Search results for: gene bank

Authors: E. Cenderelli, E. Bruno, G. Iacoviello, A. Lazzini

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The financial sector is exposed to the risk of cyber-attacks like any other industrial sector. Furthermore, the topic of CybeRisk (cyber risk) has become particularly relevant given that Information Technology (IT) attacks have increased drastically in recent years, and cannot be stopped by single organizations requiring a response at international and national level. IT risk is never a matter purely for the IT manager, although he clearly plays a key role. A bank's risk management function requires a thorough understanding of the evolving risks as well as the tools and practical techniques available to address them. Upon the request of European and national legislation regarding CybeRisk in the financial system, banks are therefore called upon to strengthen the operational model for CybeRisk management. This will require an important change with a more intense collaboration with the structures that deal with information security for the development of an ad hoc system for the evaluation and control of this type of risk. The aim of the work is to propose a framework for the management and control of CybeRisk that will bridge the gap in the literature regarding the understanding and consideration of CybeRisk as an integral part of business management. The IT function has a strong relevance in the management of CybeRisk, which is perceived mainly as operational risk, but with a positive tendency on the part of risk management to the identification of CybeRisk assessment methods that are increasingly complete, quantitative and able to better describe the possible impacts on the business. The paper provides answers to the research questions: Is it possible to define a CybeRisk governance structure able to support the comparison between risk and security? How can the relationships between IT assets be integrated into a cyberisk assessment framework to guarantee a system of protection and risks control? From a methodological point of view, this research uses a case study approach. The choice of “Monte dei Paschi di Siena” was determined by the specific features of one of Italy’s biggest lenders. It is chosen to use an intensive research strategy: an in-depth study of reality. The case study methodology is an empirical approach to explore a complex and current phenomenon that develops over time. The use of cases has also the advantage of allowing the deepening of aspects concerning the "how" and "why" of contemporary events, on which the scholar has little control. The research bases on quantitative data and qualitative information obtained through semi-structured interviews of an open-ended nature and questionnaires to directors, members of the audit committee, risk, IT and compliance managers, and those responsible for internal audit function and anti-money laundering. The added value of the paper can be seen in the development of a framework based on a mapping of IT assets from which it is possible to identify their relationships for purposes of a more effective management and control of cyber risk.

Keywords: bank, CybeRisk, information technology, risk management

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Authors: Laabidi Mounira, Zayani Rafk, Bouallegue Ridha

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Filter Bank Multicarrier with Offset Quadrature Amplitude Modulation (FBMC/OQAM) is presently known as a sustainable alternative to conventional Orthogonal Frequency Division Multiplexing (OFDM) for signal transmission over multi-path fading channels. Like all multicarrier systems, FBMC/OQAM suffers from high Peak to Average Power Ratio (PAPR). Due to the symbol overlap inherent in the FBMC/OQAM system, the direct application of conventional OFDM PAPR reduction scheme is far from being effective. This paper suggests a novel scheme termed Multi-Blocks Selective Mapping (MB-SLM) whose simulation results show that its performance in terms of PAPR reduction is almost identical to that of OFDM system.

Keywords: FBMC/OQAM, multi-blocks, OFDM, PAPR, SLM

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Authors: Huma Khan, Faiza Akhtar

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The present study investigates the effects of burnout toward job performance and job satisfaction with the moderating role of hope and self-efficacy. Findings from 310 frontline employees of Pakistani commercial banks (Lahore, Karachi & Islamabad) disclosed burnout has negative significant effects on job performance and job satisfaction. Simple random sampling technique was used to collect data and inferential statistics were applied to analyzed the data. However, results disclosed no moderation effect of hope on burnout, job performance or with job satisfaction. Moreover, Data significantly supported the moderation effect of self-efficacy. Study further shed light on the development of psychological capital. Importance of the implication of the current finding is discussed.

Keywords: burnout, hope, job performance, job satisfaction, psychological capital, self-efficacy

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Authors: Nuha Mansour Alhazmi, Magda Mohamed Aly, Fardus M. Bokhari, Ahmed Bahieldin, Sherif Edris

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Out of 30 fungal isolates, 2 new isolates were proven to degrade poly-β-hydroxybutyrate (PHB). Enzyme assay for these isolates indicated the optimal environmental conditions required for depolymerase enzyme to induce the highest level of biopolymer degradation. The two isolates were basically characterized at the morphological level as Trichoderma asperellum (isolate S1), and Aspergillus fumigates (isolate S2) using standard approaches. The aim of the present study was to characterize these two isolates at the molecular level based on the highly diverged rRNA gene(s). Within this gene, two domains of the ribosome large subunit (LSU) namely internal transcribed spacer (ITS) and 26S were utilized in the analysis. The first domain comprises the ITS1/5.8S/ITS2 regions ( > 500 bp), while the second domain comprises the D1/D2/D3 regions ( > 1200 bp). Sanger sequencing was conducted at Macrogen (Inc.) for the two isolates using primers ITS1/ITS4 for the first domain, while primers LROR/LR7 for the second domain. Sizes of the first domain ranged between 594-602 bp for S1 isolate and 581-594 bp for S2 isolate, while those of the second domain ranged between 1228-1238 bp for S1 isolate and 1156-1291 for S2 isolate. BLAST analysis indicated 99% identities of the first domain of S1 isolate with T. asperellum isolates XP22 (ID: KX664456.1), CTCCSJ-G-HB40564 (ID: KY750349.1), CTCCSJ-F-ZY40590 (ID: KY750362.1) and TV (ID: KU341015.1). BLAST of the first domain of S2 isolate indicated 100% identities with A. fumigatus isolate YNCA0338 (ID: KP068684.1) and strain MEF-Cr-6 (ID: KU597198.1), while 99% identities with A. fumigatus isolate CCA101 (ID: KT877346.1) and strain CD1621 (ID: JX092088.1). Large numbers of other T. asperellum and A. fumigatus isolates and strains showed high level of identities with S1 and S2 isolates, respectively, based on the diversity of the first domain. BLAST of the second domain of S1 isolate indicated 99 and 100% identities with only two strains of T. asperellum namely TR 3 (ID: HM466685.1) and G (ID: KF723005.1), respectively. However, other T. species (ex., atroviride, hamatum, deliquescens, harzianum, etc.) also showed high level of identities. BLAST of the second domain of S2 isolate indicated 100% identities with A. fumigatus isolate YNCA0338 (ID: KP068684.1) and strain MEF-Cr-6 (ID: KU597198.1), while 99% identities with A. fumigatus isolate CCA101 (ID: KT877346.1) and strain CD1621 (ID: JX092088.1). Large numbers of other A. fumigatus isolates and strains showed high level of identities with S2 isolate. Overall, the results of molecular characterization based on rRNA diversity for the two isolates of T. asperellum and A. fumigatus matched those obtained by morphological characterization. In addition, ITS domain proved to be more sensitive than 26S domain in diversity profiling of fungi at the species level.

Keywords: Aspergillus fumigates, Trichoderma asperellum, PHB, degradation, BLAST, ITS, 26S, rRNA

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Authors: Suhartono Suhartono

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Issue of cost efficiency is then becoming pivotal point because public expect cost of banking operation reducing and benefited of consumers. This study examines the determinants of cost efficiency of banks operating in 8 member countries of the Association of Southeast Asian Nations (ASEAN). This study uses economics theory approach to examine the existence of economies of scale in the ASEAN Banking market especially on its impact on cost efficiency. We apply concept of average cost (AC) as a proxy for the cost efficiency. We find that economies of scale is existing in the banking market indicating scale and scope economies should be considered in the industrial policy. The stronger capital position is also positive to efficiency means stronger capitalized banks are more efficient. Bank that remunerates better tend to be more efficient as result economic capital effect.

Keywords: cost efficiency, ASEAN, economies of scale, issue of cost

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Authors: Yazhi Huang, Jing Yang, Dingge Ying, Yan Zhang, Vorasuk Shotelersuk, Nattiya Hirankarn, Pak Chung Sham, Yu Lung Lau, Wanling Yang

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Human leukocyte antigen (HLA) typing from next generation sequencing (NGS) data has the potential for applications in clinical laboratories and population genetic studies. Here we introduce a novel technique for HLA typing from NGS data based on read-mapping using a comprehensive reference panel containing all known HLA alleles and de novo assembly of the gene-specific short reads. An accurate HLA typing at high-digit resolution was achieved when it was tested on publicly available NGS data, outperforming other newly-developed tools such as HLAminer and PHLAT.

Keywords: human leukocyte antigens, next generation sequencing, whole exome sequencing, HLA typing

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Authors: M. Bhattarai, B. B. Rana, M. Kamimukai, I. Takamure, T. Kawano, M. Murai

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The sd1-d allele at the sd1 locus on chromosome 1, originating from Taiwanese variety Dee-geo-woo-gen, has been playing important role for developing short-culm and lodging-resistant indica varieties such as IR36 in rice. The dominant allele SD1 for long culm at the locus is differentiated into SD1-in and SD1-ja which are harbored in indica and japonica subspecies’s, respectively. The sd1-d of an indica variety IR36 was substituted with SD1-in or SD1-ja by recurrent backcrosses of 17 times with IR36, and two isogenic tall lines regarding the respective dominant alleles were developed by using an indica variety IR5867 and a japonica one ‘Koshihikari’ as donors, which were denoted by '5867-36' and 'Koshi-36', respectively. The present study was conducted to examine the effect of sd1-d on yield and related traits as compared with SD1-in and SD1-ja, by using the two isogenic tall lines. Seedlings of IR36 and the two isogenic lines were transplanted on an experimental field of Kochi University, by the planting distance of 30 cm × 15 cm with two seedlings per hill, on May 3, 2017. Chemical fertilizers were supplied by basal application and top-dressing at a rate of 8.00, 6.57 and 7.52 g/m², respectively, for N, P₂O₅ and K₂O in total. Yield, yield components, and other traits were measured. Culm length (cm) was in the order of 5867-36 (101.9) > Koshi-36 (80.1) > IR36 (60.0), where '>' indicates statistically significant difference at the 5% level. Accordingly, sd1-d reduced culm by 41.9 and 20.1 cm, compared with SD1-in and SD1-ja, respectively, and the effect of elongating culm was higher in the former allele than in the latter one. Total brown rice yield (g/m²), including unripened grains, was in the order of IR36 (611) ≧ 5867-36 (586) ≧ Koshi-36 (572), indicating non-significant differences among them. Yield-1.5mm sieve (g/m²) was in the order of IR36 (596) ≧ 5867-36 (575) ≧ Koshi-36 (558). Spikelet number per panicle was in the order of 5867-36 (89.2) ≧ IR36 (84.7) ≧ Koshi-36 (79.8), and 5867-36 > Koshi-36. Panicle number per m² was in the order of IR36 (428) ≧ Koshi-36 (403) ≧ 5867-36 (353), and IR36 > 5867-36, suggesting that sd1-d increased number of panicles compared with SD1-in. Ripened-grain percentage-1.5mm sieve was in the order of Koshi-36 (86.0) ≧ 5867-36 (85.0) ≧ IR36 (82.7), and Koshi-36 > IR36. Thousand brown-rice-grain weight-1.5mm sieve (g) was in the order of 5867-36 (21.5) > Koshi-36 (20.2) ≧ IR36 (19.9). Total dry weight at maturity (g/m²) was in the order of 5867-36 (1404 ) ≧ IR36 (1310) ≧ Kosihi-36 (1290). Harvest index of total brown rice (%) was in the order of IR36 (39.6) > Koshi-36 (37.7) > 5867-36 (35.5). Hence, sd1-d did not exert significant effect on yield in indica genetic background. However, lodging was observed from the late stage of maturity in 5867-36 and Koshi-36, particularly in the former, which was principally due to their long culms. Consequently, sd1-d enables higher yield with higher fertilizer application, by enhancing lodging resistance, particularly in indica subspecies.

Keywords: rice, dwarfing gene, sd1-d, SD1-in, SD1-ja, yield

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Authors: Deden Misbahudin Muayyad, Lavlimatria Esya

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Up to the month of June 2015, Indonesia has 12 Islamic Commercial Banks, 22 Islamic Business Unit, 327 offices in 33 provinces. The initial purpose of the establishment of Islamic financial institutions is to achieve and the welfare of the people in this world and in the hereafter. To realize these goals, the Islamic financial institutions in every kind of aspect of product development and in terms of operations should be based on maqashid sharia, namely keeping the faith, keep the soul, keep the sense, maintain the property, keeping the offspring. To see whether Islamic banking grounded in maqasid sharia, the Islamic banking performance measurements based on the principles of maqasid sharia. Banking performance measurement is not only focusing on profit and other financial measures, but put other values of banks reflects the size of the benefit of non-profit in accordance with the bank's objectives. The measurement using the measurement of financial performance called maqasid sharia index. Maqasid syariah index is a model of Islamic banking performance measurement in accordance with the objectives and characteristics of Islamic banking. Maqasid syariah index was developed based on three main factors, namely the education of individuals, the creation of justice, the achievement of well-being, where the three factors were in accordance with the common goal of maqasid sharia is achieving prosperity and avoid evil. Maqasid syariah index shows that maqasid sharia approach can be a strategic alternative approach to describe how good the performance of the banking system and it can be implemented in the comprehensive policy strategy. This study uses a model of performance measurement framework based on maqasid syariah, in addition to financial performance measures that already exist. Methods to develop the idea of a performance measurement framework of Islamic banking by maqasid sharia is the Sekaran method. Operationally, the methods have now able to describe the elements that will be measured by this study. This is done by observing the behavior of the dimensions illustrated through a concept that has been set. These dimensions translate into derivative elements that can be observed and more scalable, so it can establish measurement indices. This research is descriptive quantitative. Techniques are being made to collect data in this paper is by using purposive sampling method, with 12 Islamic Commercial Banks that qualify as research samples. The financial data taken at 12 banks was sourced from the annual financial statements the period 2008 to 2012 with consideration of the database and ease of access to data. The ratio measured in this study only 7 ratio used in determining the performance of Islamic banking, namely: four ratio refers to the sharia objectives related to education. three ratio while again referring to sharia objectives related to the achievement of welfare. While other ratios associated with justice can not be used in this study because of the limited data used. Total overall calculation of performance indicators and performance ratios on each goal for each bank describes the maqasid syariah index.

Keywords: Islamic banking, Maslahah, maqashid syariah, maqashid syariah index

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Authors: M. Sai Veerendra

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Today, money laundering (ML) poses a serious threat not only to financial institutions but also to the nation. This criminal activity is becoming more and more sophisticated and seems to have moved from the cliché of drug trafficking to financing terrorism and surely not forgetting personal gain. Most of the financial institutions internationally have been implementing anti-money laundering solutions (AML) to fight investment fraud activities. However, traditional investigative techniques consume numerous man-hours. Recently, data mining approaches have been developed and are considered as well-suited techniques for detecting ML activities. Within the scope of a collaboration project on developing a new data mining solution for AML Units in an international investment bank in Ireland, we survey recent data mining approaches for AML. In this paper, we present not only these approaches but also give an overview on the important factors in building data mining solutions for AML activities.

Keywords: data mining, clustering, money laundering, anti-money laundering solutions

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Authors: Alison L. Miles

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Almost all major financial institutions in the world suffered losses due to the financial crisis of 2007, but the extent varied widely. The causes of the crash of 2007 are well documented and predominately focus on the role and complexity of the financial markets. The dominant theme of the literature suggests the causes of the crash were a combination of globalization, financial sector innovation, moribund regulation and short termism. While these arguments are undoubtedly true, they do not tell the whole story. A key weakness in the current analysis is the lack of consideration of those leading the banks pre and during times of crisis. This purpose of this study is to examine the possible link between the leadership styles and characteristics of the CEO, CFO and chairman and the financial institutions that failed or needed recapitalization. As such, it contributes to the literature and debate on international financial crises and systemic risk and also to the debate on risk management and regulatory reform in the banking sector. In order to first test the proposition (p1) that there are prevalent leadership characteristics or traits in financial institutions, an initial study was conducted using a sample of the top 65 largest global banks and financial institutions according to the Banker Top 1000 banks 2014. Secondary data from publically available and official documents, annual reports, treasury and parliamentary reports together with a selection of press articles and analyst meeting transcripts was collected longitudinally from the period 1998 to 2013. A computer aided key word search was used in order to identify the leadership styles and characteristics of the chairman, CEO and CFO. The results were then compared with the leadership models to form a picture of leadership in the sector during the research period. As this resulted in separate results that needed combining, SPSS data editor was used to aggregate the results across the studies using the variables ‘leadership style’ and ‘company financial performance’ together with the size of the company. In order to test the proposition (p2) that there was a prevalent leadership style in the banks that failed and the proposition (P3) that this was different to those that did not, further quantitative analysis was carried out on the leadership styles of the chair, CEO and CFO of banks that needed recapitalization, were taken over, or required government bail-out assistance during 2007-8. These included: Lehman Bros, Merrill Lynch, Royal Bank of Scotland, HBOS, Barclays, Northern Rock, Fortis and Allied Irish. The findings show that although regulatory reform has been a key mechanism of control of behavior in the banking sector, consideration of the leadership characteristics of those running the board are a key factor. They add weight to the argument that if each crisis is met with the same pattern of popular fury with the financier, increased regulation, followed by back to business as usual, the cycle of failure will always be repeated and show that through a different lens, new paradigms can be formed and future clashes avoided.

Keywords: banking, financial crisis, leadership, risk

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Authors: Oluwafunmibi Omotayo Fasanya, Augustine Kena Adjei

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Diabetic nephropathy (DN) is a major complication of diabetes, with fibrosis and propionate metabolism playing critical roles in its progression. Identifying biomarkers linked to these pathways may provide novel insights into DN diagnosis and treatment. This study aims to identify biomarkers associated with fibrosis and propionate metabolism in DN. Analyze the biological pathways and regulatory mechanisms of these biomarkers. Develop a machine learning model to predict DN-related biomarkers and validate their functional roles. Publicly available transcriptome datasets related to DN (GSE96804 and GSE104948) were obtained from the GEO database (https://www.ncbi.nlm.nih.gov/gds), and 924 propionate metabolism-related genes (PMRGs) and 656 fibrosis-related genes (FRGs) were identified. The analysis began with the extraction of DN-differentially expressed genes (DN-DEGs) and propionate metabolism-related DEGs (PM-DEGs), followed by the intersection of these with fibrosis-related genes to identify key intersected genes. Instead of relying on traditional models, we employed a combination of deep neural networks (DNNs) and ensemble methods such as Gradient Boosting Machines (GBM) and XGBoost to enhance feature selection and biomarker discovery. Recursive feature elimination (RFE) was coupled with these advanced algorithms to refine the selection of the most critical biomarkers. Functional validation was conducted using convolutional neural networks (CNN) for gene set enrichment and immunoinfiltration analysis, revealing seven significant biomarkers—SLC37A4, ACOX2, GPD1, ACE2, SLC9A3, AGT, and PLG. These biomarkers are involved in critical biological processes such as fatty acid metabolism and glomerular development, providing a mechanistic link to DN progression. Furthermore, a TF–miRNA–mRNA regulatory network was constructed using natural language processing models to identify 8 transcription factors and 60 miRNAs that regulate these biomarkers, while a drug–gene interaction network revealed potential therapeutic targets such as UROKINASE–PLG and ATENOLOL–AGT. This integrative approach, leveraging deep learning and ensemble models, not only enhances the accuracy of biomarker discovery but also offers new perspectives on DN diagnosis and treatment, specifically targeting fibrosis and propionate metabolism pathways.

Keywords: diabetic nephropathy, deep neural networks, gradient boosting machines (GBM), XGBoost

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Authors: Danielle Sandler dos Passos, Helder Coelho, Flávia Mori Sarti

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Complexity science seeks the understanding of systems adopting diverse theories from various areas. Network analysis has been gaining space and credibility, namely with the biological, social and economic systems. Significant part of the literature focuses only monolayer representations of connections among agents considering one level of their relationships, and excludes other levels of interactions, leading to simplistic results in network analysis. Therefore, this work aims to demonstrate the advantages of the use of multilayer networks for the representation and analysis of networks. For this, we analyzed an interbank network, composed of 42 banks, comparing the centrality measures of the agents (degree and PageRank) resulting from each method (monolayer x multilayer). This proved to be the most reliable and efficient the multilayer analysis for the study of the current networks and highlighted JP Morgan and Deutsche Bank as the most important banks of the analyzed network.

Keywords: complexity, interbank networks, multilayer networks, network analysis

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Authors: Eun-Young Kwon, Myung-Sook Choi, Su-Jung Cho, Ji-Young Choi, So Young Kim, Youngji Han

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Overweight and obesity have been linked to a low-grade chronic inflammatory response and an increased risk of developing metabolic syndrome including insulin resistance, type 2 diabetes mellitus and certain types of cancers. Luteolin is a dietary flavonoid with anti-inflammatory, anti-oxidant, anti-cancer and anti-diabetic properties. However, little is known about the detailed mechanism associated with the effect of luteolin on inflammation-related obesity and its complications. The aim of the present study was to reveal the anti-diabetic effect of luteolin in diet-induced obesity mice using “transcriptomics” tool. Thirty-nine male C57BL/6J mice (4-week-old) were randomly divided into 3 groups and were fed normal diet, high-fat diet (HFD, 20% fat) and HFD+0.005% (w/w) luteolin for 16 weeks. Luteolin improved insulin resistance, as measured by HOMA-IR and glucose tolerance, along with preservation action of pancreatic β-cells, compared to the HFD group. Luteoiln was significantly decreased the levels of leptin and ghrelin that play a pivotal role in energy balance, and the macrophage low-grade inflammation marker sCD163 (soluble Cd antigen 163) in plasma. Activities of hepatic anti-oxidant enzymes (catalase and glutathione peroxidase) were increased, while the levels of plasma transaminase (GOT and GPT) and oxidative damage markers (hepatic mitochondria H2O2 and TBARS) were markedly decreased by luteolin supplementation. In addition, luteolin increased oxidative capacity and fatty acid utilization by presenting decrease in enzyme activities of citrate synthase, cytochrome C oxidase and β-hydroxyacyl CoA dehydrogenase and UCP3 gene expression compared to high-fat diet. Moreover, our microarray results of muscle also revealed down-regulated gene expressions associated with TCA cycle by HFD were reversed to normal level by luteolin treatment. Taken together, our results indicate that luteolin is one of bioactive components for improving insulin resistance by increasing oxidative capacity, modulating anti-oxidant metabolism and suppressing inflammatory signaling cascades in diet-induced obese mice. These results provide possible therapeutic targets for prevention and treatment of diet-induced obesity and its complications.

Keywords: anti-oxidant metabolism, diabetes, luteolin, oxidative capacity

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Authors: Ahmad Rouhani

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Iran has several potentials for using renewable energies, so use them could significantly contribute to energy supply. The purpose of this paper is to identify the potential of the country and select the appropriate DG technologies with consideration the potential and primary energy resources in the regions. In this context, hybrid energy systems proportionate with the potential of different regions will be determined based on technical, economic, and environmental aspect. In the following, the proposed structure will be optimized in terms of size and cost. DG technologies used in this project include the photovoltaic system, wind turbine, diesel generator, and battery bank. The HOMER software is applied for choosing the appropriate structure and the optimization of system sizing. The results have been analyzed in terms of technical and economic. The performance and the cost of each project demonstrate the appropriate structure of hybrid energy system in that region.

Keywords: feasibility, hybrid energy system, Iran, renewable energy

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Authors: Debbarma Asis, Guha Chandan

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Tumor Protein-53 (P53) is one of the tumor suppressor proteins. P53 regulates the cell cycle that conserves stability by preventing genome mutation. It is named so as it runs as 53-kilodalton (kDa) protein on Polyacrylamide gel electrophoresis although the actual mass is 43.7 kDa. Experimental evidence has indicated that P53 cancer mutants loses tumor suppression activity and subsequently gain oncogenic activities to promote tumourigenesis. Tumor-specific DNA has recently been detected in the plasma of breast cancer patients. Detection of tumor-specific genetic materials in cancer patients may provide a unique and valuable tumor marker for diagnosis and prognosis. Commercially available MDA-468 breast cancer cell line was used for the proposed study.

Keywords: tumor protein (P53), cancer mutants, MDA-468, tumor suppressor gene

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Authors: Keigo Ide, Toru Maruyama, Michihiro Ito, Hiroyuki Fujimura, Yoshikatu Nakano, Shoichiro Suda, Sachiyo Aburatani, Haruko Takeyama

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Understanding environmental system is one of the important tasks. In recent years, conservation of coral environments has been focused for biodiversity issues. The damage of coral reef under environmental impacts has been observed worldwide. However, the casual relationship between damage of coral and environmental impacts has not been clearly understood. On the other hand, structure/diversity of marine bacterial community may be relatively robust under the certain strength of environmental impact. To evaluate the coral environment conditions, it is necessary to investigate relationship between marine bacterial composition in coral reef and environmental factors. In this study, the Time Scale Network Analysis was developed and applied to analyze the marine environmental data for investigating the relationship among coral, bacterial community compositions and environmental factors. Seawater samples were collected fifteen times from November 2014 to May 2016 at two locations, Ishikawabaru and South of Sesoko in Sesoko Island, Okinawa. The physicochemical factors such as temperature, photosynthetic active radiation, dissolved oxygen, turbidity, pH, salinity, chlorophyll, dissolved organic matter and depth were measured at the coral reef area. Metagenome and metatranscriptome in seawater of coral reef were analyzed as the biological factors. Metagenome data was used to clarify marine bacterial community composition. In addition, functional gene composition was estimated from metatranscriptome. For speculating the relationships between physicochemical and biological factors, cross-correlation analysis was applied to time scale data. Even though cross-correlation coefficients usually include the time precedence information, it also included indirect interactions between the variables. To elucidate the direct regulations between both factors, partial correlation coefficients were combined with cross correlation. This analysis was performed against all parameters such as the bacterial composition, the functional gene composition and the physicochemical factors. As the results, time scale network analysis revealed the direct regulation of seawater temperature by photosynthetic active radiation. In addition, concentration of dissolved oxygen regulated the value of chlorophyll. Some reasonable regulatory relationships between environmental factors indicate some part of mechanisms in coral reef area.

Keywords: coral environment, marine microbiology, network analysis, omics data analysis

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Authors: Veerle Van Hoeck, Ingrid Somers, Dany Morisset

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Anti-nutritional factors such as non-starch polysaccharides (NSP) are present in viscous cereals used to feed poultry. Therefore, exogenous carbohydrases are commonly added to monogastric feed to degrade these NSP. Our hypothesis is that xylanase not only improves laying hen performance and digestibility but also induces a significant shift in microbial composition within the intestinal tract and, thereby, can cause a prebiotic effect. In this context, a better understanding of whether and how the chicken gut flora can be modulated by xylanase is needed. To do so, in the herein laying hen study, the effects of dietary supplementation of xylanase on performance, digestibility, and cecal microbiome were evaluated. A total of 96 HiSex laying hens was used in this experiment (3 diets and 16 replicates of 2 hens). Xylanase was added to the diets at concentrations of 0, 45,000 (15 g/t XygestTM HT) and 90,000 U/kg (30 g/t Xygest HT). The diets were based on wheat (~55 %), soybean, and sunflower meal. The lowest dosage, 45,000 U/kg, significantly increased average egg weight and improved feed efficiency compared to the control treatment (p < 0.05). Egg quality parameters were significantly improved in the experiment in response to the xylanase addition. For example, during the last 28 days of the trial, the 45,000 U/kg and the 90,000 U/kg treatments exhibited an increase in Haugh units and albumin heights (p < 0.05). Compared with the control, organic matter digestibility and N retention were drastically improved in the 45,000 U/kg treatment group, which implies better nutrient digestibility at this lowest recommended dosage compared to the control (p < 0.05). Furthermore, gross energy and crude fat digestibility were improved significantly for birds fed 90,000 U/kg group compared to the control. Importantly, 16S rRNA gene analysis revealed that xylanase at 45,000 U/kg dosages can exert a prebiotic effect. This conclusion was drawn based on studying the sequence variation in the 16S rRNA gene in order to characterize diverse microbial communities of the cecal content. A significant increase in beneficial bacteria (Lactobacilli spp and Enterococcus casseliflavus) was documented when adding 45,000 U/kg xylanase to the diet of laying hens. In conclusion, dietary supplementation of xylanase, even at the lowest dose of (45,000 U/kg), significantly improved laying hen performance and digestibility. Furthermore, it is generally accepted that a proper bacterial balance between the number of beneficial bacteria and pathogenic bacteria in the intestine is vital for the host. It seems that the xylanase enzyme is able to modulate the laying hen microbiome beneficially and thus exerts a prebiotic effect. This microbiome plasticity in response to the xylanase provides an attractive target for stimulating intestinal health.

Keywords: laying hen, prebiotic, XygestTM HT, xylanase

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Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

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Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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Authors: Sonia Bedhiaf-Romdhani

Abstract:

The sheep (Ovis aries) was domesticated, approximately 11,000 years ago (YBP), in the Fertile Crescent from Asian Mouflon (Ovis Orientalis). The Northern African (NA) sheep is 7,000 years old, represents a remarkable diversity of sheep populations reared under traditional and low input farming systems (LIFS) over millennia. The majority of small ruminants in developing countries are encountered in low input production systems and the resilience of local communities in rural areas is often linked to the wellbeing of small ruminants. Regardless of the rich biodiversity encountered in sheep ecotypes there are four main sheep breeds in the country with 61,6 and 35.4 percents of Barbarine (fat tail breed) and Queue Fine de l’Ouest (thin tail breed), respectively. Phoenicians introduced the Barbarine sheep from the steppes of Central Asia in the Carthaginian period, 3000 years ago. The Queue Fine de l’Ouest is a thin-tailed meat breed heavily concentrated in the Western and the central semi-arid regions. The Noire de Thibar breed, involving mutton-fine wool producing animals, has been on the verge of extinction, it’s a composite black coated sheep breed found in the northern sub-humid region because of its higher nutritional requirements and non-tolerance of the prevailing harsher condition. The D'Man breed, originated from Morocco, is mainly located in the southern oases of the extreme arid ecosystem. A genetic investigation of Tunisian sheep breeds using a genome-wide scan of approximately 50,000 SNPs was performed. Genetic analysis of relationship between breeds highlighted the genetic differentiation of Noire de Thibar breed from the other local breeds, reflecting the effect of past events of introgression of European gene pool. The Queue Fine de l’Ouest breed showed a genetic heterogeneity and was close to Barbarine. The D'Man breed shared a considerable gene flow with the thin-tailed Queue Fine de l'Ouest breed. Native small ruminants breeds, are capable to be efficiently productive if essential ingredients and coherent breeding schemes are implemented and followed. Assessing the status of genetic variability of native sheep breeds could provide important clues for research and policy makers to devise better strategies for the conservation and management of genetic resources.

Keywords: sheep, farming systems, diversity, SNPs.

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Authors: Kamal Ray, Tapati Bhattacharya

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Private use of public office for private gain could be a tentative definition of corruption and most distasteful event of corruption is that it is not there, nor that it is pervasive, but it is socially acknowledged in the global economy, especially in the developing nations. We attempted to assess the interrelationship between the Corruption perception index (CPI) and the principal components of governance indicators as per World Bank like Control of Corruption (CC), rule of law (RL), regulatory quality (RQ) and government effectiveness (GE). Our empirical investigation concentrates upon the degree of reflection of governance indicators upon the CPI in order to single out the most powerful corruption-generating indicator in the selected countries. We have collected time series data on above governance indicators such as CC, RL, RQ and GE of the selected eleven countries from the year of 1996 to 2012 from World Bank data set. The countries are USA, UK, France, Germany, Greece, China, India, Japan, Thailand, Brazil, and South Africa. Corruption Perception Index (CPI) of the countries mentioned above for the period of 1996 to 2012is also collected. Graphical method of simple line diagram against the time series data on CPI is applied for quick view for the relative positions of different trend lines of different nations. The correlation coefficient is enough to assess primarily the degree and direction of association between the variables as we get the numerical data on governance indicators of the selected countries. The tool of Granger Causality Test (1969) is taken into account for investigating causal relationships between the variables, cause and effect to speak of. We do not need to verify stationary test as length of time series is short. Linear regression is taken as a tool for quantification of a change in explained variables due to change in explanatory variable in respect of governance vis a vis corruption. A bilateral positive causal link between CPI and CC is noticed in UK, index-value of CC increases by 1.59 units as CPI increases by one unit and CPI rises by 0.39 units as CC rises by one unit, and hence it has a multiplier effect so far as reduction in corruption is concerned in UK. GE causes strongly to the reduction of corruption in UK. In France, RQ is observed to be a most powerful indicator in reducing corruption whereas it is second most powerful indicator after GE in reducing of corruption in Japan. Governance-indicator like GE plays an important role to push down the corruption in Japan. In China and India, GE is proactive as well as influencing indicator to curb corruption. The inverse relationship between RL and CPI in Thailand indicates that ongoing machineries related to RL is not complementary to the reduction of corruption. The state machineries of CC in S. Africa are highly relevant to reduce the volume of corruption. In Greece, the variations of CPI positively influence the variations of CC and the indicator like GE is effective in controlling corruption as reflected by CPI. All the governance-indicators selected so far have failed to arrest their state level corruptions in USA, Germany and Brazil.

Keywords: corruption perception index, governance indicators, granger causality test, regression

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Authors: Ummu Salma Al Azizah, Herri Mulyono, Anisa Mauliata Suryana

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The significance of corporate governance regarding to the agency problem have been transparent. This study examine the impact of corporate governance on the performance of Islamic banking in Indonesia. By using fixed effect model and added some control variable, the current study try to explore the correlation between the theoretical framework on corporate governance, such as agency theory and risk management theory. The bank performance (Return on Asset and Return on Equity) which are operational performance and financial performance. And Corporate governance based on Board size, CEO duality, Audit committee and Shariah supervisory board. The limitation of this study only focus on the Islamic banks performance from year 2015 to 2020. The study fill the gap in the literature by addressing the issue of corporate governance on Islamic banks performance in Indonesia.

Keywords: corporate governance, financial performance, islamic banks, listed companies, Indonesia

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Authors: Lillian Musila, Valerie Oundo, Daniel Erwin, Willie Sang

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Staphylococcus aureus infections are a major cause of nosocomial infections in Kenya. Methicillin resistant S. aureus (MRSA) infections are a significant burden to public health and are associated with considerable morbidity and mortality. At a hospital in Western Kenya two clusters of MRSA cases emerged within short periods of time. In this study we explored whether these clusters represented a nosocomial outbreak by characterizing the isolates using phenotypic and molecular assays and examining epidemiological data to identify possible transmission patterns. Specimens from the site of infection of the subjects were collected, cultured and S. aureus isolates identified phenotypically and confirmed by APIStaph™. MRSA were identified by cefoxitin disk screening per CLSI guidelines. MRSA were further characterized based on their antibiotic susceptibility patterns and spa gene typing. Characteristics of cases with MRSA isolates were compared with those with MSSA isolated around the same time period. Two cases of MRSA infection were identified in the two week period between 21 April and 4 May 2015. A further 2 MRSA isolates were identified on the same day on 7 September 2015. The antibiotic resistance patterns of the two MRSA isolates in the 1st cluster of cases were different suggesting that these were distinct isolates. One isolate had spa type t2029 and the other had a novel spa type. The 2 isolates were obtained from urine and an open skin wound. In the 2nd cluster of MRSA isolates, the antibiotic susceptibility patterns were similar but isolates had different spa types: one was t037 and the other a novel spa type different from the novel MRSA spa type in the first cluster. Both cases in the second cluster were admitted into the hospital but one infection was community- and the other hospital-acquired. Only one of the four MRSA cases was classified as an HAI from an infection acquired post-operatively. When compared to other S. aureus strains isolated within the same time period from the same hospital only one spa type t2029 was found in both MRSA and non-MRSA strains. None of the cases infected with MRSA in the two clusters shared any common epidemiological characteristic such as age, sex or known risk factors for MRSA such as prolonged hospitalization or institutionalization. These data suggest that the observed MRSA clusters were multi strain clusters and not an outbreak of a single strain. There was no clear relationship between the isolates by spa type suggesting that no transmission was occurring within the hospital between these cluster cases but rather that the majority of the MRSA strains were circulating in the community. There was high diversity of spa types among the MRSA strains with none of the isolates sharing spa types. Identification of disease clusters in space and time is critical for immediate infection control action and patient management. Spa gene typing is a rapid way of confirming or ruling out MRSA outbreaks so that costly interventions are applied only when necessary.

Keywords: cluster, Kenya, MRSA, spa typing

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Authors: Sabir Tehrankhan Hasanov, Mir Movsum Anar Dadashev

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The article provides a brief overview of irrigation systems and canals applied to slopes, landslide-prone, seismic areas, and swelling and collapsing soils. The contemporary construction of the canal used for irrigation, energy, and water supply purposes is described. In order to ensure the durability, longevity, and reliability of the channel, a damping mat made of cast material is created under its cover, and the top is covered with a waterproof screen. Dowels are placed on the bottom and sides of the channel, and the bottom dowel is riveted to the solid bedrock and connected with piles placed at certain distances. Drainage was placed next to the bottom dowel, an operation road was created on one side of the channel, and a berm road was created on the other side. A bathtub was built on the side of the road, and a forest-bush strip was built on its bank.

Keywords: slope, channel, landslide, collapse, swell, soil, structure

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Authors: Haytham Yassine

Abstract:

This article mainly aims to detect and understand how money laundering activities are executed by transport of cash, identifying the underlying factors and separating legitimate from illegitimate usage of cash and how it is being used. This research provides academics with additional literature and provides bank supervisors and practitioners with a better understanding of sources and uses of cash in criminal activities and how cash is used in the laundering mechanism. Data are gathered through survey in the Middle East and North Africa region and review of the available research. The results of the analysis will help distinguish the factors affecting preference for cash rather other payment instruments in the region, identify what causes the tendency to launder illegal proceeds through cash transportation and how illegal cash is being laundered and moved. On the other hand, this paper sheds the light on major cash generating criminal activities, its sources and main destinations.

Keywords: illegitimate activities, cash, money laundering, terrorism financing

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Authors: M. Acin-Albiac, P. Filannino, R. Coda, Carlo G. Rizzello, M. Gobbetti, R. Di Cagno

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Demand for smart management of large amounts of agro-food by-products has become an area of major environmental and economic importance worldwide. Brewers' spent grain (BSG), the most abundant by-product generated in the beer-brewing process, represents an example of valuable raw material and source of health-promoting compounds. To the date, the valorization of BSG as a food ingredient has been limited due to poor technological and sensory properties. Tailored bioprocessing through lactic acid bacteria (LAB) fermentation is a versatile and sustainable means for the exploitation of food industry by-products. Indigestible carbohydrates (e.g., hemicelluloses and celluloses), high phenolic content, and mostly lignin make of BSG a hostile environment for microbial survival. Hence, the selection of tailored starters is required for successful fermentation. Our study investigated the metabolic strategies of Leuconostoc pseudomesenteroides and Lactobacillus plantarum strains to exploit BSG as a food ingredient. Two distinctive BSG samples from different breweries (Italian IT- and Finish FL-BSG) were microbially and chemically characterized. Growth kinetics, organic acid profiles, and the evolution of phenolic profiles during the fermentation in two BSG model media were determined. The results were further complemented with gene expression targeting genes involved in the degradation cellulose, hemicelluloses building blocks, and the metabolism of anti-nutritional factors. Overall, the results were LAB genus dependent showing distinctive metabolic capabilities. Leuc. pseudomesenteroides DSM 20193 may degrade BSG xylans while sucrose metabolism could be furtherly exploited for extracellular polymeric substances (EPS) production to enhance BSG pro-technological properties. Although L. plantarum strains may follow the same metabolic strategies during BSG fermentation, the mode of action to pursue such strategies was strain-dependent. L. plantarum PU1 showed a great preference for β-galactans compared to strain WCFS1, while the preference for arabinose occurred at different metabolic phases. Phenolic compounds profiling highlighted a novel metabolic route for lignin metabolism. These findings will allow an improvement of understanding of how lactic acid bacteria transform BSG into economically valuable food ingredients.

Keywords: brewery by-product valorization, metabolism of plant phenolics, metabolism of lactic acid bacteria, gene expression

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Authors: Saima Akbar

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The global financial crisis severely and adversely impacted the Pakistanis’ financial setups with far-reaching consequences for its victims. This study aimed to analyze the various determinants of the banks’ financial performance in Pakistan. The stepwise multiple regression analysis and pre-post analysis were carried out in this regard by using SPSS ver 22. The study found that the assets quality is the most influential determinant of return over assets followed by bank size and solvency. Advances, liquidity, investments, and size have positive while poor assets quality and deposits have a negative impact on the return over assets. The comparison of the pre-crisis and post-crisis coefficient values of the independent variables revealed that the global financial crisis had exerted a significant impact on the relative ability of the financial performance determinants to explain variations in return over assets.

Keywords: pre-crisis, post-crisis, coefficient values, determinants

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Authors: Muhammad Haroon, LI Xiangju

Abstract:

C. communis L. is an important weed of many crop, but very little information about the adaptation strategies of C. communis L. biotypes under drought stress. We investigated five biotypes of C. communis L under drought stress to identify the adaptation mechanism. The expression of drought stress related genes (DRS1, EREB and HRB1) was up-regulated in biotypes, while in some biotypes their expression was down regulated. All five biotypes can thus regulate water balance to consume less water to maintain their status under drought stress condition. This result concluded that C. communis L. biotypes can survive longer under drought stress condition. Weed scientist should seek more effective management strategies to deal with C. communis L.

Keywords: C. communis, biotypes, drought stress, gene expression

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Authors: Angel Champion

Abstract:

Chemotherapy and radiation use an acidified approach to induce apoptosis, which only kills mature cancer cells while resulting in gene and cell damage with significant levels of toxicity in tumor-affected tissues and organs. The acid approach, where the cells exterminated are not differentiated, induces the disappearance of white blood cells from the blood. This increases susceptibility to infection in severe forms of cancer spread. However, chemotherapy and radiation cannot kill cancer stem cells that metastasize, being the leading cause of 98% of cancer fatalities. With over 12 million new cancer cases symptomatic each year, including common malignancies such as Hepatocellular Carcinoma (HCC), this study aims to assess the bioactive constituents and phytochemical composition of Taraxacum Officinale (Dandelion). This analysis enables pharmaceutical quality and potency to be applied to studies on cancer cell proliferation and apoptosis. A phytochemical screening is carried out to identify the antioxidant components of Dandelion root, stem, and flower extract. The constituents tested for are phlorotannins, carbohydrates, glycosides, saponins, flavonoids, alkaloids, sterols, triterpenes, and anthraquinone glycosides. To conserve the existing phenolic compounds, a portion of the constituent tests will be examined with an acid, alcohol, or aqueous solvent. As a result, the qualitative and quantitative variations within the Dandelion extract that measure uniform effective potency are vital to the conformity for producing medicinal products. These medicines will be constructed with a consistent, uniform composition that physicians can use to control and effectively eradicate malignant diseases safely. Taraxacum Officinale's phytochemical composition comprises a highly-graded potency due to present bioactive contents that will essentially drive out malignant disease within the human body. Its high potency rate is powerful enough to eliminate both mature cancer cells and cancer stem cells without the cell and gene damage induced by chemotherapy and radiation. Correspondingly, the high margins of cancer mortality on a global scale are mitigated. This remarkable contribution to modern therapeutics will essentially optimize the margins of natural products and their derivatives, which account for 50% of pharmaceuticals in modern therapeutics, while preventing the adverse effects of radiation and chemotherapy drugs.

Keywords: antioxidant, apoptosis, metastasize, phytochemical, proliferation, potency

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Authors: M. Sakthivel, A. Devaki, D. Balasubramanyam, P. Kumarasamy, A. Raja, R. Anilkumar, H. Gopi

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The New Zealand White breed of rabbit is one of the most commonly used, well adapted exotic breeds in India. Earlier studies were limited only to analyze the environmental factors affecting the growth and reproductive performance. In the present study, the population of the New Zealand White rabbits in a closed herd was evaluated for its genetic structure. Data on pedigree information (n=2508) for 18 years (1995-2012) were utilized for the study. Pedigree analysis and the estimates of population genetic parameters based on gene origin probabilities were performed using the software program ENDOG (version 4.8). The analysis revealed that the mean values of generation interval, coefficients of inbreeding and equivalent inbreeding were 1.489 years, 13.233 percent and 17.585 percent, respectively. The proportion of population inbred was 100 percent. The estimated mean values of average relatedness and the individual increase in inbreeding were 22.727 and 3.004 percent, respectively. The percent increase in inbreeding over generations was 1.94, 3.06 and 3.98 estimated through maximum generations, equivalent generations, and complete generations, respectively. The number of ancestors contributing the most of 50% genes (fₐ₅₀) to the gene pool of reference population was 4 which might have led to the reduction in genetic variability and increased amount of inbreeding. The extent of genetic bottleneck assessed by calculating the effective number of founders (fₑ) and the effective number of ancestors (fₐ), as expressed by the fₑ/fₐ ratio was 1.1 which is indicative of the absence of stringent bottlenecks. Up to 5th generation, 71.29 percent pedigree was complete reflecting the well-maintained pedigree records. The maximum known generations were 15 with an average of 7.9 and the average equivalent generations traced were 5.6 indicating of a fairly good depth in pedigree. The realized effective population size was 14.93 which is very critical, and with the increasing trend of inbreeding, the situation has been assessed to be worse in future. The proportion of animals with the genetic conservation index (GCI) greater than 9 was 39.10 percent which can be used as a scale to use such animals with higher GCI to maintain balanced contribution from the founders. From the study, it was evident that the herd was completely inbred with very high inbreeding coefficient and the effective population size was critical. Recommendations were made to reduce the probability of deleterious effects of inbreeding and to improve the genetic variability in the herd. The present study can help in carrying out similar studies to meet the demand for animal protein in developing countries.

Keywords: effective population size, genetic structure, pedigree analysis, rabbit genetics

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Authors: Atsuko Okazaki, Jurg Ott

Abstract:

Some genetic diseases (‘digenic traits’) are due to the interaction between two DNA variants. For example, certain forms of Retinitis Pigmentosa (a genetic form of blindness) occur in the presence of two mutant variants, one in the ROM1 gene and one in the RDS gene, while the occurrence of only one of these mutant variants leads to a completely normal phenotype. Detecting such digenic traits by genetic methods is difficult. A common approach to finding disease-causing variants is to compare 100,000s of variants between individuals with a trait (cases) and those without the trait (controls). Such genome-wide association studies (GWASs) have been very successful but hinge on genetic effects of single variants, that is, there should be a difference in allele or genotype frequencies between cases and controls at a disease-causing variant. Frequent pattern mining (FPM) methods offer an avenue at detecting digenic traits even in the absence of single-variant effects. The idea is to enumerate pairs of genotypes (genotype patterns) with each of the two genotypes originating from different variants that may be located at very different genomic positions. What is needed is for genotype patterns to be significantly more common in cases than in controls. Let Y = 2 refer to cases and Y = 1 to controls, with X denoting a specific genotype pattern. We are seeking association rules, ‘X → Y’, with high confidence, P(Y = 2|X), significantly higher than the proportion of cases, P(Y = 2) in the study. Clearly, generally available FPM methods are very suitable for detecting disease-associated genotype patterns. We use fpgrowth as the basic FPM algorithm and built a framework around it to enumerate high-frequency digenic genotype patterns and to evaluate their statistical significance by permutation analysis. Application to a published dataset on opioid dependence furnished results that could not be found with classical GWAS methodology. There were 143 cases and 153 healthy controls, each genotyped for 82 variants in eight genes of the opioid system. The aim was to find out whether any of these variants were disease-associated. The single-variant analysis did not lead to significant results. Application of our FPM implementation resulted in one significant (p < 0.01) genotype pattern with both genotypes in the pattern being heterozygous and originating from two variants on different chromosomes. This pattern occurred in 14 cases and none of the controls. Thus, the pattern seems quite specific to this form of substance abuse and is also rather predictive of disease. An algorithm called Multifactor Dimension Reduction (MDR) was developed some 20 years ago and has been in use in human genetics ever since. This and our algorithms share some similar properties, but they are also very different in other respects. The main difference seems to be that our algorithm focuses on patterns of genotypes while the main object of inference in MDR is the 3 × 3 table of genotypes at two variants.

Keywords: digenic traits, DNA variants, epistasis, statistical genetics

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