Search results for: drug target
Commenced in January 2007
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Edition: International
Paper Count: 4433

Search results for: drug target

383 Corpus Linguistics as a Tool for Translation Studies Analysis: A Bilingual Parallel Corpus of Students’ Translations

Authors: Juan-Pedro Rica-Peromingo

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Nowadays, corpus linguistics has become a key research methodology for Translation Studies, which broadens the scope of cross-linguistic studies. In the case of the study presented here, the approach used focuses on learners with little or no experience to study, at an early stage, general mistakes and errors, the correct or incorrect use of translation strategies, and to improve the translational competence of the students. Led by Sylviane Granger and Marie-Aude Lefer of the Centre for English Corpus Linguistics of the University of Louvain, the MUST corpus (MUltilingual Student Translation Corpus) is an international project which brings together partners from Europe and worldwide universities and connects Learner Corpus Research (LCR) and Translation Studies (TS). It aims to build a corpus of translations carried out by students including both direct (L2 > L1) an indirect (L1 > L2) translations, from a great variety of text types, genres, and registers in a wide variety of languages: audiovisual translations (including dubbing, subtitling for hearing population and for deaf population), scientific, humanistic, literary, economic and legal translation texts. This paper focuses on the work carried out by the Spanish team from the Complutense University (UCMA), which is part of the MUST project, and it describes the specific features of the corpus built by its members. All the texts used by UCMA are either direct or indirect translations between English and Spanish. Students’ profiles comprise translation trainees, foreign language students with a major in English, engineers studying EFL and MA students, all of them with different English levels (from B1 to C1); for some of the students, this would be their first experience with translation. The MUST corpus is searchable via Hypal4MUST, a web-based interface developed by Adam Obrusnik from Masaryk University (Czech Republic), which includes a translation-oriented annotation system (TAS). A distinctive feature of the interface is that it allows source texts and target texts to be aligned, so we can be able to observe and compare in detail both language structures and study translation strategies used by students. The initial data obtained point out the kind of difficulties encountered by the students and reveal the most frequent strategies implemented by the learners according to their level of English, their translation experience and the text genres. We have also found common errors in the graduate and postgraduate university students’ translations: transfer errors, lexical errors, grammatical errors, text-specific translation errors, and cultural-related errors have been identified. Analyzing all these parameters will provide more material to bring better solutions to improve the quality of teaching and the translations produced by the students.

Keywords: corpus studies, students’ corpus, the MUST corpus, translation studies

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382 The Effects of Chamomile on Serum Levels of Inflammatory Indexes to a Bout of Eccentric Exercise in Young Women

Authors: K. Azadeh, M. Ghasemi, S. Fazelifar

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Aim: Changes in stress hormones can be modify response of immune system. Cortisol as the most important body corticosteroid is anti-inflammatory and immunosuppressive hormone. Normal levels of cortisol in humans has fluctuated during the day, In other words, cortisol is released periodically, and regulate through the release of ACTH circadian rhythm in every day. Therefore, the aim of this study was to determine the effects of Chamomile on serum levels of inflammatory indexes to a bout of eccentric exercise in young women. Methodology: 32 women were randomly divided into 4 groups: high dose of Chamomile, low dose of Chamomile, ibuprofen and placebo group. Eccentric exercise included 5 set and rest period between sets was 1 minute. For this purpose, subjects warm up 10 min and then done eccentric exercise. Each participant completed 15 repetitions with optional 20 kg weight or until can’t continue moving. When the subject was no longer able to continue to move, immediately decreased 5 kg from the weight and the protocol continued until cause exhaustion or complete 15 repetitions. Also, subjects received specified amount of ibuprofen and Chamomile capsules in target groups. Blood samples in 6 stages (pre of starting pill, pre of exercise protocol, 4, 24, 48 and 72 hours after eccentric exercise) was obtained. The levels of cortisol and adrenocorticotropic hormone levels were measured by ELISA way. K-S test to determine the normality of the data and analysis of variance for repeated measures was used to analyze the data. A significant difference in the p < 0/05 accepted. Results: The results showed that Individual characteristics including height, weight, age and body mass index were not significantly different among the four groups. Analyze of data showed that cortisol and ACTH basic levels significantly decreased after supplementation consumption, but then gradually significantly increased in all stages of post exercise. In High dose of Chamomile group, increasing tendency of post exercise somewhat less than other groups, but not to a significant level. The inter-group analysis results indicate that time effect had a significant impact in different stages of the groups. Conclusion: The results of this study, one session of eccentric exercise increased cortisol and ACTH hormone. The results represent the effect of high dose of Chamomile in the prevention and reduction of increased stress hormone levels. As regards use of medicinal plants and ibuprofen as a pain medication and inflammation has spread among athletes and non-athletes, the results of this research can provide information about the advantages and disadvantages of using medicinal plants and ibuprofen.

Keywords: chamomile, inflammatory indexes, eccentric exercise, young girls

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381 Women's Pathways to Prison in Thailand

Authors: Samantha Jeffries, Chontit Chuenurah

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Thailand incarcerates the largest number of women and has the highest female incarceration rate in South East Asia. Since the 1990s, there has been a substantial increase in the number, rate and proportion of women imprisoned. Thailand places a high priority on the gender specific contexts out of which offending arises and the different needs of women in the criminal justice system. This is manifested in work undertaken to guide the development of the United Nations Rules for the Treatment of Women Prisoners and Non-Custodial Measures for Women Offenders (the Bangkok Rules); adopted by the United Nations General Assembly in 2010. The Bangkok Rules make a strong statement about Thailand’s recognition of and commitment to the fair and equitable treatment of women throughout their contact with the criminal justice system including at sentencing and in prison. This makes the comparatively high use of imprisonment for women in Thailand particularly concerning and raises questions about the relationship between gender, crime and criminal justice. While there is an extensive body of research in Western jurisdictions exploring women’s pathways to prison, there is a relative dearth of methodologically robust research examining the possible gendered circumstances leading to imprisonment in Thailand. In this presentation, we will report preliminary findings from a qualitative study of women’s pathways to prison in Thailand. Our research aims were to ascertain: 1) the type, frequency, and context of criminal behavior that led to women’s incarceration, 2) women’s experiences of the criminal justice system, 3) the broader life experiences and circumstances that led women to prison in Thailand. In-depth life history interviews (n=77) were utilized to gain a comprehensive understanding of women’s journeys into prison. The interview schedule was open-ended consisting of prisoner responses to broad discussion topics. This approach provided women with the opportunity to describe significant experiences in their lives, to bring together distinct chronologies of events, and to analyze links between their varied life experiences, offending, and incarceration. Analyses showed that women’s journey’s to prison take one of eight pathways which tentatively labelled as follows, the: 1) harmed and harming pathway, 2) domestic/family violence victimization pathway, 3) drug connected pathway, 4) street woman pathway, 5) economically motivated pathway, 6) jealousy anger and/or revenge pathway, 7) naivety pathway, 8) unjust and/or corrupted criminal justice pathway. Each will be fully discussed during the presentation. This research is significant because it is the first in-depth methodologically robust exploration of women’s journeys to prison in Thailand and one of a few studies to explore gendered pathways outside of western contexts. Understanding women’s pathways into Thailand’s prisons is crucial to the development of effective planning, policy and program responses not only while women are in prison but also post-release. To best meet women’s needs in prison and effectively support their reintegration, we must have a comprehensive understanding of who these women are, what offenses they commit, the reasons that trigger their confrontations with the criminal justice system and the impact of the criminal justice system on them.

Keywords: pathways, prison, women, Thailand

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380 Nursing Students’ Learning Effects of Online Visits for Mothers Rearing Infants during the COVID-19 Pandemic

Authors: Saori Fujimoto, Hiromi Kawasaki, Mari Murakami, Yoko Ueno

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Background: Coronavirus disease (COVID-19) has been spreading throughout the world. In Japan, many nursing universities have conducted online clinical practices to secure students’ learning opportunities. In the field of women’s health nursing, even after the pandemic ended, it will be worthwhile to utilize online practice in declining birthrate and reducing the burden of mothers. This study examined the learning effects of conducting online visits for mothers with infants during the COVID-19 pandemic by nursing students to enhance the students’ ability to carry out the online practice even in ordinary times effectively. Methods: Students were divided into groups of three, and information on the mothers was assessed, and the visits were planned. After role-play was conducted by the students and teachers, an online visit was conducted. The analysis target was the self-evaluation score of nine students who conducted online visits in June 2020 and had consented to participate. The evaluation contents included three items for assessment, two items for planning, one item for ethical consideration, five items for nursing practice, and two items for evaluation. The self-evaluation score ranged from 4 (‘Can do with a little advice’) to 1 (‘Can’t do with a little advice’). A univariate statistical analysis was performed. This study was approved by the Ethical Committee for Epidemiology of Hiroshima University. Results: The items with the highest mean (standard deviation) scores were ‘advocates for the dignity and the rights of mothers’ (3.89 (0.31)) and ‘communication behavior needed to create a trusting relationship’ (3.89 (0.31)).’ Next were the ‘individual nursing practice tailored to mothers (3.78 (0.42))’ and ‘review own practice and work on own task (3.78 (0.42)).’ The mean (standard deviation) of the items by type were as follows: three assessment items, 3.26 (0.70), two planning items, 3.11 (0.49), one ethical consideration item, 3.89 (0.31), five nursing practice items, 3.56 (0.54), and two evaluation items, 3.67 (0.47). Conclusion: The highest self-evaluations were for ‘advocates for the dignity and the rights of mothers’ and ‘communication behavior needed to create a trusting relationship.’ These findings suggest that the students were able to form good relationships with the mothers by improving their ability to effectively communicate and by presenting a positive attitude, even when conducting health visits online. However, the self-evaluation scores for assessment and planning were lower than those of ethical consideration, nursing practice, and evaluation. This was most likely due to a lack of opportunities and time to gather information and the need to modify and add plans in a short amount of time during one online visit. It is necessary to further consider the methods used in conducting online visits from the following viewpoints: methods of gathering information and the ability to make changes through multiple visits.

Keywords: infants, learning effects, mothers, online visit practice

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379 Use of Proton Pump Inhibitors Medications during the First Years of Life and Late Complications

Authors: Kamelia Hamza

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Background: Proton pump inhibitors (PPIs) are the most prescribed drug classes for pediatric gastroesophageal reflux disease (GERD).Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux (GER), even in the absence of proved causal relationship. There is an impression of increase use of PPI's treatment for reflux in "clalit health services," the largest health organization in Israel. In the recent years, the medicine is given without restriction, it's not limited to pediatric gastroenterologists only, but pediatricians and family doctors. The objective of this study is to evaluate the hypothesis that exposure to PPIs during the first year of life is associated with an increased risk of developing late adverse diseases: pneumonia, asthma, AGE, IBD, celiac disease, allergic disorders, obesity, attention deficit hyperactivity disorders (ADHD), autism spectrum disorders (ASD). Methods: The study is a retrospective case-control cohort study based on a computerized database of Clalit Health Services (CHS). It includes 9844 children born between 2002-2018 and reported to complain of at least one of the symptoms (reflux/ spitting up, irritability, feeding difficulties, colics). The study population included the study group (n=4922) of children exposed to PPIs at any time prior to the first year of life and a control group (n=4922) child not exposed to PPIs who were matched to each case of the study group on age, race, socioeconomic status, and year of birth. The prevalence of late complications/diseases in the study group was compared with the prevalence of late complications/diseases diagnosis between 2002-2020 in the control group. Odds ratios and 95% confidence intervals were calculated by using logistic regression models. Results: We found that compared to the control group, children exposed to PPIs in the first year of life had an increased risk of developing several late complications/ disorders: pneumonia, asthma, various allergies (urticaria, allergic rhinitis, or allergic conjunctivitis) OR, inhalant allergies, and food allergies. In addition, they showed an increased risk of being diagnosed with ADHD or ASD, but children exposed to PPIs in the first year of life had decrease the risk of obesity by 17% (OR 0.825, 95%CI 0.697-0.976). Conclusions: We found significant associations between the use of PPIs during the first year of life and subsequent development of late complications/diseases such as respiratory diseases, allergy diseases, ADHD, and ASD. More studies are needed to prove causality and determine the mechanism behind the effect of PPIs and the development of late complications.

Keywords: acid suppressing medications, proton pump inhibitors, histamine 2 blocker, late complications, gastroesophageal reflux, gastroesophageal reflux disease, acute gastroenteritis, community acquired pneumonia, asthma, allergic diseases, obesity, inflammatory bowel diseases, ulcerative colitis, crohn disease, attention deficit hyperactivity disorders, autism spectrum disorders

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378 Childhood Adversity and Delinquency in Youth: Self-Esteem and Depression as Mediators

Authors: Yuhui Liu, Lydia Speyer, Jasmin Wertz, Ingrid Obsuth

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Childhood adversities refer to situations where a child's basic needs for safety and support are compromised, leading to substantial disruptions in their emotional, cognitive, social, or neurobiological development. Given the prevalence of adversities (8%-39%), their impact on developmental outcomes is challenging to completely avoid. Delinquency is an important consequence of childhood adversities, given its potential causing violence and other forms of victimisation, influencing victims, delinquents, their families, and the whole of society. Studying mediators helps explain the link between childhood adversity and delinquency, which aids in designing effective intervention programs that target explanatory variables to disrupt the path and mitigate the effects of childhood adversities on delinquency. The Dimensional Model of Adversity and Psychopathology suggests that threat-based adversities influence outcomes through emotion processing, while deprivation-based adversities do so through cognitive mechanisms. Thus, considering a wide range of threat-based and deprivation-based adversities and their co-occurrence and their associations with delinquency through cognitive and emotional mechanisms is essential. This study employs the Millennium Cohort Study, tracking the development of approximately 19,000 individuals born across England, Scotland, Wales and Northern Ireland, representing a nationally representative sample. Parallel mediation models compare the mediating roles of self-esteem (cognitive) and depression (affective) in the associations between childhood adversities and delinquency. Eleven types of childhood adversities were assessed both individually and through latent class analysis, considering adversity experiences from birth to early adolescence. This approach aimed to capture how threat-based, deprived-based, or combined threat and deprived-based adversities are associated with delinquency. Eight latent classes were identified: three classes (low adversity, especially direct and indirect violence; low childhood and moderate adolescent adversities; and persistent poverty with declining bullying victimisation) were negatively associated with delinquency. In contrast, three classes (high parental alcohol misuse, overall high adversities, especially regarding household instability, and high adversity) were positively associated with delinquency. When mediators were included, all classes showed a significant association with delinquency through depression, but not through self-esteem. Among the eleven single adversities, seven were positively associated with delinquency, with five linked through depression and none through self-esteem. The results imply the importance of affective variables, not just for threat-based but also deprivation-based adversities. Academically, this suggests exploring other mechanisms linking adversities and delinquency since some adversities are linked through neither depression nor self-esteem. Clinically, intervention programs should focus on affective variables like depression to mitigate the effects of childhood adversities on delinquency.

Keywords: childhood adversity, delinquency, depression, self-esteem

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377 Family Income and Parental Behavior: Maternal Personality as a Moderator

Authors: Robert H. Bradley, Robert F. Corwyn

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There is abundant research showing that socio-economic status is implicated in parenting. However, additional factors such as family context, parent personality, parenting history and child behavior also help determine how parents enact the role of caregiver. Each of these factors not only helps determine how a parent will act in a given situation, but each can serve to moderate the influence of the other factors. Personality has long been studied as a factor that influences parental behavior, but it has almost never been considered as a moderator of family contextual factors. For this study, relations between three maternal personality characteristics (agreeableness, extraversion, neuroticism) and four aspects of parenting (harshness, sensitivity, stimulation, learning materials) were examined when children were 6 months, 36 months, and 54 months old and again at 5th grade. Relations between these three aspects of personality and the overall home environment were also examined. A key concern was whether maternal personality characteristics moderated relations between household income and the four aspects of parenting and between household income and the overall home environment. The data for this study were taken from the NICHD Study of Early Child Care and Youth Development (NICHD SECCYD). The total sample consisted of 1364 families living in ten different sites in the United States. However, the samples analyzed included only those with complete data on all four parenting outcomes (i.e., sensitivity, harshness, stimulation, and provision of learning materials), income, maternal education and all three measures of personality (i.e., agreeableness, neuroticism, extraversion) at each age examined. Results from hierarchical regression analysis showed that mothers high in agreeableness were more likely to demonstrate sensitivity and stimulation as well as provide more learning materials to their children but were less likely to manifest harshness. Maternal agreeableness also consistently moderated the effects of low income on parental behavior. Mothers high in extraversion were more likely to provide stimulation and learning materials, with extraversion serving as a moderator of low income on both. By contrast, mothers high in neuroticism were less likely to demonstrate positive aspects of parenting and more likely to manifest negative aspects (e.g., harshness). Neuroticism also served to moderate the influence of low income on parenting, especially for stimulation and learning materials. The most consistent effects of parent personality were on the overall home environment, with significant main and interaction effects observed in 11 of the 12 models tested. These findings suggest that it may behoove professional who work with parents living in adverse circumstances to consider parental personality in helping to better target prevention or intervention efforts aimed at supporting parental efforts to act in ways that benefit children.

Keywords: home environment, household income, learning materials, personality, sensitivity, stimulation

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376 The Beneficial Effects of Inhibition of Hepatic Adaptor Protein Phosphotyrosine Interacting with PH Domain and Leucine Zipper 2 on Glucose and Cholesterol Homeostasis

Authors: Xi Chen, King-Yip Cheng

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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

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375 Using Lysosomal Immunogenic Cell Death to Target Breast Cancer via Xanthine Oxidase/Micro-Antibody Fusion Protein

Authors: Iulianna Taritsa, Kuldeep Neote, Eric Fossel

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Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence – a gap that can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells, which can later present those tumorigenic antigens to T cells. Previous research has shown that oxidative agents administered in the tumor microenvironment can initiate LIICD. We generated a fusion protein between an oxidative agent known as xanthine oxidase (XO) and a mini-antibody specific for EGFR/HER2-sensitive breast tumor cells. The anti-EGFR single domain antibody fragment is uniquely sourced from llama, which is functional without the presence of a light chain. These llama micro-antibodies have been shown to be better able to penetrate tissues and have improved physicochemical stability as compared to traditional monoclonal antibodies. We demonstrate that the fusion protein created is stable and can induce early markers of immunogenic cell death in an in vitro human breast cancer cell line (SkBr3). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of SkBr3 cells dosed with doxorubicin (a known inducer of LIICD) and a negative control dosed with cisplatin (a known inducer of cell death, but not of the immunogenic variety). We looked at each marker at various time points after cancer cells were treated with the XO/antibody fusion protein, doxorubicin, and cisplatin. Upregulated biomarkers after treatment with the fusion protein indicate an immunogenic response. We thus show the potential for this fusion protein to induce an anticancer effect paired with an adaptive immune response against EGFR/HER2+ cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method for patients and serves as the gateway to developing a new treatment approach against breast cancer.

Keywords: apoptosis, breast cancer, immunogenic cell death, lysosome

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374 Winter Wheat Yield Forecasting Using Sentinel-2 Imagery at the Early Stages

Authors: Chunhua Liao, Jinfei Wang, Bo Shan, Yang Song, Yongjun He, Taifeng Dong

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Winter wheat is one of the main crops in Canada. Forecasting of within-field variability of yield in winter wheat at the early stages is essential for precision farming. However, the crop yield modelling based on high spatial resolution satellite data is generally affected by the lack of continuous satellite observations, resulting in reducing the generalization ability of the models and increasing the difficulty of crop yield forecasting at the early stages. In this study, the correlations between Sentinel-2 data (vegetation indices and reflectance) and yield data collected by combine harvester were investigated and a generalized multivariate linear regression (MLR) model was built and tested with data acquired in different years. It was found that the four-band reflectance (blue, green, red, near-infrared) performed better than their vegetation indices (NDVI, EVI, WDRVI and OSAVI) in wheat yield prediction. The optimum phenological stage for wheat yield prediction with highest accuracy was at the growing stages from the end of the flowering to the beginning of the filling stage. The best MLR model was therefore built to predict wheat yield before harvest using Sentinel-2 data acquired at the end of the flowering stage. Further, to improve the ability of the yield prediction at the early stages, three simple unsupervised domain adaptation (DA) methods were adopted to transform the reflectance data at the early stages to the optimum phenological stage. The winter wheat yield prediction using multiple vegetation indices showed higher accuracy than using single vegetation index. The optimum stage for winter wheat yield forecasting varied with different fields when using vegetation indices, while it was consistent when using multispectral reflectance and the optimum stage for winter wheat yield prediction was at the end of flowering stage. The average testing RMSE of the MLR model at the end of the flowering stage was 604.48 kg/ha. Near the booting stage, the average testing RMSE of yield prediction using the best MLR was reduced to 799.18 kg/ha when applying the mean matching domain adaptation approach to transform the data to the target domain (at the end of the flowering) compared to that using the original data based on the models developed at the booting stage directly (“MLR at the early stage”) (RMSE =1140.64 kg/ha). This study demonstrated that the simple mean matching (MM) performed better than other DA methods and it was found that “DA then MLR at the optimum stage” performed better than “MLR directly at the early stages” for winter wheat yield forecasting at the early stages. The results indicated that the DA had a great potential in near real-time crop yield forecasting at the early stages. This study indicated that the simple domain adaptation methods had a great potential in crop yield prediction at the early stages using remote sensing data.

Keywords: wheat yield prediction, domain adaptation, Sentinel-2, within-field scale

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373 Reaching the Goals of Routine HIV Screening Programs: Quantifying and Implementing an Effective HIV Screening System in Northern Nigeria Facilities Based on Optimal Volume Analysis

Authors: Folajinmi Oluwasina, Towolawi Adetayo, Kate Ssamula, Penninah Iutung, Daniel Reijer

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Objective: Routine HIV screening has been promoted as an essential component of efforts to reduce incidence, morbidity, and mortality. The objectives of this study were to identify the optimal annual volume needed to realize the public health goals of HIV screening in the AIDS Healthcare Foundation supported hospitals and establish an implementation process to realize that optimal annual volume. Methods: Starting in 2011 a program was established to routinize HIV screening within communities and government hospitals. In 2016 Five-years of HIV screening data were reviewed to identify the optimal annual proportions of age-eligible patients screened to realize the public health goals of reducing new diagnoses and ending late-stage diagnosis (tracked as concurrent HIV/AIDS diagnosis). Analysis demonstrated that rates of new diagnoses level off when 42% of age-eligible patients were screened, providing a baseline for routine screening efforts; and concurrent HIV/AIDS diagnoses reached statistical zero at screening rates of 70%. Annual facility based targets were re-structured to meet these new target volumes. Restructuring efforts focused on right-sizing HIV screening programs to align and transition programs to integrated HIV screening within standard medical care and treatment. Results: Over one million patients were screened for HIV during the five years; 16, 033 new HIV diagnoses and access to care and treatment made successfully for 82 % (13,206), and concurrent diagnosis rates went from 32.26% to 25.27%. While screening rates increased by 104.7% over the 5-years, volume analysis demonstrated that rates need to further increase by 62.52% to reach desired 20% baseline and more than double to reach optimal annual screening volume. In 2011 facility targets for HIV screening were increased to reflect volume analysis, and in that third year, 12 of the 19 facilities reached or exceeded new baseline targets. Conclusions and Recommendation: Quantifying targets against routine HIV screening goals identified optimal annual screening volume and allowed facilities to scale their program size and allocate resources accordingly. The program transitioned from utilizing non-evidence based annual volume increases to establishing annual targets based on optimal volume analysis. This has allowed efforts to be evaluated on the ability to realize quantified goals related to the public health value of HIV screening. Optimal volume analysis helps to determine the size of an HIV screening program. It is a public health tool, not a tool to determine if an individual patient should receive screening.

Keywords: HIV screening, optimal volume, HIV diagnosis, routine

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372 Risk Based Inspection and Proactive Maintenance for Civil and Structural Assets in Oil and Gas Plants

Authors: Mohammad Nazri Mustafa, Sh Norliza Sy Salim, Pedram Hatami Abdullah

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Civil and structural assets normally have an average of more than 30 years of design life. Adding to this advantage, the assets are normally subjected to slow degradation process. Due to the fact that repair and strengthening work for these assets are normally not dependent on plant shut down, the maintenance and integrity restoration of these assets are mostly done based on “as required” and “run to failure” basis. However unlike other industries, the exposure in oil and gas environment is harsher as the result of corrosive soil and groundwater, chemical spill, frequent wetting and drying, icing and de-icing, steam and heat, etc. Due to this type of exposure and the increasing level of structural defects and rectification in line with the increasing age of plants, assets integrity assessment requires a more defined scope and procedures that needs to be based on risk and assets criticality. This leads to the establishment of risk based inspection and proactive maintenance procedure for civil and structural assets. To date there is hardly any procedure and guideline as far as integrity assessment and systematic inspection and maintenance of civil and structural assets (onshore) are concerned. Group Technical Solutions has developed a procedure and guideline that takes into consideration credible failure scenario, assets risk and criticality from process safety and structural engineering perspective, structural importance, modeling and analysis among others. Detailed inspection that includes destructive and non-destructive tests (DT & NDT) and structural monitoring is also being performed to quantify defects, assess severity and impact on integrity as well as identify the timeline for integrity restoration. Each defect and its credible failure scenario is assessed against the risk on people, environment, reputation and production loss. This technical paper is intended to share on the established procedure and guideline and their execution in oil & gas plants. In line with the overall roadmap, the procedure and guideline will form part of specialized solutions to increase production and to meet the “Operational Excellence” target while extending service life of civil and structural assets. As the result of implementation, the management of civil and structural assets is now more systematically done and the “fire-fighting” mode of maintenance is being gradually phased out and replaced by a proactive and preventive approach. This technical paper will also set the criteria and pose the challenge to the industry for innovative repair and strengthening methods for civil & structural assets in oil & gas environment, in line with safety, constructability and continuous modification and revamp of plant facilities to meet production demand.

Keywords: assets criticality, credible failure scenario, proactive and preventive maintenance, risk based inspection

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371 A Prospective Study of a Clinically Significant Anatomical Change in Head and Neck Intensity-Modulated Radiation Therapy Using Transit Electronic Portal Imaging Device Images

Authors: Wilai Masanga, Chirapha Tannanonta, Sangutid Thongsawad, Sasikarn Chamchod, Todsaporn Fuangrod

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The major factors of radiotherapy for head and neck (HN) cancers include patient’s anatomical changes and tumour shrinkage. These changes can significantly affect the planned dose distribution that causes the treatment plan deterioration. A measured transit EPID images compared to a predicted EPID images using gamma analysis has been clinically implemented to verify the dose accuracy as part of adaptive radiotherapy protocol. However, a global gamma analysis dose not sensitive to some critical organ changes as the entire treatment field is compared. The objective of this feasibility study is to evaluate the dosimetric response to patient anatomical changes during the treatment course in HN IMRT (Head and Neck Intensity-Modulated Radiation Therapy) using a novel comparison method; organ-of-interest gamma analysis. This method provides more sensitive to specific organ change detection. Random replanned 5 HN IMRT patients with causes of tumour shrinkage and patient weight loss that critically affect to the parotid size changes were selected and evaluated its transit dosimetry. A comprehensive physics-based model was used to generate a series of predicted transit EPID images for each gantry angle from original computed tomography (CT) and replan CT datasets. The patient structures; including left and right parotid, spinal cord, and planning target volume (PTV56) were projected to EPID level. The agreement between the transit images generated from original CT and replanned CT was quantified using gamma analysis with 3%, 3mm criteria. Moreover, only gamma pass-rate is calculated within each projected structure. The gamma pass-rate in right parotid and PTV56 between predicted transit of original CT and replan CT were 42.8%( ± 17.2%) and 54.7%( ± 21.5%). The gamma pass-rate for other projected organs were greater than 80%. Additionally, the results of organ-of-interest gamma analysis were compared with 3-dimensional cone-beam computed tomography (3D-CBCT) and the rational of replan by radiation oncologists. It showed that using only registration of 3D-CBCT to original CT does not provide the dosimetric impact of anatomical changes. Using transit EPID images with organ-of-interest gamma analysis can provide additional information for treatment plan suitability assessment.

Keywords: re-plan, anatomical change, transit electronic portal imaging device, EPID, head, and neck

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370 Approaches to Inducing Obsessional Stress in Obsessive-Compulsive Disorder (OCD): An Empirical Study with Patients Undergoing Transcranial Magnetic Stimulation (TMS) Therapy

Authors: Lucia Liu, Matthew Koziol

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Obsessive-compulsive disorder (OCD), a long-lasting anxiety disorder involving recurrent, intrusive thoughts, affects over 2 million adults in the United States. Transcranial magnetic stimulation (TMS) stands out as a noninvasive, cutting-edge therapy that has been shown to reduce symptoms in patients with treatment-resistant OCD. The Food and Drug Administration (FDA) approved protocol pairs TMS sessions with individualized symptom provocation, aiming to improve the susceptibility of brain circuits to stimulation. However, limited standardization or guidance exists on how to conduct symptom provocation and which methods are most effective. This study aims to compare the effect of internal versus external techniques to induce obsessional stress in a clinical setting during TMS therapy. Two symptom provocation methods, (i) Asking patients thought-provoking questions about their obsessions (internal) and (ii) Requesting patients to perform obsession-related tasks (external), were employed in a crossover design with repeated measurement. Thirty-six treatments of NeuroStar TMS were administered to each of two patients over 8 weeks in an outpatient clinic. Patient One received 18 sessions of internal provocation followed by 18 sessions of external provocation, while Patient Two received 18 sessions of external provocation followed by 18 sessions of internal provocation. The primary outcome was the level of self-reported obsessional stress on a visual analog scale from 1 to 10. The secondary outcome was self-reported OCD severity, collected biweekly in a four-level Likert-scale (1 to 4) of bad, fair, good and excellent. Outcomes were compared and tested between provocation arms through repeated measures ANOVA, accounting for intra-patient correlations. Ages were 42 for Patient One (male, White) and 57 for Patient Two (male, White). Both patients had similar moderate symptoms at baseline, as determined through the Yale-Brown Obsessive Compulsive Scale (YBOCS). When comparing obsessional stress induced across the two arms of internal and external provocation methods, the mean (SD) was 6.03 (1.18) for internal and 4.01 (1.28) for external strategies (P=0.0019); ranges were 3 to 8 for internal and 2 to 8 for external strategies. Internal provocation yielded 5 (31.25%) bad, 6 (33.33%) fair, 3 (18.75%) good, and 2 (12.5%) excellent responses for OCD status, while external provocation yielded 5 (31.25%) bad, 9 (56.25%) fair, 1 (6.25%) good, and 1 (6.25%) excellent responses (P=0.58). Internal symptom provocation tactics had a significantly stronger impact on inducing obsessional stress and led to better OCD status (non-significant). This could be attributed to the fact that answering questions may prompt patients to reflect more on their lived experiences and struggles with OCD. In the future, clinical trials with larger sample sizes are warranted to validate this finding. Results support the increased integration of internal methods into structured provocation protocols, potentially reducing the time required for provocation and achieving greater treatment response to TMS.

Keywords: obsessive-compulsive disorder, transcranial magnetic stimulation, mental health, symptom provocation

Procedia PDF Downloads 42
369 Necessity for a Standardized Occupational Health and Safety Management System: An Exploratory Study from the Danish Offshore Wind Sector

Authors: Dewan Ahsan

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Denmark is well ahead in generating electricity from renewable sources. The offshore wind sector is playing the pivotal role to achieve this target. Though there is a rapid growth of offshore wind sector in Denmark, still there is a dearth of synchronization in OHS (occupational health and safety) regulation and standards. Therefore, this paper attempts to ascertain: i) what are the major challenges of the company specific OHS standards? ii) why does the offshore wind industry need a standardized OHS management system? and iii) who can play the key role in this process? To achieve these objectives, this research applies the interview and survey techniques. This study has identified several key challenges in OHS management system which are; gaps in coordination and communication among the stakeholders, gaps in incident reporting systems, absence of a harmonized OHS standard and blame culture. Furthermore, this research has identified eleven key stakeholders who are actively involve with the offshore wind business in Denmark. As noticed, the relationships among these stakeholders are very complex specially between operators and sub-contractors. The respondent technicians are concerned with the compliance of various third-party OHS standards (e.g. ISO 31000, ISO 29400, Good practice guidelines by G+) which are applying by various offshore companies. On top of these standards, operators also impose their own OHS standards. From the technicians point of angle, many of these standards are not even specific for the offshore wind sector. So, it is a big challenge for the technicians and sub-contractors to comply with different company specific standards which also elevate the price of their services offer to the operators. For instance, when a sub-contractor is competing for a bidding, it must fulfill a number of OHS requirements (which demands many extra documantions) set by the individual operator and/the turbine supplier. According to sub-contractors’ point of view these extra works consume too much time to prepare the bidding documents and they also need to train their employees to pass the specific OHS certification courses to accomplish the demand for individual clients and individual project. The sub-contractors argued that in many cases these extra documentations and OHS certificates are inessential to ensure the quality service. So, a standardized OHS management procedure (which could be applicable for all the clients) can easily solve this problem. In conclusion, this study highlights that i) development of a harmonized OHS standard applicable for all the operators and turbine suppliers, ii) encouragement of technicians’ active participation in the OHS management, iii) development of a good safety leadership, and, iv) sharing of experiences among the stakeholders (specially operators-operators-sub contractors) are the most vital strategies to overcome the existing challenges and to achieve the goal of 'zero accident/harm' in the offshore wind industry.

Keywords: green energy, offshore, safety, Denmark

Procedia PDF Downloads 202
368 Analysis of Taxonomic Compositions, Metabolic Pathways and Antibiotic Resistance Genes in Fish Gut Microbiome by Shotgun Metagenomics

Authors: Anuj Tyagi, Balwinder Singh, Naveen Kumar B. T., Niraj K. Singh

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Characterization of diverse microbial communities in specific environment plays a crucial role in the better understanding of their functional relationship with the ecosystem. It is now well established that gut microbiome of fish is not the simple replication of microbiota of surrounding local habitat, and extensive species, dietary, physiological and metabolic variations in fishes may have a significant impact on its composition. Moreover, overuse of antibiotics in human, veterinary and aquaculture medicine has led to rapid emergence and propagation of antibiotic resistance genes (ARGs) in the aquatic environment. Microbial communities harboring specific ARGs not only get a preferential edge during selective antibiotic exposure but also possess the significant risk of ARGs transfer to other non-resistance bacteria within the confined environments. This phenomenon may lead to the emergence of habitat-specific microbial resistomes and subsequent emergence of virulent antibiotic-resistant pathogens with severe fish and consumer health consequences. In this study, gut microbiota of freshwater carp (Labeo rohita) was investigated by shotgun metagenomics to understand its taxonomic composition and functional capabilities. Metagenomic DNA, extracted from the fish gut, was subjected to sequencing on Illumina NextSeq to generate paired-end (PE) 2 x 150 bp sequencing reads. After the QC of raw sequencing data by Trimmomatic, taxonomic analysis by Kraken2 taxonomic sequence classification system revealed the presence of 36 phyla, 326 families and 985 genera in the fish gut microbiome. At phylum level, Proteobacteria accounted for more than three-fourths of total bacterial populations followed by Actinobacteria (14%) and Cyanobacteria (3%). Commonly used probiotic bacteria (Bacillus, Lactobacillus, Streptococcus, and Lactococcus) were found to be very less prevalent in fish gut. After sequencing data assembly by MEGAHIT v1.1.2 assembler and PROKKA automated analysis pipeline, pathway analysis revealed the presence of 1,608 Metacyc pathways in the fish gut microbiome. Biosynthesis pathways were found to be the most dominant (51%) followed by degradation (39%), energy-metabolism (4%) and fermentation (2%). Almost one-third (33%) of biosynthesis pathways were involved in the synthesis of secondary metabolites. Metabolic pathways for the biosynthesis of 35 antibiotic types were also present, and these accounted for 5% of overall metabolic pathways in the fish gut microbiome. Fifty-one different types of antibiotic resistance genes (ARGs) belonging to 15 antimicrobial resistance (AMR) gene families and conferring resistance against 24 antibiotic types were detected in fish gut. More than 90% ARGs in fish gut microbiome were against beta-lactams (penicillins, cephalosporins, penems, and monobactams). Resistance against tetracycline, macrolides, fluoroquinolones, and phenicols ranged from 0.7% to 1.3%. Some of the ARGs for multi-drug resistance were also found to be located on sequences of plasmid origin. The presence of pathogenic bacteria and ARGs on plasmid sequences suggested the potential risk due to horizontal gene transfer in the confined gut environment.

Keywords: antibiotic resistance, fish gut, metabolic pathways, microbial diversity

Procedia PDF Downloads 127
367 The Use of Vasopressin in the Management of Severe Traumatic Brain Injury: A Narrative Review

Authors: Nicole Selvi Hill, Archchana Radhakrishnan

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Introduction: Traumatic brain injury (TBI) is a leading cause of mortality among trauma patients. In the management of TBI, the main principle is avoiding cerebral ischemia, as this is a strong determiner of neurological outcomes. The use of vasoactive drugs, such as vasopressin, has an important role in maintaining cerebral perfusion pressure to prevent secondary brain injury. Current guidelines do not suggest a preferred vasoactive drug to administer in the management of TBI, and there is a paucity of information on the therapeutic potential of vasopressin following TBI. Vasopressin is also an endogenous anti-diuretic hormone (AVP), and pathways mediated by AVP play a large role in the underlying pathological processes of TBI. This creates an overlap of discussion regarding the therapeutic potential of vasopressin following TBI. Currently, its popularity lies in vasodilatory and cardiogenic shock in the intensive care setting, with increasing support for its use in haemorrhagic and septic shock. Methodology: This is a review article based on a literature review. An electronic search was conducted via PubMed, Cochrane, EMBASE, and Google Scholar. The aim was to identify clinical studies looking at the therapeutic administration of vasopressin in severe traumatic brain injury. The primary aim was to look at the neurological outcome of patients. The secondary aim was to look at surrogate markers of cerebral perfusion measurements, such as cerebral perfusion pressure, cerebral oxygenation, and cerebral blood flow. Results: Eight papers were included in the final number. Three were animal studies; five were human studies, comprised of three case reports, one retrospective review of data, and one randomised control trial. All animal studies demonstrated the benefits of vasopressors in TBI management. One animal study showed the superiority of vasopressin in reducing intracranial pressure and increasing cerebral oxygenation over a catecholaminergic vasopressor, phenylephrine. All three human case reports were supportive of vasopressin as a rescue therapy in catecholaminergic-resistant hypotension. The retrospective review found vasopressin did not increase cerebral oedema in TBI patients compared to catecholaminergic vasopressors; and demonstrated a significant reduction in the requirements of hyperosmolar therapy in patients that received vasopressin. The randomised control trial results showed no significant differences in primary and secondary outcomes between TBI patients receiving vasopressin versus those receiving catecholaminergic vasopressors. Apart from the randomised control trial, the studies included are of low-level evidence. Conclusion: Studies favour vasopressin within certain parameters of cerebral function compared to control groups. However, the neurological outcomes of patient groups are not known, and animal study results are difficult to extrapolate to humans. It cannot be said with certainty whether vasopressin’s benefits stand above usage of other vasoactive drugs due to the weaknesses of the evidence. Further randomised control trials, which are larger, standardised, and rigorous, are required to improve knowledge in this field.

Keywords: catecholamines, cerebral perfusion pressure, traumatic brain injury, vasopressin, vasopressors

Procedia PDF Downloads 56
366 COVID-19: Potential Effects of Nutritional Factors on Inflammation Relief

Authors: Maryam Nazari

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COVID-19 is a respiratory disease triggered by the novel coronavirus, SARS-CoV-2, that has reached pandemic status today. Acute inflammation and immune cells infiltration into lung injuries result in multi-organ failure. The presence of other non-communicable diseases (NCDs) with systemic inflammation derived from COVID-19 may exacerbate the patient's situation and increase the risk for adverse effects and mortality. This pandemic is a novel situation and the scientific community at this time is looking for vaccines or drugs to treat the pathology. One of the biggest challenges is focused on reducing inflammation without compromising the correct immune response of the patient. In this regard, addressing the nutritional factors should not be overlooked not only as a matter of avoiding the presence of NCDs with severe infections but also as an adjunctive way to modulate the inflammatory status of the patients. Despite the pivotal role of nutrition in modifying immune response, due to the novelty of the COVID-19 disease, information about the effects of specific dietary agents is limited in this area. From the macronutrients point of view, protein deficiency (quantity or quality) has negative effects on the number of functional immunoglobulins and gut-associated lymphoid tissue (GALT). High biological value proteins or some amino acids like arginine and glutamine are well known for their ability to augment the immune system. Among lipids, fish oil has the ability to inactivate enveloped viruses, suppress pro-inflammatory prostaglandin production and block platelet-activating factors and their receptors. In addition, protectin D1, which is an Omega-3 PUFAs derivation, is a novel antiviral drug. So it seems that these fatty acids can reduce the severity and/or improve recovery of patients with COVID-19. Carbohydrates with lower glycemic index and fibers are associated with lower levels of inflammatory cytokines (CRP, TNF-α, and IL-6). Short-Chain Fatty acids not only exert a direct anti-inflammatory effect but also provide appropriate gut microbial, which is important in gastrointestinal issues related to COVID-19. From the micronutrients point of view, Vitamins A, C, D, E, iron, magnesium, zinc, selenium and copper play a vital role in the maintenance of immune function. Inadequate status in these nutrients may result in decreased resistance against COVID-19 infection. There are specific bioactive compounds in the diet that interact with the ACE2 receptor, which is the gateway for SARS and SARS-CoV-2, and thus controls the viral infection. Regarding this, the potential benefits of probiotics, resveratrol (a polyphenol found in grape), oleoylethanolamide (derived from oleic acid), and natural peroxisome proliferator-activated receptor γ agonists in foodstuffs (like curcumin, pomegranate, hot pepper) are suggested. Yet, it should be pointed out that most of these results have been reported in animal models and further human studies are needed to be verified.

Keywords: Covid-19, inflammation, nutrition, dietary agents

Procedia PDF Downloads 158
365 A Qualitative Exploration of the Beliefs and Experiences of HIV-Related Self-Stigma Amongst Young Adults Living with HIV in Zimbabwe

Authors: Camille Rich, Nadine Ferris France, Ann Nolan, Webster Mavhu, Vongai Munatsi

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Background and Aim: Zimbabwe has one of the highest HIV rates in the world, with a 12.7% adult prevalence rate. Young adults are a key group affected by HIV, and one-third of all new infections in Zimbabwe are amongst people ages 18-24 years. Stigma remains one of the main barriers to managing and reducing the HIV crisis, especially for young adults. There are several types of stigma, including enacted stigma, the outward discrimination towards someone and self-stigma, the negative self-judgments one has towards themselves. Self-stigma can have severe consequences, including feelings of worthlessness, shame, suicidal thoughts, and avoidance of medical help. This can have detrimental effects on those living with HIV. However, the unique beliefs and impacts of self-stigma amongst key groups living with HIV have not yet been explored. Therefore, the focus of this study is on the beliefs and experiences of HIV-related self-stigma, as experienced by young adults living in Harare, Zimbabwe. Research Methods: A qualitative approach was taken for this study, using sixteen semi-structured interviews with young adults (18-24 years) who are living with HIV in Harare. Participants were conveniently and purposefully sampled as members of Africa, an organization dedicated to young people living with HIV. Interviews were conducted over Zoom due to the COVID-19 pandemic, recorded and then coded using the software NVivo. The data was analyzed using both inductive and deductive Thematic Analysis to find common themes. Results: All of the participants experienced HIV-related self-stigma, and both beliefs and experiences were explored. These negative self-perceptions included beliefs of worthlessness, hopelessness, and negative body image. The young adults described believing they were not good enough to be around HIV negative people or that they could never be loved due to their HIV status. Developing self-stigmatizing thoughts came from internalizing negative cultural values, stereotypes about people living with HIV, and adverse experiences. Three main themes of self-stigmatizing experiences emerged: disclosure difficulties, relationship complications, and being isolated. Fear of telling someone their status, rejection in a relationship, and being excluded by others due to their HIV status contributed to their self-stigma. These experiences caused feelings of loneliness, sadness, shame, fear, and low self-worth. Conclusions: This study explored the beliefs and experiences of HIV-related self-stigma of these young adults. The emergence of negative self-perceptions demonstrated deep-rooted beliefs of HIV-related self-stigma that adversely impact the participants. The negative self-perceptions and self-stigmatizing experiences caused the participants to feel worthless, hopeless, shameful, and alone-negatively impacting their physical and mental health, personal relationships, and sense of self-identity. These results can now be used to pursue interventions to target the specific beliefs and experiences of young adults living with HIV and reduce the adverse consequences of self-stigma.

Keywords: beliefs, HIV, self-stigma, stigma, Zimbabwe

Procedia PDF Downloads 97
364 Learning to Translate by Learning to Communicate to an Entailment Classifier

Authors: Szymon Rutkowski, Tomasz Korbak

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We present a reinforcement-learning-based method of training neural machine translation models without parallel corpora. The standard encoder-decoder approach to machine translation suffers from two problems we aim to address. First, it needs parallel corpora, which are scarce, especially for low-resource languages. Second, it lacks psychological plausibility of learning procedure: learning a foreign language is about learning to communicate useful information, not merely learning to transduce from one language’s 'encoding' to another. We instead pose the problem of learning to translate as learning a policy in a communication game between two agents: the translator and the classifier. The classifier is trained beforehand on a natural language inference task (determining the entailment relation between a premise and a hypothesis) in the target language. The translator produces a sequence of actions that correspond to generating translations of both the hypothesis and premise, which are then passed to the classifier. The translator is rewarded for classifier’s performance on determining entailment between sentences translated by the translator to disciple’s native language. Translator’s performance thus reflects its ability to communicate useful information to the classifier. In effect, we train a machine translation model without the need for parallel corpora altogether. While similar reinforcement learning formulations for zero-shot translation were proposed before, there is a number of improvements we introduce. While prior research aimed at grounding the translation task in the physical world by evaluating agents on an image captioning task, we found that using a linguistic task is more sample-efficient. Natural language inference (also known as recognizing textual entailment) captures semantic properties of sentence pairs that are poorly correlated with semantic similarity, thus enforcing basic understanding of the role played by compositionality. It has been shown that models trained recognizing textual entailment produce high-quality general-purpose sentence embeddings transferrable to other tasks. We use stanford natural language inference (SNLI) dataset as well as its analogous datasets for French (XNLI) and Polish (CDSCorpus). Textual entailment corpora can be obtained relatively easily for any language, which makes our approach more extensible to low-resource languages than traditional approaches based on parallel corpora. We evaluated a number of reinforcement learning algorithms (including policy gradients and actor-critic) to solve the problem of translator’s policy optimization and found that our attempts yield some promising improvements over previous approaches to reinforcement-learning based zero-shot machine translation.

Keywords: agent-based language learning, low-resource translation, natural language inference, neural machine translation, reinforcement learning

Procedia PDF Downloads 114
363 Neuroprotection against N-Methyl-D-Aspartate-Induced Optic Nerve and Retinal Degeneration Changes by Philanthotoxin-343 to Alleviate Visual Impairments Involve Reduced Nitrosative Stress

Authors: Izuddin Fahmy Abu, Mohamad Haiqal Nizar Mohamad, Muhammad Fattah Fazel, Renu Agarwal, Igor Iezhitsa, Nor Salmah Bakar, Henrik Franzyk, Ian Mellor

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Glaucoma is the global leading cause of irreversible blindness. Currently, the available treatment strategy only involves lowering intraocular pressure (IOP); however, the condition often progresses despite lowered or normal IOP in some patients. N-methyl-D-aspartate receptor (NMDAR) excitotoxicity often occurs in neurodegeneration-related glaucoma; thus it is a relevant target to develop a therapy based on neuroprotection approach. This study investigated the effects of Philanthotoxin-343 (PhTX-343), an NMDAR antagonist, on the neuroprotection of NMDA-induced glaucoma to alleviate visual impairments. Male Sprague-Dawley rats were equally divided: Groups 1 (control) and 2 (glaucoma) were intravitreally injected with phosphate buffer saline (PBS) and NMDA (160nM), respectively, while group 3 was pre-treated with PhTX-343 (160nM) 24 hours prior to NMDA injection. Seven days post-treatments, rats were subjected to visual behavior assessments and subsequently euthanized to harvest their retina and optic nerve tissues for histological analysis and determination of nitrosative stress level using 3-nitrotyrosine ELISA. Visual behavior assessments via open field, object, and color recognition tests demonstrated poor visual performance in glaucoma rats indicated by high exploratory behavior. PhTX-343 pre-treatment appeared to preserve visual abilities as all test results were significantly improved (p < 0.05). H&E staining of the retina showed a marked reduction of ganglion cell layer thickness in the glaucoma group; in contrast, PhTX-343 significantly increased the number by 1.28-folds (p < 0.05). PhTX-343 also increased the number of cell nuclei/100μm2 within inner retina by 1.82-folds compared to the glaucoma group (p < 0.05). Toluidine blue staining of optic nerve tissues showed that PhTX-343 reduced the degeneration changes compared to the glaucoma group which exhibited vacuolation overall sections. PhTX-343 also decreased retinal 3- nitrotyrosine concentration by 1.74-folds compared to the glaucoma group (p < 0.05). All results in PhTX-343 group were comparable to control (p > 0.05). We conclude that PhTX-343 protects against NMDA-induced changes and visual impairments in the rat model by reducing nitrosative stress levels.

Keywords: excitotoxicity, glaucoma, nitrosative stress , NMDA receptor , N-methyl-D-aspartate , philanthotoxin, visual behaviour

Procedia PDF Downloads 120
362 Calibration of Residential Buildings Energy Simulations Using Real Data from an Extensive in situ Sensor Network – A Study of Energy Performance Gap

Authors: Mathieu Bourdeau, Philippe Basset, Julien Waeytens, Elyes Nefzaoui

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As residential buildings account for a third of the overall energy consumption and greenhouse gas emissions in Europe, building energy modeling is an essential tool to reach energy efficiency goals. In the energy modeling process, calibration is a mandatory step to obtain accurate and reliable energy simulations. Nevertheless, the comparison between simulation results and the actual building energy behavior often highlights a significant performance gap. The literature discusses different origins of energy performance gaps, from building design to building operation. Then, building operation description in energy models, especially energy usages and users’ behavior, plays an important role in the reliability of simulations but is also the most accessible target for post-occupancy energy management and optimization. Therefore, the present study aims to discuss results on the calibration ofresidential building energy models using real operation data. Data are collected through a sensor network of more than 180 sensors and advanced energy meters deployed in three collective residential buildings undergoing major retrofit actions. The sensor network is implemented at building scale and in an eight-apartment sample. Data are collected for over one year and half and coverbuilding energy behavior – thermal and electricity, indoor environment, inhabitants’ comfort, occupancy, occupants behavior and energy uses, and local weather. Building energy simulations are performed using a physics-based building energy modeling software (Pleaides software), where the buildings’features are implemented according to the buildingsthermal regulation code compliance study and the retrofit project technical files. Sensitivity analyses are performed to highlight the most energy-driving building features regarding each end-use. These features are then compared with the collected post-occupancy data. Energy-driving features are progressively replaced with field data for a step-by-step calibration of the energy model. Results of this study provide an analysis of energy performance gap on an existing residential case study under deep retrofit actions. It highlights the impact of the different building features on the energy behavior and the performance gap in this context, such as temperature setpoints, indoor occupancy, the building envelopeproperties but also domestic hot water usage or heat gains from electric appliances. The benefits of inputting field data from an extensive instrumentation campaign instead of standardized scenarios are also described. Finally, the exhaustive instrumentation solution provides useful insights on the needs, advantages, and shortcomings of the implemented sensor network for its replicability on a larger scale and for different use cases.

Keywords: calibration, building energy modeling, performance gap, sensor network

Procedia PDF Downloads 140
361 Investigating Secondary Students’ Attitude towards Learning English

Authors: Pinkey Yaqub

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The aim of this study was to investigate secondary (grades IX and X) students’ attitudes towards learning the English language based on the medium of instruction of the school, the gender of the students and the grade level in which they studied. A further aim was to determine students’ proficiency in the English language according to their gender, the grade level and the medium of instruction of the school. A survey was used to investigate the attitudes of secondary students towards English language learning. Simple random sampling was employed to obtain a representative sample of the target population for the research study as a comprehensive list of established English medium schools, and newly established English medium schools were available. A questionnaire ‘Attitude towards English Language Learning’ (AtELL) was adapted from a research study on Libyan secondary school students’ attitudes towards learning English language. AtELL was reviewed by experts (n=6) and later piloted on a representative sample of secondary students (n= 160). Subsequently, the questionnaire was modified - based on the reviewers’ feedback and lessons learnt during the piloting phase - and directly administered to students of grades 9 and 10 to gather information regarding their attitudes towards learning the English language. Data collection spanned a month and a half. As the data were not normally distributed, the researcher used Mann-Whitney tests to test the hypotheses formulated to investigate students’ attitudes towards learning English as well as proficiency in the language across the medium of instruction of the school, the gender of the students and the grade level of the respondents. Statistical analyses of the data showed that the students of established English medium schools exhibited a positive outlook towards English language learning in terms of the behavioural, cognitive and emotional aspects of attitude. A significant difference was observed in the attitudes of male and female students towards learning English where females showed a more positive attitude in terms of behavioural, cognitive and emotional aspects as compared to their male counterparts. Moreover, grade 10 students had a more positive attitude towards learning English language in terms of behavioural, cognitive and emotional aspects as compared to grade 9 students. Nonetheless, students of newly established English medium schools were more proficient in English as gauged by their examination scores in this subject as compared to their counterparts studying in established English medium schools. Moreover, female students were more proficient in English while students studying in grade 9 were less proficient in English than their seniors studying in grade 10. The findings of this research provide empirical evidence to future researchers wishing to explore the relationship between attitudes towards learning language and variables such as the medium of instruction of the school, gender and the grade level of the students. Furthermore, policymakers might revisit the English curriculum to formulate specific guidelines that promote a positive and gender-balanced outlook towards learning English for male and female students.

Keywords: attitude, behavioral aspect of attitude, cognitive aspect of attitude, emotional aspect of attitude

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360 Management Problems in a Patient With Long-term Undiagnosed Permanent Hypoparathyroidism

Authors: Babarina Maria, Andropova Margarita

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Introduction: Hypoparathyroidism (HypoPT) is a rare endocrine disorder with an estimated prevalence of 0.25 per 1000 individuals. The most common cause of HypoPT is the loss of active parathyroid tissue following thyroid or parathyroid surgery. Sometimes permanent postoperative HypoPT occures, manifested by hypocalcemia in combination with low levels of PTH during 6 months or more after surgery. Cognitive impairments in patients with hypocalcemia due to chronic HypoPT are observed, and this can lead to problems and challenges in everyday living: memory loss and impaired concentration, that may be the cause of poor compliance. Clinical case: Patient K., 66 years old, underwent thyroidectomy in 2013 (at the age of 55) because of papillary thyroid cancer T1NxMx, histopathology findings confirmed the diagnosis. 5 years after the surgery, she was followed up on an outpatient basis, TSH levelsonly were monitored, and the dose of levothyroxine was adjusted. In 2018 due to, increasing complaints include tingling and cramps in the arms and legs, memory loss, sleep disorder, fatigue, anxiety, hair loss, muscle pain, tachycardia, positive Chvostek, and Trousseau signs were diagnosed during examination, also in blood analyses: total Ca 1.86 mmol/l (2.15-2.55), Ca++ 0.96 mmol/l (1.12-1.3), P 1.55 mmol/l (0.74-1.52), Mg 0.79 mmol/l (0.66-1.07) - chronic postoperative HypoPT was diagnosed. Therapy was initiated: alfacalcidol 0.5 mcg per day, calcium carbonate 2000 mg per day, cholecalciferol 1000 IU per day, magnesium orotate 3000 mg per day. During the case follow-up, hypocalcemia, hyperphosphatemia persisted, hypercalciuria15.7 mmol/day (2.5-6.5) was diagnosed. Dietary recommendations were given because of the high content of phosphorus rich foods, and therapy was adjusted: the dose of alfacalcidol was increased to 2.5 mcg per day, and the dose of calcium carbonate was reduced to 1500 mg per day. As part of the screening for complications of hypoPT, data for cataracts, Fahr syndrome, nephrocalcinosis, and kidney stone disease were not obtained. However, HypoPT compensation was not achieved, and therefore hydrochlorothiazide 25 mg was initiated, the dose of alfacalcidol was increased to 3 mcg per day, calcium carbonate to 3000 mg per day, magnesium orotate and cholecalciferol were continued at the same doses. Therapeutic goals were achieved: calcium phosphate product <4.4 mmol2/l2, there were no episodes of hypercalcemia, twenty-four-hour urinary calcium excretion was significantly reduced. Conclusion: Timely prescription, careful explanation of drugs usage rules, and monitoring and maintaining blood and urine parameters within the target contribute to the prevention of HypoPT complications development and life-threatening events.

Keywords: hypoparathyroidism, hypocalcemia, hyperphosphatemia, hypercalciuria

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359 Impact of the Achyranthes aspera (Amaranthaceae) Extracts on the Survival and Histological Architecture of the Midgut Epithelial Tissue of Early Fourth Instars of Aedes aegypti (Diptera: Culicidae)

Authors: Aarti Sharma, Sarita Kumar, Pushplata Tripathi

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Aedes aegypti L. is one of the most important insect vectors in the world transmitting several diseases of concern; dengue fever, dengue haemorrhagic fever and yellow fever. Though since ages the control of dengue vector is primarily relied upon the use of synthetic chemical insecticides, the continued and indiscriminate use of insecticides for their control has received wide public apprehension because of multifarious problems including insecticide resistance, resurgence of pest species, environmental pollution, toxic hazards to humans and non-target organisms. These problems have necessitated the need to explore and develop alternative strategies using eco-friendly and bio-degradable plant products. Bio-insecticides, despite being the focus of research nowadays, have not been investigated much regarding their physiological effects on the mosquitoes. Thus, the present studies were carried out to investigate the anti-mosquito potential of the leaf and stem hexane extracts of Achyranthes aspera against early fourth instars of Aedes aegypti L and their effects on the histological architecture of their midgut. The larvicidal bioassays conducted with the A. aspera leaf hexane extracts revealed the respective LC30, LC50 and LC90 values of 66.545 ppm, 82.555 ppm, 139.817 ppm while the assays with stem hexane extracts resulted in respective values of 54.982 ppm, 68.133 ppm, 115.075 ppm. The studies clearly indicate the efficacy of extracts as larvicidal agents against Ae. aegypti, the stem extracts being found more effective than the leaf extracts. When the larvae assayed with extracts were investigated for the modifications in the histo-architecture of the midgut, the studies showed significant damage, shrinkage, distortion and vacuolization of gut tissues and peritrophic membrane causing disintegration of epithelial cells and cytoplasmic organelles; extent of toxicity and damage varied depending upon the concentration and exposure time period. These changes revealed appreciable stomach poison potential of A. aspera extracts against Ae. aegypti larvae, which may have also caused adverse impact on the growth and development of larvae. These effects were also found to be more pronounced with the stem extract than the leaf extract. Our findings may prove significant suggesting the use of A. aspera extract as a bio-insecticide against early fourth instar larvae of Ae. aegypti. Further studies are needed to identify the bioactive component in the extracts and to ascertain the use of component in the fields as anti-mosquito control agent.

Keywords: Achyranthes aspera, Aedes aegypti, histological architecture, larvicidal, midgut, stomach poison

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358 Eggshell Waste Bioprocessing for Sustainable Acid Phosphatase Production and Minimizing Environmental Hazards

Authors: Soad Abubakr Abdelgalil, Gaber Attia Abo-Zaid, Mohamed Mohamed Yousri Kaddah

Abstract:

Background: The Environmental Protection Agency has listed eggshell waste as the 15th most significant food industry pollution hazard. The utilization of eggshell waste as a source of renewable energy has been a hot topic in recent years. Therefore, finding a sustainable solution for the recycling and valorization of eggshell waste by investigating its potential to produce acid phosphatase (ACP) and organic acids by the newly-discovered B. sonorensis was the target of the current investigation. Results: The most potent ACP-producing B. sonorensis strain ACP2 was identified as a local bacterial strain obtained from the effluent of paper and pulp industries on basis of molecular and morphological characterization. The use of consecutive statistical experimental approaches of Plackett-Burman Design (PBD), and Orthogonal Central Composite Design (OCCD), followed by pH-uncontrolled cultivation conditions in a 7 L bench-top bioreactor, revealed an innovative medium formulation that substantially improved ACP production, reaching 216 U L⁻¹ with ACP yield coefficient Yp/x of 18.2 and a specific growth rate (µ) of 0.1 h⁻¹. The metals Ag+, Sn+, and Cr+ were the most efficiently released from eggshells during the solubilization process by B. sonorensis. The uncontrolled pH culture condition is the most suited and favored setting for improving the ACP and organic acids production simultaneously. Quantitative and qualitative analyses of produced organic acids were carried out using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Lactic acid, citric acid, and hydroxybenzoic acid isomer were the most common organic acids produced throughout the cultivation process. The findings of thermogravimetric analysis (TGA), differential scan calorimeter (DSC), scanning electron microscope (SEM), energy-dispersive spectroscopy (EDS), Fourier-Transform Infrared Spectroscopy (FTIR), and X-Ray Diffraction (XRD) analysis emphasize the significant influence of organic acids and ACP activity on the solubilization of eggshells particles. Conclusions: This study emphasized robust microbial engineering approaches for the large-scale production of a newly discovered acid phosphatase accompanied by organic acids production from B. sonorensis. The biovalorization of the eggshell waste and the production of cost-effective ACP and organic acids were integrated into the current study, and this was done through the implementation of a unique and innovative medium formulation design for eggshell waste management, as well as scaling up ACP production on a bench-top scale.

Keywords: chicken eggshells waste, bioremediation, statistical experimental design, batch fermentation

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357 Targeting Apoptosis by Novel Adamantane Analogs as an Emerging Therapy for the Treatment of Hepatocellular Carcinoma Through EGFR, Bcl-2/BAX Cascade

Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam

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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.

Keywords: adamantane, EGFR, HCC, apoptosis

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356 ePA-Coach: Design of the Intelligent Virtual Learning Coach for Senior Learners in Support of Digital Literacy in the Context of Electronic Patient Record

Authors: Ilona Buchem, Carolin Gellner

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Over the last few years, the call for the support of senior learners in the development of their digital literacy has become prevalent, mainly due to the progression towards ageing societies paired with advances in digitalisation in all spheres of life, including e-health and electronic patient record (EPA). While major research efforts in supporting senior learners in developing digital literacy have been invested so far in e-learning focusing on knowledge acquisition and cognitive tasks, little research exists in learning models which target virtual mentoring and coaching with the help of pedagogical agents and address the social dimensions of learning. Research from studies with students in the context of formal education has already provided methods for designing intelligent virtual agents in support of personalised learning. However, this research has mostly focused on cognitive skills and has not yet been applied to the context of mentoring/coaching of senior learners, who have different characteristics and learn in different contexts. In this paper, we describe how insights from previous research can be used to develop an intelligent virtual learning coach (agent) for senior learners with a focus on building the social relationship between the agent and the learner and the key task of the agent to socialize learners to the larger context of digital literacy with a focus on electronic health records. Following current approaches to mentoring and coaching, the agent is designed not to enhance and monitor the cognitive performance of the learner but to serve as a trusted friend and advisor, whose role is to provide one-to-one guidance and support sharing of experiences among learners (peers). Based on literature review and synopsis of research on virtual agents and current coaching/mentoring models under consideration of the specific characteristics and requirements of senior learners, we describe the design framework which was applied to design an intelligent virtual learning coach as part of the e-learning system for digital literacy of senior learners in the ePA-Coach project founded by the German Ministry of Education and Research. This paper also presents the results from the evaluation study, which compared the use of the first prototype of the virtual learning coach designed according to the design framework with a voice narration in a multimedia learning environment with senior learners. The focus of the study was to validate the agent design in the context of the persona effect (Lester et al., 1997). Since the persona effect is related to the hypothesis that animated agents are perceived as more socially engaging, the study evaluated possible impacts of agent coaching in comparison with voice coaching on motivation, engagement, experience, and digital literacy.

Keywords: virtual learning coach, virtual mentor, pedagogical agent, senior learners, digital literacy, electronic health records

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355 Exploring Bio-Inspired Catecholamine Chemistry to Design Durable Anti-Fungal Wound Dressings

Authors: Chetna Dhand, Venkatesh Mayandi, Silvia Marrero Diaz, Roger W. Beuerman, Seeram Ramakrishna, Rajamani Lakshminarayanan

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Sturdy Insect Cuticle Sclerotization, Incredible Substrate independent Mussel’s bioadhesion, Tanning of Leather are some of catechol(amine)s mediated natural processes. Chemical contemplation spots toward a mechanism instigated with the formation of the quinone moieties from the respective catechol(amine)s, via oxidation, followed by the nucleophilic addition of the amino acids/proteins/peptides to this quinone leads to the development of highly strong, cross-linked and water-resistant proteinacious structures. Inspired with this remarkable catechol(amine)s chemistry towards amino acids/proteins/peptides, we attempted to design highly stable and water-resistant antifungal wound dressing mats with exceptional durability using collagen (protein), dopamine (catecholamine) and antifungal drugs (Amphotericin B and Caspofungin) as the key materials. Electrospinning technique has been used to fabricate desired nanofibrous mat including Collagen (COLL), COLL/Dopamine (COLL/DP) and calcium incorporated COLL/DP (COLL-DP-Ca2+). The prepared protein-based scaffolds have been studied for their microscopic investigations (SEM, TEM, and AFM), structural analysis (FT-IR), mechanical properties, water wettability characteristics and aqueous stability. Biocompatibility of these scaffolds has been analyzed for dermal fibroblast cells using MTS assay, Cell TrackerTM Green CMFDA and confocal imaging. Being the winner sample, COLL-DP-Ca2+ scaffold has been selected for incorporating two antifungal drugs namely Caspofungin (Peptide based) and Amphotericin B (Non-Peptide based). Antifungal efficiency of the designed mats has been evaluated for eight diverse fungal strains employing different microbial assays including disc diffusion, cell-viability assay, time kill kinetics etc. To confirm the durability of these mats, in term of their antifungal activity, drug leaching studies has been performed and monitored using disc diffusion assay each day. Ex-vivo fungal infection model has also been developed and utilized to validate the antifungal efficacy of the designed wound dressings. Results clearly reveal dopamine mediated crosslinking within COLL-antifungal scaffolds that leads to the generation of highly stable, mechanical tough, biocompatible wound dressings having the zone of inhabitation of ≥ 2 cm for almost all the investigated fungal strains. Leaching studies and Ex-vivo model has confirmed the durability of these wound dressing for more than 3 weeks and certified their suitability for commercialization. A model has also been proposed to enlighten the chemical mechanism involved for the development of these antifungal wound dressings with exceptional robustness.

Keywords: catecholamine chemistry, electrospinning technique, antifungals, wound dressings, collagen

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354 Modification of Escherichia coli PtolT Expression Vector via Site-Directed Mutagenesis

Authors: Yakup Ulusu, Numan Eczacıoğlu, İsa Gökçe, Helen Waller, Jeremy H. Lakey

Abstract:

Besides having the appropriate amino acid sequence to perform the function of proteins, it is important to have correct conformation after this sequence to process. To consist of this conformation depends on the amino acid sequence at the primary structure, hydrophobic interaction, chaperones and enzymes in charge of folding etc. Misfolded proteins are not functional and tend to be aggregated. Cysteine originating disulfide cross-links make stable this conformation of functional proteins. When two of the cysteine amino acids come side by side, disulfide bond is established that forms a cystine bridge. Due to this feature cysteine plays an important role on the formation of three-dimensional structure of many proteins. There are two cysteine amino acids (C44, C69) in the Tol-A-III protein. Unlike protein disulfide bonds from within his own, any non-specific cystine bridge causes a change in the three dimensional structure of the protein. Proteins can be expressed in various host cells as directly or fusion (chimeric). As a result of overproduction of the recombinant proteins, aggregation of insoluble proteins in the host cell can occur by forming a crystal structure called inclusion body. In general fusion proteins are produced for provide affinity tags to make proteins more soluble and production of some toxic proteins via fusion protein expression system like pTolT. Proteins can be modified by using a site-directed mutagenesis. By this way, creation of non-specific disulfide crosslinks can be prevented at fusion protein expression system via the present cysteine replaced by another amino acid such as serine, glycine or etc. To do this, we need; a DNA molecule that contains the gene that encodes for the target protein, required primers for mutation to be designed according to site directed mutagenesis reaction. This study was aimed to be replaced cysteine encoding codon TGT with serine encoding codon AGT. For this sense and reverse primers designed (given below) and used site-directed mutagenesis reaction. Several new copy of the template plasmid DNA has been formed with above mentioned mutagenic primers via polymerase chain reaction (PCR). PCR product consists of both the master template DNA (wild type) and the new DNA sequences containing mutations. Dpn-l endonuclease restriction enzyme which is specific for methylated DNA and cuts them to the elimination of the master template DNA. E. coli cells obtained after transformation were incubated LB medium with antibiotic. After purification of plasmid DNA from E. coli, the presence of the mutation was determined by DNA sequence analysis. Developed this new plasmid is called PtolT-δ.

Keywords: site directed mutagenesis, Escherichia coli, pTolT, protein expression

Procedia PDF Downloads 348