Search results for: transcription regulation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1688

Search results for: transcription regulation

518 A Framework for Auditing Multilevel Models Using Explainability Methods

Authors: Debarati Bhaumik, Diptish Dey

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Multilevel models, increasingly deployed in industries such as insurance, food production, and entertainment within functions such as marketing and supply chain management, need to be transparent and ethical. Applications usually result in binary classification within groups or hierarchies based on a set of input features. Using open-source datasets, we demonstrate that popular explainability methods, such as SHAP and LIME, consistently underperform inaccuracy when interpreting these models. They fail to predict the order of feature importance, the magnitudes, and occasionally even the nature of the feature contribution (negative versus positive contribution to the outcome). Besides accuracy, the computational intractability of SHAP for binomial classification is a cause of concern. For transparent and ethical applications of these hierarchical statistical models, sound audit frameworks need to be developed. In this paper, we propose an audit framework for technical assessment of multilevel regression models focusing on three aspects: (i) model assumptions & statistical properties, (ii) model transparency using different explainability methods, and (iii) discrimination assessment. To this end, we undertake a quantitative approach and compare intrinsic model methods with SHAP and LIME. The framework comprises a shortlist of KPIs, such as PoCE (Percentage of Correct Explanations) and MDG (Mean Discriminatory Gap) per feature, for each of these three aspects. A traffic light risk assessment method is furthermore coupled to these KPIs. The audit framework will assist regulatory bodies in performing conformity assessments of AI systems using multilevel binomial classification models at businesses. It will also benefit businesses deploying multilevel models to be future-proof and aligned with the European Commission’s proposed Regulation on Artificial Intelligence.

Keywords: audit, multilevel model, model transparency, model explainability, discrimination, ethics

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517 Antifungal Susceptibility of Saprolegnia parasitica Isolated from Rainbow Trout and Its Host Pathogen Interaction in Zebrafish Disease Model

Authors: Sangyeop Shin, D. C. M. Kulatunga, S. H. S. Dananjaya, Chamilani Nikapitiya, Jehee Lee, Mahanama De Zoysa

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Saprolegniasis is one of the most devastating fungal diseases in freshwater fish which is caused by species in the genus Saprolegnia including Saprolegnia parasitica. In this study, we isolated the strain of S. parasitica from diseased rainbow trout in Korea. Morphological and molecular based identification confirmed that isolated fungi belong to the member of S. parasitica, supported by its typical fungal features including cotton-like whitish mycelium, zoospores (primary and secondary) and phylogenetic analysis with internal transcribed spacer (ITS) region. Pathogenicity of isolated S. parasitica was developed in embryo, larvae, juvenile and adult zebrafish as a disease model. Up regulation of host genes encoding ZfTnf-α, Zfc-Rel, ZfIl-12, ZfLyz-c, Zfβ-def, and ZfHsp-70 was identified in zebrafish larvae after experimental challenge of S. parasitica showing the host immune responses against the S. parasitica. Survival of the juveniles upon fungal infection might be due to the increased immune protection in the host. Investigation of antifungal susceptibility of S. parasitica with natural lawsone (2-hydroxy-1,4-naphthoquinone) revealed the minimum inhibitory concentration (MIC) and percentage inhibition of radial growth (PIRG %) as 200 µg/mL and 31.8%, respectively. Lawsone was able to change the membrane permeability, and cause irreversible damage and disintegration to the cellular membranes of S. parasitica which might have effect on fungi growth inhibition. Moreover, the mycelium exposed to lawsone (MIC level) changed the transcriptional responses of S. parasitica genes. Overall results indicate that lawsone could be a potential and novel anti-S. parasitica agent for controlling S. parasitica infection.

Keywords: host-pathogen interactions, lawsone, rainbow trout, Saprolegnia parasitica, Saprolegniasis, zebrafish

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516 Regulation Aspects for a Radioisotope Production Installation in Brazil

Authors: Rian O. Miranda, Lidia V. de Sa, Julio C. Suita

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The Brazilian Nuclear Energy Commission (CNEN) is the main manufacturer of radiopharmaceuticals in Brazil. The Nuclear Engineering Institute (IEN), located at Rio de Janeiro, is one of its main centers of research and production, attending public and private hospitals in the state. This radiopharmaceutical production is used in diagnostic and therapy procedures and allows one and a half million nuclear medicine procedures annually. Despite this, the country is not self-sufficient to meet national demand, creating the need for importation and consequent dependence on other countries. However, IEN facilities were designed in the 60's, and today its structure is inadequate in relation to the good manufacturing practices established by sanitary regulator (ANVISA) and radiological protection leading to the need for a new project. In order to adapt and increase production in the country, a new plant will be built and integrated to the existing facilities with a new 30 MeV Cyclotron that is actually in project detailing process. Thus, it is proposed to survey current CNEN and ANVISA standards for radiopharmaceutical production facilities, as well as the radiological protection analysis of each area of the plant, following good manufacturing practices recommendations adopted nationally besides licensing exigencies for radioactive facilities. In this way, the main requirements for proper operation, equipment location, building materials, area classification, and maintenance program have been implemented. The access controls, interlocks, segregation zones and pass-through boxes integrated into the project were also analyzed. As a result, IEN will in future have the flexibility to produce all necessary radioisotopes for nuclear medicine application, more efficiently by simultaneously bombarding two targets, allowing the simultaneous production of two different radioisotopes, minimizing radiation exposure and saving operating costs.

Keywords: cyclotron, legislation, norms, production, radiopharmaceuticals

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515 The Development of Nursing Model for Pregnant Women to Prevention of Early Postpartum Hemorrhage

Authors: Wadsana Sarakarn, Pimonpan Charoensri, Baliya Chaiyara

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Objectives: To study the outcomes of the developed nursing model to prevent early postpartum hemorrhage (PPH). Materials and Methods: The analytical study was conducted in Sunpasitthiprasong Hospital during October 1st, 2015, until May 31st, 2017. After review the prevalence, risk factors, and outcomes of postpartum hemorrhage of the parturient who gave birth in Sunpasitthiprasong Hospital, the nursing model was developed under research regulation of Kemmis&McTaggart using 4 steps of operating procedures: 1) analyzing problem situation and gathering 2) creating the plan 3) noticing and performing 4) reflecting the result of the operation. The nursing model consisted of the screening tools for risk factors associated with PPH, the clinical nursing practice guideline (CNPG), and the collecting bag for measuring postpartum blood loss. Primary outcome was early postpartum hemorrhage. Secondary outcomes were postpartum hysterectomy, maternal mortality, personnel’s practice, knowledge, and satisfaction of the nursing model. The data were analyzed by using content analysis for qualitative data and descriptive statistics for quantitative data. Results: Before using the nursing model, the prevalence of early postpartum hemorrhage was under estimated (2.97%). There were 5 cases of postpartum hysterectomy and 2 cases of maternal death due to postpartum hemorrhage. During the study period, there was 22.7% prevalence of postpartum hemorrhage among 220 pregnant women who were vaginally delivered at Sunpasitthiprasong Hospital. No maternal death or postpartum hysterectomy was reported after using the nursing model. Among 16 registered nurses at the delivery room who evaluated using of the nursing model, they reported the high level of practice, knowledge, and satisfaction Conclusion: The nursing model for the prevention of early PPH is effective to decrease early PPH and other serious complications.

Keywords: the development of a nursing model, prevention of postpartum hemorrhage, pregnant women, postpartum hemorrhage

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514 Impact of Totiviridae L-A dsRNA Virus on Saccharomyces Cerevisiae Host: Transcriptomic and Proteomic Approach

Authors: Juliana Lukša, Bazilė Ravoitytė, Elena Servienė, Saulius Serva

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Totiviridae L-A virus is a persistent Saccharomyces cerevisiae dsRNA virus. It encodes the major structural capsid protein Gag and Gag-Pol fusion protein, responsible for virus replication and encapsulation. These features also enable the copying of satellite dsRNAs (called M dsRNAs) encoding a secreted toxin and immunity to it (known as killer toxin). Viral capsid pore presumably functions in nucleotide uptake and viral mRNA release. During cell division, sporogenesis, and cell fusion, the virions remain intracellular and are transferred to daughter cells. By employing high throughput RNA sequencing data analysis, we describe the influence of solely L-A virus on the expression of genes in three different S. cerevisiae hosts. We provide a new perception into Totiviridae L-A virus-related transcriptional regulation, encompassing multiple bioinformatics analyses. Transcriptional responses to L-A infection were similar to those induced upon stress or availability of nutrients. It also delves into the connection between the cell metabolism and L-A virus-conferred demands to the host transcriptome by uncovering host proteins that may be associated with intact virions. To better understand the virus-host interaction, we applied differential proteomic analysis of virus particle-enriched fractions of yeast strains that harboreither complete killer system (L-A-lus and M-2 virus), M-2 depleted orvirus-free. Our analysis resulted in the identification of host proteins, associated with structural proteins of the virus (Gag and Gag-Pol). This research was funded by the European Social Fund under the No.09.3.3-LMT-K-712-19-0157“Development of Competences of Scientists, other Researchers, and Students through Practical Research Activities” measure.

Keywords: totiviridae, killer virus, proteomics, transcriptomics

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

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

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

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

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512 Integrative Transcriptomic Profiling of NK Cells and Monocytes: Advancing Diagnostic and Therapeutic Strategies for COVID-19

Authors: Salma Loukman, Reda Benmrid, Najat Bouchmaa, Hicham Hboub, Rachid El Fatimy, Rachid Benhida

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In this study, it use integrated transcriptomic datasets from the GEO repository with the purpose of investigating immune dysregulation in COVID-19. Thus, in this context, we decided to be focused on NK cells and CD14+ monocytes gene expression, considering datasets GSE165461 and GSE198256, respectively. Other datasets with PBMCs, lung, olfactory, and sensory epithelium and lymph were used to provide robust validation for our results. This approach gave an integrated view of the immune responses in COVID-19, pointing out a set of potential biomarkers and therapeutic targets with special regard to standards of physiological conditions. IFI27, MKI67, CENPF, MBP, HBA2, TMEM158, THBD, HBA1, LHFPL2, SLA, and AC104564.3 were identified as key genes from our analysis that have critical biological processes related to inflammation, immune regulation, oxidative stress, and metabolic processes. Consequently, such processes are important in understanding the heterogeneous clinical manifestations of COVID-19—from acute to long-term effects now known as 'long COVID'. Subsequent validation with additional datasets consolidated these genes as robust biomarkers with an important role in the diagnosis of COVID-19 and the prediction of its severity. Moreover, their enrichment in key pathophysiological pathways presented them as potential targets for therapeutic intervention.The results provide insight into the molecular dynamics of COVID-19 caused by cells such as NK cells and other monocytes. Thus, this study constitutes a solid basis for targeted diagnostic and therapeutic development and makes relevant contributions to ongoing research efforts toward better management and mitigation of the pandemic.

Keywords: SARS-COV-2, RNA-seq, biomarkers, severity, long COVID-19, bio analysis

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511 Effect of a GABA/5-HTP Mixture on Behavioral Changes and Biomodulation in an Invertebrate Model

Authors: Kyungae Jo, Eun Young Kim, Byungsoo Shin, Kwang Soon Shin, Hyung Joo Suh

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Gamma-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) are amino acids of digested nutrients or food ingredients and these can possibly be utilized as non-pharmacologic treatment for sleep disorder. We previously investigated the GABA/5-HTP mixture is the principal concept of sleep-promoting and activity-repressing management in nervous system of D. melanogaster. Two experiments in this study were designed to evaluate sleep-promoting effect of GABA/5-HTP mixture, to clarify the possible ratio of sleep-promoting action in the Drosophila invertebrate model system. Behavioral assays were applied to investigate distance traveled, velocity, movement, mobility, turn angle, angular velocity and meander of two amino acids and GABA/5-HTP mixture with caffeine treated flies. In addition, differentially expressed gene (DEG) analyses from next generation sequencing (NGS) were applied to investigate the signaling pathway and functional interaction network of GABA/5-HTP mixture administration. GABA/5-HTP mixture resulted in significant differences between groups related to behavior (p < 0.01) and significantly induced locomotor activity in the awake model (p < 0.05). As a result of the sequencing, the molecular function of various genes has relationship with motor activity and biological regulation. These results showed that GABA/5-HTP mixture administration significantly involved the inhibition of motor behavior. In this regard, we successfully demonstrated that using a GABA/5-HTP mixture modulates locomotor activity to a greater extent than single administration of each amino acid, and that this modulation occurs via the neuronal system, neurotransmitter release cycle and transmission across chemical synapses.

Keywords: sleep, γ-aminobutyric acid, 5-hydroxytryptophan, Drosophila melanogaster

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510 Stem Cell Differentiation Toward Secretory Progenitors after Intestinal Ischemia-Reperfusion in a Rat is Accompanied by Inhibited Notch Signaling Cascade

Authors: Igor Sukhotnik

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Objectives: Notch signaling is thought to act to drive cell versification in the lining of the small intestine. When Notch signaling is blocked, proliferation ceases, and epithelial cells become secretory. The purpose of the present study was to evaluate the role of Notch signaling pathway in stem cell differentiation in a rat model of intestinal ischemia-reperfusion (IR). Methods: Male Sprague-Dawley rats were randomly divided into four experimental groups: Sham-24 and Sham-48 rats underwent laparotomy and were killed 24 or 48 h later, respectively; IR-24 and IR-48 rats underwent occlusion of SMA and portal vein for 30 min followed by 24 or 48 h of reperfusion, respectively. Notch-related gene and protein expression were determined using Real Time PCR, Western blotting and immunohistochemistry. Wax histology and immunohistochemistry was used to determine cell differentiation toward absorptive (enterocytes) or secretory progenitors (goblet cells, enteroendocrine cells or Paneth cells). Results: IR-48 rats exhibited a significant decrease in Notch-1 protein expression (Western blot) that was coincided with a significant decrease in the number of Notch-1 positive cells (immunohistochemistry) in jejunum and ileum as well as Hes-1 positive cells in jejunum and ileum compared to Sham-48 rats. A significant down-regulation of Notch signaling related genes and proteins in IR animals was accompanied by a significant increase in the number of goblet and Paneth cells and decreased number of absorptive cells compared to control rats. Conclusions: Forty-eight hours following intestinal IR in rats, inhibited Notch signaling pathway was accompanied by intestinal stem cells differentiation toward secretory progenitors.

Keywords: Intestine, notch, ischemia-reperfusion, cell differentiation, secretory

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509 Vertical Distribution of the Monthly Average Values of the Air Temperature above the Territory of Kakheti in 2012-2017

Authors: Khatia Tavidashvili, Nino Jamrishvili, Valerian Omsarashvili

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Studies of the vertical distribution of the air temperature in the atmosphere have great value for the solution of different problems of meteorology and climatology (meteorological forecast of showers, thunderstorms, and hail, weather modification, estimation of climate change, etc.). From the end of May 2015 in Kakheti after 25-year interruption, the work of anti-hail service was restored. Therefore, in connection with climate change, the need for the detailed study of the contemporary regime of the vertical distribution of the air temperature above this territory arose. In particular, the indicated information is necessary for the optimum selection of rocket means with the works on the weather modification (fight with the hail, the regulation of atmospheric precipitations, etc.). Construction of the detailed maps of the potential damage distribution of agricultural crops from the hail, etc. taking into account the dimensions of hailstones in the clouds according to the data of radar measurements and height of locality are the most important factors. For now, in Georgia, there is no aerological probing of atmosphere. To solve given problem we processed information about air temperature profiles above Telavi, at 27 km above earth's surface. Information was gathered during four observation time (4, 10, 16, 22 hours with local time. After research, we found vertical distribution of the average monthly values of the air temperature above Kakheti in ‎2012-2017 from January to December. Research was conducted from 0.543 to 27 km above sea level during four periods of research. In particular, it is obtained: -during January the monthly average air temperature linearly diminishes with 2.6 °C on the earth's surface to -57.1 °C at the height of 10 km, then little it changes up to the height of 26 km; the gradient of the air temperature in the layer of the atmosphere from 0.543 to 8 km - 6.3 °C/km; height of zero isotherm - is 1.33 km. -during July the air temperature linearly diminishes with 23.5 °C to -64.7 °C at the height of 17 km, then it grows to -47.5 °C at the height of 27 km; the gradient of the air temperature of - 6.1 °C/km; height of zero isotherm - is 4.39 km, which on 0.16 km is higher than in the sixties of past century.

Keywords: hail, Kakheti, meteorology, vertical distribution of the air temperature

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508 Analysing “The Direction of Artificial Intelligence Legislation from a Global Perspective” from the Perspective of “AIGC Copyright Protection” Content

Authors: Xiaochen Mu

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Due to the diversity of stakeholders and the ambiguity of ownership boundaries, the current protection models for Artificial Intelligence Generated Content (AIGC) have many disadvantages. In response to this situation, there are three different protection models worldwide. The United States Copyright Office stipulates that works autonomously generated by artificial intelligence ‘lack’ the element of human creation, and non-human AI cannot create works. To protect and promote investment in the field of artificial intelligence, UK legislation, through Section 9(3) of the CDPA, designates the author of AI-generated works as ‘the person by whom the arrangements necessary for the creation of the work are undertaken.’ China neither simply excludes the work attributes of AI-generated content based on the lack of a natural person subject as the sole reason, nor does it generalize that AIGC should or should not be protected. Instead, it combines specific case circumstances and comprehensively evaluates the degree of originality of AIGC and the contributions of natural persons to AIGC. In China's first AI drawing case, the court determined that the image in question was the result of the plaintiff's design and selection through inputting prompt words and setting parameters, reflecting the plaintiff's intellectual investment and personalized expression, and should be recognized as a work in the sense of copyright law. Despite opposition, the ruling also established the feasibility of the AIGC copyright protection path. The recognition of the work attributes of AIGC will not lead to overprotection that hinders the overall development of the AI industry. Just as with the legislation and regulation of AI by various countries, there is a need for a balance between protection and development. For example, the provisional agreement reached on the EU AI Act, based on a risk classification approach, seeks a dynamic balance between copyright protection and the development of the AI industry.

Keywords: generative artificial intelligence, originality, works, copyright

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507 Role of Human Wharton’s Jelly Mesenchymal Stem Cells Conditioned Media in Alleviating Kidney Injury via Inhibition of Renin-Angiotensin System in Diabetic Nephropathy

Authors: Pardis Abolghasemi, Benyamin Hatamsaz

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Background: Diabetic nephropathy is a serious health problem described by specific kidney structure and functional disturbance. Renoprotective effects of the stem cells secretase have been shown in many kidney diseases. The aim is to evaluate the capability of human Wharton’s jelly mesenchymal stem cells conditioned media (hWJMSCs-CM) to alleviate DN in streptozotocin (STZ)-induced diabetes. Methods: Diabetic nephropathy was induced by injection of STZ (60 mg/kg, IP) in twenty rats. Conditioned media was extracted from hWJMSCs at third passages. At week 8, diabetic rats were divided into two groups: treated (hWJMSCs-CM, 500 μl/rat for three weeks, IP) and not treated (DN). In the 11th week, three groups (control, DN and DN+hWJMSCs-CM) were kept in metabolic cages and urine was collected for 24h. Blood pressure (BP) and heart rate (HR) were continuously recorded. The serum samples were maintained for measuring BUN, Cr and angiotensin-converting enzyme (ACE) activity. The left kidney was kept at -80°C for ACE activity assessment. The right kidney and pancreas were used for histopathologic evaluation. Result: Diabetic nephropathy was detected by microalbuminuria and increased albumin/creatinine ratio, as well as the pancreas and renal structural disturbance. Glomerular filtration rate, BP and HR increased in the DN group. The ACE activity was elevated in the serum and kidneys of the DN group. Administration of hWJMSCs-CM modulated the renal functional and structural disturbance and decreased the ACE activity. Conclusion: Conditioned media was extracted from hWJMSCs may have a Renoprotective effect in diabetic nephropathy. This may happen through regulation of ACE activity and renin-angiotensin system inhibition.

Keywords: diabetic nephropathy, mesenchymal stem cells, immunomodulation, anti-inflammation

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506 Hsa-miR-192-5p, and Hsa-miR-129-5p Prominent Biomarkers in Regulation Glioblastoma Cancer Stem Cells Genes Microenvironment

Authors: Rasha Ahmadi

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Glioblastoma is one of the most frequent brain malignancies, having a high mortality rate and limited survival in individuals with this malignancy. Despite different treatments and surgery, recurrence of glioblastoma cancer stem cells may arise as a subsequent tumor. For this reason, it is crucial to research the markers associated with glioblastoma stem cells and specifically their microenvironment. In this study, using bioinformatics analysis, we analyzed and nominated genes in the microenvironment pathways of glioblastoma stem cells. In this study, an appropriate database was selected for analysis by referring to the GEO database. This dataset comprised gene expression patterns in stem cells derived from glioblastoma patients. Gene clusters were divided as high and low expression. Enrichment databases such as Enrichr, STRING, and GEPIA were utilized to analyze the data appropriately. Finally, we extracted the potential genes 2700 high-expression and 1100 low-expression genes are implicated in the metabolic pathways of glioblastoma cancer progression. Cellular senescence, MAPK, TNF, hypoxia, zimosterol biosynthesis, and phosphatidylinositol metabolism pathways were substantially expressed and the metabolic pathways were downregulated. After assessing the association between protein networks, MSMP, SOX2, FGD4 ,and CNTNAP3 genes with high expression and DMKN and SBSN genes with low were selected. All of these genes were observed in the survival curve, with a survival of fewer than 10 percent over around 15 months. hsa-mir-192-5p, hsa-mir-129-5p, hsa-mir-215-5p, hsa-mir-335-5p, and hsa-mir-340-5p played key function in glioblastoma cancer stem cells microenviroments. We introduced critical genes through integrated and regular bioinformatics studies by assessing the amount of gene expression profile data that can play an important role in targeting genes involved in the energy and microenvironment of glioblastoma cancer stem cells. Have. This study indicated that hsa-mir-192-5p, and hsa-mir-129-5p are appropriate candidates for this.

Keywords: Glioblastoma, Cancer Stem Cells, Biomarker Discovery, Gene Expression Profiles, Bioinformatics Analysis, Tumor Microenvironment

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505 Potentials and Challenges of Implementing Participatory Irrigation Management, Tanzania

Authors: Pilly Joseph Kagosi

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The study aims at assessing challenges observed during implementation of participatory irrigation management (PIM) approach for food security in semi-arid areas of Tanzania. Data were collected through questionnaire, PRA tools, key informants discussion, Focus Group Discussion (FGD), participant observation and literature review. Data collected from questionnaire was analyzed using SPSS while PRA data was analyzed with the help of local communities during PRA exercise. Data from other methods were analyzed using content analysis. The study revealed that PIM approach has contribution in improved food security at household level due to involvement of communities in water management activities and decision making which enhanced availability of water for irrigation and increased crop production. However there were challenges observed during implementation of the approach including; minimum participation of beneficiaries in decision making during planning and designing stages, meaning inadequate devolution of power among scheme owners; Inadequate and lack of transparency on income expenditure in Water Utilization Associations’ (WUAs), water conflict among WUAs members, conflict between farmers and livestock keepers and conflict between WUAs leaders and village government regarding training opportunities and status; WUAs rules and regulation are not legally recognized by the National court and few farmers involved in planting trees around water sources. However it was realized that some of the mentioned challenges were rectified by farmers themselves facilitated by government officials. The study recommends that, the identified challenges need to be rectified for farmers to realize impotence of PIM approach as it was realized by other Asian countries.

Keywords: potentials of implementing participatory approach, challenges of participatory approach, irrigation management, Tanzania

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504 MicroRNA-211 Regulates Oxidative Phosphorylation and Energy Metabolism in Human Vitiligoa

Authors: Anupama Sahoo, Bongyong Lee, Katia Boniface, Julien Seneschal, Sanjaya K. Sahoo, Tatsuya Seki, Chunyan Wang, Soumen Das, Xianlin Han, Michael Steppie, Sudipta Seal, Alain Taieb, Ranjan J. Perera

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Vitiligo is a common, chronic skin disorder characterized by loss of epidermal melanocytes and progressive depigmentation. Vitiligo has a complex immune, genetic, environmental, and biochemical etiology, but the exact molecular mechanisms of vitiligo development and progression, particularly those related to metabolic control, are poorly understood. Here we characterized the human vitiligo cell line PIG3V and the normal human melanocytes, HEM-l by RNA-sequencing, targeted metabolomics, and shotgun lipidomics. Melanocyte-enriched miR-211, a known metabolic switch in non-pigmented melanoma cells, was severely downregulated in vitiligo cell line PIG3V and skin biopsies from vitiligo patients, while its novel predicted targets transcriptional co-activator PGC1-α (PPARGC1A), ribonucleotide reductase regulatory subunit M2 (RRM2), and serine-threonine protein kinase TAO1 (TAOK1) were reciprocally upregulated. miR-211 binds to PGC1-α 3’UTR locus and represses it. Although mitochondrial numbers were constant, mitochondrial complexes I, II, and IV and respiratory responses were defective in vitiligo cells. Nanoparticle-coated miR-211 partially augmented the oxygen consumption rate in PIG3V cells. The lower oxygen consumption rate, changes in lipid and metabolite profiles, and increased reactive oxygen species production observed in vitiligo cells appear to be partly due to abnormal regulation of miR-211 and its target genes. These genes represent potential biomarkers and therapeutic targets in human vitiligo.

Keywords: metabolism, microRNA, mitochondria, vitiligo

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503 Need for Privacy in the Technological Era: An Analysis in the Indian Perspective

Authors: Amrashaa Singh

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In the digital age and the large cyberspace, Data Protection and Privacy have become major issues in this technological era. There was a time when social media and online shopping websites were treated as a blessing for the people. But now the tables have turned, and the people have started to look at them with suspicion. They are getting aware of the privacy implications, and they do not feel as safe as they used to initially. When Edward Snowden informed the world about the snooping United States Security Agencies had been doing, that is when the picture became clear for the people. After the Cambridge Analytica case where the data of Facebook users were stored without their consent, the doubts arose in the minds of people about how safe they actually are. In India, the case of spyware Pegasus also raised a lot of concerns. It was used to snoop on a lot of human right activists and lawyers and the company which invented the spyware claims that it only sells it to the government. The paper will be dealing with the privacy concerns in the Indian perspective with an analytical methodology. The Supreme Court here had recently declared a right to privacy a Fundamental Right under Article 21 of the Constitution of India. Further, the Government is also working on the Data Protection Bill. The point to note is that India is still a developing country, and with the bill, the government aims at data localization. But there are doubts in the minds of many people that the Government would actually be snooping on the data of the individuals. It looks more like an attempt to curb dissenters ‘lawfully’. The focus of the paper would be on these issues in India in light of the European Union (EU) General Data Protection Regulation (GDPR). The Indian Data Protection Bill is also said to be loosely based on EU GDPR. But how helpful would these laws actually be is another concern since the economic and social conditions in both countries are very different? The paper aims at discussing these concerns, how good or bad is the intention of the government behind the bill, and how the nations can act together and draft common regulations so that there is some uniformity in the laws and their application.

Keywords: Article 21, data protection, dissent, fundamental right, India, privacy

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502 Association of Brain-Derived Neurotrophic Factor (BDNF) Gene with Obesity and Metabolic Traits in Malaysian Adults

Authors: Yamunah Devi Apalasamy, Sanjay Rampal, Tin Tin Su, Foong Ming Moy, Hazreen Abdul Majid, Awang Bulgiba, Zahurin Mohamed

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Obesity is a growing global health issue. Obesity results from a combination of environmental and genetics factors. Brain-derived neurotrophic factor (BDNF), a gene encodes the BDNF protein and the BDNF gene have been linked to regulation of body weight and appetite. Genome-wide association studies have identified the BDNF variants to be related to obesity among Caucasians, East Asians, and Filipinos. However, the role of BDNF in other ethnic groups remains inconclusive. This case control study aims to investigate the associations of BDNF gene polymorphisms with obesity and metabolic parameters in Malaysian Malays. BDNF rs4074134, BDNF rs10501087 and BDNF rs6265 were genotyped using Sequenom MassARRAY. Anthropometric, body fat, fasting lipids and glucose levels were measured. A total of 663 subjects (194 obese and 469 non-obese) were included in this study. There were no significant associations association between BDNF SNPs and obesity. The allelic and genotype frequencies of the BDNF SNPs were similar in the obese and non-obese groups. After adjustment for age and sex, the BDNF variants were not associated with obesity, body fat, fasting lipids and glucose levels. Haplotypes at the BDNF gene region, were not significantly associated with obesity. The BDNF rs4074134 was in strong LD with BDNF rs10501087 (D'=0.98) and BDNF rs6265 (D'=0.87). The BDNF rs10501087 was also in strong LD with BDNF rs6265 (D'=0.91). Our findings suggest that the BDNF variants and the haplotypes of BDNF gene were not associated with obesity and metabolic traits in this study population. Further research is needed to explore other BDNF variants with a larger sample size with gene-environment interactions in multi ethnic Malaysian population.

Keywords: genomics of obesity, SNP, BMI, haplotypes

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501 Rating Agreement: Machine Learning for Environmental, Social, and Governance Disclosure

Authors: Nico Rosamilia

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The study evaluates the importance of non-financial disclosure practices for regulators, investors, businesses, and markets. It aims to create a sector-specific set of indicators for environmental, social, and governance (ESG) performances alternative to the ratings of the agencies. The existing literature extensively studies the implementation of ESG rating systems. Conversely, this study has a twofold outcome. Firstly, it should generalize incentive systems and governance policies for ESG and sustainable principles. Therefore, it should contribute to the EU Sustainable Finance Disclosure Regulation. Secondly, it concerns the market and the investors by highlighting successful sustainable investing. Indeed, the study contemplates the effect of ESG adoption practices on corporate value. The research explores the asset pricing angle in order to shed light on the fragmented argument on the finance of ESG. Investors may be misguided about the positive or negative effects of ESG on performances. The paper proposes a different method to evaluate ESG performances. By comparing the results of a traditional econometric approach (Lasso) with a machine learning algorithm (Random Forest), the study establishes a set of indicators for ESG performance. Therefore, the research also empirically contributes to the theoretical strands of literature regarding model selection and variable importance in a finance framework. The algorithms will spit out sector-specific indicators. This set of indicators defines an alternative to the compounded scores of ESG rating agencies and avoids the possible offsetting effect of scores. With this approach, the paper defines a sector-specific set of indicators to standardize ESG disclosure. Additionally, it tries to shed light on the absence of a clear understanding of the direction of the ESG effect on corporate value (the problem of endogeneity).

Keywords: ESG ratings, non-financial information, value of firms, sustainable finance

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500 Association of MMP-2,-9 Overexpression and Imbalance PGR-A/PGR-B Ratio in Endometriosis

Authors: P. Afsharian, S. Mousazadeh, M. Shahhoseini, R. Aflatoonian

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Introduction: Matrix MetalloProteinases (MMPs) degrade extracellular matrix components to provide normal remodeling and contribute to pathological tissue destruction and cell migration in endometriosis. It is accepted that MMPs are resistant to suppression by progesterone in endometriotic tissues. The physiological effects of progesterone are mediated by its two progesterone receptor (PGR) isoforms, namely PGR-A and PGR-B. The capacity of progesterone affect to gene expression is dependent on the PGR-A/PGR-B ratio. The imbalance ratio in endometriotic tissue may be an important mechanism to be resulted in Progesterone resistance and modify progesterone action via differential regulation of specific progesterone response genes and improve endometriosis disease. Material and methods: RNA was extracted from twenty ectopic (endometriotic) and eutopic (endometrial) tissue samples of women undergoing laparoscopy for endometriosis and 20 healthy fertile women at Royan Institute, Tehran, Iran. Analysis of PGR-A, PGR-B, MMP-2 and MMP-9 mRNA expression was performed using Real-time PCR in ectopic and eutopic tissues. Then, Statistical analysis was calculated according to the 2-ΔΔCT equation for all samples. Results: Quantitative RT–PCR analyses of PGR-A and PGR-B mRNA revealed that there were differences in both isoformes of PGRs mRNA expressions between ectopic and control eutopic tissues. We were able to demonstrate low expression levels of PGR-B isoforms in ectopic tissues. Although, PGR-A expression was significantly higher in the same ectopic samples compare to controls.This method permitted us to demonstrate significant overexpression of MMP-2 and MMP-9 in ectopic samples compared to control endometrial tissues, as well. Conclusions: Our data suggest that low expression levels of PGR-B and overexpression of PGR-A can alter PGR-A/PGR-B ratio in endometriotic ectopic tissues. Imbalance ratio of PGRs in endometriotic tissue may be able to consequence MMP-2 and MMP-9 overexpression which can be important in pathogenesis and treatment of disease.

Keywords: endometriosis, matrix metalloproteinases, progesterone receptor -A and -B, PGR-A/PGR-B ratio

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499 Dogmatic Analysis of Legal Risks of Using Artificial Intelligence: The European Union and Polish Perspective

Authors: Marianna Iaroslavska

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ChatGPT is becoming commonplace. However, only a few people think about the legal risks of using Large Language Model in their daily work. The main dilemmas concern the following areas: who owns the copyright to what somebody creates through ChatGPT; what can OpenAI do with the prompt you enter; can you accidentally infringe on another creator's rights through ChatGPT; what about the protection of the data somebody enters into the chat. This paper will present these and other legal risks of using large language models at work using dogmatic methods and case studies. The paper will present a legal analysis of AI risks against the background of European Union law and Polish law. This analysis will answer questions about how to protect data, how to make sure you do not violate copyright, and what is at stake with the AI Act, which recently came into force in the EU. If your work is related to the EU area, and you use AI in your work, this paper will be a real goldmine for you. The copyright law in force in Poland does not protect your rights to a work that is created with the help of AI. So if you start selling such a work, you may face two main problems. First, someone may steal your work, and you will not be entitled to any protection because work created with AI does not have any legal protection. Second, the AI may have created the work by infringing on another person's copyright, so they will be able to claim damages from you. In addition, the EU's current AI Act imposes a number of additional obligations related to the use of large language models. The AI Act divides artificial intelligence into four risk levels and imposes different requirements depending on the level of risk. The EU regulation is aimed primarily at those developing and marketing artificial intelligence systems in the EU market. In addition to the above obstacles, personal data protection comes into play, which is very strictly regulated in the EU. If you violate personal data by entering information into ChatGPT, you will be liable for violations. When using AI within the EU or in cooperation with entities located in the EU, you have to take into account a lot of risks. This paper will highlight such risks and explain how they can be avoided.

Keywords: EU, AI act, copyright, polish law, LLM

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498 The Predictive Value of Micro Rna 451 on the Outcome of Imatinib Treatment in Chronic Myeloid Leukemia Patients

Authors: Nehal Adel Khalil, Amel Foad Ketat, Fairouz Elsayed Mohamed Ali, Nahla Abdelmoneim Hamid, Hazem Farag Manaa

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Background: Chronic myeloid leukemia (CML) represents 15% of adult leukemias. Imatinib Mesylate (IM) is the gold standard treatment for new cases of CML. Treatment with IM results in improvement of the majority of cases. However, about 25% of cases may develop resistance. Sensitive and specific early predictors of IM resistance in CML patients have not been established to date. Aim: To investigate the value of miR-451 in CML as an early predictor for IM resistance in Egyptian CML patients. Methods: The study employed Real time Polymerase Reaction (qPCR) technique to investigate the leucocytic expression of miR-451 in fifteen newly diagnosed CML patients (group I), fifteen IM responder CML patients (group II), fifteen IM resistant CML patients (group III) and fifteen healthy subjects of matched age and sex as a control group (group IV). The response to IM was defined as < 10% BCR-ABL transcript level after 3 months of therapy. The following parameters were assessed in subjects of all the studied groups: 1- Complete blood count (CBC). 2- Measurement of plasma level of miRNA 451 using real-time Polymerase Chain Reaction (qPCR). 3- Detection of BCR-ABL gene mutation in CML using qPCR. Results: The present study revealed that miR-451 was significantly down-regulated in leucocytes of newly diagnosed CML patients as compared to healthy subjects. IM responder CML patients showed an up-regulation of miR- 451 compared with IM resistant CML patients. Conclusion: According to the data from the present study, it can be concluded that leucocytic miR- 451 expression is a useful additional follow-up marker for the response to IM and a promising prognostic biomarker for CML.

Keywords: chronic myeloid leukemia, imatinib resistance, microRNA 451, Polymerase Chain Reaction

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497 The Impact of Corporate Finance on Financial Stability in the Western Balkan Countries

Authors: Luan Vardari, Dena Arapi-Vardari

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Financial stability is a critical component of economic growth and development, and it has been recognized as a key policy objective in many countries around the world. In the Western Balkans, financial stability has been a key issue in recent years, with a number of challenges facing the region, including high levels of public debt, weak banking systems, and economic volatility. Corporate finance, which refers to the financial management practices of firms, is an important factor that can impact financial stability. This paper aims to investigate corporate finance's impact on financial stability in Western Balkan countries. This study will use a mixed-methods approach to investigate the impact of corporate finance on financial stability in the Western Balkans. The study will begin with a comprehensive review of the existing literature on corporate finance and financial stability, focusing on the Western Balkan region. This will be followed by an empirical analysis of regional corporate finance practices using data from various industries and firms. The analysis will explore the relationship between corporate finance practices and financial stability, taking into account factors such as regulatory frameworks, economic conditions, and firm size. The results of the study are expected to provide insights into the impact of corporate finance on financial stability in the Western Balkans. Specifically, the study will identify the key corporate finance practices that contribute to financial stability in the region, as well as the challenges and obstacles that firms face in implementing effective corporate finance strategies. The study will also provide recommendations for policymakers and firms looking to enhance financial stability and resilience in the region.

Keywords: financial regulation, debt management, investment decisions, dividend policies, economic volatility, banking systems, public debt, prudent financial management, firm size, policy recommendations

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496 Conceptual Understanding for the Adoption of Energy Assessment Methods in the United Arab Emirates Built Environment

Authors: Amna I. Shibeika, Batoul Y. Hittini, Tasneem B. Abd Bakri

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Regulation and integration of public policy, economy, insurance industry, education, and construction stakeholders are the main contributors to achieve sustainable development. Building environmental assessment methods were introduced in the field to address issues such as global warming and conservation of natural resources. In the UAE, Estidama framework with its associated Pearl Building Rating System (PBRS) has been introduced in 2010 to address and spread sustainability practices within the country’s fast-growing built environment. Based on literature review of relevant studies investigating different project characteristics that influence sustainability outcomes, this paper presents a conceptual framework for understanding the adoption of PBRS in UAE projects. The framework also draws on Diffusion of Innovations theory to address the questions of how the assessment method is chosen in the first place and what is the impact of PBRS on the multi-disciplinary design and construction processes. The study highlights the mandatory nature of the adoption of PBRS for government buildings as well as imbedding Estidama principles within Abu Dhabi building codes as key factors for raising awareness about sustainable practices. Moreover, several project-related elements are addressed to understand their relationship with the adoption process, including project team collaboration; communication and coordination; levels of commitment and engagement; and the involvement of key actors as sustainability champions. This conceptualization of the adoption of PBRS in UAE projects contributes to the growing literature on the adoption of energy assessment tools and addresses the UAE vision is to be at the forefront of innovative sustainable development by 2021.

Keywords: adoption, building assessment, design management, innovation, sustainability

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495 Honey Contamination in the Republic of Kazakhstan

Authors: B. Sadepovich Maikanov, Z. Shabanbayevich Adilbekov, R. Husainovna Mustafina, L. Tyulegenovna Auteleyeva

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This study involves detailed information about contaminants of honey in the Republic of Kazakhstan. The requirements of the technical regulation ‘Requirements to safety of honey and bee products’ and GOST 19792-2001 were taken into account in this research. Contamination of honey by antibiotics wqs determined by the IEA (immune-enzyme analysis), Ridder analyzer and Tecna produced test systems. Voltammetry (TaLab device) was used to define contamination by salts of heavy metals and gamma-beta spectrometry, ‘Progress BG’ system, with preliminary ashing of the sample of honey was used to define radioactive contamination. This article pointed out that residues of chloramphenicol were detected in 24% of investigated products, in 22% of them –streptomycin, in 7.3% - sulfanilamide, in 2.4% - tylosin, and in 12% - combined contamination was noted. Geographically, the greatest degree of contamination of honey with antibiotics occurs in the Northern Kazakhstan – 54.4%, and Southern Kazakhstan - 50%, and the lowest in Central and Eastern Kazakhstan with 30% and 25%, respectively. Generally, pollution by heavy metals is within acceptable limits, but the contamination from lead is highest in the Akmola region. The level of radioactive cesium and strontium is also within acceptable concentrations. The highest radioactivity in terms of cesium was observed in the East Kazakhstan region - 49.00±10 Bq/kg, in Akmola, North Kazakhstan and Almaty - 12.00±5, 11.05±3 and 19.0±8 Bq/kg, respectively, while the norm is 100 Bq/kg. In terms of strontium, the radioactivity in the East Kazakhstan region is 25.03±15 Bq/kg, while in Akmola, North Kazakhstan and Almaty regions it is 12.00±3, 10.2±4 and 1.0±2 Bq/kg, respectively, with the norm of 80 Bq/kg. This accumulation is mainly associated with the environmental degradation, feeding and treating of bees. Moreover, in the process of collecting nectar, external substances can penetrate honey. Overall, this research determines factors and reasons of honey contamination.

Keywords: antibiotics, contamination of honey, honey, radionuclides

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494 Influence of Water Reservoir Parameters on the Climate and Coastal Areas

Authors: Lia Matchavariani

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Water reservoir construction on the rivers flowing into the sea complicates the coast protection, seashore starts to degrade causing coast erosion and disaster on the backdrop of current climate change. The instruments of the impact of a water reservoir on the climate and coastal areas are its contact surface with the atmosphere and the area irrigated with its water or humidified with infiltrated waters. The Black Sea coastline is characterized by the highest ecological vulnerability. The type and intensity of the water reservoir impact are determined by its morphometry, type of regulation, level regime, and geomorphological and geological characteristics of the adjoining area. Studies showed the impact of the water reservoir on the climate, on its comfort parameters is positive if it is located in the zone of insufficient humidity and vice versa, is negative if the water reservoir is found in the zone with abundant humidity. There are many natural and anthropogenic factors determining the peculiarities of the impact of the water reservoir on the climate, which can be assessed with maximum accuracy by the so-called “long series” method, which operates on the meteorological elements (temperature, wind, precipitations, etc.) with the long series formed with the stationary observation data. This is the time series, which consists of two periods with statistically sufficient duration. The first period covers the observations up to the formation of the water reservoir and another period covers the observations accomplished during its operation. If no such data are available, or their series is statistically short, “an analog” method is used. Such an analog water reservoir is selected based on the similarity of the environmental conditions. It must be located within the zone of the designed water reservoir, under similar environmental conditions, and besides, a sufficient number of observations accomplished in its coastal zone.

Keywords: coast-constituent sediment, eustasy, meteorological parameters, seashore degradation, water reservoirs impact

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493 A Critique of Contemporary Sexual Liberation: A Third Way Analysis

Authors: Sydelle Barreto

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Sexual liberation has been thought of as a movement, an idea, and an antithesis of material oppression. Within feminism it has consistently resisted definition - different feminist schools of thought had entirely different constructions of what liberated feminine sexuality could look like and how we might get there. This paper will critique the current definition of sexual liberation as being limited and carceral in its perspectives of sexual assault and extremely reductive in its imaginings of sexual liberation. The ultimate goal of this assessment is to potentially outline what true sexual liberation might look like in a way that is inclusive but not ignorant of the realities of the patriarchy. The first critique of sexual liberation included in the paper centers around the limits of consent, carceral feminism and sexual subjectivity. The argument will build off the traditionally sex-negative critiques of consent as being limited in scope by explaining how a lack of nuance is even more dangerous to victims of sexual violations. The discussion will also expand an interrogant of consent to an interrogation of wantedness and desire. If we understand that critiquing the conditions of consent is important, we must also critique the way patriarchy and compulsory sexuality have affected desire. Using the aforementioned concept of compulsory sexuality, the paper will argue that while sexual liberation has begun to include queer and transgender individuals, it is still overwhelmingly allonormative. Sex positivity and its opponents both fail to include asexuality. This ultimately leads to a conflation of sexual liberation with genuine material liberation. Just as we cannot divorce our constructions of sexual liberation from the realities of the patriarchy and rape culture, we should consider compulsory sexuality as its own system of social regulation. The conclusion will begin to construct an alternative vision of sexual liberation, leveraging concepts of sexual subjectivity, including a rejection of carceral feminism as a response to sexual violence, and finally, leading to the beginnings of a deconstruction of compulsory sexuality. The paper concludes with a vision of sexual liberation that does not confuse itself with material liberation or mere sexual oppression, but rather a key way stops on the road to constructing our most authentic sexual selves.

Keywords: feminism, sexual assault, sexual liberation, consent

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492 The Effect of Perceived Parental Overprotection on Morality in College Students

Authors: Sunghyun Cho, Seung-Ah Lee

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Parental overprotection is known to have negative effects such as low independence, immature emotion regulation, and immoral behaviors on children’s development. This study investigated the effects of parental overprotection on Korean college students’ moral behaviors. In order to test the hypothesis that overprotected participants are more likely to show immoral behaviors in moral dilemma situations, we measured perceived parental overprotection using Korean-Parental Overprotection Scale (K-POS), Helicopter Parenting Behaviors, and Helicopter Parenting Instrument (HPI) for 200 college students. Participants’ level of morality was assessed using two types of online experimental tasks consisting of a word-searching puzzle and a visual perception task. Based on the level of perceived parental overprotection, 14 participants with high total scores in overparenting scales and 14 participants with average total scores in the scales were assigned to a high perceived overparenting student group, and control group, respectively. Results revealed that the high perceived overparenting group submitted significantly more untruthful answers compared to the control group in the visual perception task (t = 2.72, p < .05). However, there was no significant difference in immorality in the word-searching puzzle(t = 1.30, p > .05), yielding inconsistent results for the relationship between. These inconsistent results of two tasks assessing morality may be because submitting untruthful answers in the word-searching puzzle initiated a larger sense of immorality compared to the visual perception task. Thus, even the perceived overparenting participants seemingly tended not to submit immoral answers. Further implications and limitations of the study are discussed.

Keywords: college students, morality, overparenting, parental overprotection

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491 Monitoring of Sustainability of Decorated Confectionary Product 'Moskva Cake' in Order to Define the Expiration Date

Authors: Radovan Cobanovic, Milica Rankov-Sicar

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The fresh cake is in the group of perishable food which cannot be kept a long period of time. The study of sustainability has been done in order to extend the shelf-life of the product which was 10 days. According to the plan of sustainability, it was defined that 5 samples had to be stored for 20 days at max +8°C and analyzed every 5th day from the day of reception until the 20th day. The shelf life of cake has expired during the study of sustainability in the period between 10th and 20th day of analyses. Cake samples were subjected to sensory analysis (appearance, odor, taste, color, aroma) and bacteriological analysis (Listeria monocytogenes, Salmonella spp. and Enterobacteriaceae) according to Serbian state regulation. All analysis were tested according to ISO methodology: sensory analysis ISO 6658, Listeria monocytogenes ISO 11290-1, Salmonella spp ISO 6579, and Enterobacteriaceae ISO 21258-2. Analyses showed that after ten days of storage at a temperature defined by the manufacturers and within the product's shelf life, the cake did not have any noticeable changes in sensory characteristics. Smell and taste are unaffected there was no presence of strange smell or taste. As far as microbiological analyses are concerned, neither one pathogen was detected and number of Enterobacteriaceae was at level less than 102 cfu/g. After expiry of shelf life in a period of 15th and 20th day of storage, the sensory analysis showed the presence of strange sour-milky smell and rancid taste. Concerning microbiological analyses, there still were not positive results for pathogen microorganisms but the number of Enterobacteriaceae was at level more than 103cfu/g. Reviewing the results of sensory analysis indicates that it is not recommended to extend the shelf-life of the product comparing to the already defined shelf-life because occurred changes may adversely affect the consumer desire for the choice of this product.

Keywords: confectionary product, extension of shelf life, sensory and microbiological analyses, sustainability

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490 Anti-TNF: Possibilities of Rising Anti-Phosphorylcholine Antibodies

Authors: Md. Mizanur Rahman, Anquan Liu, Anna Frostegård, Johan Frostegård

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The role of the human immune system is essential in cardiovascular diseases and atherosclerosis. Activated cells in atherosclerosis produce abundant amounts of cytokines, but the exact mechanisms involved in the effects of these inflammatory cytokines are not clear in atherosclerosis. In a large clinical cohort, we have previously determined that antibodies against phosphorylcholine (anti-PC) are negatively and independently associated with both development of atherosclerosis and also a low risk of cardiovascular disease. Further, we reported that rheumatoid arthritis patients who were non-responders to TNF-inhibitors, where those with low anti-PC levels. Upon anti-TNF treatment, anti-PC levels increased. We, therefore, hypothesised that proinflammatory cytokines such as TNF could play a role in anti-PC regulation. Peripheral blood mononuclear cells (PBMC) were cultured with or without TNF and anti-TNF. The cell supernatants were collected after six days for ELISA measurements. In separate experiments, cells were cultured for 24 hours in both polystyrene plates and ELISPOT plates under a similar condition for ELISA and ELISPOT assays respectively. Total RNA was extracted after 6 hours of cell culture to perform RT-qPCR. Cell viability was confirmed by trypan blue staining and MTT assays. ELISA measurements detected less than 40% of anti-PC in TNF-treated cells, in comparison to control cells, whereas anti-PC production was recovered by anti-TNF treatment. ELISPOT assays showed that TNF suppresses anti-PC production by inhibiting anti-PC producing B-cells. In addition, RT-qPCR and ELISA showed that TNF also has effects also on B-cell activation as BAFF expression was inhibited by TNF treatment. Atherosclerosis is a major cause of cardiovascular diseases, but anti-PC is a protection marker for atherosclerosis development. Our findings show that TNF is a negative regulator of anti-PC production. Immune modulation and rising of anti-PC could be of major significance for the patients.

Keywords: anti-PC, Anti-TNF, atherosclerosis, cardiovascular diseases, phosphorylecholine

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489 Effect of Salinity and Heavy Metal Toxicity on Gene Expression, and Morphological Characteristics in Stevia rebaudiana Plants

Authors: Umara Nissar Rafiqi, Irum Gul, Nazima Nasrullah, Monica Saifi, Malik Z. Abdin

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Background: Stevia rebaudiana, a member of Asteraceae family is an important medicinal plant and produces a commercially used non-caloric natural sweetener, which is also an alternate herbal cure for diabetes. Steviol glycosides are the main sweetening compounds present in these plants. Secondary metabolites are crucial to the adaption of plants to the environment and its overcoming stress conditions. In agricultural procedures, the abiotic stresses like salinity, high metal toxicity and drought, in particular, are responsible for the majority of the reduction that differentiates yield potential from harvestable yield. Salt stress and heavy metal toxicity lead to increased production of reactive oxygen species (ROS). To avoid oxidative damage due to ROS and osmotic stress, plants have a system of anti-oxidant enzymes along with several stress induced enzymes. This helps in scavenging the ROS and relieve the osmotic stress in different cell compartments. However, whether stress induced toxicity modulates the activity of these enzymes in Stevia rebaudiana is poorly understood. Aim: The present study focussed on the effect of salinity, heavy metal toxicity (lead and mercury) on physiological traits and transcriptional profiling of Stevia rebaudiana. Method: Stevia rebaudiana plants were collected from the Central Institute of Medicinal and Aromatic plants (CIMAP), Patnagar, India and maintained under controlled conditions in a greenhouse at Hamdard University, Delhi, India. The plants were subjected to different concentrations of salt (0, 25, 50 and 75 mM respectively) and heavy metals, lead and mercury (0, 100, 200 and 300 µM respectively). The physiological traits such as shoot length, root numbers, leaf growth were evaluated. The samples were collected at different developmental stages and analysed for transcription profiling by RT-PCR. Transcriptional studies in stevia rebaudiana involves important antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), cytochrome P450 monooxygenase (CYP) and stress induced aquaporin (AQU), auxin repressed protein (ARP-1), Ndhc gene. The data was analysed using GraphPad Prism and expressed as mean ± SD. Result: Low salinity and lower metal toxicity did not affect the fresh weight of the plant. However, this was substantially decreased by 55% at high salinity and heavy metal treatment. With increasing salinity and heavy metal toxicity, the values of all studied physiological traits were significantly decreased. Chlorosis in treated plants was also observed which could be due to changes in Fe:Zn ratio. At low concentrations (upto 25 mM) of NaCl and heavy metals, we did not observe any significant difference in the gene expressions of treated plants compared to control plants. Interestingly, at high salt concentration and high metal toxicity, a significant increase in the expression profile of stress induced genes was observed in treated plants compared to control (p < 0.005). Conclusion: Stevia rebaudiana is tolerant to lower salt and heavy metal concentration. This study also suggests that with the increase in concentrations of salt and heavy metals, harvest yield of S. rebaudiana was hampered.

Keywords: Stevia rebaudiana, natural sweetener, salinity, heavy metal toxicity

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