Search results for: GAF domain protein

Authors: Vaishali Patil, Neeraj Masand

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In older people, Alzheimer’s disease (AD) is turning out to be a lethal disease. According to the amyloid hypothesis, aggregation of the amyloid β–protein (Aβ), particularly its 42-residue variant (Aβ42), plays direct role in the pathogenesis of AD. Aβ is generated through sequential cleavage of amyloid precursor protein (APP) by β–secretase (BACE) and γ–secretase (GS). Thus in the treatment of AD, γ-secretase modulators (GSMs) are potential disease-modifying as they selectively lower pathogenic Aβ42 levels by shifting the enzyme cleavage sites without inhibiting γ–secretase activity. This possibly avoids known adverse effects observed with complete inhibition of the enzyme complex. Virtual screening, via drug-like ADMET filter, QSAR and molecular docking analyses, has been utilized to identify novel γ–secretase modulators with sulphonamide nucleus. Based on QSAR analyses and docking score, some novel analogs have been synthesized. The results obtained by in silico studies have been validated by performing in vivo analysis. In the first step, behavioral assessment has been carried out using Scopolamine induced amnesia methodology. Later the same series has been evaluated for neuroprotective potential against the oxidative stress induced by Scopolamine. Biochemical estimation was performed to evaluate the changes in biochemical markers of Alzheimer’s disease such as lipid peroxidation (LPO), Glutathione reductase (GSH), and Catalase. The Scopolamine induced amnesia model has shown increased Acetylcholinesterase (AChE) levels and the inhibitory effect of test compounds in the brain AChE levels have been evaluated. In all the studies Donapezil (Dose: 50µg/kg) has been used as reference drug. The reduced AChE activity is shown by compounds 3f, 3c, and 3e. In the later stage, the most potent compounds have been evaluated for Aβ42 inhibitory profile. It can be hypothesized that this series of alkyl-aryl sulphonamides exhibit anti-AD activity by inhibition of Acetylcholinesterase (AChE) enzyme as well as inhibition of plaque formation on prolong dosage along with neuroprotection from oxidative stress.

Keywords: gamma-secretase inhibitors, Alzzheimer's disease, sulphonamides, QSAR

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Authors: Matthew F. Gibson, Narasimha D. Rao, Raphael B. Slade, Joana Portugal Pereira, Joeri Rogelj

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Globally, India’s population is among the most severely impacted by nutrient deficiency, yet millions of tonnes of food are lost before reaching consumers. Across food groups, grains represent the largest share of daily calories and overall losses by mass in India. If current losses remain unresolved and follow projected population rates, we estimate, by 2030, losses from grains for human consumption could increase by 1.3-1.8 million tonnes (Mt) per year against current levels of ~10 Mt per year. This study quantifies energy input to minimise storage losses across India, responsible for a quarter of grain supply chain losses. In doing so, we identify and explore a Sustainable Development Goal (SDG) triplet between SDG₂, SDG₇, and SDG₁₂ and provide insight for development of joined up agriculture and health policy in the country. Analyzing rice, wheat, maize, bajra, and sorghum, we quantify one route to reduce losses in supply chains, by modelling the energy input to maintain favorable climatic conditions in modern silo storage. We quantify key nutrients (calories, protein, zinc, iron, vitamin A) contained within these losses and calculate roughly how much deficiency in these dietary components could be reduced if grain losses were eliminated. Our modelling indicates, with appropriate uncertainty, maize has the highest energy input intensity for storage, at 110 kWh per tonne of grain (kWh/t), and wheat the lowest (72 kWh/t). This energy trade-off represents 8%-16% of the energy input required in grain production. We estimate if grain losses across the supply chain were saved and targeted to India’s nutritionally deficient population, average protein deficiency could reduce by 46%, calorie by 27%, zinc by 26%, and iron by 11%. This study offers insight for development of Indian agriculture, food, and health policy by first quantifying and then presenting benefits and trade-offs of tackling food grain losses.

Keywords: energy, food loss, grain storage, hunger, India, sustainable development goal, SDG

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Authors: Mujde Turkkan, Nurkan Yagiz

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The vibrations, caused by the irregularities of the road surface, are to be suppressed via suspension systems. In this paper, sliding mode control for a half bus model with air suspension system is presented. The bus is modelled as five degrees of freedom (DoF) system. The mathematical model of the half bus is developed using Lagrange Equations. For time domain analysis, the bus model is assumed to travel at certain speed over the bump road. The numerical results of the analysis indicate that the sliding mode controllers can be effectively used to suppress the vibrations and to improve the ride comfort of the busses.

Keywords: active suspension system, air suspension, bus model, sliding mode control

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Authors: Mayowa Saheed Sanusi A, Musiliu Olushola Sunmonua, Abdulquadri Alakab Owolabi Raheema, Adeyemi Ikimot Adejokea

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The development of healthy cookies for health-conscious consumers cannot be overemphasized in the present global health crisis. This study was aimed to evaluate and model the influence of ripeness levels of papaya puree (unripe, ripe and overripe), oven temperature (130°C, 150°C and 170°C) and oven rack speed (stationary, 10 and 20 rpm) on physicochemical properties of papaya-based cookies using Response Surface Methodology (RSM). The physicochemical properties (baking time, cookies mass, cookies thickness, spread ratio, proximate composition, Calcium, Vitamin C and Total Phenolic Content) were determined using standard procedures. The data obtained were statistically analysed at p≤0.05 using ANOVA. The polynomial regression model of response surface methodology was used to model the physicochemical properties. The adequacy of the models was determined using the coefficient of determination (R²) and the response optimizer of RSM was used to determine the optimum physicochemical properties for the papaya-based cookies. Cookies produced from overripe papaya puree were observed to have the shortest baking time; ripe papaya puree favors cookies spread ratio, while the unripe papaya puree gives cookies with the highest mass and thickness. The highest crude protein content, fiber content, calcium content, Vitamin C and Total Phenolic Content (TPC) were observed in papaya based-cookies produced from overripe puree. The models for baking time, cookies mass, cookies thickness, spread ratio, moisture content, crude protein and TPC were significant, with R2 ranging from 0.73 – 0.95. The optimum condition for producing papaya based-cookies with desirable physicochemical properties was obtained at 149°C oven temperature, 17 rpm oven rack speed and with the use of overripe papaya puree. The Information on the use of puree from unripe, ripe and overripe papaya can help to increase the use of underutilized unripe or overripe papaya and also serve as a strategic means of obtaining a fat substitute to produce new products with lower production cost and health benefit.

Keywords: papaya based-cookies, modeling, response surface methodology, physicochemical properties

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Authors: Abhishek Bhardwaj, Manish Kumar Bajpai

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An image with its content and schema of colors presents an effective mode of information sharing and processing. By changing its color schema different visions and prospect are discovered by the users. This phenomenon of color transfer is being used by Social media and other channel of entertainment. Reinhard et al’s algorithm was the first one to solve this problem of color transfer. In this paper, we make this algorithm efficient by introducing domain parallelism among different processors. We also comment on the factors that affect the speedup of this problem. In the end by analyzing the experimental data we claim to propose a novel and efficient parallel Reinhard’s algorithm.

Keywords: Reinhard et al’s algorithm, color transferring, parallelism, speedup

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Authors: Sairi Satari

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Introduction: Six-sigma is a metric that quantifies the performance of processes as a rate of Defects-Per-Million Opportunities. Sigma methodology can be applied in chemical pathology laboratory for evaluating process performance with evidence for process improvement in quality assurance program. In the laboratory, these methods have been used to improve the timeliness of troubleshooting, reduce the cost and frequency of quality control and minimize pre and post-analytical errors. Aim: The aim of this study is to evaluate the sigma values of the Cobas 8000 analyzer based on the minimum requirement of the specification. Methodology: Twenty-one analytes were chosen in this study. The analytes were alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), Amylase, aspartate transaminase (AST), total bilirubin, calcium, chloride, cholesterol, HDL-cholesterol, creatinine, creatinine kinase, glucose, lactate dehydrogenase (LDH), magnesium, potassium, protein, sodium, triglyceride, uric acid and urea. Total error was obtained from Clinical Laboratory Improvement Amendments (CLIA). The Bias was calculated from end cycle report of Royal College of Pathologists of Australasia (RCPA) cycle from July to December 2016 and coefficient variation (CV) from six-month internal quality control (IQC). The sigma was calculated based on the formula :Sigma = (Total Error - Bias) / CV. The analytical performance was evaluated based on the sigma, sigma > 6 is world class, sigma > 5 is excellent, sigma > 4 is good and sigma < 4 is satisfactory and sigma < 3 is poor performance. Results: Based on the calculation, we found that, 96% are world class (ALT, albumin, ALP, amylase, AST, total bilirubin, cholesterol, HDL-cholesterol, creatinine, creatinine kinase, glucose, LDH, magnesium, potassium, triglyceride and uric acid. 14% are excellent (calcium, protein and urea), and 10% ( chloride and sodium) require more frequent IQC performed per day. Conclusion: Based on this study, we found that IQC should be performed frequently for only Chloride and Sodium to ensure accurate and reliable analysis for patient management.

Keywords: sigma matrics, analytical performance, total error, bias

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Authors: Ejay Nsugbe, Andrew Starr, Ian Jennions, Cristobal Ruiz-Carcel

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This works investigates the possibility of using Acoustic Emissions (AE) to estimate the Particle Size Distribution (PSD) of a mixture of particles that comprise of particles of different densities and geometry. The experiments carried out involved the mixture of a set of glass and polyethylene particles that ranged from 150-212 microns and 150-250 microns respectively and an experimental rig that allowed the free fall of a continuous stream of particles on a target plate which the AE sensor was placed. By using a time domain based multiple threshold method, it was observed that the PSD of the particles in the mixture could be estimated.

Keywords: acoustic emissions, particle sizing, process monitoring, signal processing

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Authors: Maryam Amiri Resketi, Sakineh Yeganeh, Khosro Jani Khalili

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The aim of this study was to investigate the effect of dietary lemon peel essential oil (Citrus limon) on serum parameters and liver enzyme activity of rainbow trout (Oncorhynchus mykiss) was exposed to deltamethrin. The 96-hour lethal concentrations of the toxin on rainbow trout (Oncorhynchus mykiss), was determined according to standard procedures O.E.C.D in static (Static). 96-hour LC50 was obtained 0.0082 mg/l by using statistical methods Probit program version. The maximum allowable concentration of deltamethrin was calculated 0.00082 mg/l in natural environment and was used for this experiment. Eight treatments were designed based on 3 levels of lemon essential oil 200, 400 and 600 mg/kg and 2 levels of deltamethrin 0 and 0.00082. Rainbow trout with an average weight of 95.14 ± 3.8 g were distributed in 300-liter tanks and cultured for eight weeks. Fish were fed in an amount of 2% of body weight. Water changes were done on a daily basis (90 percent of the tank). About the tanks containing 10 % deltamethrin, after dewatering, suitable concentration of toxin was added to water. At the end of the test, serum biochemical parameters (total protein, albumin, glucose, cholesterol, and triglycerides) and liver enzymes (ALP, AST, ALT and LDH) were evaluated. In treatments without and with toxin, increasing 400 mg/kg oil increased total protein and albumin levels and lower cholesterol and triglycerides were observed (p < 0.05). Rise to the level of 400 mg/kg of lemon peel essential oil treatments contain pesticides, reduced the amount of enzymes ALP, ALT and LDH compared to treatment of toxin-free lemon peel essential oil (p < 0.05). The results showed that usage of lemon peel essential oil in fish diet can increase the immune system parameters and strengthen it with strong antioxidant activity followed by reducing the effect of deltamethrin on the immune system of fish and effective dose can prevent the adverse effects of toxin due to the weakening of the fish immune system at the time of toxic pollutant entrance in fish farms.

Keywords: deltamethrin, Oncorhynchus mykiss, LC5096h, lemon peel (citrus limon) essential oil, serum parameters, liver enzymes

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Authors: Nizar Chaira

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Dates, main products of the oases, due to their therapeutic interests, are considered highly nutritious fruit. Several studies on the valuation biotechnology and technology of dates are made, and several products are already prepared. Isolation of the yeast Saccharomyces cerevisiae, naturally presents in a scrap of date, optimization of growth in the medium based on date syrup and production biomass can potentially expand the range of secondary products of dates. To this end, this paper tries to study the suitability for processing dates technology and biotechnology to use the date pulp as a carbon source for biological transformation. Two strains of Saccharomyces cerevisiae isolated from date syrup (S1, S2) and a commercial strain have used for this study. After optimization of culture conditions, production in a fermenter on two different media (date syrup and beet molasses) was performed. This is followed by studying the kinetics of growth, protein production and consumption of sugars in crops strain 1, 2 and the commercial strain and on both media. The results obtained showed that a concentration of 2% sugar, 2.5 g/l yeast extract, pH 4.5 and a temperature between 25 and 35°C are the optimal conditions for cultivation in a bioreactor. The exponential phase of the specific growth rate of a strain on both media showed that it is about 0.3625 h-1 for the production of a medium based on date syrup and 0.3521 h-1 on beet molasses with a generation time equal to 1.912 h and on the medium based on date syrup, yeast consumes preferentially the reducing sugars. For the production of protein, we showed that this latter presents an exponential phase when the medium starts to run out of reducing sugars. For strain 2, the specific growth rate is about 0.261h-1 for the production on a medium based on date syrup and 0207 h-1 on beet molasses and the base medium syrup date of the yeast consumes preferentially reducing sugars. For the invertase and other metabolits, these increases rapidly after exhaustion of reducing sugars. The comparison of productivity between the three strains on the medium based on date syrup showed that the maximum value is obtained with the second strain: p = 1072 g/l/h as it is about of 0923 g/l/h for strain 1 and 0644 g/l/h for the commercial strain. Thus, isolates of date syrup are more competitive than the commercial strain and can give the same performance in a shorter time with energy gain.

Keywords: date palm, fermentation, molasses, Saccharomyces, syrup

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Authors: B. Moueddene, B. Labbaci, L. Missoum, R. Abdeldjebar

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Quality estimation of the experimental simulation of boundary conditions is one of the problems encountered while performing an experimental program. In fact, it is not easy to estimate directly the effective influence of these simulations on the results of experimental investigation. The aim of this is article to evaluate the effect of boundary conditions uncertainties on structure response, using the change of the dynamics characteristics. The experimental models used and the correlation by the Frequency Domain Assurance Criterion (FDAC) allowed an interpretation of the change in the dynamic characteristics. The application of this strategy to stratified composite structures (glass/ polyester) has given satisfactory results.

Keywords: vibration, composite, endommagement, correlation

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Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi

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There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.

Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development

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Authors: Danutė Jablonskytė-Raščė, Vidas Damanauskas

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The wheat (Triticum) genus is divided into many species, of which only two are widely distributed in the world - common wheat (Triticum aestivum L.) and durum wheat (Triticum durum Desf.). Common (soft) wheat is the most common type of wheat in the world and the most suitable for the harsh climate of Lithuania, but the grains have lower protein content and poorer nutritional properties. Durum wheat is characterized by a high protein content of the grain, but it is a crop of warmer climates grown in southern countries, Italy, Spain, the United States, Egypt, etc. Today's important issue is food, its resources and quality. The research focuses on healthier food grown in our conditions, the quality of which recently depends a lot not only on the cultivation technology but also on the warming climate conditions. Climatic conditions change the distribution of fungi and their hosts. Plants that have grown in our climate for many years have adapted to the use of fungicides, so the aim is to study cereal varieties grown in warmer climates and compare them with our country's varieties, studying their nutritional value and the spread of fungal diseases. The field experiments of different varieties of wheat were conducted at Joniškėlis Experimental Station of the Lithuanian Research Centre for Agriculture and Forestry in 2023. The soil of the experimental site was Endocalcari-Endohypogleyic Cambisol (CMg-n-w-can). The research was designed to identify the resistance to leaf diseases and the nutritional value of various wheat varieties. This research aims to focus on healthier food grown in our conditions, the quality of which recently depends a lot not only on the cultivation technology but also on the conditions of the warming climate. The study found that hot and humid summer weather led to the spread of foliar diseases in wheat. Tan spot (Pyrenophora tritici-repentis) is mostly spread in wheat crops. This disease had an average prevalence of 86.90%. The wheat crop was sparse, so this year was unfavorable for the spread of powdery mildew (Blumeria graminis). Dry weather prevailed during the period of flowering of cereals, which prevented the spread of ear diseases. Examining the qualitative indicators of grain, it was found that durum wheat had the best parameters.

Keywords: varieties, wheat, leaf disease, grain quality

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Authors: Richard McGregor, Carmen Reaiche, Stephen Boyle

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Cyber threats are a relatively recent phenomenon and offer cyber insurers a dynamic and intelligent peril. As individuals en mass become increasingly digitally dependent, Personal Cyber Insurance (PCI) offers an attractive option to mitigate cyber risk at a personal level. This abstract proposes a literature review that conceptualises a framework for siting Personal Cyber Insurance (PCI) within the context of cyberspace. The lack of empirical research within this domain demonstrates an immediate need to define the scope of PCI to allow cyber insurers to understand personal cyber risk threats and vectors, customer awareness, capabilities, and their associated needs. Additionally, this will allow cyber insurers to conceptualise appropriate frameworks allowing effective management and distribution of PCI products and services within a landscape often in-congruent with risk attributes commonly associated with traditional personal line insurance products. Cyberspace has provided significant improvement to the quality of social connectivity and productivity during past decades and allowed enormous capability uplift of information sharing and communication between people and communities. Conversely, personal digital dependency furnish ample opportunities for adverse cyber events such as data breaches and cyber-attacksthus introducing a continuous and insidious threat of omnipresent cyber risk–particularly since the advent of the COVID-19 pandemic and wide-spread adoption of ‘work-from-home’ practices. Recognition of escalating inter-dependencies, vulnerabilities and inadequate personal cyber behaviours have prompted efforts by businesses and individuals alike to investigate strategies and tactics to mitigate cyber risk – of which cyber insurance is a viable, cost-effective option. It is argued that, ceteris parabus, the nature of cyberspace intrinsically provides characteristic peculiarities that pose significant and bespoke challenges to cyber insurers, often in-congruent with risk attributes commonly associated with traditional personal line insurance products. These challenges include (inter alia) a paucity of historical claim/loss data for underwriting and pricing purposes, interdependencies of cyber architecture promoting high correlation of cyber risk, difficulties in evaluating cyber risk, intangibility of risk assets (such as data, reputation), lack of standardisation across the industry, high and undetermined tail risks, and moral hazard among others. This study proposes a thematic overview of the literature deemed necessary to conceptualise the challenges to issuing personal cyber coverage. There is an evident absence of empirical research appertaining to PCI and the design of operational business models for this business domain, especially qualitative initiatives that (1) attempt to define the scope of the peril, (2) secure an understanding of the needs of both cyber insurer and customer, and (3) to identify elements pivotal to effective management and profitable distribution of PCI - leading to an argument proposed by the author that postulates that the traditional general insurance customer journey and business model are ill-suited for the lineaments of cyberspace. The findings of the review confirm significant gaps in contemporary research within the domain of personal cyber insurance.

Keywords: cyberspace, personal cyber risk, personal cyber insurance, customer journey, business model

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Authors: Angélique Laurent, Marie-Josée Letarte, Jean-Pascal Lemelin, Marie-France Morin

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This study aims at exploring teacher-child interactions within learning contexts in public prekindergartens of the province of Québec (Canada). It is based on previous research showing that teacher-child interactions in preschools have direct and determining effects on the quality of early childhood education and could directly or indirectly influence child development. However, throughout a typical preschool day, children experience different learning contexts to promote their learning opportunities. Depending on these specific contexts, teacher-child interactions could vary, for example, between free play and shared book reading. Indeed, some studies have found that teacher-directed or child-directed contexts might lead to significant variations in teacher-child interactions. This study drew upon both the bioecological and the Teaching Through Interactions frameworks. It was conducted through a descriptive and correlational design. Fifteen teachers were recruited to participate in the study. At Time 1 in October, they completed a diary to report the learning contexts they proposed in their classroom during a typical week. At Time 2, seven months later (May), they were videotaped three times in the morning (two weeks’ time between each recording) during a typical morning class. The quality of teacher-child interactions was then coded with the Classroom Assessment Scoring System (CLASS) through the contexts identified. This tool measures three main domains of interactions: emotional support, classroom organization, and instruction support, and10 dimensions scored on a scale from 1 (low quality) to 7 (high quality). Based on the teachers’ reports, five learning contexts were identified: 1) shared book reading, 2) free play, 3) morning meeting, 4) teacher-directed activity (such as craft), and 5) snack. Based on preliminary statistical analyses, little variation was observed within the learning contexts for each domain of the CLASS. However, the instructional support domain showed lower scores during specific learning contexts, specifically free play and teacher-directed activity. Practical implications for how preschool teachers could foster specific domains of interactions depending on learning contexts to enhance children’s social and academic development will be discussed.

Keywords: teacher practices, teacher-child interactions, preschool education, learning contexts, child development

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Authors: Salina Yahya Saddick

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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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Authors: Djamila Benhaddouche, Abdelkader Benyettou

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In this paper, we used data mining to extract biomedical knowledge. In general, complex biomedical data collected in studies of populations are treated by statistical methods, although they are robust, they are not sufficient in themselves to harness the potential wealth of data. For that you used in step two learning algorithms: the Decision Trees and Support Vector Machine (SVM). These supervised classification methods are used to make the diagnosis of thyroid disease. In this context, we propose to promote the study and use of symbolic data mining techniques.

Keywords: biomedical data, learning, classifier, algorithms decision tree, knowledge extraction

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Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

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Authors: Diego Liberati

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Standard molecular modeling is traditionally done through Schroedinger equations via the help of powerful tools helping to manage them atom by atom, often needing High Performance Computing. Here, a full portfolio of new tools, conjugating statistical inference in the so called eXplainable Artificial Intelligence framework (in the form of Machine Learning of understandable rules) to the more traditional modeling and simulation control theory of mixed dynamic logic hybrid processes, is offered as quite a general purpose even if making an example to a popular chemical physics set of problems.

Keywords: understandable rules ML, k-means, PCA, PieceWise Affine Auto Regression with eXogenous input

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Authors: Urom Scholastica Mgbo, Ifeanyichukwu, Vivian, Anaba, Uchemadu Martins, Arusiaba, Nelson Chijioke

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The study was investigated to determine the growth performance , haematological and serum biochemistry of broiler fed graded levels of cocoyam (Xanthosoma sagittifolium). One hundred and twenty (120) day old broiler chicks of Anak strain were used for the study. The birds were randomly divided into 4 treatment groups of 30 birds per group, and each group was further divided into 3 replicates of 10 birds per replicate in group. Cooked cocoyam was used to formulate diets at inclusion levels of 0.00% for T1 (control), while T2, T3 and T4 contained 10.00%, 20.00% and 30.00% inclusion of cocoyam in partial replacement of maize in a Completely Randomized Design (CRD). At the end of the research, the haematological indices of broiler showed that packed cell volume (PCV) of birds fed diets 1(42.26%) and 3 (42.42%) were significantly (p<0.05) higher than birds fed diets 2 (39.72%) and 4 (38.78%).The Haemoglobin (Hb) of birds fed diets 3 (12.58g/dl) and 4 (12.26g/dl) were significantly (p<0.05) higher than birds fed diets 1 (11.60g/dl) and 2 (11.42g/dl). The values of the white blood cell (WBC) of the broiler chickens placed on cocoyam diet increased significantly (P<0.05) compared with the values obtained in the control (T1) . The serum protein value for birds fed diet I (5.45g/dl) were statistically (P>0.05) similar to those fed diets 2 (5.10g/dl) and 3 (5.38g/dl) but differ significantly (P<0.05) from diet 4 (4.97g/dl) which had the least protein value. Final weight of the birds showed that diet 4 (2370.85g) had the highest (P<0.05) value which was followed closely by diet 3 (2225.55g), while birds fed diets 1 (2165.70g) and diet 2 (2145.00g) recorded the least values Similar pattern was observed in the weight gain of the birds. Birds fed diet 4 (2270.30g) had higher (P<0.05) value, followed by birds on diet 3 (2125.45g), while birds fed diet 1 (2065.15g) and 2 (2044.90g) had the least values.. This study showed that birds fed diet 3 (50.60g) and diet 4 (54.05g) gave significantly (P<0.05) higher weight than the control diet (49.17g). There was significant (P<0.05) difference among the treatments for feed conversion ratio (FCR), were birds fed diet 4 (1.74) performed better, having the least feed conversion ratio. Economics of broiler chickens showed that Cost/kg of feed favored diet 4 (₦158.65) followed by diets 3 (₦165.95), 2 (₦178.52) and control diet 1 (₦197.14). From the result, the higher weight recorded in T4 4 showed that cocoyam meal can successfully replace maize up to 30% in the diet of broiler chickens. The low cost recorded in cocoyam based diets showed that the diets were more economical and beneficial compared to control diet 1. Therefore, feeding diet 4 (30%) cocoyam meal as replacement of maize in broiler chickens is recommended.

Keywords: cocoyam, growth, heamatology, serum biochemistry

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Authors: Ogechi Nzeagwu, Assumpta Osuagwu, Charlse Nkwoala

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Malnutrition in infants due to poverty, poor feeding practices, and high cost of commercial complementary foods among others is a concern in developing countries. The study evaluated the proximate, vitamin and mineral compositions, antinutrients and functional properties, biochemical, haematological and sensory evaluation of complementary food made from sorghum, groundnut, crayfish and paw-paw flour blends using standard procedures. The blends were formulated on protein requirement of infants (18 g/day) using Nutrisurvey linear programming software in ratio of sorghum(S), groundnut(G), crayfish(C) and pawpaw(P) flours as 50:25:10:15(SGCP1), 60:20:10:10 (SGCP2), 60:15:15:10 (SGCP3) and 60:10:20:10 (SGCP4). Plain-pap (fermented maize flour)(TCF) and cerelac (commercial complementary food) served as basal and control diets. Thirty weanling male albino rats aged 28-35 days weighing 33-60 g were purchased and used for the study. The rats after acclimatization were fed with gruel produced with the experimental diets and the control with water ad libitum daily for 35days. Effect of the blends on lipid profile, blood glucose, haematological (RBC, HB, PCV, MCV), liver and kidney function and weight gain of the rats were assessed. Acceptability of the gruel was conducted at the end of rat feeding on forty mothers of infants’ ≥ 6 months who gave their informed consent to participate using a 9 point hedonic scale. Data was analyzed for means and standard deviation, analysis of variance and means were separated using Duncan multiple range test and significance judged at 0.05, all using SPSS version 22.0. The results indicated that crude protein, fibre, ash and carbohydrate of the formulated diets were either comparable or higher than values in cerelac. The formulated diets (SGCP1- SGCP4) were significantly (P>0.05) higher in vitamin A and thiamin compared to cerelac. The iron content of the formulated diets SGCP1- SGCP4 (4.23-6.36 mg/100) were within the recommended iron intake of infants (0.55 mg/day). Phytate (1.56-2.55 mg/100g) and oxalate (0.23-0.35 mg/100g) contents of the formulated diets were within the permissible limits of 0-5%. In functional properties, bulk density, swelling index, % dispersibility and water absorption capacity significantly (P<0.05) increased and compared favourably with cerelac. The essential amino acids of the formulated blends were within the amino acid profile of the FAO/WHO/UNU reference protein for children 0.5 -2 years of age. Urea concentration of rats fed with SGCP1-SGCP4 (19.48 mmol/L),(23.76 mmol/L),(24.07 mmol/L),(23.65 mmol/L) respectively was significantly higher than that of rat fed cerelac (16.98 mmol/L); however, plain pap had the least value (9.15 mmol/L). Rats fed with SGCP1-SGCP4 (116 mg/dl), (119 mg/dl), (115 mg/dl), (117 mg/dl) respectively had significantly higher glucose levels those fed with cerelac (108 mg/dl). Liver function parameters (AST, ALP and ALT), lipid profile (triglyceride, HDL, LDL, VLDL) and hematological parameters of rats fed with formulated diets were within normal range. Rats fed SGCP1 gained more weight (90.45 g) than other rats fed with SGCP2-SGCP4 (71.65 g, 79.76 g, 75.68 g), TCF (20.13 g) and cerelac (59.06 g). In all the sensory attributes, the control was preferred with respect to the formulated diets. The formulated diets were generally adequate and may likely have potentials to meet nutrient requirements of infants as complementary food.

Keywords: biochemical, chemical evaluation, complementary food, quadrimix

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Authors: A. K. Faizah, G. Vadamalai, S. K. Balasundram, W. L. Lim

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Pineapple (Ananas comosus) is a common crop in tropical and subtropical areas of the world. Malaysia once ranked as one of the top 3 pineapple producers in the world in the 60's and early 70's, after Hawaii and Brazil. Moreover, government’s recognition of the pineapple crop as one of priority commodities to be developed for the domestics and international markets in the National Agriculture Policy. However, pineapple industry in Malaysia still faces numerous challenges, one of which is the management of disease and pest. Red tip disease on pineapple was first recognized about 20 years ago in a commercial pineapple stand located in Simpang Renggam, Johor, Peninsular Malaysia. Since its discovery, there has been no confirmation on its causal agent of this disease. The epidemiology of red tip disease is still not fully understood. Nevertheless, the disease symptoms and the spread within the field seem to point toward viral infection. Bioassay test on nucleic acid extracted from the red tip-affected pineapple was done on Nicotiana tabacum cv. Coker by rubbing the extracted sap. Localised lesions were observed 3 weeks after inoculation. Negative staining of the fresh inoculated Nicotiana tabacum cv. Coker showed the presence of membrane-bound spherical particles with an average diameter of 94.25nm under transmission electron microscope. The shape and size of the particles were similar to tospovirus. SDS-PAGE analysis of partial purified virions from inoculated N. tabacum produced a strong and a faint protein bands with molecular mass of approximately 29 kDa and 55 kDa. Partial purified virions of symptomatic pineapple leaves from field showed bands with molecular mass of approximately 29 kDa, 39 kDa and 55kDa. These bands may indicate the nucleocapsid protein identity of tospovirus. Furthermore, a handheld sensor, Greenseeker, was used to detect red tip symptoms on pineapple non-destructively based on spectral reflectance, measured as Normalized Difference Vegetation Index (NDVI). Red tip severity was estimated and correlated with NDVI. Linear regression models were calibrated and tested developed in order to estimate red tip disease severity based on NDVI. Results showed a strong positive relationship between red tip disease severity and NDVI (r= 0.84).

Keywords: pineapple, diagnosis, virus, NDVI

Procedia PDF Downloads 791

Authors: Dugeree Otgongerel, Kyong Jin Cho, Yu-Han Kim, Sangmee Ahn Jo

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Excessive activation of glutamate receptor is thought to be involved in retinal ganglion cell (RGC) death after ischemia- reperfusion damage. Glutamate carboxypeptidase II (GCPII) is an enzyme responsible for the synthesis of glutamate. Several studies showed that inhibition of GCPII prevents or reduces cellular damage in brain diseases. Thus, in this study, we examined the expression of GCPII in rat retina and the role of GCPII in acute high IOP ischemia-reperfusion damage of eye by using a GCPII inhibitor, 2-(phosphonomethyl) pentanedioic acid (2-PMPA). Animal model of ischemia-reperfusion was induced by raising the intraocular pressure for 60 min and followed by reperfusion for 3 days. Rats were randomly divided into four groups: either intra-vitreous injection of 2-PMPA (11 or 110 ng per eye) or PBS after ischemia-reperfusion, 2-PMPA treatment without ischemia-reperfusion and sham-operated normal control. GCPII immunoreactivity in normal rat retina was detected weakly in retinal nerve fiber layer (RNFL) and retinal ganglionic cell layer (RGL) and also inner plexiform layer (IPL) and outer plexiform layer (OPL) strongly where are co-stained with an anti-GFAP antibody, suggesting that GCPII is expressed mostly in Muller and astrocytes. Immunostaining with anti-BRN antibody showed that ischemia- reperfusion caused RGC death (31.5 %) and decreased retinal thickness in all layers of damaged retina, but the treatment of 2-PMPA twice at 0 and 48 hour after reperfusion blocked these retinal damages. GCPII level in RNFL layer was enhanced after ischemia-reperfusion but was blocked by PMPA treatment. This result was confirmed by western blot analysis showing that the level of GCPII protein after ischemia- reperfusion increased by 2.2- fold compared to control, but this increase was blocked almost completely by 110 ng PMPA treatment. Interestingly, GFAP immunoreactivity in the retina after ischemia- reperfusion followed by treatment with PMPA showed similar pattern to GCPII, increase after ischemia-reperfusion but reduction to the normal level by PMPA treatment. Our data demonstrate that increase of GCPII protein level after ischemia-reperfusion injury is likely to cause glial activation and/or retinal cell death which are mediated by glutamate, and GCPII inhibitors may be useful in treatment of retinal disorders in which glutamate excitotoxicity is pathogenic.

Keywords: glutamate carboxypepptidase II, glutamate excitotoxicity, ischemia-reperfusion, retinal ganglion cell

Procedia PDF Downloads 340

Authors: M. Abouelatta, A. Shaker, M. El-Banna, G. T. Sayah, C. Gontrand, A. Zekry

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In this paper, a methodology for physically modeling the intrinsic MOS part and the drift region of the n-channel Laterally Double-diffused MOSFET (LDMOS) is presented. The basic physical effects like velocity saturation, mobility reduction, and nonuniform impurity concentration in the channel are taken into consideration. The analytical model is implemented using MATLAB. A comparison of the simulations from technology computer aided design (TCAD) and that from the proposed analytical model, at room temperature, shows a satisfactory accuracy which is less than 5% for the whole voltage domain.

Keywords: LDMOS, MATLAB, RESURF, modeling, TCAD

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Authors: Vinay Singh, Chandra Deo, Asit Chakrabarti, Lopamudra Sahoo, Mahak Singh, Rakesh Kumar, Dinesh Kumar, H. Bharati, Biswajit Das, V. K. Mishra

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The most widely used feed resources in poultry feed, like maize and soybean, are expensive as well as in short supply. Hence, there is a need to utilize non-conventional feed ingredients to cut down feed costs. As an alternative, brewery by-products like brewers’ dried grains are potential non-conventional feed resources. North-East India is inhabited by many tribes, and most of these tribes prepare their indigenous local brew, mostly using rice grains as the primary substrate. Choak, a homemade rice beer waste, is an excellent and cheap source of protein and other nutrients. Fresh homemade rice beer waste (rice brewer’s grain) was collected locally. The proximate analysis indicated 28.53% crude protein, 92.76% dry matter, 5.02% ether extract, 7.83% crude fibre, 2.85% total ash, 0.67% acid insoluble ash, 0.91% calcium, and 0.55% total phosphorus. A feeding trial with 5 treatments (incorporating rice beer waste at the inclusion levels of 0,10,20,30 & 40% by replacing maize and soybean from basal diet) was conducted with 25 laying hens per treatment for 16 weeks under completely randomized design in order to study the production performance, blood-biochemical parameters, immunity, egg quality and cost economics of laying hens. The results showed substantial variations (P<0.01) in egg production, egg mass, FCR per dozen eggs, FCR per kg egg mass, and net FCR. However, there was not a substantial difference in either body weight or feed intake or in egg weight. Total serum cholesterol reduced significantly (P<0.01) at 40% inclusion of rice beer waste. Additionally, the egg haugh unit grew considerably (P<0.01) when the graded levels of rice beer waste increased. The inclusion of 20% rice brewers dried grain reduced feed cost per kg egg mass and per dozen egg production by Rs. 15.97 and 9.99, respectively. Choak (homemade rice beer waste) can thus be safely incorporated into the diet of laying hens at a 20% inclusion level for better production performance and cost-effectiveness.

Keywords: choak, rice beer waste, laying hen, production performance, cost economics

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Authors: Anindita Patra, Prasad K. Bhaskaran

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The atmosphere-ocean is a dynamically linked system that influences the exchange of energy, mass, and gas at the air-sea interface. The exchange of energy takes place in the form of sensible heat, latent heat, and momentum commonly referred to as fluxes along the atmosphere-ocean boundary. The large scale features such as El Nino and Southern Oscillation (ENSO) is a classic example on the interaction mechanism that occurs along the air-sea interface that deals with the inter-annual variability of the Earth’s Climate System. Most importantly the ocean and atmosphere as a coupled system acts in tandem thereby maintaining the energy balance of the climate system, a manifestation of the coupled air-sea interaction process. The present work is an attempt to understand the long-term variability in atmospheric parameters (from surface to upper levels) and investigate their role in influencing the surface ocean variables. More specifically the influence of atmospheric circulation and its variability influencing the mean Sea Level Pressure (SLP) has been explored. The study reports on a critical examination of both ocean-atmosphere parameters during a monsoon season over the head Bay of Bengal region. A trend analysis has been carried out for several atmospheric parameters such as the air temperature, geo-potential height, and omega (vertical velocity) for different vertical levels in the atmosphere (from surface to the troposphere) covering a period from 1992 to 2012. The Reanalysis 2 dataset from the National Centers for Environmental Prediction-Department of Energy (NCEP-DOE) was used in this study. The study signifies that the variability in air temperature and omega corroborates with the variation noticed in geo-potential height. Further, the study advocates that for the lower atmosphere the geo-potential heights depict a typical east-west contrast exhibiting a zonal dipole behavior over the study domain. In addition, the study clearly brings to light that the variations over different levels in the atmosphere plays a pivotal role in supporting the observed dipole pattern as clearly evidenced from the trends in SLP, associated surface wind speed and significant wave height over the study domain.

Keywords: air temperature, geopotential height, head Bay of Bengal, long-term variability, NCEP reanalysis 2, omega, wind-waves

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Authors: Habtamu Ayenew Asegie

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Wealth, as opposed to income or consumption, implies a more stable and permanent status. Due to natural and human-made difficulties, households' economies will be diminished, and their well-being will fall into trouble. Hence, governments and humanitarian agencies offer considerable resources for poverty and malnutrition reduction efforts. One key factor in the effectiveness of such efforts is the accuracy with which low-income or poor populations can be identified. As a result, this study aims to predict a household’s wealth status using ensemble Machine learning (ML) algorithms. In this study, design science research methodology (DSRM) is employed, and four ML algorithms, Random Forest (RF), Adaptive Boosting (AdaBoost), Light Gradient Boosted Machine (LightGBM), and Extreme Gradient Boosting (XGBoost), have been used to train models. The Ethiopian Demographic and Health Survey (EDHS) dataset is accessed for this purpose from the Central Statistical Agency (CSA)'s database. Various data pre-processing techniques were employed, and the model training has been conducted using the scikit learn Python library functions. Model evaluation is executed using various metrics like Accuracy, Precision, Recall, F1-score, area under curve-the receiver operating characteristics (AUC-ROC), and subjective evaluations of domain experts. An optimal subset of hyper-parameters for the algorithms was selected through the grid search function for the best prediction. The RF model has performed better than the rest of the algorithms by achieving an accuracy of 96.06% and is better suited as a solution model for our purpose. Following RF, LightGBM, XGBoost, and AdaBoost algorithms have an accuracy of 91.53%, 88.44%, and 58.55%, respectively. The findings suggest that some of the features like ‘Age of household head’, ‘Total children ever born’ in a family, ‘Main roof material’ of their house, ‘Region’ they lived in, whether a household uses ‘Electricity’ or not, and ‘Type of toilet facility’ of a household are determinant factors to be a focal point for economic policymakers. The determinant risk factors, extracted rules, and designed artifact achieved 82.28% of the domain expert’s evaluation. Overall, the study shows ML techniques are effective in predicting the wealth status of households.

Keywords: ensemble machine learning, households wealth status, predictive model, wealth status prediction

Procedia PDF Downloads 39

Authors: Rodriguez Diego, Del Valle Martin, Hargreaves Matias, Riveros Jose Luis

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Nutrient deficiencies due to a diet low in quantitative and qualitative terms, are prevalent throughout the developing world, especially in sub-Saharan Africa. Children and women of childbearing age are especially vulnerable. Limited availability, access and intake of animal foods at home and lack of knowledge about their value in the diet and the role they play in health, contribute to poor diet quality. Poor bioavailability of micronutrients in diets based on foods high in fiber and phytates, the low content of some micronutrients in these foods are further factors to consider. Goats are deeply embedded in almost every Sub-Saharan African rural culture, generally kept for their milk, meat, hair or leather. Goats have played an important role in African social life, especially in food security. Goat meat has good properties for human wellbeing, with a special role in lower income households. It has a high-quality protein (20 protein g/100 meat g) including all essential amino acids, good unsaturated/satured fatty acids relationship, and it is an important B-vitamin source with high micronutrients bioavailability. Mozambique has major food security problems, with poor food access and utilization, undiversified diets, chronic poverty and child malnutrition. Our objective was to design a nutritional intervention based on a dietary diversification, nutritional education, cultural beliefs and local resources, aimed to strengthen food security of children at Barrio Broma village (15°43'58.78"S; 32°46'7.27"E) in Chitima, Mozambique. Two surveys were conducted first of socio-productive local databases and then to 100 rural households about livelihoods, food diversity and anthropometric measurements in children under 5 years. Our results indicate that the main economic activity is goat production, based on a native breed with two deliveries per year in the absence of any management. Adult goats weighted 27.2±10.5 kg and raised a height of 63.5±3.8 cm. Data showed high levels of poverty, with a food diversity score of 2.3 (0-12 points), where only 30% of households consume protein and 13% iron, zinc, and B12 vitamin. The main constraints to food security were poor access to water and low income to buy food. Our dietary intervention was based on improving diet quality by increasing the access to dried goat meat, fresh vegetables, and legumes, and its utilization by a nutritional education program. This proposal was based on local culture and living conditions characterized by the absence of electricity power and drinkable water. The drying process proposed would secure the food maintenance under local conditions guaranteeing food safety for a longer period. Additionally, an ancient local drying technique was rescued and used. Moreover, this kind of dietary intervention would be the most efficient way to improve the infant nutrition by delivering macro and micronutrients on time to these vulnerable populations.

Keywords: child malnutrition, dietary diversification, food security, goat meat

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Authors: Mohammad Alhajeri

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This paper reports a computational fluid dynamics (CFD) investigation of cylindrical filter. Silicon carbide cylindrical filter elements have proven to be an effective mean of removing particulates to levels exceeding the new source performance standard. The CFD code is used here to understand the deposition process and the factors that affect the particles distribution over the filter element surface. Different approach cross flow velocity to filter face velocity ratios and different face velocities (ranging from 2 to 5 cm/s) are used in this study. Particles in the diameter range 1 to 100 microns are tracked through the domain. The radius of convergence (or the critical trajectory) is compared and plotted as a function of many parameters.

Keywords: filtration, CFD, CCF, hot gas filtration

Procedia PDF Downloads 462

Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

Procedia PDF Downloads 159

Authors: Virve Pääkkönen, Heidi M. Cuffaro, Leo Tjäderhane

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Objectives: Odontoblasts are the outermost cell layer of dental pulp and form the dentin. Importance of bacterial products, e.g. lipoteichoic acid (LTA), a cell wall component of Gram-positive bacteria and lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, have been indicated in the pathogenesis of pulpitis. Gram-positive bacteria are more prevalent in superficial carious lesion while the amount gram-negative is higher in the deep lesions. Objective of this study was to investigate the effect of these bacterial products on inflammatory response of pulp tissue. Interleukins (IL) were of special interest. Various ILs have been observed in the dentin-pulp complex of carious tooth in vivo. Methods: Tissue culture method was used for testing the effect of LTA and LPS on human odontoblasts. Enzymatic isolation technique was used to extract living odontoblasts for cell cultures. DNA microarray and quantitative PCR (qPCR) were used to characterize the changes in the expression profile of the tissue cultured odontoblasts. Laser microdissection was used to cut healthy and affected dentin and odontoblast layer directly under carious lesion for experiments. Cytokine array detecting 80 inflammatory cytokines was used to analyze the protein content of conditioned culture media as well as dentin and odontoblasts from the carious teeth. Results: LPS caused increased gene expression IL-1α, and -8 and decrease of IL-1β, 12 , -15 and -16 after 1h treatment, while after 24h treatment decrease of IL-8, -11 and 23 mRNAs was observed. LTA treatment caused cell death in the tissue cultured odontoblasts but in in the cell culture but not in cell culture. Cytokine array revealed at least 2-fold down-regulation of IL-1β, -10 and -12 in response to LPS treatment. Cytokine array of odontoblasts of carious teeth, as well as LPS-treated tissue-cultured odontoblasts, revealed increased protein amounts of IL-16, epidermal growth factor (EGF), angiogenin and IGFBP-1 as well as decreased amount of fractalkine. In carious dentin, increased amount of IL-1β, EGF and fractalkine was observed, as well as decreased level of GRO-1 and HGF. Conclusion: LPS caused marked changes in the expression of inflammatory cytokines in odontoblasts. Similar changes were observed in the odontoblasts cut directly under the carious lesion. These results help to shed light on the inflammatory processes happening during caries.

Keywords: inflammation, interleukin, lipoteichoic acid, odontoblasts

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