Search results for: gene relationships

Authors: Giorgio Bertolazzi, Panayiotis Benos, Michele Tumminello, Claudia Coronnello

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MicroRNAs are small non-coding RNAs that post-transcriptionally regulate the expression levels of messenger RNAs. MicroRNA regulation activity depends on the recognition of binding sites located on mRNA molecules. ComiR (Combinatorial miRNA targeting) is a user friendly web tool realized to predict the targets of a set of microRNAs, starting from their expression profile. ComiR incorporates miRNA expression in a thermodynamic binding model, and it associates each gene with the probability of being a target of a set of miRNAs. ComiR algorithms were trained with the information regarding binding sites in the 3’UTR region, by using a reliable dataset containing the targets of endogenously expressed microRNA in D. melanogaster S2 cells. This dataset was obtained by comparing the results from two different experimental approaches, i.e., inhibition, and immunoprecipitation of the AGO1 protein; this protein is a component of the microRNA induced silencing complex. In this work, we tested whether including coding region binding sites in the ComiR algorithm improves the performance of the tool in predicting microRNA targets. We focused the analysis on the D. melanogaster species and updated the ComiR underlying database with the currently available releases of mRNA and microRNA sequences. As a result, we find that the ComiR algorithm trained with the information related to the coding regions is more efficient in predicting the microRNA targets, with respect to the algorithm trained with 3’utr information. On the other hand, we show that 3’utr based predictions can be seen as complementary to the coding region based predictions, which suggests that both predictions, from 3'UTR and coding regions, should be considered in a comprehensive analysis. Furthermore, we observed that the lists of targets obtained by analyzing data from one experimental approach only, that is, inhibition or immunoprecipitation of AGO1, are not reliable enough to test the performance of our microRNA target prediction algorithm. Further analysis will be conducted to investigate the effectiveness of the tool with data from other species, provided that validated datasets, as obtained from the comparison of RISC proteins inhibition and immunoprecipitation experiments, will be available for the same samples. Finally, we propose to upgrade the existing ComiR web-tool by including the coding region based trained model, available together with the 3’UTR based one.

Keywords: AGO1, coding region, Drosophila melanogaster, microRNA target prediction

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Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

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Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

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Authors: Ezzati Givi M., Hoveizi E., Nezhad Marani N.

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Platinum-based anticancer therapeutics are the most widely used drugs in clinical chemotherapy but have major limitations and various side effects in clinical applications. Gonadotoxicity and sterility is one of the most common complications for cancer survivors, which seem to be drug-specific and dose-related. Therefore, many efforts have been dedicated to discovering a new structure of platinum-based anticancer agents with improved therapeutic index, fewer side effects. In this regard, new Pt(II)-phosphane complexes containing heterocyclic thionate ligands (PCTL) have been synthesized, which show more potent antitumor activities in comparison to cisplatin. Cisplatin, the best leading metal-based antitumor drug in the field, induces testicular toxicity on Leydig and Sertoli cells leading to serious side effects such as azoospermia and infertility. Therefore in the present study, we aimed to investigate the cytotoxicity effect of PCTL on mice TM4 Sertoli cells with particular emphasis on the role of autophagy in comparison to cisplatin. In this study, an MTT assay was performed to evaluate the IC50 of PCTL and to analyze the TM3 Leydig cell's viability. Cells morphology was evaluated via invert microscope and Changing in morphology for nuclei swelling or autophagic vacuoles formation were assessed by DAPI and MDC staining. Testosterone production in the culture medium was measured using an ELISA kit. Finally, the expression of Autophagy-related genes, Atg5, Beclin1 and p62, were analyzed by qPCR. Based on the obtained results by MTT, the IC50 value of PCTL was 50 μM in TM3 cells and cytotoxic effects was in a dose- and time-dependent manner. Cells morphological changes investigated by inverted microscopy, DAPI, and MDC staining which showed the cytotoxic concentrations of PCTL was significantly higher than cisplatin in the treated TM3 Leydig cells. The results of PCR showed a lack of expression of the p62, Atg5 and Beclin1 gene in TM3 cells treated with PCTL in comparison to cisplatin and control groups. It should be noted that the effects of 25 μM PCTL concentration on TM3 cells have been associated with increased testosterone production and secretion, which requires further study to explain the possible causes and involved molecular mechanisms. The results of the study showed that the PCTL had less-lethal effects on TM3 cells in comparison to cisplatin and probably did not induce autophagy in TM3 cells.

Keywords: platinum-based anticancer agents, cisplatin, Leydig TM3 cells, autophagy

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Authors: Mohammadjavad Sotoudeheian

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COVID-19, which began in December 2019, uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter and spread through the cells. ACE2 mRNA is present in almost every organ, including nasopharynx, lung, as well as the brain. Ports of entry of SARS-CoV-2 into the central nervous system (CNS) may include arterial circulation, while viremia is remarkable. However, it is imperious to develop neurological symptoms evaluation CSF analysis in patients with COVID-19, but theoretically, ACE2 receptors are expressed in cerebellar cells and may be a target for SARS-CoV-2 infection in the brain. Recent evidence agrees that SARS-CoV-2 can impact the brain through direct and indirect injury. Two biomarkers for CNS injury, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NFL) detected in the plasma of patients with COVID-19. NFL, an axonal protein expressed in neurons, is related to axonal neurodegeneration, and GFAP is over-expressed in CNS inflammation. GFAP cytoplasmic accumulation causes Schwan cells to misfunction, so affects myelin generation, reduces neuroskeletal support over NfLs during CNS inflammation, and leads to axonal degeneration. Interleukin-6 (IL-6), which extensively over-express due to interleukin storm during COVID-19 inflammation, regulates gene expression, as well as GFAP through STAT molecular pathway. IL-6 also impresses the phosphoinositide 3-kinase (PI3K)/STAT/smads pathway. The PI3K/ protein kinase B (Akt) pathway is the main modulator upstream of the mammalian target of rapamycin (mTOR), and alterations in this pathway are common in neurodegenerative diseases. Most neurodegenerative diseases show a disruption of autophagic function and display an abnormal increase in protein aggregation that promotes cellular death. Therefore, induction of autophagy has been recommended as a rational approach to help neurons clear abnormal protein aggregates and survive. The mTOR is a major regulator of the autophagic process and is regulated by cellular stressors. The mTORC1 pathway and mTORC2, as complementary and important elements in mTORC1 signaling, have become relevant in the regulation of the autophagic process and cellular survival through the extracellular signal-regulated kinase (ERK) pathway.

Keywords: mTORC1, COVID-19, PI3K, autophagy, neurodegeneration

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Authors: Chen-Chi An, Jun-Yi He, Cheng-Han Hsieh, Chen-Ching Ting

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This research has successfully developed an intelligent table tennis ball machine with human play simulate all situations of human play to take the service. It is well known; an excellent ball machine can help the table tennis coach to provide more efficient teaching, also give players the good technical training and entertainment. An excellent ball machine should be able to service all balls based on human play simulation due to the conventional competitions are today all taken place for people. In this work, two counter-rotating wheels are used to service the balls, where changing the absolute rotating speeds of the two wheels and the differences of rotating speeds between the two wheels can adjust the struck forces and the rotating speeds of the ball. The relationships between the absolute rotating speed of the two wheels and the struck forces of the ball as well as the differences rotating speeds between the two wheels and the rotating speeds of the ball are experimentally determined for technical development. The outlet speed, the ejected distance, and the rotating speed of the ball were measured by changing the absolute rotating speeds of the two wheels in terms of a series of differences in rotating speed between the two wheels for calibration of the ball machine; where the outlet speed and the ejected distance of the ball were further converted to the struck forces of the ball. In process, the balls serviced by the intelligent ball machine were based on the received calibration curves with help of the computer. Experiments technically used photosensitive devices to detect the outlet and rotating speed of the ball. Finally, this research developed some teaching programs for technical training using three ball machines and received more efficient training.

Keywords: table tennis, ball machine, human play simulation, counter-rotating wheels

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Authors: Fareena Alladin

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In the Caribbean, issues of food security, health and taste are intricately linked, seen most clearly in the increasing incidence of lifestyle diseases among children coupled with a taste for high calorie and Westernized diets. In order to fully appreciate this link, the role of nutrition environments must be examined. To this end, the present study incorporates tenets of Bourdieu’s social constructivist theory with the Community Nutrition Environment Model. The aim of this study was to examine the relationships between availability of and access to healthy/unhealthy foods within nutrition environments, namely the household and school, and the development of taste preferences for healthy/unhealthy foods among primary school children in a selected educational district in Trinidad and Tobago. A cross-sectional survey of 400 children between the ages of 9 and 11 years was conducted. Data analysis was conducted using SPSS 24. Results indicated that availability of healthy food at home was positively correlated with preference for vegetables, and negatively correlated with preference for salty snacks and fast food. The availability of unhealthy food within the home was found to be negatively correlated with preference for vegetables and positively correlated with preference for salty snacks. Access to unhealthy foods at school had a positive correlation with preference for fast food. These findings highlight the role of the food environment in shaping taste preferences, and point to the need for interrogating the centrality of food security concerns in emerging health concerns of Caribbean countries. Such interrogations are a necessary part of the development of research agendas, and policy formulation and implementation.

Keywords: food security, nutrition environment, taste preference, Trinidad and Tobago

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Authors: Xiaoyu Sun

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In recent years, the rapid development of Artificial Intelligence (AI) has extensively promoted medicine, pharmaceutical, and other related fields. The medical research and development of artificial intelligence by scientific and commercial organizations are on the fast track. The ethics review is one of the critical procedures of registration to get the products approved and launched. However, the SOPs for ethics review is not enough to guide the healthy and rapid development of artificial intelligence in healthcare in China. Ethical Review Measures for Biomedical Research Involving Human Beings was enacted by the National Health Commission of the People's Republic of China (NHC) on December 1st, 2016. However, from a legislative design perspective, it was neither updated timely nor in line with the trends of AI international development. Therefore, it was great that NHC published a consultation paper on the updated version on March 16th, 2021. Based on the most updated laws and regulations in the States and EU, and in-depth-interviewed 11 subject matter experts in China, including lawmakers, regulators, and key members of ethics review committees, heads of Regulatory Affairs in SaMD industry, and data scientists, several suggestions were proposed on top of the updated version. Although the new version indicated that the Ethics Review Committees need to be created by National, Provincial and individual institute levels, the review authorities of different levels were not clarified. The suggestion is that the precise scope of review authorities for each level should be identified based on Risk Analysis and Management Model, such as the complicated leading technology, gene editing, should be reviewed by National Ethics Review Committees, it will be the job of individual institute Ethics Review Committees to review and approve the clinical study with less risk such as an innovative cream to treat acne. Furthermore, to standardize the research and development of artificial intelligence in healthcare in the age of AI, more clear guidance should be given to data security in the layers of data, algorithm, and application in the process of ethics review. In addition, transparency and responsibility, as two of six principles in the Rome Call for AI Ethics, could be further strengthened in the updated version. It is the shared goal among all countries to manage well and develop AI to benefit human beings. Learned from the other countries who have more learning and experience, China could be one of the most advanced countries in artificial intelligence in healthcare.

Keywords: biomedical research involving human beings, data security, ethics committees, ethical review, medical artificial intelligence

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Authors: Haris Karnezi, Kevin Tierney

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Cognitive Behaviour Drama is a research-based intervention model that brought together the science of psychology with the art form of drama to create an unobtrusive and exciting approach that would provide children on the higher end of the autism spectrum the motivation to explore the rules of social interaction and develop competencies associated with communicative success. The method involves engaging the participants in exciting fictional scenarios and encouraging them to seek various solutions on a number of problems that will lead them to an understanding of causal relationships and how a different course of action may lead to a different outcome. The sessions are structured to offer opportunities to the participants to practice target behaviours and understand the functions they serve. The study involved six separate interventions and employed both single case and group designs. Overall 8 children aged between 6 to 13 years, diagnosed with ASD participated in the study. Outcomes were measured using theory of mind tests, executive functioning tests, behavioural observations, pre and post intervention standardised social competence questionnaires for parents and teachers. Collectively, the results indicated positive changes in the self esteem and behaviour of all eight participants. In particular, improvements in the ability to solve theory of mind tasks were noted in the younger group; and qualitative improvements in social communication, in terms of verbal (content) and non verbal expression (body posture, vocal expression, fluency, eye contact, reduction of ritualistic mannerisms) were noted in the older group. The need for reliable impact measures to assess the effectiveness of the model in generating global changes in the participants’ behaviour outside the therapeutic context was identified.

Keywords: autism, drama, intervention, social skills

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Authors: Racha El Kadiri, Mohamed Sultan, Henrique Momm, Zachary Blair, Rachel Schultz, Tamer Al-Bayoumi

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The Mediterranean Basin is a very diverse region of nationalities and climate zones, with a strong dependence on agricultural activities. Predicting long term (with a lead of 1 to 12 months) rainfall, and future droughts could contribute in a sustainable management of water resources and economical activities. In this study, an integrated approach was adopted to construct predictive tools with lead times of 0 to 12 months to forecast rainfall amounts over nine subzones of the Mediterranean Basin region. The following steps were conducted: (1) acquire, assess and intercorrelate temporal remote sensing-based rainfall products (e.g. The CPC Merged Analysis of Precipitation [CMAP]) throughout the investigation period (1979 to 2016), (2) acquire and assess monthly values for all of the climatic indices influencing the regional and global climatic patterns (e.g., Northern Atlantic Oscillation [NOI], Southern Oscillation Index [SOI], and Tropical North Atlantic Index [TNA]); (3) delineate homogenous climatic regions and select nine pilot study zones, (4) apply data mining methods (e.g. neural networks, principal component analyses) to extract relationships between the observed rainfall and the controlling factors (i.e. climatic indices with multiple lead-time periods) and (5) use the constructed predictive tools to forecast monthly rainfall and dry and wet periods. Preliminary results indicate that rainfall and dry/wet periods were successfully predicted with lead zones of 0 to 12 months using the adopted methodology, and that the approach is more accurately applicable in the southern Mediterranean region.

Keywords: rainfall, neural networks, climatic indices, Mediterranean

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Authors: Gileade P. Freitas, Helena B. Lopes, Alann T. P. Souza, Paula G. F. P. Oliveira, Adriana L. G. Almeida, Paulo G. Coelho, Marcio M. Beloti, Adalberto L. Rosa

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Bone tissue presents great capacity to regenerate when injured by trauma, infectious processes, or neoplasia. However, the extent of injury may exceed the inherent tissue regeneration capability demanding some kind of additional intervention. In this scenario, cell therapy has emerged as a promising alternative to treat challenging bone defects. This study aimed at evaluating the effect of local injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs) on bone regeneration of rat calvaria defects. BM-MSCs and AT-MSCs were isolated and characterized by expression of surface markers; cell viability was evaluated after injection through a 21G needle. Defects of 5 mm in diameter were created in calvaria and after two weeks a single injection of BM-MSCs, AT-MSCs or vehicle-PBS without cells (Control) was carried out. Cells were tracked by bioluminescence and at 4 weeks post-injection bone formation was evaluated by micro-computed tomography (μCT) and histology, nanoindentation, and through gene expression of bone remodeling markers. The data were evaluated by one-way analysis of variance (p≤0.05). BM-MSCs and AT-MSCs presented characteristics of mesenchymal stem cells, kept viability after passing through a 21G needle and remained in the defects until day 14. In general, injection of both BM-MSCs and AT-MSCs resulted in higher bone formation compared to Control. Additionally, this bone tissue displayed elastic modulus and hardness similar to the pristine calvaria bone. The expression of all evaluated genes involved in bone formation was upregulated in bone tissue formed by BM-MSCs compared to AT-MSCs while genes involved in bone resorption were upregulated in AT-MSCs-formed bone. We show that cell therapy based on the local injection of BM-MSCs or AT-MSCs is effective in delivering viable cells that displayed local engraftment and induced a significant improvement in bone healing. Despite differences in the molecular cues observed between BM-MSCs and AT-MSCs, both cells were capable of forming bone tissue at comparable amounts and properties. These findings may drive cell therapy approaches toward the complete bone regeneration of challenging sites.

Keywords: cell therapy, mesenchymal stem cells, bone repair, cell culture

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Authors: Jean Paul Muambangu Milambo, Peter Nyasulu, John Akudugu, Leonidas Ndayisaba, Joyce Tsoka-Gwegweni, Lebwaze Massamba Bienvenu, Mitshindo Mwambangu Chiro

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In 2018, non-communicable diseases (NCDs) were responsible for 48% of deaths in the Democratic Republic of Congo (DRC), with cancer contributing to 5% of these deaths. There is a notable absence of cancer registries, capacity-building activities, budgets, and treatment roadmaps in the DRC. Current cancer estimates are primarily based on mathematical modeling with limited data from neighboring countries. This study aimed to assess cancer subtype prevalence in Kinshasa hospitals and compare these findings with WHO model estimates. Methods: A retrospective observational study was conducted from 2018 to 2020 at HJ Hospitals in Kinshasa. Data were collected using American Cancer Society (ACS) questionnaires and physician logs. Descriptive analysis was performed using STATA version 16 to estimate cancer burden and provide evidence-based recommendations. Results: The results from the chart review at HJ Hospitals in Kinshasa (2018-2020) indicate that out of 6,852 samples, approximately 11.16% were diagnosed with cancer. The distribution of cancer subtypes in this cohort was as follows: breast cancer (33.6%), prostate cancer (21.8%), colorectal cancer (9.6%), lymphoma (4.6%), and cervical cancer (4.4%). These figures are based on histopathological confirmation at the facility and may not fully represent the broader population due to potential selection biases related to geographic and financial accessibility to the hospital. In contrast, the World Health Organization (WHO) model estimates for cancer prevalence in the DRC show different proportions. According to WHO data, the distribution of cancer types is as follows: cervical cancer (15.9%), prostate cancer (15.3%), breast cancer (14.9%), liver cancer (6.8%), colorectal cancer (5.9%), and other cancers (41.2%) (WHO, 2020). Conclusion: The data indicate a rising cancer prevalence in DRC but highlight significant gaps in clinical, biomedical, and genetic cancer data. The establishment of a population-based cancer registry (PBCR) and a defined cancer management pathway is crucial. The current estimates are limited due to data scarcity and inconsistencies in clinical practices. There is an urgent need for multidisciplinary cancer management, integration of palliative care, and improvement in care quality based on evidence-based measures.

Keywords: cancer, risk factors, DRC, gene-environment interactions, survivors

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Authors: Hirokatsu Kawashima

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One important element of teaching/learning listening is intensive listening such as listening for precise sounds, words, grammatical, and semantic units. Several classroom-based investigations have been conducted to explore the usefulness of auditory recognition of phonological, grammatical and semantic errors in such a context. The current study reports the results of one such investigation, which targeted auditory recognition of phonological, grammatical, and semantic errors at the sentence level. 56 Japanese EFL learners participated in this investigation, in which their recognition performance of phonological, grammatical and semantic errors was measured on a 9-point scale by learners’ self-evaluation from the perspective of 1) two types of similar English sound (vowel and consonant minimal pair words), 2) two types of sentence word order (verb phrase-based and noun phrase-based word orders), and 3) two types of semantic consistency (verb-purpose and verb-place agreements), respectively, and their general listening proficiency was examined using standardized tests. A number of findings have been made about the interactive relationships between the three types of auditory error recognition and general listening proficiency. Analyses based on the OPLS (Orthogonal Projections to Latent Structure) regression model have disclosed, for example, that the three types of auditory error recognition are linked in a non-linear way: the highest explanatory power for general listening proficiency may be attained when quadratic interactions between auditory recognition of errors related to vowel minimal pair words and that of errors related to noun phrase-based word order are embraced (R2=.33, p=.01).

Keywords: auditory error recognition, intensive listening, interaction, investigation

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Authors: Yakubu Adamu, Baba Alfa, Salahudeen Adamu Gene

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As the drive towards clean, renewable and sustainable energy generation is gradually been reshaped by renewable penetration over time, energy storage has thus, become an optimal solution for utilities looking to reduce transmission and capacity cost, therefore the need for capacity resources to be adjusted accordingly such that renewable energy storage may have the opportunity to substitute for retiring conventional energy systems with higher capacity factors. Considering the Nigeria scenario, where Over 80% of the current Nigerian primary energy consumption is met by petroleum, electricity demand is set to more than double by mid-century, relative to 2025 levels. With renewable energy penetration rapidly increasing, in particular biomass, hydro power, solar and wind energy, it is expected to account for the largest share of power output in the coming decades. Despite this rapid growth, the imbalance between load and resources has created a hindrance to the development of energy storage capacity, load and resources, hence forecasting energy storage capacity will therefore play an important role in maintaining the balance between load and resources including supply and demand. Therefore, the degree to which this might occur, its timing and more importantly its sustainability, is the subject matter of the current research. Here, we forecast the future energy storage capacity rating and thus, evaluate the load and resource scenario in Nigeria. In doing so, We used the scenario-based International Energy Agency models, the projected energy demand and supply structure of the country through 2030 are presented and analysed. Overall, this shows that in high renewable (solar) penetration scenarios in Nigeria, energy storage with 4-6h duration can obtain over 86% capacity rating with storage comprising about 24% of peak load capacity. Therefore, the general takeaway from the current study is that most power systems currently used has the potential to support fairly large penetrations of 4-6 hour storage as capacity resources prior to a substantial reduction in capacity ratings. The data presented in this paper is a crucial eye-opener for relevant government agencies towards developing these energy resources in tackling the present energy crisis in Nigeria. However, if the transformation of the Nigeria. power system continues primarily through expansion of renewable generation, then longer duration energy storage will be needed to qualify as capacity resources. Hence, the analytical task from the current survey will help to determine whether and when long-duration storage becomes an integral component of the capacity mix that is expected in Nigeria by 2030.

Keywords: capacity, energy, power system, storage

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Authors: Muhammad Younas, Zimal Naveed

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Introduction : TB is caused by the bacillus Mycobacterium tuberculosis, which is spread when people who are sick with TB expel bacteria into the air (e.g. by coughing). The 30 high TB burden countries accounted for 87% of all estimated incident cases worldwide, and eight of these countries accounted for more than two thirds of the global total: India (27%), Indonesia (10%), China (7.1%), the Philippines (7.0%), Pakistan (5.7%), Nigeria (4.5%), Bangladesh (3.6%) and the Democratic Republic of the Congo (3.0%). Objective : To analyze prevalence of tuberculosis among the people who presented at THQ hospital Bhalwal between April 2024 to June 2024. Method : Total of 9200 patients presented in the OPD of THQ hospital Bhalwal were included in the study. These presumed cases underwent diagnostic testing by sputum for AFB, Gene expert and chest x rays. The data was then classified based Pulmonary and Extra-pulmonary TB disease and further classified on the basis of bacteriology positive and clinically diagnosed TB. The registered TB cases were then classified in 8 age groups in years and according to the gender. All the registered TB cases were then tested for HIV to observe the relation between Tuberculosis and HIV. Results : The total of 9200 patients presented to OPD during the period of 3 months between April 2024 to June 2024. Total registered cases of Tuberculosis were 161 (comprising 153 new cases and 8 cases after treatment failure). Out of the new cases 83 were males and 70 female cases were identified. The majority of males that were identified lies between age 55-64 and 65 and above while the majority of females that were diagnosed lies in the age group of 5-14 and 15-24. All the registered cases were then tested for HIV but none of them were found to be positive. Conclusion : According to World Health Organisation Global Tuberculosis Report, the incidence of Tubeculosis per 100000 people was 258, equivalent to 0.258 %. However, the study reveals an exceptionally high frequency of TB cases. The prevalence of Tuberculosis per 100000 people was found to be 1750 which is equivalent to 1.75 %. The study revealed that larger proportion of the population is currently affected by TB compared to the global average incidence reported by the WHO. The findings of the study indicates that the prevalence of tuberculosis (TB) among females is most common in the younger population, specifically between the ages of 5 to 24, and particularly within the peak fertility age group of 15 to 24 years. The health of women in their peak fertility years is crucial for maternal and child health outcomes. This highlights the need for targeted public health interventions in this area to manage and reduce the burden of TB.

Keywords: AGE, AFB, female, male

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Authors: Javed Mohammed

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Right now, bio-medical infrastructure lags well behind the curve. Our healthcare system is dispersed and disjointed; medical records are a bit of a mess; and we do not yet have the capacity to store and process the crazy amounts of data coming our way from widespread whole-genome sequencing. And then there are privacy issues. Despite these infrastructure challenges, some researchers are plunging into bio medical Big Data now, in hopes of extracting new and actionable knowledge. They are doing delving into molecular-level data to discover bio markers that help classify patients based on their response to existing treatments; and pushing their results out to physicians in novel and creative ways. Computer scientists and bio medical researchers are able to transform data into models and simulations that will enable scientists for the first time to gain a profound under-standing of the deepest biological functions. Solving biological problems may require High-Performance Computing HPC due either to the massive parallel computation required to solve a particular problem or to algorithmic complexity that may range from difficult to intractable. Many problems involve seemingly well-behaved polynomial time algorithms (such as all-to-all comparisons) but have massive computational requirements due to the large data sets that must be analyzed. High-throughput techniques for DNA sequencing and analysis of gene expression have led to exponential growth in the amount of publicly available genomic data. With the increased availability of genomic data traditional database approaches are no longer sufficient for rapidly performing life science queries involving the fusion of data types. Computing systems are now so powerful it is possible for researchers to consider modeling the folding of a protein or even the simulation of an entire human body. This research paper emphasizes the computational biology's growing need for high-performance computing and Big Data. It illustrates this article’s indispensability in meeting the scientific and engineering challenges of the twenty-first century, and how Protein Folding (the structure and function of proteins) and Phylogeny Reconstruction (evolutionary history of a group of genes) can use HPC that provides sufficient capability for evaluating or solving more limited but meaningful instances. This article also indicates solutions to optimization problems, and benefits Big Data and Computational Biology. The article illustrates the Current State-of-the-Art and Future-Generation Biology of HPC Computing with Big Data.

Keywords: high performance, big data, parallel computation, molecular data, computational biology

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Authors: Shikuku Emmanuel Tsikhungu

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Theatre and religion have enjoyed a symbiotic relationship from time immemorial, each transforming in different epochs and into different forms of practice but gaining from each other’s growth. Despite the fact that religion has more or less looked at the theatre and its dramatic rituals with distaste, the two human engagements have had dynamic and reciprocal relationships. In Kenya, there is an emerging innovation and transformation of theatre for religion in which churches and sects are consciously developing a youth wing that is vibrant in theatre practice. The imagination that youth and children derive pleasure and vibrancy in theatre has led to a lively competition among churches that is now creating a new form of theatre in Kenya. This has given rise to a practice in which art engages the religious not at the spiritual level but at the social-cultural level. Thus theatre is finding itself in sanctums that it had been banished; not for its own sake but as a tool for keeping the youth nearer the church if not the church This article analyses findings of a study carried out in December of 2017 among theatre festivals for the Catholic Church held in Kitui School, KituiCounty, and the Methodist Church of Kenya festival held in Ntemwene Church, Nkubu, Meru County, Kenya. One of the findings of interest was that while they were not theatres of religion nor religious theatres since they did not fuse the religious rituals with the dramatic rituals, the festivals never the less qualify as theatres for religion for they link the former to the latter. Secondly, while they claimed to be youth or children theatre festivals, they lacked youth-centredness nor child-centredness associated with such. Thirdly and most importantly the style of dramatic execution ranged from bibliodramatic to secular drama with Christian messages. Fourthly, by this stroke of acceptance in formerly forbidden sanctums, theatre is re-inventing itself back to its ‘old’ nature and function. It may be argued conclusively that this sprouting movement of theatre for religion may be comparable to the Jesuit Theatre fronted by Ignatius Loyola but clothed in modern African theatre practice.

Keywords: theatre, religion, theatre for religion, social constructs, socio-cultural

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Authors: Andres Diaz Garcia

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The successful technological development of any bioproduct, including those of the biostimulant type, requires to adequately completion of a series of stages allied to different disciplines that are related to microbiological, engineering, pharmaceutical chemistry, legal and market components, among others. Engineering as a discipline has a key contribution in different aspects of fermentation processes such as the design and optimization of culture media, the standardization of operating conditions within the bioreactor and the scaling of the production process of the active ingredient that it will be used in unit operations downstream. However, all aspects mentioned must take into account many biological factors of the microorganism such as the growth rate, the level of assimilation to various organic and inorganic sources and the mechanisms of action associated with its biological activity. This paper focuses on the practical experience within the Colombian Corporation for Agricultural Research (Agrosavia), which led to the development of a biostimulant bioproduct based on native rhizobacteria Bacillus amyloliquefaciens, oriented mainly to plant growth promotion in cape gooseberry nurseries and fruit crops in Colombia, and the challenges that were overcome from the expertise in the area of engineering. Through the application of strategies and engineering tools, a culture medium was optimized to obtain concentrations higher than 1E09 CFU (colony form units)/ml in liquid fermentation, the process of biomass production was standardized and a scale-up strategy was generated based on geometric (H/D of bioreactor relationships), and operational criteria based on a minimum dissolved oxygen concentration and that took into account the differences in the capacity of control of the process in the laboratory and pilot scales. Currently, the bioproduct obtained through this technological process is in stages of registration in Colombia for cape gooseberry fruits for export.

Keywords: biochemical engineering, liquid fermentation, plant growth promoting, scale-up process

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Authors: Ellina Zipman

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This research investigates the place of music education in aged care facilities through the implementation of a program of regular piano lessons for residents. Using a qualitative case study methodology, the research explores aged care residents’ experiences in learning to play the piano. Since the aged care homes are unlikely places for formal learning and since older adults, especially in residential care, are not considered likely candidates for learning, this research opens the door for innovative and transformative thinking about where and to whom educational programs can be delivered. By addressing the educational needs of residents in aged care facilities, this research fills the gap in the literature. The research took place in Australia in two of Melbourne’s residential aged care facilities, engaging two residents (a nonagenarian female and an octogenarian male) to participate in 12-months weekly individual piano lessons. The data was collected through video recording of lessons, observations, interviews, emails, and a reflective journal. Data analysis was done using Nvivo and hard copy analysis with identifications of themes. The case studies revealed that passion for music was a major driver in participants’ motivation to engage in a long-term piano lessons program. This participation led to experiences of positive emotions, positive attitude, successes and challenges, the exercise of control, maintaining and building new relationships, improved self-confidence through autonomy and independent skills development, and discovering new identities through finding a new purpose and new roles in life. Speaking through participants’ voices, this research project demonstrates the importance of music education for older adults and hopes to influence transformation in the residential aged care sector.

Keywords: adult music education, quality of life, passion, positive ageing, wellbeing

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Authors: Ejovi Eghwubare Augustine

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This study delved into the traditional mechanisms of conflict resolution in Africa, a pathway to sustainable peace in Nigeria. It deployed the quantitative and qualitative methods of data collection and content analysis. The work adopted the Peace Process theory propounded by John Darby and Roger Macunity. It ascertained that disputes or disagreements are unarguably and necessarily an inevitable part of human existence, flowing directly from communication, interaction, and relationships which can occur at individual and national levels, even at international levels in view of the current trend of globalization. The alternative Dispute Resolution (ADR) mechanism is a basket of procedures outside the traditional process of litigation or strict determination of legal rights. It may also be elucidated as a range of procedures that serve as generally involve the intercession and assistance of a neutral and impartial third party. The traditional mechanisms of conflict resolution in Africa are alien to the Western world; this paper is of utmost importance to the Western world and also enriched their pool of literature. Nigeria is a country that is dominated by various ethnic groups anchored on diverse cultures, customs, and traditions. It is, therefore, not surprising to see conflicts arise, and despite the various attempts at resolving these conflicts through litigation, they still remained unabated. The paper investigated the lessons learned from Traditional Mechanisms of Conflict resolution; it also interrogated its impact and the way forward. In light of the lessons that were learned and the impact of the traditional mechanisms of conflict resolution, suggestions on how to attain a sustainable, peaceful society were proffered. In conclusion, the study crystallized reforms on the alternative dispute resolution introduced through the traditional mechanism, which includes, amongst others, that constitutional recognition should be given to traditional institutions of conflict resolution to enable quick dispensation of matters.

Keywords: traditional, conflict, peace, resolution

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Authors: Methembe Mdlalose

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This paper synthesizes the findings of a study that utilized a purposive sampling methodology laced within a grounded theory analytical framework with LED managers, mayors, and traditional leaders representing six municipalities of uThukela District of KwaZulu-Natal, South Africa. The paper critiques the two institution’s micro-relations within local governance and their overall impact on the general development discourse of rural areas. The study is located in the province of KwaZulu-Natal, a part of South Africa that experiences extremely low levels of development in rural areas and suffers from high rates of inequality, poverty, and unemployment. The paper unpacks the role of two significant stakeholders in the local sphere. Considered as the two dominant stakeholders at the local level, questions of compatibility between traditional leaders and municipal councillors often surge, as the two institutions (who represent two autonomous entities) that operate within the same operational boarders. The discussion around community development lies very deeply on accountability, which assures citizens that fruitless spending is curbed and good governance is maintained. If development is to be assured, it is vital to monitor accountability within government spheres and its departments. It is further essential to monitor the relations within local government. The findings of this research confirmed how relationships between traditional leaders and councillors can and have contributed to economic development or its stagnation thereof in rural areas. In addition, the findings revealed that there is an extensive need for the two stakeholders to work collectively, as this is a vital move in planning for development. Furthermore, the better accountability of local government and a better understanding of how clear policy and its implementation is may be a valuable asset in the discourse of community economic development in rural areas.

Keywords: economic development, traditional leadership, democratically elected councillors, local governance

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Authors: Pierre-Louis Lucas, Corinne Loutelier-Bourhis, Narimane Mati-Baouche, Philippe Chan Tchi-Song, Patrice Lerouge, Elodie Mathieu-Rivet, Muriel Bardor

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N-glycosylation is a post-translational modification taking place in the Endoplasmic Reticulum and the Golgi apparatus where defined glycan features are added on protein in a very specific sequence Asn-X-Thr/Ser/Cys were X can be any amino acid except proline. Because it is well-established that those N-glycans play a critical role in protein biological activity, protein half-life and that a different N-glycan structure may induce an immune response, they are very important in Biopharmaceuticals which are mainly glycoproteins bearing N-glycans. From now, most of the biopharmaceuticals are produced by mammalian cells like Chinese Hamster Ovary cells (CHO) for their N-glycosylation similar to the human, but due to the high production costs, several other species are investigated as the possible alternative system. In this purpose, the green microalgae Chlamydomonas reinhardtii was investigated as the potential production system for Biopharmaceuticals. This choice was influenced by the facts that C. reinhardtii is a well-study microalgae which is growing fast with a lot of molecular biology tools available. This organism is also producing N-glycan on its endogenous proteins. However, the analysis of the N-glycan structure of this microalgae has revealed some differences as compared to the human. Rather than in Human where the glycans are processed by key enzymes called N-acetylglucosaminyltransferase I and II (GnTI and GnTII) adding GlcNAc residue to form a GlcNAc₂Man₃GlcNAc₂ core N-glycan, C. reinhardtii lacks those two enzymes and possess a GnTI independent glycosylation pathway. Moreover, some enzymes like xylosyltransferases and methyltransferases not present in human are supposed to act on the glycans of C. reinhardtii. Furthermore, the recent structural study by mass spectrometry shows that the N-glycosylation precursor supposed to be conserved in almost all eukaryotic cells results in a linear Man₅GlcNAc₂ rather than a branched one in C. reinhardtii. In this work, we will discuss the new released MS information upon C. reinhardtii N-glycan structure and their impact on our attempt to modify the glycan in a Human manner. Two strategies will be discussed. The first one consisted in the study of Xylosyltransferase insertional mutants from the CLIP library in order to remove xyloses from the N-glycans. The second will go further in the humanization by transforming the microalgae with the exogenous gene from Toxoplasma gondii having an activity similar to GnTI and GnTII with the aim to synthesize GlcNAc₂Man₃GlcNAc₂ in C. reinhardtii.

Keywords: Chlamydomonas reinhardtii, N-glycosylation, glycosyltransferase, mass spectrometry, humanization

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Authors: Svetlana S. Saveysheva, Victoria E. Vasilenko

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The purpose of the research was to study the emotional and personal characteristics of preschool children in relation to the characteristics of child-parent interaction and deviant parental attitudes. The study involved 172 mothers and 172 children (85 boys and 87 girls) aged 4,5 to 7 years (mean age 6 years) living in St. Petersburg, Russia. Methods used were, demographic questionnaire, projective drawing method 'House-Tree-Man', Test of anxiety (Temml, Dorki, Amen), technique of studying self-esteem 'Ladder', expert evaluation of sociability and aggressiveness, questionnaire for children-parent emotional interaction (E.I. Zaharova) and questionnaire 'Analysis of family relationships' (E.G. Eidemiller, V.V. Yustitsky). Results. The greatest number of links with personal characteristics have received such parental deviant attitudes as overprotection and characteristics of authoritarian style (prohibitions, sanctions). If the mother has such peculiarities of the parental relationship, the child is characterized by lower self-esteem, increased anxiety, distrust of themselves and hostility. Children have more pronounced manifestations of aggression in a conniving and unstable style of parenting. The sensitivity of the mother is positively associated with children’s self-esteem. Unconditional acceptance of the child, the predominance of a positive emotional background, orientation to the state of the child during interaction promote the development of communication skills and reduce of aggressiveness. But the excessive closeness of the mother with the child can make it difficult to develop the communicative skills. Conclusions. The greatest influence on emotional and personal characteristics is provided by such features of the parental relation as overprotection, characteristics of authoritarian style, underdevelopment of the sphere of parental feelings, sensitivity of mother and behavioral manifestations of emotional interaction. Research is supported by RFBR №18-013-00990.

Keywords: characteristics of personality, child-parent interaction, children, deviant parental attitudes

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Authors: Newton Muhury, Armando A. Apan, Tek N. Marasani, Gebiaw T. Ayele

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The changing climate has degraded freshwater availability in Australia that influencing vegetation growth to a great extent. This study assessed the vegetation responses to groundwater using Terra’s moderate resolution imaging spectroradiometer (MODIS), Normalised Difference Vegetation Index (NDVI), and soil water content (SWC). A hydrological model, SWAT, has been set up in a southeast Australian river catchment for groundwater analysis. The model was calibrated and validated against monthly streamflow from 2001 to 2006 and 2007 to 2010, respectively. The SWAT simulated soil water content for 43 sub-basins and monthly MODIS NDVI data for three different types of vegetation (forest, shrub, and grass) were applied in the machine learning tool, Waikato Environment for Knowledge Analysis (WEKA), using two supervised machine learning algorithms, i.e., support vector machine (SVM) and random forest (RF). The assessment shows that different types of vegetation response and soil water content vary in the dry and wet seasons. The WEKA model generated high positive relationships (r = 0.76, 0.73, and 0.81) between NDVI values of all vegetation in the sub-basins against soil water content (SWC), the groundwater flow (GW), and the combination of these two variables, respectively, during the dry season. However, these responses were reduced by 36.8% (r = 0.48) and 13.6% (r = 0.63) against GW and SWC, respectively, in the wet season. Although the rainfall pattern is highly variable in the study area, the summer rainfall is very effective for the growth of the grass vegetation type. This study has enriched our knowledge of vegetation responses to groundwater in each season, which will facilitate better floodplain vegetation management.

Keywords: ArcSWAT, machine learning, floodplain vegetation, MODIS NDVI, groundwater

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Authors: Anila Xhahysa, Migena Ceyhan, Neki Kuka, Klajdi Qoshi, Damiano Koxhaj

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The seismic event catalog has been updated in the framework of a bilateral project supported by the Central European Investment Fund and with the extensive support of Global Earthquake Model Foundation to update Albania's national seismic hazard model. The earthquake catalogue prepared within this project covers the Western Balkan area limited by 38.0° - 48°N, 12.5° - 24.5°E and includes 41,806 earthquakes that occurred in the region between 510 BC and 2022. Since the moment magnitude characterizes the earthquake size accurately and the selected ground motion prediction equations for the seismic hazard assessment employ this scale, it was chosen as the uniform magnitude scale for the catalogue. Therefore, proxy values of moment magnitude had to be obtained by using new magnitude conversion equations between the local and other magnitude types to this unified scale. The Global Centroid Moment Tensor Catalogue was considered the most authoritative for moderate to large earthquakes for moment magnitude reports; hence it was used as a reference for calibrating other sources. The best fit was observed when compared to some regional agencies, whereas, with reports of moment magnitudes from Italy, Greece and Turkey, differences were observed in all magnitude ranges. For teleseismic magnitudes, to account for the non-linearity of the relationships, we used the exponential model for the derivation of the regression equations. The obtained regressions for the surface wave magnitude and short-period body-wave magnitude show considerable differences with Global Earthquake Model regression curves, especially for low magnitude ranges. Moreover, a conversion relation was obtained between the local magnitude of Albania and the corresponding moment magnitude as reported by the global and regional agencies. As errors were present in both variables, the Deming regression was used.

Keywords: regression, seismic catalogue, local magnitude, tele-seismic magnitude, moment magnitude

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Authors: C. van den Berg, C. Pokpas

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Popular discourse touts entrepreneurship as a universal solution for underdevelopment, unemployment, and poverty. Moreover, claims are made that women and other disadvantaged groups can achieve material and personal success through digital entrepreneurship. This paper examines the potential of digital technology in entrepreneurial ventures to stimulate economic growth for marginalized groups and communities. Although digital entrepreneurship is hailed as a means to empower under-resourced and socially marginalized people, these opportunities still exist within the confines of existing social and cultural practices. The perspectives of female digital entrepreneurs in developing countries are sorely understudied, particularly concerning an understanding of the complex underlying socio-cultural factors impeding women’s entrepreneurial behaviors. This qualitative study, guided by a feminist phenomenological perspective, focused on the experiences of digital female entrepreneurs in the Western Cape of South Africa. Data were collected via semi-structured interviews and analyzed through the interpretative phenomenological analysis (IPA) approach to determine the relationships between digital entrepreneurship and structural and agential enabling conditions. Findings show that digital entrepreneurship is not a panacea for economic growth in marginalized groups and communities and highlight the importance of addressing socio-cultural gender inequality to enable successful entrepreneurial activity. The paper concludes with recommendations for specialized training initiatives aimed at female entrepreneurs that address internalized constraints and barriers that keep women subservient and measures to shift gender and power beliefs. The outcome will benefit the stimulation of gender-specific public policies to develop a successful digital start-up ecosystem further.

Keywords: digital innovation, female digital entrepreneurs, feminist phenomenology, gender, marginalised communities

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Authors: Mohamed M. Elsherbiny, Ahmed T. Helal Ibrahim

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Social isolation is one of the common problems faced visual impaired students especially in new situations. It refers to lack of interactions with others (students, staff members, and others) and dissatisfaction of social networks with others. In addition, it means "a lack of quantity and quality of social contacts". The situation became more complicated if we know that visual impaired students at Sultan Qaboos University were in special schools for the blind completely away from any integration with regular student, which may lead to isolation for being with regular students for the first time. Because the researcher is an academic advisor for all blind students in the College of Arts and Social Sciences at Sultan Qaboos University, he has noted (from the regular meetings with them) some aspects of isolation and many complaints from staff which motivated the researcher to try to alleviate the problem. Logotherapy is an important therapy used in clinical social work with various problems to help children and young people who are facing problems related to the lack of meaning in their life. So, the aim of the therapy is to find meaning in life and to be satisfied with that life. The basic meaning for visual impaired students in this study is to provide opportunities to build relationships and friendships with others and help them to be satisfied about interactions with their networks. The study aimed to identify whether there is a relationship between the use of logotherapy and alleviating social isolation for visual impaired students. This study is considered one of the quasi-experimental studies, the researcher has used experimental method. The researcher used one design which is before and after experiment on two groups, one control (did not apply to the therapy) and experimental group which is applied to the therapy. About the study tools, social isolation scale (SIS) was used to assess the degree of isolation. The sample was (20) of the visually impaired students at the College of Arts and Social Sciences, Sultan Qaboos University. The results showed the effectiveness of logotherapy in alleviating isolation for students.

Keywords: social isolation, logotherapy, visually impaired, disability

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Authors: M. Hilmi Ozdemir, Gokhan Ozkan

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Performance Based Logistics (PBL) is a strategic approach that enables creating long-term and win-win relations among stakeholders in the acquisition. Contrary to the traditional single transactions, the expected value is created by the performance of the service pertaining to the strategic relationships in this approach. PBL motivates all relevant stakeholders to focus on their core competencies to produce the desired outcome in a collective way. The desired outcome can only be assured with a cost effective way as long as it is periodically measured with the right performance parameters. Thus, defining these parameters is a crucial step for the PBL contracts. In performance parameter determination, Analytic Hierarchy Process (AHP), which is a multi-criteria decision making methodology for complex cases, was used within this study for a complex system. AHP has been extensively applied in various areas including supply chain, inventory management, outsourcing, and logistics. This methodology made it possible to convert end-user’s main operation and maintenance requirements to sub criteria contained by a single performance parameter. Those requirements were categorized and assigned weights by the relevant stakeholders. Single performance parameter capable of measuring the overall performance of a complex system is the major outcome of this study. The parameter deals with the integrated assessment of different functions spanning from training, operation, maintenance, reporting, and documentation that are implemented within a complex system. The aim of this study is to show the methodology and processes implemented to identify a single performance parameter for measuring the whole performance of a complex system within a PBL contract. AHP methodology is recommended as an option for the researches and the practitioners who seek for a lean and integrated approach for performance assessment within PBL contracts. The implementation of AHP methodology in this study may help PBL practitioners from methodological perception and add value to AHP in becoming prevalent.

Keywords: analytic hierarchy process, performance based logistics, performance measurement, performance parameters

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Authors: Karl Gerrard Tiu See

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Military bases are an indelible mark of prolonged US defense relationships in the Pacific. Bases like the Subic Naval Base in Olongapo City have irreversible consequences for their host communities, not all of which are positive. One consequence the Subic Naval Base had for Olongapo City was the rise of vibrant sex industry. While the Philippine Senate voted to remove US bases like Subic in 1991, the question remains as to why did prostitution not end after the bases pull-out? To answer this question, the study used an institutionalist lens coupled with focus group discussions from the sex industry. It found that prostitution persisted due to two main reasons. The first was that like Olongapo City; the sex industry successfully shifted its reliance from the military to foreign tourism. The second was that agreements such as the 1996 Visiting Forces Agreement (VFA) ensured that the sex industry continued to receive US military clientele. With the contextual factors as the backdrop, this study used the Theory of Institutional Change to study institutions pivotal in altering Olongapo City and its sex industry after Subic Naval Base. These include local government, civil society actors such as NGOs, and the city’s economic base. The study found that policy such as the VFA allowed the bases period status quo to revive (Symbionts). This led to renewed exploitation from the military presence coupled with foreign tourism (Opportunists). The local government, however, shifted focus away from base reliance which allowed a reinvigorated civil society to effect a gradual change (Subversives). Furthermore, uncertainties like rising HIV incidence, abandoned children born from US soldiers, and the Enhanced Defence Cooperation Agreement (EDCA) remain to change the sex industry’s future, for better or worse.

Keywords: Philippine-USA defence relations, overseas USA basing, 1991 Philippine-USA bases pull-out, Olongapo city, Subic naval base, institutional change

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Authors: Ljiljana Stojković, Manja Zec, Maja Zivkovic, Maja Bundalo, Marija Glibetić, Dragan Alavantić, Aleksandra Stankovic

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Cardiovascular disease (CVD) is associated with alterations in DNA methylation, the latter modulated by dietary polyphenols. The present pilot study (part of the original clinical study registered as NCT02800967 at www.clinicaltrials.gov) aimed to investigate the impact of 4-week daily consumption of polyphenol-rich Aronia melanocarpa juice on Long Interspersed Nucleotide Element-1 (LINE-1) methylation in peripheral blood leukocytes, in subjects (n=34, age of 41.1±6.6 years) at moderate CVD risk, including an increased body mass index, central obesity, high normal blood pressure and/or dyslipidemia. The goal was also to examine whether factors known to affect DNA methylation, such as folate intake levels, MTHFR C677T gene variant, as well as the anthropometric and metabolic parameters, modulated the LINE-1 methylation levels upon consumption of polyphenol-rich Aronia juice. The experimental analysis of LINE-1 methylation was done by the MethyLight method. MTHFR C677T genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Folate intake was assessed by processing the data from the food frequency questionnaire and repeated 24-hour dietary recalls. Serum lipid profile was determined by using Roche Diagnostics kits. The statistical analyses were performed using the Statistica software package. In women, after vs. before the treatment period, a significant decrease in LINE-1 methylation levels was observed (97.54±1.50% vs. 98.39±0.86%, respectively; P=0.01). The change (after vs. before treatment) in LINE-1 methylation correlated directly with MTHFR 677T allele presence, average daily folate intake and the change in serum low-density lipoprotein cholesterol, while inversely with the change in serum triacylglycerols (R=0.72, R2=0.52, adjusted R2=0.36, P=0.03). The current results imply potential cardioprotective effects of habitual polyphenol-rich Aronia juice consumption achieved through the modifications of DNA methylation pattern in subjects at CVD risk, which should be further confirmed. Hence, the precision nutrition-driven modulations of DNA methylation may become targets for new approaches in the prevention and treatment of CVD.

Keywords: Aronia melanocarpa, cardiovascular risk, LINE-1, methylation, peripheral blood leukocytes, polyphenol

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Authors: Yanling Li, Linying Ji, Zita Oravecz, Timothy R. Brick, Michael D. Hunter, Sy-Miin Chow

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Assessing several individuals intensively over time yields intensive longitudinal data (ILD). Even though ILD provide rich information, they also bring other data analytic challenges. One of these is the increased occurrence of missingness with increased study length, possibly under non-ignorable missingness scenarios. Multiple imputation (MI) handles missing data by creating several imputed data sets, and pooling the estimation results across imputed data sets to yield final estimates for inferential purposes. In this article, we introduce dynr.mi(), a function in the R package, Dynamic Modeling in R (dynr). The package dynr provides a suite of fast and accessible functions for estimating and visualizing the results from fitting linear and nonlinear dynamic systems models in discrete as well as continuous time. By integrating the estimation functions in dynr and the MI procedures available from the R package, Multivariate Imputation by Chained Equations (MICE), the dynr.mi() routine is designed to handle possibly non-ignorable missingness in the dependent variables and/or covariates in a user-specified dynamic systems model via MI, with convergence diagnostic check. We utilized dynr.mi() to examine, in the context of a vector autoregressive model, the relationships among individuals’ ambulatory physiological measures, and self-report affect valence and arousal. The results from MI were compared to those from listwise deletion of entries with missingness in the covariates. When we determined the number of iterations based on the convergence diagnostics available from dynr.mi(), differences in the statistical significance of the covariate parameters were observed between the listwise deletion and MI approaches. These results underscore the importance of considering diagnostic information in the implementation of MI procedures.

Keywords: dynamic modeling, missing data, mobility, multiple imputation

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