana. The construction sector has long been seen as a high-risk business. It entails a variety of hazardous and challenging labor duties, such as lifting and working at a height, among others. The accident rate is a standard indicator for comparing the safety performance of construction projects. Because of its high-risk and fast-changing work environment, the construction business is regarded as one of the industries with the highest accident rates in the world. Many mishaps and work-related diseases have occurred there, and construction workers are particularly vulnerable to catastrophic calamities such as falls, collapses, and burial. The study's main goals were to discover characteristics that have a substantial impact on construction site safety, to evaluate the safety management methods utilized on construction sites, and to assess the obstacles associated with construction site safety management. The study was conducted using a quantitative research method and a purposive sampling strategy. Google forms were used to distribute self-administered surveys to 85 responders. 72 of the 85 questionnaires were completed and submitted for analysis, accounting for 84.7 percent of the total. The variables were analyzed using descriptive statistics, mean score ranking, and Cronbach's Alpha Coefficient to ensure the scale's reliability. The formal safety organization structure and the Safety checklist were identified as the key practices of safety management on site as part of the study goals. In addition, it was discovered that the most serious problem with safety management is ineffective supervision. To guarantee efficient monitoring and proper implementation of health and safety rules on building sites, management must be on the ball.

Keywords: construction, safety, risk, management

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2843 Evaluation of Site Laboratory Conditions Effect on Seismic Design Characteristics in Ramhormoz

Authors: Sayyed Yaghoub Zolfegharifar, Khairul Anuar Kassim, Hossein Khoramrooz, Khodayar Farhadiasl, Sadegh Jahan

Abstract:

Iran is one of the world's seismically active countries so that it experiences many small to medium earthquakes annually and a large earthquake every ten years. Due to seism tectonic conditions and special geographical and climatic position, Iran has the potential to create numerous severe earthquakes. Therefore, seismicity studies and seismic zonation of seismic zones of the country are necessary. In this article, the effect of local site conditions on the characteristics of seismic design in Rahmormoz will be examined. After analyzing the seismic hazard for Rahmormoz through deterministic and statistical methods and preparing the necessary geotechnical models based on available data, the ground response will be analyzed for different parts of the city based on four inputs and acceleration level estimated for bedrock through the equivalent linear method and by means of Deep Soil program. Finally, through the analysis of the obtained results, the seismic profiles of the ground surface for different parts of the city will be presented.

Keywords: seismic microzonation, ground response, resonance spectrum, period, site conditions

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2842 Design of RF Generator and Its Testing in Heating of Nickel Ferrite Nanoparticles

Authors: D. Suman, M. Venkateshwara Rao

Abstract:

Cancer is a disease caused by an uncontrolled division of abnormal cells in a part of the body, which is affecting millions of people leading to death. Even though there have been tremendous developments taken place over the last few decades the effective therapy for cancer is still not a reality. The existing techniques of cancer therapy are chemotherapy and radio therapy which are having their limitations in terms of the side effects, patient discomfort, radiation hazards and the localization of treatment. This paper describes a novel method for cancer therapy by using RF-hyperthermia application of nanoparticles. We have synthesized ferromagnetic nanoparticles and characterized by using XRD and TEM. These nanoparticles after the biocompatibility studies will be injected in to the body with a suitable tracer element having affinity to the specific tumor site. When RF energy is applied to the nanoparticles at the tumor site it produces heat of excess room temperature and nearly 41-45°C is sufficient to kill the tumor cells. We have designed a RF source generator provided with a temperature feedback controller to control the radiation induced temperature of the tumor site. The temperature control is achieved through a negative feedback mechanism of the thermocouple and a relay connected to the power source of the RF generator. This method has advantages in terms of its effect like localized therapy, less radiation, and no side effects. It has several challenges in designing the RF source provided with coils suitable for the tumour site, biocompatibility of the nanomaterials, cooling system design for the RF coil. If we can overcome these challenges this method will be a huge benefit for the society.

Keywords: hyperthermia, cancer therapy, RF source generator, nanoparticles

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2841 An Investigation on Orthopedic Rehabilitation by Avoiding Thermal Necrosis

Authors: R. V. Dahibhate, A. B. Deoghare, P. M. Padole

Abstract:

Maintaining natural integrity of biosystem is paramount significant for orthopedic surgeon while performing surgery. Restoration is challenging task to rehabilitate trauma patient. Drilling is an inevitable procedure to fix implants. The task leads to rise in temperature at the contact site which intends to thermal necrosis. A precise monitoring can avoid thermal necrosis. To accomplish it, data acquiring instrument is integrated with the drill bit. To contemplate it, electronic feedback system is developed. It not only measures temperature without any physical contact in between measuring device and target but also visualizes the site and monitors correct movement of tool path. In the current research work an infrared thermometer data acquisition system is used which monitors variation in temperature at the drilling site and a camera captured movement of drill bit advancement. The result is presented in graphical form which represents variations in temperature, drill rotation and time. A feedback system helps in keeping drill speed in threshold limit.

Keywords: thermal necrosis, infrared thermometer, drilling tool, feedback system

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2840 Noncovalent Antibody-Nanomaterial Conjugates: A Simple Approach to Produce Targeted Nanomedicines

Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

Abstract:

One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

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2839 Late Neolithic Cemeteries Funerary and Their Indications of Societies Changes and Religion Emergences of Sudan: Qalaat Shanan Site Case Study

Authors: Ahmed Hamid Nassr

Abstract:

The significant of the old stone ages in the Sudan, seems from the longest times and the large differentiation in antiquities, so many Neolithic cemeteries have been discovered in the Sudan, which the studies revealed costumes’ funerary from the Form of grave and the contents has been contrasted in some elements and constant in the others. Many interpretations of the late Neolithic cemeteries tradition written from the earlier studies, most of them focus of the development and change in the burial from society’s development and ideas of afterlife beginnings. Another emphasis undertaken is the relationship between societies cultural aspects and the environmental conditions of the period; it has been considered that it hyper-affected the development of farming in one way or another. The site of Qalaat Shanan noted in earlier 1990 and excavated by the Author from 2011-2013, the site located north of Khartoum about 170 km in Shendi town. Site setting lies amongst a group of Neolithic sites in the Shendi area, it reflected a succession of various Neolithic activities from the early to the late horizons. Excavation revealed many late Neolithic graves, the adult and child graves show large funerary content, different in quality and quantity, which indicates of societies development and related to religion and ideas about the afterlife. This presentation discusses the variations of the Late Neolithic cemeteries in Galaat Shanan site from the grave form, content and differentiation of the sex and age and compared with other late Neolithic discoveries in Sudan and the Nile valley. The study shows many changes in the graves related to the societies changes in late Neolithic in Sudan, climate and economic subsistence's are well reasons, but also the idea change is the main reason for the changes. That is clear from the variations of grave shape and content in age and sex and might be society’s status and levels.

Keywords: Sudan, Shendi town, Qalaat Shanan, late neolithic, cemeteries, funerary, tradition

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2838 Comparison of Accumulated Stress Based Pore Pressure Model and Plasticity Model in 1D Site Response Analysis

Authors: Saeedullah J. Mandokhail, Shamsher Sadiq, Meer H. Khan

Abstract:

This paper presents the comparison of excess pore water pressure ratio (ru) predicted by using accumulated stress based pore pressure model and plasticity model. One dimensional effective stress site response analyses were performed on a 30 m deep sand column (consists of a liquefiable layer in between non-liquefiable layers) using accumulated stress based pore pressure model in Deepsoil and PDMY2 (PressureDependentMultiYield02) model in Opensees. Three Input motions with different peak ground acceleration (PGA) levels of 0.357 g, 0.124 g, and 0.11 g were used in this study. The developed excess pore pressure ratio predicted by the above two models were compared and analyzed along the depth. The time history of the ru at mid of the liquefiable layer and non-liquefiable layer were also compared. The comparisons show that the two models predict mostly similar ru values. The predicted ru is also consistent with the PGA level of the input motions.

Keywords: effective stress, excess pore pressure ratio, pore pressure model, site response analysis

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2837 3-Dimensional Contamination Conceptual Site Model: A Case Study Illustrating the Multiple Applications of Developing and Maintaining a 3D Contamination Model during an Active Remediation Project on a Former Urban Gasworks Site

Authors: Duncan Fraser

Abstract:

A 3-Dimensional (3D) conceptual site model was developed using the Leapfrog Works® platform utilising a comprehensive historical dataset for a large former Gasworks site in Fitzroy, Melbourne. The gasworks had been constructed across two fractured geological units with varying hydraulic conductivities. A Newer Volcanic (basaltic) outcrop covered approximately half of the site and was overlying a fractured Melbourne formation (Siltstone) bedrock outcropping over the remaining portion. During the investigative phase of works, a dense non-aqueous phase liquid (DNAPL) plume (coal tar) was identified within both geological units in the subsurface originating from multiple sources, including gasholders, tar wells, condensers, and leaking pipework. The first stage of model development was undertaken to determine the horizontal and vertical extents of the coal tar in the subsurface and assess the potential causality between potential sources, plume location, and site geology. Concentrations of key contaminants of interest (COIs) were also interpolated within Leapfrog to refine the distribution of contaminated soils. The model was subsequently used to develop a robust soil remediation strategy and achieve endorsement from an Environmental Auditor. A change in project scope, following the removal and validation of the three former gasholders, necessitated the additional excavation of a significant volume of residual contaminated rock to allow for the future construction of two-story underground basements. To assess financial liabilities associated with the offsite disposal or thermal treatment of material, the 3D model was updated with three years of additional analytical data from the active remediation phase of works. Chemical concentrations and the residual tar plume within the rock fractures were modelled to pre-classify the in-situ material and enhance separation strategies to prevent the unnecessary treatment of material and reduce costs.

Keywords: 3D model, contaminated land, Leapfrog, remediation

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2836 Locating Potential Site for Biomass Power Plant Development in Central Luzon Philippines Using GIS-Based Suitability Analysis

Authors: Bryan M. Baltazar, Marjorie V. Remolador, Klathea H. Sevilla, Imee Saladaga, Loureal Camille Inocencio, Ma. Rosario Concepcion O. Ang

Abstract:

Biomass energy is a traditional source of sustainable energy, which has been widely used in developing countries. The Philippines, specifically Central Luzon, has an abundant source of biomass. Hence, it could supply abundant agricultural residues (rice husks), as feedstock in a biomass power plant. However, locating a potential site for biomass development is a complex process which involves different factors, such as physical, environmental, socio-economic, and risks that are usually diverse and conflicting. Moreover, biomass distribution is highly dispersed geographically. Thus, this study develops an integrated method combining Geographical Information Systems (GIS) and methods for energy planning; Multi-Criteria Decision Analysis (MCDA) and Analytical Hierarchy Process (AHP), for locating suitable site for biomass power plant development in Central Luzon, Philippines by considering different constraints and factors. Using MCDA, a three level hierarchy of factors and constraints was produced, with corresponding weights determined by experts by using AHP. Applying the results, a suitability map for Biomass power plant development in Central Luzon was generated. It showed that the central part of the region has the highest potential for biomass power plant development. It is because of the characteristics of the area such as the abundance of rice fields, with generally flat land surfaces, accessible roads and grid networks, and low risks to flooding and landslide. This study recommends the use of higher accuracy resource maps, and further analysis in selecting the optimum site for biomass power plant development that would account for the cost and transportation of biomass residues.

Keywords: analytic hierarchy process, biomass energy, GIS, multi-criteria decision analysis, site suitability analysis

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2835 Assessment of Heavy Metal Contamination in Soil and Groundwater Due to Leachate Migration from an Open Dumping Site

Authors: Kali Prasad Sarma

Abstract:

Indiscriminate disposal of municipal solid waste (MSW) in open dumping site is a common scenario in developing countries like India which poses a risk to the environment as well as human health. The objective of the present investigation was to find out the concentration of heavy metals (Pb, Cr, Ni, Mn, Zn, Cu, and Cd) and other physicochemical parameters of leachate and soil collected from an open dumping site of Tezpur town, Assam, India and its associated potential ecological risk. Tezpur is an urban agglomeration coming under the category of Class I UAs/Towns with a population of 105,377 as per data released by Government of India for Census 2011. Impact of the leachate on the groundwater was also addressed in our study. The concentrations of heavy metals were determined using ICP-OES. Energy dispersive X-Ray (SEM-EDS) microanalysis was also conducted to see the presence of the studied metals in the soil. X-Ray diffraction analysis (XRD) and Fourier Transform Infrared (FTIR) spectroscopy were also used to identify dominant minerals present in the soil samples. The trend of measured heavy metals in the soil samples was found in the following order: Mn > Pb > Cu > Zn > Cr > Ni > Cd. The assessment of heavy metal contamination in the soil was carried out by calculating enrichment factor (EF), geo-accumulation index (Igeo), contamination factor (Cfi), degree of contamination (Cd), pollution load index (PLI) and ecological risk factor (Eri). The study showed that the concentrations of Pb, Cu, and Cd were much higher than their respective average shale value and the EF of the soil samples depicted very severe enrichment for Pb, Cu, and Cd; moderate enrichment for Cr and Zn. Calculated Igeo values indicated that the soil is moderate to strongly contaminated with Pb and uncontaminated to moderately contaminated with Cd and Cu. The Cfi value for Pb indicates a very strong contamination level of the metal in the soil. The Cfi values for Cu and Cd were 2.37 and 1.65 respectively indicating moderate contamination level. To apportion the possible sources of heavy metal contamination in soil, principal components analysis (PCA) has been adopted. From the leachate, heavy metals are accumulated at the dumping site soil which could easily percolate through the soil and reach the groundwater. The possible relation of groundwater contamination due to leachate percolation was examined by analyzing the heavy metal concentrations in groundwater with respect to distance from the dumping site. The concentrations of Cd and Pb in groundwater (at a distance of 20m from dumping site) exceeded the permissible limit for drinking water as set by WHO. Occurrence of elevated concentration of potentially toxic heavy metals such as Pb and Cd in groundwater and soil are much environmental concern as it is detrimental to human health and ecosystem.

Keywords: groundwater, heavy metal contamination, leachate, open dumping site

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2834 Temporal Effects on Chemical Composition of Treated Wastewater and Borehole Water Used for Irrigation in Limpopo Province, South Africa

Authors: Pholosho M. Kgopa, Phatu W. Mashela, Alen Manyevere

Abstract:

Increasing incidents of drought spells in most Sub-Saharan Africa call for using alternative sources of water for irrigation in arid and semi-arid regions. A study was conducted to investigate chemical composition of borehole and treated wastewater from different sampling disposal sites at University of Limpopo Experimental Farm (ULEF). A 4 × 5 factorial experiment, with the borehole as a reference sampling site and three other sampling sites along the wastewater disposal system was conducted over five months. Water samples were collected at four sites namely, (a) exit from Pond 16 into the furrow, (b) entry into night-dam, (c) exit from night dam to irrigated fields and (d) exit from borehole to irrigated fields. Water samples were collected in the middle of each month, starting from July to November 2016. Samples were analysed for pH, EC, Ca, Mg, Na, K, Al, B, Zn, Cu, Cr, Pb, Cd and As. The site × time interactions were highly significant for Ca, Mg, Zn, Cu, Cr, Pb, Cd, and As variables, but not for Na and K. Sampling site was highly significant on all variables, with sampling period not significant for K and Na. Relative to water from the borehole, Na concentration in wastewater samples from the night-dam exit, night-dam entry and Pond16 exit were lower by 69, 34 and 55%, respectively. Relative to borehole water, Al was higher in wastewater sampling sites. In conclusion, both sampling site and period affected the chemical composition of treated wastewater.

Keywords: irrigation water quality, spatial effects, temporal effects, water reuse, water scarcity

Procedia PDF Downloads 239
2833 Identification of Peroxisome Proliferator-Activated Receptors α/γ Dual Agonists for Treatment of Metabolic Disorders, Insilico Screening, and Molecular Dynamics Simulation

Authors: Virendra Nath, Vipin Kumar

Abstract:

Background: TypeII Diabetes mellitus is a foremost health problem worldwide, predisposing to increased mortality and morbidity. Undesirable effects of the current medications have prompted the researcher to develop more potential drug(s) against the disease. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors family and take part in a vital role in the regulation of metabolic equilibrium. They can induce or repress genes associated with adipogenesis, lipid, and glucose metabolism. Aims: Investigation of PPARα/γ agonistic hits were screened by hierarchical virtual screening followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) analysis using approved PPAR α/γ dual agonist. Methods: The PPARα/γ agonistic activity of compounds was searched by using Maestro through structure-based virtual screening and molecular dynamics (MD) simulation application. Virtual screening of nuclear-receptor ligands was done, and the binding modes with protein-ligand interactions of newer entity(s) were investigated. Further, binding energy prediction, Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit along with the structural comparative analysis of approved PPARα/γ agonists with screened hit was done for knowledge-based SAR. Results and Discussion: The silicone chip-based approach recognized the most capable nine hits and had better predictive binding energy as compared to the reference drug compound (Tesaglitazar). In this study, the key amino acid residues of binding pockets of both targets PPARα/γ were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit (ChemDiv-3269-0443). Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit and found root mean square deviation (RMSD) stabile around 2Å and 2.1Å, respectively. Frequency distribution data also revealed that the key residues of both proteins showed maximum contacts with a potent hit during the MD simulation of 20 nanoseconds (ns). The knowledge-based SAR studies of PPARα/γ agonists were studied using 2D structures of approved drugs like aleglitazar, tesaglitazar, etc. for successful designing and synthesis of compounds PPARγ agonistic candidates with anti-hyperlipidimic potential.

Keywords: computational, diabetes, PPAR, simulation

Procedia PDF Downloads 103