Search results for: statistical area
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 12324

Search results for: statistical area

4314 Anti-lipidemic and Hematinic Potentials of Moringa Oleifera Leaves: A Clinical Trial on Type 2 Diabetic Subjects in a Rural Nigerian Community

Authors: Ifeoma C. Afiaenyi, Elizabeth K. Ngwu, Rufina N. B. Ayogu

Abstract:

Diabetes has crept into the rural areas of Nigeria, causing devastating effects on its sufferers; most of them could not afford diabetic medications. Moringa oleifera has been used extensively in animal models to demonstrate its antilipidaemic and haematinic qualities; however, there is a scarcity of data on the effect of graded levels of Moringa oleifera leaves on the lipid profile and hematological parameters in human diabetic subjects. The study determined the effect of Moringa oleifera leaves on the lipid profile and hematological parameters of type 2 diabetic subjects in Ukehe, a rural Nigerian community. Twenty-four adult male and female diabetic subjects were purposively selected for the study. These subjects were shared into four groups of six subjects each. The diets used in the study were isocaloric. A control group (diabetics, group 1) was fed diets without Moringa oleifera leaves. Experimental groups 2, 3 and 4 received 20g, 40g and 60g of Moringa oleifera leaves daily, respectively, in addition to the diets. The subjects' lipid profile and hematological parameters were measured prior to the feeding trial and at the end of the feeding trial. The feeding trial lasted for fourteen days. The data obtained were analyzed using the computer program Statistical Product for Service Solution (SPSS) for windows version 21. A Paired-samples t-test was used to compare the means of values collected before and after the feeding trial within the groups and significance was accepted at p < 0.05. There was a non-significant (p > 0.05) decrease in the mean total cholesterol of the subjects in groups 1, 2 and 3 after the feeding trial. There was a non-significant (p > 0.05) decrease in the mean triglyceride levels of the subjects in group 1 after the feeding trial. Groups 1 and 3 subjects had a non-significant (p > 0.05) decrease in their mean low-density lipoprotein (LDL) cholesterol after the feeding trial. Groups 1, 2 and 4 had a significant (p < 0.05) increase in their mean high-density lipoprotein (HDL) cholesterol after the feeding trial. A significant (p < 0.05) decrease in the mean hemoglobin level was observed only in group 4 subjects. Similarly, there was a significant (p < 0.05) decrease in the mean packed cell volume of group 4 subjects. It was only in group 4 that a significant (p < 0.05) decrease in the mean white blood cells of the subjects was also observed. The changes observed in the parameters assessed were not dose-dependent. Therefore, a similar study of longer duration and more samples is imperative to authenticate these results.

Keywords: anemia, diabetic subjects, lipid profile, moringa oleifera

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4313 Understanding the Selectional Preferences of the Twitter Mentions Network

Authors: R. Sudhesh Solomon, P. Y. K. L. Srinivas, Abhay Narayan, Amitava Das

Abstract:

Users in social networks either unicast or broadcast their messages. At mention is the popular way of unicasting for Twitter whereas general tweeting could be considered as broadcasting method. Understanding the information flow and dynamics within a Social Network and modeling the same is a promising and an open research area called Information Diffusion. This paper seeks an answer to a fundamental question - understanding if the at-mention network or the unicasting pattern in social media is purely random in nature or is there any user specific selectional preference? To answer the question we present an empirical analysis to understand the sociological aspects of Twitter mentions network within a social network community. To understand the sociological behavior we analyze the values (Schwartz model: Achievement, Benevolence, Conformity, Hedonism, Power, Security, Self-Direction, Stimulation, Traditional and Universalism) of all the users. Empirical results suggest that values traits are indeed salient cue to understand how the mention-based communication network functions. For example, we notice that individuals possessing similar values unicast among themselves more often than with other value type people. We also observe that traditional and self-directed people do not maintain very close relationship in the network with the people of different values traits.

Keywords: information diffusion, personality and values, social network analysis, twitter mentions network

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4312 Predicting Success and Failure in Drug Development Using Text Analysis

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

Abstract:

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

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

Procedia PDF Downloads 153
4311 Assessment and Prediction of Vehicular Emissions in Commonwealth Avenue, Quezon City at Various Policy and Technology Scenarios Using Simple Interactive Model (SIM-Air)

Authors: Ria M. Caramoan, Analiza P. Rollon, Karl N. Vergel

Abstract:

The Simple Interactive Models for Better Air Quality (SIM-air) is an integrated approach model that allows the available information to support the integrated urban air quality management. This study utilized the vehicular air pollution information system module of SIM-air for the assessment of vehicular emissions in Commonwealth Avenue, Quezon City, Philippines. The main objective of the study is to assess and predict the contribution of different types of vehicles to the vehicular emissions in terms of PM₁₀, SOₓ, and NOₓ at different policy and technology scenarios. For the base year 2017, the results show vehicular emissions of 735.46 tons of PM₁₀, 108.90 tons of SOₓ, and 2,101.11 tons of NOₓ. Motorcycle is the major source of particulates contributing about 52% of the PM₁₀ emissions. Meanwhile, Public Utility Jeepneys contribute 27% of SOₓ emissions and private cars using gasoline contribute 39% of NOₓ emissions. Ambient air quality monitoring was also conducted in the study area for the standard parameters of PM₁₀, S0₂, and NO₂. Results show an average of 88.11 µg/Ncm, 47.41 µg/Ncm and 22.54 µg/Ncm for PM₁₀, N0₂, and SO₂, respectively, all were within the DENR National Ambient Air Quality Guideline Values. Future emissions of PM₁₀, NOₓ, and SOₓ are estimated at different scenarios. Results show that in the year 2030, PM₁₀ emissions will be increased by 186.2%. NOₓ emissions and SOₓ emissions will also be increased by 38.9% and 5.5%, without the implementation of the scenarios.

Keywords: ambient air quality, emissions inventory, mobile air pollution, vehicular emissions

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4310 English for Specific Purposes: Its Definition, Characteristics, and the Role of Needs Analysis

Authors: Karima Tayaa, Amina Bouaziz

Abstract:

The rapid expansion in the scientific fields and the growth of communication technology increased the use of English as international language in the world. Hence, over the past few decades, many researchers have been emphasizing on how the teaching and learning of English as a foreign or as an additional language can best help students to perform successfully. English for specific purpose is today quite literally regarded as the most global language discipline which existed practically in every country in the world. ESP (English for Specific Purposes) involves teaching and learning the specific skills and language needed by particular learners for a particular purpose. The P in ESP is always a professional purpose which is a set of skills that learners currently need in their work or will need in their professional careers. It has had an early origin since 1960’s and has grown to become one of the most prominent of English language teaching today. Moreover, ESP learners are usually adults who have some quittances with English and learn the language so as to communicate and perform particular profession. Related activities are based on specific purposes and needs. They are integrated into subject matter area important to the learners. Unlike general English which focuses on teaching general language courses and all four language skills are equally stressed, ESP and practically needs analysis determine which language skills are the most needed by the learners and syllabus designed accordingly. This paper looked into the origin, characteristics, development of ESP, the difference between ESP and general English. Finally, the paper critically reviews the role of needs analysis in the ESP.

Keywords: English language teaching, English for general purposes, English for specific purposes, needs analysis

Procedia PDF Downloads 401
4309 Climate Change and Its Impact on Water Security and Health in Coastal Community: A Gender Outlook

Authors: Soorya Vennila

Abstract:

The present study answers the questions; how does climate change affect the water security in drought prone Ramanathapuram district? and what has water insecurity done to the health of the coastal community? The study area chosen is Devipattinam in Ramanathapuram district. Climate change evidentially wreaked havoc on the community with saltwater intrusion, water quality degradation, water scarcity and its eventual economic, social like power inequality within family and community and health hazards. The climatological data such as rainfall, minimum temperature and maximum temperature were statistically analyzed for trend using Mann-Kendall test. The test was conducted for 14 years (1989-2002) of rainfall data, maximum and minimum temperature and the data were statistically analyzed. At the outset, the water quality samples were collected from Devipattinam to test its physical and chemical parameters and their spatial variation. The results were derived as shown in ARC GIS. Using the water quality test water quality index were framed. And finally, key Informant interview, questionnaire were conducted to capture the gender perception and problem. The data collected were thereafter interpreted using SPSS software for recommendations and suggestions to overcome water scarcity and health problems.

Keywords: health, watersecurity, water quality, climate change

Procedia PDF Downloads 70
4308 Structuring Paraphrases: The Impact Sentence Complexity Has on Key Leader Engagements

Authors: Meaghan Bowman

Abstract:

Soldiers are taught about the importance of effective communication with repetition of the phrase, “Communication is key.” They receive training in preparing for, and carrying out, interactions between foreign and domestic leaders to gain crucial information about a mission. These interactions are known as Key Leader Engagements (KLEs). For the training of KLEs, doctrine mandates the skills needed to conduct these “engagements” such as how to: behave appropriately, identify key leaders, and employ effective strategies. Army officers in training learn how to confront leaders, what information to gain, and how to ask questions respectfully. Unfortunately, soldiers rarely learn how to formulate questions optimally. Since less complex questions are easier to understand, we hypothesize that semantic complexity affects content understanding, and that age and education levels may have an effect on one’s ability to form paraphrases and judge their quality. In this study, we looked at paraphrases of queries as well as judgments of both the paraphrases’ naturalness and their semantic similarity to the query. Queries were divided into three complexity categories based on the number of relations (the first number) and the number of knowledge graph edges (the second number). Two crowd-sourced tasks were completed by Amazon volunteer participants, also known as turkers, to answer the research questions: (i) Are more complex queries harder to paraphrase and judge and (ii) Do age and education level affect the ability to understand complex queries. We ran statistical tests as follows: MANOVA for query understanding and two-way ANOVA to understand the relationship between query complexity and education and age. A probe of the number of given-level queries selected for paraphrasing by crowd-sourced workers in seven age ranges yielded promising results. We found significant evidence that age plays a role and marginally significant evidence that education level plays a role. These preliminary tests, with output p-values of 0.0002 and 0.068, respectively, suggest the importance of content understanding in a communication skill set. This basic ability to communicate, which may differ by age and education, permits reproduction and quality assessment and is crucial in training soldiers for effective participation in KLEs.

Keywords: engagement, key leader, paraphrasing, query complexity, understanding

Procedia PDF Downloads 157
4307 Value-Based Argumentation Frameworks and Judicial Moral Reasoning

Authors: Sonia Anand Knowlton

Abstract:

As the use of Artificial Intelligence is becoming increasingly integrated in virtually every area of life, the need and interest to logically formalize the law and judicial reasoning is growing tremendously. The study of argumentation frameworks (AFs) provides promise in this respect. AF’s provide a way of structuring human reasoning using a formal system of non-monotonic logic. P.M. Dung first introduced this framework and demonstrated that certain arguments must prevail and certain arguments must perish based on whether they are logically “attacked” by other arguments. Dung labelled the set of prevailing arguments as the “preferred extension” of the given argumentation framework. Trevor Bench-Capon’s Value-based Argumentation Frameworks extended Dung’s AF system by allowing arguments to derive their force from the promotion of “preferred” values. In VAF systems, the success of an attack from argument A to argument B (i.e., the triumph of argument A) requires that argument B does not promote a value that is preferred to argument A. There has been thorough discussion of the application of VAFs to the law within the computer science literature, mainly demonstrating that legal cases can be effectively mapped out using VAFs. This article analyses VAFs from a jurisprudential standpoint to provide a philosophical and theoretical analysis of what VAFs tell the legal community about the judicial reasoning, specifically distinguishing between legal and moral reasoning. It highlights the limitations of using VAFs to account for judicial moral reasoning in theory and in practice.

Keywords: nonmonotonic logic, legal formalization, computer science, artificial intelligence, morality

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4306 Influence of Deposition Temperature on Supercapacitive Properties of Reduced Graphene Oxide on Carbon Cloth: New Generation of Wearable Energy Storage Electrode Material

Authors: Snehal L. Kadam, Shriniwas B. Kulkarni

Abstract:

Flexible electrode material with high surface area and good electrochemical properties is the current trend captivating the researchers across globe for application in the next generation energy storage field. In the present work, crumpled sheet like reduced graphene oxide grown on carbon cloth by the hydrothermal method with a series of different deposition temperatures at fixed time. The influence of the deposition temperature on the structural, morphological, optical and supercapacitive properties of the electrode material was investigated by XRD, RAMAN, XPS, TEM, FE-SEM, UV-VISIBLE and electrochemical characterization techniques.The results show that the hydrothermally synthesized reduced graphene oxide on carbon cloth has sheet like mesoporous structure. The reduced graphene oxide material at 160°C exhibits the best supercapacitor performance, with a specific capacitance of 443 F/g at scan rate 5mV/sec. Moreover, stability studies show 97% capacitance retention over 1000 CV cycles. This result shows that hydrothermally synthesized RGO on carbon cloth is the potential electrode material and would be used in the next-generation wearable energy storage systems. The detailed analysis and results will be presented at the conference.

Keywords: graphene oxide, reduced graphene oxide, carbon cloth, deposition temperature, supercapacitor

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4305 Building in Language Support in a Hong Kong Chemistry Classroom with English as a Medium of Instruction: An Exploratory Study

Authors: Kai Yip Michael Tsang

Abstract:

Science writing has played a crucial part in science assessments. This paper reports a study in an area that has received little research attention – how Language across the Curriculum (LAC, i.e. science language and literacy) learning activities in science lessons can increase the science knowledge development of English as a foreign language (EFL) students in Hong Kong. The data comes from a school-based interventional study in chemistry classrooms, with written data from questionnaires, assessments and teachers’ logs and verbal data from interviews and classroom observations. The effectiveness of the LAC teaching and learning activities in various chemistry classrooms were compared and evaluated, with discussion of some implications. Students in the treatment group with lower achieving students received LAC learning and teaching activities while students in the control group with higher achieving students received conventional learning and teaching activities. After the study, they performed better in control group in formative assessments. Moreover, they had a better attitude to learning chemistry content with a richer language support. The paper concludes that LAC teaching and learning activities yielded positive learning outcomes among chemistry learners with low English ability.

Keywords: science learning and teaching, content and language integrated learning, language across the curriculum, English as a foreign language

Procedia PDF Downloads 186
4304 Radiation Protection Study for the Assessment of Mixed Fields Ionizing Radiation

Authors: Avram Irina, Coiciu Eugenia-Mihaela, Popovici Mara-Georgiana, Mitu Iani Octavian

Abstract:

ELI-NP stands as a cutting-edge facility globally, hosting unique radiological setups. It conducts experiments leveraging high-power lasers capable of producing extremely brief 10 PW pulses on two fronts. Moreover, it houses an exceptional gamma beam system with distinctive spectral characteristics. The facility hosts various experiments across designated experimental areas, encompassing ultra-short high-power laser tests, high-intensity gamma beam trials, and combined experiments utilizing both setups. The facility hosts a dosimetry laboratory, which recently obtained accreditation, where the radiation safety group employs a host of different types of detectors for monitoring the personnel, environment, and public exposure to ionizing radiation generated in experiments performed. ELI-NP's design was shaped by radiological protection assessments conducted through Monte Carlo simulations. The poster exemplifies an assessment conducted using the FLUKA code in an experimental area where a high-power laser system is implemented, and the future diagnostic system for variable energy gamma beams will soon be operational.

Keywords: radiation protection, Monte Carlo simulation, FLUKA, dosimetry

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4303 Disposition Kinetics of Ciprofloxacin after Intramuscular Administration in Lohi Sheep

Authors: Zahid Iqbal, Ijaz Javed, Riaz Hussain, Ibadullah Jan, Amir Ali Khan

Abstract:

This study was conducted to investigate the disposition kinetics of ciprofloxacin and calculate its optimal dosage in Pakistani sheep of Lohi breed. Injectable preparation of ciprofloxacin was given intramuscularly to eight sheep at a dose of 5 mg/Kg. Before administration of drug blood sample was drawn from each animal. Post drug administration, blood samples were also drawn at various predetermined time periods. Drug concentration in the blood samples was assessed through high performance liquid chromatograph (HPLC). Data were best described by two compartment open model and different pharmacokinetic (PK) parameters were calculated. Cmax of 1.97 ± 0.15 µg/ml was reached at Tmax of 0.88 ± 0.09 hours. Half life of absorption (t1/2 abs) was observed to be 0.63 ± 0.16 hours while t1/2 α (distribution half life) and t1/2 ß (elimination half life) were found to be 0.46 ± 0.05 and 2.93 ± 0.45 hours, respectively. Vd (apparent volume of distribution) was calculated as 2.89 ± 0.30 L/kg while AUC (area under the curve) was 7.19 ± 0.38 µg.hr/mL and CL (total body clearance) was 0.75 ± 0.04 L/hr/kg. Using these parameters, an optimal intramuscular dosage of ciprofloxacin in adult Lohi sheep was calculated as 21.43 mg/kg, advised to be repeated after 24 hours. From this, we came to the conclusion that calculated dose was much higher than the dose advised by the foreign manufacturer and to avoid antimicrobial resistance, it is advised that this locally investigated dosage regimen should be strictly followed in local sheep.

Keywords: pharmacokinetics, dosage regimen, ciprofloxacin, HPLC, sheep

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4302 Adsorbent Removal of Oil Spills Using Bentonite Clay

Authors: Saad Mohamed Elsaid Abdelrahman

Abstract:

The adsorption method is one of the best modern techniques used in removing pollutants, especially organic hydrocarbon compounds, from polluted water. Through this research, bentonite clay can be used to remove organic hydrocarbon compounds, such as heptane and octane, resulting from oil spills in seawater. Bentonite clay can be obtained from the Kholayaz area, located north of Jeddah, at a distance of 80 km. Chemical analysis shows that bentonite clay consists of a mixture of silica, alumina and oxides of some elements. Bentonite clay can be activated in order to raise its adsorption efficiency and to make it suitable for removing pollutants using an ionic organic solvent. It is necessary to study some of the factors that could be in the efficiency of bentonite clay in removing oily organic compounds, such as the time of contact of the clay with heptane and octane solutions, pH and temperature, in order to reach the highest adsorption capacity of bentonite clay. The temperature can be a few degrees Celsius higher. The adsorption capacity of the clay decreases when the temperature is raised more than 4°C to reach its lowest value at the temperature of 50°C. The results show that the friction time of 30 minutes and the pH of 6.8 is the best conditions to obtain the highest adsorption capacity of the clay, 467 mg in the case of heptane and 385 mg in the case of octane compound. Experiments conducted on bentonite clay were encouraging to select it to remove heavy molecular weight pollutants such as petroleum compounds under study.

Keywords: adsorbent, bentonite clay, oil spills, removal

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4301 Atomistic Insight into the System of Trapped Oil Droplet/ Nanofluid System in Nanochannels

Authors: Yuanhao Chang, Senbo Xiao, Zhiliang Zhang, Jianying He

Abstract:

The role of nanoparticles (NPs) in enhanced oil recovery (EOR) is being increasingly emphasized. In this study, the motion of NPs and local stress distribution of tapped oil droplet/nanofluid in nanochannels are studied with coarse-grained modeling and molecular dynamic simulations. The results illustrate three motion patterns for NPs: hydrophilic NPs are more likely to adsorb on the channel and stay near the three-phase contact areas, hydrophobic NPs move inside the oil droplet as clusters and more mixed NPs are trapped at the oil-water interface. NPs in each pattern affect the flow of fluid and the interfacial thickness to various degrees. Based on the calculation of atomistic stress, the characteristic that the higher value of stress occurs at the place where NPs aggregate can be obtained. Different occurrence patterns correspond to specific local stress distribution. Significantly, in the three-phase contact area for hydrophilic NPs, the local stress distribution close to the pattern of structural disjoining pressure is observed, which proves the existence of structural disjoining pressure in molecular dynamics simulation for the first time. Our results guide the design and screen of NPs for EOR and provide a basic understanding of nanofluid applications.

Keywords: local stress distribution, nanoparticles, enhanced oil recovery, molecular dynamics simulation, trapped oil droplet, structural disjoining pressure

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4300 In Vitro Study on the Antimicrobial Activity of Ass Hay (Donkey Skin) On Some Pathogenic Microorganisms

Authors: Emmanuel Jaluchimike Iloputaife, Kelechi Nkechinyere Mbah-Omeje

Abstract:

This study was designed to determine the antimicrobial activities and minimum inhibitory concentration of three different batches (Fresh, Oven dried and Sundried) of Ass Hay extracted with water, ethanol and methanolagainst selected human pathogenic microorganisms (Escherichia coli, Klebsiella Pneumonia, Staphylococcus aureus, Aspergillus niger and Candidaalbicans). All extracts were reconstituted with peptone water and tested for antimicrobial activity. The antimicrobial activity, the Minimum Inhibitory Concentration and Minimum Bactericidal/Fungicidal concentrations were determined by agar well diffusion methodagainst test organismsin which aseptic conditions were observed. The antimicrobial activities of the different batches of Ass Hay on the test organisms varied considerably. The highest inhibition zone diameter at 200 mg/ml for the different batches of Ass Hay was recorded by sundried methanol extract against Escherichia coli at 36.4 ± 0.2 mm while fresh methanol extract inhibited Klebsiela pneumonia with the least inhibition zone diameter at 20.1 ± 0.1mm. At 100 mg/ml the highest inhibition zone diameter was recorded by oven dried water extract against Escherichia coli at 30.3 ± 0.3 mm while sun dried water extract inhibited Staphylococcus aureus with the least inhibition zone diameter at 15.1 ± 0.1 mm. At 50mg/ml, the highest inhibition zone diameter was recorded by fresh water extract against Escherichia coli at 25.9 ± 0.1 mm while oven dried water extract inhibited Klebsiela pneumonia with least inhibition zone diameter at 12.1 ± 0.2 mm. At 25mg/ml, the highest inhibition zone diameter was recorded by fresh water extract against Escherichia coli at 18.3 ± 0.2 mm while sun dried ethanol extract inhibited Escherichia coli with least inhibition zone diameter at 10.1 ± 0.1 mm. The MIC and MBC result of ethanol extract of fresh Ass Hay showed a uniform value of 6.25 mg/ml and 12.5 mg/ml respectively for all test bacterial isolates. The Minimum Inhibitory concentration and Minimum bactericidal concentration results of Oven dried ethanol Ass Hay extract showed a uniform value of 3.125 mg/ml and 6.25 mg/ml respectively for all test bacterial isolates and Minimum fungicidal concentration value of 12.5 mg/ml for Aspergillus niger. Statistical analysis showed there is significant difference in mean zone inhibition diameter of the products at p < 0.05, p = 0.019. This study has shown there is antimicrobial potential in Ass Hay and at such there is need to further exploit Donkey Ass Hay in order to maximize the potential.

Keywords: microorganisms, Ass Hay, antimicrobial activity, extracts

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4299 Stratafix Barbed Suture Versus Polydioxanone Suture on the Rate of Pancreatic Fistula After Pancreaticoduodenectomy

Authors: Saniya Ablatt, Matthew Jacobsson, Jamie Whisler, Austin Forbes

Abstract:

Postoperative pancreatic fistula (POPF) is a complication that occurs in up to 41% of patients after pancreaticoduodenectomy. Although certain characteristics such as individual patient anatomy are known risk factors for POPF, the effect of barbed suture techniques remains underexplored. This study examines whether the use of Stratafix barbed suture versus PDS impacts the risk of developing POPF. After obtaining IRB exemption, a retrospective chart review was initiated involving patients who underwent pancreaticoduodenectomy for the treatment of malignant or premalignant lesions of the pancreas at our institution between April 1st 2020 and April 30th 2022. Patients were stratified into 2 groups respective to the technique used to suture the pancreatico-jejunal anastomosis: Group 1 was composed to patients in which 4.0 Stratafix® suture was used n=41. Group 1 was composed to patients in which 4.0 PDS suture was used n=42. Data regarding patient age, sex, BMI, presence or absence of biochemical leak, presence or absence of grade B & C postoperative pancreatic fistulas, rate and type of in hospital complication, rate of reoperation, 30 day readmission rate, 90 day mortality, and total mortality were compared between groups. 83 patients were included in our study with 42 receiving Stratafix and 41 receiving PDS (50.6% vs 49.4%). Stratafix patients had less biochemical leaks (0.0% vs 4.8%, p=0.19) and higher rates of POPF but this was not statistically significant (7.2% vs 2.4%, p=0.26). Additionally, there was no difference between the use of stratafix versus PDS on the risk of clinically relevant grade B or C POPF (p=0.26, OR=3.25 [CI= 0.74-16.43]). Of the independent variables including age, race, sex, BMI, and ASA class, BMI greater than 25 increased the risk of clinically relevant POPF by 7.7 times compared to patients with BMI less than 25 (p=0.03, OR=7.79 [1.04-88.51]). Despite no significant difference in primary outcomes, the Stratafix group had lower rates of secondary outcomes including 90-day mortality; bleeding, cardiac, and infectious complications; reoperation; and 30-day readmission. On statistical analysis, Stratafix decreased the risk of 30-day readmission (p=0.04, OR=0.21, CI=0.04-0.97) and had a marginally significant effect on the risk of reoperation (p=0.08, OR=0.24, CI=0.04-1.26). There was no difference between the use of Stratafix versus PDS on the risk of POPF (p=0.26). However, Stratafix decreased the risk of 30-day readmission (p=0.04) and BMI greater than 25 increased the risk of clinically relevant POPF (p=0.03).

Keywords: pancreas, hepatobiliary surgery, hepatobiliary, pancreatic leak, biochemical leak, fistula, pancreatic fistula

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4298 Systematic Review of Sexual Assault Prevention Methods for Older Adults: Exploring the Hidden Needs of a Growing Population

Authors: Michelle Hand, Brieanne Beaujolais

Abstract:

Rape stereotypes have long involved the assault of young females by strangers desiring sex. As such, older adult women and men have largely been excluded from research, policies, and awareness raising initiatives to address sexual violence. Moreover sexual assault accounts for the most underreported type of abuse experienced by older adults, highlighting a need to expand our knowledge base in this area. Thus a systematic review of peer-reviewed scholarly articles and reports was conducted to explore the ways sexual assault has been prevented among older adults in recent years and to identify implications for researchers and practitioners as they aim to meet the needs of this population. Articles and reports published during or after 2007 were eligible if their focus included methods to address sex abuse among older adults as well as practice or research implications. Forty-four articles met this criteria and were included in this systematic review. The findings from this review will provide an in-depth understanding of the under-researched issue of sexual violence among older adult women and men as well as current prevention strategies. In addition, implications and recommendations will be provided for practitioners, educators and researchers as they aim to meet the hidden needs of this growing yet under-researched population.

Keywords: elder, rape, sexual assault, sexual violence

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4297 Memory and Myth in Future Cities Case Study: Walking to Imam Reza Holy Shrine of Mashhad, Iran

Authors: Samaneh Eshraghi Ivaria, Torkild Thellefsenb

Abstract:

The article discusses the significance of understanding the semiotics of future cities and recognizing the signs of cultural identity in contributing to the preservation of citizens' memories. The identities of citizens are conveyed through memories in urban planning, and with the rapid advancements in technology, cities are constantly changing. Therefore, preserving memories in the design of future cities is essential in maintaining a quality environment that reflects the citizens' identities. The article focuses on the semiotics of the movement pattern morphology in Mashhad city's historical area, using the historical interpretation method. The practice of walking to the shrine of Imam Reza as a religious building has been a historical and religious custom among Shiites from the past until now. By recognizing the signs that result from this religious and cultural approach on the morphology of the city, the aim of the research is to preserve the place of memories in future cities. Overall, the article highlights the importance of recognizing the cultural and historical significance of cities in designing future urban spaces. By doing so, it is possible to preserve the memories and identities of citizens, ensuring that the urban environment reflects the unique cultural heritage of a place.

Keywords: memories, future cities, movement pattern, mashhad, semiotics

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4296 Lifelong Education for Teachers: A Tool for Achieving Effective Teaching and Learning in Secondary Schools in Benue State, Nigeria

Authors: Adzongo Philomena Ibuh, Aloga O. Austin

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The purpose of the study was to examine lifelong education for teachers as a tool for achieving effective teaching and learning. Lifelong education enhances social inclusion, personal development, citizenship, employability, teaching and learning, community and the nation, and the challenges of lifelong education were also discussed. Descriptive survey design was adopted for the study. A simple random sampling technique was used to select 80 teachers as sample from a population of 105 senior secondary school teachers in Makurdi local government area of Benue state. A 20-item self designed questionnaire subjected to expert validation and reliability was used to collect data. The reliability Alpha coefficient of 0.87 was established using Crombach Alpha technique, mean scores and standard deviation were used to answer the 2 research questions while chi-square was used to analyze data for the 2 hypotheses. The findings of the study revealed that, lifelong education for teachers can be used to achieve as a tool for achieving effective teaching and learning, and the study recommended among others that government, organizations and individuals should in collaboration put lifelong education programmes for teachers on the priority list. The paper concluded that the strategic position of lifelong education for teachers towards enhanced teaching and learning makes it imperative for all hands to be on deck to support the programme financially and otherwise.

Keywords: effective teaching and learning, lifelong education, teachers, tool

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4295 Characteristics of Regional Issues in Local Municipalities of Japan in Consideration of Socio-Economic Condition

Authors: Akiko Kondo, Akio Kondo

Abstract:

We are facing serious problems related to a long-term depopulation and an aging society with a falling birth rate in Japan. In this situation, we are suffering from a shortfall in human resources as well as a shortage of workforce in rural regions. In addition, we are struggling with a protracted economic slump and excess concentration of population in the Tokyo Metropolitan area. It is an urgent national issue to consider how to live in this country and what kind of structure of society and administration policy is needed. It is necessary to clarify people’s desire for their way of living and social assistance to be provided. The aim of this study is to clarify the characteristics of regional issues and the degree of their seriousness in local municipalities of Japan. We conducted a questionnaire survey about regional agenda in all local municipalities in Japan. We obtained responses concerning the degree of seriousness of regional issues and degree of importance of policies. Based on the data gathered from the survey, it is apparent that many local municipalities are facing an aging population and declining population. We constructed a model to analyze factors for declining population. Using the model, it was clarified that a population’s age structure, job opportunities, and income level affect the decline of population. In addition, we showed the way of the evaluation of the state of a local municipality.

Keywords: evaluation, local municipality, regional analysis, regional issue

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4294 Development of a Turbulent Boundary Layer Wall-pressure Fluctuations Power Spectrum Model Using a Stepwise Regression Algorithm

Authors: Zachary Huffman, Joana Rocha

Abstract:

Wall-pressure fluctuations induced by the turbulent boundary layer (TBL) developed over aircraft are a significant source of aircraft cabin noise. Since the power spectral density (PSD) of these pressure fluctuations is directly correlated with the amount of sound radiated into the cabin, the development of accurate empirical models that predict the PSD has been an important ongoing research topic. The sound emitted can be represented from the pressure fluctuations term in the Reynoldsaveraged Navier-Stokes equations (RANS). Therefore, early TBL empirical models (including those from Lowson, Robertson, Chase, and Howe) were primarily derived by simplifying and solving the RANS for pressure fluctuation and adding appropriate scales. Most subsequent models (including Goody, Efimtsov, Laganelli, Smol’yakov, and Rackl and Weston models) were derived by making modifications to these early models or by physical principles. Overall, these models have had varying levels of accuracy, but, in general, they are most accurate under the specific Reynolds and Mach numbers they were developed for, while being less accurate under other flow conditions. Despite this, recent research into the possibility of using alternative methods for deriving the models has been rather limited. More recent studies have demonstrated that an artificial neural network model was more accurate than traditional models and could be applied more generally, but the accuracy of other machine learning techniques has not been explored. In the current study, an original model is derived using a stepwise regression algorithm in the statistical programming language R, and TBL wall-pressure fluctuations PSD data gathered at the Carleton University wind tunnel. The theoretical advantage of a stepwise regression approach is that it will automatically filter out redundant or uncorrelated input variables (through the process of feature selection), and it is computationally faster than machine learning. The main disadvantage is the potential risk of overfitting. The accuracy of the developed model is assessed by comparing it to independently sourced datasets.

Keywords: aircraft noise, machine learning, power spectral density models, regression models, turbulent boundary layer wall-pressure fluctuations

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4293 Mineral Nitrogen Retention, Nitrogen Availability and Plant Growth in the Soil Influenced by Addition of Organic and Mineral Fertilizers: Lysimetric Experiment

Authors: Lukáš Plošek, Jaroslav Hynšt, Jaroslav Záhora, Jakub Elbl, Antonín Kintl, Ivana Charousová, Silvia Kovácsová

Abstract:

Compost can influence soil fertility and plant health. At the same time compost can play an important role in the nitrogen cycle and it can influence leaching of mineral nitrogen from soil to underground water. This paper deals with the influence of compost addition and mineral nitrogen fertilizer on leaching of mineral nitrogen, nitrogen availability in microbial biomass and plant biomass production in the lysimetric experiment. Twenty-one lysimeters were filed with topsoil and subsoil collected in the area of protection zone of underground source of drinking water - Březová nad Svitavou. The highest leaching of mineral nitrogen was detected in the variant fertilized only mineral nitrogen fertilizer (624.58 mg m-2), the lowest leaching was recorded in the variant with high addition of compost (315.51 mg m-2). On the other hand, losses of mineral nitrogen are not in connection with the losses of available form of nitrogen in microbial biomass. Because loss of mineral nitrogen was detected in variant with the least change in the availability of N in microbial biomass. The leaching of mineral nitrogen, yields as well as the results concerning nitrogen availability from the first year of long term experiment suggest that compost can positive influence the leaching of nitrogen into underground water.

Keywords: nitrogen, compost, biomass production, lysimeter

Procedia PDF Downloads 345
4292 Metal-Organic Frameworks-Based Materials for Volatile Organic Compounds Sensing Applications: Strategies to Improve Sensing Performances

Authors: Claudio Clemente, Valentina Gargiulo, Alessio Occhicone, Giovanni Piero Pepe, Giovanni Ausanio, Michela Alfè

Abstract:

Volatile organic compound (VOC) emissions represent a serious risk to human health and the integrity of the ecosystems, especially at high concentrations. For this reason, it is very important to continuously monitor environmental quality and develop fast and reliable portable sensors to allow analysis on site. Chemiresistors have become promising candidates for VOC sensing as their ease of fabrication, variety of suitable sensitive materials, and simple sensing data. A chemoresistive gas sensor is a transducer that allows to measure the concentration of an analyte in the gas phase because the changes in resistance are proportional to the amount of the analyte present. The selection of the sensitive material, which interacts with the target analyte, is very important for the sensor performance. The most used VOC detection materials are metal oxides (MOx) for their rapid recovery, high sensitivity to various gas molecules, easy fabrication. Their sensing performance can be improved in terms of operating temperature, selectivity, and detection limit. Metal-organic frameworks (MOFs) have attracted a lot of attention also in the field of gas sensing due to their high porosity, high surface area, tunable morphologies, structural variety. MOFs are generated by the self-assembly of multidentate organic ligands connecting with adjacent multivalent metal nodes via strong coordination interactions, producing stable and highly ordered crystalline porous materials with well-designed structures. However, most MOFs intrinsically exhibit low electrical conductivity. To improve this property, MOFs can be combined with organic and inorganic materials in a hybrid fashion to produce composite materials or can be transformed into more stable structures. MOFs, indeed, can be employed as the precursors of metal oxides with well-designed architectures via the calcination method. The MOF-derived MOx partially preserved the original structure with high surface area and intrinsic open pores, which act as trapping centers for gas molecules, and showed a higher electrical conductivity. Core-shell heterostructures, in which the surface of a metal oxide core is completely coated by a MOF shell, forming a junction at the core-shell heterointerface, can also be synthesized. Also, nanocomposite in which MOF structures are intercalated with graphene related materials can also be produced, and the conductivity increases thanks to the high mobility of electrons of carbon materials. As MOF structures, zinc-based MOFs belonging to the ZIF family were selected in this work. Several Zn-based materials based and/or derived from MOFs were produced, structurally characterized, and arranged in a chemo resistive architecture, also exploring the potentiality of different approaches of sensing layer deposition based on PLD (pulsed laser deposition) and, in case of thermally labile materials, MAPLE (Matrix Assisted Pulsed Laser Evaporation) to enhance the adhesion to the support. The sensors were tested in a controlled humidity chamber, allowing for the possibility of varying the concentration of ethanol, a typical analyte chosen among the VOCs for a first survey. The effect of heating the chemiresistor to improve sensing performances was also explored. Future research will focus on exploring new manufacturing processes for MOF-based gas sensors with the aim to improve sensitivity, selectivity and reduce operating temperatures.

Keywords: chemiresistors, gas sensors, graphene related materials, laser deposition, MAPLE, metal-organic frameworks, metal oxides, nanocomposites, sensing performance, transduction mechanism, volatile organic compounds

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4291 Enhancing Academic and Social Skills of Elementary School Students with Autism Spectrum Disorder by an Intensive and Comprehensive Teaching Program

Authors: Piyawan Srisuruk, Janya Boonmeeprasert, Romwarin Gamlunglert, Benjamaporn Choikhruea, Ornjira Jaraepram, Jarin Boonsuchat, Sakdadech Singkibud, Kusalaporn Chaiudomsom, Chanatiporn Chonprai, Pornchanaka Tana, Suchat Paholpak

Abstract:

Objective: To develop an Intensive and comprehensive program (ICP) for the Inclusive Class Teacher (ICPICT) to teach elementary students (ES) with ASD in order to enhance the students’ academic and social skills (ASS) and to study the effect of the teaching program. Methods: The purposive sample included 15 Khon Kaen inclusive class teachers and their 15 elementary students. All the students were diagnosed by a child and adolescent psychiatrist to have DSM-5 level 1 ASD. The study tools included 1) an ICP to teach teachers about ASD, a teaching method to enhance academic and social skills for ES with ASD, and an assessment tool to assess the teacher’s knowledge before and after the ICP. 2) an ICPICT to teach ES with ASD to enhance their ASS. The project taught 10 sessions, 3 hours each. The ICPICT had its teaching structure. Teaching media included: pictures, storytelling, songs, and plays. The authors taught and demonstrated to the participant teachers how to teach with the ICPICT until the participants could display the correct teaching method. Then the teachers taught ICPICT at school by themselves 3) an assessment tool to assess the students’ ASS before and after the completion of the study. The ICP to teach the teachers, the ICPICT, and the relevant assessment tools were developed by the authors and were adjusted until consensus agreed as appropriate for researching by 3 curriculum of teaching children with ASD experts. The data were analyzed by descriptive and analytic statistics via SPSS version 26. Results: After the briefing, the teachers increased the mean score, though not with statistical significance, of knowledge of ASD and how to teach ES with ASD on ASS (p = 0.13). Teaching ES with ASD with the ICPICT could increase the mean scores of the students’ skills in learning and expressing social emotions, relationships with a friend, transitioning, and skills in academic function 3.33, 2.27, 2.94, and 3.00 scores (full scores were 18, 12, 15 and 12, Paired T-Test p = 0.007, 0.013, 0.028 and 0.003 respectively). Conclusion: The program to teach academic and social skills simultaneously in an intensive and comprehensive structure could enhance both the academic and social skills of elementary students with ASD. Keywords: Elementary students, autism spectrum, academic skill, social skills, intensive program, comprehensive program, integration.

Keywords: academica and social skills, students with autism, intensive and comprehensive, teaching program

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4290 Effect of Cocoa Pod Ash and Poultry Manure on Soil Properties and Cocoyam Productivity of Nutrient-Depleted Tropical Alfisol

Authors: T. M. Agbede, A. O. Adekiya

Abstract:

An experiment was carried out for three consecutive years at Owo, southwest Nigeria. The objective of the investigation was to determine the effect of Cocoa Pod Ash (CPA) and Poultry Manure (PM) applied solely and their combined form, as sources of fertilizers on soil properties, leaf nutrient composition, growth and yield of cocoyam. Three soil amendments: CPA, PM (sole forms), CPA and PM (mixture), were applied at 7.5 t ha-1 with an inorganic fertilizer (NPK 15-15-15) at 400 kg ha-1 as a reference and a natural soil fertility, NSF (control), arranged in a randomized complete block design with three replications. Results showed that soil amendments significantly increased (p = 0.05) corm and cormel weights and growth of cocoyam, soil and leaf N, P, K, Ca and Mg, soil pH and organic carbon (OC) concentrations compared with the NSF (control). The mixture of CPA+PM treatment increased corm and cormel weights, plant height and leaf area of cocoyam by 40, 39, 42, and 48%, respectively, compared with inorganic fertilizer (NPK) and 13, 12, 15 and 7%, respectively, compared with PM alone. Sole or mixed forms of soil amendments showed remarkable improvement in soil physical properties compared with NPK and the NSF (control). The mixture of CPA+PM applied at 7.5 t ha-1 was the most effective treatment in improving cocoyam yield and growth parameters, soil and leaf nutrient composition.

Keywords: Cocoa pod ash, cocoyam, poultry manure, soil and leaf nutrient composition.

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4289 The Appropriate Number of Test Items That a Classroom-Based Reading Assessment Should Include: A Generalizability Analysis

Authors: Jui-Teng Liao

Abstract:

The selected-response (SR) format has been commonly adopted to assess academic reading in both formal and informal testing (i.e., standardized assessment and classroom assessment) because of its strengths in content validity, construct validity, as well as scoring objectivity and efficiency. When developing a second language (L2) reading test, researchers indicate that the longer the test (e.g., more test items) is, the higher reliability and validity the test is likely to produce. However, previous studies have not provided specific guidelines regarding the optimal length of a test or the most suitable number of test items or reading passages. Additionally, reading tests often include different question types (e.g., factual, vocabulary, inferential) that require varying degrees of reading comprehension and cognitive processes. Therefore, it is important to investigate the impact of question types on the number of items in relation to the score reliability of L2 reading tests. Given the popularity of the SR question format and its impact on assessment results on teaching and learning, it is necessary to investigate the degree to which such a question format can reliably measure learners’ L2 reading comprehension. The present study, therefore, adopted the generalizability (G) theory to investigate the score reliability of the SR format in L2 reading tests focusing on how many test items a reading test should include. Specifically, this study aimed to investigate the interaction between question types and the number of items, providing insights into the appropriate item count for different types of questions. G theory is a comprehensive statistical framework used for estimating the score reliability of tests and validating their results. Data were collected from 108 English as a second language student who completed an English reading test comprising factual, vocabulary, and inferential questions in the SR format. The computer program mGENOVA was utilized to analyze the data using multivariate designs (i.e., scenarios). Based on the results of G theory analyses, the findings indicated that the number of test items had a critical impact on the score reliability of an L2 reading test. Furthermore, the findings revealed that different types of reading questions required varying numbers of test items for reliable assessment of learners’ L2 reading proficiency. Further implications for teaching practice and classroom-based assessments are discussed.

Keywords: second language reading assessment, validity and reliability, Generalizability theory, Academic reading, Question format

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4288 Features of Normative and Pathological Realizations of Sibilant Sounds for Computer-Aided Pronunciation Evaluation in Children

Authors: Zuzanna Miodonska, Michal Krecichwost, Pawel Badura

Abstract:

Sigmatism (lisping) is a speech disorder in which sibilant consonants are mispronounced. The diagnosis of this phenomenon is usually based on the auditory assessment. However, the progress in speech analysis techniques creates a possibility of developing computer-aided sigmatism diagnosis tools. The aim of the study is to statistically verify whether specific acoustic features of sibilant sounds may be related to pronunciation correctness. Such knowledge can be of great importance while implementing classifiers and designing novel tools for automatic sibilants pronunciation evaluation. The study covers analysis of various speech signal measures, including features proposed in the literature for the description of normative sibilants realization. Amplitudes and frequencies of three fricative formants (FF) are extracted based on local spectral maxima of the friction noise. Skewness, kurtosis, four normalized spectral moments (SM) and 13 mel-frequency cepstral coefficients (MFCC) with their 1st and 2nd derivatives (13 Delta and 13 Delta-Delta MFCC) are included in the analysis as well. The resulting feature vector contains 51 measures. The experiments are performed on the speech corpus containing words with selected sibilant sounds (/ʃ, ʒ/) pronounced by 60 preschool children with proper pronunciation or with natural pathologies. In total, 224 /ʃ/ segments and 191 /ʒ/ segments are employed in the study. The Mann-Whitney U test is employed for the analysis of stigmatism and normative pronunciation. Statistically, significant differences are obtained in most of the proposed features in children divided into these two groups at p < 0.05. All spectral moments and fricative formants appear to be distinctive between pathology and proper pronunciation. These metrics describe the friction noise characteristic for sibilants, which makes them particularly promising for the use in sibilants evaluation tools. Correspondences found between phoneme feature values and an expert evaluation of the pronunciation correctness encourage to involve speech analysis tools in diagnosis and therapy of sigmatism. Proposed feature extraction methods could be used in a computer-assisted stigmatism diagnosis or therapy systems.

Keywords: computer-aided pronunciation evaluation, sigmatism diagnosis, speech signal analysis, statistical verification

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4287 Delineation of Oil – Polluted Sites in Ibeno LGA, Nigeria, Using Geophysical Techniques

Authors: Ime R. Udotong, Justina I. R. Udotong, Ofonime U. M. John

Abstract:

Ibeno, Nigeria hosts the operational base of Mobil Producing Nigeria Unlimited (MPNU), a subsidiary of ExxonMobil and the current highest oil and condensate producer in Nigeria. Besides MPNU, other oil companies operate onshore, on the continental shelf and deep offshore of the Atlantic Ocean in Ibeno, Nigeria. This study was designed to delineate oil polluted sites in Ibeno, Nigeria using geophysical methods of electrical resistivity (ER) and ground penetrating radar (GPR). Results obtained revealed that there have been hydrocarbon contaminations of this environment by past crude oil spills as observed from high resistivity values and GPR profiles which clearly show the distribution, thickness and lateral extent of hydrocarbon contamination as represented on the radargram reflector tones. Contaminations were of varying degrees, ranging from slight to high, indicating levels of substantial attenuation of crude oil contamination over time. Moreover, the display of relatively lower resistivities of locations outside the impacted areas compared to resistivity values within the impacted areas and the 3-D Cartesian images of oil contaminant plume depicted by red, light brown and magenta for high, low and very low oil impacted areas, respectively confirmed significant recent pollution of the study area with crude oil.

Keywords: electrical resistivity, geophysical investigations, ground penetrating radar, oil-polluted sites

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4286 The Effect of PM10 Dispersion from Industrial, Residential and Commercial Areas in Arid Environment

Authors: Meshari Al-Harbi

Abstract:

A comparative area-season-elemental-wise time series analysis by Dust Track monitor (2012-2013) revealed high PM10 dispersion in the outdoor environment in the sequence of industrial> express highways>residential>open areas. Time series analysis from 7AM-6AM (until next day), 30d (monthly), 3600sec. (for any given period of a month), and 12 months (yearly) showed peak PM10 dispersion during 1AM-7AM, 1d-4d and 25d-31d of every month, 1500-3600 with the exception in PM10 dispersion in residential areas, and in the months-March to June, respectively. This time-bound PM10 dispersion suggests the primary influence of human activities (peak mobility and productivity period for a given time frame) besides the secondary influence of meteorological parameters (high temperature and wind action) and, occasional dust storms. Whereas, gravimetric analysis reveals the influence of precipitation, low temperature and low volatility resulting high trace metals in PM10 during winter than in summer and primarily attributes to the influence of nature besides, the secondary attributes of smoke stack emission from various industries and automobiles. Furthermore, our study recommends residents to limit outdoor air pollution exposures and take precautionary measures to inhale PM10 pollutants from the atmosphere.

Keywords: aerosol, pollution, respirable particulates, trace-metals

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4285 A Biophysical Model of CRISPR/Cas9 on- and off-Target Binding for Rational Design of Guide RNAs

Authors: Iman Farasat, Howard M. Salis

Abstract:

The CRISPR/Cas9 system has revolutionized genome engineering by enabling site-directed and high-throughput genome editing, genome insertion, and gene knockdowns in several species, including bacteria, yeast, flies, worms, and human cell lines. This technology has the potential to enable human gene therapy to treat genetic diseases and cancer at the molecular level; however, the current CRISPR/Cas9 system suffers from seemingly sporadic off-target genome mutagenesis that prevents its use in gene therapy. A comprehensive mechanistic model that explains how the CRISPR/Cas9 functions would enable the rational design of the guide-RNAs responsible for target site selection while minimizing unexpected genome mutagenesis. Here, we present the first quantitative model of the CRISPR/Cas9 genome mutagenesis system that predicts how guide-RNA sequences (crRNAs) control target site selection and cleavage activity. We used statistical thermodynamics and law of mass action to develop a five-step biophysical model of cas9 cleavage, and examined it in vivo and in vitro. To predict a crRNA's binding specificities and cleavage rates, we then compiled a nearest neighbor (NN) energy model that accounts for all possible base pairings and mismatches between the crRNA and the possible genomic DNA sites. These calculations correctly predicted crRNA specificity across 5518 sites. Our analysis reveals that cas9 activity and specificity are anti-correlated, and, the trade-off between them is the determining factor in performing an RNA-mediated cleavage with minimal off-targets. To find an optimal solution, we first created a scheme of safe-design criteria for Cas9 target selection by systematic analysis of available high throughput measurements. We then used our biophysical model to determine the optimal Cas9 expression levels and timing that maximizes on-target cleavage and minimizes off-target activity. We successfully applied this approach in bacterial and mammalian cell lines to reduce off-target activity to near background mutagenesis level while maintaining high on-target cleavage rate.

Keywords: biophysical model, CRISPR, Cas9, genome editing

Procedia PDF Downloads 399