Search results for: activity learning

Authors: Said Belaaouad

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This study aimed to explore the quantitative structure-activity relationship (QSAR) of 1,2,4-Triazine-3(2H)-one derivative as a potential anticancer agent against breast cancer. The electronic descriptors were obtained using the Density Functional Theory (DFT) method, and a multiple linear regression techniques was employed to construct the QSAR model. The model exhibited favorable statistical parameters, including R2=0.849, R2adj=0.656, MSE=0.056, R2test=0.710, and Q2cv=0.542, indicating its reliability. Among the descriptors analyzed, absolute electronegativity (χ), total energy (TE), number of hydrogen bond donors (NHD), water solubility (LogS), and shape coefficient (I) were identified as influential factors. Furthermore, leveraging the validated QSAR model, new derivatives of 1,2,4-Triazine-3(2H)-one were designed, and their activity and pharmacokinetic properties were estimated. Subsequently, molecular docking (MD) and molecular dynamics (MD) simulations were employed to assess the binding affinity of the designed molecules. The Tubulin colchicine binding site, which plays a crucial role in cancer treatment, was chosen as the target protein. Through the simulation trajectory spanning 100 ns, the binding affinity was calculated using the MMPBSA script. As a result, fourteen novel Tubulin-colchicine inhibitors with promising pharmacokinetic characteristics were identified. Overall, this study provides valuable insights into the QSAR of 1,2,4-Triazine-3(2H)-one derivative as potential anticancer agent, along with the design of new compounds and their assessment through molecular docking and dynamics simulations targeting the Tubulin-colchicine binding site.

Keywords: QSAR, molecular docking, ADMET, 1, 2, 4-triazin-3(2H)-ones, breast cancer, anticancer, molecular dynamic simulations, MMPBSA calculation

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Authors: Mohammed Flaih Alotaibi, Rasheed Ahemad Shaik, Mohammed Z. Nasrullah

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Diabetic foot ulcers are the foremost global healthcare burden. Hyperglycemia in diabetics is incriminating in impeding wound healing and it can allow for more severe medical issues. The study was intended to establish a nanoconjugate of cordycepin-melittin (COR-MEL) and evaluate its healing effects in wounded diabetic rats. Diabetes induced by injecting streptozotocin intraperitoneally (50 mg/kg, body weight). Therefore, animals were classified into various groups; diabetic untreated, vehicle-treated, COR alone, MEL alone, and COR-MEL nanoconjugate treated, respectively. Animals with diabetes were exposed to excision and treated with Vehicle, COR, MEL, or COR-MEL nanoconjugate topically. After 14 days, the wounded skin was sliced and subjected to histological and biochemical assessments. The formulated nanoconjugate has a particle size of 253.5± 17.4 nm by a polydispersity index of 0.36 ± 0.05, and a zeta potential of 1.72 ± 0.3 mV. The study demonstrated an accelerated wound contraction in COR-MEL-treated diabetic rats, which was further validated by histological analysis. The nanoconjugate further exhibited antioxidant activities by inhibiting the accumulation of malondialdehyde and exhaustion of superoxide dismutase and glutathione peroxidase enzymatic activities. The nanoconjugate further demonstrated an enhanced anti-inflammatory activity by retarding the expression of proinflammatory cytokines (IL-6 and TNF-α). Additionally, the nanoconjugate exhibits a strong expression of growth factors (TGF-β1, VEGF-A, and PDGFR-β), indicating enrichment of proliferation. Likewise, nanoconjugate increased the concentration of hydroxyproline as well as the mRNA expression of collagen, type I, alpha 1. Thus, it is concluded that the nanoconjugate possesses a potent wound-healing activity in diabetic rats via antioxidant, anti-inflammatory, and pro-angiogenetic mechanisms.

Keywords: diabetic wounds, cordycepin, melittin, nanoconjugate, wound healing

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Authors: Thuy Phuong Nhat Tran, Ashutosh Thakur, Toshiaki Taniike

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Recently, covalently linked graphene oxide frameworks (GOFs) have attracted considerable attention in gas absorbance and water purification as well-defined microporous materials. In spite of their potential advantages such as a controllable pore dimension, adjustable hydrophobicity, and structural stability, these materials have been scarcely employed in heterogeneous catalysis. Here we demonstrate a novel and facile method to synthesize Pd nanoparticles (NPs) confined in a GOF (Pd@GOF). The GOF with uniform interlayer space was obtained by the intercalation of diboronic acid between graphene oxide layers. It was found that Pd NPs were generated inside the graphitic gallery spaces of the GOF, and thus, formed Pd NPs were well-dispersed with a narrow particle size distribution. The synthesized Pd@GOF emerged as an efficient nanocatalyst based on its superior performance (product yield and recyclability) toward Suzuki-Miyaura cross-coupling reaction in both polar and apolar solvents, which has been hardly observed for previously reported graphene-based Pd nanocatalysts. Furthermore, the rational comparison of the catalytic performance between two kinds of Pd@GOF (Pd NPs encapsulated in a diboronic ester-intercalated GOF and in a monoboronic ester-intercalated GOF) firmly confirmed the essential role of a rigid framework design in the stabilization of Pd NPs. Based on these results, the covalently assembled GOF was proposed as a promising scaffold for hosting noble metal NPs to construct desired metal@GOF nanocatalysts with improved activity and durability.

Keywords: graphene oxide framework, palladium nanocatalyst, pore confinement, Suzuki-Miyaura cross-coupling reaction

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Authors: Mustafa Kucukoduk, Evren Yildiztugay, A. Hediye Sekmen, Ismail Turkan, Yavuz Bagci

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In this study, physiological and biochemical responses of Centaurea tuzgoluensis, a Turkish endemic halophyte, to salinity were studied. Therefore, the changes in shoot growth, leaf relative water content (RWC), ion concentrations, lipid peroxidation, hydroxyl (OH.) radical scavenging activity, proline (Pro) content, and antioxidant system [superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR)] were investigated. The 60 days (d) old C. tuzgoluensis seedlings were subjected to 0, 150 and 300 mM NaCl for 7 d and 14 d. The relative shoot growth was generally did not change in the 150 mM NaCl, but reduced with 300 mM NaCl stress at 7 d and 14 d. RWC was higher in 150 mM NaCl-treated leaves than that of 300 mM NaCl. Salinity decreased K+/Na+ ratio, but increased Na+, Cl, Ca+2 and Na+/Cl ratio in the leaves. On the other hand, it did not change or increase the K+ content at 150 and 300 mM NaCl, respectively. MDA content in the 150 and 300 mM NaCl-treated leaves remained close to control at 7 d. This was related to enhanced activities of SOD, CAT, APX and GR enzymes, and their isoenzymes especially Fe-SOD in the leaves. On the other hand, the higher sensitivity to 300 mM NaCl at 14 d was associated with inadequate increase in antioxidant enzymes and the decreased OH radical scavenging activity. All these results suggest that C. tuzgoluensis has different antioxidant metabolisms between short- (7 d) and long-term (14 d) salt treatments and salinity tolerance of C. tuzgoluensis might be closely related to increased capacity of antioxidative system to scavenge reactive oxygen species (ROS) and accumulation of osmoprotectant proline under salinity conditions.

Keywords: antioxidant enzymes, endemic halophyte, ion exchange, lipid peroxidation, antioxidant, enzymes, endemic halophyte, ion exchange, lipid peroxidation, proline, Centaurea tuzgoluensis

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Authors: Michal Wolk, Bat-Sheva Hadad, Orly Rubinsten

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Objective: The visuospatial perception system process that allows us to decompose and recompose small quantities into a whole is often called “groupitizing.” Previous studies have been found that adults use groupitizing processes in quantity estimation tasks and link this ability of subgroups recognition to arithmetic proficiency. This pilot study examined if adults with math difficulties benefit from visuospatial grouping cues when asked to estimate the quantity of a given set. It also compared the tipping point in which a significant improvement occurs in adults with typical development compared to adults with math difficulties. Method: In this pilot research, we recruited adults with low arithmetic abilities and matched controls. Participants were asked to estimate the quantity of a given set. Different grouping cues were displayed (space, color, or none) with different visual configurations (different quantities-different shapes, same quantities- different shapes, same quantities- same shapes). Results: Both groups showed significant performance improvement when grouping cues appeared. However, adults with low arithmetic abilities benefited from the grouping cues already in very small quantities as four. Conclusion: impaired perceptual groupitizing abilities may be a characteristic of low arithmetic abilities.

Keywords: groupitizing, math learning disability, quantity estimation, visual perception system

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Authors: Sheila Santharamohana, Susan Bennett

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Historically, the attrition rates in secondary schools of Indigenous people or Orang Asli of Malaysia have been a cause for nationwide concern. Efforts to increase student engagement focusing on curriculum re-design and aid have not had the targeted impact. The scope of the research explored a change model incorporating project-based learning and wrap-around support through school-community partnerships to increase Orang Asli engagement, student outcomes and improve cultural connectedness. The evaluation methodology was mixed-method comprising a student questionnaire, interviews, and document analysis. Data and evidence were gathered from school staff, community, the Orang Asli governmental authority (JAKOA) and external agencies. Findings from the year-long research suggests shared values and goals in school-community partnerships foster responsive leadership and is key to safeguarding vulnerable Orang Asli, resulting in improved student outcomes. The research highlighted the barriers to the recognition and distinct needs and unique values of the Orang Asli that impact their educational equity and outcomes.

Keywords: Indigenous Education, Cultural Connectedness, School-Community Partnership, Student Outcomes

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Authors: Abdel-Monem Sayed Mohamed

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Lake Aswan is one of the largest man-made reservoirs in the world. The reservoir began to fill in 1964 and the level rose gradually, with annual irrigation cycles, until it reached a maximum water level of 181.5 m in November 1999, with a capacity of 160 km3. The filling of such large reservoir changes the stress system either through increasing vertical compressional stress by loading and/or increased pore pressure through the decrease of the effective normal stress. The resulted effect on fault zones changes stability depending strongly on the orientation of pre-existing stress and geometry of the reservoir/fault system. The main earthquake occurred on November 14, 1981, with magnitude 5.5. This event occurred after 17 years of the reservoir began to fill, along the active part of the Kalabsha fault and located not far from the High Dam. Numerous of small earthquakes follow this earthquake and continue till now. For this reason, 13 seismograph stations (radio-telemetry network short-period seismometers) were installed around the northern part of Lake Aswan. The main purpose of the network is to monitor the earthquake activity continuously within Aswan region. The data described here are obtained from the continuous record of earthquake activity and lake-water level variation through the period from 1982 to 2015. The seismicity is concentrated in the Kalabsha area, where there is an intersection of the easterly trending Kalabsha fault with the northerly trending faults. The earthquake foci are distributed in two seismic zones, shallow and deep in the crust. Shallow events have focal depths of less than 12 km while deep events extend from 12 to 28 km. Correlation between the seismicity and the water level variation in the lake provides great suggestion to distinguish the micro-earthquakes, particularly, those in shallow seismic zone in the reservoir–triggered seismicity category. The water loading is one factor from several factors, as an activating medium in triggering earthquakes. The common factors for all cases of induced seismicity seem to be the presence of specific geological conditions, the tectonic setting and water loading. The role of the water loading is as a supplementary source of earthquake events. So, the earthquake activity in the area originated tectonically (ML ≥ 4) and the water factor works as an activating medium in triggering small earthquakes (ML ≤ 3). Study of the inducing seismicity from the water level variation in Aswan Lake is of great importance and play great roles necessity for the safety of the High Dam body and its economic resources.

Keywords: Aswan lake, Aswan seismic network, seismicity, water level variation

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Authors: Lily Parm, Irma Nool, Liina Männiksaar, Mare Tupits, Ivi Prits, Merilin Kuhi, Valentina Raudsepp

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Background: The results of previous clinical satisfaction surveys show that nursing students swhounderw entinternships in the pediatricwardhadthelowestsatisfactioncomparedtootherwards, but the quality of students' practicaltrainingexperienceisanimportant determinant in nursing education. The aim of theresearchwastodescribenursingstudents` assessment to the clinical learning environment and supervision in pediatric wards Method: Theresearchisquantitative. All studentswhohadpracticaltraining in the pediatric ward participated in the study (N = 39). FordatacollectionClinicalLearningEnvironment, Supervision, and NurseTeacher (CLES + T) evaluationscalewasused, wherethescalewasanswered on a 5-point Likert scale. In addition, 10 backgroundvariableswereused in the questionnaire. IBM SPSS Statistics 28.0 wasusedfordataanalysis. Descriptive statistics and Spearmanncorrelationanalysiswasusedtofindcorrelatinsbetweenbackgroundvariables and satisfaction with supervision.Permissiontoconductthestudy (No 695) hasbeenobtainedbytheEthicsCommittee of theInstituteforHealthDevelopment. Results: Of therespondents, 28 (71.8%) werefirst-year, 9 (23.1%) second-year and 2 (5.1%) fourth-yearstudents. Thelargestshare of the last practicaltrainigwas in nursing, with 27 (69.2%) respondents. Mainlythementorswerenursesfor 32 (82,1%) of students.Satisfactionwiththementoring (4.4 ± 0.83) and wardnursemanager`sleaderhiostyle (4.4 ± 0.7), ratedthehighest and therole of thenurseteacherwasratedthelowest (3,7 ± 0.83.In Spearmann'scorrelationanalysis, therewas a statisticallystrongcorrelationbetween a positiveattitudetowardsthesupervisor'ssupervision and receivingfeedbackfromthesupervisor (r =0.755; p <0.001), studentsatisfactionwithsupervision (r = 0.742; p <0.001), supervisionbased on cooperation (r = 0.77) and instructionbased on theprinciple of equalitythatpromotedlearning (r = 0.755; p <0.001). Conclusions: Theresults of theresearchshowedhighsatisfactionwiththesupervisionand therole of wardmanager. Stillbettercooperationisneededbetweenpracticalplacement and nursingschooltoenhancethestudents`satisfactionwithsupervision.

Keywords: CLES+T, clinical environment, nurse teacher, statisfaction, pediatric ward, mentorship

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Authors: B. Samuel Raj, Solomon R. D. Jebakumar

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Microbial fuel cells (MFCs) are an emerging and promising method for achieving sustainable energy since they can remove contaminated organic matter and simultaneously generate electricity. Our approach was driven in three different ways like Bacterial fuel cell, Soil Microbial fuel cell (Soil MFC) and Plant Microbial fuel cell (Plant MFC). Bacterial MFC: Sulphate reducing bacteria (SRB) were isolated and identified as the efficient electricigens which is able to produce ±2.5V (689mW/m2) and it has sustainable activity for 120 days. Experimental data with different MFC revealed that high electricity production harvested continuously for 90 days 1.45V (381mW/m2), 1.98V (456mW/m2) respectively. Biofilm formation was confirmed on the surface of the anode by high content screening (HCS) and scanning electron Microscopic analysis (SEM). Soil MFC: Soil MFC was constructed with low cost and standard Mudwatt soil MFC was purchased from keegotech (USA). Vermicompost soil (V1) produce high energy (± 3.5V for ± 400 days) compared to Agricultural soil (A1) (± 2V for ± 150 days). Biofilm formation was confirmed by HCS and SEM analysis. This finding provides a method for extracting energy from organic matter, but also suggests a strategy for promoting the bioremediation of organic contaminants in subsurface environments. Our Soil MFC were able to run successfully a 3.5V fan and three LED continuously for 150 days. Plant MFC: Amaranthus candatus (P1) and Triticum aestivium (P2) were used in Plant MFC to confirm the electricity production from plant associated microbes, four uniform size of Plant MFC were constructed and checked for energy production. P2 produce high energy (± 3.2V for 40 days) with harvesting interval of two times and P1 produces moderate energy without harvesting interval (±1.5V for 24 days). P2 is able run 3.5V fan continuously for 10days whereas P1 needs optimization of growth conditions to produce high energy.

Keywords: microbial fuel cell, biofilm, soil microbial fuel cell, plant microbial fuel cell

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Authors: Agata Chudzicka-Czupała, Nadiya Hapon, Liudmyla Karamushka, Marta żywiołek-Szeja

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Objectives: The study is about the determinants of coping with stress connected with volunteer activity for Russo-Ukrainian war 2022 refugees. We examined the mental health reactions, chosen psychological traits, and motivational functions of volunteers working in Poland and Ukraine in relation to their coping with stress styles. The study was financed with funds from the Foundation for Polish Science in the framework of the FOR UKRAINE Programme. Material and Method: The study was conducted in 2022. The study was a quantitative, questionnaire-based survey. Data was collected through an online survey. The volunteers were asked to assess their propensity to use different styles of coping with stress connected with their activity for Russo-Ukrainian war refugees using The Brief Coping Orientation to Problems Experienced Inventory (Brief-COPE) questionnaire. Depression, anxiety, and stress were measured using the Depression, Anxiety, and Stress (DASS)-21 item scale. Chosen psychological traits, psychological capital and hardiness, were assessed by The Psychological Capital Questionnaire and The Norwegian Revised Scale of Hardiness (DRS-15R). Then The Volunteer Function Inventory (VFI) was used. The significance of differences between the variable means of the samples was tested by the Student's t-test. We used multivariate linear regression to identify factors associated with coping with stress styles separately for each national sample. Results: The sample consisted of 720 volunteers helping war refugees (in Poland, 435 people, and 285 in Ukraine). The results of the regression analysis indicate variables that are significant predictors of the propensity to use particular styles of coping with stress (problem-focused style, emotion-focused style and avoidant coping). These include levels of depression and stress, individual psychological characteristics and motivational functions, different for Polish and Ukrainians. Ukrainian volunteers are significantly more likely to use all three coping with stress styles than Polish ones. The results also prove significant differences in the severity of anxiety, stress and depression, the selected psychological traits and motivational functions studied, which led volunteers to participate in activities for war refugees. Conclusions: The results show that depression and stress severity, as well as psychological capital and hardiness, and motivational factors are connected with coping with stress behavior. The results indicate the need for increased attention to the well-being of volunteers acting under stressful conditions. They also prove the necessity of guiding the selection of people for specific types of volu

Keywords: anxiety, coping with stress styles, depression, hardiness, mental health, motivational functions, psychological capital, resilience, stress, war, volunteer, civil society

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Authors: Mario Chiasson, Monique Boudreau

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Problem statement: Innovation in education has become a central topic of discussion at various levels, including schools and scholarly literature, driven by the global technological advancements of Industry 4.0. This study aims to contribute to the ongoing dialogue by examining the role of innovation in transforming school culture through the reimagination of traditional structures. The study argues that such a transformation necessitates an understanding and experience of systems leadership. This paper presents the case of the Francophone South School District, where a transformative initiative created an innovative learning environment by engaging students, teachers, and community members collaboratively through eco-communities. Traditional barriers and structures in education were dismantled to facilitate this process. The research component of this paper focuses on the Intr’Appreneur project, a unique initiative launched by the district team in the New Brunswick, Canada to support a system-wide transformation towards progressive and innovative organizational models. Methods This study is part of a larger research project that focuses on the transformation of educational systems in six pilot schools involved in the Intr’Appreneur project. Due to COVID-19 restrictions, the project was downscaled to three schools, and virtual qualitative interviews were conducted with volunteer teachers and administrators. Data was collected from students, teachers, and principals regarding their perceptions of the new learning environment and experiences. The analysis process involved developing categories, establishing codes for emerging themes, and validating the findings. The study emphasizes the importance of system leadership in achieving successful transformation. Results: The findings demonstrate that school principals played a vital role in enabling system-wide change by fostering a dynamic, collaborative, and inclusive culture, coordinating and mobilizing community members, and serving as educational role models who facilitated active and personalized pedagogy among the teaching staff. These qualities align with the characteristics of Leadership 4.0 and are crucial for successful school system transformations. Conclusion: This paper emphasizes the importance of systems leadership in driving educational transformations that extend beyond pedagogical and technological advancements. The research underscores the potential impact of such a leadership approach on teaching, learning, and leading processes in Education 4.0.

Keywords: leadership, system transformation, innovation, innovative learning environment, Education 4.0, system leadership

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Authors: Han-Jeong Hwang, Jae-Hyun Jo, Fatemeh Alimardani

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An accurate diagnosis of psychiatric diseases is a challenging issue, in particular when distinct symptoms for different diseases are overlapped, such as delusions appeared in bipolar mood disorder (BMD) and schizophrenia (SCH). In the present study, we propose a useful way to discriminate BMD and SCH using electroencephalography (EEG). A total of thirty BMD and SCH patients (15 vs. 15) took part in our experiment. EEG signals were measured with nineteen electrodes attached on the scalp using the international 10-20 system, while they were exposed to a visual stimulus flickering at 16 Hz for 95 s. The flickering visual stimulus induces a certain brain signal, known as steady-state visual evoked potential (SSVEP), which is differently observed in patients with BMD and SCH, respectively, in terms of SSVEP amplitude because they process the same visual information in own unique way. For classifying BDM and SCH patients, machine learning technique was employed in which leave-one-out-cross validation was performed. The SSVEPs induced at the fundamental (16 Hz) and second harmonic (32 Hz) stimulation frequencies were extracted using fast Fourier transformation (FFT), and they were used as features. The most discriminative feature was selected using the Fisher score, and support vector machine (SVM) was used as a classifier. From the analysis, we could obtain a classification accuracy of 83.33 %, showing the feasibility of discriminating patients with BMD and SCH using EEG. We expect that our approach can be utilized for psychiatrists to more accurately diagnose the psychiatric disorders, BMD and SCH.

Keywords: bipolar mood disorder, electroencephalography, schizophrenia, machine learning

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Authors: G. Suja, J. Sreekumar, A. N. Jyothi, V. S. Santhosh Mithra

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Worldwide concerns regarding food safety, environmental degradation and threats to human health have generated interest in alternative systems like organic farming. Tropical tuber crops, cassava, sweet potato, yams, and aroids are food-cum-nutritional security-cum climate resilient crops. These form stable or subsidiary food for about 500 million global population. Cassava, yams (white yam, greater yam, and lesser yam) and edible aroids (elephant foot yam, taro, and tannia) are high energy tuberous vegetables with good taste and nutritive value. Seven on-station field experiments at ICAR-Central Tuber Crops Research Institute, Thiruvananthapuram, India and seventeen on-farm trials in three districts of Kerala, were conducted over a decade (2004-2015) to compare the varietal response, yield, quality and soil properties under organic vs conventional system in these crops and to develop a learning system based on the data generated. The industrial, as well as domestic varieties of cassava, the elite and local varieties of elephant foot yam and taro and the three species of Dioscorea (yams), were on a par under both systems. Organic management promoted yield by 8%, 20%, 9%, 11% and 7% over conventional practice in cassava, elephant foot yam, white yam, greater yam and lesser yam respectively. Elephant foot yam was the most responsive to organic management followed by yams and cassava. In taro, slight yield reduction (5%) was noticed under organic farming with almost similar tuber quality. The tuber quality was improved with higher dry matter, starch, crude protein, K, Ca and Mg contents. The anti-nutritional factors, oxalate content in elephant foot yam and cyanogenic glucoside content in cassava were lowered by 21 and 12.4% respectively. Organic plots had significantly higher water holding capacity, pH, available K, Fe, Mn and Cu, higher soil organic matter, available N, P, exchangeable Ca and Mg, dehydrogenase enzyme activity and microbial count. Organic farming scored significantly higher soil quality index (1.93) than conventional practice (1.46). The soil quality index was driven by water holding capacity, pH and available Zn followed by soil organic matter. Organic management enhanced net profit by 20-40% over chemical farming. A case in point is the cost-benefit analysis in elephant foot yam which indicated that the net profit was 28% higher and additional income of Rs. 47,716 ha-1 was obtained due to organic farming. Cost-effective technologies were field validated. The on-station technologies developed were validated and popularized through on-farm trials in 10 sites (5 ha) under National Horticulture Mission funded programme in elephant foot yam and seven sites in yams and taro. The technologies are included in the Package of Practices Recommendations for crops of Kerala Agricultural University. A learning system developed using artificial neural networks (ANN) predicted the performance of elephant foot yam organic system. Use of organically produced seed materials, seed treatment in cow-dung, neem cake, bio-inoculant slurry, farmyard manure incubated with bio-inoculants, green manuring, use of neem cake, bio-fertilizers and ash formed the strategies for organic production. Organic farming is an eco-friendly management strategy that enables 10-20% higher yield, quality tubers and maintenance of soil health in tuber crops.

Keywords: eco-agriculture, quality, root crops, healthy soil, yield

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Authors: A. Hamza, H. Kathyayini, N. Nagaraju

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Aluminophosphates, both amorphous and crystalline materials find applications as adsorbents, ceramics, and pigments and as catalysts/catalyst supports in organic fine chemical synthesis. Most of the applications are varied depending on the type of metal incorporated, particle size, surface area, porosity and morphology of aluminophosphate. The porous and surface properties of these materials are normally fine-tuned by adopting various preparation methodologies. Numerous crystalline microporous and mesoporous aluminophosphates and metal-aluminophosphates have been reported in literature, in which the synthesis has been carried out by using structure directing organic molecules/surfactants. In present work, amorphous aluminophosphate (AlP) and metal-aluminophosphates MAlP (M = Cu, Zn, Cr, Fe, Ce and Zr) and their mixed forms M-1M2AlP are prepared under a typical precipitation condition, i.e. at low temperature in order to keep the Von-Weirmann relative super saturation of the precipitating medium and obtain small size precipitate particles. These materials are prepared without using any surfactants. All materials are thoroughly characterised for surface and bulk properties by N2 adsorption-desorption technique, XRD, FT-IR, TG and SEM. The materials are also analysed for the amount and the strength of their surface acid sites, by NH3-TPD and CO2-TPD techniques respectively. All the materials prepared in the work are investigated for their catalytic activity in following applications in the synthesis of industrially important Jasminaldehyde via, aldol condensation of n-heptanal and benzaldehyde, in the synthesis of biologically important chalcones by Claisen-shmidth condensation of benzaldehyde and substituted chalcones. The effect of the amount of the catalysts, duration of the reaction, temperature of the reaction, molar ratio of the reactants has been studied. The porosity of pure aluminophosphate is found to be changed significantly by the incorporation of transition metals during preparation of aluminophosphate. The pore size increased from microporous to mesoporous and finally to macroporous by following order of metals Cu = Zn < Cr < Ce < Fe = Zr. The change in surface area and porosity of double metal-aluminophosphates depended on the concentration of both the metals. The acidity of aluminophosphate is either increased or decreased which depended on the type and valence of metals loaded. A good number of basic sites are created in metal-aluminophosphates irrespective of the metals used. A maximum catalytic activity for synthesis of both jasminaldehyde and chalcone is obtained by FeAlP as catalysts; these materials are characterized by decreased strength and concentration of acidic sites with optimum level basic sites.

Keywords: amorphous metal-aluminophosphates, surface properties, acidic-basic properties, Aldol, Claisen-Shmidth condensation, jasminaldehyde, chalcone

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Authors: Fernando Augusto Ullmann Tobe, Moacyr Amaral Domingues, Figueiredo, Stephany Rie Yamamoto Gushiken

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The purpose of this paper is to present the process of elaborating the layout of an assembly line of a welding industry using the principles of lean manufacturing as the main driver. The objective of this paper is relevant since the current layout of the assembly line causes non-productive times for operators, being related to the lean waste of unnecessary movements. The methodology used for the project development was Project-based Learning (PBL), which is an active way of learning focused on real problems. The process of selecting the methodology for layout planning was developed considering three criteria to evaluate the most relevant one for this paper's goal. As a result of this evaluation, Systematic Layout Planning was selected, and three steps were added to it – Value Stream Mapping for the current situation and after layout changed and the definition of lean tools and layout type. This inclusion was to consider lean manufacturing in the layout redesign of the industry. The layout change resulted in an increase in the value-adding time of operations carried out in the sector, reduction in movement times between previous and final assemblies, and in cost savings regarding the man-hour value of the employees, which can be invested in productive hours instead of movement times.

Keywords: assembly line, layout, lean manufacturing, systematic layout planning

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Authors: Soni Ariawan

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The discourse of language and culture relation is an interesting issue to be researched. The debate is not about what comes first, language or culture, but it strongly argues that learning foreign language also means learning the culture of the language. The more interesting issue found once constructing an EFL textbook dealing with proportional representation among source culture, target culture and international culture. This study investigates cultural content representation in EFL textbook grade 10 year 2017 in Indonesia. Cortazzi and Jin’s theoretical framework is employed to analyse the reading texts, conversations, and images. The finding shows that national character as the main agenda of Indonesian government is revealed in this textbook since the textbook more frequently highlights the source culture (Indonesian culture) compared to target and international culture. This is aligned with the aim of Indonesian government to strengthen the national identity and promoting local culture awareness through education. To conclude, the study is expected to be significant in providing the idea for government to consider cultural balances representation in constructing textbook. Furthermore, teachers and students should be aware of cultural content revealed in the EFL textbook and be able to enhance intercultural communication not only in the classroom but also in a wider society.

Keywords: EFL textbook, intercultural communication, local culture, target culture, international culture

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Authors: Mehar Fatima

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This study intends to make analysis of Emotional Intelligence (EI) in the process of pedagogy and look into its repercussions in different educational institutions including school, college, and university in the capital state of India, Delhi in 2015. Field of education is a complex area with challenging issues in a modern society. Education is the breeding ground for nurturing human souls, and personalities. Since antiquity, man has been in search of truth, wisdom, contentment, peace. His efforts have brought him to acquire these through hardship, evidently through the process of teaching and learning. Computer aids and artificial intelligence have made life easy but complex. Efficient pedagogy involves direct human intervention despite the flux of technological advancements. Time and again, pedagogical practices demand sincere human efforts to understand and improve upon life’s many pragmatic concerns. Apart from the intense academic scientific approaches, EI in academia plays a vital role in the growth of education, positively achieving national progression; ‘pedagogy of pragmatic purpose.’ Use of literature is found to be one of the valuable pragmatic tools of Emotional Intelligence. This research examines the way literature provides useful influence in building better practices in teaching-learning process. The present project also scrutinizes various pieces of world literature and translation, incorporating efforts of intellectuals in promoting comprehensive amity. The importance of EI in educational arena with its pragmatic uses was established by the study of interviews, and questionnaire collected from teachers and students. In summary the analysis of obtained empirical data makes it possible to accomplish that the use Emotional Intelligence in academic scenario yields multisided positive pragmatic outcomes; positive attitude, constructive aptitude, value-added learning, enthusiastic participation, creative thinking, lower apprehension, diminished fear, leading to individual as well as collective advancement, progress, and growth of pedagogical agents.

Keywords: emotional intelligence, human efforts, pedagogy, pragmatic concerns

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Authors: Nargess Fasihmardanloo

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The aim of this study was to comparatively study the motivations of women to physical activity in Iran and selected Arab countries Based on individual, social and Islamic components. The present study was a descriptive comparative study that was performed by field method. The statistical population of the study included female athletes in Iran and Arab countries. A total of 184 people from Iran and 179 people from Arab countries (Iraq, UAE, and Jordan) were selected through available sampling as a research sample. The research tool included a questionnaire. The validity of the questionnaire was confirmed and its reliability in a pilot study was 0.95 through Cronbach's alpha. The questionnaire was translated into Persian in Iran and translated into Arabic for the selected countries and was provided to the participants electronically and through cyberspace. Finally, 363 questionnaires were collected. Manova multivariate analysis of variance using spss22 software was used to analyze the data. Findings showed that between Iranian women athletes and women athletes in selected Arab countries in the components of intrapersonal motivation (p = 0.009 and f = 6.978), interpersonal motivation (p = 0.050 and f = 3.875), There is a significant difference between social motives (p = 0.001 and f = 27.619) and Islamic motives (p = 0.001 and f = 11.339). And this difference is significant at the level of p <0.01 and p <0.05. In other words, in the component of intrapersonal motivations, the average of this component in Iranian female athletes (M = 59.77) was higher than female athletes in selected Arab countries (M = 55.53). In the interpersonal motivations component, the average of this component in Iranian female athletes (M = 26.87) was lower than in female athletes in selected Arab countries (M = 28.62). In the component of social motivations, the average of this component in Iranian female athletes (M = 33.08) was lower than female athletes in selected Arab countries (M = 39.64). In the component of Islamic motives, the average of this component in Iranian female athletes (M = 21.55) was higher than female athletes in selected Arab countries (M = 19.04).

Keywords: athletes, motivation, women, Islamic

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Authors: Michael Smalenberger

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Intelligent tutoring systems (ITS) are computer-based platforms which can incorporate artificial intelligence to provide step-by-step guidance as students practice problem-solving skills. ITS can replicate the benefits of one-on-one tutoring, foster transactivity in collaborative environments, and lead to substantial learning gains when used to supplement the instruction of a teacher or when used as the sole method of instruction. Developments improving the ease of ITS creation have recently increased their proliferation, leading many K-12 schools and institutions of higher education in the United States to regularly use ITS within classrooms. We investigated how students perceive their experience using an ITS. In this study, 111 undergraduate students used an ITS in a college-level introductory statistics course and were subsequently asked for feedback on their experience. Results show that their perceptions were generally favorable of the ITS, and most would seek to use an ITS both for STEM and non-STEM courses in the future. Along with detailed transaction-level data, this feedback also provides insights on the design of user-friendly interfaces, guidance on accessibility for students with impairments, the sequencing of exercises, students’ expectation of achievement, and comparisons to other tutoring experiences. We discuss how these findings are important for the creation, implementation, and evaluation of ITS as a mode and method of teaching and learning.

Keywords: college statistics course, intelligent tutoring systems, in vivo study, student perceptions of tutoring

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Authors: Joy Cao, Min Zhou

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Purpose: Acute Type A aortic dissection is a well-known cause of extremely high mortality rate. A highly accurate and cost-effective non-invasive predictor is critically needed so that the patient can be treated at earlier stage. Although various CFD approaches have been tried to establish some prediction frameworks, they are sensitive to uncertainty in both image segmentation and boundary conditions. Tedious pre-processing and demanding calibration procedures requirement further compound the issue, thus hampering their clinical applicability. Using the latest physics informed deep learning methods to establish an accurate and cost-effective predictor framework are amongst the main goals for a better Type A aortic dissection treatment. Methods: Via training a novel physics-informed deep residual network, with non-invasive 4D MRI displacement vectors as inputs, the trained model can cost-effectively calculate all these biomarkers: aortic blood pressure, WSS, and OSI, which are used to predict potential type A aortic dissection to avoid the high mortality events down the road. Results: The proposed deep learning method has been successfully trained and tested with both synthetic 3D aneurysm dataset and a clinical dataset in the aortic dissection context using Google colab environment. In both cases, the model has generated aortic blood pressure, WSS, and OSI results matching the expected patient’s health status. Conclusion: The proposed novel physics-informed deep residual network shows great potential to create a cost-effective, non-invasive predictor framework. Additional physics-based de-noising algorithm will be added to make the model more robust to clinical data noises. Further studies will be conducted in collaboration with big institutions such as Cleveland Clinic with more clinical samples to further improve the model’s clinical applicability.

Keywords: type-a aortic dissection, deep residual networks, blood flow modeling, data-driven modeling, non-invasive diagnostics, deep learning, artificial intelligence.

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Authors: Mina Adel Shokry Fahim, Jūratė Sužiedelytė Visockienė

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With the growing concern over air pollution (AP), it is clear that this has gained more prominence than ever before. The level of consciousness has increased and a sense of knowledge now has to be forwarded as a duty by those enlightened enough to disseminate it to others. This realisation often comes after an understanding of how poor air quality indices (AQI) damage human health. The study focuses on assessing air pollution prediction models specifically for Lithuania, addressing a substantial need for empirical research within the region. Concentrating on Vilnius, it specifically examines particulate matter concentrations 10 micrometers or less in diameter (PM10). Utilizing Gaussian Process Regression (GPR) and Regression Tree Ensemble, and Regression Tree methodologies, predictive forecasting models are validated and tested using hourly data from January 2020 to December 2022. The study explores the classification of AP data into anthropogenic and natural sources, the impact of AP on human health, and its connection to cardiovascular diseases. The study revealed varying levels of accuracy among the models, with GPR achieving the highest accuracy, indicated by an RMSE of 4.14 in validation and 3.89 in testing.

Keywords: air pollution, anthropogenic and natural sources, machine learning, Gaussian process regression, tree ensemble, forecasting models, particulate matter

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Authors: Eldar Mammadov, Konul Mammadova, Aytaj Ilyaszada

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Background: According to many studies, it is known that H. pylori transform into the coccoid form, which cannot be cultured and has poor metabolic activity.In this study, we succeeded in preserving the spiral shape of H.pylori for a long time by preparing a biphase transport medium with a hard bottom (Muller Hinton with 7% HRBC (horse red blood cells) agar 5ml) and liquid top part (BH (brain heart) broth + HS (horse serum)+7% HRBC+antibiotics (Vancomycin 5 mg, Trimethoprim lactate 25 mg, Polymyxin B 1250 I.U.)) in cell culture flasks with filter caps. For comparison, we also used a BH broth medium with 7% HRBC used for the transport of H.pylori. Methods: Rapid urease test positive 7 biopsy specimens were also inoculated into biphasic and BH broth medium with 7% HRBC, then put in CO2 Gaspak packages and sent to the laboratory. Then both mediums were kept in the thermostat at 37 °C for 1 day. After microscopic, PCR and urease test diagnosis, they were transferred to Columbia Agar with 7% HRBC. Incubated at 37°C for 5-7 days, cultures were examined for colony characteristics and bacterial morphology. E-test antimicrobial susceptibility test was performed. Results: There were 3 growths from biphasic transport medium passed to Columbia agar with 7% HRBC and only 1 growth from BH broth medium with 7% HRBC. It was also observed that after the first 3 days in BH broth medium with 7%, H.pylori passed into coccoid form and its biochemical activity weakened, while its spiral shape did not change for 2-3 weeks in the biphase transport medium. Conclusions: By using the biphase transport medium we have prepared; we can culture the bacterium by preventing H.pylori from spiraling into the coccoid form. In our opinion, this may result in the wide use of culture method for diagnosis of H.pylori, study of antibiotic susceptibility and molecular genetic analysis.

Keywords: clinical trial, H.pylori, coccoid form, transport medium

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Authors: Karin Eines, Riki Tesler

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Introduction: The Mamanet Cachibol League (MCL) is a community-based model developed in Israel to promote physical activity (PA) and amateur team sports among women. team sports are not just groups in the context of specific sport activity but also incorporated into a person’s sense of self and become influencing factor on sport-related behavior among the players. While in the non-Arabic sector, sport venues are available for the local authority population, the Arabic sector authorities face limited access sport facilities, with 168 sport venues and authorities with no venues at all. Within the Arab community, women participation in sports has traditionally been limited and, even more so for participation in team sports. Aims: The purpose of the study was to explore attributes of women MCL activity via: (1) assess differences between participants in the MCL and non-participants among Arab women regarding well-being level; (2) to examine among MCL participants the relationship between health maintenance characteristics and the likelihood of participating in the MCL; and (3) Use qualitative approach to shed light over the question why Arabic women participate in MCL and continue their engagement in PA. Methods: An explanatory sequential mixed-method design was employed to gain a deeper understanding of the advantages and motivations among women participating in community-based team sports. A cross-sectional survey was conducted among Israeli Arab women aged 25–59. Demographic characteristics, well-being (SRH and psychosomatic symptoms), eating habits, and social support were analyzed using two-way analyses of covariance and multiple regression models with a sequential entry of the variables. Quantitative results were further explored in qualitative in-depth interviews among 30 of the MCL participants, which shed light on additional reasons for participation in PA. Results: MCL participants reported better self-reported health (p < 0.001) and lower rates of psychosomatic symptoms (p < 0.001) compared to non-participants. Participation in MCL was also related to higher levels of well-being and healthy eating habits. Women who participated also experienced a profound sense of belonging, leading to enhanced social interactions and positivity in their personal and professional lives. They were dedicated to the group and felt empowered by the reciprocal commitment. The group promoted equality, making the women feel valued and respected, resulting in community admiration. Their involvement positively impacted their families, justifying their time commitment.

Keywords: wellbeing, obesity, community based sports, healthy eating habits, arab women

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Authors: Sanjay Shukla, A. Nayak, R. K. Sharma, A. P. Singh, S. P. Tiwari

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Excessive use of antibiotics is a major problem in the treatment of wounds and other chronic infections, and antibiotic treatment is frequently non-curative, thus alternative treatment is necessary. Phage therapy is considered one of the most promising approaches to treat multi-drug resistant bacterial pathogens. Infections caused by Staphylococcus aureus are very efficiently controlled with phage cocktails, containing a different individual phages lysate infecting a majority of known pathogenic S. aureus strains. The aim of the present study was to evaluate the efficacy of a purified phage cocktail for prophylactic as well as therapeutic application in mouse model and in large animals with chronic septic infection of wounds. A total of 150 sewage samples were collected from various livestock farms. These samples were subjected for the isolation of bacteriophage by the double agar layer method. A total of 27 sewage samples showed plaque formation by producing lytic activity against S. aureus in the double agar overlay method out of 150 sewage samples. In TEM, recovered isolates of bacteriophages showed hexagonal structure with tail fiber. In the bacteriophage (ØVS) had an icosahedral symmetry with the head size 52.20 nm in diameter and long tail of 109 nm. Head and tail were held together by connector and can be classified as a member of the Myoviridae family under the order of Caudovirale. Recovered bacteriophage had shown the antibacterial activity against the S. aureus in vitro. Cocktail (ØVS1, ØVS5, ØVS9, and ØVS 27) of phage lysate were tested to know in vivo antibacterial activity as well as the safety profile. Result of mice experiment indicated that the bacteriophage lysate were very safe, did not show any appearance of abscess formation, which indicates its safety in living system. The mice were also prophylactically protected against S. aureus when administered with cocktail of bacteriophage lysate just before the administration of S. aureuswhich indicates that they are good prophylactic agent. The S. aureusinoculated mice were completely recovered by bacteriophage administration with 100% recovery, which was very good as compere to conventional therapy. In the present study, ten chronic cases of the wound were treated with phage lysate, and follow up of these cases was done regularly up to ten days (at 0, 5, and 10 d). The result indicated that the six cases out of ten showed complete recovery of wounds within 10 d. The efficacy of bacteriophage therapy was found to be 60% which was very good as compared to the conventional antibiotic therapy in chronic septic wounds infections. Thus, the application of lytic phage in single dose proved to be innovative and effective therapy for the treatment of septic chronic wounds.

Keywords: phage therapy, S aureus, antimicrobial resistance, lytic phage, and bacteriophage

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Authors: Madhavi-Priya Singh, Liam Lowe, Farouk Arnaout, Ludmilla Pillay, Giordan Perez, Luke Mischker, Steve Costa

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Introduction: An Emergency Department consultant identified the failure of medical students to complete the task of clerking a patient in its entirety. As six medical students on our first clinical placement, we recognised our own failure and endeavored to examine why this failure was consistent among all medical students that had been given this task, despite our best motivations as adult learners. Aim: Our aim is to understand and investigate the elements which impeded our ability to learn and perform as medical students in the clinical environment, with reference to the prescribed task. We also aim to generate a discussion around the delivery of medical education with potential solutions to these barriers. Methods: Six medical students gathered together to have a comprehensive reflective discussion to identify possible factors leading to the failure of the task. First, we thoroughly analysed the delivery of the instructions with reference to the literature to identify potential flaws. We then examined personal, social, ethical, and cultural factors which may have impacted our ability to complete the task in its entirety. Results: Through collation of our shared experiences, with support from discussion in the field of medical education and ethics, we identified two major areas that impacted our ability to complete the set task. First, we experienced an ethical conflict where we believed the inconvenience and potential harm inflicted on patients did not justify the positive impact the patient interaction would have on our medical learning. Second, we identified a lack of confidence stemming from multiple factors, including the conflict between preclinical and clinical learning, perceptions of perfectionism in the culture of medicine, and the influence of upward social comparison. Discussion: After discussions, we found that the various factors we identified exacerbated the fears and doubts we already had about our own abilities and that of the medical education system. This doubt led us to avoid completing certain aspects of the tasks that were prescribed and further reinforced our vulnerability and perceived incompetence. Exploration of philosophical theories identified the importance of the role of doubt in education. We propose the need for further discussion around incorporating both pedagogic and andragogic teaching styles in clinical medical education and the acceptance of doubt as a driver of our learning. Conclusion: Doubt will continue to permeate our thoughts and actions no matter what. The moral or psychological distress that arises from this is the key motivating factor for our avoidance of tasks. If we accept this doubt and education embraces this doubt, it will no longer linger in the shadows as a negative and restrictive emotion but fuel a brighter dialogue and positive learning experience, ultimately assisting us in achieving our full potential.

Keywords: ethics, medical student, doubt, medical education, faith

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Authors: Junjie Zhong, Kai Hong, Lei Wang

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Passage Retrieval (PR) plays an important role in many Natural Language Processing (NLP) tasks. Traditional efficient retrieval models relying on exact term-matching, such as TF-IDF or BM25, have nowadays been exceeded by pre-trained language models which match by semantics. Though they gain effectiveness, deep language models often require large memory as well as time cost. To tackle the trade-off between efficiency and effectiveness in PR, this paper proposes Graph Passage Retriever (GraphPR), a graph-based model inspired by the development of graph learning techniques. Different from existing works, GraphPR is end-to-end and integrates both term-matching information and semantics. GraphPR constructs a passage-level graph from BM25 retrieval results and trains a GCN-like model on the graph with graph-based objectives. Passages were regarded as nodes in the constructed graph and were embedded in dense vectors. PR can then be implemented using embeddings and a fast vector-similarity search. Experiments on a variety of real-world retrieval datasets show that the proposed model outperforms related models in several evaluation metrics (e.g., mean reciprocal rank, accuracy, F1-scores) while maintaining a relatively low query latency and memory usage.

Keywords: efficiency, effectiveness, graph learning, language model, passage retrieval, term-matching model

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Authors: Rasheed A. Saliu, Sunday E. Ogundipe, Oluwaseun A. Adefila

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Information and Communication Technology (ICT) in recent time has transformed the means by which we inform ourselves, with world events and areas of personal interests, and further our learning. Today, for many, books and journals are no longer the first or primary source of information or learning. We now regularly rely on images, video, animations and sound to acquire information and to learn. Increased and improved access to the internet has accelerated this phenomenon. We now acquire and access information in ways fundamentally different from the pre-ICT era. But to what extent is academic staff in colleges of education, having access to and the utilising of ICT devices in their lecture deliveries especially in School of Science and Vocational and Technical? The main focus of this paper is to proffer solution to this salient question. It is essentially an empirical study carried out in five colleges of education in south-west zone of Nigeria. The target population was the academic staff in the selected institution. A total number of 150 male and female lecturers were contacted for the study. The main instrument was questionnaire. The finding reveals that male lecturers are much more ICT inclined than women folk in the academics. Some recommendations were made to endear academics to utilizing ICT at their disposal to foster qualitative delivery in this digital era.

Keywords: education, gender, ICT, Nigeria

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Authors: Chokri Slim

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The objective of this research is attempting to respond to this question: Is there a significant difference between the regression model and statistical learning models in predicting credit risk management? A Multiple Linear Regression (MLR) model was compared with neural networks including Multi-Layer Perceptron (MLP), and a Support vector regression (SVR). The population of this study includes 50 listed Banks in Tunis Stock Exchange (TSE) market from 2000 to 2016. Firstly, we show the factors that have significant effect on the quality of loan portfolios of banks in Tunisia. Secondly, it attempts to establish that the systematic use of objective techniques and methods designed to apprehend and assess risk when considering applications for granting credit, has a positive effect on the quality of loan portfolios of banks and their future collectability. Finally, we will try to show that the bank governance has an impact on the choice of methods and techniques for analyzing and measuring the risks inherent in the banking business, including the risk of non-repayment. The results of empirical tests confirm our claims.

Keywords: credit risk management, multiple linear regression, principal components analysis, artificial neural networks, support vector machines

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Authors: Shanna Swart, Caryn Fenner, Athanasios Kotsiopoulos, Susan Harrison

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Linear alkanes are produced as by-products from the increasing use of gas-to-liquid fuel technologies for synthetic fuel production and offer great potential for value addition. Their current use as low-value fuels and solvents do not maximize this potential. Therefore, attention has been drawn towards direct activation of these aliphatic alkanes to more useful products such as alcohols, aldehydes, carboxylic acids and derivatives. Cytochrome P450 monooxygenases (P450s) can be used for activation of these aliphatic alkanes using whole-cells or cell-free systems. Some limitations of whole-cell systems include reduced mass transfer, stability and possible side reactions. Since the P450 systems are little studied as cell-free systems, they form the focus of this study. Challenges of a cell-free system include co-factor regeneration, substrate availability and enzyme stability. Enzyme immobilization offers a positive outlook on this dilemma, as it may enhance stability of the enzyme. In the present study, 2 different P450s (CYP153A6 and CYP102A1) as well as the relevant accessory enzymes required for electron transfer (ferredoxin and ferredoxin reductase) and co-factor regeneration (glucose dehydrogenase) have been expressed in E. coli and purified by metal affinity chromatography. Glucose dehydrogenase (GDH), was used as a model enzyme to assess the potential of various enzyme immobilization strategies including; surface attachment on MagReSyn® microspheres with various functionalities and on electrospun nanofibers, using self-assembly based methods forming Cross Linked Enzymes (CLE), Cross Linked Enzyme Aggregates (CLEAs) and spherezymes as well as in a sol gel. The nanofibers were synthesized by electrospinning, which required the building of an electrospinning machine. The nanofiber morphology has been analyzed by SEM and binding will be further verified by FT-IR. Covalent attachment based methods showed limitations where only ferredoxin reductase and GDH retained activity after immobilization which were largely attributed to insufficient electron transfer and inactivation caused by the crosslinkers (60% and 90% relative activity loss for the free enzyme when using 0.5% glutaraldehyde and glutaraldehyde/ethylenediamine (1:1 v/v), respectively). So far, initial experiments with GDH have shown the most potential when immobilized via their His-tag onto the surface of MagReSyn® microspheres functionalized with Ni-NTA. It was found that Crude GDH could be simultaneously purified and immobilized with sufficient activity retention. Immobilized pure and crude GDH could be recycled 9 and 10 times, respectively, with approximately 10% activity remaining. The immobilized GDH was also more stable than the free enzyme after storage for 14 days at 4˚C. This immobilization strategy will also be applied to the P450s and optimized with regards to enzyme loading and immobilization time, as well as characterized and compared with the free enzymes. It is anticipated that the proposed immobilization set-up will offer enhanced enzyme stability (as well as reusability and easy recovery), minimal mass transfer limitation, with continuous co-factor regeneration and minimal enzyme leaching. All of which provide a positive outlook on this robust multi-enzyme system for efficient activation of linear alkanes as well as the potential for immobilization of various multiple enzymes, including multimeric enzymes for different bio-catalytic applications beyond alkane activation.

Keywords: alkane activation, cytochrome P450 monooxygenase, enzyme catalysis, enzyme immobilization

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Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

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The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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