Search results for: causal discovery
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 997

Search results for: causal discovery

457 Comparative Policy Analysis on Agropolitan Territorial Development in Rural Area: A Study Case in Bojonegoro Regency, Indonesia

Authors: Fatihin Khoirul, Muhammad Muqorrobin Ist

Abstract:

Bojonegoro Regency is one of the districts that use the concept Agropolitan as the Territorial Development Policy. Three sub-district designated as Area Development District of Agropolitan are Kapas, Dander, and Kalitidu or commonly called KADEKA. Current policy has been shown results, but there was an inequality of results in some areas. One of them occurred in the Ngringinrejo village with the main commodities is Starfruit and Wedi village with the main commodities is Salak fruit. Therefore, a comparative study is used to search for causal factors of inequality result of the policy by using the 5 aspects compared, namely: (1) Management Development Agropolitan; (2) Physical Condition agropolitan Region; (3) Implementing Agency at the Village Level; (4) Village Government Support; and (5) Community support. Based on the discussion of qualitative analysis, it was found that five aspects have their respective roles in creating inequality of outcomes that occur in both villages. But beyond that, there are conditions where the two villages experienced the same condition that is when the initial implementation of the policy. The condition is referred to as 'the phenomenon of price trap.' The condition is caused by lower commodity prices, causing the village government's commitment in implementing policies too low, followed by public awareness in support of the policy is also low, so care for commodities is also low, and the quality is too low lead and eventually back causing low price. However, the difference is that the village Ngringinrejo able to get out of this condition with 'the new culture of administration' at the end of 2013. While the conditions in the village of Wedi compounded by not respected request assistance by the irrigation district.

Keywords: comparative policy analysis, qualitative comparative, inequallity, price trap, new culture of administration

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456 Geographical Parthenogenesis in Plants

Authors: Elvira Hörandl

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The term “Geographical parthenogenesis” describes the phenomenon that asexual organisms usually occupy larger and more northern distribution areas than their sexual relatives and tend to colonize previously glaciated areas. Several case studies in flowering plants confirm the geographical pattern, but the causal factors behind the phenomenon are still unclear. Previous authors regarded predominant polyploidy in asexual (apomictic) plants as the main factor. However, the geographical pattern is not the rule for sexual polyploids. Recent research confirmed a previous hypothesis of the author that a combination of factors is acting: Although uniparental reproduction provides better colonization abilities, it is most efficient in combination with polyploidy. I will present results on case studies in the genus Ranunculus of both autopolyploid and allopolyploid species and species complexes reproducing via facultative apomixis. Polyploidy seems to contribute mainly to a better tolerance of colder climates and temperate extremes, whereby epigenetic flexibility, changes in gene expression, and phenotypic plasticity play an important role in occupying ecological niches under harsh conditions. Phylogenomic studies entangle complex hybrid origins of asexual taxa, which increases intragenomic heterozygosity of asexual plants. Interestingly, our results suggest an association of sexuality with abiotic stresses, specifically with light stress, which might explain that still, most plants in high altitudes and in southern areas retain sexual reproduction despite other climatic conditions that would favor apomictic plants. We conclude that geographical parthenogenesis results from the complex interplay of the genomic constitution, mode of reproduction and environmental factors.

Keywords: apomixis, polyploidy, hybridization, abiotic stress, epigenetics, phylogenomics

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455 Multi-Source Data Fusion for Urban Comprehensive Management

Authors: Bolin Hua

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In city governance, various data are involved, including city component data, demographic data, housing data and all kinds of business data. These data reflects different aspects of people, events and activities. Data generated from various systems are different in form and data source are different because they may come from different sectors. In order to reflect one or several facets of an event or rule, data from multiple sources need fusion together. Data from different sources using different ways of collection raised several issues which need to be resolved. Problem of data fusion include data update and synchronization, data exchange and sharing, file parsing and entry, duplicate data and its comparison, resource catalogue construction. Governments adopt statistical analysis, time series analysis, extrapolation, monitoring analysis, value mining, scenario prediction in order to achieve pattern discovery, law verification, root cause analysis and public opinion monitoring. The result of Multi-source data fusion is to form a uniform central database, which includes people data, location data, object data, and institution data, business data and space data. We need to use meta data to be referred to and read when application needs to access, manipulate and display the data. A uniform meta data management ensures effectiveness and consistency of data in the process of data exchange, data modeling, data cleansing, data loading, data storing, data analysis, data search and data delivery.

Keywords: multi-source data fusion, urban comprehensive management, information fusion, government data

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454 An Exploration of Cross-culture Consumer Behaviour - The Characteristics of Chinese Consumers’ Decision Making in Europe

Authors: Yongsheng Guo, Xiaoxian Zhu, Mandella Osei-Assibey Bonsu

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This study explores the effects of national culture on consumer behaviour by identifying the characteristics of Chinese consumers’ decision making in Europe. It offers a better understanding of how cultural factors affect consumers’ behaviour, and how consumers make decisions in other nations with different culture. It adopted a grounded theory approach and conducted twenty-four in-depth interviews. Grounded theory models are developed to link the causal conditions, process and consequences. Results reveal that some cultural factors including conservatism, emotionality, acquaintance community, long-term orientation and principles affect Chinese consumers when making purchase decisions in Europe. Most Chinese consumers plan and prepare their expenditure and stay in Europe as cultural learners, and purchase durable products or assets as investment, and share their experiences within a community. This study identified potential problems such as political and social environment, complex procedures, and restrictions. This study found that external factors influence on internal factors and then internal characters determine consumer behaviour. This study proposes that cultural traits developed in convergence evolution through social selection and Chinese consumers persist most characters but adapt some perceptions and actions overtime in other countries. This study suggests that cultural marketing could be adopted by companies to reflect consumers’ preferences. Agencies, shops, and the authorities could take actions to reduce the complexity and restrictions.

Keywords: national culture, consumer behaviour, decision making, cultural marketing

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453 Chitosan Modified Halloysite Nanomaterials for Efficient and Effective Vaccine Delivery in Farmed Fish

Authors: Saji George, Eng Khuan Seng, Christof Luda

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Nanotechnology has been recognized as an important tool for modern agriculture and has the potential to overcome some of the pressing challenges faced by aquaculture industry. A strategy for optimizing nanotechnology-based therapeutic delivery platform for immunizing farmed fish was developed. Accordingly, a compositional library of nanomaterials of natural chemistry (Halloysite (clay), Chitosan, Hydroxyapatite, Mesoporous Silica and a composite material of clay-chitosan) was screened for their toxicity and efficiency in delivering models antigens in cellular and zebrafish embryo models using high throughput screening platforms. Through multi-parametric optimization, chitosan modified halloysite (clay) nanomaterial was identified as an optimal vaccine delivery platform. Further, studies conducted in juvenile seabass showed the potential of clay-chitosan in delivering outer membrane protein of Tenacibaculum maritimum- TIMA (pathogenic bacteria) to and its efficiency in eliciting immune responses in fish. In short, as exemplified by this work, the strategy of using compositional nanomaterial libraries and their biological profiling using high-throughput screening platform could fasten the discovery process of nanomaterials with potential applications in food and agriculture.

Keywords: nanotechnology, fish-vaccine, drug-delivery, halloysite-chitosan

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452 A Novel Small-Molecule Inhibitor of Influenza a Virus Acts by Suppressing PA Endonuclease Activity of the Viral Polymerase

Authors: Shuafeng Yuan, Bojian Zheng

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The RNA-dependent RNA polymerase of influenza a virus comprises conserved and independently folded subdomains with defined functionalities. The N-terminal domain of the PA subunit (PAN) harbors the endonuclease function so that it can serve as a desired target for drug discovery. To identify a class of anti-influenza inhibitors that impedes PAN endonuclease activity, a screening approach that integrated the fluorescence resonance energy transfer based endonuclease inhibitor assay with the DNA gel-based endonuclease inhibitor assay was conducted, followed by the evaluation of antiviral efficacies and potential cytotoxicity of the primary hits in vitro and in vivo. A small-molecule compound ANA-0 was identified as a potent inhibitor against the replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2, in cell cultures. Combinational treatment of zanamivir and ANA-0 exerted synergistic anti-influenza effect in vitro. Intranasal administration of ANA-0 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted ANA-0 bound the endonuclease cavity of PAN by interacting with the metal-binding and catalytic residues. In summary, ANA-0 shows potential to be developed to novel anti-influenza agents.

Keywords: anti-influenza, novel compound, inhibition of endonuclease, PA

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451 Assessment of Estrogenic Contamination and Potential Risk in Taihu Lake, China

Authors: Guanghua Lu, Zhenhua Yan

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To investigate the estrogenic contamination and potential risk of Taihu Lake, eight active biomonitoring points in the northern section of Taihu Lake were set up and located in Wangyuhe River outlet (P1), Gonghu Bay (P2 and P3), Meiliang Bay (P4 and P5), Zhushan Bay (P6 and P7) and Lake Centre (P8). A suite of biomarkers in caged fish after in situ exposure for 28 days, coupled with six selected exogenous estrogens in water, were determined in May and December 2011. Six target estrogens, namely estrone (E1), 17b-estradiol (E2), ethinylestradiol (EE2), estriol (E3), diethylstilbestrol (DES) and bisphenol A (BPA), were quantified using UPLC/MS/MS. The concentrations of E1, E2, E3, EE2, DES and BPA ranged from ND to 3.61 ng/L, ND to 17.3 ng/L, ND to 1.65 ng/L, ND to 10.2 ng/L, ND to 34.6 ng/L, and 3.95 to 207 ng/L, respectively. BPA was detected at all sampling points at all test periods, E2 was detected at 95% of samples, E1 and EE2 was detected at 75% of samples, and E3 was detected only in December 2011 with quite low concentrations. Each individual estrogen concentration measured at each sampling point was multiplied by its relative potency to gain the estradiol equivalent (EEQ). The total EEQ values in all the monitoring points ranged from 5.69 to 17.8 ng/L in May 2011, and from 4.46 to 21.1 ng/L in December 2011. E2 and EE2 were thought to be the major causal agents responsible for the estrogenic activities. Serum vitellogenin and E2 levels, gonadal DNA damage, and gonadosomatic index were measured in the in situ exposed fish. An enhanced integrated biomarker response (EIBR) was calculated and used to evaluate potential feminization risk of fish in the polluted area of Taihu Lake. EIBR index showed good agreement with the observed total EEQ levels in water. Our results indicated that Gong bay and the lake center had a low estrogenic risk, whereas Wangyuhe River, Meiliang Bay, and Zhushan Bay might present a higher risk to fish.

Keywords: active biomonitoring, estrogen, feminization risk, Taihu Lake

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450 Does Clinical Guidelines Affect Healthcare Quality and Populational Health: Quebec Colorectal Cancer Screening Program

Authors: Nizar Ghali, Bernard Fortin, Guy Lacroix

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In Quebec, colonoscopies volumes have continued to rise in recent years in the absence of effective monitoring mechanism for the appropriateness and the quality of these exams. In 2010, November, Quebec Government introduced the colorectal cancer-screening program in the objective to control for volume and cost imperfection. This program is based on clinical standards and was initiated for first group of institutions. One year later, Government adds financial incentives for participants institutions. In this analysis, we want to assess for the causal effect of the two components of this program: clinical pathways and financial incentives. Especially we assess for the reform effect on healthcare quality and population health in the context that medical remuneration is not directly dependent on this additional funding offered by the program. We have data on admissions episodes and deaths for 8 years. We use multistate model analog to difference in difference approach to estimate reform effect on the transition probability between different states for each patient. Our results show that the reform reduced length of stay without deterioration in hospital mortality or readmission rate. In the other hand, the program contributed to decrease the hospitalization rate and a less invasive treatment approach for colorectal surgeries. This is a sign of healthcare quality and population health improvement. We demonstrate in this analysis that physicians’ behavior can be affected by both clinical standards and financial incentives even if offered to facilities.

Keywords: multi-state and multi-episode transition model, healthcare quality, length of stay, transition probability, difference in difference

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449 Polyphosphate Kinase 1 Active Site Characterization for the Identification of Novel Antimicrobial Targets

Authors: Sanaa Bardaweel

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Inorganic polyphosphate (poly P) is present in all living forms tested to date, from each of the three kingdoms of life. Studied mainly in prokaryotes, poly P and its associated enzymes are vital in diverse basic metabolism, in at least some structural functions and, notably, in stress responses. These plentiful and unrelated roles for poly P are probably the consequence of its presence in life-forms early in evolution. The genomes of many bacterial species, including pathogens, encode a homologue of a major poly P synthetic enzyme, poly P kinase 1 (PPK1). Genetic deletion of ppk1 results in reduced poly P levels and loss of pathogens virulence towards protozoa and animals. Thus far, no PPK1 homologue has been identified in higher-order eukaryotes and, therefore, PPK1 represents a novel target for chemotherapy. The idea of the current study is to purify the PPK1 from Escherichia coli to homogeneity in order to study the effect of active site point mutations on PPK1 catalysis via the application of site-directed mutagenesis strategy. The knowledge obtained about the active site of PPK1 will be utilized to characterize the catalytic and kinetic mechanism of PPK1 with model substrates. Comprehensive understanding of the enzyme kinetic mechanism and catalysis will be used to design and screen a library of synthetic compounds for potential discovery of selective PPK1-inhibitors.

Keywords: antimicobial, Escherichia coli, inorganic polyphosphate, PPK1-inhibitors

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448 The Impact of Iso 9001 Certification on Brazilian Firms’ Performance: Insights from Multiple Case Studies

Authors: Matheus Borges Carneiro, Fabiane Leticia Lizarelli, José Carlos De Toledo

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The evolution of quality management by companies was strongly enabled by, among others, ISO 9001 certification, which is considered a crucial requirement for several customers. Likewise, performance measurement provides useful insights for companies to identify the reflection of their decision-making process on their improvement. One of the most used performance measurement models is the balanced scorecard (BSC), which uses four perspectives to address a firm’s performance: financial, internal process, customer satisfaction, and learning and growth. Studies related to ISO 9001 and business performance have mostly adopted a quantitative approach to identify the standard’s causal effect on a firm’s performance. However, to verify how this influence may occur, an in-depth analysis within a qualitative approach is required. Therefore, this paper aims to verify the impact of ISO 9001:2015 on Brazilian firms’ performance based on the balanced scorecard perspective. Hence, nine certified companies located in the Southeast region of Brazil were studied through a multiple case study approach. Within this study, it was possible to identify the positive impact of ISO 9001 on firms’ overall performance, and four Critical Success Factors (CSFs) were identified as relevant on the linkage among ISO 9001 and firms’ performance: employee involvement, top management, process management, and customer focus. Due to the COVID-19 pandemic, the number of interviews was limited to the quality manager specialist, and the sample was limited since several companies were closed during the period of the study. This study presents an in-depth analysis of how the relationship between ISO 9001 certification and firms’ performance in a developing country is.

Keywords: balanced scorecard, Brazilian firms’ performance, critical success factors, ISO 9001 certification, performance measurement

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447 Nasopharyngeal Cancer in Children and Adolescents: Experience of Emir Abdelkader Cancer Center of Oran Algeria

Authors: Taleb L., Benarbia M., Brahmi M., Belmiloud H., Boukerche A.

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Introduction and purpose of the study: Cavum cancer in children and adolescents is rare and represents 8% of all nasopharyngeal cancers treated in our department. Our objective is to study its epidemiological, clinical, therapeutic, and evolutionary particularities. Material and methods: Retrospective study of 39 patients under 20 years old, treated for undifferentiated non-metastatic carcinoma of the nasopharynx at the Emir Abdelkader Cancer Center between 2014 and 2020. Results and statistical analysis: Median age was 14 years [7-19 years], with a sex ratio of 2.9. The median time to diagnosis was 5.6 months [1 to 14 months], the circumstances of the discovery of which were dominated by lymph node syndrome in 43.6% of cases (n=17) followed by a rhinological syndrome in 30.8% of cases (n=13). The tumor stage was T1 for two patients (5.1%), T2 for 8 (20.5%), T3 for 9 (23.1%), T4 for 20 (51.3%), N0 for 2 (5 .1%) N1 for 4 (10.3%), N2 for 28 (71.8%) and N3 for 5 (12.8%). All patients received induction chemotherapy followed by concomitant radiotherapy with cisplatin. The dose of irradiation delivered to the cavum and adenopathies was 66 Gy with fractionation of 2 Gy per session in 69.2% of cases (n=27) and 1.8 Gy in 30.8% of cases (n=12). With a median follow-up of 51 months (15 to 97 months), the locoregional, metastatic, specific, and overall relapse-free survival rates at five years were 91.1%, 73.5%, 66.1%, and 68.4, respectively. Conclusion: Chemotherapy and radiotherapy treatment of cavum cancer in children and adolescents has allowed excellent locoregional control despite the advanced stage of the disease. However, the frequency of metastatic relapses could justify the possible use of systemic maintenance treatment.

Keywords: cancer, nasopharynx, radiotherapy, chemotherapy, survival

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446 Discovering New Organic Materials through Computational Methods

Authors: Lucas Viani, Benedetta Mennucci, Soo Young Park, Johannes Gierschner

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Organic semiconductors have attracted the attention of the scientific community in the past decades due to their unique physicochemical properties, allowing new designs and alternative device fabrication methods. Until today, organic electronic devices are largely based on conjugated polymers mainly due to their easy processability. In the recent years, due to moderate ET and CT efficiencies and the ill-defined nature of polymeric systems the focus has been shifting to small conjugated molecules with well-defined chemical structure, easier control of intermolecular packing, and enhanced CT and ET properties. It has led to the synthesis of new small molecules, followed by the growth of their crystalline structure and ultimately by the device preparation. This workflow is commonly followed without a clear knowledge of the ET and CT properties related mainly to the macroscopic systems, which may lead to financial and time losses, since not all materials will deliver the properties and efficiencies demanded by the current standards. In this work, we present a theoretical workflow designed to predict the key properties of ET of these new materials prior synthesis, thus speeding up the discovery of new promising materials. It is based on quantum mechanical, hybrid, and classical methodologies, starting from a single molecule structure, finishing with the prediction of its packing structure, and prediction of properties of interest such as static and averaged excitonic couplings, and exciton diffusion length.

Keywords: organic semiconductor, organic crystals, energy transport, excitonic couplings

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445 Functional Analysis of Barriers in Disability Care Research: An Integrated Developmental Approach

Authors: Asma Batool

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Immigrant families raising a child with developmental disabilities in Canada encounter many challenges during the process of disability care. Starting from the early screening of their child for diagnosis followed by challenges associated with treatment, access and service utilization. A substantial amount of research focuses on identifying barriers. However, the functional aspects of barriers in terms of their potential influences on parents and children with disabilities are unexplored yet. This paper presents functional analysis of barriers in disability care research by adopting a method of integrated approach. Juxtaposition of two developmental approaches, Bronfenbrenner’s ecological model and parents ‘transformational process model is generating multiple hypotheses to be considered while empirically investigating causal relationships and mediating or moderating factors among various variables related with disability care research. This functional analysis suggests that barriers have negative impacts on the physical and emotional development of children with disabilities as well as on the overall quality of family life (QOFL). While, barriers have facilitating impacts on parents, alternatively, the process of transformation in parents expedite after experiencing barriers. Consequently, parents reconstruct their philosophy of life and experience irreversible but continuous developmental change in terms of transformations simultaneously with their developing child and may buffer the expected negative impacts of barriers on disabled child and QOFL. Overall, this paper is suggesting implications for future research and parents’ transformations are suggesting potential pathways to minimize the negative influences of barriers that parents experience during disability care, hence improving satisfaction in QOFL in general.

Keywords: barriers in disability care, developmental disabilities, parents’ transformations, quality of family life

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444 Attitudinal Change: A Major Therapy for Non–Technical Losses in the Nigerian Power Sector

Authors: Fina O. Faithpraise, Effiong O. Obisung, Azele E. Peter, Chris R. Chatwin

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This study investigates and identifies consumer attitude as a major influence that results in non-technical losses in the Nigerian electricity supply sector. This discovery is revealed by the combination of quantitative and qualitative research to complete a survey. The dataset employed is a simple random sampling of households using electricity (public power supply), and the number of units chosen is based on statistical power analysis. The units were subdivided into two categories (household with and without electrical meters). The hypothesis formulated was tested and analyzed using a chi-square statistical method. The results obtained shows that the critical value for the household with electrical prepared meter (EPM) was (9.488 < 427.4) and those without electrical prepared meter (EPMn) was (9.488 < 436.1) with a p-value of 0.01%. The analysis demonstrated so far established the real-time position, which shows that the wrong attitude towards handling the electricity supplied (not turning off light bulbs and electrical appliances when not in use within the rooms and outdoors within 12 hours of the day) characterized the non-technical losses in the power sector. Therefore the adoption of efficient lighting attitudes in individual households as recommended by the researcher is greatly encouraged. The results from this study should serve as a model for energy efficiency and use for the improvement of electricity consumption as well as a stable economy.

Keywords: attitudinal change, household, non-technical losses, prepared meter

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443 Associations and Interactions of Delivery Mode and Antibiotic Exposure with Infant Cortisol Level: A Correlational Study

Authors: Samarpreet Singh, Gerald Giesbrecht

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Both c-section and antibiotic exposure are linked to gut microbiota imbalance in infants. Such disturbance is associated with the Hypothalamic-Pituitary-Adrenal (HPA) axis function. However, the literature only has contradicting evidence for the association between c-sections and the HPA axis. Therefore, this study aims to test if the mode of delivery and antibiotics exposure is associated with the HPA axis. Also, whether exposure to both interacts with the HPA-axis. It was hypothesized that associations and interactions would be observed. Secondary data analysis was used for this co-relational study. Data for the mode of delivery and antibiotics exposure variables were documented from hospital records or self-questionnaires. In addition, cortisol levels (Area under the curve with respect to increasing (AUCi) and Area under the curve with respect to ground (AUCg)) were based on saliva collected from three months old during the infant’s visit to the lab and after drawing blood. One-way and between-subject ANOVA analyses were run on data. No significant association between delivery mode and infant cortisol level was found, AUCi and AUCg, p > .05. Only the infant’s AUCg was found to be significantly higher if there were antibiotics exposure at delivery (p = .001) or their mothers were exposed during pregnancy (p < .05). Infants born by c-section and exposed to antibiotics at three months had higher AUCi than those born vaginally, p < .02. These results imply that antibiotic exposure before three months is associated with an infant’s stress response. The association might increase if antibiotic exposure occurs three months after a c-section birth. However, more robust and causal evidence in future studies is needed, given a variable group’s statistically weak sample size. Nevertheless, the results of this study still highlight the unintended consequences of antibiotic exposure during delivery and pregnancy.

Keywords: HPA-axis, antibiotics, c-section, gut-microbiota, development, stress

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442 Benchmarking Machine Learning Approaches for Forecasting Hotel Revenue

Authors: Rachel Y. Zhang, Christopher K. Anderson

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A critical aspect of revenue management is a firm’s ability to predict demand as a function of price. Historically hotels have used simple time series models (regression and/or pick-up based models) owing to the complexities of trying to build casual models of demands. Machine learning approaches are slowly attracting attention owing to their flexibility in modeling relationships. This study provides an overview of approaches to forecasting hospitality demand – focusing on the opportunities created by machine learning approaches, including K-Nearest-Neighbors, Support vector machine, Regression Tree, and Artificial Neural Network algorithms. The out-of-sample performances of above approaches to forecasting hotel demand are illustrated by using a proprietary sample of the market level (24 properties) transactional data for Las Vegas NV. Causal predictive models can be built and evaluated owing to the availability of market level (versus firm level) data. This research also compares and contrast model accuracy of firm-level models (i.e. predictive models for hotel A only using hotel A’s data) to models using market level data (prices, review scores, location, chain scale, etc… for all hotels within the market). The prospected models will be valuable for hotel revenue prediction given the basic characters of a hotel property or can be applied in performance evaluation for an existed hotel. The findings will unveil the features that play key roles in a hotel’s revenue performance, which would have considerable potential usefulness in both revenue prediction and evaluation.

Keywords: hotel revenue, k-nearest-neighbors, machine learning, neural network, prediction model, regression tree, support vector machine

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441 Akt: Isoform-Specific Regulation of Cellular Signaling in Cancer

Authors: Bhumika Wadhwa, Fayaz Malik

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The serine/threonine protein kinase B (PKB) also known as Akt, is one of the multifaceted kinase in human kinome, existing in three isoforms. Akt plays a vital role in phosphoinositide 3-kinase (PI3K) mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. The functional significance of an individual isoform of Akt is not redundant in cancer cell proliferation and metastasis instead Akt isoforms play distinct roles during metastasis; thereby regulating EMT. This study aims to determine isoform specific functions of Akt in cancer. The results obtained suggest that Akt1 restrict tumor invasion, whereas Akt2 promotes cell migration and invasion by various techniques like MTT, wound healing and invasion assay. Similarly, qRT-PCR also revealed that Akt3 has shown promising results in promoting cancer cell migration. Contrary to pro-oncogenic properties attributed to Akt, it is to be understood how various isoforms of Akt compensates each other in the regulation of common pathways during cancer progression and drug resistance. In conclusion, this study aims to target selective isoforms which is essential to inhibit cancer. However, the question now is whether, and how much, Akt inhibition will be tolerated in the clinic remains to be answered and the experiments will have to address the question of which combinations of newly devised Akt isoform specific inhibitors exert a favourable therapeutic effect in in vivo models of cancer to provide the therapeutic window with minimal toxicity.

Keywords: Akt isoforms, cancer, drug resistance, epithelial mesenchymal transition

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440 Development of Lectin-Based Biosensor for Glycoprofiling of Clinical Samples: Focus on Prostate Cancer

Authors: Dominika Pihikova, Stefan Belicky, Tomas Bertok, Roman Sokol, Petra Kubanikova, Jan Tkac

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Since aberrant glycosylation is frequently accompanied by both physiological and pathological processes in a human body (cancer, AIDS, inflammatory diseases, etc.), the analysis of tumor-associated glycan patterns have a great potential for the development of novel diagnostic approaches. Moreover, altered glycoforms may assist as a suitable tool for the specificity and sensitivity enhancement in early-stage prostate cancer diagnosis. In this paper we discuss the construction and optimization of ultrasensitive sandwich biosensor platform employing lectin as glycan-binding protein. We focus on the immunoassay development, reduction of non-specific interactions and final glycoprofiling of human serum samples including both prostate cancer (PCa) patients and healthy controls. The fabricated biosensor was measured by label-free electrochemical impedance spectroscopy (EIS) with further lectin microarray verification. Furthermore, we analyzed different biosensor interfaces with atomic force microscopy (AFM) in nanomechanical mapping mode showing a significant differences in the altitude. These preliminary results revealing an elevated content of α-2,3 linked sialic acid in PCa patients comparing with healthy controls. All these experiments are important step towards development of point-of-care devices and discovery of novel glyco-biomarkers applicable in cancer diagnosis.

Keywords: biosensor, glycan, lectin, prostate cancer

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439 Induced Affectivity and Impact on Creativity: Personal Growth and Perceived Adjustment when Narrating an Intense Emotional Experience

Authors: S. Da Costa, D. Páez, F. Sánchez

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We examine the causal role of positive affect on creativity, the association of creativity or innovation in the ideation phase with functional emotional regulation, successful adjustment to stress and dispositional emotional creativity, as well as the predictive role of creativity for positive emotions and social adjustment. The study examines the effects of modification of positive affect on creativity. Participants write three poems, narrate an infatuation episode, answer a scale of personal growth after this episode and perform a creativity task, answer a flow scale after creativity task and fill a dispositional emotional creativity scale. High and low positive effect was induced by asking subjects to write three poems about high and low positive connotation stimuli. In a neutral condition, tasks were performed without previous affect induction. Subjects on the condition of high positive affect report more positive and less negative emotions, more personal growth (effect size r = .24) and their last poem was rated as more original by judges (effect size r = .33). Mediational analysis showed that positive emotions explain the influence of the manipulation on personal growth - positive affect correlates r = .33 to personal growth. The emotional creativity scale correlated to creativity scores of the creative task (r = .14), to the creativity of the narration of the infatuation episode (r = .21). Emotional creativity was also associated, during performing the creativity task, with flow (r = .27) and with affect balance (r = .26). The mediational analysis showed that emotional creativity predicts flow through positive affect. Results suggest that innovation in the phase of ideation is associated with a positive affect balance and satisfactory performance, as well as dispositional emotional creativity is adaptive.

Keywords: affectivity, creativity, induction, innovation, psychological factors

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438 Free Will and Compatibilism in Decision Theory: A Solution to Newcomb’s Paradox

Authors: Sally Heyeon Hwang

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Within decision theory, there are normative principles that dictate how one should act in addition to empirical theories of actual behavior. As a normative guide to one’s actual behavior, evidential or causal decision-theoretic equations allow one to identify outcomes with maximal utility values. The choice that each person makes, however, will, of course, differ according to varying assignments of weight and probability values. Regarding these different choices, it remains a subject of considerable philosophical controversy whether individual subjects have the capacity to exercise free will with respect to the assignment of probabilities, or whether instead the assignment is in some way constrained. A version of this question is given a precise form in Richard Jeffrey’s assumption that free will is necessary for Newcomb’s paradox to count as a decision problem. This paper will argue, against Jeffrey, that decision theory does not require the assumption of libertarian freedom. One of the hallmarks of decision-making is its application across a wide variety of contexts; the implications of a background assumption of free will is similarly varied. One constant across the contexts of decision is that there are always at least two levels of choice for a given agent, depending on the degree of prior constraint. Within the context of Newcomb’s problem, when the predictor is attempting to guess the choice the agent will make, he or she is analyzing the determined aspects of the agent such as past characteristics, experiences, and knowledge. On the other hand, as David Lewis’ backtracking argument concerning the relationship between past and present events brings to light, there are similarly varied ways in which the past can actually be dependent on the present. One implication of this argument is that even in deterministic settings, an agent can have more free will than it may seem. This paper will thus argue against the view that a stable background assumption of free will or determinism in decision theory is necessary, arguing instead for a compatibilist decision theory yielding a novel treatment of Newcomb’s problem.

Keywords: decision theory, compatibilism, free will, Newcomb’s problem

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437 Generalized Additive Model for Estimating Propensity Score

Authors: Tahmidul Islam

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Propensity Score Matching (PSM) technique has been widely used for estimating causal effect of treatment in observational studies. One major step of implementing PSM is estimating the propensity score (PS). Logistic regression model with additive linear terms of covariates is most used technique in many studies. Logistics regression model is also used with cubic splines for retaining flexibility in the model. However, choosing the functional form of the logistic regression model has been a question since the effectiveness of PSM depends on how accurately the PS been estimated. In many situations, the linearity assumption of linear logistic regression may not hold and non-linear relation between the logit and the covariates may be appropriate. One can estimate PS using machine learning techniques such as random forest, neural network etc for more accuracy in non-linear situation. In this study, an attempt has been made to compare the efficacy of Generalized Additive Model (GAM) in various linear and non-linear settings and compare its performance with usual logistic regression. GAM is a non-parametric technique where functional form of the covariates can be unspecified and a flexible regression model can be fitted. In this study various simple and complex models have been considered for treatment under several situations (small/large sample, low/high number of treatment units) and examined which method leads to more covariate balance in the matched dataset. It is found that logistic regression model is impressively robust against inclusion quadratic and interaction terms and reduces mean difference in treatment and control set equally efficiently as GAM does. GAM provided no significantly better covariate balance than logistic regression in both simple and complex models. The analysis also suggests that larger proportion of controls than treatment units leads to better balance for both of the methods.

Keywords: accuracy, covariate balances, generalized additive model, logistic regression, non-linearity, propensity score matching

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436 From Electroencephalogram to Epileptic Seizures Detection by Using Artificial Neural Networks

Authors: Gaetano Zazzaro, Angelo Martone, Roberto V. Montaquila, Luigi Pavone

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Seizure is the main factor that affects the quality of life of epileptic patients. The diagnosis of epilepsy, and hence the identification of epileptogenic zone, is commonly made by using continuous Electroencephalogram (EEG) signal monitoring. Seizure identification on EEG signals is made manually by epileptologists and this process is usually very long and error prone. The aim of this paper is to describe an automated method able to detect seizures in EEG signals, using knowledge discovery in database process and data mining methods and algorithms, which can support physicians during the seizure detection process. Our detection method is based on Artificial Neural Network classifier, trained by applying the multilayer perceptron algorithm, and by using a software application, called Training Builder that has been developed for the massive extraction of features from EEG signals. This tool is able to cover all the data preparation steps ranging from signal processing to data analysis techniques, including the sliding window paradigm, the dimensionality reduction algorithms, information theory, and feature selection measures. The final model shows excellent performances, reaching an accuracy of over 99% during tests on data of a single patient retrieved from a publicly available EEG dataset.

Keywords: artificial neural network, data mining, electroencephalogram, epilepsy, feature extraction, seizure detection, signal processing

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435 Synthesis of a Library of Substituted Isoquinolines Based on a Triazolization Strategy, and Their Anti-HIV and C-X-C Chemokine Receptor Type 4 Antagonist Activity

Authors: Mastaneh Safarnejad Shad, Wim Dehaen, Steven De Jonghe

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Since CXCR4 is the main coreceptor of HIV-1 and plays an important role in human immunodeficiency virus (HIV) entry, numerous efforts were directed towards the discovery of new classes of small molecules that act as CXCR4 antagonists. In addition, CXCR4 antagonists are potentially useful in the treatment of several other disorders, such as cancer cell metastasis, leukemia cell proliferation, rheumatoid arthritis, and pulmonary fibrosis. Since AMD3100 (plerixafor) is the only CXCR4 antagonist which obtained approval by the Food and Drug Administration (FDA), we were motivated to investigate a new category of molecules as CXCR4 antagonists. Most of the scaffolds which have been studied so far as CXCR4 antagonists are based on the tetrahydroquinoline (THQ) moiety in which AMD11070 (mavorixafor), GSK-812394, and TIQ15 displayed the most potent CXCR4 antagonism. Due to the high potency of these scaffolds, two different series of compounds were prepared in this work. In the first set, the THQ moiety is coupled to an amine chain and various isoquinoline derivatives (prepared by an in-house developed triazolization strategy), of which the upper part of molecules is identical to AMD11070 and TIQ15. In the second category of compounds, the THQ moiety was simplified by the synthesis of a substituted pyridine moiety. In order to investigate if CXCR4 antagonism requires the presence of an isoquinoline moiety, the corresponding pyridine analogues were also prepared. In both series of compounds, potent CXCR4 antagonism was noticed.

Keywords: CXCR4 coreceptor, CXCR4 antagonists, HIV inhibitor, tetrahydroquinoline

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434 Analyzing the Influence of Principals’ Cultural Intelligence on Teachers’ Perceived Diversity Climate

Authors: Meghry Nazarian, Ibrahim Duyar

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Effective management of a diverse workforce in the United Arab Emirates (UAE) presents peculiar importance as two-thirds of residents are expatriates who have diverse ethnic and cultural backgrounds. Like any other organization in the country, UAE schools have become upmost diverse settings in the world. The purpose of this study was to examine whether principals’ cultural intelligence has direct and indirect (moderating) influences on teachers’ perceived diversity climate. A quantitative causal-comparative research design was employed to analyze the data. Participants included random samples of principals and teachers working in the private and charter schools in the Emirate of Abu Dhabi. The data-gathering online questionnaires included previously developed and validated scales as the measures of study variables. More specifically, the multidimensional short-form measure of Cultural Intelligence (CQ) and the diversity climate scale were used to measure the study variables. Multivariate statistics, including the analysis of multivariate analysis of variance (MANCOVA) and structural equation modeling (SEM), were employed to examine the relationships between the study variables. The preliminary analyses of data showed that principals and teachers have differing views of diversity management and climate in schools. Findings also showed that principals’ cultural intelligence has both direct and moderating influences on teachers’ perceived diversity climate. The study findings are expected to inform policymakers and practicing educational leaders in addressing diversity management in a country where the majority of the residents are the minority who have diverse ethnic and cultural backgrounds.

Keywords: diversity management, united arab emirates, school principals’ cultural intelligence (CQ), teachers’ perceived diversity climate

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433 Epigenetic Drugs for Major Depressive Disorder: A Critical Appraisal of Available Studies

Authors: Aniket Kumar, Jacob Peedicayil

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Major depressive disorder (MDD) is a common and important psychiatric disorder. Several clinical features of MDD suggest an epigenetic basis for its pathogenesis. Since epigenetics (heritable changes in gene expression not involving changes in DNA sequence) may underlie the pathogenesis of MDD, epigenetic drugs such as DNA methyltransferase inhibitors (DNMTi) and histone deactylase inhibitors (HDACi) may be useful for treating MDD. The available literature indexed in Pubmed on preclinical drug trials of epigenetic drugs for the treatment of MDD was investigated. The search terms we used were ‘depression’ or ‘depressive’ and ‘HDACi’ or ‘DNMTi’. Among epigenetic drugs, it was found that there were 3 preclinical trials using HDACi and 3 using DNMTi for the treatment of MDD. All the trials were conducted on rodents (mice or rats). The animal models of depression that were used were: learned helplessness-induced animal model, forced swim test, open field test, and the tail suspension test. One study used a genetic rat model of depression (the Flinders Sensitive Line). The HDACi that were tested were: sodium butyrate, compound 60 (Cpd-60), and valproic acid. The DNMTi that were tested were: 5-azacytidine and decitabine. Among the three preclinical trials using HDACi, all showed an antidepressant effect in animal models of depression. Among the 3 preclinical trials using DNMTi also, all showed an antidepressant effect in animal models of depression. Thus, epigenetic drugs, namely, HDACi and DNMTi, may prove to be useful in the treatment of MDD and merit further investigation for the treatment of this disorder.

Keywords: DNA methylation, drug discovery, epigenetics, major depressive disorder

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432 Search for the Sacred: A conceptual Analysis of Divine Relationship

Authors: Monir Ahmed

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The main purpose of this paper is to analyze existing conceptual papers on the divine relationship. The primary objective of the paper is to illustrate cognitive orientation as a determinant of divine relationship. A further aim of the paper is to establish whether spiritual or religious practices, rituals, or acts alone could confirm a relationship with the sacred or the divine. Searching for the sacred or the divine is known to be a novel way of understanding the meaning and purpose of human existence, including the existence of everything around us. Inevitably, searching for the sacred provides an opportunity for human beings to form a relationship with the divine. Research suggests that discovering meaning and purpose through searching for the sacred or forming relationship with the divine enhances psychological well-being and eventually helps individuals to flourish. The search for the sacred and the discovery of the divine relationship thus have become interesting areas of study in Psychology of Religion and Spirituality. The existing conceptual papers on the relationship with the transcendent source, i.e., the divine creator, were systematically reviewed and analyzed. The outcome of the review reveals that the existing understanding of the relationship with the divine source is inadequate and that such understanding is unable to indicate or confirm a relationship with psychological well-being, including spiritual well-being. The importance of cognitive orientation, including cognitive processes as well as ‘creatio ex nihilo’ doctrine in searching for the sacred, is indicated. The author of this paper proposes that cognitive-theological understanding involving faith and belief about the creation and the divine source, the transcendent God is likely to offer a comprehensive understanding of the divine relationship.

Keywords: divine, well-being, analysis, cognitive orientation, ‘creatio ex nihilo’ doctrine

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431 Production of Nitric Oxide by Thienopyrimidine TP053

Authors: Elena G. Salina, Laurent R. Chiarelli, Maria R. Pasca, Vadim A. Makarov

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Tuberculosis is one of the most challenging threats to human health, confronted by the problem of drug resistance. Evidently, new drugs for tuberculosis are urgently needed. Thienopyrimidine TP053 is one of the most promising new antitubercular prodrugs. Mycothiol-dependent reductase Mrx2, encoded by rv2466c, is known to be a TP053 activator; however, the precise mode of action of this compound remained unclear. Being highly active against both replicating and non-replicating tuberculosis bacilli, TP053 also revealed dose-escalating activity for M. tuberculosis-infected murine macrophages. The chemical structure of TP053 is characterized by the presence of NO₂ group which was suggested to be responsible for the toxic effects of the activated compound. Reduction of a nitroaromatic moiety of TP53 by Mrx2 was hypothesized to result in NO release. Analysis of the products of enzymatic activation of TP053 by Mrx2 by the Greiss reagent clearly demonstrated production of nitric oxide in a time-dependent manner. Mass-spectra of cell lysates of TP-treated M. tuberculosis bacilli demonstrated the transformation of TP053 to its non-active metabolite with Mw=261 that corresponds NO release. The mechanism of NO toxicity for bacteria includes DNA damage and degradation of iron-sulfur centers, especially under oxygen depletion. Thus, TP-053 drug-like scaffold is prospective for further development of novel anti-TB drug. This work was financially supported by the Russian Foundation for Basic Research (Grant 17-04-00342).

Keywords: drug discovery, M. tuberculosis, nitric oxide, NO donors

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430 Cell Line Screens Identify Biomarkers of Drug Sensitivity in GLIOMA Cancer

Authors: Noora Al Muftah, Reda Rawi, Richard Thompson, Halima Bensmail

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Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. There is an urgent need to identify biomarkers that predict which patients with are most likely to respond to treatment. Systematic efforts to correlate tumor mutational data with biologic dependencies may facilitate the translation of somatic mutation catalogs into meaningful biomarkers for patient stratification. To identify genomic features associated with drug sensitivity and uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we have screened and integrated a panel of several hundred cancer cell lines from different databases, mutation, DNA copy number, and gene expression data for hundreds of cell lines with their responses to targeted and cytotoxic therapies with drugs under clinical and preclinical investigation. We found mutated cancer genes were associated with cellular response to most currently available Glioma cancer drugs and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Keywords: cancer, gene network, Lasso, penalized regression, P-values, unbiased estimator

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429 GeneNet: Temporal Graph Data Visualization for Gene Nomenclature and Relationships

Authors: Jake Gonzalez, Tommy Dang

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This paper proposes a temporal graph approach to visualize and analyze the evolution of gene relationships and nomenclature over time. An interactive web-based tool implements this temporal graph, enabling researchers to traverse a timeline and observe coupled dynamics in network topology and naming conventions. Analysis of a real human genomic dataset reveals the emergence of densely interconnected functional modules over time, representing groups of genes involved in key biological processes. For example, the antimicrobial peptide DEFA1A3 shows increased connections to related alpha-defensins involved in infection response. Tracking degree and betweenness centrality shifts over timeline iterations also quantitatively highlight the reprioritization of certain genes’ topological importance as knowledge advances. Examination of the CNR1 gene encoding the cannabinoid receptor CB1 demonstrates changing synonymous relationships and consolidating naming patterns over time, reflecting its unique functional role discovery. The integrated framework interconnecting these topological and nomenclature dynamics provides richer contextual insights compared to isolated analysis methods. Overall, this temporal graph approach enables a more holistic study of knowledge evolution to elucidate complex biology.

Keywords: temporal graph, gene relationships, nomenclature evolution, interactive visualization, biological insights

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428 The Effect of Language and Literature Integration on the Teaching of English Vocabulary and Grammar in Secondary Schools in Zamfara State, Nigeria

Authors: Umar Bello

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Literature has become an invaluable subject which has added a great value and contribution to the teaching of English language and the discovery of many other developed ideas. Literature produces an exhilarating impulse that imprints a lasting picture on the mind of a learner. Many researchers have devised various means and approaches to language Teaching methods which remain unconvinging and which yield little result, but it has remained unconvincing because it has only produced little results. Devicing a method that eliminates monotony and boredome to learners is a good factor that enhances students’ motivation to learning. In this sense, literature and language become unavoidable components that aid intellectual development. This study examines the indispensability of literature as a means of English Language teaching to secondary school classes. The researcher has developed many instructive activities which are believed will help students to improve their study in grammar and vocabulary. The researcher has used quasi-experimental approach using experimental group and control group to find out how literature enhances the students grammar as well as their vocabulary. The findings revealed a positive performance in the experimental group doing better than the control group using simple percentage. The results make it clear that literature allows learners to pay more attention and develop more interest to their studies. In giving a perspicacious linguistic development, literature therefore remains an essential tool for language teaching classrooms, thereby enhancing their grammatical and vocabulary usage.

Keywords: teaching vocabulary, integration, poetry, classroom

Procedia PDF Downloads 95