Search results for: hierarchical modulation

Authors: Kaomud Tyagi, Rajasree Chakraborty, Shantanu Kundu, Devkant Singha, Kailash Chandra, Vikas Kumar

Abstract:

The melon thrips, Thrips palmi is a serious pest of a wide range of agriculture crops and also act as vectors for plant viruses (genus Tospovirus, family Bunyaviridae). More molecular data on this species is required to understand the cryptic speciation and evolutionary affiliations. Mitochondrial genomes have been widely used in phylogenetic and evolutionary studies in insect. So far, mitogenomes of five thrips species (Anaphothrips obscurus, Frankliniella intonsa, Frankliniella occidentalis, Scirtothrips dorsalis and Thrips imaginis) is available in the GenBank database. In this study, we sequenced the first complete mitogenome T. palmi and compared it with available thrips mitogenomes. We assembled the mitogenome from the whole genome sequencing data generated using Illumina Hiseq2500. Annotation was performed using MITOS web-server to estimate the location of protein coding genes (PCGs), transfer RNA (tRNAs), ribosomal RNAs (rRNAs) and their secondary structures. The boundaries of PCGs and rRNAs was confirmed manually in NCBI. Phylogenetic analyses were performed using the 13 PCGs data using maximum likelihood (ML) in PAUP, and Bayesian inference (BI) in MrBayes 3.2. The complete mitogenome of T. palmi was 15,333 base pairs (bp), which was greater than the genomes of A. obscurus (14,890bp), F. intonsa (15,215 bp), F. occidentalis (14,889 bp) and S. dorsalis South Asia strain (SA1) (14,283 bp), but smaller than the genomes of T. imaginis (15,407 bp) and S. dorsalis East Asia strain (EA1) (15,343bp). Like in other thrips species, the mitochondrial genome of T. palmi was represented by 37 genes, including 13 PCGs, large and small ribosomal RNA (rrnL and rrnS) genes, 22 transfer RNA (tRNAs) genes (with one extra gene for trn-Serine) and two A+T-rich control regions (CR1 and CR2). Thirty one genes were observed on heavy (H) strand and six genes on the light (L) strand. The six tRNA genes (trnG,trnK, trnY, trnW, trnF, and trnH) were found to be conserved in all thrips species mitogenomes in their locations relative to a protein-coding or rRNA gene upstream or downstream. The gene arrangements of T. palmi is very close to T. imaginis except the rearrangements in tRNAs genes: trnR (arginine), and trnE (glutamic acid) were found to be located between cox3 and CR2 in T. imaginis which were translocated between atp6 and CR1 in T. palmi; trnL1 (Leucine) and trnS1(Serine) were located between atp6 and CR1 in T. imaginis which were translocated between cox3 and CR2 in T. palmi. The location of CR1 upstream of nad5 gene was suggested to be ancestral condition of the thrips species in subfamily Thripinae, was also observed in T. palmi. Both the Maximum likelihood (ML) and Bayesian Inference (BI) phylogenetic trees generated resulted in similar topologies. The T. palmi was clustered with T. imaginis. We concluded that more molecular data on the diverse thrips species from different hierarchical level is needed, to understand the phylogenetic and evolutionary relationships among them.

Keywords: thrips, comparative mitogenomics, gene rearrangements, phylogenetic analysis

Procedia PDF Downloads 168

Authors: Saneeya Qureshi

Abstract:

This paper reports doctoral research into the impact of Special Educational Needs Coordinators (SENCOs) on teachers in England, UK. Since 1994, it has been compulsory for all mainstream schools in the UK to have a SENCO who co-ordinates assessment and provision for supporting pupils with Special Educational Needs (SEN), helping teachers to develop and implement optimal SEN planning and resources. SENCOs’ roles have evolved as various policies continually redefined SEN provision, impacting their positioning within the school hierarchical structure. SENCOs in England are increasingly recognised as key members of school senior management teams. In this paper, It will be argued that despite issues around the transformative ‘professionalisation’ of their role, and subsequent conflict around boundaries and power relations, SENCOs enhance teachers’ abilities in terms of delivering optimal SEN provision. There is a significant international dimension to the issue: a similar role in respect of SEN management already exists in countries such as Ireland, Finland and Singapore, whilst in other countries, such as Italy and India, the introduction of a role similar to that of a SENCO is currently under discussion. The research question addressed is: do SENCOs enhance teachers’ abilities to be effective teachers of children with Special Educational Needs? The theoretical framework of the project is that of interpretivism, as it is acknowledged that there are contexts and realities are social constructions. The study applied a mixed method approach consisting of two phases. The first phase involved a purposive survey (n=42) of 223 primary school SENCOs, which enabled a deeper insight into SENCOs’ perceptions of their roles in relation to teachers. The second phase consisted of semi-structured interviews (n=36) of SENCOs, teachers and head teachers, in addition to school SEN-related documentation scrutiny. ‘Trustworthiness’ was accomplished through data and methodological triangulation, in addition to a rigorous process of coding and thematic analysis. The research was informed by an Ethical Code as per national guidelines. Research findings point to the evolutionary aspect of the SENCO role having engendered a culture of expectations amongst practitioners, as SENCOs transition from being ‘fixers’ to being ‘enablers’ of teachers. Outcomes indicate that SENCOs can empower teaching staff through the dissemination of specialist knowledge. However, there must be resources clearly identified for such dissemination to take place. It is imperative that both SENCOs and teachers alike address the issue of absolution of responsibility that arises when the ownership and accountability for the planning and implementation of SEN provision are not clarified so as to ensure the promotion of a positive school ethos around inclusive practices. Optimal outcomes through effective SEN interventions and teaching practices are positively correlated with the inclusion of teachers in the planning and execution of SEN provisions. An international audience can consider how the key findings are being manifest in a global context, with reference to their own educational settings. Research outcomes can aid the development of specific competencies needed to shape optimal inclusive educational settings in accordance with the official global priorities pertaining to inclusion.

Keywords: inclusion, school professionals, school leadership, special educational needs (SEN), special educational needs coordinators (SENCOs)

Procedia PDF Downloads 194

Authors: Elizaveta S. Prokofyeva, Svetlana V. Maltseva, Roman D. Zaitsev

Abstract:

Rapidly evolving modern data analysis technologies in healthcare play a large role in understanding the operation of the system and its characteristics. Nowadays, one of the key tasks in urban healthcare is to optimize the resource allocation. Thus, the application of data analysis in medical institutions to solve optimization problems determines the significance of this study. The purpose of this research was to establish the dependence between the indicators of the effectiveness of the medical institution and its resources. Hospital discharges by diagnosis; hospital days of in-patients and in-patient average length of stay were selected as the performance indicators and the demand of the medical facility. The hospital beds by type of care, medical technology (magnetic resonance tomography, gamma cameras, angiographic complexes and lithotripters) and physicians characterized the resource provision of medical institutions for the developed models. The data source for the research was an open database of the statistical service Eurostat. The choice of the source is due to the fact that the databases contain complete and open information necessary for research tasks in the field of public health. In addition, the statistical database has a user-friendly interface that allows you to quickly build analytical reports. The study provides information on 28 European for the period from 2007 to 2016. For all countries included in the study, with the most accurate and complete data for the period under review, predictive models were developed based on historical panel data. An attempt to improve the quality and the interpretation of the models was made by cluster analysis of the investigated set of countries. The main idea was to assess the similarity of the joint behavior of the variables throughout the time period under consideration to identify groups of similar countries and to construct the separate regression models for them. Therefore, the original time series were used as the objects of clustering. The hierarchical agglomerate algorithm k-medoids was used. The sampled objects were used as the centers of the clusters obtained, since determining the centroid when working with time series involves additional difficulties. The number of clusters used the silhouette coefficient. After the cluster analysis it was possible to significantly improve the predictive power of the models: for example, in the one of the clusters, MAPE error was only 0,82%, which makes it possible to conclude that this forecast is highly reliable in the short term. The obtained predicted values of the developed models have a relatively low level of error and can be used to make decisions on the resource provision of the hospital by medical personnel. The research displays the strong dependencies between the demand for the medical services and the modern medical equipment variable, which highlights the importance of the technological component for the successful development of the medical facility. Currently, data analysis has a huge potential, which allows to significantly improving health services. Medical institutions that are the first to introduce these technologies will certainly have a competitive advantage.

Keywords: data analysis, demand modeling, healthcare, medical facilities

Procedia PDF Downloads 144

Authors: Rosemary R. Carlton, Roxane Caron

Abstract:

Almost three decades ago, bell hooks (1994) identified the classroom as “the most radical space of possibility in the academy”. A feminist scholar, educator, and activist, hooks urged educators to transgress the boundaries of what might be customary or considered acceptable in teaching, thus encouraging the pursuit of new ways of knowing and different strategies for sharing knowledge. This paper reflects upon a particular response to hooks’ still relevant call for transgression in teaching. Specifically, this paper reports on the design, implementation, and preliminary analysis of a social work course integrating active pedagogy and transnational exchange to encourage students’ critical thinking and autonomous learning in their development as social workers in a global context. The bachelor’s level course, Pratiques spécifiques: Projet international, was developed collaboratively across three francophone institutions of higher learning in Belgium, Canada, and France: the Haute École de Namur-Liège-Luxembourg (Hénallux); the Université de Montréal; and, the Institut d’enseignement supérieur et professionnel, l’IRTS Paris Île-de-France. The driving aims of the course are to promote autonomous learning and critical thinking through a lens of transnational understandings of social problems -competencies indispensable to students’ development as social workers. The course is offered to two paired cohorts, one addressing the subject of “migrations” (Canada/France) and the other the subject of “sexual exploitation” (Canada/Belgium). Through the adaptation of a critical pedagogy of problem-based learning, students are called upon to actively engage in acquiring and applying knowledge to respond to “real life” social issues relating to migration or sexual exploitation. At the conclusion of the course, each cohort of students is brought together for a week-long intensive period of transnational exchange either at the Université de Montréal in Canada or at Hénallux in Belgium. Extending the bounds of the classroom across international borders allows students novel opportunities to deepen and expand their understandings of issues relating to predefined social issues and to critically examine associated social work practices. The paper opens with a presentation of the social work course. Specifically, the authors will outline their adaptation of a pedagogy of problem-based learning integrating transnational exchange in the design and implementation of the course. Returning to hooks’ notion of transgression in teaching, the paper offers a preliminary analysis of how and with what effect the course provides opportunities to transgress hierarchical student-teacher relationships; transgress conventional modes of learning to explore diverse sources of knowledge and transgress the walls of the university to engage with and learn from local and global partners. The paper concludes with a consideration of the potential influence of such transgressions in teaching for students’ development of critical thinking in their practice of social work in global context.

Keywords: active learning, critical pedagogy, social work intervention, transnational learning

Procedia PDF Downloads 165

Authors: Larysa Novak-Kalyayeva, Aleksander Kuczabski, Orystlava Sydorchuk, Nataliia Fersman, Tatyana Zemlinskaia

Abstract:

The article presents the results of the creative analysis and comparison of trends in the development of the theory of public administration during the period from the second half of the 20^th to the beginning of the 21^st century. The process of conceptualization of the priorities of public administration in the dynamics of reforming was held under the influence of such factors as globalization, integration, information and technological changes and human rights is examined. The priorities of the social state in the concepts of the second half of the 20^th century are studied. Peculiar approaches to determining the priorities of public administration in the countries of "Soviet dictatorship" in Central and Eastern Europe in the same period are outlined. Particular attention is paid to the priorities of public administration regarding the interaction between public power and society and the development of conceptual foundations for the modern managerial process. There is a thought that the dynamics of the formation of concepts of the European governance is characterized by the sequence of priorities: from socio-economic and moral-ethical to organizational-procedural and non-hierarchical ones. The priorities of the "welfare state" were focused on the decent level of material wellbeing of population. At the same time, the conception of "minimal state" emphasized priorities of human responsibility for their own fate under the conditions of minimal state protection. Later on, the emphasis was placed on horizontal ties and redistribution of powers and competences of "effective state" with its developed procedures and limits of responsibility at all levels of government and in close cooperation with the civil society. The priorities of the contemporary period are concentrated on human rights in the concepts of "good governance" and all the following ones, which recognize the absolute priority of public administration with compliance, provision and protection of human rights. There is a proved point of view that civilizational changes taking place under the influence of information and technological imperatives also stipulate changes in priorities, redistribution of emphases and update principles of managerial concepts on the basis of publicity, transparency, departure from traditional forms of hierarchy and control in favor of interactivity and inter-sectoral interaction, decentralization and humanization of managerial processes. The necessity to permanently carry out the reorganization, by establishing the interaction between different participants of public power and social relations, to establish a balance between political forces and social interests on the basis of mutual trust and mutual understanding determines changes of social, political, economic and humanitarian paradigms of public administration and their theoretical comprehension. The further studies of theoretical foundations of modern public administration in interdisciplinary discourse in the context of ambiguous consequences of the globalizational and integrational processes of modern European state-building would be advisable. This is especially true during the period of political transformations and economic crises which are the characteristic of the contemporary Europe, especially for democratic transition countries.

Keywords: concepts of public administration, democratic transition countries, human rights, the priorities of public administration, theory of public administration

Procedia PDF Downloads 174

Authors: Serena Salvi

Abstract:

Ageistic stereotypes and practices have become a normal and therefore pervasive phenomenon in various aspects of everyday life. Over the past years, renewed awareness towards self-directed age stereotyping in older adults has given rise to a line of research focused on the potential role of attitudes towards ageing on seniors’ health and functioning. This set of studies has showed how a negative internalisation of ageistic stereotypes would discourage older adults in seeking medical advice, in addition to be associated to negative subjective health evaluation. An important dimension of mental health that is often affected in older adults is represented by sleep quality. Self-reported sleep quality among older adults has shown to be often unreliable when compared to their objective sleep measures. Investigations focused on self-reported sleep quality among older adults have suggested how this portion of the population would tend to accept disrupted sleep if believed to be up to standard for their age. On the other hand, unrealistic expectations, and dysfunctional beliefs towards sleep in ageing, might prompt older adults to report sleep disruption even in the absence of objective disrupted sleep. Objective of this study is to examine an association between personal attitudes towards ageing in adults aged 60+ and dysfunctional sleep related cognition. More in detail, this study aims to investigate a potential association between personal attitudes towards ageing, sleep locus of control and dysfunctional beliefs towards sleep among this portion of the population. Data in this study were statistically analysed in SPSS software. Participants were recruited through the online participants recruitment system Prolific. Inclusion of attention check questions throughout the questionnaire and consistency of responses were looked at. Prior to the commencement of this study, Ethical Approval was granted (ref. 39396). Descriptive statistics were used to determine the frequency, mean, and SDs of the variables. Pearson coefficient was used for interval variables, independent T-test for comparing means between two independent groups, analysis of variance (ANOVA) test for comparing the means in several independent groups, and hierarchical linear regression models for predicting criterion variables based on predictor variables. In this study self-perceptions of ageing were assessed using APQ-B’s subscales, while dysfunctional sleep related cognition was operationalised using the SLOC and the DBAS16 scales. Of the final subscales taken in consideration in the brief version of the APQ questionnaire, Emotional Representations (ER), Control Positive (PC) and Control and Consequences Negative (NC) have shown to be of particularly relevance for the remits of this study. Regression analysis show how an increase in the APQ-B subscale Emotional Representations (ER) predicts an increase in dysfunctional beliefs and attitudes towards sleep in this sample, after controlling for subjective sleep quality, level of depression and chronological age. A second regression analysis showed that APQ-B subscales Control Positive (PC) and Control and Consequences Negative (NC) were significant predictors in the change of variance of SLOC, after controlling for subjective sleep quality, level of depression and dysfunctional beliefs about sleep.

Keywords: sleep-related cognition, perceptions of aging, older adults, sleep quality

Procedia PDF Downloads 103

Authors: Naghmeh M. Bandari, Javad Dargahi, Muthukumaran Packirisamy

Abstract:

Robot-assisted minimally invasive surgery (RMIS) has been widely performed around the world during the last two decades. RMIS demonstrates significant advantages over conventional surgery, e.g., improving the accuracy and dexterity of a surgeon, providing 3D vision, motion scaling, hand-eye coordination, decreasing tremor, and reducing x-ray exposure for surgeons. Despite benefits, surgeons cannot touch the surgical site and perceive tactile information. This happens due to the remote control of robots. The literature survey identified the lack of force feedback as the riskiest limitation in the existing technology. Without the perception of tool-tissue contact force, the surgeon might apply an excessive force causing tissue laceration or insufficient force causing tissue slippage. The primary use of force sensors has been to measure the tool-tissue interaction force in real-time in-situ. Design of a tactile sensor is subjected to a set of design requirements, e.g., biocompatibility, electrical-passivity, MRI-compatibility, miniaturization, ability to measure static and dynamic force. In this study, a planar optical fiber-based sensor was proposed to mount at the surgical grasper. It was developed based on the light intensity modulation principle. The deflectable part of the sensor was a beam modeled as a cantilever Euler-Bernoulli beam on rigid substrates. A semi-cylindrical indenter was attached to the bottom surface the beam at the mid-span. An optical fiber was secured at both ends on the same rigid substrates. The indenter was in contact with the fiber. External force on the sensor caused deflection in the beam and optical fiber simultaneously. The micro-bending of the optical fiber would consequently result in light power loss. The sensor was simulated and studied using finite element methods. A laser light beam with 800nm wavelength and 5mW power was used as the input to the optical fiber. The output power was measured using a photodetector. The voltage from photodetector was calibrated to the external force for a chirp input (0.1-5Hz). The range, resolution, and hysteresis of the sensor were studied under monotonic and harmonic external forces of 0-2.0N with 0 and 5Hz, respectively. The results confirmed the validity of proposed sensing principle. Also, the sensor demonstrated an acceptable linearity (R2 > 0.9). A minimum external force was observed below which no power loss was detectable. It is postulated that this phenomenon is attributed to the critical angle of the optical fiber to observe total internal reflection. The experimental results were of negligible hysteresis (R2 > 0.9) and in fair agreement with the simulations. In conclusion, the suggested planar sensor is assessed to be a cost-effective solution, feasible, and easy to use the sensor for being miniaturized and integrated at the tip of robotic graspers. Geometrical and optical factors affecting the minimum sensible force and the working range of the sensor should be studied and optimized. This design is intrinsically scalable and meets all the design requirements. Therefore, it has a significant potential of industrialization and mass production.

Keywords: force sensor, minimally invasive surgery, optical sensor, robotic surgery, tactile sensor

Procedia PDF Downloads 230

Authors: Thiago E. Goto, Carla C. Lopes, Helena B. Nader, Anielle C. A. Silva, Noelio O. Dantas, José R. Siqueira Jr., Luciano Caseli

Abstract:

Quantum dots (QD) are semiconductor nanocrystals that can be employed in biological research as a tool for fluorescence imagings, having the potential to expand in vivo and in vitro analysis as cancerous cell biomarkers. Particularly, cadmium selenide (CdSe) magic-sized quantum dots (MSQDs) exhibit stable luminescence that is feasible for biological applications, especially for imaging of tumor cells. For these facts, it is interesting to know the mechanisms of action of how such QDs mark biological cells. For that, simplified models are a suitable strategy. Among these models, Langmuir films of lipids formed at the air-water interface seem to be adequate since they can mimic half a membrane. They are monomolecular films formed at liquid-gas interfaces that can spontaneously form when organic solutions of amphiphilic compounds are spread on the liquid-gas interface. After solvent evaporation, the monomolecular film is formed, and a variety of techniques, including tensiometric, spectroscopic and optic can be applied. When the monolayer is formed by membrane lipids at the air-water interface, a model for half a membrane can be inferred where the aqueous subphase serve as a model for external or internal compartment of the cell. These films can be transferred to solid supports forming the so-called Langmuir-Blodgett (LB) films, and an ampler variety of techniques can be additionally used to characterize the film, allowing for the formation of devices and sensors. With these ideas in mind, the objective of this work was to investigate the specific interactions of CdSe MSQDs with tumorigenic and non-tumorigenic cells using Langmuir monolayers and LB films of lipids and specific cell extracts as membrane models for diagnosis of cancerous cells. Surface pressure-area isotherms and polarization modulation reflection-absorption spectroscopy (PM-IRRAS) showed an intrinsic interaction between the quantum dots, inserted in the aqueous subphase, and Langmuir monolayers, constructed either of selected lipids or of non-tumorigenic and tumorigenic cells extracts. The quantum dots expanded the monolayers and changed the PM-IRRAS spectra for the lipid monolayers. The mixed films were then compressed to high surface pressures and transferred from the floating monolayer to solid supports by using the LB technique. Images of the films were then obtained with atomic force microscopy (AFM) and confocal microscopy, which provided information about the morphology of the films. Similarities and differences between films with different composition representing cell membranes, with or without CdSe MSQDs, was analyzed. The results indicated that the interaction of quantum dots with the bioinspired films is modulated by the lipid composition. The properties of the normal cell monolayer were not significantly altered, whereas for the tumorigenic cell monolayer models, the films presented significant alteration. The images therefore exhibited a stronger effect of CdSe MSQDs on the models representing cancerous cells. As important implication of these findings, one may envisage for new bioinspired surfaces based on molecular recognition for biomedical applications.

Keywords: biomembrane, langmuir monolayers, quantum dots, surfaces

Procedia PDF Downloads 196

Authors: A. Afrashi

Abstract:

Introduction: Synaesthesia is a term denoting the perception or description of the perception of one sense modality in terms of another. In literature, synaesthesia refers to a technique adopted by writers to present ideas, characters or places in such a manner that they appeal to more than one sense like hearing, seeing, smell etc. at a given time. In everyday language too we find many examples of synaesthesia. We commonly hear phrases like ‘loud colors’, ‘frozen silence’ and ‘warm colors’, ‘bitter cold’ etc. Empirical cognitive studies have proved that synaesthetic representations both in literature and everyday languages are constrained ie. they do not map randomly among sensory domains. From the beginning of the 20th century Synaesthesia has been a research domain both in literature and structural linguistics. However the exploration of cognitive mechanisms motivating synaesthesia, have made it an important topic in 21st century cognitive linguistics and literary studies. Synaesthetic metaphors are linguistic representations of those mental mechanisms, the study of which reveals invaluable facts about perception, cognition and conceptualization. According to the main tenets of cognitive approach to language and literature, unified and similar cognitive mechanisms are active both in everyday language and literature, and synaesthesia is one of those cognitive mechanisms. Main objective of the present research is to answer the following questions: What types of sense transfers are accessible in Persian synaesthetic metaphors. How are these types of sense transfers cognitively explained. What are the results of cross-linguistic comparative study of synaestetic metaphors based on the existing observations? Methodology: The present research employs a cognitive - corpus based method, and the theoretical framework adopted to analyze linguistic synaesthesia is the contemporary theory of metaphor, where conceptual metaphor is the result of systemic mappings across cognitive domains. Persian Language Data- base (PLDB) in the Institute for Humanities and Cultural Studies which consists mainly of Persian modern prose, is searched for synaesthetic metaphors. Then for each metaphorical structure, the source and target domains are determined. Then sense transfers are identified and the types of synaesthetic metaphors recognized. Findings: Persian synaesthetic metaphors conform to the hierarchical distribution principle, according to which transfers tend to go from touch to taste to smell to sound and to sight, not vice versa. In other words mapping from more accessible or basic concepts onto less accessible or less basic ones seems more natural. Furthermore the most frequent target domain in Persian synaesthetic metaphors is sound. Certain characteristics of Persian synaesthetic metaphors are comparable with existing related researches carried on English, French, Hungarian and Chinese synaesthetic metaphors. Conclusion: Cognitive corpus based approaches to linguistic synaesthesia, are applicable to stylistics and literary criticism and this recent research domain is an efficient approach to study cross linguistic variations to find out which of the five senses is dominant cross linguistically and cross culturally as the target domain in metaphorical mappings , and so forth receiving dominance in conceptualizations.

Keywords: cognitive semantics, conceptual metaphor, synaesthesia, corpus based approach

Procedia PDF Downloads 562

Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

Abstract:

Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

Procedia PDF Downloads 98

Authors: Hoda Manafian, Stephen Holland

Abstract:

Problem statement: Rural areas in Iran are one of the most popular tourism destinations. Abyaneh Village is one of them with a long history behind it (more than 1500 years) which is a national heritage site and also is nominated as a world heritage site in UNESCO tentative list from 2007. There is a considerable foundation of religious-cultural heritage and also agricultural history and activities. However, this heritage site suffers from mass tourism which is beyond its social and physical carrying capacity, since the annual number of tourists exceed 500,000. While there are four adjacent villages around Abyaneh which can benefit from advantages of tourism. Local managers also can at the same time prorate the tourists’ flux of Abyaneh on those other villages especially in high-season. The other villages have some cultural and natural tourism attractions as well. Goal: The main goal of this study is to identify a feasible development strategy according to the current strengths, weaknesses, opportunities and threats of rural tourism in this area (Abyaneh Village and four adjacent villages). This development strategy can lead to sustainable management of these destinations. Method: To this end, we used SWOT analysis as a well-established tool for conducting a situational analysis to define a sustainable development strategy. The procedures included following steps: 1) Extracting variables of SWOT chart based on interviewing tourism experts (n=13), local elites (n=17) and personal observations of researcher. 2) Ranking the extracted variables from 1-5 by 13 tourism experts in Isfahan Cultural Heritage, Handcrafts and Tourism Organization (ICHTO). 3) Assigning weights to the ranked variables using Expert Choice Software and the method of Analytical Hierarchical Process (AHP). 4) Defining the Total Weighted Score (TWS) for each part of SWOT chart. 5) Identifying the strategic position according to the TWS 6) Selecting the best development strategy based on the defined position using the Strategic Position and Action Evaluation (SPACE) matrix. 7) Assessing the Probability of Strategic Success (PSS) for the preferred strategy using relevant formulas. 8) Defining two feasible alternatives for sustainable development. Results and recommendations: Cultural heritage attractions were first-ranked variable in strength chart and also lack of sufficient amenities for one-day tourists (catering, restrooms, parking, and accommodation) was firs-ranked weakness. The strategic position was in ST (Strength-Threat) quadrant which is a maxi-mini position. According this position we would suggest ‘Competitive Strategy’ as a development strategy which means relying on strengths in order to neutralization threats. The result of Probability of Strategic Success assessment which was 0.6 shows that this strategy could be successful. The preferred approach for competitive strategy could be rebranding the market of tourism in this area. Rebranding the market can be achieved by two main alternatives which are based on the current strengths and threats: 1) Defining a ‘Heritage Corridor’ from first adjacent village to Abyaneh as a final destination. 2) Focus on ‘educational tourism’ versus mass tourism and also green tourism by developing agritourism in that corridor.

Keywords: Abyaneh village, rural tourism, SWOT analysis, sustainable strategies

Procedia PDF Downloads 384

Authors: Christina Tran, Lu Khoo, Andrea Waylen

Abstract:

Introduction: The evolution of the dental consultation from paternalism to partnership has been well documented in developed Western countries. Great emphasis is now placed on the importance of empowering patients to make decisions regarding their care, obtaining informed consent, and maintaining patient privacy and confidentiality. With the majority of communication occurring non-verbally, clinicians often adopt behaviours which suggest an approachable and positive attitude. However, evidence indicates that in Asia, a paternalistic model may be favored in medicine. The power imbalance occurring in doctor-patient relationships worldwide may be exacerbated by various factors in Southeast Asia: the strong hierarchical culture, and the large education gap between doctor and patient. Further insight into this matter can be gained by observing patient-dentist communication in Cambodia. The dentist:population ratio in Cambodia is approximately 1:33,000, with rural areas remaining extremely underserviced. We have carried out an observational study of communication in a voluntary dental clinic in Cambodia with the aim of describing whether the patient-dentist relationship follows a paternalistic or patient-centred model. Method: Over a period of two weeks, two clinicians provided dental care as part of a voluntary program in two Cambodian settings: a temporary, rural clinic and a permanent clinic in Phnom Penh. The clinicians independently recorded their experiences in diaries, making observations on the verbal and non-verbal communication between patients and staff. General observations such as the clinic environment were also made. The diaries were then compared and analyzed using a thematic approach. Results: The overall themes that emerged were regarding the clinic environment, verbal communication, and non-verbal communication. Regarding the clinic environment, the rural clinic was arranged in order to easily direct patients from one dentist to another, with little emphasis on continuous patient care. There was also little consideration for patient privacy: patients were often treated in the presence of many observers, including other waiting patients. However, the permanent clinic was structured to allow greater patient privacy, with continuous patient care occurring throughout the appointment. Regarding verbal communication, there was a strongly paternalistic approach to gaining consent and giving instruction. Patients rarely asked questions regarding their treatment, with dentists doing little to encourage patient involvement. Non-verbal communication between patients and dentists was generally paternalistic, with the dentist often addressing the supine patient from above. Patients often avoided making eye-contact, which may have indicated discomfort or lack of engagement. Both adult and paediatric patients rarely raised verbal concerns regarding pain during treatment, despite displaying non-verbal signs of experiencing pain. Anxious paediatric patients were sometimes managed with physical restraint by their mothers to facilitate treatment. Conclusion: Patient-professional communication in the Cambodian dental setting was observed to be generally paternalistic in nature, although more patient-centred aspects were observed in the established, urban setting. However, it should be noted that these observations are subjective in nature, and that the patients’ actual perceptions of their communication experience were unexplored. Further observations in variety of dental settings in Cambodia are needed before any definitive conclusions can be made.

Keywords: patient-dentist communication, paternalism, patient-centered, non-verbal communication

Procedia PDF Downloads 122

Authors: O. O. Sufyani, M. E. Oraiby, S. A. Qumaiy, A. I. Alaamri, Z. M. Eisa, A. M. Hakami, M. A. Attafi, O. M. Alhassan, W. M. Elsideeg, E. M. Noureldin, Y. A. Hobani, Y. Q. Majrabi, I. A. Khardali, A. B. Maashi, A. A. Al Mane, A. H. Hakami, I. M. Alkhyat, A. A. Sahly, I. M. Attafi

Abstract:

According to the Food and Agriculture Organization (FAO) Pesticides Use Database, pesticide use in agriculture in Saudi Arabia has more than doubled from 4539 tons in 2009 to 10496 tons in 2019. Among pesticides, pyrethroids is commonly used in Saudi Arabia. Pesticides may increase susceptibility to a variety of diseases, particularly among pesticide workers, due to their extensive use, indiscriminate use, and long-term exposure. Therefore, analyzing blood chemo-profiles and evaluating the detected substances as biomarkers for pyrethroid pesticide exposure may assist to identify and predicting adverse effects of exposure, which may be used for both preventative and risk assessment purposes. The purpose of this study was to (a) analyze chemo-profiling by Gas Chromatography-Mass Spectrometry (GC-MS) analysis, (b) identify the most commonly detected chemicals in a time-exposure-dependent manner using a Venn diagram, and (c) identify their associated disease among pesticide workers using analyzer tools on the Comparative Toxicogenomics Database (CTD) website, (250 healthy male volunteers (20-60 years old) who deal with pesticides in the Jazan region of Saudi Arabia (exposure intervals: 1-2, 4-6, 6-8, more than 8 years) were included in the study. A questionnaire was used to collect demographic information, the duration of pesticide exposure, and the existence of chronic conditions. Blood samples were collected for biochemistry analysis and extracted by solid-phase extraction for gas chromatography-mass spectrometry (GC-MS) analysis. Biochemistry analysis reveals no significant changes in response to the exposure period; however, an inverse association between the albumin level and the exposure interval was observed. The blood chemo-profiling was differentially expressed in an exposure time-dependent manner. This analysis identified the common chemical set associated with each group and their associated significant occupational diseases. While some of these chemicals are associated with a variety of diseases, the distinguishing feature of these chemically associated disorders is their applicability for prevention measures. The most interesting finding was the identification of several chemicals; erucic acid, pelargonic acid, alpha-linolenic acid, dibutyl phthalate, diisobutyl phthalate, dodecanol, myristic Acid, pyrene, and 8,11,14-eicosatrienoic acid, associated with pneumoconiosis, asbestosis, asthma, silicosis and berylliosis. Chemical-disease association study also found that cancer, digestive system disease, nervous system disease, and metabolic disease were the most often recognized disease categories in the common chemical set. The hierarchical clustering approach was used to compare the expression patterns and exposure intervals of the chemicals found commonly. More study is needed to validate these chemicals as early markers of pyrethroid insecticide-related occupational disease, which might assist evaluate and reducing risk. The current study contributes valuable data and recommendations to public health.

Keywords: occupational, toxicology, chemo-profiling, pesticide, pyrethroid, GC-MS

Procedia PDF Downloads 102

Authors: Faheemah N. Mustafaa, Tamarie Macon, Tabbye Chavous

Abstract:

A major concern of university leaders worldwide is how to create environments where students from diverse racial/ethnic, national, and cultural backgrounds can thrive. Over the past decade or so in the United States, African American women have done exceedingly well in terms of college enrollment, academic performance, and completion. However, the relative academic successes of African American women in higher education has in some ways overshadowed social challenges many Black women continue to encounter on college campuses in the United States. Within predominantly White institutions (PWIs) in particular, there is consistent evidence that many Black students experience racially hostile climates. However, research studies on racial climates within PWIs have mostly focused on cross-sectional comparisons of minority and majority group experiences, and few studies have examined campus racial climate in relation to short- and longer-term well-being. One longitudinal study reported that African American women’s psychological well-being was positively related to their comfort in cross-racial interactions (a concept closely related to campus climate). Thus, our primary research question was: Do African American women’s perceptions of campus climate (tension and positive association) during their freshman year predict their reports of psychological distress and well-being (self-acceptance) during their sophomore year? Participants were part of a longitudinal survey examining African American college students’ academic identity development, particularly in Science, Technology, Engineering, and Mathematics (STEM) fields. The final subsample included 134 self-identified African American/Black women enrolled in PWIs. Accounting for background characteristics (mother’s education, family income, interracial contact, and prior levels of outcomes), we employed hierarchical regression to examine relationships between campus racial climate during freshman year and psychological adjustment one year later. Both regression models significantly predicted African American women’s psychological outcomes (for distress, F(7,91)= 4.34, p < .001; and for self-acceptance, F(7,90)= 4.92, p < .001). Although none of the controls were significant predictors, perceptions of racial tension on campus were associated with both distress and self-acceptance. More perceptions of tension were related to African American women’s greater psychological distress the following year (B= 0.22, p= .01). Additionally, racial tension predicted later self-acceptance in the expected direction: Higher first-year reports of racial tension were related to less positive attitudes toward the self during the sophomore year (B= -0.16, p= .04). However, perceptions that it was normative for Black and White students to socialize on campus (or positive association scores) were unrelated to psychological distress or self-acceptance. Findings highlight the relevance of examining multiple facets of campus racial climate in relation to psychological adjustment, with possible emphasis on the import of racial tension on African American women’s psychological adjustment. Results suggest that negative dimensions of campus racial climate may have lingering effects on psychological well-being, over and above more positive aspects of climate. Thus, programs targeted toward improving student relations on campus should consider addressing cross-racial tensions.

Keywords: higher education, psychological adjustment, university climate, university students

Procedia PDF Downloads 385

Authors: Michelle Mansfield

Abstract:

Introduction: This paper uses the work of Deleuze and Guattari to consider the street art practice of youth in the Indonesian city of Yogyakarta, a hub of arts and culture in Central Java. Around the world young people have taken to city streets to populate the new informal exhibition spaces outside the galleries of official art institutions. However, rarely is the focus outside the urban metropolis of the ‘Global North.' This paper looks at these practices in a ‘Global South’ Asian context. Space and place are concepts central to understanding youth cultural expression as it emerges on the streets. Deleuze and Guattari’s notion of assemblage enriches understanding of this complex spatial and creative relationship. Yogyakarta street art combines global patterns and motifs with local meanings, symbolism, and language to express local youth voices that convey a unique sense of place on the world stage. Street art has developed as a global urban youth art movement and is theorised as a way in which marginalised young people reclaim urban space for themselves. Methodologies: This study utilised a variety of qualitative methodologies to collect and analyse data. This project took a multi-method approach to data collection, incorporating the qualitative social research methods of ethnography, nongkrong (deep hanging out), participatory action research, online research, in-depth interviews and focus group discussions. Both interviews and focus groups employed photo-elicitation methodology to stimulate rich data gathering. To analyse collected data, rhizoanalytic approaches incorporating discourse analysis and visual analysis were utilised. Street art practice is a fluid and shifting phenomenon, adding to the complexity of inquiry sites. A qualitative approach to data collection and analysis was the most appropriate way to map the components of the street art assemblage and to draw out complexities of this youth cultural practice in Yogyakarta. Major Findings: The rhizoanalytic approach devised for this study proved a useful way of examining in the street art assemblage. It illustrated the ways in which the street art assemblage is constructed. Especially the interaction of inspiration, materials, creative techniques, audiences, and spaces operate in the creations of artworks. The study also exposed the generational tensions between the senior arts practitioners, the established art world, and the young artists. Conclusion: In summary, within the spatial processes of the city, street art is inextricably linked with its audience, its striving artistic community and everyday life in the smooth rather than the striated worlds of the state and the official art world. In this way, the anarchic rhizomatic art practice of nomadic urban street crews can be described not only as ‘becoming-artist’ but as constituting ‘nomos’, a way of arranging elements which are not dependent on a structured, hierarchical organisation practice. The site, streets, crews, neighbourhood and the passers by can all be examined with the concept of assemblage. The assemblage effectively brings into focus the complexity, dynamism, and flows of desire that is a feature of street art practice by young people in Yogyakarta.

Keywords: assemblage, Indonesia, street art, youth

Procedia PDF Downloads 182

Authors: Hadush Kidane Meresa

Abstract:

The hydrological extremes frequency analysis is the foundation for the hydraulic engineering design, flood protection, drought management and water resources management and planning to utilize the available water resource to meet the desired objectives of different organizations and sectors in a country. This spatial variation of the statistical characteristics of the extreme flood and drought events are key practice for regional flood and drought analysis and mitigation management. For different hydro-climate of the regions, where the data set is short, scarcity, poor quality and insufficient, the regionalization methods are applied to transfer at-site data to a region. This study aims in regional high and low flow frequency analysis for Poland River Basins. Due to high frequent occurring of hydrological extremes in the region and rapid water resources development in this basin have caused serious concerns over the flood and drought magnitude and frequencies of the river in Poland. The magnitude and frequency result of high and low flows in the basin is needed for flood and drought planning, management and protection at present and future. Hydrological homogeneous high and low flow regions are formed by the cluster analysis of site characteristics, using the hierarchical and C- mean clustering and PCA method. Statistical tests for regional homogeneity are utilized, by Discordancy and Heterogeneity measure tests. In compliance with results of the tests, the region river basin has been divided into ten homogeneous regions. In this study, frequency analysis of high and low flows using AM for high flow and 7-day minimum low flow series is conducted using six statistical distributions. The use of L-moment and LL-moment method showed a homogeneous region over entire province with Generalized logistic (GLOG), Generalized extreme value (GEV), Pearson type III (P-III), Generalized Pareto (GPAR), Weibull (WEI) and Power (PR) distributions as the regional drought and flood frequency distributions. The 95% percentile and Flow duration curves of 1, 7, 10, 30 days have been plotted for 10 stations. However, the cluster analysis performed two regions in west and east of the province where L-moment and LL-moment method demonstrated the homogeneity of the regions and GLOG and Pearson Type III (PIII) distributions as regional frequency distributions for each region, respectively. The spatial variation and regional frequency distribution of flood and drought characteristics for 10 best catchment from the whole region was selected and beside the main variable (streamflow: high and low) we used variables which are more related to physiographic and drainage characteristics for identify and delineate homogeneous pools and to derive best regression models for ungauged sites. Those are mean annual rainfall, seasonal flow, average slope, NDVI, aspect, flow length, flow direction, maximum soil moisture, elevation, and drainage order. The regional high-flow or low-flow relationship among one streamflow characteristics with (AM or 7-day mean annual low flows) some basin characteristics is developed using Generalized Linear Mixed Model (GLMM) and Generalized Least Square (GLS) regression model, providing a simple and effective method for estimation of flood and drought of desired return periods for ungauged catchments.

Keywords: flood , drought, frequency, magnitude, regionalization, stochastic, ungauged, Poland

Procedia PDF Downloads 602

Authors: T. Heiman, D. Olenik-Shemesh

Abstract:

Over the past decade, with the rapid growth of electronic communication, the internet and, in particular, social networking has become an inseparable part of people's daily lives. Along with its benefits, a new type of online aggression has emerged, defined as cyber bullying, a form of interpersonal aggressive behavior that takes place through electronic means. Cyber-bullying is characterized by repetitive behavior over time of maladaptive authority and power usage using computers and cell phones via sending insulting messages and hurtful pictures. Preliminary findings suggest that the prevalence of involvement in cyber-bullying among higher education students varies between 10 and 35%. As to date, universities are facing an uphill effort in trying to restrain online misbehavior. As no studies examined the relationships between cyber-bullying involvement with personal aspects, and its impacts on academic achievement and work functioning, this present study examined the nature of cyber-bullying involvement among 1,052 undergraduate students (mean age = 27.25, S.D = 4.81; 66.2% female), coping with, as well as the effects of social support, perceived self-efficacy, well-being, and body-perception, in relation to cyber-victimization. We assume that students in higher education are a vulnerable population and at high risk of being cyber-victims. We hypothesize that social support might serve as a protective factor and will moderate the relationships between the socio-emotional variables and the occurrence of cyber- victimization. The findings of this study will present the relationships between cyber-victimization and the social-emotional aspects, which constitute risk and protective factors. After receiving approval from the Ethics Committee of the University, a Google Drive questionnaire was sent to a random sample of students, studying in the various University study centers. Students' participation was voluntary, and they completed the five questionnaires anonymously: Cyber-bullying, perceived self-efficacy, subjective well-being, social support and body perception. Results revealed that 11.6% of the students reported being cyber-victims during last year. Examining the emotional and behavioral reactions to cyber-victimization revealed that female emotional and behavioral reactions were significantly greater than the male reactions (p < .001). Moreover, females reported on a significant higher social support compared to men; male reported significantly on a lower social capability than female; and men's body perception was significantly more positive than women's scores. No gender differences were observed for subjective well-being scale. Significant positive correlations were found between cyber-victimization and fewer friends, lower grades, and work ineffectiveness (r = 0.37- .40, p < 0 .001). The results of the Hierarchical regression indicated significantly that cyber-victimization can be predicted by lower social support, lower body perception, and gender (female), that explained 5.6% of the variance (R2 = 0.056, F(5,1047) = 12.47, p < 0.001). The findings deepen our understanding of the students' involvement in cyber-bullying, and present the relationships of the social-emotional and academic aspects on cyber-victim students. In view of our findings, higher education policy could help facilitate coping with cyber-bullying incidents, and student support units could develop intervention programs aimed at reducing cyber-bullying and its impacts.

Keywords: academic and personal factors, cyber-victimization, social support, higher education

Procedia PDF Downloads 289

Authors: Amine Ganibardi, Cherif Arab Ali

Abstract:

This paper addresses the data cleaning issue as a part of web usage data preprocessing within the scope of Web Usage Mining. Weblog data recorded by web servers within log files reflect usage activity, i.e., End-users’ clicks and underlying user-agents’ hits. As Web Usage Mining is interested in End-users’ behavior, user-agents’ hits are referred to as noise to be cleaned-off before mining. Filtering hits from clicks is not trivial for two reasons, i.e., a server records requests interlaced in sequential order regardless of their source or type, website resources may be set up as requestable interchangeably by end-users and user-agents. The current methods are content-centric based on filtering heuristics of relevant/irrelevant items in terms of some cleaning attributes, i.e., website’s resources filetype extensions, website’s resources pointed by hyperlinks/URIs, http methods, user-agents, etc. These methods need exhaustive extra-weblog data and prior knowledge on the relevant and/or irrelevant items to be assumed as clicks or hits within the filtering heuristics. Such methods are not appropriate for dynamic/responsive Web for three reasons, i.e., resources may be set up to as clickable by end-users regardless of their type, website’s resources are indexed by frame names without filetype extensions, web contents are generated and cancelled differently from an end-user to another. In order to overcome these constraints, a clustering-based cleaning method centered on the logging structure is proposed. This method focuses on the statistical properties of the logging structure at the requested and referring resources attributes levels. It is insensitive to logging content and does not need extra-weblog data. The used statistical property takes on the structure of the generated logging feature by webpage requests in terms of clicks and hits. Since a webpage consists of its single URI and several components, these feature results in a single click to multiple hits ratio in terms of the requested and referring resources. Thus, the clustering-based method is meant to identify two clusters based on the application of the appropriate distance to the frequency matrix of the requested and referring resources levels. As the ratio clicks to hits is single to multiple, the clicks’ cluster is the smallest one in requests number. Hierarchical Agglomerative Clustering based on a pairwise distance (Gower) and average linkage has been applied to four logfiles of dynamic/responsive websites whose click to hits ratio range from 1/2 to 1/15. The optimal clustering set on the basis of average linkage and maximum inter-cluster inertia results always in two clusters. The evaluation of the smallest cluster referred to as clicks cluster under the terms of confusion matrix indicators results in 97% of true positive rate. The content-centric cleaning methods, i.e., conventional and advanced cleaning, resulted in a lower rate 91%. Thus, the proposed clustering-based cleaning outperforms the content-centric methods within dynamic and responsive web design without the need of any extra-weblog. Such an improvement in cleaning quality is likely to refine dependent analysis.

Keywords: clustering approach, data cleaning, data preprocessing, weblog data, web usage data

Procedia PDF Downloads 170

Authors: I. Martinez-Conesa, E. Garcia-Meca, M. Barradas-Quiroz

Abstract:

The objective of this study is to assess the impact on earnings management of latest two Hofstede cultural dimensions: long-term orientation and indulgence. Long-term orientation represents the alignment of a society towards the future and indulgence expresses the extent to which a society exhibits willingness, or restrain, to realise their impulses. Additionally, this paper tests if there are relevant differences by testing the moderating role of the legal tradition, Continental versus Anglo-Saxon. Our sample comprises 15 countries: Belgium, Canada, Germany, Spain, France, Great Britain, Hong Kong, India, Japan, Korea, Netherlands, Philippines, Portugal, Sweden, and Thailand, with a total of 12,936 observations from 2003 to 2013. Our results show that managers in countries with high levels of long-term orientation reduce their levels of discretionary accruals. The findings do not confirm the effect of indulgence on earnings management. In addition, our results confirm previous literature regarding the effect of individualism, noting that firms in countries with high levels of collectivism might be more inclined to use earnings discretion to protect the welfare of the collective group of firm stakeholders. Uncertainty avoidance results in downwards earnings management as well as high disclosure, suggesting that less manipulation takes place when transparency is higher. Indulgence is the cultural dimension that confronts wellbeing versus survival; dimension is formulated including happiness, the perception of live control and the importance of leisure. Indulgence shows a weak negative correlation with power distance indicating a slight tendency for more hierarchical societies to be less indulgent. Anglo-Saxon countries are a positive effect of individualism and a negative effect of masculinity, uncertainty avoidance, and disclosure. With respect to continental countries, we can see a significant and positive effect of individualism and a significant and negative effect of masculinity, long-term orientation, and indulgence. Therefore, we observe the negative effect on earnings management provoked by higher disclosure and uncertainty avoidance only happens in Anglo-Saxon countries. Meanwhile, the improvement in reporting quality motivated by higher long-term orientation and higher indulgence is dominant in Continental countries. Our results confirm that there is a moderating effect of the legal system in the association between culture and earnings management. This effect is especially relevant in the dimensions related to uncertainty avoidance, long term orientation, indulgence, and disclosure. The negative effect of long-term orientation on earnings management only happens in those countries set in continental legal systems because of the Anglo-Saxon legal systems is supported by the decisions of the courts and the traditions, so it already has long-term orientation. That does not occur in continental systems, depending mainly of contend of the law. Sensitivity analysis used with Jones modified CP model, Jones Standard model and Jones Standard CP model confirm the robustness of these results. This paper collaborates towards a better understanding on how earnings management, culture and legal systems relate to each other, and contribute to previous literature by examining the influence of the two latest Hofstede’s dimensions not previously studied in papers.

Keywords: Hofstede, long-term-orientation, earnings management, indulgence

Procedia PDF Downloads 240

Authors: Phenphak Horadee, Rodchares Hanrinth, Saithip Suttiruksa

Abstract:

Inappropriate use of antibiotics has happened in several hospitals, Thailand. Drug use evaluation (DUE) is one strategy to overcome this difficulty. However, most community hospitals still encounter incomplete evaluation resulting overuse of antibiotics with high cost. Consequently, drug-resistant bacteria have been rising due to inappropriate antibiotic use. The aim of this study was to involve stakeholders in conceptualizing, developing, and prioritizing a feasible intervention strategy to promote and support appropriate antibiotic prescribing in a community hospital, Thailand. Study antibiotics included four antibiotics such as Meropenem, Piperacillin/tazobactam, Amoxicillin/clavulanic acid, and Vancomycin. The study was conducted for the 1-year period between March 1, 2018, and March 31, 2019, in a community hospital in the northeastern part of Thailand. Concept mapping was used in a purposive sample, including doctors (one was an administrator), pharmacists, and nurses who involving drug use evaluation of antibiotics. In-depth interviews for each participant and survey research were conducted to seek the problems for inappropriate use of antibiotics based on drug use evaluation system. Seventy-seven percent of DUE reported appropriate antibiotic prescribing, which still did not reach the goal of 80 percent appropriateness. Meropenem led other antibiotics for inappropriate prescribing. The causes of the unsuccessful DUE program were classified into three themes such as personnel, lack of public relation and communication, and unsupported policy and impractical regulations. During the first meeting, stakeholders (n = 21) expressed the generation of interventions. During the second meeting, participants who were almost the same group of people in the first meeting (n = 21) were requested to independently rate the feasibility and importance of each idea and to categorize them into relevant clusters to facilitate multidimensional scaling and hierarchical cluster analysis. The outputs of analysis included the idealist, cluster list, point map, point rating map, cluster map, and cluster rating map. All of these were distributed to participants (n = 21) during the third meeting to reach consensus on an intervention model. The final proposed intervention strategy included 29 feasible and crucial interventions in seven clusters: development of information technology system, establishing policy and taking it into the action plan, proactive public relations of the policy, action plan and workflow, in cooperation of multidisciplinary teams in drug use evaluation, work review and evaluation with performance reporting, promoting and developing professional and clinical skill for staff with training programs, and developing practical drug use evaluation guideline for antibiotics. These interventions are relevant and fit to several intervention strategies for antibiotic stewardship program in many international organizations such as participation of the multidisciplinary team, developing information technology to support antibiotic smart use, and communication. These interventions were prioritized for implementation over a 1-year period. Once the possibility of each activity or plan is set up, the proposed program could be applied and integrated into hospital policy after evaluating plans. Effectiveness of each intervention could be promoted to other community hospitals to promote and support antibiotic smart use.

Keywords: antibiotic, concept mapping, drug use evaluation, multidisciplinary teams

Procedia PDF Downloads 119

Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink

Abstract:

The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, Poland

Keywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway

Procedia PDF Downloads 419

Authors: Pomozova Kseniia, Gorlachev Gennadiy, Chernyaev Aleksandr, Golanov Andrey

Abstract:

In clinical practice, and especially in stereotactic radiosurgery planning, the significance of diffusion-weighted imaging (DWI) is growing. This makes the existence of software capable of quickly processing and reliably visualizing diffusion data, as well as equipped with tools for their analysis in terms of different tasks. We are developing the «MRDiffusionImaging» software on the standard C++ language. The subject part has been moved to separate class libraries and can be used on various platforms. The user interface is Windows WPF (Windows Presentation Foundation), which is a technology for managing Windows applications with access to all components of the .NET 5 or .NET Framework platform ecosystem. One of the important features is the use of a declarative markup language, XAML (eXtensible Application Markup Language), with which you can conveniently create, initialize and set properties of objects with hierarchical relationships. Graphics are generated using the DirectX environment. The MRDiffusionImaging software package has been implemented for processing diffusion magnetic resonance imaging (dMRI), which allows loading and viewing images sorted by series. An algorithm for "masking" dMRI series based on T2-weighted images was developed using a deformable surface model to exclude tissues that are not related to the area of interest from the analysis. An algorithm of distortion correction using deformable image registration based on autocorrelation of local structure has been developed. Maximum voxel dimension was 1,03 ± 0,12 mm. In an elementary brain's volume, the diffusion tensor is geometrically interpreted using an ellipsoid, which is an isosurface of the probability density of a molecule's diffusion. For the first time, non-parametric intensity distributions, neighborhood correlations, and inhomogeneities are combined in one segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) algorithm. A tool for calculating the coefficient of average diffusion and fractional anisotropy has been created, on the basis of which it is possible to build quantitative maps for solving various clinical problems. Functionality has been created that allows clustering and segmenting images to individualize the clinical volume of radiation treatment and further assess the response (Median Dice Score = 0.963 ± 0,137). White matter tracts of the brain were visualized using two algorithms: deterministic (fiber assignment by continuous tracking) and probabilistic using the Hough transform. The proposed algorithms test candidate curves in the voxel, assigning to each one a score computed from the diffusion data, and then selects the curves with the highest scores as the potential anatomical connections. White matter fibers were visualized using a Hough transform tractography algorithm. In the context of functional radiosurgery, it is possible to reduce the irradiation volume of the internal capsule receiving 12 Gy from 0,402 cc to 0,254 cc. The «MRDiffusionImaging» will improve the efficiency and accuracy of diagnostics and stereotactic radiotherapy of intracranial pathology. We develop software with integrated, intuitive support for processing, analysis, and inclusion in the process of radiotherapy planning and evaluating its results.

Keywords: diffusion-weighted imaging, medical imaging, stereotactic radiosurgery, tractography

Procedia PDF Downloads 85

Authors: M. Balordi, G. Santucci de Magistris, F. Pini, P. Marcacci

Abstract:

The increasing of extreme meteorological events represents the most important causes of damages and blackouts of the whole electric system. In particular, the icing on ground-wires and overheads lines, due to snowstorms or harsh winter conditions, very often gives rise to the collapse of cables and towers both in cold and warm climates. On the other hand, the high concentration of contaminants in the air, due to natural and/or antropic causes, is reflected in high levels of pollutants layered on glass and ceramic insulators, causing frequent and unpredictable flashover events. Overheads line and insulator failures lead to blackouts, dangerous and expensive maintenances and serious inefficiencies in the distribution service. Inducing superhydrophobic (SHP) properties to conductors, ground-wires and insulators, is one of the ways to face all these problems. Indeed, in some cases, the SHP surface can delay the ice nucleation time and decrease the ice nucleation temperature, preventing ice formation. Besides, thanks to the low surface energy, the adhesion force between ice and a superhydrophobic material are low and the ice can be easily detached from the surface. Moreover, it is well known that superhydrophobic surfaces can have self-cleaning properties: these hinder the deposition of pollution and decrease the probability of flashover phenomena. Here this study presents three different studies to impart superhydrophobicity to aluminum, zinc and glass specimens, which represent the main constituent materials of conductors, ground-wires and insulators, respectively. The route to impart the superhydrophobicity to the metallic surfaces can be summarized in a three-step process: 1) sandblasting treatment, 2) chemical-hydrothermal treatment and 3) coating deposition. The first step is required to create a micro-roughness. In the chemical-hydrothermal treatment a nano-scale metallic oxide (Al or Zn) is grown and, together with the sandblasting treatment, bring about a hierarchical micro-nano structure. By coating an alchilated or fluorinated siloxane coating, the surface energy decreases and gives rise to superhydrophobic surfaces. In order to functionalize the glass, different superhydrophobic powders, obtained by a sol-gel synthesis, were prepared. Further, the specimens were covered with a commercial primer and the powders were deposed on them. All the resulting metallic and glass surfaces showed a noticeable superhydrophobic behavior with a very high water contact angles (>150°) and a very low roll-off angles (<5°). The three optimized processes are fast, cheap and safe, and can be easily replicated on industrial scales. The anti-icing and self-cleaning properties of the surfaces were assessed with several indoor lab-tests that evidenced remarkable anti-icing properties and self-cleaning behavior with respect to the bare materials. Finally, to evaluate the anti-snow properties of the samples, some SHP specimens were exposed under real snow-fall events in the RSE outdoor test-facility located in Vinadio, western Alps: the coated samples delay the formation of the snow-sleeves and facilitate the detachment of the snow. The good results for both indoor and outdoor tests make these materials promising for further development in large scale applications.

Keywords: superhydrophobic coatings, anti-icing, self-cleaning, anti-snow, overheads lines

Procedia PDF Downloads 183

Authors: Camilo Cerda Sarabia, Fernanda Bravo Cornejo, Diego Santibanez Oyarce, Hugo Osses Prado, Esteban Gómez Terán, Belén Diaz Diaz, Raúl Caulier-Cisterna, Jorge Vergara-Quezada, Ana Moya-Beltrán

Abstract:

Antimicrobial resistance (AMR) represents a significant and rapidly escalating global health threat. Projections estimate that by 2050, AMR infections could claim up to 10 million lives annually. Respiratory infections, in particular, pose a severe risk not only to individual patients but also to the broader public health system. Despite the alarming rise in resistant respiratory infections, AMR within the lung microbiome (microbial community) remains underexplored and poorly characterized. The lungs, as a complex and dynamic microbial environment, host diverse communities of microorganisms whose interactions and resistance mechanisms are not fully understood. Unlike studies that focus on individual genomes, analyzing the entire microbiome provides a comprehensive perspective on microbial interactions, resistance gene transfer, and community dynamics, which are crucial for understanding AMR. However, this holistic approach introduces significant computational challenges and exposes the limitations of traditional analytical methods such as the difficulty of identifying the AMR. Machine learning has emerged as a powerful tool to overcome these challenges, offering the ability to analyze complex genomic data and uncover novel insights into AMR that might be overlooked by conventional approaches. This study investigates microbial resistance within the lung microbiome using unsupervised machine learning approaches to uncover resistance patterns and potential clinical associations. it downloaded and selected lung microbiome data from HumanMetagenomeDB based on metadata characteristics such as relevant clinical information, patient demographics, environmental factors, and sample collection methods. The metadata was further complemented by details on antibiotic usage, disease status, and other relevant descriptions. The sequencing data underwent stringent quality control, followed by a functional profiling focus on identifying resistance genes through specialized databases like Antibiotic Resistance Database (CARD) which contains sequences of AMR gene sequence and resistance profiles. Subsequent analyses employed unsupervised machine learning techniques to unravel the structure and diversity of resistomes in the microbial community. Some of the methods employed were clustering methods such as K-Means and Hierarchical Clustering enabled the identification of sample groups based on their resistance gene profiles. The work was implemented in python, leveraging a range of libraries such as biopython for biological sequence manipulation, NumPy for numerical operations, Scikit-learn for machine learning, Matplotlib for data visualization and Pandas for data manipulation. The findings from this study provide insights into the distribution and dynamics of antimicrobial resistance within the lung microbiome. By leveraging unsupervised machine learning, we identified novel resistance patterns and potential drivers within the microbial community.

Keywords: antibiotic resistance, microbial community, unsupervised machine learning., sequences of AMR gene

Procedia PDF Downloads 23

Authors: Natasa Ilic, Alisa Gruden-Movsesijan, Maja Kosanovic, Sofija Glamoclija, Marina Bekic, Ljiljana Sofronic-Milosavljevic, Sergej Tomic

Abstract:

As a very promising candidate for modulation of immune response in the sense of biasing the inflammatory towards an anti-inflammatory type of response, Trichinella spiralis infection was shown to successfully alleviate the severity of experimental autoimmune encephalomyelitis, the animal model of human disease multiple sclerosis. This effect is achieved via its excretory-secretory muscle larvae (ES L1) products which affect the maturation status and function of dendritic cells (DCs) by inducing the tolerogenic status of DCs, which leads to the mitigation of the Th1 type of response and the activation of a regulatory type of immune response both in vitro and in vivo. ES L1 alone or via treated DCs successfully mitigated EAE in the same manner as the infection itself. On the other hand, it has been shown that T. spiralis infection slows down the tumour growth and significantly reduces the tumour size in the model of mouse melanoma, while ES L1 possesses a pro-apoptotic and anti-survival effect on melanoma cells in vitro. Hence, although the mechanisms still need to be revealed, T. spiralis infection and its ES L1 products have a bit of controversial potential to modulate both inflammatory diseases and malignancies. The recent discovery of T. spiralis extracellular vesicles (TsEVs) suggested that the induction of complex regulation of the immune response requires simultaneous delivery of different signals in nano-sized packages. This study aimed to explore whether TsEVs bare the similar potential as ES L1 to influence the status of DCs in initiation, progression and regulation of immune response, but also to investigate the effect of both ES L1 and TsEVs on myeloid derived suppressor cells (MDSC) which present the regular tumour tissue environment. TsEVs were enriched from the conditioned medium of T. spiralis muscle larvae by differential centrifugation and used for the treatment of human monocyte-derived DCs and MDSC. On DCs, TsEVs induced low expression of HLA DR and CD40, moderate CD83 and CD86, and increased expression of ILT3 and CCR7 on treated DCs, i.e., they induced tolerogenic DCs. Such DCs possess the capacity to polarize T cell immune response towards regulatory type, with an increased proportion of IL-10 and TGF-β producing cells, similarly to ES L1. These findings indicated that the ability of TsEVs to induce tolerogenic DCs favoring anti-inflammatory responses may be helpful in coping with diseases that involve Th1/Th17-, but also Th2-mediated inflammation. In MDSC in vitro model, although both ES L1 and TsEVs had the same impact on MDSC phenotype i.e., they acted suppressive, ES L1 treated MDSC, unlike TsEVs treated ones, induced T cell response characterized by the increased RoRγT and IFN-γ, while the proportion of regulatory cells was decreased followed by the decrease in IL-10 and TGF-β positive cells proportion within this population. These findings indicate the interesting ability of ES L1 to modulate T cells response via MDSC towards pro-inflamatory type, suggesting that, unlike TsEVs which consistently demonstrate the suppresive effect on inflammatory response, it could be used also for the development of new approaches aimed for the treatment of malignant diseases. Acknowledgment: This work was funded by the Promis project – Nano-MDCS-Thera, Science Fund, Republic of Serbia.

Keywords: dendritic cells, myeloid derived suppressor cells, immunomodulation, Trichinella spiralis

Procedia PDF Downloads 204

Authors: Thanthrige Thiunuwan Priyathilaka, Don Anushka Sandaruwan Elvitigala, Bong-Soo Lim, Hyung-Bok Jeong, Jehee Lee

Abstract:

Toll like receptors (TLRs) are a phylogeneticaly conserved family of pattern recognition receptors, which participates in the host immune responses against various pathogens and pathogen derived mitogen. TLR21, a non-mammalian type, is almost restricted to the fish species even though those can be identified rarely in avians and amphibians. Herein, this study was carried out to identify and characterize TLR21 from rock bream (Oplegnathus fasciatus) designated as RbTLR21, at transcriptional and genomic level. In this study, the full length cDNA and genomic sequence of RbTLR21 was identified using previously constructed cDNA sequence database and BAC library, respectively. Identified RbTLR21 sequence was characterized using several bioinformatics tools. The quantitative real time PCR (qPCR) experiment was conducted to determine tissue specific expressional distribution of RbTLR21. Further, transcriptional modulation of RbTLR21 upon the stimulation with Streptococcus iniae (S. iniae), rock bream iridovirus (RBIV) and Edwardsiella tarda (E. tarda) was analyzed in spleen tissues. The complete coding sequence of RbTLR21 was 2919 bp in length which can encode a protein consisting of 973 amino acid residues with molecular mass of 112 kDa and theoretical isoelectric point of 8.6. The anticipated protein sequence resembled a typical TLR domain architecture including C-terminal ectodomain with 16 leucine rich repeats, a transmembrane domain, cytoplasmic TIR domain and signal peptide with 23 amino acid residues. Moreover, protein folding pattern prediction of RbTLR21 exhibited well-structured and folded ectodomain, transmembrane domain and cytoplasmc TIR domain. According to the pair wise sequence analysis data, RbTLR21 showed closest homology with orange-spotted grouper (Epinephelus coioides) TLR21with 76.9% amino acid identity. Furthermore, our phylogenetic analysis revealed that RbTLR21 shows a close evolutionary relationship with its ortholog from Danio rerio. Genomic structure of RbTLR21 consisted of single exon similar to its ortholog of zebra fish. Sevaral putative transcription factor binding sites were also identified in 5ʹ flanking region of RbTLR21. The RBTLR 21 was ubiquitously expressed in all the tissues we tested. Relatively, high expression levels were found in spleen, liver and blood tissues. Upon induction with rock bream iridovirus, RbTLR21 expression was upregulated at the early phase of post induction period even though RbTLR21 expression level was fluctuated at the latter phase of post induction period. Post Edwardsiella tarda injection, RbTLR transcripts were upregulated throughout the experiment. Similarly, Streptococcus iniae induction exhibited significant upregulations of RbTLR21 mRNA expression in the spleen tissues. Collectively, our findings suggest that RbTLR21 is indeed a homolog of TLR21 family members and RbTLR21 may be involved in host immune responses against bacterial and DNA viral infections.

Keywords: rock bream, toll like receptor 21 (TLR21), pattern recognition receptor, genomic characterization

Procedia PDF Downloads 541

Authors: Roland F. Karthaus, Rachel S. O'Brien

Abstract:

Over the past decade, the authors have undertaken applied research aimed at enabling transformation within the prison service to improve conditions and outcomes for those living, working and visiting in prisons in the UK and the communities they serve. The research has taken place against a context of reducing resources and public discontent at increasing levels of violence, deteriorating conditions and persistently high levels of re-offending. Top-down governmental policies have mainly been ineffectual and in some cases counter-productive. The prison service is characterised by hierarchical organisation, and the research has applied design thinking at multiple levels to challenge and precipitate change: top-down, middle-out and bottom-up. The research employs three distinct but related approaches, system design (top-down): working at the national policy level to analyse the changing policy context, identifying opportunities and challenges; engaging with the Ministry of Justice commissioners and sector organisations to facilitate debate, introducing new evidence and provoking creative thinking, place-based design (middle-out): working with individual prison establishments as pilots to illustrate and test the potential for local empowerment, creative change, and improved architecture within place-specific contexts and organisational hierarchies, everyday design (bottom-up): working with individuals in the system to explore the potential for localised, significant, demonstrator changes; including collaborative design, capacity building and empowerment in skills, employment, communication, training, and other activities. The research spans a series of projects, through which the methodological approach has developed responsively. The projects include a place-based model for the re-purposing of Ministry of Justice land assets for the purposes of rehabilitation; an evidence-based guide to improve prison design for health and well-being; capacity-based employment, skills and self-build project as a template for future open prisons. The overarching research has enabled knowledge to be developed and disseminated through policy and academic networks. Whilst the research remains live and continuing; key findings are emerging as a basis for a new methodological approach to effecting change in the UK prison service. An interdisciplinary approach is necessary to overcome the barriers between distinct areas of the prison service. Sometimes referred to as total environments, prisons encompass entire social and physical environments which themselves are orchestrated by institutional arms of government, resulting in complex systems that cannot be meaningfully engaged through narrow disciplinary lenses. A scalar approach is necessary to connect strategic policies with individual experiences and potential, through the medium of individual prison establishments, operating as discrete entities within the system. A reflexive process is necessary to connect research with action in a responsive mode, learning to adapt as the system itself is changing. The role of individuals in the system, their latent knowledge and experience and their ability to engage and become agents of change are essential. Whilst the specific characteristics of the UK prison system are unique, the approach is internationally applicable.

Keywords: architecture, design, policy, prison, system, transformation

Procedia PDF Downloads 133

Authors: Yong H Sheng, Beatriz Garcillán, Eden Whitlock, Yukli Freedman, SiLing Yang, M Arifur Rahman, Nicholas Weber, Fabienne Mackay

Abstract:

Chronic lymphocytic leukemia (CLL) is closely associated with immune dysfunction, yet the mechanisms underlying this immune deficiency remain poorly understood. Transmembrane Activator and CAML Interactor (TACI), a receptor known for its role in IL-10 regulation and autoimmunity, to the best of our knowledge has not been investigated in the context of anti-tumor immunity or its impact on CLL progression. This study addresses the gap by exploring the role of TACI in regulating CLL cells within the tumor microenvironment and its broader effects on disease progression and immune competence. We utilized the Eµ-TCL1 mouse model to generate CLL mice deficient in TACI and examined the consequences of TACI loss in adoptive transfer models over a five-week period. Comprehensive transcriptomic analysis, including RNA sequencing and microarray, was employed to determine TACI’s influence on the CLL gene expression profile. Additionally, we studied TACI’s direct role in CLL cell migration and immune modulation using patient-derived CLL cells in culture and Patient-Derived Xenograph (PDX) models. Our findings demonstrate that TACI signaling plays a pivotal role in promoting CLL progression and immune suppression. Loss of TACI signaling significantly inhibited CLL development and enhanced immune functionality. When TACI+/+ or TACI-/- TCL1 CLL cells were transferred into wild-type recipient mice, those receiving TACI-deficient cells showed reduced disease progression and lower incidence of CLL. Mice with TACI-/- CLL cells exhibited normalized serum levels of pro-inflammatory cytokines IL-6 and IL-10, restored proportions of T-cell subsets, and improved immune compartment function compared to counterparts with TACI+/+ CLL cells. Mechanistically, TACI-deficient CLL cells expressed significantly lower levels of IL-10, TNF, and inhibitory receptors such as PD-L1 and PD-L2. These cells also display restored circulating immunoglobulin levels and responses to T cell-dependent antigens, highlighting a recovery of immune competence. Further mechanistic studies revealed that TACI signaling drives CLL cell migration and homing to the spleen, where these cells actively establish an immunosuppressive microenvironment that supports immune evasion and tumor growth. Patient-derived CLL cells and PDX models confirmed TACI’s direct role in enhancing CLL cell migration and fostering immune suppression, emphasizing its critical function in the tumor microenvironment. By disrupting TACI signaling, we observed a reduction in CLL-associated immune suppression and tumor progression, offering a promising therapeutic avenue. This study establishes, for the first time, that targeting TACI disrupts key mechanisms underlying CLL progression while preserving vital immune functions. Unlike existing treatments that often impair immunity and lead to infection-related complications, TACI inhibition offers the dual benefit of controlling disease and maintaining immune homeostasis. These findings provide a strong rationale for developing therapeutic strategies that inhibit TACI as a means to improve outcomes in CLL patients. Beyond its implications for CLL, this research underscores the broader importance of TACI in regulating immune-tumor interactions, paving the way for future studies into its role in other malignancies.

Keywords: chronic lymphocytic leukemia, TACI, IL-10, immune suppression

Procedia PDF Downloads 5

Authors: Przemysław Adamczyk, Mirosław Wyczesany, Aleksandra Domagalik, Artur Daren, Kamil Cepuch, Piotr Błądziński, Tadeusz Marek, Andrzej Cechnicki

Abstract:

The present study aimed at evaluation of neural correlates of humor comprehension impairments observed in schizophrenia. To investigate the nature of this deficit in schizophrenia and to localize cortical areas involved in humor processing we used functional magnetic resonance imaging (fMRI). The study included chronic schizophrenia outpatients (SCH; n=20), and sex, age and education level matched healthy controls (n=20). The task consisted of 60 stories (setup) of which 20 had funny, 20 nonsensical and 20 neutral (not funny) punchlines. After the punchlines were presented, the participants were asked to indicate whether the story was comprehensible (yes/no) and how funny it was (1-9 Likert-type scale). fMRI was performed on a 3T scanner (Magnetom Skyra, Siemens) using 32-channel head coil. Three contrasts in accordance with the three stages of humor processing were analyzed in both groups: abstract vs neutral stories - incongruity detection; funny vs abstract - incongruity resolution; funny vs neutral - elaboration. Additionally, parametric modulation analysis was performed using both subjective ratings separately in order to further differentiate the areas involved in incongruity resolution processing. Statistical analysis for behavioral data used U Mann-Whitney test and Bonferroni’s correction, fMRI data analysis utilized whole-brain voxel-wise t-tests with 10-voxel extent threshold and with Family Wise Error (FWE) correction at alpha = 0.05, or uncorrected at alpha = 0.001. Between group comparisons revealed that the SCH subjects had attenuated activation in: the right superior temporal gyrus in case of irresolvable incongruity processing of nonsensical puns (nonsensical > neutral); the left medial frontal gyrus in case of incongruity resolution processing of funny puns (funny > nonsensical) and the interhemispheric ACC in case of elaboration of funny puns (funny > neutral). Additionally, the SCH group revealed weaker activation during funniness ratings in the left ventro-medial prefrontal cortex, the medial frontal gyrus, the angular and the supramarginal gyrus, and the right temporal pole. In comprehension ratings the SCH group showed suppressed activity in the left superior and medial frontal gyri. Interestingly, these differences were accompanied by protraction of time in both types of rating responses in the SCH group, a lower level of comprehension for funny punchlines and a higher funniness for absurd punchlines. Presented results indicate that, in comparison to healthy controls, schizophrenia is characterized by difficulties in humor processing revealed by longer reaction times, impairments of understanding jokes and finding nonsensical punchlines more funny. This is accompanied by attenuated brain activations, especially in the left fronto-parietal and the right temporal cortices. Disturbances of the humor processing seem to be impaired at the all three stages of the humor comprehension process, from incongruity detection, through its resolution to elaboration. The neural correlates revealed diminished neural activity of the schizophrenia brain, as compared with the control group. The study was supported by the National Science Centre, Poland (grant no 2014/13/B/HS6/03091).

Keywords: communication skills, functional magnetic resonance imaging, humor, schizophrenia

Procedia PDF Downloads 213

Authors: Vijayalaxmi Khopade

Abstract:

The Prima facie caste system is intrinsic to Indian society. It is an ancient system of intense social stratification based upon birth and enjoying religious sanction. The uppermost strata and privileges are ascribed and enjoyed by brahmins (priestly class), while the lowest strata are occupied by Dalits who are not ascribed with any privileges. The caste system is inherently hierarchical, patriarchal, and systematic and thrives solely on exploitation justified through means of the Brahminical system of hegemony based singularly on birth. The caste system has extended its tentacles to other religions like Christianity, Buddhism, Jainism, and Islam in South Asia. Term Dalit is colloquially used to categorize persons belonging to lower strata in the caste hierarchy. However, this category is heterogenous and highly stratified, following practices like untouchability and exclusion amongst themselves. The modern Indian legal system acknowledges the existence of Caste and its perils. Therefore, by virtue of the Indian Constitution, provisions for affirmative action for the protection and development of Dalits are made. Courts in India have liberally interpreted laws to benefit Dalits. However, the modern system of governance is not immune from Caste based biases. These biases are reflected in the implementation of governance, including the dispensation of justice. The economic reforms of the 1990s gave a huge boost to the Indian diaspora. Persons of Indian origin are now seen making great strides in almost every sector and enjoying positions of power globally. As one peels off the layer of ethnic Indian origin, a deep seated layer of Caste and Caste based patriarchy is clearly visible. Indian diaspora enjoying positions of power essentially belongs to upper castes and carry Caste based biases with them. These castes have long enjoyed the benefits of education; therefore, they were the first ones to benefit from LPG (Liberalization, Privatization, Globalization) model adopted in the 1990s. Dalits, however, had little formal education until recently. The western legal system, to the best of our knowledge, does not recognize Caste and, therefore, cannot afford protection for Dalits, wherein discrimination and exploitation take place solely on the basis of Caste. Therefore, Dalits are left with no legal remedy outside domestic jurisdiction. Countries like the UK have made an attempt to include Caste in their Equality Bill 2010. This has met with tough resistance from Upper caste Hindus who shy away from recognizing their caste privileges and, therefore, the existence of Caste. In this paper, an attempt for comparative analysis is made between various legal protections accorded to Dalits in India vis-à-vis international human rights as protected by the United Nations under its declaration of Universal Human rights. An attempt has been made to mark a distinction between race and Caste and to establish a position of women in Caste based hierarchy. The paper also makes an argument for the inclusion of atrocities committed against Dalits as a violation of international human rights, their protection by the United Nations, and the trial of their violations by International Courts. The paper puts into perspective the need for an external agency like the United Nations and International courts to interfere in rights guaranteed by the Indian Constitution, even with the existence of a modern legal system in a sovereign democratic country.

Keywords: atrocity, caste, diaspora, legal framework

Procedia PDF Downloads 215