Search results for: in silico laboratory
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2456

Search results for: in silico laboratory

2366 Urban Laboratory for Community Involvement in Urban Design Process

Authors: Anja Jutraz, Tadeja Zupancic

Abstract:

This article explores urban laboratory, which presents a combination of different physical and digital methods and tools for public participation in urban design. The city consists of built and unbuilt environments, which can be defined as a community of people, who live there. Communities should have the option to express opinions and decide about the future of their city, from the early stages of the design process onwards. In this paper, we presented the possibility of involving community into renewal of Banska Štiavnica in Slovakia (more exactly the old mining shaft and lake Michal Štolna) and the methods to promote the community building. As a case study we presented the eTHNo project, Education about Technical, Historical and Natural opportunities of Michal Štolna. Moreover, we discussed the possibility of using virtual digital tools for public participation in urban design, where we especially focused on Virtual Urban Laboratory, VuLab.

Keywords: community building, digital tools, public participation, urban design

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2365 Evaluation of Ficus racemosa (Moraceae) as a Potential Source for Drug Formulation Against Coccidiosis

Authors: Naveeda Akhtar Qureshi, Wajiha

Abstract:

Coccidiosis is a protozoan parasitic disease of genus Eimeria. It is an avian infection causing a great economic loss of 3 billion USD per year globally. A number of anticoccidial drugs are in use however many of them have side effects and cost effective. With increase in poultry demand throughout the world there is a need of more drugs and vaccines against coccidiosis. The present study is based upon the use of F. racemosa a medicinal plant to be a potential source of anticoccidial agents. The methanolic leaves extract was fractionated by column and thin layer chromatography and got nineteen fractions. Each fraction different concentrations was evaluated for its anticoccidial properties in an invitro experiment against E. tenella, E. necatrix and E. mitis. The anticoccidial active fractions were further characterized by spectroscopy (UV-Vis, FTIR) and GC-MS analysis. The in silico molecular docking of active fractions identified compounds were carried out. Among all fractions significantly maximum sporulation inhibition efficacy was shown by F-19 (67.11±2.18) followed by F-15 (65.21±1.34) at concentration of 30mg/ml against E. tenella. The significantly highest sporozoites viability inhibition was shown by F-19 (69.23±2.11) followed by F-15 (67.14±1.52) against E. necatrix at concentration 30mg/ml. Anticoccidial active fractions 15 and 19 showed peak spectrum at 207 and 202nm respectively by UV analysis. Their FTIR analysis confirmed the presence of carboxylic acid, amines, phenols, etc. Anticoccidial active compounds like Cyclododecane methanol, oleic acid, Octadecanoic acid, etc were identified by GC-MS analysis. Identified compounds in silico molecular docking study showed that cyclododecane methanol of F-19 and oleic acid of F-15 showed highest binding affinity with target S-Adenosylmethionine synthase. Hence for further authentication in vivo anticoccidial studies are recommended.

Keywords: ficus racemosa, cluster fig, column chromatography, anticoccidial fractions, GC-MS, molecular docking., s-adenosylmethionine synthase

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2364 Implementation of a Quality Management Approach in the Laboratory of Quality Control and the Repression of Fraud (CACQE) of the Wilaya of Bechar

Authors: Khadidja Mebarki, Naceur Boussouar, Nabila Ihaddadene, M. Akermi

Abstract:

Food products are particularly sensitive, since they concern the health of the consumer, whether it’s be from the health point of view or commercial, this kind of product must be subjected to rigorous controls, in order to prevent any fraud. Quality and safety are essential for food security, public health and economic development. The strengthening of food security is essential to increase food security which is considered reached when all individuals can at any time access safe and nutritious food they need to lead healthy and active lives. The objective of this project is to initiate a quality approach in the laboratories of the quality control and the repression of fraud. It will be directed towards the application of good laboratory practices, traceability, management of quality documents (quality, procedures and specification manual) and quality audits. And to prepare the ground for a possible accreditation by ISO 17025 standard of BECHAR laboratory’s. The project will take place in four main stages: 1- Preparation of an audit grid; 2- Realization of a quality audit according to the method of 5 M completed by a section on quality documentation; 3- Drafting of an audit report and proposal for recommendations; 4- Implementation of corrective actions on the ground. This last step consisted in the formalization of the cleaning disinfection plan; work on good hygiene practices, establishment of a mapping of processes and flow charts of the different processes of the laboratory, classifying quality documents and formalizing the process of document management. During the period of the study within the laboratory, all facets of the work were almost appreciated, as we participated in the expertise performed in within it.

Keywords: quality, management, ISO 17025 accreditation, GLP

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2363 Functional Analysis of Variants Implicated in Hearing Loss in a Cohort from Argentina: From Molecular Diagnosis to Pre-Clinical Research

Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

Abstract:

Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

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2362 Performance of the New Laboratory-Based Algorithm for HIV Diagnosis in Southwestern China

Authors: Yanhua Zhao, Chenli Rao, Dongdong Li, Chuanmin Tao

Abstract:

The Chinese Centers for Disease Control and Prevention (CCDC) issued a new laboratory-based algorithm for HIV diagnosis on April 2016, which initially screens with a combination HIV-1/HIV-2 antigen/antibody fourth-generation immunoassay (IA) followed, when reactive, an HIV-1/HIV-2 undifferentiated antibody IA in duplicate. Reactive specimens with concordant results undergo supplemental tests with western blots, or HIV-1 nucleic acid tests (NATs) and non-reactive specimens with discordant results receive HIV-1 NATs or p24 antigen tests or 2-4 weeks follow-up tests. However, little data evaluating the application of the new algorithm have been reported to date. The study was to evaluate the performance of new laboratory-based HIV diagnostic algorithm in an inpatient population of Southwest China over the initial 6 months by compared with the old algorithm. Plasma specimens collected from inpatients from May 1, 2016, to October 31, 2016, are submitted to the laboratory for screening HIV infection performed by both the new HIV testing algorithm and the old version. The sensitivity and specificity of the algorithms and the difference of the categorized numbers of plasmas were calculated. Under the new algorithm for HIV diagnosis, 170 of the total 52 749 plasma specimens were confirmed as positively HIV-infected (0.32%). The sensitivity and specificity of the new algorithm were 100% (170/170) and 100% (52 579/52 579), respectively; while 167 HIV-1 positive specimens were identified by the old algorithm with sensitivity 98.24% (167/170) and 100% (52 579/52 579), respectively. Three acute HIV-1 infections (AHIs) and two early HIV-1 infections (EHIs) were identified by the new algorithm; the former was missed by old procedure. Compared with the old version, the new algorithm produced fewer WB-indeterminate results (2 vs. 16, p = 0.001), which led to fewer follow-up tests. Therefore, the new HIV testing algorithm is more sensitive for detecting acute HIV-1 infections with maintaining the ability to verify the established HIV-1 infections and can dramatically decrease the greater number of WB-indeterminate specimens.

Keywords: algorithm, diagnosis, HIV, laboratory

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2361 Structure Modification of Leonurine to Improve Its Potency as Aphrodisiac

Authors: Ruslin, R. E. Kartasasmita, M. S. Wibowo, S. Ibrahim

Abstract:

An aphrodisiac is a substance contained in food or drug that can arouse sexual instinct and increase pleasure while working, these substances derived from plants, animals, and minerals. When consuming substances that have aphrodisiac activity and duration can improve the sexual instinct. The natural aphrodisiac effect can be obtained through plants, animals, and minerals. Leonurine compound has aphrodisiac activity, these compounds can be isolated from plants of Leonurus Sp, Sundanese people is known as deundereman, this plant is empirical has aphrodisiac activity and based on the isolation of active compounds from plants known to contain compounds leonurine, so that the compound is expected to have activity aphrodisiac. Leonurine compound can be isolated from plants or synthesized chemically with material dasa siringat acid. Leonurine compound can be obtained commercial and derivatives of these compounds can be synthesized in an effort to increase its activity. This study aims to obtain derivatives leonurine better aphrodisiac activity compared with the parent compound, modified the structure of the compounds in the form leonurin guanidino butyl ester group with butyl amin and bromoetanol. ArgusLab program version 4.0.1 is used to determine the binding energy, hydrogen bonds and amino acids involved in the interaction of the compound PDE5 receptor. The in vivo test leonurine compounds and derivatives as an aphrodisiac ingredients and hormone testosterone levels using 27 male rats Wistar strain and 9 female mice of the same species, ages ranged from 12 weeks rats weighing + 200 g / tail. The test animal is divided into 9 groups according to the type of compounds and the dose given. Each treatment group was orally administered 2 ml per day for 5 days. On the sixth day was observed male rat sexual behavior and taking blood from the heart to measure testosterone levels using ELISA technique. Statistical analysis was performed in this study is the ANOVA test Least Square Differences (LSD) using the program Statistical Product and Service Solutions (SPSS). Aphrodisiac efficacy of the leonurine compound and its derivatives have proven in silico and in vivo test, the in silico testing leonurine derivatives have smaller binding energy derivatives leonurine so that activity better than leonurine compounds. Testing in vivo using rats of wistar strain that better leonurine derivative of this compound shows leonurine that in silico studies in parallel with in vivo tests. Modification of the structure in the form of guanidine butyl ester group with butyl amin and bromoethanol increase compared leonurine compound for aphrodisiac activity, testosterone derivatives of compounds leonurine experienced a significant improvement especial is 1RD compounds especially at doses of 100 and 150 mg/bb. The results showed that the compound leonurine and its compounds contain aphrodisiac activity and increase the amount of testosterone in the blood. The compound test used in this study acts as a steroid precursor resulting in increased testosterone.

Keywords: aphrodisiac dysfunction erectile leonurine 1-RD 2-RD, dysfunction, erectile leonurine, 1-RD 2-RD

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2360 Analysis of the Annual Proficiency Testing Procedure for Intermediate Reference Laboratories Conducted by the National Reference Laboratory from 2013 to 2017

Authors: Reena K., Mamatha H. G., Somshekarayya, P. Kumar

Abstract:

Objectives: The annual proficiency testing of intermediate reference laboratories is conducted by the National Reference Laboratory (NRL) to assess the efficiency of the laboratories to correctly identify Mycobacterium tuberculosis and to determine its drug susceptibility pattern. The proficiency testing results from 2013 to 2017 were analyzed to determine laboratories that were consistent in reporting quality results and those that had difficulty in doing so. Methods: A panel of twenty cultures were sent out to each of these laboratories. The laboratories were expected to grow the cultures in their own laboratories, set up drug susceptibly testing by all the methods they were certified for and report the results within the stipulated time period. The turnaround time for reporting results, specificity, sensitivity positive and negative predictive values and efficiency of the laboratory in identifying the cultures were analyzed. Results: Most of the laboratories had reported their results within the stipulated time period. However, there was enormous delay in reporting results from few of the laboratories. This was mainly due to improper functioning of the biosafety level III laboratory. Only 40% of the laboratories had 100% efficiency in solid culture using Lowenstein Jensen medium. This was expected as a solid culture, and drug susceptibility testing is not used for diagnosing drug resistance. Rapid molecular methods such as Line probe assay and Genexpert are used to determine drug resistance. Automated liquid culture system such as the Mycobacterial growth indicator tube is used to determine prognosis of the patient while on treatment. It was observed that 90% of the laboratories had achieved 100% in the liquid culture method. Almost all laboratories had achieved 100% efficiency in the line probe assay method which is the method of choice for determining drug-resistant tuberculosis. Conclusion: Since the liquid culture and line probe assay technologies are routinely used for the detection of drug-resistant tuberculosis the laboratories exhibited higher level of efficiency as compared to solid culture and drug susceptibility testing which are rarely used. The infrastructure of the laboratory should be maintained properly so that samples can be processed safely and results could be declared on time.

Keywords: annual proficiency testing, drug susceptibility testing, intermediate reference laboratory, national reference laboratory

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2359 In Silico Study of Antiviral Drugs Against Three Important Proteins of Sars-Cov-2 Using Molecular Docking Method

Authors: Alireza Jalalvand, Maryam Saleh, Somayeh Behjat Khatouni, Zahra Bahri Najafi, Foroozan Fatahinia, Narges Ismailzadeh, Behrokh Farahmand

Abstract:

Object: In the last two decades, the recent outbreak of Coronavirus (SARS-CoV-2) imposed a global pandemic in the world. Despite the increasing prevalence of the disease, there are no effective drugs to treat it. A suitable and rapid way to afford an effective drug and treat the global pandemic is a computational drug study. This study used molecular docking methods to examine the potential inhibition of over 50 antiviral drugs against three fundamental proteins of SARS-CoV-2. METHODS: Through a literature review, three important proteins (a key protease, RNA-dependent RNA polymerase (RdRp), and spike) were selected as drug targets. Three-dimensional (3D) structures of protease, spike, and RdRP proteins were obtained from the Protein Data Bank. Protein had minimal energy. Over 50 antiviral drugs were considered candidates for protein inhibition and their 3D structures were obtained from drug banks. The Autodock 4.2 software was used to define the molecular docking settings and run the algorithm. RESULTS: Five drugs, including indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, exhibited the highest inhibitory potency against all three proteins based on the binding energies and drug binding positions deduced from docking and hydrogen-bonding analysis. Conclusions: According to the results, among the drugs mentioned, saquinavir and lopinavir showed the highest inhibitory potency against all three proteins compared to other drugs. It may enter laboratory phase studies as a dual-drug treatment to inhibit SARS-CoV-2.

Keywords: covid-19, drug repositioning, molecular docking, lopinavir, saquinavir

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2358 The Interplay between Autophagy and Macrophages' Polarization in Wound Healing: A Genetic Regulatory Network Analysis

Authors: Mayada Mazher, Ahmed Moustafa, Ahmed Abdellatif

Abstract:

Background: Autophagy is a eukaryotic, highly conserved catabolic process implicated in many pathophysiologies such as wound healing. Autophagy-associated genes serve as a scaffolding platform for signal transduction of macrophage polarization during the inflammatory phase of wound healing and tissue repair process. In the current study, we report a model for the interplay between autophagy-associated genes and macrophages polarization associated genes. Methods: In silico analysis was performed on 249 autophagy-related genes retrieved from the public autophagy database and gene expression data retrieved from Gene Expression Omnibus (GEO); GSE81922 and GSE69607 microarray data macrophages polarization 199 DEGS. An integrated protein-protein interaction network was constructed for autophagy and macrophage gene sets. The gene sets were then used for GO terms pathway enrichment analysis. Common transcription factors for autophagy and macrophages' polarization were identified. Finally, microRNAs enriched in both autophagy and macrophages were predicated. Results: In silico prediction of common transcription factors in DEGs macrophages and autophagy gene sets revealed a new role for the transcription factors, HOMEZ, GABPA, ELK1 and REL, that commonly regulate macrophages associated genes: IL6,IL1M, IL1B, NOS1, SOC3 and autophagy-related genes: Atg12, Rictor, Rb1cc1, Gaparab1, Atg16l1. Conclusions: Autophagy and macrophages' polarization are interdependent cellular processes, and both autophagy-related proteins and macrophages' polarization related proteins coordinate in tissue remodelling via transcription factors and microRNAs regulatory network. The current work highlights a potential new role for transcription factors HOMEZ, GABPA, ELK1 and REL in wound healing.

Keywords: autophagy related proteins, integrated network analysis, macrophages polarization M1 and M2, tissue remodelling

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2357 Investigation of the Decisive Factors on the Slump Loss: A Case Study of Cement Factors (Portland Cement Type 2)

Authors: M. B. Ahmadi, A. A. Kaffash B., B. Mobaraki

Abstract:

Slump loss, which refers to the gradual reduction of workability and the amount of slump in fresh concrete over time, is one of the significant challenges in the ready-mixed concrete industry. Therefore, having accurate knowledge of the factors affecting slump loss is a crucial solution in this field. In this paper, an attempt was made to investigate the effect of cement produced by different units on the slump of concrete in a laboratory setting. For this purpose, 12 cement samples were prepared from 6 different production units. Physical and chemical tests were performed on the cement samples. Subsequently, a laboratory concrete mix with a slump of 13 ± 1 cm was prepared with each cement sample, and the slump was measured at 0, 15, 30, 45, and 60 minutes. Although the environmental factors, mix design specifications, and execution conditions—factors that significantly influence the slump loss trend—were constant in all 12 laboratory concrete mixes, the slump loss trends differed among them. These trends were categorized based on the results, and the relationship between the slump loss percentage in 60 minutes, the water-cement ratio, and the LOI and K2O values of different cements were introduced.

Keywords: concrete, slump loss, portland cement, efficiency

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2356 Process Evaluation for a Trienzymatic System

Authors: C. Müller, T. Ortmann, S. Scholl, H. J. Jördening

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Multienzymatic catalysis can be used as an alternative to chemical synthesis or hydrolysis of polysaccharides for the production of high value oligosaccharides from cheap resources such as sucrose. However, development of multienzymatic processes is complex, especially with respect to suitable conditions for enzymes originating from different organisms. Furthermore, an optimal configuration of the catalysts in a reaction cascade has to be found. These challenges can be approached by design of experiments. The system investigated in this study is a trienzymatic catalyzed reaction which results in laminaribiose production from sucrose and comprises covalently immobilized sucrose phosphorylase (SP), glucose isomerase (GI) and laminaribiose phosphorylase (LP). Operational windows determined with design of experiments and kinetic data of the enzymes were used to optimize the enzyme ratio for maximum product formation and minimal production of byproducts. After adjustment of the enzyme activity ratio to 1: 1.74: 2.23 (SP: LP: GI), different process options were investigated in silico. The considered options included substrate dependency, the use of glucose as co-substrate and substitution of glucose isomerase by glucose addition. Modeling of batch operation in a stirred tank reactor led to yields of 44.4% whereas operation in a continuous stirred tank reactor resulted in product yields of 22.5%. The maximum yield in a bienzymatic system comprised of sucrose phosphorylase and laminaribiose phosphorylase was 67.7% with sucrose and different amounts of glucose as substrate. The experimental data was in good compliance with the process model for batch operation. The continuous operation will be investigated in further studies. Simulation of operational process possibilities enabled us to compare various operational modes regarding different aspects such as cost efficiency, with the minimum amount of expensive and time-consuming practical experiments. This gives us more flexibility in process implementation and allows us, for example, to change the production goal from laminaribiose to higher oligosaccharides.

Keywords: design of experiments, enzyme kinetics, multi-enzymatic system, in silico process development

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2355 Forensic Entomology in Algeria

Authors: Meriem Taleb, Ghania Tail, Fatma Zohra Kara, Brahim Djedouani, T. Moussa

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Forensic entomology is the use of insects and their arthropod relatives as silent witnesses to aid legal investigations by interpreting information concerning a death. The main purpose of forensic entomology is to establish the postmortem interval or PMI Postmortem interval is a matter of crucial importance in the investigations of homicide and other untimely deaths when the body found is after three days. Forensic entomology has grown immensely as a discipline in the past thirty years. In Algeria, forensic entomology was introduced in 2010 by the National Institute for Criminalistics and Criminology of the National Gendarmerie (NICC). However, all the work that has been done so far in this growing field in Algeria has been unknown at both the national and international levels. In this context, the aim of this paper is to describe the state of forensic entomology in Algeria. The Laboratory of Entomology of the NICC is the only one of its kind in Algeria. It started its activities in 2010, consisting of two specialists. The main missions of the laboratory are estimation of the PMI by the analysis of entomological evidence, and determination if the body was moved. Currently, the laboratory is performing different tasks such as the expert work required by investigators to estimate the PMI using the insects. The estimation is performed by the accumulated degree days method (ADD) in most of the cases except for those where the cadaver is in dry decay. To assure the quality of the entomological evidence, crime scene personnel are trained by the laboratory of Entomology of the NICC. Recently, undergraduate and graduate students have been studying carrion ecology and insect activity in different geographic locations of Algeria using rabbits and wild boar cadavers as animal models. The Laboratory of Entomology of the NICC has also been involved in some of these research projects. Entomotoxicology experiments are also conducted with the collaboration of the Toxicology Department of the NICC. By dint of hard work that has been performed by the Laboratory of Entomology of the NICC, official bodies have been adopting more and more the use of entomological evidence in criminal investigations in Algeria, which is commendable. It is important, therefore, that steps are taken to fill in the gaps in the knowledge necessary for entomological evidence to have a useful future in criminal investigations in Algeria.

Keywords: forensic entomology, corpse, insects, postmortem interval, expertise, Algeria

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2354 Regular Laboratory Based Neonatal Simulation Program Increases Senior Clinicians’ Knowledge, Skills and Confidence Caring for Sick Neonates

Authors: Madeline Tagg, Choihoong Mui, Elizabeth Lek, Jide Menakaya

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Introduction: Simulation technology is used by neonatal teams to learn and refresh skills and gain the knowledge and confidence to care for sick neonates. In-situ simulation is considered superior to laboratory-based programmes as it closely mirrors real life situations. This study reports our experience of running regular laboratory-based simulation sessions for senior clinicians and nurses and its impact on their knowledge, skills and confidence. Methods: A before and after questionnaire survey was carried out on senior clinicians and nurses that attended a scheduled laboratory-based simulation session. Participants were asked to document their expectations before a 3-hour monthly laboratory programme started and invited to feedback their reflections at the end of the session. The session included discussion of relevant clinical guidelines, immersion in a scenario and video led debrief. The results of the survey were analysed in three skills based categories - improved, no change or a worsened experience. Results: 45 questionnaires were completed and analysed. Of these 25 (55%) were completed by consultants seven and six by nurses and trainee doctors respectively, and seven respondents were unknown. 40 (88%) rated the session overall and guideline review as good/excellent, 39 respondents (86%) rated the scenario session good/excellent and 40/45 fed back a good/excellent debrief session. 33 (73%) respondents completed the before and after questionnaire. 21/33 (63%) reflected an improved knowledge, skill or confidence in caring for sick new-bon babies, eight respondents reported no change and four fed back a worse experience after the session. Discussion: Most respondents found the laboratory based structured simulation session beneficial for their professional development. They valued equally the whole content of the programme such as guideline review and equipment training as well as the simulation and debrief sessions. Two out three participants stated their knowledge of caring for sick new-born babies had been transformed positively by the session. Sessions where simulation equipment failed or relevant staff were absent contributed to a poor educational experience. Summary: A regular structured laboratory-based simulation programme with a rich content is a credible educational resource for improving the knowledge, skills and confidence of senior clinicians caring for sick new born babies.

Keywords: knowledge, laboratory based, neonates, simulation

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2353 The Importance of Water Temperature and Curing Conditions on Concrete Curing

Authors: Ahmad Javid Zia, Abdulkerim Ilgun, Suleyman Kamil Akin, Mustafa Altin

Abstract:

Curing conditions that help concrete, which is one of the most widely used building materials in construction sector, gain strength today is one the important issues. In this study the varying concrete strength depending on water temperature at curing stage is investigated through tests at laboratory. At laboratory the curing conditions has been determined according to both TS EN 12390-2 and regular construction site while performing the experiments on specimens. Five samples have been taken from concrete and cured under five different curing conditions and the compressive strength results of concrete specimens have been compared. One of these five curing conditions has been prepared accordance with TS EN 12390-2, the sample cured at 20 ± 2 ˚C and accepted as reference samples. Two of the remaining sample groups have been cured in 5 ± 2 ˚C and 15 ± 2 ˚C and the other two have been cured outside of the laboratory. One group of the samples which have been cured outside has been watered twice a day and the other group has not been watered at all. The experiments have been carried out on 150x150x150 mm cube samples of C20 (200 kg/cm2) and C25 (250 kg/cm2). 7 and 28 days compressive strength of specimens have been measured and compared.

Keywords: concrete curing, curing conditions, water temperature, concrete compressive strength

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2352 Characterizing Nanoparticles Generated from the Different Working Type and the Stack Flue during 3D Printing Process

Authors: Kai-Jui Kou, Tzu-Ling Shen, Ying-Fang Wang

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The objectives of the present study are to characterize nanoparticles generated from the different working type in 3D printing room and the stack flue during 3D printing process. The studied laboratory (10.5 m× 7.2 m × 3.2 m) with a ventilation rate of 500 m³/H is installed a 3D metal printing machine. Direct-reading instrument of a scanning mobility particle sizer (SMPS, Model 3082, TSI Inc., St. Paul, MN, USA) was used to conduct static sampling for nanoparticle number concentration and particle size distribution measurements. The SMPS obtained particle number concentration at every 3 minutes, the diameter of the SMPS ranged from 11~372 nm when the aerosol and sheath flow rates were set at 0.6 and 6 L/min, respectively. The concentrations of background, printing process, clearing operation, and screening operation were performed in the laboratory. On the other hand, we also conducted nanoparticle measurement on the 3D printing machine's stack flue to understand its emission characteristics. Results show that the nanoparticles emitted from the different operation process were the same distribution in the form of the uni-modal with number median diameter (NMD) as approximately 28.3 nm to 29.6 nm. The number concentrations of nanoparticles were 2.55×10³ count/cm³ in laboratory background, 2.19×10³ count/cm³ during printing process, 2.29×10³ count/cm³ during clearing process, 3.05×10³ count/cm³ during screening process, 2.69×10³ count/cm³ in laboratory background after printing process, and 6.75×10³ outside laboratory, respectively. We found that there are no emission nanoparticles during the printing process. However, the number concentration of stack flue nanoparticles in the ongoing print is 1.13×10⁶ count/cm³, and that of the non-printing is 1.63×10⁴ count/cm³, with a NMD of 458 nm and 29.4 nm, respectively. It can be confirmed that the measured particle size belongs to easily penetrate the filter in theory during the printing process, even though the 3D printer has a high-efficiency filtration device. Therefore, it is recommended that the stack flue of the 3D printer would be equipped with an appropriate dust collection device to prevent the operators from exposing these hazardous particles.

Keywords: nanoparticle, particle emission, 3D printing, number concentration

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2351 Early Age Behavior of Wind Turbine Gravity Foundations

Authors: Janet Modu, Jean-Francois Georgin, Laurent Briancon, Eric Antoinet

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The current practice during the repowering phase of wind turbines is deconstruction of existing foundations and construction of new foundations to accept larger wind loads or once the foundations have reached the end of their service lives. The ongoing research project FUI25 FEDRE (Fondations d’Eoliennes Durables et REpowering) therefore serves to propose scalable wind turbine foundation designs to allow reuse of the existing foundations. To undertake this research, numerical models and laboratory-scale models are currently being utilized and implemented in the GEOMAS laboratory at INSA Lyon following instrumentation of a reference wind turbine situated in the Northern part of France. Sensors placed within both the foundation and the underlying soil monitor the evolution of stresses from the foundation’s early age to stresses during service. The results from the instrumentation form the basis of validation for both the laboratory and numerical works conducted throughout the project duration. The study currently focuses on the effect of coupled mechanisms (Thermal-Hydro-Mechanical-Chemical) that induce stress during the early age of the reinforced concrete foundation, and scale factor considerations in the replication of the reference wind turbine foundation at laboratory-scale. Using THMC 3D models on COMSOL Multi-physics software, the numerical analysis performed on both the laboratory-scale and the full-scale foundations simulate the thermal deformation, hydration, shrinkage (desiccation and autogenous) and creep so as to predict the initial damage caused by internal processes during concrete setting and hardening. Results show a prominent effect of early age properties on the damage potential in full-scale wind turbine foundations. However, a prediction of the damage potential at laboratory scale shows significant differences in early age stresses in comparison to the full-scale model depending on the spatial position in the foundation. In addition to the well-known size effect phenomenon, these differences may contribute to inaccuracies encountered when predicting ultimate deformations of the on-site foundation using laboratory scale models.

Keywords: cement hydration, early age behavior, reinforced concrete, shrinkage, THMC 3D models, wind turbines

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2350 Moderating Effects of Future Career Interest in Science and Gender on Students' Achievement in Basic Science in Oyo State, Nigeria

Authors: Segun Jacob Ogunkunle

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The study examined the moderating effects of future career interest in science and gender on achievement in basic science of students taught in a simulated laboratory and enriched laboratory guide material environments. It adopted the pretest-posttest control group quasi experimental design with a 3x2x2 factorial matrix. A total of 277 (130 males, 147 females; ± 17 years) junior secondary three students randomly selected from six purposively selected secondary schools based on availability of functional computer and physics laboratories participated in the study. Data were collected using achievement test in basic science (r=0.87) and future career interest in science (r=0.99) while analysis of covariance and estimated marginal means were used to test three hypotheses at 0.05 level of significance. The findings of the study show that future career interest in science had significant effect on students’ achievement in basic science whereas gender did not. The interaction effect of future career interest in science and gender on students’ achievement in basic science was not significant. It is therefore recommended that prior knowledge of students’ future career interest in science could be used to improve participation in basic science practical in order to enhance achievement in biology, chemistry, and physics at the post-basic education level in Nigeria.

Keywords: future career interest in science, basic science, simulated laboratory, enriched laboratory guide materials, achievement in science

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2349 Molecular Epidemiology of Anthrax in Georgia

Authors: N. G. Vepkhvadze, T. Enukidze

Abstract:

Anthrax is a fatal disease caused by strains of Bacillus anthracis, a spore-forming gram-positive bacillus that causes the disease anthrax in animals and humans. Anthrax is a zoonotic disease that is also well-recognized as a potential agent of bioterrorism. Infection in humans is extremely rare in the developed world and is generally due to contact with infected animals or contaminated animal products. Testing of this zoonotic disease began in 1907 in Georgia and is still being tested routinely to provide accurate information and efficient testing results at the State Laboratory of Agriculture of Georgia. Each clinical sample is analyzed by RT-PCR and bacteriology methods; this study used Real-Time PCR assays for the detection of B. anthracis that rely on plasmid-encoded targets with a chromosomal marker to correctly differentiate pathogenic strains from non-anthracis Bacillus species. During the period of 2015-2022, the State Laboratory of Agriculture (SLA) tested 250 clinical and environmental (soil) samples from several different regions in Georgia. In total, 61 out of the 250 samples were positive during this period. Based on the results, Anthrax cases are mostly present in Eastern Georgia, with a high density of the population of livestock, specifically in the regions of Kakheti and Kvemo Kartli. All laboratory activities are being performed in accordance with International Quality standards, adhering to biosafety and biosecurity rules by qualified and experienced personnel handling pathogenic agents. Laboratory testing plays the largest role in diagnosing animals with anthrax, which helps pertinent institutions to quickly confirm a diagnosis of anthrax and evaluate the epidemiological situation that generates important data for further responses.

Keywords: animal disease, baccilus anthracis, edp, laboratory molecular diagnostics

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2348 Antimicrobial Action and Its Underlying Mechanism by Methanolic Seed Extract of Syzygium cumini on Bacillus subtilis

Authors: Alok Kumar Yadav, Saurabh Saraswat, Preeti Sirohi, Manjoo Rani, Sameer Srivastava, Manish Pratap Singh, Nand K. Singh

Abstract:

The development of antibiotic resistance in bacteria is increasing at an alarming rate, and this is considered as one of the most serious threats in the history of medicine, and an alternative solution should be derived so as to tackle this problem. In many countries, people use the medicinal plants for the treatment of various diseases as these are cheaper, easily available and least toxic. Syzygium cumini is used for the treatment of various kinds of diseases but their mechanism of action is not reported. The antimicrobial activity of Syzygium cumini was tested by the well diffusion assay and zone of inhibition was reported to be 20.06 mm as compared to control with MIC of 0.3 mg/ml. Genomic DNA fragmentation of Bacillus subtilis revealed apoptosis and FE-SEM indicate cell wall cracking on several intervals of time. Propidium iodide staining results showed that few bacterial cells were stained in the control and population of stained cells increase after exposing them for various period of time. Flow cytometric kinetic data analysis on the membrane permeabilization in bacterial cell showed the significant contribution of antimicrobial potential of the seed extract on antimicrobial-induced permeabilization. Two components of Syzygium cumini methanolic seed extract was found to be quite active against four enzymes like PDB ID- 1W5D, 4OX3, 3MFD and 5E2F which have a very crucial role in membrane synthesis in Bacillus subtilis by in silico analysis. Through in silico analysis, lupeol showed highest binding energy for macromolecule 1W5D and 4OX3 whereas stigmasterol showed the highest binding energy for macromolecule 3MFD and 5E2F respectively. It showed that methanolic seed extract of Syzygium cumini can be used for the inhibition of foodborne infections caused by Bacillus subtilis and also as an alternative of prevalent antibiotics.

Keywords: antibiotics, Bacillus subtilis, inhibition, Syzygium cumini

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2347 Emblica officinalis Fruit Extract Ameliorates Cisplatin-Induced Nephrotoxicity in Experimental Rats

Authors: Prerna Kalra, Surender Singh

Abstract:

Cisplatin is the most common chemotherapeutic agent used in different solid tumors, but its main limiting factor is dose-dependent nephrotoxicity by generating reactive oxygen species, by stimulating inflammatory and apoptotic pathways. Additional adjuvant therapies to decrease the toxicity of this chemotherapeutic drug are essential. This study was designed to evaluate the protective role of Emblica officinalis Geartn (Indian gooseberry) against cisplatin induced nephrotoxicity. Emblica officinalis was orally administered to Wistar rats (n=6) for 10 days in 50, 100 and 200mg/kg body weight. On day 7, 8mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. Serum creatinine, blood urea nitrogen and antioxidant levels were measured on day10. The renal damage was evaluated by histopathological and transmission electron microscopy. We found that 200mg/kg dose of Emblica officinalis significantly inhibited the elevation of biochemical parameters i.e. serum creatinine, blood urea nitrogen, oxidant stress marker (malondialdehyde) and increased the reduced levels of antioxidant marker (endogenous glutathione and superoxide dismutase). Cisplatin treated rats have shown acute tubular necrosis and infiltration of inflammatory cells in rat kidney which was reversed after treating the animals with Emblica officinalis in the treatment group. In ultrastructural changes cisplatin treated group showed the damaged mitochondria (M) with dissolved cristae and large number of lysosomes (L) and vacuole (V) formation in tubular epithelial cells. EOE administered group showed visible cristae formation and sign of autophagy vacuoles at a dose of 200mg/kg. Further in-silico studies revealed that ellagic acid is responsible for its nephroprotective effect. The above findings conclude that the Emblica officinalis may be used as an adjuvant therapy in cisplatin induced nephrotoxicity.

Keywords: antioxidant, cisplatin, Emblica officinalis, in silico, nephrotoxicity

Procedia PDF Downloads 262
2346 The Influence of Ice Topography on Sliding over Ice

Authors: Ernests Jansons, Karlis Agris Gross

Abstract:

Winter brings snow and ice in the Northern Europe and with it the need to move safely over ice. It has been customary to select an appropriate material surface for movement over ice, but another way to influence the interaction with ice is to modify the ice surface. The objective of this work was to investigate the influence of ice topography on initiating movement over ice and on sliding velocity over ice in the laboratory and real-life conditions. The ice was prepared smooth, scratched or with solidified ice-droplets to represent the surface of ice after ice rain. In the laboratory, the coefficient of friction and the sliding velocity were measured, but the sliding velocity measured at the skeleton push-start facility. The scratched ice surface increased the resistance to movement and also showed the slowest sliding speed. Sliding was easier on the smooth ice and ice covered with frozen droplets. The contact surface was measured to determine the effect of contact area with sliding. Results from laboratory tests will be compared to loading under heavier loads to show the influence of load on sliding over different ice surfaces. This outcome provides a useful indicator for pedestrians and road traffic on the safety of movement over different ice surfaces as well as a reference for those involved with winter sports.

Keywords: contact area, friction, ice topography, sliding velocity

Procedia PDF Downloads 212
2345 Behavior Loss Aversion Experimental Laboratory of Financial Investments

Authors: Jihene Jebeniani

Abstract:

We proposed an approach combining both the techniques of experimental economy and the flexibility of discrete choice models in order to test the loss aversion. Our main objective was to test the loss aversion of the Cumulative Prospect Theory (CPT). We developed an experimental laboratory in the context of the financial investments that aimed to analyze the attitude towards the risk of the investors. The study uses the lotteries and is basing on econometric modeling. The estimated model was the ordered probit.

Keywords: risk aversion, behavioral finance, experimental economic, lotteries, cumulative prospect theory

Procedia PDF Downloads 436
2344 Determination of the Bearing Capacity of Granular Pumice Soils by Laboratory Tests

Authors: Mustafa Yildiz, Ali Sinan Soganci

Abstract:

Pumice soils are countered in many projects such as transportation roads, channels and residential units throughout the World. The pumice deposits are characterized by the vesicular nature of their particles. When the pumice soils are evaluated considering the geotechnical viewpoint, they differ from silica sands in terms of physical and engineering characteristics. These differences are low grain strength, high friction angle, void ratio and compressibility. At stresses greater than a few hundred kPa, the stress-strain-strength behaviour of these soils is determined by particle crushing. Particle crushing leads to changes in the density and reduction in the components of shear stress due to expansion. In this study, the bearing capacity and behaviour of granular pumice soils compared to sand-gravels were investigated by laboratory model tests. Firstly the geotechnical properties of granular pumice soils were determined; then, the behaviour of pumice soils with an equivalent diameter of sand and gravel soils were investigated by model rectangular and circular foundation types and were compared with each other. For this purpose, basic types of model footing (15*15 cm, 20*20 cm, Φ=15 cm and Φ=20 cm) have been selected. When the experimental results of model bearing capacity are analyzed, the values of sand and gravel bearing capacity tests were found to be 1.0-1.5 times higher than the bearing capacity of pumice the same size. This fact has shown that sand and gravel have a higher bearing capacity than pumice of the similar particle sizes.

Keywords: pumice soils, laboratory model tests, bearing capacity, laboratory model tests, Nevşehir

Procedia PDF Downloads 188
2343 Biochemical Approach to Renewable Energy: Enhancing Students' Perception and Understanding of Science of Energy through Integrated Hands-On Laboratory

Authors: Samina Yasmin, Anzar Khaliq, Zareen Tabassum

Abstract:

Acute power shortage in Pakistan requires an urgent attention to take preliminary steps to spread energy awareness at all levels. One such initiative is taken at Habib University (HU), Pakistan, through renewable energy course, one of the core offerings, where students are trained to investigate various aspects of renewable energy concepts. The course is offered to all freshmen enrolled at HU regardless of their academic backgrounds and degree programs. A four-credit modular course includes both theory and laboratory elements. Hands-on laboratories play an important role in science classes, particularly to enhance the motivation and deep understanding of energy science. A set of selected hands-on activities included in course introduced students to explore the latest developments in the field of renewable energy such as dye-sensitized solar cells, gas chromatography, global warming, climate change, fuel cell energy and power of biomass etc. These projects not only helped HU freshmen to build on energy fundamentals but also provided them greater confidence in investigating, questioning and experimenting with renewable energy related conceptions. A feedback survey arranged during and end of term revealed the effectiveness of the hands-on laboratory to enhance the common understanding of real world problems related to energy such as awareness of energy saving, the level of concern about global climate change, environmental pollution and science of energy behind the energy usage.

Keywords: biochemical approaches, energy curriculum, hands-on laboratory, renewable energy

Procedia PDF Downloads 228
2342 Anlaytical Studies on Subgrade Soil Using Jute Geotextile

Authors: A. Vinod Kumar, G. Sunny Deol, Rakesh Kumar, B. Chandra

Abstract:

Application of fiber reinforcement in road construction is gaining some interest in enhancing soil strength. In this paper, the natural geotextile material obtained from gunny bags was used due to its vast local availability. Construction of flexible pavement on weaker soil such as clay soils is a significant problem in construction as well as in design due to its expansive characteristics. Jute geotextile (JGT) was used on a foundation layer of flexible pavement on rural roads. This problem will be conquered by increasing the subgrade strength by decreasing sub-base layer thickness by improving their overall pavement strength characteristics which ultimately reduces the cost of construction and leads to an economical design. California Bearing Ratio (CBR), unconfined compressive strength (UCS) and triaxial laboratory tests were conducted on two different soil samples, CI and MI. Weaker soil is reinforced with JGT, JGT+Bitumen. JGT+polythene sheet was varied with heights while performing the laboratory tests. Subgrade strength evaluation was investigated by conducting soak CBR test in the laboratory for clayey and silt soils. Laboratory results reveal that reinforced soak CBR value of clayey soil (CI) observed was 10.35%, and silty soil (MI) was 15.6%. This study intends to develop new technique for reinforcing weaker soil with JGT varying parameters for the need of low volume flexible pavements. It was observed that the performance of JGT is inferior when used with bitumen and polyethylene sheets.

Keywords: CBR, jute geotextile, low volume road, weaker soil

Procedia PDF Downloads 412
2341 The Accuracy of an 8-Minute Running Field Test to Estimate Lactate Threshold

Authors: Timothy Quinn, Ronald Croce, Aliaksandr Leuchanka, Justin Walker

Abstract:

Many endurance athletes train at or just below an intensity associated with their lactate threshold (LT) and often the heart rate (HR) that these athletes use for their LT are above their true LT-HR measured in a laboratory. Training above their true LT-HR may lead to overtraining and injury. Few athletes have the capability of measuring their LT in a laboratory and rely on perception to guide them, as accurate field tests to determine LT are limited. Therefore, the purpose of this study was to determine if an 8-minute field test could accurately define the HR associated with LT as measured in the laboratory. On Day 1, fifteen male runners (mean±SD; age, 27.8±4.1 years; height, 177.9±7.1 cm; body mass, 72.3±6.2 kg; body fat, 8.3±3.1%) performed a discontinuous treadmill LT/maximal oxygen consumption (LT/VO2max) test using a portable metabolic gas analyzer (Cosmed K4b2) and a lactate analyzer (Analox GL5). The LT (and associated HR) was determined using the 1/+1 method, where blood lactate increased by 1 mMol•L-1 over baseline followed by an additional 1 mMol•L-1 increase. Days 2 and 3 were randomized, and the athletes performed either an 8-minute run on the treadmill (TM) or on a 160-m indoor track (TR) in an effort to cover as much distance as possible while maintaining a high intensity throughout the entire 8 minutes. VO2, HR, ventilation (VE), and respiratory exchange ratio (RER) were measured using the Cosmed system, and rating of perceived exertion (RPE; 6-20 scale) was recorded every minute. All variables were averaged over the 8 minutes. The total distance covered over the 8 minutes was measured in both conditions. At the completion of the 8-minute runs, blood lactate was measured. Paired sample t-tests and pairwise Pearson correlations were computed to determine the relationship between variables measured in the field tests versus those obtained in the laboratory at LT. An alpha level of <0.05 was required for statistical significance. The HR (mean +SD) during the TM (167+9 bpm) and TR (172+9 bpm) tests were strongly correlated to the HR measured during the laboratory LT (169+11 bpm) test (r=0.68; p<0.03 and r=0.88; p<0.001, respectively). Blood lactate values during the TM and TR tests were not different from each other but were strongly correlated with the laboratory LT (r=0.73; p<0.04 and r=0.66; p<0.05, respectively). VE (Lmin-1) was significantly greater during the TR (134.8+11.4 Lmin-1) as compared to the TM (123.3+16.2 Lmin-1) with moderately strong correlations to the laboratory threshold values (r=0.38; p=0.27 and r=0.58; p=0.06, respectively). VO2 was higher during TR (51.4 mlkg-1min-1) compared to TM (47.4 mlkg-1min-1) with correlations of 0.33 (p=0.35) and 0.48 (p=0.13), respectively to threshold values. Total distance run was significantly greater during the TR (2331.6+180.9 m) as compared to the TM (2177.0+232.6 m), but they were strongly correlated with each other (r=0.82; p<0.002). These results suggest that an 8-minute running field test can accurately predict the HR associated with the LT and may be a simple test that athletes and coaches could implement to aid in training techniques.

Keywords: blood lactate, heart rate, running, training

Procedia PDF Downloads 226
2340 Inhibition of Echis ocellatus Venom Metalloprotease by Flavonoid-Rich Ethyl Acetate Sub-fraction of Moringa oleifera Leaves (Lam.): in vitro and in silico Approaches

Authors: Adeyi Akindele Oluwatosin, Mustapha Kaosarat Keji, Ajisebiola Babafemi Siji, Adeyi Olubisi Esther, Damilohun Samuel Metibemu, Raphael Emuebie Okonji

Abstract:

Envenoming by Echis ocellatus is potentially life-threatening due to severe hemorrhage, renal failure, and capillary leakage. These effects are attributed to snake venom metalloproteinases (SVMPs). Due to drawbacks in the use of antivenom, natural inhibitors from plants are of interest in studies of new antivenom treatment. Antagonizing effects of bioactive compounds of Moringa oleifera, a known antisnake plant, are yet to be tested against SVMPs of E. ocellatus (SVMP-EO). Ethanol crude extract of M. oleifera was partitioned using n-hexane and ethyl acetate. Each partition was fractionated using column chromatography and tested against SVMP-EO purified through ion-exchange chromatography with EchiTab-PLUS polyvalent anti-venom as control. Phytoconstituents of ethyl acetate fraction were screened against the catalytic site of crystal of BaP1-SVMP, while drug-likeness and ADMET toxicity of compound were equally determined. The molecular weight of isolated SVMP-EO was 43.28 kDa, with a specific activity of 245 U/ml, a percentage yield of 62.83 %, and a purification fold of 0.920. The Vmax and Km values are 2 mg/ml and 38.095 μmol/ml/min, respectively, while the optimal pH and temperature are 6.0 and 40°C, respectively. Polyvalent anti-venom, crude extract, and ethyl acetate fraction of M. oleifera exhibited a complete inhibitory effect against SVMP-EO activity. The inhibitions of the P-1 and P-II metalloprotease’s enzymes by the ethyl acetate fraction are largely due to methanol, 6, 8, 9-trimethyl-4-(2-phenylethyl)-3-oxabicyclo[3.3.1]non-6-en-1-yl)- and paroxypropione, respectively. Both compounds are potential drug candidates with little or no concern of toxicity, as revealed from the in-silico predictions. The inhibitory effects suggest that this compound might be a therapeutic candidate for further exploration for treatment of Ocellatus’ envenoming.

Keywords: Echis ocellatus, Moringa oleifera, anti-venom, metalloproteases, snakebite, molecular docking

Procedia PDF Downloads 117
2339 Abridging Pharmaceutical Analysis and Drug Discovery via LC-MS-TOF, NMR, in-silico Toxicity-Bioactivity Profiling for Therapeutic Purposing Zileuton Impurities: Need of Hour

Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

Abstract:

The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity

Procedia PDF Downloads 168
2338 Investigating Anti-Tumourigenic and Anti-Angiogenic Effects of Resveratrol in Breast Carcinogenesis Using in-Silico Algorithms

Authors: Asma Zaib, Saeed Khan, Ayaz Ahmed Noonari, Sehrish Bint-e-Mohsin

Abstract:

Breast cancer is the most common cancer among females worldwide and is estimated that more than 450,000 deaths are reported each year. It accounts for about 14% of all female cancer deaths. Angiogenesis plays an essential role in Breast cancer development, invasion, and metastasis. Breast cancer predominantly begins in luminal epithelial cells lining the normal breast ducts. Breast carcinoma likely requires coordinated efforts of both increased proliferation and increased motility to progress to metastatic stages.Resveratrol: a natural stilbenoid, has anti-inflammatory and anticancer effects that inhibits proliferation of variety of human cancer cell lines, including breast, prostate, stomach, colon, pancreatic, and thyroid cancers.The objective of this study is:To investigate anti-neoangiogenesis effects of Resveratrol in breast cancer and to analyze inhibitory effects of resveratrol on aromatase, Erα, HER2/neu, and VEGFR.Docking is the computational determination of binding affinity between molecule (protein structure and ligand).We performed molecular docking using Swiss-Dock and to determine docking effects of (1) Resveratrol with Aromatase, (2) Resveratrol with ERα (3) Resveratrol with HER2/neu and (4) Resveratrol with VEGFR2.Docking results of resveratrol determined inhibitory effects on aromatase with binding energy of -7.28 kcal/mol which shows anticancerous effects on estrogen dependent breast tumors. Resveratrol also show inhibitory effects on ERα and HER2/new with binging energy -8.02, and -6.74 respectively; which revealed anti-cytoproliferative effects upon breast cancer. On the other hand resveratrol v/s VEGFR showed potential inhibitory effects on neo-angiogenesis with binding energy -7.68 kcal/mol, angiogenesis is the important phenomenon that promote tumor development and metastasis. Resveratrol is an anti-breast cancer agent conformed by in silico studies, it has been identified that resveratrol can inhibit breast cancer cells proliferation by acting as competitive inhibitor of aromatase, ERα and HER2 neo, while neo-angiogemesis is restricted by binding to VEGFR which authenticates the anti-carcinogenic effects of resveratrol against breast cancer.

Keywords: angiogenesis, anti-cytoproliferative, molecular docking, resveratrol

Procedia PDF Downloads 296
2337 Predicting COVID-19 Severity Using a Simple Parameters in Resource-Limited Settings

Authors: Sireethorn Nimitvilai, Ussanee Poolvivatchaikarn, Nuchanart Tomeun

Abstract:

Objective: To determine the simple laboratory parameters to predict disease severity among COVID-19 patients in resource-limited settings. Material and methods: A retrospective cohort study was conducted at Nakhonpathom Hospital, a 722-bed tertiary care hospital, with an average of 50,000 admissions per year, during April 15 and May 15, 2021. Eligible patients were adults aged ≥ 15 years who were hospitalized with COVID-19. Baseline characteristics, comorbid conditions ad laboratory findings at admission were collected. Predictive factors for severe COVID-19 infection were analyzed. Result: There were 207 patients (79 male and 128 female) and the mean age was 46.7 (16.8) years. Of these, 39 cases (18.8%) were severe and 168 (81.2%) cases were non-severe. Factors associated with severe COVID-19 were neutrophil to lymphocyte ratio ≥ 4 (OR 8.1, 95%CI 2.3-20.3, P < 0.001) and C-reactive protein to albumin ratio ≥ 10 (OR 3.49, 95%CI 1.3-9.1, p 0.01). Conclusions: Complete blood counts, C-reactive protein and albumin are simple, inexpensive, widely available tests and can be used to predict severe COVID-19 in resource-limited settings.

Keywords: COVID-19, predictor of severity, resource-limiting settings, simple laboratory parameters

Procedia PDF Downloads 145