Search results for: meta-teaching and regulation of cognitive

Authors: Alina Goldberg Cavalleri, Sara Franco Ortega, Nawaporn Onkokesung, Richard Dale, Melissa Brazier-Hicks, Robert Edwards

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Non-target site based resistance (NTSR) to herbicides in weeds is a polygenic trait associated with the upregulation of proteins involved in xenobiotic detoxification and translocation we have termed the xenome. Among the xenome proteins, ABC transporters play a key role in enhancing herbicide metabolism by effluxing conjugated xenobiotics from the cytoplasm into the vacuole. The importance of ABC transporters is emphasized by the fact that they often contribute to multidrug resistance in human cells and antibiotic resistance in bacteria. They also play a key role in insecticide resistance in major vectors of human diseases and crop pests. By surveying available databases, transcripts encoding ABCs have been identified as being enhanced in populations exhibiting NTSR in several weed species. Based on a transcriptomics data in black grass (Alopecurus myosuroides, Am), we have identified three proteins from the ABC-C subfamily that are upregulated in NTSR populations. ABC-C transporters are poorly characterized proteins in plants, but in Arabidopsis localize to the vacuolar membrane and have functional roles in transporting glutathionylated (GSH)-xenobiotic conjugates. We found that the up-regulation of AmABCs strongly correlates with the up-regulation of a glutathione transferase termed AmGSTU2, which can conjugate GSH to herbicides. The expression profile of the ABC transcripts was profiled in populations of black grass showing different degree of resistance to herbicides. This, together with a phylogenetic analysis, revealed that AmABCs cluster in different groups which might indicate different substrate and roles in the herbicide resistance phenotype in the different populations

Keywords: black grass, herbicide, resistance, transporters

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Authors: Mina Rabipour, Elena Pallaske, Floyd Hassenrück, Rocio Rebollido-Rios

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Protein tyrosine kinases, including Lyn kinase of the Src family kinases (SFK), regulate cell proliferation, survival, and differentiation. Lyn kinase has been implicated in various cancers, positioning it as a promising therapeutic target. However, the conserved ATP-binding pocket across SFKs makes developing selective inhibitors challenging. This study aims to address this limitation by exploring the potential for allosteric modulation of Lyn kinase, focusing on how its structural dynamics and specific oncogenic mutations impact its conformation and function. To achieve this, we combined homology modeling, molecular dynamics simulations, and data science techniques to conduct microsecond-length simulations. Our approach allowed a detailed investigation into the interplay between Lyn’s catalytic and regulatory domains, identifying key conformational states involved in allosteric regulation. Additionally, we evaluated the structural effects of Dasatinib, a competitive inhibitor, and ATP binding on Lyn active conformation. Notably, our simulations show that cancer-related mutations, specifically I364L/N and E290D/K, shift Lyn toward an inactive conformation, contrasting with the active state of the wild-type protein. This may suggest how these mutations contribute to aberrant signaling in cancer cells. We conducted a dynamical network analysis to assess residue-residue interactions and the impact of mutations on the Lyn intramolecular network. This revealed significant disruptions due to mutations, especially in regions distant from the ATP-binding site. These disruptions suggest potential allosteric sites as therapeutic targets, offering an alternative strategy for Lyn inhibition with higher specificity and fewer off-target effects compared to ATP-competitive inhibitors. Our findings provide insights into Lyn kinase regulation and highlight allosteric sites as avenues for selective drug development. Targeting these sites may modulate Lyn activity in cancer cells, reducing toxicity and improving outcomes. Furthermore, our computational strategy offers a scalable approach for analyzing other SFK members or kinases with similar properties, facilitating the discovery of selective allosteric modulators and contributing to precise cancer therapies.

Keywords: lyn tyrosine kinase, mutation analysis, conformational changes, dynamic network analysis, allosteric modulation, targeted inhibition

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Authors: Melissa C. Monney

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Psychological testing has been of interest to researchers for many years as useful tools in assessing and diagnosing various disorders as well as to assist in understanding human behavior. However, for over 20 years now, researchers and laypersons alike have been interested in using them for other purposes, such as determining factors in employee selection, promotion, and even termination. In recent years, psychological assessments have been useful in facilitating workplace decision processing, regarding employee circulation within organizations. This literature review explores four of the most commonly used psychological tests in workplace environments, namely cognitive ability, emotional intelligence, integrity, and personality tests, as organizations have used these tests to assess different factors of human behavior as predictive measures of future employee behaviors. The findings suggest that while there is much controversy and debate regarding the validity and reliability of these tests in workplace settings as they were not originally designed for these purposes, the use of such assessments in the workplace has been useful in decreasing costs and employee turnover as well as increase job satisfaction by ensuring the right employees are selected for their roles.

Keywords: cognitive ability, personality testing, predictive validity, workplace behavior

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Authors: Qingfang Guo

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Isodon rubescens is rich in a variety of terpenes such as oridonin. It has important medicinal value. MYB transcription factors are involved in the regulation of plant secondary metabolic pathways. The combined transcriptomics and metabolomics analysis revealed that IrMYB55 might be involved in the regulation of the synthesis of terpenes. The function of IrMYB55 was further verified by establishing of a genetic transformation system by CRISPR/Cas9. Obtaining a virus-mediated Isodon rubescens gene silencing material. The main research results are as follows: (1) Screening IrMYB which can regulate the synthesis of terpenes. Metabolomics and transcriptomics analyses of materials with high (TJ)-and low (FL)-content populations which revealed significant differences in terpene content and IrMYB55 expression. Correlation analysis showed that the expression level of IrMYB55 had a significant correlation with the content of terpenes. (2) Establishment of a genetic transformation system of Isodon rubescens. The IrPDS gene could be knocked out by injection of Isodon rubescens cotyledon, and the transformed material showed obvious albino phenotype. Subsequently, IrMYB55 conversion material was obtained by this method. (3) The IrMYB55 silencing material was obtained. Subcellular localization indicated that IrMYB55 was located in the nucleus, indicating that it might regulate the synthesis of terpenoids through transcription. In summary, IrMYB55 that may regulate the synthesis of oridonin was dug out from the transcriptome and metabolome data. In this study, a genetic transformation system of Isodon rubescens was successfully established. Further studies showed that IrMYB55 regulated the transcription level of genes related to the synthesis of terpenoids, thereby promoting the accumulation of oridonin.

Keywords: isodon rubescens, MYB, oridonin, CRISPR/Cas9

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Authors: Rachana Tank, Donald. M. Lyall, Kristin Flegal, Joey Ward, Jonathan Cavanagh

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Alzheimer’s research UK estimates by 2050, 2 million individuals will be living with Late Onset Alzheimer’s disease (LOAD). However, individuals experience considerable cognitive deficits and brain pathology over decades before reaching clinically diagnosable LOAD and studies have utilised gene candidate studies such as genome wide association studies (GWAS) and polygenic risk (PGR) scores to identify high risk individuals and potential pathways. This investigation aims to determine whether high genetic risk of LOAD is associated with worse brain MRI and cognitive performance in healthy older adults within the UK Biobank cohort. Previous studies investigating associations of PGR for LOAD and measures of MRI or cognitive functioning have focused on specific aspects of hippocampal structure, in relatively small sample sizes and with poor ‘controlling’ for confounders such as smoking. Both the sample size of this study and the discovery GWAS sample are bigger than previous studies to our knowledge. Genetic interaction between loci showing largest effects in GWAS have not been extensively studied and it is known that APOE e4 poses the largest genetic risk of LOAD with potential gene-gene and gene-environment interactions of e4, for this reason we  also analyse genetic interactions of PGR with the APOE e4 genotype. High genetic loading based on a polygenic risk score of 21 SNPs for LOAD is associated with worse brain MRI and cognitive outcomes in healthy individuals within the UK Biobank cohort. Summary statistics from Kunkle et al., GWAS meta-analyses (case: n=30,344, control: n=52,427) will be used to create polygenic risk scores based on 21 SNPs and analyses will be carried out in N=37,000 participants in the UK Biobank. This will be the largest study to date investigating PGR of LOAD in relation to MRI. MRI outcome measures include WM tracts, structural volumes. Cognitive function measures include reaction time, pairs matching, trail making, digit symbol substitution and prospective memory. Interaction of the APOE e4 alleles and PGR will be analysed by including APOE status as an interaction term coded as either 0, 1 or 2 e4 alleles. Models will be adjusted partially for adjusted for age, BMI, sex, genotyping chip, smoking, depression and social deprivation. Preliminary results suggest PGR score for LOAD is associated with decreased hippocampal volumes including hippocampal body (standardised beta = -0.04, P = 0.022) and tail (standardised beta = -0.037, P = 0.030), but not with hippocampal head. There were also associations of genetic risk with decreased cognitive performance including fluid intelligence (standardised beta = -0.08, P<0.01) and reaction time (standardised beta = 2.04, P<0.01). No genetic interactions were found between APOE e4 dose and PGR score for MRI or cognitive measures. The generalisability of these results is limited by selection bias within the UK Biobank as participants are less likely to be obese, smoke, be socioeconomically deprived and have fewer self-reported health conditions when compared to the general population. Lack of a unified approach or standardised method for calculating genetic risk scores may also be a limitation of these analyses. Further discussion and results are pending.

Keywords: Alzheimer's dementia, cognition, polygenic risk, MRI

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Authors: Bhawna Chandravanshi, Ramesh Bhonde

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In the present study, we focused on the improvisation of islet survival in hypoxia. The Islet-like cell aggregates (ICAs) derived from Wharton's jelly mesenchymal stem cells (WJ-MSC) were cultured with and without WJ-MSC for 48h in hypoxia and normoxia and tested for their direct trophic effect on β cell survival. The WJ MSCs themselves secreted insulin upon glucose challenge and expressed the pancreatic markers at both transcription and translational level (C-peptide, Insulin, Glucagon and Glut 2). Direct contact of MSCs with ICAs facilitate the highest viability under hypoxia as evidenced by fluorescein diacetate/propidium iodide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytokine analysis of the co-cultured ICAs revealed amplification of anti-inflammatory cytokine-like TGFβ and TNFα accompanied by depletion of pro-inflammatory cytokines. The increment in VEGF and PDGFa was also seen showing their ability to vascularize upon transplantation. This was further accompanied by reduction in total reactive oxygen species, nitric oxide, and super oxide ions and down-regulation of Caspase3, Caspase8, p53 and up regulation of Bcl2 confirming prevention of apoptosis in ICAs. There was a significant reduction in the expression of p38 protein in the presence of MSCs making the ICAs responsive to glucose. Taken together our data demonstrate for the first time that the WJ-MSC expressed pancreatic markers and their supplementation protected engineered islets against hypoxia, oxidative stress, and inflammatory cytokines by inhibiting p38 MAPK protein.

Keywords: hypoxia, islet-like cell aggregates, inflammatory cytokines, oxidative stress

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Authors: A. Van Staden, N. Purcell

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Spelling development is complex and multifaceted and relies on several cognitive-linguistic processes. This paper explored the spelling difficulties of English second language learners with auditory processing delays. This empirical study aims to address these issues by means of an intervention design. Specifically, the objectives are: (a) to develop and implement a multi-sensory spelling program for second language learners with auditory processing difficulties (APD) for a period of 6 months; (b) to assess the efficacy of the multi-sensory spelling program and whether this intervention could significantly improve experimental learners' spelling, phonological awareness, and processing (PA), rapid automatized naming (RAN), working memory (WM), word reading and reading comprehension; and (c) to determine the relationship (or interplay) between these cognitive and linguistic skills (mentioned above), and how they influence spelling development. Forty-four English, second language learners with APD were sampled from one primary school in the Free State province. The learners were randomly assigned to either an experimental (n=22) or control group (n=22). During the implementation of the spelling program, several visual, tactile and kinesthetic exercises, including the utilization of fingerspelling were introduced to support the experimental learners’ (N = 22) spelling development. Post-test results showed the efficacy of the multi-sensory spelling program, with the experimental group who were trained in utilising multi-sensory coding and fingerspelling outperforming learners from the control group on the cognitive-linguistic, spelling and reading measures. The results and efficacy of this multi-sensory spelling program and the utilisation of fingerspelling for hearing second language learners with APD open up innovative perspectives for the prevention and targeted remediation of spelling difficulties.

Keywords: English second language spellers, auditory processing delays, spelling difficulties, multi-sensory intervention program

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Authors: M. E. Joret, F. Germeys, P. Van de Craen

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Background: Previous studies have shown that ‘full’ bilingualism seems to enhance the executive functions in children, young adults and elderly people. Executive functions refer to a complex cognitive system responsible for self-controlled and planned behavior and seem to predict academic achievement. The present study aimed at investigating whether similar effects could be found in children learning their second language at school in immersion education programs. Methods: In this study, 44 children involved in immersion education for 4 to 5 years were compared to 48 children in traditional schools. All children were between 9 and 11 years old. To assess executive functions, the Simon task was used, a neuropsychological measure assessing executive functions with reaction times and accuracy on congruent and incongruent trials. To control for background measures, all children underwent the Raven’s coloured progressive matrices, to measure non-verbal intelligence and the Echelle de Vocabulaire en Images Peabody (EVIP), assessing verbal intelligence. In addition, a questionnaire was given to the parents to control for other confounding variables, such as socio-economic status (SES), home language, developmental disorders, etc. Results: There were no differences between groups concerning non-verbal intelligence and verbal intelligence. Furthermore, the immersion learners showed overall faster reaction times on both congruent and incongruent trials compared to the traditional learners, but only after 5 years of training, not before. Conclusion: These results show that the cognitive benefits found in ‘full’ bilinguals also appear in children involved in immersion education, but only after a sufficient exposure to the second language. Our results suggest that the amount of second language training needs to be sufficient before these cognitive effects may emerge.

Keywords: bilingualism, executive functions, immersion education, Simon task

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Authors: Ana Lambelho

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In an economic crisis such as the one that shook (and still shake) Europe, one does not question the importance of the measures that encourage the hiring and integration of young people into the labour market. In the mentioned context, enterprises tend to reduce the cost of labour and to seek flexible contracting instruments. The professional internships allow innovation and creativity at low cost, because, as they are not labour contracts, the enterprises do not have to respect the minimum standards related to wages, working time duration and so on. In Portugal, we observe a widespread existence of training contracts in which the trainee worked several hours without salary or was paid below the legally prescribed for the function and the work period. For this reason, under the tripartite agreement for a new system of regulation of labour relations, employment policies and social protection, between the Government and the social partners, in June 2008, foresaw a prohibition of professional internships unpaid and the legal regulation of the mandatory internships for access to an activity. The first Act about private internship contracts, i.e., internships without public funding was embodied in the Decree-Law N. 66/2011, of 1^st June. This work is dedicated to the study of the legal regime of the internship contract in Portugal, by analysing the problems brought by the new set of rules and especially those which remains unresolved. In fact, we can conclude that the number of situations covered by the Act is much lower than what was expected, because of the exclusion of the mandatory internship for access to a profession when the activity is developed autonomously. Since the majority of the activities can be developed both autonomously or subordinated, it is quite easy to out of the Act requirements and, so, out of the protection that it confers to the intern. In order to complete this study, we considered not only the mentioned legal Act, but also the few doctrine and jurisprudence about the theme.

Keywords: intern, internship contact, labour law, Portugal

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Authors: Ke Guek Nee, Wong Siew Fan, Nigel V. Marsh

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Excessive use of the Internet has become a cause for concern in many countries, including Malaysia. Such behaviour is reported to be more prevalent amongst young adults who are reported to be spending large amount of time on the Internet. The present study has three objectives. First one is designing a manual-based Cognitive Behavioural Therapy (CBT) programme to reduce problematic Internet use among young adults in Malaysia. Second one is examining the effectiveness of a manual-based CBT programme at the pilot study stage. Thirdly, the programme focuses on reducing the level of stress and anxiety in problematic Internet users. We adopted CBT with single subject experimental design method. A total of six participants completed the entire program. They were asked to report their daily Internet use and software was installed on their devices to record actual use. The data collection involved three time frame measurements: T1 (baseline), T2 (immediately during the last session of the intervention sessions), and T3 (follow-up). Three scales were used to measure the effectiveness of the program: Depression, Anxiety, Stress Scales (DASS), Social Interaction Anxiety Scale (SIAS), and Problematic Internet Use Questionnaire (PIUQ). The results revealed that the intervention programme has significantly improved two dimensions of problematic Internet use which were obsession and control disorder. The participants’ mental health also showed a deduction in means scores for depression, anxiety and stress with depression showing the greatest improvement after the intervention programme. The participants’ social anxiety showed a slight deduction in means scores. We concluded that the intervention programme designed was effective. However, its limitations need to be addressed in future research.

Keywords: excessive internet use, cognitive behavioral thearapy (CBT), psychological well-being, young adults

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Authors: Li Yuqing

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Fostering the development of intercultural (communicative) competence (IC) is one way to equip our students with the linguistic and cultural skills to communicate effectively with people from diverse backgrounds, particularly English majors who are most likely to encounter multicultural work environments in the future. The purpose of this study is to compare the English majors' intercultural competence in terms of cognitive, affective, and behavioral aspects before and after a ten-week telecollaboration program between 23 English majors at a Chinese university and 23 American students enrolled in a Chinese class at an American university, and analyze their development during the program. The results indicate that subjects' cognitive, affective, and behavioral perceptions of IC improved significantly over time. In addition, the program had significant effects on the participants' “Interaction Confidence,” “Interaction Engagement,” and “Interaction Enjoyment” - three components of intercultural sensitivity - as well as their overall intercultural effectiveness (except for “Message Skills”). With the widespread use of the internet, this type of online cultural exchange has a promising future, as suggested by the findings of the current study.

Keywords: intercultural competence, English majors, computer-mediated communication, telecollaboration

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Authors: Josephine Aikpitanyi, Friday Okonofua, Lorrettantoimo, Sandy Tubeuf

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Every day, 800 women die from conditions related to pregnancy and childbirth, resulting in an estimated 300,000 maternal deaths worldwide per year. Over 99 percent of all maternal deaths occur in developing countries, with more than half of them occurring in sub-Saharan Africa. Nigeria being the most populous nation in sub-Saharan Africa bears a significant burden of worsening maternal and child health outcomes with a maternal mortality rate of 917 per 100,000 live births and child mortality rate of 117 per 1,000 live births. While several studies have documented that financial barriers disproportionately discourage poor women from seeking needed maternal and child healthcare, other studies have indicated otherwise. Evidence shows that there are instances where health facilities with skilled healthcare providers exist, and yet maternal, and child health outcomes remain abysmally low, indicating the presence of non-cognitive and behavioural factors that may affect the utilization of healthcare services. This study investigated the influence of locus of control and self-esteem on utilization of maternal and child healthcare services in Nigeria. Specifically, it explored the differences in utilization of antenatal care, skilled birth care, postnatal care, and child vaccination by women having an internal and external locus of control and women having high and low self-esteem. We collected information on non-cognitive traits of 1411 randomly selected women, along with information on utilization of the various indicators of maternal and child healthcare. Estimating logistic regression models for various components of healthcare services utilization, we found that women’s internal locus of control was a significant predictor of utilization of antenatal care, skilled birth care, and completion of child vaccination. We also found that having high self-esteem was a significant predictor of utilization of antenatal care, postnatal care, and completion of child vaccination after adjusting for other control variables. By improving our understanding of non-cognitive traits as possible barriers to maternal and child healthcare utilization, our findings offer important insights for enhancing participant engagement in intervention programs that are initiated to improve maternal and child health outcomes in low-and-middle-income countries.

Keywords: behavioural economics, health-seeking behaviour, locus of control and self-esteem, maternal and child healthcare, non-cognitive traits, and healthcare utilization

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Authors: Mikhail Zarechnev, Bora I. Kumova

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A syllogism is a deductive inference scheme used to derive a conclusion from a set of premises. In a categorical syllogisms, there are only two premises and every premise and conclusion is given in form of a quantified relationship between two objects. The different order of objects in premises give classification known as figures. We have shown that the ordered combinations of 3 generalized quantifiers with certain figure provide in total of 108 syllogistic moods which can be considered as different inference rules. The classical syllogistic system allows to model human thought and reasoning with syllogistic structures always attracted the attention of cognitive scientists. Since automated reasoning is considered as part of learning subsystem of AI agents, syllogistic system can be applied for this approach. Another application of syllogistic system is related to inference mechanisms on the Semantic Web applications. In this paper we proposed the mathematical model and algorithm for syllogistic reasoning. Also the model of iterative syllogistic reasoning in case of continuous flows of incoming data based on case–based reasoning and possible applications of proposed system were discussed.

Keywords: categorical syllogism, case-based reasoning, cognitive architecture, inference on the semantic web, syllogistic reasoning

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Authors: Shalini Adiga, Shashikant Chetty, Jisha, Shobha Kamath

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Background: Moderate impairment of learning and memory has been observed in both type 1 and 2 diabetes mellitus in humans and experimental animals. A Change in glucose utilization and oxidative stress that occur in diabetes are considered the main reasons for cognitive dysfunction. Objective: Costus igneus (CI) which is known to possess hypoglycemic activity was evaluated in this study for its effect on learning and memory in normal and diabetic rats. Methods: Wistar rats were divided into control, CI-alcoholic extract treated normal (250 and 500mg/kg), diabetic control and CI-treated diabetic groups. CI treatment was continued for 4 weeks. For induction of diabetes, a single dose of streptozotocin was injected (30 mg/kg i.p). Entrance latency and time spent in the dark room during acquisition and at 24 and 48h after an aversive shock in a passive avoidance model was used as an index of learning and memory. Glutathione and malondialdehyde levels in brain and blood glucose were measured. Data was analysed using ANOVA. Results: During the three trials in exploration test, the diabetic control rats exhibited no significant change in entrance latency or in the total time spent in the dark compartment. During retention testing, the entrance latency of the diabetic treated groups was two times less at 24h and three times less at 48h after aversive stimulus as compared to diabetic rats. The normal drug-treated rats showed similar behaviour as the saline control. Treatment with CI significantly reduced the raised blood sugar and MDA levels of diabetic rats. Conclusion: Costus igneus prevented the cognitive dysfunction in diabetic rats which can be attributed to its antioxidant and antihyperglycemic activities.

Keywords: Costus igneous, diabetes, learning and memory, cognitive dysfunction

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Authors: Mannan Malik Muhammad Naeem, Jeong Myung Yung

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Functional near infrared spectroscopy (fNIRS) has a favorable position in non-invasive brain imaging techniques. The concentration change of oxygenated hemoglobin and de-oxygenated hemoglobin during particular cognitive activity is the basis for this neuro-imaging modality. Two wavelengths of near-infrared light can be used with modified Beer-Lambert law to explain the indirect status of neuronal activity inside brain. The temporal resolution of fNIRS is very good for real-time brain computer-interface applications. The portability, low cost and an acceptable temporal resolution of fNIRS put it on a better position in neuro-imaging modalities. In this study, an optimization model for impulse response function has been used to estimate/predict initial dip using fNIRS data. In addition, the activity strength parameter related to motor based cognitive task has been analyzed. We found an initial dip that remains around 200-300 millisecond and better localize neural activity.

Keywords: fNIRS, brain-computer interface, optimization algorithm, adaptive signal processing

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Authors: Carine Kawakami

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In French, as well as in English, there are two types of psychological predicate constructions depending on where the experiencer argument is realized; the first type is in the subject position (e.g. Je regrette d’être venu ici. ‘I regret coming here'), hereinafter called ES construction, and the second type is in the object position (e.g. Cette nouvelle m’a surpris. ‘This new surprised me.'), referred as EO construction. In the previous studies about psychological predicates, the syntactic position of the experiencer argument has been just a matter of its connection with the syntactic or semantic structure of the predicate. So that few attentions have been paid to how two types of realization of experiencer are related to the conceptualization of psychological event and to the function of the sentence describing the psychological event, in the sense of speech act theory. In this research, focusing on the French phenomena limited to the first personal pronoun and the present tense, the ES constructions and the EO constructions will be analyzed from cognitive and functional approach. It will be revealed that, due to the possibility to be used in soliloquy and the high co-occurrence with ça (‘it’), the EO constructions may have expressive function to betray what speaker feels in hic et nunc, like interjection. And in the expressive case, the experiencer is construed as a locus where a feeling appears spontaneously and is construed subjectively (e.g. Ah, ça m’énerve! ‘Oh, it irritates me!'). On the other hand, the ES constructions describe speaker’s mental state in an assertive manner rather than the expressive and spontaneously way. In other words, they describe what speaker feels to the interlocutor (e.g. Je suis énervé. ‘I am irritated.'). As a consequence, when the experiencer argument is realized in the subject position, it is construed objectively and have a participant feature in the sense of cognitive grammar. Finally, it will be concluded that the choice of construction type, at least in French, is correlated to the conceptualization of the psychological event and the discourse feature of its expression.

Keywords: french psychological verb, conceptualization, expressive function, assertive function, experiencer realization

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Authors: Sajedeh Salehi, Marco Giacalone

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This paper examines the role of existing online dispute resolution (ODR) mechanisms and their effects on ameliorating access to justice – as a protected right by Art. 47 of the EU Charter of Fundamental Rights – for consumers in EU. The major focus of this study will be on evaluating ODR as the means of dispute resolution for Business-to-Consumer (B2C) cross-border small claims raised in e-commerce transactions. The authors will elaborate the consequences of implementing ODR methods in the context of recent developments in EU regulatory safeguards on promoting consumer protection. In this analysis, both non-judiciary and judiciary ODR redress mechanisms are considered, however, the significant consideration is given to – obligatory and non-obligatory – judiciary ODR methods. For that purpose, this paper will particularly investigate the impact of the EU ODR platform as well as the European Small Claims Procedure (ESCP) Regulation 861/2007 and their role on accelerating the access to justice for consumers in B2C e-disputes. Although, considerable volume of research has been carried out on ODR for consumer claims, rather less (or no-) attention has been paid to provide a combined doctrinal and empirical evaluation of ODR’s potential in resolving cross-border small e-disputes, in EU. Hence, the methodological approach taken in this study is a mixed methodology based on qualitative (interviews) and quantitative (surveys) research methods which will be mainly based on the data acquired through the findings of the Small Claims Analysis Net (SCAN) project. This project contributes towards examining the ESCP Regulation implementation and efficiency in providing consumers with a legal watershed through using the ODR for their transnational small claims. The outcomes of this research may benefit both academia and policymakers at national and international level.

Keywords: access to justice, consumers, e-commerce, small e-Disputes

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Authors: Vanessa Caroline De Barros Bonato, Bruna Lima Gomes, Luciano Freschi, Eduardo Purgatto

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The plant hormone ethylene is closely related to the metabolic changes that occur during fruit ripening, including volatile biosynthesis. Although knowledge about the biochemistry pathways that produce flavor compounds and the importance of ethylene to these processes are extensively covered, little is known about the regulation mechanisms. In addition, growing body of evidences indicates that auxin is also involved in controlling ripening. However, there is scarce information about the involvement of auxin in fruit volatile production. This study aimed to assess auxin-ethylene interactions and its influence on tomato fruit volatile profile. Fruits from tomato cultivar Micro-Tom were treated with IAA and ethylene, separately and in combination. The hormonal treatment was performed by injection (IAA) or gas exposure (ethylene) and the volatiles were extracted by Solid Phase Microextraction (SPME) and analyzed by GC-MS. Ethylene levels and color were measured by gas chromatography and colorimetry, respectively. The results indicate that the treatment with IAA (even in the presence of high concentrations of exogenous ethylene), impacted the profile of volatile compounds derived from fatty acids, amino acids, carbohydrates and isoprenoids. Ethylene is a well-known regulator of the transition from green to red color and also is implicated in the biosynthesis of characteristic volatile compounds of tomato fruit. The effects observed suggest the existence of a crosstalk between IAA and ethylene in the aroma volatile formation in the fruit. A possible interference of IAA in the ethylene sensitivity in the fruit flesh is discussed. The data suggest that auxin plays an important role in the volatile synthesis in the tomato fruit and introduce a new level of complexity in the regulation of the fruit aroma formation during ripening.

Keywords: aroma compounds, fruit ripening, fruit quality, phytohormones

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Authors: Sakshi Chopra, Ashima Nehra, Sumit Sinha, Harsimarpreet Kaur, Ravindra Mohan Pandey

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Background: Cognitive rehabilitation aims to retrain brain injured individuals with cognitive deficits to restore or compensate lost functions. As illiterates or people with low literacy levels represent a significant proportion of the world, specific rehabilitation modules for such populations are indispensable. Literacy is significantly associated with all neuropsychological measures and retraining programs widely use written or spoken techniques which essentially require the patient to read or write. So, the aim of the study was to develop and standardize a literacy free neuropsychological rehabilitation program for improving cognitive functioning in patients with mild and moderate Traumatic Brain Injury (TBI). Several studies have pointed out to the impairments seen in memory, executive functioning, and attention and concentration post-TBI, so the rehabilitation program focussed on these domains. Visual item memorization, stick constructions, symbol cancellations, and colouring techniques were used to construct the retraining program. Methodology: The development of the program consisted of planning, preparing, analyzing, and revising the different modules. The construction focussed on areas of retraining immediate and delayed visual memory, planning ability, focused and divided attention, concentration, and response inhibition (to control irritability and aggression). A total of 98 home based retraining modules were prepared in the 4 domains (42 for memory, 42 for executive functioning, 7 for attention and concentration, and 7 for response inhibition). The standardization was done on 20 healthy controls to review, select and edit items. For each module, the time, errors made and errors per second were noted down, to establish the difficulty level of each module and were arranged in increasing level of difficulty over a period of 6 weeks. The retraining tasks were then administered on 11 brain injured individuals (5 after Mild TBI and 6 after Moderate TBI). These patients were referred from the Trauma Centre to Clinical Neuropsychology OPD, All India Institute of Medical Sciences, New Delhi, India. Results: The time was taken, errors made and errors per second were analysed for all domains. Education levels were divided into illiterates, up to 10 years, 10 years to graduation and graduation and above. Mean and standard deviations were calculated. Between group and within group analysis was done using the t-test. The performance of 20 healthy controls was analyzed and only a significant difference was observed on the time taken for the attention tasks and all other domains had non-significant differences in performance between different education levels. Comparing the errors, time taken between patient and control group, there was a significant difference in all the domains at the 0.01 level except the errors made on executive functioning, indicating that the tool can successfully differentiate between healthy controls and patient groups. Conclusions: Apart from the time taken for symbol cancellations, the entire cognitive rehabilitation program is literacy free. As it taps the major areas of impairment post-TBI, it could be a useful tool to rehabilitate the patient population with low literacy levels across the world. The next step is already underway to test its efficacy in improving cognitive functioning in a randomized clinical controlled trial.

Keywords: cognitive rehabilitation, illiterates, India, traumatic brain injury

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Authors: Divya Palaniappan

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Early Childhood assessment tools must measure the quality and the appropriateness of a curriculum with respect to culture and age of the children. Preschool assessment tools lack psychometric properties and were developed to measure only few areas of development such as specific skills in music, art and adaptive behavior. Existing preschool assessment tools in India are predominantly informal and are fraught with judgmental bias of observers. The World of Discovery TM curriculum focuses on accelerating the physical, cognitive, language, social and emotional development of pre-schoolers in India through various activities. The curriculum caters to every child irrespective of their dominant intelligence as per Gardner’s Theory of Multiple Intelligence which concluded "even students as young as four years old present quite distinctive sets and configurations of intelligences". The curriculum introduces a new theme every week where, concepts are explained through various activities so that children with different dominant intelligences could understand it. For example: The ‘Insects’ theme is explained through rhymes, craft and counting corner, and hence children with one of these dominant intelligences: Musical, bodily-kinesthetic and logical-mathematical could grasp the concept. The child’s progress is evaluated using an assessment tool that measures a cluster of inter-dependent developmental areas: physical, cognitive, language, social and emotional development, which for the first time renders a multi-domain approach. The assessment tool is a 5-point rating scale that measures these Developmental aspects: Cognitive, Language, Physical, Social and Emotional. Each activity strengthens one or more of the developmental aspects. During cognitive corner, the child’s perceptual reasoning, pre-math abilities, hand-eye co-ordination and fine motor skills could be observed and evaluated. The tool differs from traditional assessment methodologies by providing a framework that allows teachers to assess a child’s continuous development with respect to specific activities in real time objectively. A pilot study of the tool was done with a sample data of 100 children in the age group 2.5 to 3.5 years. The data was collected over a period of 3 months across 10 centers in Chennai, India, scored by the class teacher once a week. The teachers were trained by psychologists on age-appropriate developmental milestones to minimize observer’s bias. The norms were calculated from the mean and standard deviation of the observed data. The results indicated high internal consistency among parameters and that cognitive development improved with physical development. A significant positive relationship between physical and cognitive development has been observed among children in a study conducted by Sibley and Etnier. In Children, the ‘Comprehension’ ability was found to be greater than ‘Reasoning’ and pre-math abilities as indicated by the preoperational stage of Piaget’s theory of cognitive development. The average scores of various parameters obtained through the tool corroborates the psychological theories on child development, offering strong face validity. The study provides a comprehensive mechanism to assess a child’s development and differentiate high performers from the rest. Based on the average scores, the difficulty level of activities could be increased or decreased to nurture the development of pre-schoolers and also appropriate teaching methodologies could be devised.

Keywords: child development, early childhood assessment, early childhood curriculum, quantitative assessment of preschool curriculum

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Authors: Mónica Arroyo

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South America shows increasing decline in regional export values in the last years, after a strong growth of trade flows especially with China up to 2013. This change is due to the end of the commodity price boom, the slowing of the Chinese economy and the effects of the 2008 economic crisis. This paper examines the integration of regional economies in this context, particularly the situation in Brazil and Argentina. Based on transformations over the last two decades, the analysis is focused on the spatial circuits of production linked to foreign markets, contributing to the understanding of the different uses of territory and the within-country inequality. The South American regional exports, consisting basically of raw materials, are concentrated in a few companies. Large areas are intended for the production of agriculture and mining commodities, under the command of major economic groups, both domestic and foreign, relegating the local population to less productive places or, in most cases, forcing them to change their activity and to migrate to other regions in search of some source of income. On the other hand, the dynamics of these commodities’ spatial circuits of production print requirements in territories in terms of infrastructure and regulation. Capturing this movement requires understanding businesses and government’s role in territorial regulation, and consequently how regional systems are changing – for instance, economic specialisation, growing role of services, investment in roads, railways, ports, and airports. This paper aims to highlight topics for discussion on regional economic dynamics and their different degrees of internationalisation. The intention is to contribute to the debate about the relations between trade, globalization, and development.

Keywords: regional inequality, international trade, developing world, South America

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Authors: Lisete Barlach, Guilherme Ary Plonski

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Innovative ideas are not always synonymous with business opportunities. Any idea can be creative and not recognized as a potential project in which money and time will be invested, among other resources. Even in firms that promote and enhance innovation, there are two 'check-points', the first corresponding to the acknowledgment of the idea as creative and the second, its consideration as a business opportunity. Both the recognition of new business opportunities or new ideas involve cognitive and psychological frameworks which provide individuals with a basis for noticing connections between seemingly independent events or trends as if they were 'connecting the dots'. It also involves prototypes-representing the most typical member of a certain category–functioning as 'templates' for this recognition. There is a general assumption that these kinds of evaluation processes develop through experience, explaining why expertise plays a central role in this process: the more experienced a professional, the easier for him (her) to identify new opportunities in business. But, paradoxically, an increase in expertise can lead to the inflexibility of thought due to automation of procedures. And, besides this, other cognitive biases can also be present, because new ideas or business opportunities generally depend on heuristics, rather than on established algorithms. The paper presents a literature review about the Einstellung effect by tracking famous cases of rejected ideas, extracted from historical records. It also presents the results of empirical research, with data upon rejected ideas gathered from two different environments: projects rejected during first semester of 2017 at a large incubator center in Sao Paulo and ideas proposed by employees that were rejected by a well-known business company, at its Brazilian headquarter. There is an implicit assumption that Einstellung effect tends to be more and more present in contemporaneity, due to time pressure upon decision-making and idea generation process. The analysis discusses desirability, viability, and feasibility as elements that affect decision-making.

Keywords: cognitive biases, Einstellung effect, recognition of business opportunities, rejected ideas

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Authors: Linda Frazer

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A pluralistic methodology focuses on promoting an understanding that an alternative juridical framework for the regulation of transnational business negotiations (TBN) between private business parties is fundamentally required. This paper deals with the evolving assessment of the doctoral research of the author which demonstrated that due to insufficient juridical tools, negotiations are commonly misunderstood within the complexity of pluralistic and conflicting legal regimes. This inadequacy causes uncertainty in the enforcement of legal remedies, leaving business parties surprised. Consequently, parties cannot sufficiently anticipate when and how legal rights and obligations are created, often counting on oral or incomplete agreements which may lead to the misinterpretation of the extent of their legal rights and obligations. This uncertainty causes threats to business parties for fear of creating unintended legal obligations or, conversely, that law will not enforce intended agreements for failure to pass the tests of contractual validity. A need to find a manner to set default standards of communications and standards of conduct to monitor our evolving global trade would aid law to provide the security, predictability and foreseeability during alternative dispute resolution required by TBN parties. The conclusion of this study includes a proposal of new trade mechanisms, termed 'Bills of Negotiations' (BON) to enhance party autonomy and promote the ability for TBN parties to self-regulate within the boundaries of law. BON will be guided by a secure juridical institutionalized setting that caters to guiding communications during TBN and resolving disputes that arise along the negotiation processes on a fast track basis.

Keywords: alternative resolution disputes, ADR, good faith, good faith, juridical security, legal regulation, trade mechanisms, transnational business negotiations

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Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

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Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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Authors: M. Trousselard, D. Steiler, C. Drogou, P. van-Beers, G. Lamour, S. N. Crosnier, O. Bouilland, P. Dubost, M. Chennaoui, D. Léger

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According to published data, undersea navigation for long periods (nuclear-powered ballistic missile submarine, SSBN) constitutes an extreme environment in which crews are subjected to multiple stresses, including the absence of natural light, illuminance below 1,000 lux, and watch schedules that do not respect natural chronobiological rhythms, for a period of 60-80 days. These stresses seem clearly detrimental to the submariners’ sleep, with consequences for their affective (seasonal affective disorder-like) and cognitive functioning. In the long term, there are abundant publications regarding the consequences of sleep disruption for the occurrence of organic cardiovascular, metabolic, immunological or malignant diseases. It seems essential to propose countermeasures for the duration of the patrol in order to reduce the negative physiological effects on the sleep and mood of submariners. Light therapy, the preferred treatment for dysfunctions of the internal biological clock and the resulting seasonal depression, cannot be used without data to assist knowledge of submariners’ chronobiology (melatonin secretion curve) during patrols, given the unusual characteristics of their working environment. These data are not available in the literature. The aim of this project was to assess, in the course of two studies, the benefits of two environmental techniques for managing chronobiological stress: techniques for optimizing potential (TOP; study 1)3, an existing programme to help in the psychophysiological regulation of stress and sleep in the armed forces, and dawn and dusk simulators (DDS, study 2). For each experiment, psychological, physiological (sleep) or biological (melatonin secretion) data were collected on D20 and D50 of patrol. In the first experiment, we studied sleep and depressive distress in 19 submariners in an operational setting on board an SSBM during a first patrol, and assessed the impact of TOP on the quality of sleep and depressive distress in these same submariners over the course of a second patrol. The submariners were trained in TOP between the two patrols for a 2-month period, at a rate of 1 h of training per week, and assigned daily informal exercises. Results show moderate disruptions in sleep pattern and duration associated with the intensity of depressive distress. The use of TOP during the following patrol improved sleep and depressive mood only in submariners who regularly practiced the techniques. In light of these limited benefits, we assessed, in a second experiment, the benefits of DDS on chronobiology (daily secretion of melatonin) and depressive distress. Ninety submariners were randomly allocated to two groups, group 1 using DDS daily, and group 2 constituting the control group. Although the placebo effect was not controlled, results showed a beneficial effect on chronobiology and depressive mood for submariners with a morning chronotype. Conclusions: These findings demonstrate the difficulty of practicing the tools of psychophysiological management in real life. They raise the question of the subjects’ autonomy with respect to using aids that involve regular practice. It seems important to study autonomy in future studies, as a cognitive resource resulting from the interaction between internal positive resources and “coping” resources, to gain a better understanding of compliance problems.

Keywords: chronobiology, light therapy, seasonal affective disorder, sleep, stress, stress management, submarine

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Authors: Murat İskender Aktaş, Selma Söyük

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The aim of this work is to specify the levels of organizational cynicism health workers. Organizational cynicism concept is evaluated in three sub-branches and these are cognitive, affective, and behavioral. The main objective of the work is to answer the questions about the relationship of demographic characteristics like sub-branches of cynicism and age, marital status, education level, total working hours, occupational groups and income levels. As works in our country are analyzed, there have been studies about cynicism in health and other sectors. However, there were no master’s thesis or organizational cynicism research found about the public health professionals. This is why the aim was chosen as to specify the levels of organizational cynicism of public health professionals. The average of the answers of the health workers to the questions about cynicism levels are 2.86. As organizational cynicism is evaluated according to the sub-branches, cognitive subscale average score is 3.21 affective subscale average score is 2.68 and behavioral subscale average score is counted as 2.67. As the results are analyzed, it is seen that the behavioral subscale has the highest average. This shows that the workers are often criticizing the internal complaints and organizational information with their friends out of the organization.

Keywords: cynicism, organizational cynicism, health care workers

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Authors: Christine Demaecker

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Many researchers have underlined the importance of metaphors in specialised language. Their use of specific domains helps us understand the conceptualisations used to communicate new ideas or difficult topics. Within the wide area of specialised discourse, wine tasting is a very specific example because it is almost exclusively metaphoric. Wine tasting metaphors express various conceptualisations. They are not linguistic but rather conceptual, as defined by Lakoff & Johnson. They correspond to the linguistic expression of a mental projection from a well-known or more concrete source domain onto the target domain, which is the taste of wine. But unlike most specialised terminologies, the vocabulary is never clearly defined. When metaphorical terms are listed in dictionaries, their definitions remain vague, unclear, and circular. They cannot be replaced by literal linguistic expressions. This makes it impossible to transfer them into another language with the traditional linguistic translation methods. Qualitative research investigates whether wine tasting metaphors could rather be translated with the cognitive translation process, as well described by Nili Mandelblit (1995). The research is based on a corpus compiled from two high-profile wine guides; the Parker’s Wine Buyer’s Guide and its translation into French and the Guide Hachette des Vins and its translation into English. In this small corpus with a total of 68,826 words, 170 metaphoric expressions have been identified in the original English text and 180 in the original French text. They have been selected with the MIPVU Metaphor Identification Procedure developed at the Vrije Universiteit Amsterdam. The selection demonstrates that both languages use the same set of conceptualisations, which are often combined in wine tasting notes, creating conceptual integrations or blends. The comparison of expressions in the source and target texts also demonstrates the use of the cognitive translation approach. In accordance with the principle of relevance, the translation always uses target language conceptualisations, but compared to the original, the highlighting of the projection is often different. Also, when original metaphors are complex with a combination of conceptualisations, at least one element of the original metaphor underlies the target expression. This approach perfectly integrates into Lederer’s interpretative model of translation (2006). In this triangular model, the transfer of conceptualisation could be included at the level of ‘deverbalisation/reverbalisation’, the crucial stage of the model, where the extraction of meaning combines with the encyclopedic background to generate the target text.

Keywords: cognitive translation, conceptual integration, conceptual metaphor, interpretative model of translation, wine tasting metaphor

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Authors: Anjali Suresh

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Kerala is well known for its unique settlement pattern; comprising the most part, a continuous spread of habitation. The notable urbanization trend in Kerala is urban spread rather than concentration which points out the increasing urbanization of peripheral areas of existing urban centers. This has thrown a challenge for the authorities to cater the needs of the urban population like to provide affordable housing and infrastructure facilities to sustain their livelihood; which is a matter of concern that needs policy attention in fixing the optimum FSI value. Based on recent reports (Post Disaster Need Analysis –PDNA) from the UN, addressing the unsafe situation of the carpet FAR/FSI practice in the state showcasing the varying geological & climatic conditions should also be the matter of concern. The FSI (Floor space index- the ratio of the built-up space on a plot to the area of the plot) value is certainly one of the key regulation factors in checking the land utilization for the varying occupancies desired for the overall development of a state with limitation in land availability when compared to its neighbors. The pattern of urbanization, physical conditions, topography, etc., varies within the state and can change remarkably over time which identifies that the practicing FSI norms in Kerala does not fulfils the intended function. Thus the FSI regulation is expected to change dynamically from location to location. So for determining the optimum value of FSI /FAR of a region in the state of Kerala, the government agencies should consider the optimum land utilization for the growing urbanization. On the other hand, shall keep in check the overutilization of the same in par with environmental and geographic nature. Therefore the study identifies parameters that should be considered for assigning FSI within the Kerala context, and through expert surveys; opinions arrive at a methodology for assigning an optimum FSI value of a region in the state of Kerala.

Keywords: floor space index, urbanization, density, civic pressure, optimization

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Authors: Panomporn Wisuthseriwong, Hatairuk Tungkasen, Siyaporn Namsongsan, Chanikarn Srinark, Mayuva Youngsabanant-Areekijseree

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The objective of the present study was to evaluate the morphology of porcine cumulus-oocyte complexes (pCOCs) and follicular fluid during follicular development. The samples were obtained from local slaughterhouses in Nakorn Pathom Province, Thailand. Pigs were classified as either in the follicular phase or luteal phase. Porcine follicles (n = 3,510) were categorized as small (1-3 mm in diameters; n=2,910), medium (4-6 mm in diameters; n=530) and large (7-8 mm in diameters; n=70). Then pCOCs and follicular fluid were collected. Finally, we found that the oocytes can be categorized into intact cumulus cells layer oocyte, multi-cumulus cells layer oocyte, partial cumulus cells layer oocyte, completely denuded oocyte and degenerated oocyte. They showed high percentage of intact and multi-cumulus cells layer oocytes from small follicles (54.68%) medium follicles (69.06%) and large follicles (68.57%), which have high potential to develop into matured oocytes in vitro. Protein composition of the follicular fluid was separated by SDS-PAGE technique. The result shows that the protein molecular weight in the small and medium follicles are 23, 50, 66, 75, 92, 100, 132, 163, 225 and >225 kDa. Meanwhile, protein molecular weight in large follicles are 12, 16, 23, 50, 66, 75, 92, 100, 132, 163, 225 and >225 kDa. All proteins play an important role in promotion and regulation on development, maturation of oocytes and regulation of ovulation. We conclude that the results of discovery can be used porcine secretion proteins for supplement in IVM/IVF technology. Acknowledgements: The project was funded by a grant from Silpakorn University Research and Development Institute (SURDI) and Faculty of Science, Silpakorn University, Thailand.

Keywords: porcine follicles, porcine oocyte, follicular fluid, SDS-PAGE

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Authors: Mohamed A. Morsy, Azza A. El-Sheikh, Abdulla Y. Al-Taher

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Resveratrol (RES) is a well-known polyphenol antioxidant. We have previously shown that testicular protective effect of RES against the anticancer drug methotrexate (MTX)-induced toxicity involves transporter-mediated mechanisms. Here, we investigated the effect of RES on MTX-induced nephrotoxicity. Rats were administered RES (10 mg/kg/day) for 8 days, with or without a single MTX dose (20 mg/kg i.p.) at day 4 of the experiment. MTX induced nephrotoxicity evident by significantly increase in serum blood urea nitrogen and creatinine compared to control, as well as distortion of kidney microscopic structure. MTX also significantly increased renal nitric oxide level, with induction of inducible nitric oxide synthase expression. MTX also significantly up-regulated fas ligand and caspase 3. Administering RES prior to MTX significantly improved kidney function and microscopic picture, as well as significantly decreased nitrosative and apoptotic markers compared to MTX alone. RES, but not MTX, caused significant increase in expression of breast cancer resistance protein (BCRP), an apical efflux renal transporter that participates in urinary elimination of both MTX and RES. Interestingly, concomitant MTX and RES caused further up-regulation of renal Bcrp compared to RES alone. Using Human BCRP ATPase assay, both RES and MTX exhibited dose-dependent increase in ATPase activity, with Km values of 0.52 ± 0.03 and 30.9 ± 4.2 µM, respectively. Furthermore, combined RES and MTX caused ATPase activity which was significantly less than maximum ATPase activity attained by the positive control; sulfasalazine (12.5 µM). In conclusion, RES exerted nephro-protection against MTX-induced toxicity through anti-nitrosative and anti-apoptotic effects, as well as via up-regulation of renal Bcrp.

Keywords: methotrexate, resveratrol, nephrotoxicity, breast cancer resistance protein

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