Search results for: genetic differentiation

Authors: Neda Gegar Goshe, Hossein Rassi

Abstract:

The antibacterial properties of macrolide antibiotics (such as erythromycin and tylosin) depend ultimately on the glycosylation of otherwise inactive polyketide lactones. Among the sugars commonly found in such macrolides are various 6-deoxyhexoses including the 3-dimethylamino sugars mycaminose and desosamine (4-deoxymycaminose). Some macrolides (such as tylosin) possess multiple sugar moieties, whereas others (such as erythromycin) have two sugar substituents. Streptomyces fradiae is an ideal host for development of generic polyketide-overproducing strains because it contains three of the most common precursors-malonyl-CoA, methylmalonyl-CoA and ethylmalonyl-CoA-used by modular PKS, and is a host that is amenable to genetic manipulation. As patterns of glycosylation markedly influence a macrolide's drug activity, there is considerable interest in the possibility of using combinatorial biosynthesis to generate new pairings of polyketide lactones with sugars, especially 6-deoxyhexoses. Here, we report a successful attempt to alter the aminodeoxyhexose-biosynthetic capacity of Streptomyces fradiae (a producer of tylosin) by importing genes from the erythromycin producer Saccharopolyspora erythraea. The biotransformation of erythromycin-D into the desired major component erythromycin-A involves two final enzymatic reactions, EryK-catalyzed hydroxylation at the C-12 position of the aglycone and EryG-catalyzed O methylation at the C-3 position of macrose .This engineered S. fradiae produced substantial amounts of two potentially useful macrolides that had not previously been obtained by fermentation.

Keywords: Streptomyces fradiae, eryK and eryG genes, tylosin, antibiotics

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Authors: Tan Zhang, Zhongjian Wang, Jack Xin, Zhiwen Zhang

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We aim to efficiently compute the spreading speeds of reaction-diffusion-advection (RDA) fronts in divergence-free random flows under the Kolmogorov-Petrovsky-Piskunov (KPP) nonlinearity. We study a stochastic interacting particle method (IPM) for the reduced principal eigenvalue (Lyapunov exponent) problem of an associated linear advection-diffusion operator with spatially random coefficients. The Fourier representation of the random advection field and the Feynman-Kac (FK) formula of the principal eigenvalue (Lyapunov exponent) form the foundation of our method implemented as a genetic evolution algorithm. The particles undergo advection-diffusion and mutation/selection through a fitness function originated in the FK semigroup. We analyze the convergence of the algorithm based on operator splitting and present numerical results on representative flows such as 2D cellular flow and 3D Arnold-Beltrami-Childress (ABC) flow under random perturbations. The 2D examples serve as a consistency check with semi-Lagrangian computation. The 3D results demonstrate that IPM, being mesh-free and self-adaptive, is simple to implement and efficient for computing front spreading speeds in the advection-dominated regime for high-dimensional random flows on unbounded domains where no truncation is needed.

Keywords: KPP front speeds, random flows, Feynman-Kac semigroups, interacting particle method, convergence analysis

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Authors: C. Soh, S. Muktar, C. M. Malata, J. R. Benson

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Introduction Reasons for requesting CPM include prevention of recurrence, peace of mind and moving on after breast cancer. Some women seek CPM as a delayed procedure but factors influencing this are poorly understood. Methods A retrospective analysis examined patients undergoing CPM as either an immediate or delayed procedure with or without breast reconstruction (BR) between January 2009 and December 2019. A cross-sectional survey based on validated questionnaires (5 point Likert scale) explored patients’ decision-making process in terms of timing of CPM and any BR. Results A total of 123 patients with unilateral breast cancer underwent CPM with 39 (32.5%) delayed procedures with or without BR. The response rate amongst patients receiving questionnaires (n=33) was 22/33 (66%). Within this delayed CPM cohort were three reconstructive scenarios 1) unilateral immediate BR with CPM (n=12); 2) delayed CPM with concomitant bilateral BR (n=22); 3) delayed bilateral BR after delayed CPM (n=3). Two patients had delayed CPM without BR. The most common reason for delayed CPM was to complete all cancer treatments (including radiotherapy) before surgery on the unaffected breast (score 2.91). The second reason was unavailability of genetic test results at the time of therapeutic mastectomy (score 2.64) whilst the third most cited reason was a subsequent change in family cancer history. Conclusion Factors for delayed CPM are patient-driven with few women spontaneously changing their mind having initially decided against immediate CPM for reasons also including surgical duration. CPM should be offered as a potentially delayed option with informed discussion of risks and benefits.

Keywords: Breast Cancer, CPM, Prophylactic, Rationale

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Authors: Kartik Thakore, Anna-Roza Tamas, Adam Cole

Abstract:

The world health organization (WHO) reports that by 2030 more than 23.7 million deaths annually will be caused by Cardiovascular Diseases (CVDs); with a 2008 economic impact of $3.76 T. Metabolic syndrome is a disorder of multiple metabolic risk factors strongly indicated in the development of cardiovascular diseases. Guided lifestyle intervention driven by live coaching has been shown to have a positive impact on metabolic risk factors. Individuals’ path to improved (decreased) metabolic risk factors are driven by personal motivation and personalized messages delivered by coaches and augmented by technology. Using interactions captured between 400 individuals and 3 coaches over a program period of 500 days, a preliminary model was designed. A novel real time event tracking system was created to track and classify clients based on their genetic profile, baseline questionnaires and usage of a mobile application with live coaching sessions. Classification of clients and coaches was done using a support vector machines application build on Apache Spark, Stanford Natural Language Processing Library (SNLPL) and decision-modeling.

Keywords: guided lifestyle intervention, metabolic risk factors, personal coaching, support vector machines application, Apache Spark, natural language processing

Procedia PDF Downloads 431

Authors: Neda Gegar Goshe, M. Moradi, Hossein Rassi

Abstract:

The antibacterial properties of macrolide antibiotics (such as erythromycin and tylosin) depend ultimately on the glycosylation of otherwise inactive polyketide lactones. Among the sugars commonly found in such macrolides are various 6-deoxyhexoses including the 3-dimethylamino sugars mycaminose and desosamine (4-deoxymycaminose). Some macrolides (such as tylosin) possess multiple sugar moieties, whereas others (such as erythromycin) have two sugar substituents. Streptomyces fradiae is an ideal host for development of generic polyketide-overproducing strains because it contains three of the most common precursors-malonyl-CoA, methylmalonyl-CoA and ethylmalonyl-CoA-used by modular PKS, and is a host that is amenable to genetic manipulation. As patterns of glycosylation markedly influence a macrolide's drug activity, there is considerable interest in the possibility of using combinatorial biosynthesis to generate new pairings of polyketide lactones with sugars, especially 6-deoxyhexoses. Here, we report a successful attempt to alter the aminodeoxyhexose-biosynthetic capacity of Streptomyces fradiae (a producer of tylosin) by importing genes from the erythromycin producer Saccharopolyspora erythraea. The bio transformation of erythromycin-D into the desired major component erythromycin-A involves two final enzymatic reactions, EryK-catalyzed hydroxylation at the C-12 position of the aglycone and EryG-catalyzed O methylation at the C-3 position of macrose. This engineered S. fradiae produced substantial amounts of two potentially useful macrolides that had not previously been obtained by fermentation.

Keywords: tylosin, eryK and eryG genes, streptomyces fradiae

Procedia PDF Downloads 351

Authors: Anupuma Raina, Ajay Parkash

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In forensic investigation, DNA analysis helps in the identification of a particular individual under investigation. A set of Short Tandem Repeats loci are widely used for individualization at a molecular level in forensic testing. STRs with tetrameric repeats of DNA are highly polymorphic and widely used for forensic DNA analysis. Identification of an individual became challenging for forensic examiners after Hematopoietic Stem Cell Transplantation. HSCT is a well-accepted and life-saving treatment to treat malignant and nonmalignant diseases. It involves the administration of healthy donor stem cells to replace the patient’s own unhealthy stem cells. A successful HSCT results in complete donor-derived cells in a patient’s hematopoiesis and hence have the capability to change the genetic makeup of the patient. Although an individual who has undergone HSCT and then committed a crime is a very rare situation, but not impossible. Keeping such a situation in mind, various biological samples like blood, buccal swab, and hair follicle were collected and studied after a certain interval of time after HSCT. Blood was collected from both the patient and the donor before the transplant. The DNA profile of both was analyzed using a short tandem repeat kit for autosomal chromosomes. Among all exhibits studied, only hair follicles were found to be the most suitable biological exhibit, as no donor DNA profile was observed for up to 90 days of study.

Keywords: chimerism, HSCT, STRs analysis, forensic identification

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Authors: Gabriel Michel

Abstract:

The aim of our research is to find solutions for adapting university teaching to today's students and companies. To achieve this, we have tried to change the posture and behavior of those involved in the learning situation by promoting other skills. There is a gap between the expectations and functioning of students and university teaching. At the same time, the business world needs employees who are obviously competent and proficient in technology, but who are also imaginative, flexible, able to communicate, learn on their own and work in groups. These skills are rarely developed as a goal at university. The flipped classroom has been one solution. Thanks to digital tools such as Moodle, for example, but the model behind them is still centered on teachers and classic learning scenarios: it makes course materials available without really involving them and encouraging them to cooperate. It's against this backdrop that we've conducted action research to explore the possibility of changing the way we learn (rather than teach) by changing the posture of both the classic student and the teacher. We hypothesized that a tool we developed would encourage autonomy, the possibility of progressing at one's own pace, collaboration and learning using all available resources(other students, course materials, those on the web and the teacher/facilitator). Experimentation with this tool was carried out with around thirty German and French first-year students at the Université de Lorraine in Metz (France). The projected changesin the groups' learning situations were as follows: - use the flipped classroom approach but with a few traditional presentations by the teacher (materials having been put on a server) and lots of collective case solving, - engage students in their learning by inviting them to set themselves a primary objective from the outset, e.g. “Assimilating 90% of the course”, and secondary objectives (like a to-do list) such as “create a new case study for Tuesday”, - encourage students to take control of their learning (knowing at all times where they stand and how far they still have to go), - develop cooperation: the tool should encourage group work, the search for common solutions and the exchange of the best solutions with other groups. Those who have advanced much faster than the others, or who already have expertise in a subject, can become tutors for the others. A student can also present a case study he or she has developed, for example, or share materials found on the web or produced by the group, as well as evaluating the productions of others, - etc… A questionnaire and analysis of assessment results showed that the test group made considerable progress compared with a similar control group. These results confirmed our hypotheses. Obviously, this tool is only effective if the organization of teaching is adapted and if teachers are willing to change the way they work.

Keywords: pedagogy, cooperation, university, learning environment

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Authors: Sadhana Shukla, Pushplata Singh, Nidhi Didwania

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Arbuscular mycorrhizal (AM) fungi are a highly advantageous and versatile group of fungi that significantly contribute to the formation of soil organic matter by creating a demand for plant carbon (C) and distributing it through below-ground hyphal biomass, regardless of their substantial contribution in enhancing net primary productivity and accumulating additional photosynthetic fixed C in the soil. The genetic role of AM fungi in carbon cycling is largely unexplored. In our study, we propose that AM fungi significantly interact with the soil, particularly: the provision of photosynthates by plants. We have studied the expression of AM fungi genes involved in CO₂ sequestration during host-plant interaction was investigated by qPCR studies. We selected Rhizophagus proliferus (AM fungi) and Oryza sativa (Rice) (inoculated with or without 200ppg AMF inoculums per plant) and investigated the effect of AM fungi on soil organic carbon (SOC) and rice growth under field conditions. Results thus provided faster SOC turnover, 35% increased nutrient uptake in plants and pronounced hyphal biomass of AM fungi which enhanced soil carbon storage by 15% in comparison to uninoculated plants. This study will offer a foundation for delving into various carbon-soil studies while also advancing our comprehension of the relationship between AM fungi and the sustainability of agricultural ecosystems.

Keywords: arbuscular mycorrhizal (AM) fungi, carbon sequestration, gene expression, soil health, plant development.

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Authors: Opemiposi Adegbulu

Abstract:

Conflicts of interest is an elusive, diverse and engaging subject, a cross-cutting problem of governance; all levels of governance, ranging from local to global, public to corporate or financial sectors. In all these areas, its mismanagement could lead to the distortion of decision-making processes, corrosion of trust and the weakening of administration. According to Professor Peters, an expert in the area, conflict of interest, a problem at the root of many scandals has “become a pervasive ethical concern in our professional, organisational, and political life”. Conflicts of interest corrode trust, and like in the public sector, trust is mandatory for the market, consumers/clients, shareholders and other stakeholders in the private sector. However, conflicts of interest in the private sector are distinct and must be treated in like manner when regulatory efforts are made to address them. The research looks at identifying conflicts of interest in the private sector and differentiating them from those in the public sector. The public interest is submitted as a criterion which allows for such differentiation. This is significant because it would for the use of tailor-made or sector-specific approaches to addressing this complex issue. This is conducted through extensive review of literature and theories on the definition of conflicts of interest. This study will employ theoretical, doctrinal and comparative methods. The nature of conflicts of interest in the private sector will be explored, through an analysis of the public sector where the notion of conflicts of interest appears more clearly identified, reasons, why they are of business ethics concern, will be advanced, and then, once again, looking at public sector solutions and other solutions, the study will identify ways of mitigating and managing conflicts in the private sector. An exploration of public sector conflicts of interest and solutions will be carried out because the typologies of conflicts of interest in both sectors appear very similar at the core and thus, lessons can be learnt with regards to the management of these issues in the private sector. Conflicts of interest corrode trust, and like in the public sector, trust is mandatory for the market, consumers/clients, shareholders and other stakeholders in the private sector. This research will then focus on some specific challenges to understanding and identifying conflicts of interest in the private sector; origin, diverging theories, the psychological barrier to the definition, similarities with public sector conflicts of interest due to the notions of corrosion of trust, ‘being in a particular kind of situation,’ etc. The notion of public interest will be submitted as a key element at the heart of the distinction between public sector and private sector conflicts of interests. It will then be proposed that the appreciation of the notion of conflicts of interest differ according to sector, country to country, based on the public interest test, using the United Kingdom (UK), the United States of America (US), France and the Philippines as illustrations.

Keywords: conflicts of interest, corporate governance, global governance, public interest

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Authors: Sun Gang

Abstract:

A variety of functional spaces are distributed on the vast mountain waterfront. Their functional positioning presents a spontaneous form of settlement space, and the construction features show a passive impact on the natural environment. As the precious heritage of inheriting human civilization and promoting historical culture, the traditional settlement space in mountainous areas is also the local expression of landscape pattern pattern gene. Under the impact of rapid urban construction and the stimulation of the transformation of social consumption demand, the original texture, scale and ecology of the traditional mountain settlement space, especially the historical and cultural settlement space, have been affected, and the decline of characteristics hinders the development. This paper selects Anju Ancient Town, the fourth largest ancient city in China, which is located in the city of mountains and waters as the research object, and combines spatial analysis and other methods to study the characteristics and causes of its spatial morphology, analyze the internal logic in its formation and development process, build a genetic analysis map, explore the possibility of settlement inheritance and development, and provide reference for the construction, protection and inheritance of traditional mountain settlements.

Keywords: mountain traditional settlement, historical and cultural settlement space, spatial form, spatial gene

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Authors: Muhammad G. Almatar, Mohammad A. Alnasrallah

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This research focuses on the study of three main issues: 1) The temporal analysis of leukemia for a period of six years (2006-2012), 2) spatial analysis by investigating this phenomenon in the Kuwaiti society spatially in the residential areas within the six governorates, 3) the use of Geographic Information System technology in investigating the hypothesis of the research and its variables using the linear regression, to show the pattern of linear relationship. The study depends on utilizing the map to understand the distribution of blood cancer in Kuwait. Several geodatabases were created for the number of patients and air pollution. Spatial interpolation models were used to generate layers of air pollution in the study area. These geodatabases were tested over the past six years to reach the conclusion: Is there a relationship with significant significance between the two main variables of the study: blood cancer and air pollution? This study is the first to our best knowledge. As far as the researchers know, the distribution of this disease has not been studied geographically at the level of regions in Kuwait within six years and in specific areas as described above. This study investigates the concentration of this type of disease. The study found that there is no relationship of significant value between the two variables studied, and this may be due to the nature of the disease, which are often hereditary. On the other hand, this study has reached a number of suggestions and recommendations that may be useful to decision-makers and interested in the study of leukemia in Kuwait by focusing on the study of genetic diseases, which may be a cause of leukemia rather than air pollution.

Keywords: Kuwait, GIS, cancer, geography

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Authors: Ugo Rovigatti

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Neuroblastoma (NBL) has epitomized for at least 40 years our understanding of cancer cellular and molecular biology and its potential applications to novel therapeutic strategies. This includes the discovery of the very first oncogene aberrations and tumorigenesis suppression by differentiation in the 80s; the potential role of suppressor genes in the 90s; the relevance of immunotherapy in the millennium first, and the discovery of additional mutations by NGS technology in the millennium second decade. Similar discoveries were achieved in the majority of human cancers, and similar therapeutic interventions were obtained subsequently to NBL discoveries. Unfortunately, targeted therapies suggested by specific mutations (such as MYCN amplification –MNA- present in ¼ or 1/5 of cases) have not elicited therapeutic successes in aggressive NBL, where the prognosis is still dismal. The reasons appear to be linked to Tumor Heterogeneity, which is particularly evident in NBL but also a clear hallmark of aggressive human cancers generally. The new avenue of cancer immunotherapy (CIT) provided new hopes for cancer patients, but we still ignore the cellular or molecular targets. CIT is emblematic of high-risk disease (HR-NBL) since the mentioned GD2 passive immunotherapy is still providing better survival. We recently critically reviewed and evaluated the literature depicting the genomic landscapes of HR-NBL, coming to the qualified conclusion that among hundreds of affected genes, potential targets, or chromosomal sites, none correlated with anti-GD2 sensitivity. A better explanation is provided by the Micro-Foci inducing Virus (MFV) model, which predicts that neuroblasts infection with the MFV, an RNA virus isolated from a cancer-cluster (space-time association) of HR-NBL cases, elicits the appearance of MNA and additional genomic aberrations with mechanisms resembling chromothripsis. Neuroblasts infected with low titers of MFV amplified MYCN up to 100 folds and became highly transformed and malignant, thus causing neuroblastoma in young rat pups of strains SD and Fisher-344 and larger tumor masses in nu/nu mice. An association was discovered with GD2 since this glycosphingolipid is also the receptor for the family of MFV virus (dsRNA viruses). It is concluded that a dsRNA virus, MFV, appears to provide better explicatory mechanisms for the genesis of i) specific genomic aberrations such as MNA; ii) extensive tumor heterogeneity and chromothripsis; iii) the effects of passive immunotherapy with anti-GD2 monoclonals and that this and similar models should be further investigated in both pediatric and adult cancers.

Keywords: neuroblastoma, MYCN, amplification, viruses, GD2

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Authors: Naseem Fatima, A. N. Srivastava, Tasleem Raza, Vijay Kumar

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Introduction: Carcinoma gallbladder is third most common gastrointestinal lethal disease with the highest incidence and mortality rate among women in Northern India. Scientists have found several risk factors that make a person more likely to develop gallbladder cancer; among these risk factors, deregulation of miRNAs has been demonstrated to be one of the most crucial factors. The changes in the expression of specific miRNA genes result in the control of inflammation, cell cycle regulation, stress response, proliferation, differentiation, apoptosis and invasion thus mediate the process in tumorgenesis. The aim of this study was to investigate the role of MiRNA-335 and may as a molecular marker in early detection of gallbladder cancer in suspected cases. Material and Methods: A total of 20 consecutive patients with gallbladder cancer aged between 30-75 years were registered for the study. Total RNA was extracted from tissue by using the mirVANA MiRNA isolation Kit according to the manufacturer’s protocol. The MiRNA- 335 and U6 snRNA-specific cDNA were reverse-transcribed from total RNA using Taqman microRNA reverse-transcription kit according to the manufacturer’s protocol. TaqMan MiRNA probes hsa-miR-335 and Taqman Master Mix without AmpEase UNG, Individual real-time PCR assays were performed in a 20 μL reaction volume on a Real-Time PCR system (Applied Biosystems StepOnePlus™) to detect MiRNA-335 expression in tissue. Relative quantification of target MiRNA expression was evaluated using the comparative cycle threshold (CT) method. The correlation was done in between cycle threshold (CT Value) of target MiRNA in gallbladder cancer with respect to non-cancerous Cholelithiasis gallbladder. Each sample was examined in triplicate. The Newman-Keuls Multiple Comparison Test was used to determine the expression of miR-335. Results: MiRNA335 was found to be significantly downregulated in the gallbladder cancer tissue (P<0.001), when compared with non-cancerous Cholelithiasis gallbladder cases. Out of 20 cases, 75% showed reduced expression of MiRNA335, were at last stage of disease with low overall survival rate and remaining 25% were showed up-regulated expression of MiRNA335 with high survival rate. Conclusion: The present study showed that reduced expression of MiRNA335 is associated with the advancement of the disease, and its deregulation may provide important clues to understanding it as a prognostic marker and opportunities for future research.

Keywords: carcinoma gallbladder, downregulation, MiRNA-335, RT-PCR assay

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Authors: Rosa Buxeda, Lorenzo Saliceti-Piazza, Rodolfo J. Romañach, Luis Ríos, Sandra L. Maldonado-Ramírez

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Biopharmaceuticals manufacturing is one of the major economic activities worldwide. Ninety-three percent of the workforce in a biomanufacturing environment concentrates in production-related areas. As a result, strategic collaborations between industry and academia are crucial to ensure the availability of knowledgeable workforce needed in an economic region to become competitive in biomanufacturing. In the past decade, our institution has been a key strategic partner with multinational biotechnology companies in supplying science and engineering graduates in the field of industrial biotechnology. Initiatives addressing all levels of the educational pipeline, from K-12 to college to continued education for company employees have been established along a ten-year span. The Amgen BioTalents Program was designed to provide undergraduate science and engineering students with training in biomanufacturing. The areas targeted by this educational program enhance their academic development, since these topics are not part of their traditional science and engineering curricula. The educational curriculum involved the process of producing a biomolecule from the genetic engineering of cells to the production of an especially targeted polypeptide, protein expression and purification, to quality control, and validation. This paper will report and describe the implementation details and outcomes of the first sessions of the program.

Keywords: biomanufacturing curriculum, interdisciplinary learning, workforce development, industry-academia partnering

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Authors: Yefrem Yefremov

Abstract:

In Kazakhstan, there are approximately 100,000 ethnic Koreans with the ethnonym "Koryo Saram". They are part of the global Korean diaspora around the world, deported to Kazakhstan by Stalin’s decree in 1937. Koryo Saram's diasporic identity is a composite of numerous identities based on a shared cultural heritage of the USSR and independent Kazakhstan and has mosaic character. The author has conducted a sociological survey to find out the main features of the identity of the Koryo Saram diaspora. The purpose of this paper is to depict the degree of ethnic, cultural, and diasporic identity of Koryo Saram and which effect on the preserving Korean diaspora in Kazakhstna do they have. The following elements impacting the above-mentioned identities were investigated in the survey: criteria by which Koryo Saram perceive themselves to be Korean, attitude of Koryo Saram to their ethnicity, degree of feeling of ethnocultural similarity between Koreans of Kazakhstan and Koreans of the Republic of Korea, degree of association of Koreans of Kazakhstan with other Koreans living in other CIS countries, degree of practicing Korean traditions Koryo Saram's attitudes towards interethnic marriages. The primary factor in defining the identity among the respondents is the factor of ethnic origin. Nationality is the second most significant component in establishing Koryo Saram’s identity. The maintenance of "Koreanness" of Koryo Sarams in the context of a multiethnic community, particularly in Kazakhstan, is based on genetic elements as well as the preservation of the culture. In conclusion, the high level of preserving Korean identity is being observed in the Korean Diaspora of Kazakhstan.

Keywords: diasporic identity, diaspora, ethnic identity, identity markers, korean diaspora, koreans of kazakhstan, koryo saram, multiethnicity

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Authors: Petr Daniel Edward Kovarik, Malcolm Jackson, Charles Kelly, Rahul Patil, Shahid Iqbal

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Introduction: Recognition of the presence of extra capsular spread (ECS) has been a major change in the TNM 8th edition published by the American Joint Committee on Cancer in 2018. Irrespective of the size or number of lymph nodes, the presence of ECS makes N3b disease a stage IV disease. The objective of this retrospective observational study was to conduct a comparative analysis of survival outcomes in patients with lymph node-positive cutaneous head and neck squamous cell carcinoma (CHNSCC) based on their TNM 7th and TNM 8th editions classification. Materials and Methods: From January 2010 to December 2020, 71 patients with CHNSCC were identified from our centre’s database who were treated with radical surgery and adjuvant radiotherapy. All histopathological reports were reviewed, and comprehensive nodal mapping was performed. The data were collected retrospectively and survival outcomes were compared using TNM 7th and 8th editions. Results: The median age of the whole group of 71 patients was 78 years, range 54 – 94 years, 63 were male and 8 female. In total, 2246 lymph nodes were analysed; 195 were positive for cancer. ECS was present in 130 lymph nodes, which led to a change in TNM staging. The details on N-stage as per TNM 7th edition was as follows; pN1 = 23, pN2a = 14, pN2b = 32, pN2c = 0, pN3 = 2. After incorporating the TNM 8th edition criterion (presence of ECS), the details on N-stage were as follows; pN1 = 6, pN2a = 5, pN2b = 3, pN2c = 0, pN3a = 0, pN3b = 57. This showed an increase in overall stage. According to TNM 7th edition, there were 23 patients were with stage III and remaining 48 patients, stage IV. As per TNM 8th edition, there were only 6 patients with stage III as compared to 65 patients with stage IV. For all patients, 2-year disease specific survival (DSS) and overall survival (OS) were 70% and 46%. 5-year DSS and OS rates were 66% and 20% respectively. Comparing the survival between stage III and stage IV of the two cohorts using both TNM 7th and 8th editions, there is an obvious greater survival difference between the stages if TNM 8th staging is used. However, meaningful statistics were not possible as the majority of patients (n = 65) were with stage IV and only 6 patients were stage III in the TNM 8th cohort. Conclusion: Our study provides a comprehensive analysis on lymph node data mapping in this specific patient population. It shows a better differentiation between stage III and stage IV in the TNM 8th edition as compared to TNM 7th however meaningful statistics were not possible due to the imbalance of patients in the sub-cohorts of the groups.

Keywords: cutaneous head and neck squamous cell carcinoma, extra capsular spread, neck lymphadenopathy, TNM 7th and 8th editions

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Authors: I. S. R. Butswat, D. Zahraddeen

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This study identified and described some skill-based and necessity-driven entrepreneurship in animal agriculture (AA). AA is an integral segment of the world food industry, and provides a good and rapid source of income. The contribution of AA to the Sub-Saharan economy is quite significant, and there are still large opportunities that remain untapped in the sector. However, it is imperative to understand, simplify and package the various components of AA in order to pave way for rapid wealth creation, poverty eradication and women empowerment programmes in sub-Saharan Africa and other developing countries. The entrepreneurial areas of AA highlighted were animal breeding, livestock fattening, dairy production, poultry farming, meat production (beef, mutton, chevon, etc.), rabbit farming, wool/leather production, animal traction, animal feed industry, commercial pasture management, fish farming, sport animals, micro livestock production, private ownership of abattoirs, slaughter slabs, animal parks and zoos, among others. This study concludes that reproductive biotechnology such as oestrous synchronization, super-/multiple ovulation, artificial insemination and embryo transfer can be employed as a tool for improvement of genetic make-up of low-yielding animals in terms of milk, meat, egg, wool, leather production and other economic traits that will necessitate sustainable job and wealth creations.

Keywords: animal, agriculture, entreprenurship, wealth

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Authors: Sai Sankalp Vemavarapu

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This paper discusses the application of machine learning in the field of transportation engineering for predicting engineering properties of pavement more accurately and efficiently. Predicting the elastic properties aid us in assessing the current road conditions and taking appropriate measures to avoid any inconvenience to commuters. This improves the longevity and sustainability of the pavement layer while reducing its overall life-cycle cost. As an example, we have implemented differential evolution (DE) in the back-calculation of the elastic modulus of multi-layered pavement. The proposed DE global optimization back-calculation approach is integrated with a forward response model. This approach treats back-calculation as a global optimization problem where the cost function to be minimized is defined as the root mean square error in measured and computed deflections. The optimal solution which is elastic modulus, in this case, is searched for in the solution space by the DE algorithm. The best DE parameter combinations and the most optimum value is predicted so that the results are reproducible whenever the need arises. The algorithm’s performance in varied scenarios was analyzed by changing the input parameters. The prediction was well within the permissible error, establishing the supremacy of DE.

Keywords: cost function, differential evolution, falling weight deflectometer, genetic algorithm, global optimization, metaheuristic algorithm, multilayered pavement, pavement condition assessment, pavement layer moduli back calculation

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Authors: Parker Townes, Prabdeep Panesar, Chunlin Liu, Soo Youn Lee, Dan Devoe, Paul D. Arnold, Jennifer Crosbie, Russell Schachar

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Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are impairing childhood neurodevelopmental disorders with problems in executive functions. Executive functions are higher-level mental processes essential for daily functioning and goal attainment. There is genetic and neural overlap between ADHD and ASD. The aim of this meta-analysis was to evaluate if pediatric ASD and ADHD have distinct executive function profiles. This review was completed following Cochrane guidelines. Fifty-eight articles were identified through database searching, followed by a blinded screening in duplicate. A meta-analysis was performed for all task performance metrics evaluated by at least two articles. Forty-five metrics from 24 individual tasks underwent analysis. No differences were found between youth with ASD and ADHD in any domain under direct comparison. However, individuals with ASD and ADHD exhibited deficient attention, flexibility, visuospatial abilities, working memory, processing speed, and response inhibition compared to controls. No deficits in planning were noted in either disorder. Only 11 studies included a group with comorbid ASD+ADHD, making it difficult to determine whether common executive function deficits are a function of comorbidity. Further research is needed to determine if comorbidity accounts for the apparent commonality in executive function between ASD and ADHD.

Keywords: autism spectrum disorder, ADHD, neurocognition, executive function, youth

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Authors: Rema Vazhappilly, Tapas Das

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Oleic acid is a cis unsaturated fatty acid and is known to be a partially essential fatty acid due to its limited endogenous synthesis during pregnancy and lactation. Previous studies have demonstrated the role of oleic acid in neuronal differentiation and brain phospholipid synthesis. These evidences indicate a major role for oleic acid in learning and memory. Interestingly, oleic acid has been shown to enhance hippocampal long term potentiation (LTP), the physiological correlate of long term synaptic plasticity. However the effect of oleic acid on short term synaptic plasticity has not been investigated. Short term potentiation (STP) is the physiological correlate of short term synaptic plasticity which is the key underlying molecular mechanism of short term memory and neuronal information processing. STP in the hippocampal CA1 region has been known to require the activation of N-methyl-D-aspartate receptors (NMDARs). The NMDAR dependent hippocampal STP as a potential mechanism for short term memory has been a subject of intense interest for the past few years. Therefore in the present study the effect of oleic acid on NMDAR dependent hippocampal STP was determined in mouse hippocampal slices (in vitro) using Multi-electrode array system. STP was induced by weak tetanic Stimulation (one train of 100 Hz stimulations for 0.1s) of the Schaffer collaterals of CA1 region of the hippocampus in slices treated with different concentrations of oleic acid in presence or absence of NMDAR antagonist D-AP5 (30 µM) . Oleic acid at 20 (mean increase in fEPSP amplitude = ~135 % Vs. Control = 100%; P<0.001) and 30 µM (mean increase in fEPSP amplitude = ~ 280% Vs. Control = 100%); P<0.001) significantly enhanced the STP following weak tetanic stimulation. Lower oleic acid concentrations at 10 µM did not modify the hippocampal STP induced by weak tetanic stimulation. The hippocampal STP induced by weak tetanic stimulation was completely blocked by the NMDA receptor antagonist D-AP5 (30µM) in both oleic acid and control treated hippocampal slices. This lead to the conclusion that the hippocampal STP elicited by weak tetanic stimulation and enhanced by oleic acid was NMDAR dependent. Together these findings suggest that oleic acid may enhance the short term memory and neuronal information processing through the modulation of NMDAR dependent hippocampal short-term synaptic plasticity. In conclusion this study suggests the possible role of oleic acid to prevent the short term memory loss and impaired neuronal function throughout development.

Keywords: oleic acid, short-term potentiation, memory, field excitatory post synaptic potentials, NMDA receptor

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Authors: Ehsan Yadegari

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While there are several metaheuristics and exact approaches to solving the Supply Chain Network Design (SCND) problem, there still remains an unfilled gap in using the Teaching-Learning-Based Optimization (TLBO) algorithm. The algorithm has demonstrated desirable results with problems with complicated combinational optimization. The present study introduces a Discrete Self-Study TLBO (DSS-TLBO) with priority-based solution representation that can solve a supply chain network configuration model to lower the total expenses of establishing facilities and the flow of materials. The network features four layers, namely suppliers, plants, distribution centers (DCs), and customer zones. It is designed to meet the customer’s demand through transporting the material between layers of network and providing facilities in the best economic Potential locations. To have a higher quality of the solution and increase the speed of TLBO, a distinct operator was introduced that ensures self-adaptation (self-study) in the algorithm based on the four types of local search. In addition, while TLBO is used in continuous solution representation and priority-based solution representation is discrete, a few modifications were added to the algorithm to remove the solutions that are infeasible. As shown by the results of experiments, the superiority of DSS-TLBO compared to pure TLBO, genetic algorithm (GA) and firefly Algorithm (FA) was established.

Keywords: supply chain network design, teaching–learning-based optimization, improved metaheuristics, discrete solution representation

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Authors: Yalda Zarnegarnia, Shari Messinger

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Receiver operating characteristic (ROC) curves have been widely used in medical research to illustrate the performance of the biomarker in correctly distinguishing the diseased and non-diseased groups. Correlated biomarker data arises in study designs that include subjects that contain same genetic or environmental factors. The information about correlation might help to identify family members at increased risk of disease development, and may lead to initiating treatment to slow or stop the progression to disease. Approaches appropriate to a case-control design matched by family identification, must be able to accommodate both the correlation inherent in the design in correctly estimating the biomarker’s ability to differentiate between cases and controls, as well as to handle estimation from a matched case control design. This talk will review some developed methods for ROC curve estimation in settings with correlated data from case control design and will discuss the limitations of current methods for analyzing correlated familial paired data. An alternative approach using Conditional ROC curves will be demonstrated, to provide appropriate ROC curves for correlated paired data. The proposed approach will use the information about the correlation among biomarker values, producing conditional ROC curves that evaluate the ability of a biomarker to discriminate between diseased and non-diseased subjects in a familial paired design.

Keywords: biomarker, correlation, familial paired design, ROC curve

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Authors: Manali Jain, Neeta Singh, Raunaq Fatima, Soniya Nityanand, Mandakini Pradhan, Chandra Prakash Chaturvedi

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Isolated Congenital Heart Defect (ICHD) is the major cause of neonatal death worldwide among all forms of CHDs. A significant proportion of fetuses with ICHD die in the neonatal period if no treatment is provided. Recently, stem cell therapies have emerged as a potential approach to ameliorate ICHD in children. ICHD is characterized by cardiac structural abnormalities during embryogenesis due to alterations in the cardiomyogenic properties of a pool of cardiac progenitors/ stem cells associated with fetal heart development. The stem cells present in the amniotic fluid (AF) are of fetal origin and may reflect the physiological and pathological changes in the fetus during embryogenesis. Therefore, in the present study, the cardiomyogenic potential of AF-MSCs derived from fetuses with ICHD (ICHD AF-MSCs) has been evaluated and compared with that of AF-MSCs of structurally normal fetuses (normal AF-MSCs). Normal and ICHD AF-MSC were analyzed for the expression of cardiac progenitor markers viz., stage-specific embryonic antigen-1 (SSEA-1), vascular endothelial growth factor 2 (VEGFR-2) and platelet-derived growth factor receptor-alpha (PDGFR-α) by flow cytometry. The immunophenotypic characterization revealed that ICHD AF-MSCs have significantly lower expression of cardiac progenitor markers VEGFR-2 (0.14% ± 0.6 vs.48.80% ± 0.9; p <0.01), SSEA-1 (70.86% ± 2.4 vs. 88.36% ±2.7; p <0.01), and PDGFR-α (3.92% ± 1.8 vs. 47.59% ± 3.09; p <0.01) in comparison to normal AF-MSCs. Upon induction with 5’-azacytidine for 21 days, ICHD AF-MSCs showed a significantly down-regulated expression of cardiac transcription factors such as GATA-4 (0.4 ± 0.1 vs. 6.8 ± 1.2; p<0.01), ISL-1 (2.3± 0.6 vs. 14.3 ± 1.12; p<0.01), NK-x 2-5 (1.1 ± 0.3 vs. 14.1 ±2.8; p<0.01), TBX-5 (0.4 ± 0.07 vs. 4.4 ± 0.3; p<0.001), and TBX-18 (1.3 ± 0.2 vs. 4.19 ± 0.3; p<0.01) when compared with the normal AF-MSCs. Furthermore, immunocytochemical staining revealed that both types of AF-MSCs could differentiate into cardiovascular lineages and express cardiomyogenic, endothelial, and smooth muscle actin markers, viz., cardiac troponin (cTNT), CD31, and alpha-smooth muscle actin (α-SMA). However, normal AF-MSCs showed an enhanced expression of cTNT (p<0.001), CD31 (p<0.01), and α-SMA (p<0.05), compared to ICHD AF-MSCs. Overall, these results suggest that the ICHD-AF-MSCs have a defective cardiomyogenic differentiation potential and that the defects in these stem cells may have a role in the pathogenesis of ICHD.

Keywords: amniotic fluid, cardiomyogenic potential, isolated congenital heart defect, mesenchymal stem cells

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Authors: Aniket Kumar, Jacob Peedicayil

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

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

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Authors: Henrie Yunianto, Dermawan Wibisono

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PT. XYZ is a family business (private company) in Indonesia that provide an educational program and consultation services. Since its establishment in 2011, the company has run without any strategic management system implemented. Though the company could survive until now. The management of PT. XYZ sees the business opportunity for such product is huge, even though the targeted market is very specific (niche), the volume is large (due to large population of Indonesia) and numbers of competitors are low (now). It can be said if the product life cycle is in between ‘Introduction stage’ and ‘growth’ stage. It is observed that nowadays the new entrants (competitors) are increasing, thus PT. XYZ consider reacting in facing the intense business rivalry by conducting the business in an appropriate manner. A Performance Management System is important to be implemented in accordance with the business sustainability and growth. The framework of Performance Management System chosen is Integrated Performance Management System (IPMS). IPMS framework has the advantages of its simplicity, linkage between its business variables and indicators where the company can see the connections between all factors measured. IPMS framework consists of perspectives: (1) Business Result, (2) Internal Processes, (3) Resource Availability. Variables and indicators were examined through deep analysis of the business external and internal environments, Strength-Weakness-Opportunity-Threat (SWOT) analysis, Porter’s five forces analysis. Analytical Hierarchy Process (AHP) analysis was then used to quantify the weight of each variable/indicators. AHP is needed since in this study, PT. XYZ, the data of existing performance indicator was not available. Later, where the IPMS is implemented, the real data measured can be examined to determine the weight factor of each indicators using correlation analysis (or other methods). In this study of IPMS design for PT. XYZ, the analysis shows that with current company goals, along with the AHP methodology, the critical indicators for each perspective are: (1) Business results: Customer satisfaction and Employee satisfaction, (2) Internal process: Marketing performance, Supplier quality, Production quality, Continues improvement; (3) Resources Availability: Leadership and company culture & value, Personal Competences, Productivity. Company and/or organization require performance management system to help them in achieving their vision and mission. Company strategy will be effectively defined and addressed by using performance management system. Integrated Performance Management System (IPMS) framework and AHP analysis help us in quantifying the factors which influence the business output expected.

Keywords: analytical hierarchy process, business strategy, differentiation strategy, integrated performance management system

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Authors: Vijay Kumar, Mack Moyo, Johannes Van Staden

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Lachenalia viridiflora is a critically endangered bulbous plant with high potential on the international floriculture market. In the present study, an efficient protocol for in vitro plantlet regeneration through somatic embryogenesis was developed. Embryogenic callus was established on Murashige and Skoog (MS) basal medium supplemented with various concentrations and combinations of picloram and thidiazuron (TDZ). A high number of SEs (28.5 ± 1.49) with at different developmental stages of somatic embryos (SEs: globular embryos, torpedo and cotyledon embryo with bipolar characteristics) was obtained on Murashige and Skoog (MS) (Murashige and Skoog 1962) medium with 2.5 μM picloram, and 1.0 μM TDZ. Histological and scanning electron microscopic (SEM) analysis confirmed the presence of somatic embryos. Mature somatic embryos germinated and developed into plantlets after 6 weeks on half/full strength MS medium. High plant regeneration frequency (91.11 %) was achieved on full-strength MS medium supplemented with 5 μM phloroglucinol (PG). Well-developed healthy plantlets were successfully acclimatized in the greenhouse with a survival rate of 80%. The result of this study is beneficial in the mass propagation of high-quality Lachenalia viridiflora clonal plants for the commercial horticultural market and also provides a platform for future genetic transformation studies on the plant.

Keywords: horticultural plant, Lachenalia viridiflora, phloroglucinol, somatic embryogenesis, thidiazuron

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Authors: S. Salah, S. A. El-Masry, H. F. Sheba, R. A. El-Banna, W. Saad

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Background: Familial Mediterranean fever (FMF) has episodic or subclinical inflammation that may lead to a decrease in bone mineral density (BMD). Objective: To assess BMD in Egyptian children with FMF on genetic basis. Subjects and Methods: A cross sectional study included 45 FMF patients and 25 control children of both sexes, with age range between 3-16 years old. The patients were reclassified into 2 groups: Group I (A) 23 cases used colchicines for 1 month or less, and Group I (B) 22 cases used colchicines for more than 6 months. For both patients and control, MEFV mutations were defined using molecular genetics technique and BMD was measured by DXA at 2 sites: proximal femur and the lumber spines. Results: four frequent gene mutations were found in the patient group: E148Q (35.6%), V726A (33.3%), M680I (28.9.0%) and M694V (2.2%). There were also 4 heterozygous gene mutations in 40% of control children. Patients received colchicines treatment for less than 1 month had highly significant lower values of BMD at femur and lumber spines than control children (p<0.05). Patients received colchicines treatment for more than 6 months had improved values of BMD at femur compared to control, but there were still significant differences between them at lumbar spine (p>0.05). There are insignificant effect of type of gene mutation on BMD and the risk of osteopenia among the patients. Conclusion: FMF had significant effect on BMD. However, regular use of colchicines treatment improves this effect mainly at femur.

Keywords: familial mediterranean fever, bone mineral density, genes, children

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Authors: Shital Suresh Borse, Vijayalaxmi Kadroli

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E-commerce industries nowadays implement the latest AI, ML Techniques to improve their own performance and prediction accuracy. This helps to gain a huge profit from the online market. Ant Colony Optimization, Genetic algorithm, Particle Swarm Optimization, Neural Network & GWO help many e-commerce industries for up-gradation of their predictive performance. These algorithms are providing optimum results in various applications, such as stock price prediction, prediction of drug-target interaction & user ratings of similar products in e-commerce sites, etc. In this study, customer reviews will play an important role in prediction analysis. People showing much interest in buying a lot of services& products suggested by other customers. This ultimately increases net profit. In this work, a convolution neural network (CNN) is proposed which further is useful to optimize the prediction accuracy of an e-commerce website. This method shows that CNN is used to optimize hyperparameters of GWO algorithm using an appropriate coding scheme. Accurate model results are verified by comparing them to PSO results whose hyperparameters have been optimized by CNN in Amazon's customer review dataset. Here, experimental outcome proves that this proposed system using the GWO algorithm achieves superior execution in terms of accuracy, precision, recovery, etc. in prediction analysis compared to the existing systems.

Keywords: prediction analysis, e-commerce, machine learning, grey wolf optimization, particle swarm optimization, CNN

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Authors: Kyu Jin Kim, Byung Kwan Oh, Hyo Seon Park

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The seismic responses-based structural health monitoring system has been performed to reduce seismic damage. The inter-story drift ratio which is the major index of the seismic capacity assessment is employed for estimating the seismic damage of buildings. Meanwhile, seismic response analysis to estimate the structural responses of building demands significantly high computational cost due to increasing number of high-rise and large buildings. To estimate the inter-story drift ratio of buildings from the earthquake efficiently, this paper suggests the estimation method of inter-story drift for buildings using an artificial neural network (ANN). In the method, the radial basis function neural network (RBFNN) is integrated with optimization algorithm to optimize the variable through evolutionary learning that refers to evolutionary radial basis function neural network (ERBFNN). The estimation method estimates the inter-story drift without seismic response analysis when the new earthquakes are subjected to buildings. The effectiveness of the estimation method is verified through a simulation using multi-degree of freedom system.

Keywords: structural health monitoring, inter-story drift ratio, artificial neural network, radial basis function neural network, genetic algorithm

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Authors: Mohammad Hajjartabar, Tahereh Kermani Ranjbar

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P. aeruginosa EF2 was isolated and identified from human infection sources before in our previous study. The present study was performed to determine the characteristics and activity role of bioflocculant produced by the bacterium in flocculation of the wastewater active sludge treatment. The bacterium was inoculated and then was grown in an orbital shaker at 250 rpm for 5 days at 35 °C under TSB and peptone water media. After incubation period, culture broths of the bacterial strain was collected and washed. The concentration of the bacteria was adjusted. For the extraction of the bacterial bioflocculant, culture was centrifuged at 6000 rpm for 20 min at 4 °C to remove bacterial cells. Supernatant was decanted and pellet containing bioflocculant was dried at 105 °C to a constant weight according to APHA, 2005. The chemical composition of the extracted bioflocculant from the bacterial sample was then analyzed. Wastewater active sludge sample obtained from aeration tank from one of wastewater treatment plants in Tehran, was first mixed thoroughly. After addition of bioflocculant, improvements in floc density were observed with an increase in bioflocculant. The results of this study strongly suggested that the extracted bioflucculant played a significant role in flocculation of the wastewater sample. The use of wild bacteria and nutrient regulation techniques instead of genetic manipulation opens wide investigation area in the future to improve wastewater treatment processes. Also this may put a new path in front of us to attain and improve the more effective bioflocculant using the purified microbial culture in wastewater treatment.

Keywords: wastewater treatment, P. aeruginosa, sludge treatment

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