Search results for: modified Krieger and Dougherty expression

Authors: Katarzyna Bialik-Wąs, Klaudia Pluta, Dagmara Malina, Małgorzata Miastkowska

Abstract:

In recent years, biocompatible hydrogels have been used more and more in medical applications, especially as modern dressings and drug delivery systems. The main goal of this research was the characteristics of bio-hybrid hydrogel materials incorporated with the nanocarrier-drug system, which enable the release in a gradual and prolonged manner, up to 7 days. Therefore, the use of such a combination will provide protection against mechanical damage and adequate hydration. The proposed bio-hybrid hydrogels are characterized by: transparency, biocompatibility, good mechanical strength, and the dual release system, which allows for gradual delivery of the active substance, even up to 7 days. Bio-hybrid hydrogels based on sodium alginate (SA), poly(vinyl alcohol) (PVA), glycerine, and Aloe vera solution (AV) were obtained through the chemical crosslinking method using poly(ethylene glycol) diacrylate as a crosslinking agent. Additionally, a nanocarrier-drug system was incorporated into SA/PVA/AV hydrogel matrix. Here, studies were focused on the release profiles of active substances from bio-hybrid hydrogels using the USP4 method (DZF II Flow-Through System, Erweka GmbH, Langen, Germany). The equipment incorporated seven in-line flow-through diffusion cells. The membrane was placed over support with an orifice of 1,5 cm in diameter (diffusional area, 1.766 cm²). All the cells were placed in a cell warmer connected with the Erweka heater DH 2000i and the Erweka piston pump HKP 720. The piston pump transports the receptor fluid via seven channels to the flow-through cells and automatically adapts the setting of the flow rate. All volumes were measured by gravimetric methods by filling the chambers with Milli-Q water and assuming a density of 1 g/ml. All the determinations were made in triplicate for each cell. The release study of the model active substance was carried out using a regenerated cellulose membrane Spectra/Por®Dialysis Membrane MWCO 6-8,000 Carl Roth® Company. These tests were conducted in buffer solutions – PBS at pH 7.4. A flow rate of receptor fluid of about 4 ml /1 min was selected. The experiments were carried out for 7 days at a temperature of 37°C. The released concentration of the model drug in the receptor solution was analyzed using UV-Vis spectroscopy (Perkin Elmer Company). Additionally, the following properties of the modified materials were studied: physicochemical, structural (FT-IR analysis), morphological (SEM analysis). Finally, the cytotoxicity tests using in vitro method were conducted. The obtained results exhibited that the dual release system allows for the gradual and prolonged delivery of the active substances, even up to 7 days.

Keywords: wound dressings, SA/PVA hydrogels, nanocarrier-drug system, USP4 method

Procedia PDF Downloads 120

Authors: Jacqueline Y. Thompson, Sam Watson, Lee Middleton, Karla Hemming

Abstract:

Introduction: The odds ratio (estimated via logistic regression) is a well-established and common approach for estimating covariate-adjusted binary treatment effects when comparing a treatment and control group with dichotomous outcomes. Its popularity is primarily because of its stability and robustness to model misspecification. However, the situation is different for the relative risk and risk difference, which are arguably easier to interpret and better suited to specific designs such as non-inferiority studies. So far, there is no equivalent, widely acceptable approach to estimate an adjusted relative risk and risk difference when conducting clinical trials. This is partly due to the lack of a comprehensive evaluation of available candidate methods. Methods/Approach: A simulation study is designed to evaluate the performance of relevant candidate methods to estimate relative risks to represent conditional and marginal estimation approaches. We consider the log-binomial, generalised linear models (GLM) with iteratively weighted least-squares (IWLS) and model-based standard errors (SE); log-binomial GLM with convex optimisation and model-based SEs; log-binomial GLM with convex optimisation and permutation tests; modified-Poisson GLM IWLS and robust SEs; log-binomial generalised estimation equations (GEE) and robust SEs; marginal standardisation and delta method SEs; and marginal standardisation and permutation test SEs. Independent and identically distributed datasets are simulated from a randomised controlled trial to evaluate these candidate methods. Simulations are replicated 10000 times for each scenario across all possible combinations of sample sizes (200, 1000, and 5000), outcomes (10%, 50%, and 80%), and covariates (ranging from -0.05 to 0.7) representing weak, moderate or strong relationships. Treatment effects (ranging from 0, -0.5, 1; on the log-scale) will consider null (H0) and alternative (H1) hypotheses to evaluate coverage and power in realistic scenarios. Performance measures (bias, mean square error (MSE), relative efficiency, and convergence rates) are evaluated across scenarios covering a range of sample sizes, event rates, covariate prognostic strength, and model misspecifications. Potential Results, Relevance & Impact: There are several methods for estimating unadjusted and adjusted relative risks. However, it is unclear which method(s) is the most efficient, preserves type-I error rate, is robust to model misspecification, or is the most powerful when adjusting for non-prognostic and prognostic covariates. GEE estimations may be biased when the outcome distributions are not from marginal binary data. Also, it seems that marginal standardisation and convex optimisation may perform better than GLM IWLS log-binomial.

Keywords: binary outcomes, statistical methods, clinical trials, simulation study

Procedia PDF Downloads 82

Authors: Srijata Mitra, Mobina Parveen, Pranab Roy, Narayan Chandra Chattopadhyay

Abstract:

Chlorinated hydrocarbon can be a major pollution problem in groundwater as well as soil. Many people interact with these chemicals on daily accidentally or by professionally in the laboratory. One of the most common sources for Chlorinated hydrocarbon contamination of soil and groundwater are industrial effluents. The wide use and discharge of Trichloroethylene (TCE), a volatile chlorohydrocarbon from chemical industry, led to major water pollution in rural areas. TCE is an mainly used as an industrial metal degreaser in industries. Biotransformation of TCE to the potent carcinogen vinyl chloride (VC) by consortia of anaerobic bacteria might have role for the above purpose. For these reasons, the aim of current study was to isolate and characterized the genes involved in TCE metabolism and also to investigate the in silico study of those genes. To our knowledge, only one aromatic dioxygenase system, the toluene dioxygenase in Pseudomonas putida F1 has been shown to be involved in TCE degradation. This is first instance where Bacillus cereus group being used in biodegradation of trichloroethylene. A novel bacterial strain 2479 was isolated from oil depot site at Rajbandh, Durgapur (West Bengal, India) by enrichment culture technique. It was identified based on polyphasic approach and ribotyping. The bacterium was gram positive, rod shaped, endospore forming and capable of degrading trichloroethylene as the sole carbon source. On the basis of phylogenetic data and Fatty Acid Methyl Ester Analysis, strain 2479 should be placed within the genus Bacillus and species cereus. However, the present isolate (strain 2479) is unique and sharply different from the usual Bacillus strains in its biodegrading nature. Fujiwara test was done to estimate that the strain 2479 could degrade TCE efficiently. The gene for TCE biodegradation was PCR amplified from genomic DNA of Bacillus cereus 2479 by using todC1 gene specific primers. The 600bp amplicon was cloned into expression vector pUC I8 in the E. coli host XL1-Blue and expressed under the control of lac promoter and nucleotide sequence was determined. The gene sequence was deposited at NCBI under the Accession no. GU183105. In Silico approach involved predicting the physico-chemical properties of deduced Tce1 protein by using ProtParam tool. The tce1 gene contained 342 bp long ORF encoding 114 amino acids with a predicted molecular weight 12.6 kDa and the theoretical pI value of the polypeptide was 5.17, molecular formula: C559H886N152O165S8, total number of atoms: 1770, aliphatic index: 101.93, instability index: 28.60, Grand Average of Hydropathicity (GRAVY): 0.152. Three differentially expressed proteins (97.1, 40 and 30 kDa) were directly involved in TCE biodegradation, found to react immunologically to the antibodies raised against TCE inducible proteins in Western blot analysis. The present study suggested that cloned gene product (TCE1) was capable of degrading TCE as verified chemically.

Keywords: cloning, Bacillus cereus, in silico analysis, TCE

Procedia PDF Downloads 371

Authors: Vidhya Venugopal, Rekha S.

Abstract:

Introduction: Climate change and the growing frequency of higher average temperatures and heat waves have detrimental health effects, especially for certain vulnerable groups with limited socioeconomic status (SES) or physiological capacity to adapt to or endure high temperatures. Little research has been conducted on the effects of heat stress on pregnant women and fetuses in tropical regions such as India. Very high ambient temperatures may worsen Adverse Pregnancy Outcomes (APOs) and are a major worry in the scenario of climate change. The relationship between rising temperatures and APO must be better understood in order to design more effective interventions. Methodology: We conducted an observational cohort study involving 865 pregnant women in various districts of Tamil Nadu districts between 2014 and 2021. Physiological Heat Strain Indicators (HSI) such as morning and evening Core Body Temperature (CBT) and Urine Specific Gravity (USG) were monitored using an infrared thermometer and refractometer, respectively. A validated, modified version of the HOTHAPS questionnaire was utilised to collect self-reported health symptoms. A follow-up was undertaken with the mothers to collect information regarding birth outcomes and APOs, such as spontaneous abortions, stillbirths, Preterm Birth (PTB), birth abnormalities, and Low Birth Weight (LBW). Major findings of the study: According to the findings of our study, ambient temperatures (mean WBGT°C) were substantially higher (>28°C) for approximately 46% of women performing moderate daily life activities. 82% versus 43% of these women experienced dehydration and heat-related complaints. 34% of women had USG >1.020, which is symptomatic of dehydration. APOs, which include spontaneous abortions, were prevalent at 2.2%, stillbirth/preterm birth/birth abnormalities were prevalent at 2.2%, and low birth weight was prevalent at 16.3%. With exposures to WBGT>28°C, the incidence of miscarriage or unexpected abortion rose by approximately 2.7 times (95% CI: 1.1-6.9). In addition, higher WBGT exposures were associated with a 1.4-fold increased risk of unfavorable birth outcomes (95% Confidence Interval [CI]: 1.02-1.09). The risk of spontaneous abortions was 2.8 times higher among women who conceived during the hotter months (February – September) compared to those women who conceived in the cooler months (October – January) (95% CI: 1.04-7.4). Positive relationships between ambient heat and APOs found in this study necessitate further exploration into the underlying factors for extensive cohort studies to generate information to enable the formulation of policies that can effectively protect these women against excessive heat stress for enhanced maternal and fetal health.

Keywords: heat exposures, community, pregnant women, physiological strain, adverse outcome, interventions

Procedia PDF Downloads 48

Authors: Victoria Brennan, Andrea Mallaburn, Linda Seton

Abstract:

Science outreach programmes connect school pupils with external agencies to provide activities and experiences that enhance their exposure to science. It can be argued that these programmes not only aim to support teachers with curriculum engagement and promote scientific literacy but also provide pivotal opportunities to spark scientific interest in students. In turn, a further objective of these programmes is to increase awareness of career opportunities within this field. Although outreach work is also often described as a fun and satisfying venture, a plethora of researchers express caution to how successful the processes are to increases engagement post-16 in science. When researching the impact of outreach programmes, it is often student feedback regarding the activities or enrolment numbers to particular science courses post-16, which are generated and analysed. Although this is informative, the longevity of the programme’s impact could be better informed by the teacher’s perceptions; the evidence of which is far more limited in the literature. In addition, there are strong suggestions that teachers can have an indirect impact on a student’s own self-concept. These themes shape the focus and importance of this ongoing research project as it presents the rationale that teachers are under-used resources when it comes to considering the design of science outreach programmes. Therefore, the end result of the research will consist of a presentation of an ‘optimum’ model of outreach. The result of which should be of interest to the wider stakeholders such as universities or private or government organisations who design science outreach programmes in the hope to recruit future scientists. During phase one, questionnaires (n=52) and interviews (n=8) have generated both quantitative and qualitative data. These have been analysed using the Wilcoxon non-parametric test to compare teachers’ perceptions of science outreach interventions and thematic analysis for open-ended questions. Both of these research activities provide an opportunity for a cross-section of teacher opinions of science outreach to be obtained across all educational levels. Therefore, an early draft of the ‘optimum’ model of science outreach delivery was generated using both the wealth of literature and primary data. This final (ongoing) phase aims to refine this model using teacher focus groups to provide constructive feedback about the proposed model. The analysis uses principles of modified Grounded Theory to ensure that focus group data is used to further strengthen the model. Therefore, this research uses a pragmatist approach as it aims to focus on the strengths of the different paradigms encountered to ensure the data collected will provide the most suitable information to create an improved model of sustainable outreach. The results discussed will focus on this ‘optimum’ model and teachers’ perceptions of benefits and drawbacks when it comes to engaging with science outreach work. Although the model is still a ‘work in progress’, it provides both insight into how teachers feel outreach delivery can be a sustainable intervention tool within the classroom and what providers of such programmes should consider when designing science outreach activities.

Keywords: educational partnerships, science education, science outreach, teachers

Procedia PDF Downloads 98

Authors: Felipe M. de Freitas, Ícaro V. Soares, Lucas L. L. Fortes, Sandro T. M. Gonçalves, Úrsula D. C. Resende

Abstract:

There is a dispersed energy in Radio Frequencies (RF) that can be reused to power electronics circuits such as: sensors, actuators, identification devices, among other systems, without wire connections or a battery supply requirement. In this context, there are different types of energy harvesting systems, including rectennas, coil systems, graphene and new materials. A secondary step of an energy harvesting system is the rectification of the collected signal which may be carried out, for example, by the combination of one or more Schottky diodes connected in series or shunt. In the case of a rectenna-based system, for instance, the diode used must be able to receive low power signals at ultra-high frequencies. Therefore, it is required low values of series resistance, junction capacitance and potential barrier voltage. Due to this low-power condition, voltage multiplier configurations are used such as voltage doublers or modified bridge converters. Lowpass filter (LPF) at the input, DC output filter, and a resistive load are also commonly used in the rectifier design. The electronic circuits projects are commonly analyzed through simulation in SPICE (Simulation Program with Integrated Circuit Emphasis) environment. Despite the remarkable potential of SPICE-based simulators for complex circuit modeling and analysis of quasi-static electromagnetic fields interaction, i.e., at low frequency, these simulators are limited and they cannot model properly applications of microwave hybrid circuits in which there are both, lumped elements as well as distributed elements. This work proposes, therefore, the electromagnetic modelling of electronic components in order to create models that satisfy the needs for simulations of circuits in ultra-high frequencies, with application in rectifiers coupled to antennas, as in energy harvesting systems, that is, in rectennas. For this purpose, the numerical method FDTD (Finite-Difference Time-Domain) is applied and SPICE computational tools are used for comparison. In the present work, initially the Ampere-Maxwell equation is applied to the equations of current density and electric field within the FDTD method and its circuital relation with the voltage drop in the modeled component for the case of lumped parameter using the FDTD (Lumped-Element Finite-Difference Time-Domain) proposed in for the passive components and the one proposed in for the diode. Next, a rectifier is built with the essential requirements for operating rectenna energy harvesting systems and the FDTD results are compared with experimental measurements.

Keywords: energy harvesting system, LE-FDTD, rectenna, rectifier, wireless power systems

Procedia PDF Downloads 103

Authors: Christian Andrä, Pauline Hähner, Sebastian Ludyga

Abstract:

Introduction: In the recent past, discussions on the importance of physical activity for child development have contributed to a growing interest in executive functions, which refer to cognitive processes. By controlling, modulating and coordinating sub-processes, they make it possible to achieve superior goals. Major components include working memory, inhibition and cognitive flexibility. While executive functions can be trained easily in school children, there are still research deficits regarding the trainability during preschool age. Methodology: This quasi-experimental study with pre- and post-design analyzes 23 children [age: 5.0 (mean value) ± 0.7 (standard deviation)] from four different sports groups. The intervention group was made up of 13 children (IG: 4.9 ± 0.6), while the control group consisted of ten children (CG: 5.1 ± 0.9). Between pre-test and post-test, children from the intervention group participated special games that train executive functions (i.e., changing rules of the game, introduction of new stimuli in familiar games) for ten units of their weekly sports program. The sports program of the control group was not modified. A computer-based version of the Eriksen Flanker Task was employed in order to analyze the participants’ inhibition ability. In two rounds, the participants had to respond 50 times and as fast as possible to a certain target (direction of sight of a fish; the target was always placed in a central position between five fish). Congruent (all fish have the same direction of sight) and incongruent (central fish faces opposite direction) stimuli were used. Relevant parameters were response time and accuracy. The main objective was to investigate whether children from the intervention group show more improvement in the two parameters than the children from the control group. Major findings: The intervention group revealed significant improvements in congruent response time (pre: 1.34 s, post: 1.12 s, p<.01), while the control group did not show any statistically relevant difference (pre: 1.31 s, post: 1.24 s). Likewise, the comparison of incongruent response times indicates a comparable result (IG: pre: 1.44 s, post: 1.25 s, p<.05 vs. CG: pre: 1.38 s, post: 1.38 s). In terms of accuracy for congruent stimuli, the intervention group showed significant improvements (pre: 90.1 %, post: 95.9 %, p<.01). In contrast, no significant improvement was found for the control group (pre: 88.8 %, post: 92.9 %). Vice versa, the intervention group did not display any significant results for incongruent stimuli (pre: 74.9 %, post: 83.5 %), while the control group revealed a significant difference (pre: 68.9 %, post: 80.3 %, p<.01). The analysis of three out of four criteria demonstrates that children who took part in a special sports program improved more than children who did not. The contrary results for the last criterion could be caused by the control group’s low results from the pre-test. Conclusion: The findings illustrate that inhibition can be trained as early as in preschool age. The combination of familiar games with increased requirements for attention and control processes appears to be particularly suitable.

Keywords: executive functions, flanker task, inhibition, preschool children

Procedia PDF Downloads 229

Authors: Joanna Gerszon, Aleksandra Rodacka

Abstract:

In the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, protein and peptide aggregation processes play a vital role in contributing to the formation of intracellular and extracellular protein deposits. One of the major components of these deposits is the oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Therefore, the purpose of this research was to answer the question whether piceatannol, a stilbene derivative, counteracts and/or slows down oxidative stress-induced GAPDH aggregation. The study also aimed to determine if this natural occurring compound prevents unfavorable nuclear translocation of GAPDH in hippocampal cells. The isothermal titration calorimetry (ITC) analysis indicated that one molecule of GAPDH can bind up to 8 molecules of piceatannol (7.3 ± 0.9). As a consequence of piceatannol binding to the enzyme, the loss of activity was observed. Parallel with GAPDH inactivation the changes in zeta potential, and loss of free thiol groups were noted. Nevertheless, the ligand-protein binding does not influence the secondary structure of the GAPDH. Precise molecular docking analysis of the interactions inside the active center allowed to presume that these effects are due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149) which is directly involved in the catalytic reaction. Molecular docking also showed that simultaneously 11 molecules of ligand can be bound to dehydrogenase. Taking into consideration obtained data, the influence of piceatannol on level of GAPDH aggregation induced by excessive oxidative stress was examined. The applied methods (thioflavin-T binding-dependent fluorescence as well as microscopy methods - transmission electron microscopy, Congo Red staining) revealed that piceatannol significantly diminishes level of GAPDH aggregation. Finally, studies involving cellular model (Western blot analyses of nuclear and cytosolic fractions and confocal microscopy) indicated that piceatannol-GAPDH binding prevents GAPDH from nuclear translocation induced by excessive oxidative stress in hippocampal cells. In consequence, it counteracts cell apoptosis. These studies demonstrate that by binding with GAPDH, piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation as well as it prevents hippocampal cells from apoptosis by retaining GAPDH in the cytoplasm. All these findings provide a new insight into the role of piceatannol interaction with GAPDH and present a potential therapeutic strategy for some neurological disorders related to GAPDH aggregation. This work was supported by the by National Science Centre, Poland (grant number 2017/25/N/NZ1/02849).

Keywords: glyceraldehyde-3-phosphate dehydrogenase, neurodegenerative disease, neuroprotection, piceatannol, protein aggregation

Procedia PDF Downloads 138

Authors: S. A. Bhat, Ahmad Arif, Muneeb U. Rehman, Manzoor R Mir, S. Bilal, Ishraq Hussain, H. M Khan, S. Shanaz, M. I Mir, Sabhiya Majid

Abstract:

Background: Geologically Climatic conditions of the state range from sub-tropical (Jammu), temperate (Kashmir) to cold artic (Ladakh) zones, which exerts significant influence on its agro-climatic conditions. Gastrointestinal parasitism is a major problem in sheep production worldwide. Materials and Methods: The present study was to evaluate the resistance status of sheep breeds reared in Kashmir Valley for natural resistance against Haemonchus contortus by natural pasture challenge infection. Ten microsatellite markers were used in the study for evaluation of association of Ovar-MHC with parasitic resistance in association with biochemical and parasitological parameters. Following deworming, 500 animals were subjected to selected contaminated pastures in a vicinity of the livestock farms of SKUAST-K and Sheep Husbandry Kashmir. For each animal about 10-15 ml blood was collected aseptically for molecular and biochemical analysis. Weekly fecal samples (3g) were taken, directly from the rectum of all experimental animals and examined for Fecal egg count (FEC) with modified McMaster technique. Packed cell volume (PCV) was determined within 2-5 h of blood collection, all the biochemical parameters were determined in serum by semi automated analyzer. DNA was extracted from all the blood samples with phenol-chloroform method. Microsatellite analysis was done by denaturing sequencing gel electrophoresis Results: Overall sheep from Bakerwal breed followed by Corriediale breed performed relatively better in the trial; however difference between breeds remained low. Both significant (P<0.05) and non-significant differences with respect to resistance against haemonchosis were noted at different intervals in all the parameters.. All the animals were typed for the microsatellites INRA132, OarCP73, DRB1 (U0022), OLA-DQA2, BM1818, TFAP2A, HH56, BM1815, IL-3 and BM-1258. An association study including the effect of FEC, PCV, TSP, SA, LW, and the number of alleles within each marker was done. All microsatellite markers showed degree of heterozygosity of 0.72, 0.72, 0.75, 0.62, 0.84, 0.69, 0.66, 0.65, 0.73 and 0.68 respectively. Significant association between alleles and the parameters measured were only found for the OarCP73, OLA-DQA2 and BM1815 microsatellite marker. Standard alleles of the above markers showed significant effect on the TP, SA and body weight. The three sheep breeds included in the study responded differently to the nematode infection, which may be attributed to their differences in their natural resistance against nematodes. Conclusion: Our data confirms that some markers (OarCP73, OLA-DQA2 and BM1815) within Ovar-MHC are associated with phenotypic parameters of resistance and suggest superiority of Bakerwal sheep breed in natural resistance against Haemonchus contortus.

Keywords: Ovar-Mhc, ovine leukocyte antigen (OLA), sheep, parasitic resistance, Haemonchus contortus, phenotypic & genotypic markers

Procedia PDF Downloads 682

Authors: Maria F. Seran

Abstract:

In second language interaction, an EFL student always carries his knowledge of targeted language and sometimes gets influenced by his first language cultures which makes him transfer his utterances from the first language to the second language. The influence of L1 cultures somehow can lead to face-threatening act when it comes to responding on speech act, for instance, compliment. A speaker praises a compliment to show gratitude, and in return, he expects for compliment respond uttered by the hearer. While Western people use more acceptance continuum on compliment response, Indonesians utter more denial continuum which can somehow put the speakers into a face-threating situation and offense. This study investigated compliment response employed by EFL students and English native speakers. The study was distinct as none compliment response studies had been conducted to compare the compliment response between English native speakers and two different Indonesian EFL proficiency groups in which this research sought to meet this need. This study was significant for EFL teachers because it gave insight on cross-cultural understanding and brought pedagogical implication on explicit pragmatic instruction. Two research questions were set, 1. How do Indonesian EFL students and English native speakers respond compliments? 2. Is there any correlation between Indonesia EFL students’ proficiency and their compliment response use in English? The study involved three groups of participants; 5 English native speakers, 10 high-proficiency and 10 low-proficiency Indonesian EFL university students. The research instruments used in this study were as follows, an online TOEFL prediction test, focusing on grammar skill which was modified from Barron TOEFL exercise test, and a discourse completion task (DCT), consisting of 10 compliment respond items. Based on the research invitation, 20 second-year university students majoring in English education at Widya Mandira Catholic University, Kupang, East Nusa Tenggara, Indonesia who willingly participated in the research took the TOEFL prediction test online from the link provided. Students who achieved score 75-100 in test were categorized as high-proficiency students, while, students who attained score below 74 were considered as low-proficiency students. Then, the DCT survey was administered to these EFL groups and the native speaker group. Participants’ responses were coded and analyzed using categories of compliment response framework proposed by Tran. The study found out that 5 native speakers applied more compliment upgrades and appreciation token in compliment response, whereas, Indonesian EFL students combined some compliment response strategies in their utterance, such as, appreciation token, return and compliment downgrade. There is no correlation between students’ proficiency level and their CR responds as most EFL students in both groups produced less varied compliment responses and only 4 Indonesian high-proficiency students uttered more varied and were similar to the native speakers. The combination strategies used by EFL students can be explained as the influence of pragmatic transfer from L1 to L2; therefore, EFL teachers should explicitly teach more compliment response strategies to raise students’ awareness on English culture and elaborate their speaking to be more competence as close to native speakers as possible.

Keywords: compliment response, English native speakers, Indonesian EFL students, speech acts

Procedia PDF Downloads 116

Authors: Durri Andriani, Irsan Tahar, Lilian Sarah Hiariey

Abstract:

Every institution has to develop, implement, and control its policies to ensure the effectiveness of the institution. In doing so, all related stakeholders have to be involved to maximize the benefit of the policies and minimize the potential constraints and resistances. Open and distance education (ODE) institution is no different. As an education institution, ODE institution has to focus their attention to fulfilling academic needs of their students through open and distance measures. One of them is quality learning support system. Significant stakeholders in learning support system are tutors since they are the ones who directly communicate with students. Tutors are commonly seen as objects whose main responsibility is limited to implementing policies decided by management in ODE institutions. Nonetheless, tutors’ perceptions of tutorials are believed to influence tutors’ performances in facilitating learning support. It is therefore important to analyze tutors’ perception on various aspects of learning support. This paper presents analysis of tutors’ perceptions on policies of tutoriala in ODE institution using Policy Analysis Framework (PAF) modified by King, Nugent, Russell, and Lacy. Focus of this paper is on on-line tutors, those who provide tutorials via Internet. On-line tutors were chosen to stress the increasingly important used of Internet in ODE system. The research was conducted in Universitas Terbuka (UT), Indonesia. UT is purposely selected because of its large number (1,234) of courses offered and large area coverage (6000 inhabited islands). These posed UT in a unique position where learning support system has, to some extent, to be standardized while at the same time it has to be able to cater the needs of different courses in different places for students with different backgrounds. All 598 listed on-line tutors were sent the research questionnaires. Around 20% of the email addresses could not be reached. Tutors were asked to fill out open-ended questionnaires on their perceptions on definition of on-line tutorial, roles of tutors and students in on-line tutorials, requirement for on-line tutors, learning materials, and student evaluation in on-line tutorial. Data analyzed was gathered from 40 on-line tutors who sent back filled-out questionnaires. Data were analyzed qualitatively using content analysis from all 40 tutors. The results showed that using PAF as entry point in choosing learning support services as area of policy with delivery learning materials as the issue at UT has been able to provide new insights of aspects need to be consider in formulating policies in online tutorial and in learning support services. Involving tutors as source of information could be proven to be productive. In general, tutors had clear understanding about definition of online tutorial, roles of tutors and roles of students, and requirement of tutor. Tutors just need to be more involved in the policy formulation since they could provide data on students and problem faced in online tutorial. However, tutors need an adjustment in student evaluation which according tutors too focus on administrative aspects and subjective.

Keywords: distance education, on-line tutorial, tutorial policy, tutors’ perspectives

Procedia PDF Downloads 226

Authors: Enrico Maria la Forgia

Abstract:

Since the 80ies, in specific situations, France’s Muslims have enacted political actions to reply to attacks on their identity or assimilation attempts, using their religious affiliation as a resource for the organization and expression of collective claims. Indeed, despite Islam's internal sectarian and ethnic differences, religion may be politicized when minorities’ social and cultural rights are under attack. French Civil Society organizations, in this specific case with an Islamic background (ICSO - Islamic Civil Society Organizations), play an essential role in defending Muslims’ social and cultural rights. As a matter of fact, Civil Society organized on an ethnic or religious base is a way to strengthen minoritarian communities and their role as political actors, especially in multicultural contexts. Since the first 1983’s “Marche des Beurs” (slang word referring to French citizens with foreign origins), which involved many Muslims, the development of ICSO contributed to the strenghtening of Islam in France, here meant as a Social Movement aiming to constitute a French version of Islam, defending minorities’ cultural and religious rights, and change the perception of Islam itself in national society. However, since a visible and stigmatized minority, ICSO do not relate only to protests as a strategy to achieve their goals: on several occasions, pressure on authorities through personal networks and connections, or the introduction into public debates of bargaining through the exploitation of national or international crisis, might appear as more successfully - public discourses on minorities and Islam are generally considered favorable conditions to advance requests for cultural legitimation. The proposed abstract, based on a literary review and theoretical/methodological reflection on the state of knowledge on the topic, aims to open a new branch of studies and analysis of Civil Society and Social Movements in Europe, focusing on the French Islamic community as a political actor relating on ICSO to pressure society, local, and national authorities to improve Muslims' rights. The opted methodology relies on a qualitative approach based on ethnography and face-to-face interviews addressing heads and middle-high level activists from ICSO, in an attempt to individuate the strategies enacted by ICSO for mobilizing Muslims and build relations with, on one hand, local and national authorities; into the other, with actors belonging to the Civil Society/political sphere. The theoretical framework, instead, relies on the main Social Movements Theories (resources mobilization, political opportunity structure, and contentious/non-contentious movements), aiming to individuate eventual gaps in the analysis of Islamic Social Movements and Civil Society in minoritarian contexts.

Keywords: Islam, islamophobia, civil society, social movements, sociology, qualitative methodology, Islamic activism in social movement theory, political change, Islam as social movement, religious movements, protest and politics, France, Islamic civil society

Procedia PDF Downloads 57

Authors: A. M. Ferrari, L. Volpi, M. Pini, C. Siligardi, F. E. Garcia Muina, D. Settembre Blundo

Abstract:

A long tradition in the ceramic manufacturing since the 18th century, primarily due to the availability of raw materials and an efficient transport system, let to the birth and development of the Italian ceramic tiles district that nowadays represents a reference point for this sector even at global level. This economic growth has been coupled to attention towards environmental sustainability issues throughout various initiatives undertaken over the years at the level of the production sector, such as certification activities and sustainability policies. In this way, starting from an evaluation of the sustainability in all its aspects, the present work aims to develop a benchmarking helping both producers and consumers. In the present study, throughout the Life Cycle Sustainability Assessment (LCSA) framework, the sustainability has been assessed in all its dimensions: environmental with the Life Cycle Assessment (LCA), economic with the Life Cycle Costing (LCC) and social with the Social Life Cycle Assessment (S-LCA). The annual district production of stoneware tiles during the 2016 reference year has been taken as reference flow for all the three assessments, and the system boundaries cover the entire life cycle of the tiles, except for the LCC for which only the production costs have been considered at the moment. In addition, a preliminary method for the evaluation of local and indoor emissions has been introduced in order to assess the impact due to atmospheric emissions on both people living in the area surrounding the factories and workers. The Life Cycle Assessment results, obtained from IMPACT 2002+ modified assessment method, highlight that the manufacturing process is responsible for the main impact, especially because of atmospheric emissions at a local scale, followed by the distribution to end users, the installation and the ordinary maintenance of the tiles. With regard to the economic evaluation, both the internal and external costs have been considered. For the LCC, primary data from the analysis of the financial statements of Italian ceramic companies show that the higher cost items refer to expenses for goods and services and costs of human resources. The analysis of externalities with the EPS 2015dx method attributes the main damages to the distribution and installation of the tiles. The social dimension has been investigated with a preliminary approach by using the Social Hotspots Database, and the results indicate that the most affected damage categories are health and safety and labor rights and decent work. This study shows the potential of the LCSA framework applied to an industrial sector; in particular, it can be a useful tool for building a comprehensive benchmark for the sustainability of the ceramic industry, and it can help companies to actively integrate sustainability principles into their business models.

Keywords: benchmarking, Italian ceramic industry, life cycle sustainability assessment, porcelain stoneware tiles

Procedia PDF Downloads 97

Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

Abstract:

Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

Procedia PDF Downloads 100

Authors: Agnieszka Markowska-Radomska, Ewa Dluska

Abstract:

Maintaining a bioactive substances dense diet is important for the elderly, especially to prevent diseases and to support healthy ageing. Adequate bioactive substances intake can reduce the risk of developing chronic diseases (e.g. cardiovascular, osteoporosis, neurodegenerative syndromes, diseases of the oral cavity, gastrointestinal (GI) disorders, diabetes, and cancer). This can be achieved by introducing a comprehensive supplementation of components necessary for the proper functioning of the ageing body. The paper proposes the multiple emulsions of the W1/O/W2 (water-in-oil-in-water) type as carriers for effective co-encapsulation and co-delivery of bioactive substances in supplementation of the elderly. Multiple emulsions are complex structured systems ("drops in drops"). The functional structure of the W1/O/W2 emulsion enables (i) incorporation of one or more bioactive components (lipophilic and hydrophilic); (ii) enhancement of stability and bioavailability of encapsulated substances; (iii) prevention of interactions between substances, as well as with the external environment, delivery to a specific location; and (iv) release in a controlled manner. The multiple emulsions were prepared by a one-step method in the Couette-Taylor flow (CTF) contactor in a continuous manner. In general, a two-step emulsification process is used to obtain multiple emulsions. The paper contains a proposal of emulsion functionalization by introducing pH-responsive biopolymer—carboxymethylcellulose sodium salt (CMC-Na) to the external phase, which made it possible to achieve a release of components controlled by the pH of the gastrointestinal environment. The membrane phase of emulsions was soybean oil. The W1/O/W2 emulsions were evaluated for their characteristics (drops size/drop size distribution, volume packing fraction), encapsulation efficiency and stability during storage (to 30 days) at 4ºC and 25ºC. Also, the in vitro multi-substance co-release process were investigated in a simulated gastrointestinal environment (different pH and composition of release medium). Three groups of stable multiple emulsions were obtained: emulsions I with co-encapsulated vitamins B12, B6 and resveratrol; emulsions II with vitamin A and β-carotene; and emulsions III with vitamins C, E and D3. The substances were encapsulated in the appropriate emulsion phases depending on the solubility. For all emulsions, high encapsulation efficience (over 95%) and high volume packing fraction of internal droplets (0.54-0.76) were reached. In addition, due to the presence of a polymer (CMC-Na) with adhesive properties, high encapsulation stability during emulsions storage were achieved. The co-release study of encapsulated bioactive substances confirmed the possibility to modify the release profiles. It was found that the releasing process can be controlled through the composition, structure, physicochemical parameters of emulsions and pH of the release medium. The results showed that the obtained multiple emulsions might be used as potential liquid complex carriers for controlled/modified/site-specific co-delivery of bioactive substances in dietary supplementation in the elderly.

Keywords: bioactive substance co-release, co-encapsulation, elderly supplementation, multiple emulsion

Procedia PDF Downloads 175

Authors: Ayodele James Akinola

Abstract:

This study investigated the use of English in doctor-patient interaction in a university teaching hospital from a southwestern state in Nigeria with the aim of identifying the role of communication in an L2, patterns of communication, discourse strategies, pragmatic acts, and contexts that shape the interaction. Jacob Mey’s Pragmatic Acts notion complemented with Emanuel and Emanuel’s model of doctor-patient relationship provided the theoretical standpoint. Data comprising 7 audio-recorded doctors-patient interactions were collected from a University Hospital in Oyo state, Nigeria. Interactions involving the use of English language were purposefully selected. These were supplemented with patients’ case notes and interviews conducted with doctors. Transcription was patterned alongside modified Arminen’s notations of conversation analysis. In the study, interaction in English between doctor and patients has the preponderance of direct-translation, code-mixing and switching, Nigerianism and use of cultural worldviews to express medical experience. Irrespective of these, three patterns communication, namely the paternalistic, interpretive, and deliberative were identified. These were exhibited through varying discourse strategies. The paternalistic model reflected slightly casual conversational conventions and registers. These were achieved through the pragmemic activities of situated speech acts, psychological and physical acts, via patients’ quarrel-induced acts, controlled and managed through doctors’ shared situation knowledge. All these produced empathising, pacifying, promising and instructing practs. The patients’ practs were explaining, provoking, associating and greeting in the paternalistic model. The informative model reveals the use of adjacency pairs, formal turn-taking, precise detailing, institutional talks and dialogic strategies. Through the activities of the speech, prosody and physical acts, the practs of declaring, alerting and informing were utilised by doctors, while the patients exploited adapting, requesting and selecting practs. The negotiating conversational strategy of the deliberative model featured in the speech, prosody and physical acts. In this model, practs of suggesting, teaching, persuading and convincing were utilised by the doctors. The patients deployed the practs of questioning, demanding, considering and deciding. The contextual variables revealed that other patterns (such as phatic and informative) are also used and they coalesced in the hospital within the situational and psychological contexts. However, the paternalistic model was predominantly employed by doctors with over six years in practice, while the interpretive, informative and deliberative models were found among registrar and others below six years of medical practice. Doctors’ experience, patients’ peculiarities and shared cultural knowledge influenced doctor-patient communication in the study.

Keywords: pragmatics, communication pattern, doctor-patient interaction, Nigerian hospital situation

Procedia PDF Downloads 153

Authors: Ruslin, R. E. Kartasasmita, M. S. Wibowo, S. Ibrahim

Abstract:

An aphrodisiac is a substance contained in food or drug that can arouse sexual instinct and increase pleasure while working, these substances derived from plants, animals, and minerals. When consuming substances that have aphrodisiac activity and duration can improve the sexual instinct. The natural aphrodisiac effect can be obtained through plants, animals, and minerals. Leonurine compound has aphrodisiac activity, these compounds can be isolated from plants of Leonurus Sp, Sundanese people is known as deundereman, this plant is empirical has aphrodisiac activity and based on the isolation of active compounds from plants known to contain compounds leonurine, so that the compound is expected to have activity aphrodisiac. Leonurine compound can be isolated from plants or synthesized chemically with material dasa siringat acid. Leonurine compound can be obtained commercial and derivatives of these compounds can be synthesized in an effort to increase its activity. This study aims to obtain derivatives leonurine better aphrodisiac activity compared with the parent compound, modified the structure of the compounds in the form leonurin guanidino butyl ester group with butyl amin and bromoetanol. ArgusLab program version 4.0.1 is used to determine the binding energy, hydrogen bonds and amino acids involved in the interaction of the compound PDE5 receptor. The in vivo test leonurine compounds and derivatives as an aphrodisiac ingredients and hormone testosterone levels using 27 male rats Wistar strain and 9 female mice of the same species, ages ranged from 12 weeks rats weighing + 200 g / tail. The test animal is divided into 9 groups according to the type of compounds and the dose given. Each treatment group was orally administered 2 ml per day for 5 days. On the sixth day was observed male rat sexual behavior and taking blood from the heart to measure testosterone levels using ELISA technique. Statistical analysis was performed in this study is the ANOVA test Least Square Differences (LSD) using the program Statistical Product and Service Solutions (SPSS). Aphrodisiac efficacy of the leonurine compound and its derivatives have proven in silico and in vivo test, the in silico testing leonurine derivatives have smaller binding energy derivatives leonurine so that activity better than leonurine compounds. Testing in vivo using rats of wistar strain that better leonurine derivative of this compound shows leonurine that in silico studies in parallel with in vivo tests. Modification of the structure in the form of guanidine butyl ester group with butyl amin and bromoethanol increase compared leonurine compound for aphrodisiac activity, testosterone derivatives of compounds leonurine experienced a significant improvement especial is 1RD compounds especially at doses of 100 and 150 mg/bb. The results showed that the compound leonurine and its compounds contain aphrodisiac activity and increase the amount of testosterone in the blood. The compound test used in this study acts as a steroid precursor resulting in increased testosterone.

Keywords: aphrodisiac dysfunction erectile leonurine 1-RD 2-RD, dysfunction, erectile leonurine, 1-RD 2-RD

Procedia PDF Downloads 254

Authors: Su Mon Saw, Joe Rothnagel

Abstract:

Short open reading frames (sORFs) located in 5’UTR of mRNAs are known as uORFs. Characterization of uORF-encoded peptides (uPEPs) i.e., a subset of short open reading frame encoded peptides (sPEPs) and their translation regulation lead to understanding of causes of genetic disease, proteome complexity and development of treatments. Existence of uORFs within cellular proteome could be detected by LC-MS/MS. The ability of uORF to be translated into uPEP and achievement of uPEP identification will allow uPEP’s characterization, structures, functions, subcellular localization, evolutionary maintenance (conservation in human and other species) and abundance in cells. It is hypothesized that a subset of sORFs are translatable and that their encoded sPEPs are functional and are endogenously expressed contributing to the eukaryotic cellular proteome complexity. This project aimed to investigate whether sORFs encode functional peptides. Liquid chromatography-mass spectrometry (LC-MS) and bioinformatics were thus employed. Due to probable low abundance of sPEPs and small in sizes, the need for efficient peptide enrichment strategies for enriching small proteins and depleting the sub-proteome of large and abundant proteins is crucial for identifying sPEPs. Low molecular weight proteins were extracted using SDS-PAGE from Human Embryonic Kidney (HEK293) cells and Strong Cation Exchange Chromatography (SCX) from secreted HEK293 cells. Extracted proteins were digested by trypsin to peptides, which were detected by LC-MS/MS. The MS/MS data obtained was searched against Swiss-Prot using MASCOT version 2.4 to filter out known proteins, and all unmatched spectra were re-searched against human RefSeq database. ProteinPilot v5.0.1 was used to identify sPEPs by searching against human RefSeq, Vanderperre and Human Alternative Open Reading Frame (HaltORF) databases. Potential sPEPs were analyzed by bioinformatics. Since SDS PAGE electrophoresis could not separate proteins <20kDa, this could not identify sPEPs. All MASCOT-identified peptide fragments were parts of main open reading frame (mORF) by ORF Finder search and blastp search. No sPEP was detected and existence of sPEPs could not be identified in this study. 13 translated sORFs in HEK293 cells by mass spectrometry in previous studies were characterized by bioinformatics. Identified sPEPs from previous studies were <100 amino acids and <15 kDa. Bioinformatics results showed that sORFs are translated to sPEPs and contribute to proteome complexity. uPEP translated from uORF of SLC35A4 was strongly conserved in human and mouse while uPEP translated from uORF of MKKS was strongly conserved in human and Rhesus monkey. Cross-species conserved uORFs in association with protein translation strongly suggest evolutionary maintenance of coding sequence and indicate probable functional expression of peptides encoded within these uORFs. Translation of sORFs was confirmed by mass spectrometry and sPEPs were characterized with bioinformatics.

Keywords: bioinformatics, HEK293 cells, liquid chromatography-mass spectrometry, ProteinPilot, Strong Cation Exchange Chromatography, SDS-PAGE, sPEPs

Procedia PDF Downloads 161

Authors: Kristina Colovic, Mari Janikian, Nikolaos Takis, Fotini-Sonia Apergi

Abstract:

A considerable number of Afghan asylum seekers in Greece are still waiting for answers about their future and status for personal, social and societal advancement. Most have been trapped in a stalemate of continuously postponed or temporarily progressed levels of integration into the EU/Greek process of asylum. Limited quantitative research exists investigating the psychological effects of long-term displacement among Afghans refugees in Greece. The purpose of this study is to investigate factors that are associated with and predict psychological distress symptoms among this population. Data from a sample of native Afghan nationals (N > 70) living in Greece for approximately the last ten years will be collected from May to July 2016. Criteria for participation include the following: being 18 years of age or older, and emigration from Afghanistan to Greece from 2003 onwards (i.e., long-term refugees or part of the 'old system of asylum'). Snowball sampling will be used to recruit participants, as this is considered the most effective option when attempting to study refugee populations. Participants will complete self-report questionnaires, consisting of the Afghan Symptom Checklist (ASCL), a culturally validated measure of psychological distress, the World Health Organization Quality of Life scale (WHOQOL-BREF), an adapted version of the Comprehensive Trauma Inventory-104 (CTI-104), and a modified Psychological Acculturation Scale. All instruments will be translated in Greek, through the use of forward- and back-translations by bilingual speakers of English and Greek, following WHO guidelines. A pilot study with 5 Afghan participants will take place to check for discrepancies in understanding and for further adapting the instruments as needed. Demographic data, including age, gender, year of arrival to Greece and current asylum status will be explored. Three different types of analyses (descriptive statistics, bivariate correlations, and multivariate linear regression) will be used in this study. Descriptive findings for respondent demographics, psychological distress symptoms, traumatic life events and quality of life will be reported. Zero-order correlations will assess the interrelationships among demographic, traumatic life events, psychological distress, and quality of life variables. Lastly, a multivariate linear regression model will be estimated. The findings from the study will contribute to understanding the determinants of acculturation, distress and trauma on daily functioning for Afghans in Greece. The main implications of the current study will be to advocate for capacity building and empower communities through effective program evaluation and design for mental health services for all refugee populations in Greece.

Keywords: Afghan refugees, evaluation, Greece, mental health, quality of life

Procedia PDF Downloads 265

Authors: Tshepang Tshube

Abstract:

The primary purpose of this study was to examine student-athletes’ experiences, particularly an in-depth account of balancing school and sport. The secondary objective was to assess student-athletes’ susceptibility to the effects of the “dumb-jock” stereotype threat and also determine the strength of athletic and academic identity as predicated by the extent to which stereotype is perceived by student-athletes. Sub-objectives are (a) examine support structures available for student-athletes in their respective academic institutions, (b) to establish the most effective ways to address student-athletes’ learning needs, (c) to establish crucial entourage members who play a pivotal role in student-athletes’ academic pursuits, (d) and unique and effective ways lecturers and coaches can contribute to student-athletes’ learning experiences. To achieve the above stated objectives, the study used a mixed methods approach. A total of 110 student-athletes from colleges and universities in Botswana completed an online survey that was followed by semi-structured interviews with eight student-athletes, and four coaches. The online survey assessed student-athletes’ demographic variables, measured athletic (AIMS), academic (modified from AIMS) identities, and perceived stereotype threat. Student-athletes reported a slightly higher academic identity (M=5.9, SD= .85) compared to athletic identity (M=5.4, SD=1.0). Student-athletes reported a moderate mean (M=3.6, SD=.82) just above the midpoint of the 7-point scale for stereotype threat. A univariate ANOVA was conducted to determine if there was any significant difference between university and college brackets in Botswana with regard to three variables: athletic identity, student identity and stereotype threat. The only significant difference was in the academic identity (Post Hoc-Tukey Student Identity: Bracket A < Bracket B, Bracket C) with Bracket A schools being the least athletically competitive. Bracket C and B are the most athletically competitive brackets in Botswana. Follow-up interviews with student-athletes and coaches were conducted. All interviews lasted an average of 55 minutes. Following all the interviews, all recordings were transcribed which is an obvious first step in qualitative data analysis process. The researcher and an independent academic with experience in qualitative research independently listened to all recordings of the interviews and read the transcripts several times. Qualitative data results indicate that even though student-athletes reported a slightly higher student identity, there are parallels between sports and academic structures on college campuses. Results also provide evidence of lack of academic support for student-athletes. It is therefore crucial for student-athletes to have access to academic support services (e.g., tutoring, flexible study times, and reduced academic loads) to meet their academic needs. Coaches and lecturers play a fundamental role in sporting student-athletes. Coaches and professors’ academic efficacy on student-athletes enhances student-athletes’ academic confidence. Results are discussed within the stereotype threat theory.

Keywords: athletic identity, colligiate sport, sterotype threat, student athletes

Procedia PDF Downloads 438

Authors: Etibar Guliyev

Abstract:

The breakdown of the Soviet Union in 1991 has led to a considerable rise in the religious self-consciousness of Muslim population of the Central Asia. Additionally, huge amount of money spent by various states further facilitated the spread of religious ideas. According to some sources, Saudi Arabia spent 87 billion dollars to propagate Wahhabism abroad during two decades, whereas the Communist Party of the Soviet Union spent just over 7 billion dollars to spread its ideology worldwide between 1921 and 1991. As the result, today once a remote area from international politics has turned into third major source of recruitment of fighters for global terrorist organizations. In order to illustrate to scope of the involvement of the Central Asian residents in international terrorist networks it is enough to mention the name of Colonel Gulmorod Khalimov, the former head of the Tajik special police forces who served as ISIS war minister between 2016 and 2017. The importance of the topic stems from the fact that the above-mentioned republics with a territory of 4 million square km and the population of around 80 million people borders Russia, Iran Afghanistan and China. Moreover, the fact that political and military activities motivated with religious feelings in those countries have implications not only for domestic but also for regional and global political relations and all of them has root in politics of religions adds value to the research. This research aims to provide an in-depth analyses of the marked features of the state policies to regulate religious activities and approach this question both from individual, domestic, regional and global levels of analyses. The research will enable us to better understand what implications have the state of religious freedom in post-Soviet Muslim republics for international relations and the rise of global jihadi terrorism. The paper tries to find a linkage between the mentioned terror attacks and underground rise of religious extremism in Central Asia. This research is based on multiple research methods, mainly on qualitative one. The process tracing method is also employed to review religious policies implemented from 1918-1991 and after the collapse of the Soviet Union in a chronological way. In terms of the quantitative method, it chiefly will be used in a bid to process various statistics disseminated in academic and official sources. The research mostly explored constructivist, securitization and social movement theories. Findings of the research suggests that the endemic problems peculiar to authoritarian regimes of Central Asia such as crackdown on the expression of religious believe and any kind of opposition, economic decline, instrumental use of religion and corruption and tribalism further accelerated the recruitment problem. Paper also concludes that the Central Asian states in some cases misused counter-terrorism campaign as a pretext to further restrict freedom of faith in their respective countries.

Keywords: identity, political Islam, religious extremism, security, terrorism

Procedia PDF Downloads 242

Authors: Orit Wolf

Abstract:

Classical music performance is undergoing a profound transformation, marked by a confluence of technological advancements and evolving cultural dynamics. This academic paper explores the multifaceted changes and challenges faced by classical music performance, considering the impact of artificial intelligence (AI) along with other vital factors shaping this evolution. In the contemporary era, classical music is experiencing shifts in performance practices. This paper delves into these changes, emphasizing the need for adaptability within the classical music world. From repertoire selection and concert formats to artistic expression, performers and institutions navigate a delicate balance between tradition and innovation. We explore how these changes impact the authenticity and vitality of classical music performances. Furthermore, the influence of AI in the classical music concert world cannot be underestimated. AI technologies are making inroads into various aspects, from composition assistance to rehearsal and live performances. This paper examines the transformative effects of AI, considering how it enhances precision, adaptability, and creative exploration for musicians. We explore the implications for composers, performers, and the overall concert experience while addressing ethical concerns and creative opportunities. In addition to AI, there is the importance of cross-genre interactions within the classical music sphere. Mash-ups and collaborations with artists from diverse musical backgrounds are redefining the boundaries of classical music and creating works that resonate with a wider and more diverse audience. The benefits of cross-pollination in classical music seem crucial, offering a fresh perspective to listeners. As an active concert artist, Orit Wolf will share how the expectations of classical music audiences are evolving. Modern concertgoers seek not only exceptional musical performances but also immersive experiences that may involve technology, multimedia, and interactive elements. This paper examines how classical musicians and institutions are adapting to these changing expectations, using technology and innovative concert formats to deliver a unique and enriched experience to their audiences. As these changes and challenges reshape the classical music world, the need for a harmonious coexistence of tradition, technology, and innovation becomes evident. Musicians, composers, and institutions are striving to find a balance that ensures classical music remains relevant in a rapidly changing cultural landscape while maintaining the value it brings to compositions and audiences. This paper, therefore, aims to explore the evolving trends in classical music performance. It considers the influence of AI as one element within the broader context of change, highlighting the necessity of adaptability, cross-genre interactions, and a response to evolving audience expectations. By doing so, the classical music world can navigate this transformative period while preserving its timeless traditions and adding value to both performers and listeners. Orit Wolf, an international concert pianist, fulfils her vision to bring this music in new ways to mass audiences and will share her personal and professional experience as an artist who goes on stage and makes disruptive concerts.

Keywords: cross culture collaboration, music performance and ai, classical music in the digital age, classical concerts, innovation and technology, performance innovation, audience engagement in classical concerts

Procedia PDF Downloads 35

Authors: Erika Mattio

Abstract:

The aim of this project is to study the Chinese presence in Ethiopia, in the area between the Saba River and the Coptic areas of the Tigray, with detailed documentation of the Danakil region, from which the salt pickers caravans departed; the study was created to understand the relationships and consequences of the Chinese advance in these areas, inhabited by tribes linked to ancient, still practiced religious rituals, and home to unique landscapes and archaeological sites. Official estimates of the number of Chinese in Africa vary widely; on the continent, there are increasingly diverse groups of Chinese migrants in terms of language, dialect, class, education, and employment. Based on this and on a very general state of the art, it was decided to increase the studies on this phenomenon, focusing the attention on one of the most interesting countries for its diversity, cultural wealth, and for strong Chinese presence: Ethiopia. The study will be integrated with interdisciplinary investigation methods, such as landscape archeology, historiographic research, participatory anthropology, geopolitics, and cultural anthropology and ethnology. There are two main objectives of the research. The first is to predict what will happen to these populations and how the territory will be modified, trying to monitor the growth of infrastructure in the country and the effects it will have on the population. Risk analyzes will be carried out to understand what the foreign presence may entail, such as the absence of sustenance for local populations, the ghettoization of foreigners, unemployment of natives and the exodus of the population to the capital; the relationships between families and the local population will be analyzed, trying to understand the dynamics of socialization and interaction. Thanks to the use of GIS, the areas affected by the Chinese presence will be geo-referenced and mapped, delimiting the areas most affected and creating a risk analysis, both in desert areas and in archaeologically and historically relevant areas. The second point is to document the life and rituals of Ethiopian populations in order not to lose the aspects of uniqueness that risk being lost. Local interviews will collect impressions and criticisms from the local population to understand if the Chinese presence is perceived as a threat or as a solution. Furthermore, Afar leaders in the Logya area will be interviewed, in truly exclusive research, to understand their links with the foreign presence. From the north, along the Saba river, we will move to the northwest, in the Tigray region, to know the impressions in the Coptic area, currently less threatened by the Chinese presence but still affected by urbanization proposals. There will also be documented the Coptic rituals of Gennà and Timkat, unique expressions of a millennial tradition. This will allow the understanding of whether the Maoist presence could influence the religious rites and forms of belief present in the country, or the country will maintain its cultural independence.

Keywords: Ethiopia, GIS, risk perceptions, salt caravans

Procedia PDF Downloads 156

Authors: Soraia V. M. de Sá, Miguel A. Faria, José O. Fernandes, Sara C. Cunha

Abstract:

Cereals play a vital role in fulfilling the nutritional needs of children, supplying essential nutrients crucial for their growth and development. However, concerns arise due to children's heightened vulnerability due to their unique physiology, specific dietary requirements, and relatively higher intake in relation to their body weight. This vulnerability exposes them to harmful food contaminants, particularly mycotoxins, prevalent in cereals. Because of the thermal stability of mycotoxins, conventional industrial food processing often falls short of eliminating them. Children, especially those aged 4 months to 12 years, frequently encounter mycotoxins through the consumption of specialized food products, such as instant foods, breakfast cereals, bars, cookie snacks, fruit puree, and various dairy items. A close monitoring of this demographic group's exposure to mycotoxins is essential, as toxins ingestion may weaken children’s immune systems, reduce their resistance to infectious diseases, and potentially lead to cognitive impairments. The severe toxicity of mycotoxins, some of which are classified as carcinogenic, has spurred the establishment and ongoing revision of legislative limits on mycotoxin levels in food and feed globally. While EU Commission Regulation 1881/2006 addresses well-known mycotoxins in processed cereal-based foods and infant foods, the absence of regulations specifically addressing emerging mycotoxins underscores a glaring gap in the regulatory framework, necessitating immediate attention. Emerging mycotoxins have gained mounting scrutiny in recent years due to their pervasive presence in various foodstuffs, notably cereals and cereal-based products. Alarmingly, exposure to multiple mycotoxins is hypothesized to exhibit higher toxicity than isolated effects, raising particular concerns for products primarily aimed at children. This study scrutinizes the presence of 22 mycotoxins of the diverse range of chemical classes in 148 processed cereal-based foods, including 39 breakfast cereals, 25 infant formulas, 27 snacks, 25 cereal bars, and 32 cookies commercially available in Portugal. The analytical approach employed a modified QuEChERS procedure followed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. Given the paucity of information on the risk assessment of children to multiple mycotoxins in cereal and cereal-based products consumed by children of Portugal pioneers the evaluation of this critical aspect. Overall, aflatoxin B1 (AFB1) and aflatoxin G2 (AFG2) emerged as the most prevalent regulated mycotoxins, while enniatin B (ENNB) and sterigmatocystin (STG) were the most frequently detected emerging mycotoxins.

Keywords: cereal-based products, children´s nutrition, food safety, UPLC-MS/MS analysis

Procedia PDF Downloads 34

Authors: Mary Farrell, Maria Soubra, Sandra Vega, Dorothy Kakraba, Joanne Fontanilla, Moira Kendra, Danielle Tonzola, Stephanie Chiu

Abstract:

Pneumonia is the most common infectious cause of hospitalizations in the United States, with more than one million admissions annually and costs of $10 billion every year, making it the 8th leading cause of death. Aspiration pneumonia is an aggressive type of pneumonia that results from inhalation of oropharyngeal secretions and/or gastric contents and is preventable. The authors hypothesized that an evidence-based aspiration pneumonia clinical care pathway could reduce 30-day hospital readmissions and mortality rates, while improving the overall care of patients. We conducted a retrospective chart review on 979 patients discharged with aspiration pneumonia from January 2021 to December 2022 at Overlook Medical Center. The authors identified patients who were coded with aspiration pneumonia and/or stable sepsis. Secondarily, we identified 30-day readmission rates for aspiration pneumonia from a SNF. The Aspiration Pneumonia Clinical Care Pathway starts in the emergency department (ED) with the initiation of antimicrobials within 4 hours of admission and early recognition of aspiration. Once this is identified, a swallow test is initiated by the bedside nurse, and if the patient demonstrates dysphagia, they are maintained on strict nothing by mouth (NPO) followed by a speech and language pathologist (SLP) referral for an appropriate modified diet recommendation. Aspiration prevention techniques included the avoidance of straws, 45-degree positioning, no talking during meals, taking small bites, placement of the aspiration wrist band, and consuming meals out of the bed in a chair. Nursing education was conducted with a newly created online learning module about aspiration pneumonia. The authors identified 979 patients, with an average age of 73.5 years old, who were diagnosed with aspiration pneumonia on the index hospitalization. These patients were reviewed for a 30-day readmission for aspiration pneumonia or stable sepsis, and mortality rates from January 2021 to December 2022 at Overlook Medical Center (OMC). The 30-day readmission rates were significantly lower in the cohort that received the clinical care pathway (35.0% vs. 27.5%, p = 0.011). When evaluating the mortality rates in the pre and post intervention cohort the authors discovered the mortality rates were lower in the post intervention cohort (23.7% vs 22.4%, p = 0.61) Mortality among non-white (self-reported as non-white) patients were lower in the post intervention cohort (34.4% vs. 21.0% , p = 0.05). Patients who reported as a current smoker/vaper in the pre and post cohorts had increased mortality rates (5.9% vs 22%). There was a decrease in mortality for the male population but an increase in mortality for women in the pre and post cohorts (19% vs. 25%). The authors attributed this increase in mortality in the post intervention cohort to more active smokers, more former smokers, and more being admitted from a SNF. This research identified that implementation of an Aspiration Pneumonia Clinical Care Pathway showed a statistically significant decrease in readmission rates and mortality rates in non-whites. The 30-day readmission rates were lower in the cohort that received the clinical care pathway (35.0% vs. 27.5%, p = 0.011).

Keywords: aspiration pneumonia, mortality, quality improvement, 30-day pneumonia readmissions

Procedia PDF Downloads 33

Authors: Mary A. Lindell

Abstract:

Adults with intellectual disabilities (ID) are increasingly attending postsecondary institutions, including inclusive residential programs at four-year universities. The legislation, national organizations, and researchers support developing postsecondary education (PSE) options for this historically underserved population. Simultaneously, researchers are assessing the quality of life indicators (QOL) for people with ID. This study explores the quality of life characteristics for individuals with ID entering a two-year PSE program. A survey aligned with the PSE program was developed and administered to participants before they began their college program (in future studies, the same survey will be administered 6 months and 1 year after graduating). Employment, income, and housing are frequently cited QOL measures. People with disabilities, and especially people with ID, are more likely to experience unemployment and low wages than people without disabilities. PSE improves adult outcomes (e.g., employment, income, housing) for people with and without disabilities. Similarly, adults with ID who attend PSE are more likely to be employed than their peers who do not attend PSE; however, adults with ID are least likely among their typical peers and other students with disabilities to attend PSE. There is increased attention to providing individuals with ID access to PSE and more research is needed regarding the characteristics of students attending PSE. This study focuses on the participants of a fully residential two-year program for individuals with ID. Students earn an Applied Skills Certificate while focusing on five benchmarks: self-care, home care, relationships, academics, and employment. To create a QOL measure, the goals of the PSE program were identified, and possible assessment items were initially selected from the National Core Indicators (NCI) and the National Transition Longitudinal Survey 2 (NTLS2) that aligned with the five program goals. Program staff and advisory committee members offered input on potential item alignment with program goals and expected value to students with ID in the program. National experts in researching QOL outcomes of people with ID were consulted and concurred that the items selected would be useful in measuring the outcomes of postsecondary students with ID. The measure was piloted, modified, and administered to incoming students with ID. Research questions: (1) In what ways are students with ID entering a two-year PSE program similar to individuals with ID who complete the NCI and NTLS2 surveys? (2) In what ways are students with ID entering a two-year PSE program different than individuals with ID who completed the NCI and NTLS2 surveys? The process of developing a QOL measure specific to a PSE program for individuals with ID revealed that many of the items in comprehensive national QOL measures are not relevant to stake-holders of this two-year residential inclusive PSE program. Specific responses of students with ID entering an inclusive PSE program will be presented as well as a comparison to similar items on national QOL measures. This study explores the characteristics of students with ID entering a residential, inclusive PSE program. This information is valuable for, researchers, educators, and policy makers as PSE programs become more accessible for individuals with ID.

Keywords: intellectual disabilities, inclusion, post-secondary education, quality of life

Procedia PDF Downloads 76

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

Abstract:

Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

Procedia PDF Downloads 245

Authors: Nawal Alawad, Passent Ibrahim Tantawi, Mohamed Abdel Salam Ragheb

Abstract:

Providing customers with quality experiences has been confirmed to be a sustainable, competitive advantage with a distinct financial impact for companies. The success of service providers now relies on their ability to provide customer-centric services. The importance of perceived service quality and customer experience is widely recognized. The focus of this research is in the area of mobile and fixed broadband services. This study is of dual importance both academically and practically. Academically, this research applies a new model investigating the impact of customer experience quality on loyalty based on modifying the multiple-item scale for measuring customers’ service experience in a new area and did not depend on the traditional models. The integrated scale embraces four dimensions: service experience, outcome focus, moments of truth and peace of mind. In addition, it gives a scientific explanation for this relationship so this research fill the gap in such relations in which no one correlate or give explanations for these relations before using such integrated model and this is the first time to apply such modified and integrated new model in telecom field. Practically, this research gives insights to marketers and practitioners to improve customer loyalty through evolving the experience quality of broadband customers which is interpreted to suggested outcomes: purchase, commitment, repeat purchase and word-of-mouth, this approach is one of the emerging topics in service marketing. Data were collected through 412 questionnaires and analyzed by using structural equation modeling.Findings revealed that both outcome focus and moments of truth have a significant impact on loyalty while both service experience and peace of mind have insignificant impact on loyalty.In addition, it was found that 72% of the variation occurring in loyalty is explained by the model. The researcher also measured the net prompters score and gave explanation for the results. Furthermore, assessed customer’s priorities of broadband services. The researcher recommends that the findings of this research will extend to be considered in the future plans of Telecom Egypt Group. In addition, to be applied in the same industry especially in the developing countries that have the same circumstances with similar service settings. This research is a positive contribution in service marketing, particularly in telecom industry for making marketing more reliable as managers can relate investments in service experience directly with the performance closest to income for instance, repurchasing behavior, positive word of mouth and, commitment. Finally, the researcher recommends that future studies should consider this model to explain significant marketing outcomes such as share of wallet and ultimately profitability.

Keywords: broadband services, customer experience quality, loyalty, net promoters score

Procedia PDF Downloads 245

Authors: Maciej Szeląg

Abstract:

The changing nature of environmental impacts, in which cement composites are operating, are causing in the structure of the material a number of phenomena, which result in volume deformation of the composite. These strains can cause composite cracking. Cracks are merging by propagation or intersect to form a characteristic structure of cracks known as the cluster cracks. This characteristic mesh of cracks is crucial to almost all building materials, which are working in service loads conditions. Particularly dangerous for a cement matrix is a sudden load of elevated temperature – the thermal shock. Resulting in a relatively short period of time a large value of a temperature gradient between the outer surface and the material’s interior can result in cracks formation on the surface and in the volume of the material. In the paper, in order to analyze the geometry of the cluster cracks of the cement pastes, the image analysis tools were used. Tested were 4 series of specimens made of two different Portland cement. In addition, two series include microsilica as a substitute for the 10% of the cement. Within each series, specimens were performed in three w/b indicators (water/binder): 0.4; 0.5; 0.6. The cluster cracks were created by sudden loading the samples by elevated temperature of 250°C. Images of the cracked surfaces were obtained via scanning at 2400 DPI. Digital processing and measurements were performed using ImageJ v. 1.46r software. To describe the structure of the cluster cracks three stereological parameters were proposed: the average cluster area - A ̅, the average length of cluster perimeter - L ̅, and the average opening width of a crack between clusters - I ̅. The aim of the study was to identify and evaluate the relationships between measured stereological parameters, and the compressive strength and the bulk density of the modified cement pastes. The tests of the mechanical and physical feature have been carried out in accordance with EN standards. The curves describing the relationships have been developed using the least squares method, and the quality of the curve fitting to the empirical data was evaluated using three diagnostic statistics: the coefficient of determination – R2, the standard error of estimation - Se, and the coefficient of random variation – W. The use of image analysis allowed for a quantitative description of the cluster cracks’ geometry. Based on the obtained results, it was found a strong correlation between the A ̅ and L ̅ – reflecting the fractal nature of the cluster cracks formation process. It was noted that the compressive strength and the bulk density of cement pastes decrease with an increase in the values of the stereological parameters. It was also found that the main factors, which impact on the cluster cracks’ geometry are the cement particles’ size and the general content of the binder in a volume of the material. The microsilica caused the reduction in the A ̅, L ̅ and I ̅ values compared to the values obtained by the classical cement paste’s samples, which is caused by the pozzolanic properties of the microsilica.

Keywords: cement paste, cluster cracks, elevated temperature, image analysis, microsilica, stereological parameters

Procedia PDF Downloads 226

Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche

Abstract:

It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.

Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells

Procedia PDF Downloads 97