Search results for: positive interactions
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 8523

Search results for: positive interactions

7473 Harnessing the Power of Mixed Ligand Complexes: Enhancing Antimicrobial Activities with Thiosemicarbazones

Authors: Sakshi Gupta, Seema Joshi

Abstract:

Thiosemicarbazones (TSCs) have garnered significant attention in coordination chemistry due to their versatile coordination modes and pharmacological properties. Mixed ligand complexes of TSCs represent a promising area of research, offering enhanced antimicrobial activities compared to their parent compounds. This review provides an overview of the synthesis, characterization, and antimicrobial properties of mixed ligand complexes incorporating thiosemicarbazones. The synthesis of mixed ligand complexes typically involves the reaction of a metal salt with TSC ligands and additional ligands, such as nitrogen- or oxygen-based ligands. Various transition metals, including copper, nickel, and cobalt, have been employed to form mixed ligand complexes with TSCs. Characterization techniques such as spectroscopy, X-ray crystallography, and elemental analysis are commonly utilized to confirm the structures of these complexes. One of the key advantages of mixed ligand complexes is their enhanced antimicrobial activity compared to pure TSC compounds. The synergistic effect between the TSC ligands and additional ligands contributes to increased efficacy, possibly through improved metal-ligand interactions or enhanced membrane permeability. Furthermore, mixed ligand complexes offer the potential for selective targeting of microbial species while minimizing toxicity to mammalian cells. This selectivity arises from the specific interactions between the metal center, TSC ligands, and biological targets within microbial cells. Such targeted antimicrobial activity is crucial for developing effective treatments with minimal side effects. Moreover, the versatility of mixed ligand complexes allows for the design of tailored antimicrobial agents with optimized properties. By varying the metal ion, TSC ligands, and additional ligands, researchers can fine-tune the physicochemical properties and biological activities of these complexes. This tunability opens avenues for the development of novel antimicrobial agents with improved efficacy and reduced resistance. In conclusion, mixed ligand complexes of thiosemicarbazones represent a promising class of compounds with potent antimicrobial activities. Further research in this field holds great potential for the development of novel therapeutic agents to combat microbial infections effectively.

Keywords: metal complex, thiosemicarbazones, mixed ligand, selective targeting, antimicrobial activity

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7472 Development of Terrorist Threat Prediction Model in Indonesia by Using Bayesian Network

Authors: Hilya Mudrika Arini, Nur Aini Masruroh, Budi Hartono

Abstract:

There are more than 20 terrorist threats from 2002 to 2012 in Indonesia. Despite of this fact, preventive solution through studies in the field of national security in Indonesia has not been conducted comprehensively. This study aims to provide a preventive solution by developing prediction model of the terrorist threat in Indonesia by using Bayesian network. There are eight stages to build the model, started from literature review, build and verify Bayesian belief network to what-if scenario. In order to build the model, four experts from different perspectives are utilized. This study finds several significant findings. First, news and the readiness of terrorist group are the most influent factor. Second, according to several scenarios of the news portion, it can be concluded that the higher positive news proportion, the higher probability of terrorist threat will occur. Therefore, the preventive solution to reduce the terrorist threat in Indonesia based on the model is by keeping the positive news portion to a maximum of 38%.

Keywords: Bayesian network, decision analysis, national security system, text mining

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7471 Automatic Detection of Proliferative Cells in Immunohistochemically Images of Meningioma Using Fuzzy C-Means Clustering and HSV Color Space

Authors: Vahid Anari, Mina Bakhshi

Abstract:

Visual search and identification of immunohistochemically stained tissue of meningioma was performed manually in pathologic laboratories to detect and diagnose the cancers type of meningioma. This task is very tedious and time-consuming. Moreover, because of cell's complex nature, it still remains a challenging task to segment cells from its background and analyze them automatically. In this paper, we develop and test a computerized scheme that can automatically identify cells in microscopic images of meningioma and classify them into positive (proliferative) and negative (normal) cells. Dataset including 150 images are used to test the scheme. The scheme uses Fuzzy C-means algorithm as a color clustering method based on perceptually uniform hue, saturation, value (HSV) color space. Since the cells are distinguishable by the human eye, the accuracy and stability of the algorithm are quantitatively compared through application to a wide variety of real images.

Keywords: positive cell, color segmentation, HSV color space, immunohistochemistry, meningioma, thresholding, fuzzy c-means

Procedia PDF Downloads 195
7470 Observation on Microbiological Profile of Type2 Diabetic Foot Ulcer and Its Antimicrobial Sensitivity Pattern in a Tertiary Care Hospital in Eastern India

Authors: Pampita Chakraborty, Sukumar Mukherjee

Abstract:

Diabetes Mellitus (DM) is commonly encountered metabolic disorder in clinical practice. An estimated 25 percent of DM patients develop foot problems. Foot ulceration and infection are one of the major causes of morbidity, hospitalization or even amputation. Objective: To isolate and identify bacterial pathogens in Diabetic Foot Ulcer (DFU) and to observe its antimicrobial sensitivity pattern. Methodology: A prospective study was conducted for a period of 9 months at the Department of Microbiology, GD Hospital & Diabetes Institute, Kolkata. 75 DFU patients were recruited in the study. Specimens for microbiological studies obtained from ulcer base were examined as gram stained smear and was cultured aerobically on Nutrient agar, Blood agar and MacConkey agar plates. Antimicrobial sensitivity test was performed by disc diffusion techniques according to CLSI guidelines. Result: In this study out of 75cases, 73% (55/75) were male and 27% (20/75) were females with mean (SD) age of 51.11(±10) years. Out of 75 pus cultures, 63(84%) showed growth of microorganism making total of 81 bacterial isolates with 71.42% of monomicrobial infection and 28.57% of polymicrobial infection. Out of 81 isolates 53(65.43%) were gram negative and 21(25.92%) were gram positive. E.coli was relatively common isolate 21(26%) followed by Staphylococcus aureus 15(18.5%), Klebsiella pneumonia 14(17.28%), Pseudomonas aeruginosa 12 (14.81%), Proteus spp. 3 (3.70%), and Enterococcus faecalis 6 (7.40%). 75% of Gram-negative microorganism were extended Beta-lactamase enzyme (ESBL) producer and around 20 % of Klebsiella and Proteus spp. were carbapenemase enzyme producer. Among Gram positive, around 50% of S.aureus was MRSA, sensitive only to Vancomycin, Teicoplanin & Linezolid. Conclusion: More prevalence of monomicrobial gram-negative bacteria than gram-positive bacteria in DFU was observed. This study emphasizes that Beta-Lactam group of antibiotics should not be the empirical treatment of choice for Gram-negative isolates; instead alternatives like Carbapenems, Amikacin could be a better option. On the other hand, Vancomycin and Linezolid are preferred for most of the infection with gram-positive aerobes. Continuous surveillance of resistant bacteria is required for empiric therapy.

Keywords: antibiotic resistant, antimicrobial susceptibility, diabetic foot ulcer, surveillance

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7469 Tourism Industry, Cultural Exchange Affect on Public and International Health Status

Authors: Farshad Kalantari

Abstract:

Tourism industry has gained a progressive trend within the past years, which affect the cultural exchange among different nations. It is obvious that each country has its own culture, heritage and history, which can be manifested in the population lifestyle and pattern of living. the lifestyle can be considered as an indicator for health status, as the culture may affect way of living, which known as lifestyle and its components, including dietary pattern, physical activity status and other social behaviours. As a result, it seems that each culture can transfer the lifestyle to other societies by international communications. Moreover, different regions and countries may benefit from natural resources, which can be a leading cause for tourist attraction, in the other words, natural resources and culture, can affect the tourist turnover in a region, and as a result, it can be hypothesised that it may affect the exchange of lifestyle including dietary pattern and physical activity. In the positive way, this can make a region to health pole for other nationalities to gain benefit from that culture in order to improve their quality of life and health status. In this paper has aimed to assess the effect of culture and heritage on tourism rate and the effect of natural resources along with cultural lifestyle on public health and international exchange between other regions. It was hypothesised that by using culture in a positive manner, positive aspect of lifestyle, including ancient physical activity patter, can be transfer and exchange with other regions, which can improve health status as a result. Moreover, it was focused on how to design and recruit strategies to improve the way of gaining benefits from resources and lifestyle in order to improve tourism industry and its rate, which may bring beneficial outcomes, including financial, cultural and health outcomes.

Keywords: toursim, health, culture, sport, lifestyle

Procedia PDF Downloads 52
7468 Relationship Quality, Value Creation Practices and Brand Loyalty in Virtual Communities: Evidence from Facebook Communities

Authors: Zoya Khan, Amina Muzaffar

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Social media based brand communities are communities that are developed around a brand. In the highly globalized world of today, Facebook is undoubtedly being regarded and has been widely recognized as a trendy and well-accepted medium of marketing. By means of a Facebook fan page, organizations can effectually create, enhance, and sustain customer-brand relationship. In this article, we explore whether brand communities based on social media (a special type of online brand communities) have positive effects on the main community elements and value creation practices in the communities as well as on brand trust and brand loyalty. A survey was conducted and 201 valid responses were used for analysis. The results of structural equation modeling show that brand communities established on social media have positive effects on value creation practices. Brand use, impression management practices and brand identification has an impact on brand trust and this brand trust then further leads to brand loyalty.

Keywords: relationship quality, impression management practices, brand identification, brand trust, brand loyalty

Procedia PDF Downloads 467
7467 Nexus among Foreign Private Investment, CO2 Emissions, Energy Consumption and Sustainable Economic Growth

Authors: Aysha Zamir

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This study examines to what extent foreign private investment (FPI) affects the clean industrial environment and sustainable economic growth through developed countries investment in China. Moreover, this study investiage an association among FPI, CO2 emission, energy consumption, and sustainable economic growth. This study uses random effects and generalized least squares (GLS) and panel VAR estimators for data analysis. The results indicate that the Chinese economy has a vastly positive influenced regarding the location and choice of emerging and developed countries’ investment in the domestic market. Furthermore, emerging and developed economies investment increases the contribution among domestic firms, environment sustainability toward the national economy. The further results show that foreign private investment and gross domestic investment have a positive impact on sustainable economic growth.

Keywords: clean industrial environment, energy consumption, CO2 emmission, foreign private investment, developed and emerging economies

Procedia PDF Downloads 115
7466 Experiences of HIV Positive Serostatus Disclosure to Sexual Partner Among Individuals in Discordant Couples in Mbarara City, Southwestern Uganda

Authors: Humphrey Atwijukiire, Gladys Nakidde, Anne Tweheyo Otwine, Jane Kabami

Abstract:

Experiences of HIV Positive Serostatus Disclosure to Sexual Partner Among Individuals in Discordant Couples in Mbarara City, Southwestern Uganda Introduction: Disclosure of HIV status is key in HIV management. Despite many studies on serostatus disclosure, there is a gap in experiences regarding HIV status disclosure among discordant couples. This study explored the lived experiences of serostatus disclosure among discordant couples in Mbarara City, South Western Uganda. Methods: We conducted 12 in-depth interviews using translated interview guide, and audio recorders. Participants were purposively enrolled in the study. The study was conducted at three public health facilities in Mbarara City. Data was analyzed using thematic content analysis. Approval for this research was obtained from Mbarara University Research Ethics Committee and administrative clearance from city clerk of Mbarara City. Results: The mean age of participants was 38 years. An equal number of males (six) and females participated. Most of them had at least secondary level education, only three had primary education. Experienced benefits of HIV serostatus disclosure included: social support and care; decisions regarding health, fertility, and child bearing; sharing information on HIV prevention and protection; positive living; and, ease of HIV disclosure. The challenges included: misunderstandings in the families. Conclusion: Socially, psychologically and financially PLWHIV have benefited from their negative partners. Health wise, they have been supported, and cared for, but some have faced challenges, such as family misunderstandings. Couple HIV counseling and testing by a trained health worker is beneficial in HIV care and could mitigate the challenges related HIV serostatus disclosure.

Keywords: discordant couples, disclosure, experiences, HIV

Procedia PDF Downloads 123
7465 The Influence of the Intellectual Capital on the Firms’ Market Value: A Study of Listed Firms in the Tehran Stock Exchange (TSE)

Authors: Bita Mashayekhi, Seyed Meisam Tabatabaie Nasab

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Intellectual capital is one of the most valuable and important parts of the intangible assets of enterprises especially in knowledge-based enterprises. With respect to increasing gap between the market value and the book value of the companies, intellectual capital is one of the components that can be placed in this gap. This paper uses the value added efficiency of the three components, capital employed, human capital and structural capital, to measure the intellectual capital efficiency of Iranian industries groups, listed in the Tehran Stock Exchange (TSE), using a 8 years period data set from 2005 to 2012. In order to analyze the effect of intellectual capital on the market-to-book value ratio of the companies, the data set was divided into 10 industries, Banking, Pharmaceutical, Metals & Mineral Nonmetallic, Food, Computer, Building, Investments, Chemical, Cement and Automotive, and the panel data method was applied to estimating pooled OLS. The results exhibited that value added of capital employed has a positive significant relation with increasing market value in the industries, Banking, Metals & Mineral Nonmetallic, Food, Computer, Chemical and Cement, and also, showed that value added efficiency of structural capital has a positive significant relation with increasing market value in the Banking, Pharmaceutical and Computer industries groups. The results of the value added showed a negative relation with the Banking and Pharmaceutical industries groups and a positive relation with computer and Automotive industries groups. Among the studied industries, computer industry has placed the widest gap between the market value and book value in its intellectual capital.

Keywords: capital employed, human capital, intellectual capital, market-to-book value, structural capital, value added efficiency

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7464 Teachers’ Perception of the Implementation of Inclusive Creative Arts Education

Authors: William Kwabena Nantwi

Abstract:

This quantitative study investigates Creative Arts teachers' perceptions regarding the implementation of an Inclusive Creative Arts curriculum. The research employs a descriptive approach utilizing a 5-point Likert scale questionnaire comprising 15 items to gather data from Creative Arts educators. The Census with a disproportionate stratified sampling method was utilized to select 226 teachers from five educational circuits (Circuit A, B, C, D & E) within Offinso Municipality, Ghana. The findings indicate that most Creative Arts teachers hold a positive perception towards implementing an inclusive Creative Arts curriculum. Positive perceptions and attitudes among teachers are correlated with increased student engagement and participation in class activities. This study recommends organizing workshops and in-service training sessions focused on inclusive Creative Arts education for Creative Arts teachers. Additionally, it suggests that Colleges of Education and Universities responsible for teacher training integrate foundational courses in Creative Arts and Special Education into their primary education teacher preparation programs.

Keywords: perception, attitude, inclusive education, creative art, creative arts teachers, Ghana

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7463 Structuring Paraphrases: The Impact Sentence Complexity Has on Key Leader Engagements

Authors: Meaghan Bowman

Abstract:

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

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

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7462 Transcriptome Sequencing of the Spleens Reveals Genes Involved in Antiviral Response in Chickens Infected with Castv

Authors: Sajewicz-Krukowska Joanna, Domańska-Blicharz Katarzyna, Tarasiuk Karolina, Marzec-Kotarska Barbara

Abstract:

Astroviral infections pose a significant problem in the poultry industry, leading to multiple adverse effects such as decreased egg production, breeding disorders, poor weight gain, and even increased mortality. Commonly observed chicken astrovirus (CAstV) was recently reported to be responsible for "white chicks syndrome" associated with increased embryo/chick mortality. The CAstV-mediated pathogenesis in chicken occurs due to complex interactions between the infectious pathogen and the immune system. Many aspects of CAstV-chicken interactions remain unclear, and there is no information available regarding gene expression changes in the chicken's spleen in response to CAstV infection. We aimed to investigate the molecular background triggered by CAstV infection. Ten 21-day-old SPF White Leghorn chickens were divided into two groups of 5 birds each. One group was inoculated with CAstV, and the other was used as the negative control. On 4th dpi, spleen samples were collected and immediately frozen at -70°C for RNA isolation. We analysed transcriptional profiles of the chickens' spleens at the 4th day following infection using RNA-seq to establish differentially expressed genes (DEGs). The RNA-seq findings were verified by quantitative real-time PCR (qRT-PCR). A total of 31959 transcripts were identified in response to CAstV infection. Eventually 45 DEGs (p-value<0.05; Log2Foldchange>1)were recognized in the spleen after CAstV infection (26 upregulated DEGs and 19 downregulated DEGs). qRT-PCR performed on 4 genes (IFIT5, OASL, RASD1, DDX60) confirmed RNAseq results. Top differentially expressed genes belonged to novel putative IFN-induced CAstV restriction factors. Most of the DEGs were associated with RIG-I–like signalling pathway or, more generally, with an innate antiviral response(upregulated: BLEC3, CMPK2, IFIT5, OASL, DDX60, IFI6, and downregulated: SPIK5, SELENOP, HSPA2, TMEM158, RASD1, YWHAB). The study provided a global analysis of host transcriptional changes that occur during CAstV infection in vivo and proved the cell cycle in the spleen and immune signalling in chickens were predominantly affected upon CAstV infection.

Keywords: chicken astrovirus, CastV, RNA-seq, transcriptome, spleen

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7461 Alignment and Antagonism in Flux: A Diachronic Sentiment Analysis of Attitudes towards the Chinese Mainland in the Hong Kong Press

Authors: William Feng, Qingyu Gao

Abstract:

Despite the extensive discussions about Hong Kong’s sentiments towards the Chinese Mainland since the sovereignty transfer in 1997, there has been no large-scale empirical analysis of the changing attitudes in the mainstream media, which both reflect and shape sentiments in the society. To address this gap, the present study uses an optimised semantic-based automatic sentiment analysis method to examine a corpus of news about China from 1997 to 2020 in three main Chinese-language newspapers in Hong Kong, namely Apple Daily, Ming Pao, and Oriental Daily News. The analysis shows that although the Hong Kong press had a positive emotional tone toward China in general, the overall trend of sentiment was becoming increasingly negative. Meanwhile, the alignment and antagonism toward China have both increased, providing empirical evidence of attitudinal polarisation in the Hong Kong society. Specifically, Apple Daily’s depictions of China have become increasingly negative, though with some positive turns before 2008, whilst Oriental Daily News has consistently expressed more favourable sentiments. Ming Pao maintained an impartial stance toward China through an increased but balanced representation of positive and negative sentiments, with its subjectivity and sentiment intensity growing to an industry-standard level. The results provide new insights into the complexity of sentiments towards China in the Hong Kong press and media attitudes in general in terms of the “us” and “them” positioning by explicating the cross-newspaper and cross-period variations using an enhanced sentiment analysis method which incorporates sentiment-oriented and semantic role analysis techniques.

Keywords: media attitude, sentiment analysis, Hong Kong press, one country two systems

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7460 The Prognostic Prediction Value of Positive Lymph Nodes Numbers for the Hypopharyngeal Squamous Cell Carcinoma

Authors: Wendu Pang, Yaxin Luo, Junhong Li, Yu Zhao, Danni Cheng, Yufang Rao, Minzi Mao, Ke Qiu, Yijun Dong, Fei Chen, Jun Liu, Jian Zou, Haiyang Wang, Wei Xu, Jianjun Ren

Abstract:

We aimed to compare the prognostic prediction value of positive lymph node number (PLNN) to the American Joint Committee on Cancer (AJCC) tumor, lymph node, and metastasis (TNM) staging system for patients with hypopharyngeal squamous cell carcinoma (HPSCC). A total of 826 patients with HPSCC from the Surveillance, Epidemiology, and End Results database (2004–2015) were identified and split into two independent cohorts: training (n=461) and validation (n=365). Univariate and multivariate Cox regression analyses were used to evaluate the prognostic effects of PLNN in patients with HPSCC. We further applied six Cox regression models to compare the survival predictive values of the PLNN and AJCC TNM staging system. PLNN showed a significant association with overall survival (OS) and cancer-specific survival (CSS) (P < 0.001) in both univariate and multivariable analyses, and was divided into three groups (PLNN 0, PLNN 1-5, and PLNN>5). In the training cohort, multivariate analysis revealed that the increased PLNN of HPSCC gave rise to significantly poor OS and CSS after adjusting for age, sex, tumor size, and cancer stage; this trend was also verified by the validation cohort. Additionally, the survival model incorporating a composite of PLNN and TNM classification (C-index, 0.705, 0.734) performed better than the PLNN and AJCC TNM models. PLNN can serve as a powerful survival predictor for patients with HPSCC and is a surrogate supplement for cancer staging systems.

Keywords: hypopharyngeal squamous cell carcinoma, positive lymph nodes number, prognosis, prediction models, survival predictive values

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7459 The Impact of Social Customer Relationship Management on Brand Loyalty and Reducing Co-Destruction of Value by Customers

Authors: Sanaz Farhangi, Habib Alipour

Abstract:

The main objective of this paper is to explore how social media as a critical platform would increase the interactions between the tourism sector and stakeholders. Nowadays, human interactions through social media in many areas, especially in tourism, provide various experiences and information that users share and discuss. Organizations and firms can gain customer loyalty through social media platforms, albeit consumers' negative image of the product or services. Such a negative image can be reduced through constant communication between produces and consumers, especially with the availability of the new technology. Therefore, effective management of customer relationships in social media creates an extraordinary opportunity for organizations to enhance value and brand loyalty. In this study, we seek to develop a conceptual model for addressing factors such as social media, SCRM, and customer engagement affecting brand loyalty and diminish co-destruction. To support this model, we scanned the relevant literature using a comprehensive category of ideas in the context of marketing and customer relationship management. This will allow exploring whether there is any relationship between social media, customer engagement, social customer relationship management (SCRM), co-destruction, and brand loyalty. SCRM has been explored as a moderating factor in the relationship between customer engagement and social media to secure brand loyalty and diminish co-destruction of the company’s value. Although numerous studies have been conducted on the impact of social media on customers and marketing behavior, there are limited studies for investigating the relationship between SCRM, brand loyalty, and negative e-WOM, which results in the reduction of the co-destruction of value by customers. This study is an important contribution to the tourism and hospitality industry in orienting customer behavior in social media using SCRM. This study revealed that through social media platforms, management can generate discussion and engagement about the product and services, which facilitates customers feeling in an appositive way towards the firm and its product. Study has also revealed that customers’ complaints through social media have a multi-purpose effect; it can degrade the value of the product, but at the same time, it will motivate the firm to overcome its weaknesses and correct its shortcomings. This study has also implications for the managers and practitioners, especially in the tourism and hospitality sector. Future research direction and limitations of the research were also discussed.

Keywords: brand loyalty, co-destruction, customer engagement, SCRM, tourism and hospitality

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7458 Prognostic Value of Tumor Markers in Younger Patients with Breast Cancer

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

Abstract:

Background: Breast cancer occupies the first place among the cancer in women in the world. It is urgent today to study the role of molecular markers which are capable of predicting the dynamics and outcome of the disease. The aim of this study is to define the prognostic value of the content of estrogen receptor (ER), progesterone receptor (PgR), and amplification of HER-2 / neu oncoprotein by studying 3 and 5-year overall and relapse-free survival in 470 patients with primary operable and 280 patients with locally–advanced breast cancer. Materials and methods: Study results of 3 and 5-year overall and relapse-free survival, depending on the content of RE, PgR in primary operable patients showed that ER positive (+) and PgR (+) survival was 100 (96.2%) and 97.3 (94.6%), for ER negative (-) and PgR (-) - 69.2 (60.3%) and 65.4 (57.7%), for ER positive (+) and negative PgR (-) 87.4 (80.1%) and 81.5 (79.3%), for ER negative (-) and positive PgR (+) - 97.4 (93.4%) and 90.4 (88.5%), respectively. Survival results depended also on the level of HER-2 / neu expression. In patients with HER-2 / neu negative the survival rates were as follows: 98.6 (94.7%) and 96.2 (92.3%). In group of patients with the level of HER-2 / neu (2+) expression these figures were: 45.3 (44.3%) and 45.1 (40.2%), and in group of patients with the level of HER-2 / neu (3+) expression - 41.2 (33.1%) and 34.3 (29.4%). The combination of ER negative (-), PgR (-), HER-2 / neu (-) they were 27.2 (25.4%) and 19.5 (15.3%), respectively. In patients with locally-advanced breast cancer the results of 3 and 5-year OS and RFS for ER (+) and PgR (+) were 76.3 (69.3%) and 62.2 (61.4%), for ER (-) and RP (-) 29.1 (23.7%) and 18.3 (12.6%), for ER (+) and PgR (-) 61.2 (47.2%) and 39.4 (25.6%), for ER (-) and PgR (+) 54.3 (43.1%) and 41.3 (18.3%), respectively. The level of HER-2 / neu expression also affected the survival results. Therefore, in HER-2/ neu negative patients the survival rate was 74.1 (67.6%) and 65.1 (57.3%), with the level of expression (2+) 20.4 (14.2%) and 8.6 (6.4%), with the level of expression (3+) 6.2 (3.1%) and 1.2 (1.5%), respectively. The combination for ER, PgR, HER-2 / neu negative was 22.1 (14.3%) and 8.4 (1.2%). Conclusion: Thus, the presence of steroid hormone receptors in breast tumor tissues at primary operable and locally- advanced process as the lack of HER-2/neu oncoprotein correlates with the highest rates of 3- and 5-year overall and relapse-free survival. The absence of steroid hormone receptors as well as of HER-2/neu overexpression in malignant breast tissues significantly degrades the 3- and 5-year overall and relapse-free survival. Tumors with ER, PgR and HER-2/neu negative have the most unfavorable prognostics.

Keywords: breast cancer, estrogen receptor, oncoprotein, progesterone receptor

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7457 Wave of Islamic Fintech: Revolutionizing Malaysia's Islamic Banking and Finance Regulatory Landscape

Authors: Ho Wen Hui, Azwina Wati Abdull Manaf, Asfarina Kartika Mohd Shakri

Abstract:

The global trend of Fintech had taken the Malaysian shore by storm in recent years, thus making the studies and observations of its impacts more critical than ever. Additionally, Fintech has grown to become an unavoidable subject in the Islamic Banking and Finance (IBF) industry. In relation to that, this paper seeks to analyze the development of Fintech parallel with the IBF industry and its connection to Islamic economics. While the scarcity of studies on this area is apparent, it is found that there is a need to regulate the development of the Fintech Industry and its effects while analyzing the ramifications and positive effects of Fintech towards parties involved in IBF industry. This paper objectively studies the phenomenon of Islamic Fintech around the world as a whole as well as more specifically in Malaysia. The paper will then explore on the existing regulatory instruments in Malaysia, study their boundaries as well as limitations and contribute on possible reform to regulate Islamic Fintech in this jurisdiction. It is aimed that this paper will prompt and encourage more thorough studies to be conducted on the topic of Fintech which would subsequently contribute to a positive growth of the IBF industry worldwide.

Keywords: financial technology, FinTech, Islamic banking & finance, regulation

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7456 Synthesis and Antibacterial Evaluation of Natural Bioactive 3,4-DihydroisocoumarinAnalogues

Authors: Hummera Rafique, Aamer Saeed

Abstract:

Synthesis of structural analogues of various well known bioactive natural 3,4-dihydroisocoumarins viz. Scorzocreticin, Annulatomarin, Montroumarin, and Thunberginol B, have been carried out starting from 3,5-dimethoxy-4-methylphenyl acetic acid. 3,5-Dimethoxy-4-methylphenyl acetic acid was then condensed with various aryl acid chlorides (a-e) to afford the corresponding 6,8-dimethoxy-7-methyl-3-aryl isocoumarins (5a-e). The alkaline hydrolysis of isocoumarins yields keto-acids (3a-e), which were then reduced to hydroxyacids, followed by cyclodehydration with acetic anhydride furnish corresponding 3,4-dihydroisocoumarins (7a-e). Finally, demethylation of 3,4-dihydroisocoumarins was carried out to afford 6,8-dihydroxy-7-methyl-3-aryl-3,4-dihydroisocoumarins (7a-e). Antibacterial evaluation of all the synthesized compounds were carried out against ten bacterial strains, it was concluded that isocoumarins (5a-e) and 3,4-dihydroisocoumarins (7a-e) are more active against gram positive bacteria then gram negative. However, the 6,8-dihydroxy-3,4-dihydroisocoumarin derivatives (8a-e) are more active against gram negative then gram positive.

Keywords: 3, 5-Dimethoxy-4-methylhomophthalic acid, natural 3, 4-Dihydroisocoumarin analogues, antibacterial activity, isocoumarins, demethylation

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7455 Growing Pains and Organizational Development in Growing Enterprises: Conceptual Model and Its Empirical Examination

Authors: Maciej Czarnecki

Abstract:

Even though growth is one of the most important strategic objectives for many enterprises, we know relatively little about this phenomenon. This research contributes to broaden our knowledge of managerial consequences of growth. Scales for measuring organizational development and growing pains were developed. Conceptual model of connections among growth, organizational development, growing pains, selected development factors and financial performance were examined. The research process contained literature review, 20 interviews with managers, examination of 12 raters’ opinions, pilot research and 7 point Likert scale questionnaire research on 138 Polish enterprises employing 50-249 people which increased their employment at least by 50% within last three years. Factor analysis, Pearson product-moment correlation coefficient, student’s t-test and chi-squared test were used to develop scales. High Cronbach’s alpha coefficients were obtained. The verification of correlations among the constructs was carried out with factor correlations, multiple regressions and path analysis. When the enterprise grows, it is necessary to implement changes in its structure, management practices etc. (organizational development) to meet challenges of growing complexity. In this paper, organizational development was defined as internal changes aiming to improve the quality of existing or to introduce new elements in the areas of processes, organizational structure and culture, operational and management systems. Thus; H1: Growth has positive effects on organizational development. The main thesis of the research is that if organizational development does not catch up with growing complexity of growing enterprise, growing pains will arise (lower work comfort, conflicts, lack of control etc.). They will exert a negative influence on the financial performance and may result in serious organizational crisis or even bankruptcy. Thus; H2: Growth has positive effects on growing pains, H3: Organizational development has negative effects on growing pains, H4: Growing pains have negative effects on financial performance, H5: Organizational development has positive effects on financial performance. Scholars considered long lists of factors having potential influence on organizational development. The development of comprehensive model taking into account all possible variables may be beyond the capacity of any researcher or even statistical software used. After literature review, it was decided to increase the level of abstraction and to include following constructs in the conceptual model: organizational learning (OL), positive organization (PO) and high performance factors (HPF). H1a/b/c: OL/PO/HPF has positive effect on organizational development, H2a/b/c: OL/PO/HPF has negative effect on growing pains. The results of hypothesis testing: H1: partly supported, H1a/b/c: supported/not supported/supported, H2: not supported, H2a/b/c: not supported/partly supported/not supported, H3: supported, H4: partly supported, H5: supported. The research seems to be of a great value for both scholars and practitioners. It proved that OL and HPO matter for organizational development. Scales for measuring organizational development and growing pains were developed. Its main finding, though, is that organizational development is a good way of improving financial performance.

Keywords: organizational development, growth, growing pains, financial performance

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7454 The Relationship between the Feeling of Distributive Justice and National Identity of the Youth

Authors: Leila Batmany

Abstract:

This research studies the relationship between the feeling of distributive justice and national identity of the youth. The present analysis intends to experimentally investigate the various dimensions of the justice feeling and its effect on the national identity components. The study has taken justice into consideration from four different points of view on the basis of availability of valuable social sources such as power, wealth, knowledge and status in the political, economic, and cultural and status justice respectively. Furthermore, the national identity has been considered as the feeling of honour, attachment and commitment towards national society and its seven components i.e. history, language, culture, political system, religion, geographical territory and society. The 'field study' has been used as the method for the research with the individual as unit, taking 368 young between the age of 18 and 29 living in Tehran, chosen randomly according to Cochran formula. The individual samples have been randomly chosen among five districts in north, south, west, east, and centre of Tehran, based on the multistage cluster sampling. The data collection has been performed with the use of questionnaire and interview. The most important results are as follows: i) The feeling of economic justice is the weakest one among the youth. ii) The strongest and the weakest dimensions of the national identity are, respectively, the historical and the social dimension. iii) There is a positive and meaningful relationship between the feeling political and statues justice and then national identity, whereas no meaningful relationship exists between the economic and cultural justice and the national identity. iv) There is a positive and meaningful relationship between the feeling of justice in all dimensions and legitimacy of the political system. There is also such a relationship between the legitimacy of the political system and national identity. v) Generally, there is a positive and meaningful relationship between the feeling of distributive justice and national identity among the youth. vi) It is through the legitimacy of the political system that justice feeling can have an influence on the national identity.

Keywords: distributive justice, national identity, legitimacy of political system, Cochran formula, multistage cluster sampling

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7453 Maintenance of Non-Crop Plants Reduces Insect Pest Population in Tropical Chili Pepper Agroecosystems

Authors: Madelaine Venzon, Dany S. S. L. Amaral, André L. Perez, Natália S. Diaz, Juliana A. Martinez Chiguachi, Maira C. M. Fonseca, James D. Harwood, Angelo Pallini

Abstract:

Integrating strategies of sustainable crop production and promoting the provisioning of ecological services on farms and within rural landscapes is a challenge for today’s agriculture. Habitat management, through increasing vegetational diversity, enhances heterogeneity in agroecosystems and has the potential to improve the recruitment of natural enemies of pests, which promotes biological control services. In tropical agroecosystems, however, there is a paucity of information pertaining to the resources provided by associated plants and their interactions with natural enemies. The maintenance of non-crop plants integrated into and/or surrounding crop fields provides the farmer with a low-investment option to enhance biological control. We carried out field experiments in chili pepper agroecosystems with small stakeholders located in the Zona da Mata, State of Minas Gerais, Brazil, from 2011 to 2015 where we assessed: (a) whether non-crop plants within and around chili pepper fields affect the diversity and abundance of aphidophagous species; (b) whether there are direct interactions between non-crop plants and aphidophagous arthropods; and (c) the importance of non-crop plant resources for survival of Coccinellidae and Chrysopidae species. Aphidophagous arthropods were dominated by Coccinellidae, Neuroptera, Syrphidae, Anthocoridae and Araneae. These natural enemies were readily observed preying on aphids, feeding on flowers or extrafloral nectaries and using plant structures for oviposition and/or protection. Aphid populations were lower on chili pepper fields associated with non-crop plants that on chili pepper monocultures. Survival of larvae and adults of different species of Coccinellidae and Chrysopidae on non-crop resources varied according to the plant species. This research provides evidence that non-crop plants in chili pepper agroecosystems can affect aphid abundance and their natural enemy abundance and survival. It is also highlighting the need for further research to fully characterize the structure and function of plant resources in these and other tropical agroecosystems. Financial support: CNPq, FAPEMIG and CAPES (Brazil).

Keywords: Conservation biological control, aphididae, Coccinellidae, Chrysopidae, plant diversification

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7452 Targeting APP IRE mRNA to Combat Amyloid -β Protein Expression in Alzheimer’s Disease

Authors: Mateen A Khan, Taj Mohammad, Md. Imtaiyaz Hassan

Abstract:

Alzheimer’s disease is characterized by the accumulation of the processing products of the amyloid beta peptide cleaved by amyloid precursor protein (APP). Iron increases the synthesis of amyloid beta peptides, which is why iron is present in Alzheimer's disease patients' amyloid plaques. Iron misregulation in the brain is linked to the overexpression of APP protein, which is directly related to amyloid-β aggregation in Alzheimer’s disease. The APP 5'-UTR region encodes a functional iron-responsive element (IRE) stem-loop that represents a potential target for modulating amyloid production. Targeted regulation of APP gene expression through the modulation of 5’-UTR sequence function represents a novel approach for the potential treatment of AD because altering APP translation can be used to improve both the protective brain iron balance and provide anti-amyloid efficacy. The molecular docking analysis of APP IRE RNA with eukaryotic translation initiation factors yields several models exhibiting substantial binding affinity. The finding revealed that the interaction involved a set of functionally active residues within the binding sites of eIF4F. Notably, APP IRE RNA and eIF4F interaction were stabilized by multiple hydrogen bonds with residues of APP IRE RNA and eIF4F. It was evident that APP IRE RNA exhibited a structural complementarity that tightly fit within binding pockets of eIF4F. The simulation studies further revealed the stability of the complexes formed between RNA and eIF4F, which is crucial for assessing the strength of these interactions and subsequent roles in the pathophysiology of Alzheimer’s disease. In addition, MD simulations would capture conformational changes in the IRE RNA and protein molecules during their interactions, illustrating the mechanism of interaction, conformational change, and unbinding events and how it may affect aggregation propensity and subsequent therapeutic implications. Our binding studies correlated well with the translation efficiency of APP mRNA. Overall, the outcome of this study suggests that the genomic modification and/or inhibiting the expression of amyloid protein by targeting APP IRE RNA can be a viable strategy to identify potential therapeutic targets for AD and subsequently be exploited for developing novel therapeutic approaches.

Keywords: Alzheimer's disease, Protein-RNA interaction analysis, molecular docking simulations, conformational dynamics, binding stability, binding kinetics, protein synthesis.

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7451 Recovery of Physical Performance in Postpartum Women: An Effective Physical Education Program

Authors: Julia A. Ermakova

Abstract:

This study aimed to investigate the efficacy of a physical rehabilitation program for postpartum women. The program was developed with the purpose of restoring physical performance in women during the postpartum period. The research employed a variety of methods, including an analysis of scientific literature, pedagogical testing and experimentation, mathematical processing of study results, and physical performance assessment using a range of tests. The program recommends refraining from abdominal exercises during the first 6-8 months following a cesarean section and avoiding exercises with weights. Instead, a feasible training regimen that gradually increases in intensity several times a week is recommended, along with moderate cardio exercises such as walking, bodyweight training, and a separate workout component that targets posture improvement. Stretching after strength training is also encouraged. The necessary equipment includes comfortable sports attire with a chest support top, mat, push-ups, resistance band, timer, and clock. The motivational aspect of the program is paramount, and the mentee's positive experience with the workout regimen includes feelings of lightness in the body, increased energy, and positive emotions. The gradual reduction of body size and weight loss due to an improved metabolism also serves as positive reinforcement. The mentee's progress can be measured through various means, including an external assessment of her form, body measurements, weight, BMI, and the presence or absence of slouching in everyday life. The findings of this study reveal that the program is effective in restoring physical performance in postpartum women. The mentee achieved weight loss and almost regained her pre-pregnancy shape while her self-esteem improved. Her waist, shoulder, and hip measurements decreased, and she displayed less slouching in her daily life. In conclusion, the developed physical rehabilitation program for postpartum women is an effective means of restoring physical performance. It is crucial to follow the recommended training regimen and equipment to avoid limitations and ensure safety during the postpartum period. The motivational component of the program is also fundamental in encouraging positive reinforcement and improving self-esteem.

Keywords: physical rehabilitation, postpartum, methodology, postpartum recovery, rehabilitation

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7450 Potential Serological Biomarker for Early Detection of Pregnancy in Cows

Authors: Shveta Bathla, Preeti Rawat, Sudarshan Kumar, Rubina Baithalu, Jogender Singh Rana, Tushar Kumar Mohanty, Ashok Kumar Mohanty

Abstract:

Pregnancy is a complex process which includes series of events such as fertilization, formation of blastocyst, implantation of embryo, placental formation and development of fetus. The success of these events depends on various interactions which are synchronized by endocrine interaction between a receptive dam and competent embryo. These interactions lead to change in expression of hormones and proteins. But till date no protein biomarker is available which can be used to detect successful completion of these events. We employed quantitative proteomics approach to develop putative serological biomarker which has diagnostic applicability for early detection of pregnancy in cows. For this study, sera were collected from control (non-pregnant, n=6) and pregnant animals on successive days of pregnancy (7, 19, 45, n=6). The sera were subjected to depletion for removal of albumin using Norgen depletion kit. The tryptic peptides were labeled with iTRAQ. The peptides were pooled and fractionated using bRPLC over 80 min gradient. Then 12 fractions were injected to nLC for identification and quantitation in DDA mode using ESI. Identification using Mascot search revealed 2056 proteins out of which 352 proteins were differentially expressed. Twenty proteins were upregulated and twelve proteins were down-regulated with fold change > 1.5 and < 0.6 respectively (p < 0.05). The gene ontology studies of DEPs using Panther software revealed that majority of proteins are actively involved in catalytic activities, binding and enzyme regulatory activities. The DEP'S such as NF2, MAPK, GRIPI, UGT1A1, PARP, CD68 were further subjected to pathway analysis using KEGG and Cytoscape plugin Cluego that showed involvement of proteins in successful implantation, maintenance of pluripotency, regulation of luteal function, differentiation of endometrial macrophages, protection from oxidative stress and developmental pathways such as Hippo. Further efforts are continuing for targeted proteomics, western blot to validate potential biomarkers and development of diagnostic kit for early pregnancy diagnosis in cows.

Keywords: bRPLC, Cluego, ESI, iTRAQ, KEGG, Panther

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7449 A Numerical Investigation of Segmental Lining Joints Interactions in Tunnels

Authors: M. H. Ahmadi, A. Mortazavi, H. Zarei

Abstract:

Several authors have described the main mechanism of formation of cracks in the segment lining during the construction of tunnels with tunnel boring machines. A comprehensive analysis of segmental lining joints may help to guarantee a safe construction during Tunneling and serviceable stages. The most frequent types of segment damage are caused by a condition of uneven segment matching due to contact deficiencies. This paper investigated the interaction mechanism of precast concrete lining joints in tunnels. The Discrete Element Method (DEM) was used to analyze a typical segmental lining model consisting of six segment rings. In the analyses, typical segmental lining design parameters of the Ghomrood water conveyance tunnel, Iran were employed in the study. In the conducted analysis, the worst-case scenario of loading faced during the boring of Ghomrood tunnel was considered. This was associated with the existence of a crushed zone dipping at 75 degree at the location of the key segment. In the analysis, moreover, the effect of changes in horizontal stress ratio on the loads on the segment was assessed. The boundary condition associated with K (ratio of the horizontal to the vertical stress) values of 0.5, 1, 1.5 and 2 were applied to the model and separate analysis was conducted for each case. Important parameters such as stress, moments, and displacements were measured at joint locations and the surrounding rock. Accordingly, the segment joint interactions were assessed and analyzed. Moreover, rock mass properties of the Ghomrood in Ghom were adopted. In this study, the load acting on segments joints are included a crushed zone stratum force that intersect tunnel with 75 slopes in the location of the key segment, gravity force of segments and earth pressures. A numerical investigation was used for different coefficients of stress concentration of 0.5, 1, 1.5, 2 and different geological conditions of saturated crushed zone under the critical scenario. The numerical results also demonstrate that maximum bending moments in longitudinal joints occurred for crushed zone with the weaken strengths (Sandstone). Besides that, increasing the load in segment-stratum interfaces affected radial stress in longitudinal joints and finally the opening of joints occurred.

Keywords: joint, interface, segment, contact

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7448 Exploring Penicillin Resistance in Gonococcal Penicillin Binding Protein-2: Molecular Docking and Ligand Interaction Analysis

Authors: Sinethemba Yakobi, Lindiwe Zuma, Ofentse Pooe

Abstract:

Gonococcal infections present a notable public health issue, and the major approach for treatment involves using β-lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in Neisseria gonorrhoeae. This study examines the influence of flavonoids, namely rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research clarifies the structural effects of particular mutations, such as inserting an aspartate residue at position 345 (Asp-345a) in the PBP2 protein. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely P551S and F504L, significantly impact the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasizing its exceptional binding affinity and potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin's exceptional antioxidant effects and strong affinity for the substrate binding site. The study's wider ramifications pertain to the pressing requirement for antiviral treatments in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in N. gonorrhoeae. Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant N. gonorrhoeae bacteria. The verified simulation outcomes establish a basis for creating potent inhibitors and medicinal therapies to combat infectious illnesses.

Keywords: phytochemicals, penicillin-binding protein 2, gonococcal infection, ligand-protein interaction, binding energy, neisseria gonorrhoeae FA19, neisseria gonorrhoeae FA6140, flavonoids

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7447 Effect of Nano-Copper Oxide Synthesized by Solution-Based Chemical Precipitation Method on Antibacterial Polyester Nanocopper Oxide Composite

Authors: Jordy Herfandi, Faris Naufal, Anne Zulfia Syahrial

Abstract:

Antibacterial materials have become future textile materials due to the escalation of people’s awareness regarding the importance of maintaining health. Textile materials with antibacterial properties are examples in application which has positive results in various aspects. In this research polyester nano-copper oxide composite with nanoparticle is synthesized by solution-based chemical precipitation method from Cu(NO3)2 solution. Parameters such as precursor concentration is varied to determine which composition would result in effective properties of antibacterial composite. The antibacterial property is observed using disk diffusion method and SEM observation is conducted on each specimen. The composites produced are able to inhibit the growth of both positive gram bacteria (i.e. S. aureus) and negative gram bacteria (i.e. E. coli), thus, highly capable of helping to prevent the spread of disease.

Keywords: copper oxide nanoparticle, antibacterial, solution-based chemical precipitation, polyester composite

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7446 Organizational Learning, Job Satisfaction and Work Performance among Nurses

Authors: Rafia Rafique, Arifa Khadim

Abstract:

This research investigates the moderating role of job satisfaction between organizational learning and work performance among nurses. Correlation research design was used. Non-probability purposive sampling technique was utilized to recruit a sample of 110 nurses from public hospitals situated in the city of Lahore. The construct of organizational learning was measured using subscale of Integrated Scale for Measuring Organizational Learning. Job satisfaction was measured with the help of Job Satisfaction Survey. Performance of employees (task performance, contextual performance and counterproductive work behavior) was assessed by Individual Work Performance Questionnaire. Job satisfaction negatively moderates the relationship between organizational learning and counterproductive work behavior. Education has a significant positive relationship with organizational learning. Age, current hospital experience, marital satisfaction and salary of the nurses have positive relationship while number of children has significant negative relationship with counterproductive work behavior. These outcomes can be insightful in understanding the dynamics involved in work performance. Based on the result of this study relevant solutions can be proposed to improve the work performance of nurses.

Keywords: counterproductive work behavior, nurses, organizational learning, work performance

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7445 Investors' Ratio Analysis and the Profitability of Listed Firms: Evidence from Nigeria

Authors: Abisola Akinola, Akinsulere Femi

Abstract:

The stock market has continually been a source of economic development in most developing countries. This study examined the relationship between investors’ ratio analysis and profitability of quoted companies in Nigeria using secondary data obtained from the annual reports of forty-two (42) companies. The study employed the multiple regression technique to analyze the relationship between investors’ ratio analysis (measured by dividend per share and earning per share) and profitability (measured by the return on equity). The results from the analysis show that investors’ ratio analysis, when measured by earnings per share, have a positive and significant impact on profitability. However, the study noted that investors’ ratio analysis, when measured by dividend per share, tend to have a positive impact on profitability but it is statistically insignificant. By implication, investors and other stakeholders that are interested in investing in stocks can predict the earning capacity of listed firms in the stock market.

Keywords: dividend per share, earnings per share, profitability, return on equity

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7444 LncRNA-miRNA-mRNA Networks Associated with BCR-ABL T315I Mutation in Chronic Myeloid Leukemia

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

Abstract:

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

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

Procedia PDF Downloads 146