Search results for: transcription regulation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1664

Search results for: transcription regulation

1184 Determination Optimum Strike Price of FX Option Call Spread with USD/IDR Volatility and Garman–Kohlhagen Model Analysis

Authors: Bangkit Adhi Nugraha, Bambang Suripto

Abstract:

On September 2016 Bank Indonesia (BI) release regulation no.18/18/PBI/2016 that permit bank clients for using the FX option call spread USD/IDR. Basically, this product is a combination between clients buy FX call option (pay premium) and sell FX call option (receive premium) to protect against currency depreciation while also capping the potential upside with cheap premium cost. BI classifies this product as a structured product. The structured product is combination at least two financial instruments, either derivative or non-derivative instruments. The call spread is the first structured product against IDR permitted by BI since 2009 as response the demand increase from Indonesia firms on FX hedging through derivative for protecting market risk their foreign currency asset or liability. The composition of hedging products on Indonesian FX market increase from 35% on 2015 to 40% on 2016, the majority on swap product (FX forward, FX swap, cross currency swap). Swap is formulated by interest rate difference of the two currency pairs. The cost of swap product is 7% for USD/IDR with one year USD/IDR volatility 13%. That cost level makes swap products seem expensive for hedging buyers. Because call spread cost (around 1.5-3%) cheaper than swap, the most Indonesian firms are using NDF FX call spread USD/IDR on offshore with outstanding amount around 10 billion USD. The cheaper cost of call spread is the main advantage for hedging buyers. The problem arises because BI regulation requires the call spread buyer doing the dynamic hedging. That means, if call spread buyer choose strike price 1 and strike price 2 and volatility USD/IDR exchange rate surpass strike price 2, then the call spread buyer must buy another call spread with strike price 1’ (strike price 1’ = strike price 2) and strike price 2’ (strike price 2’ > strike price 1‘). It could make the premium cost of call spread doubled or even more and dismiss the purpose of hedging buyer to find the cheapest hedging cost. It is very crucial for the buyer to choose best optimum strike price before entering into the transaction. To help hedging buyer find the optimum strike price and avoid expensive multiple premium cost, we observe ten years 2005-2015 historical data of USD/IDR volatility to be compared with the price movement of the call spread USD/IDR using Garman–Kohlhagen Model (as a common formula on FX option pricing). We use statistical tools to analysis data correlation, understand nature of call spread price movement over ten years, and determine factors affecting price movement. We select some range of strike price and tenor and calculate the probability of dynamic hedging to occur and how much it’s cost. We found USD/IDR currency pairs is too uncertain and make dynamic hedging riskier and more expensive. We validated this result using one year data and shown small RMS. The study result could be used to understand nature of FX call spread and determine optimum strike price for hedging plan.

Keywords: FX call spread USD/IDR, USD/IDR volatility statistical analysis, Garman–Kohlhagen Model on FX Option USD/IDR, Bank Indonesia Regulation no.18/18/PBI/2016

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1183 The Transformation of Beauty and Ugliness in Art Aesthetics

Authors: Wenjin Li, Jing Sun

Abstract:

Since the mid-eighteenth century, when philosophers began to talk about aesthetic consciousness, beauty gradually became an independent system, and ugliness was often considered the opposite of beauty and neglected. Yet, ugliness itself has its self-regulation and aesthetic value. This paper explores the relationship between beauty and ugliness and the three forms of transformation between beauty and ugliness in artworks, looking at the history of ugliness in the East and the West, and giving an insight into the role of the artist in the transformation between beauty and ugliness.

Keywords: artistic aesthetics, arts theory, aesthetic of the ugly, beauty and ugliness, arts of east and west

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1182 New Roles of Telomerase and Telomere-Associated Proteins in the Regulation of Telomere Length

Authors: Qin Yang, Fan Zhang, Juan Du, Chongkui Sun, Krishna Kota, Yun-Ling Zheng

Abstract:

Telomeres are specialized structures at chromosome ends consisting of tandem repetitive DNA sequences [(TTAGGG)n in humans] and associated proteins, which are necessary for telomere function. Telomere lengths are tightly regulated within a narrow range in normal human somatic cells, the basis of cellular senescence and aging. Previous studies have extensively focused on how short telomeres are extended and have demonstrated that telomerase plays a central role in telomere maintenance through elongating the short telomeres. However, the molecular mechanisms of regulating excessively long telomeres are unknown. Here, we found that telomerase enzymatic component hTERT plays a dual role in the regulation of telomeres length. We analyzed single telomere alterations at each chromosomal end led to the discoveries that hTERT shortens excessively long telomeres and elongates short telomeres simultaneously, thus maintaining the optimal telomere length at each chromosomal end for an efficient protection. The hTERT-mediated telomere shortening removes large segments of telomere DNA rapidly without inducing telomere dysfunction foci or affecting cell proliferation, thus it is mechanistically distinct from rapid telomere deletion. We found that expression of hTERT generates telomeric circular DNA, suggesting that telomere homologous recombination may be involved in this telomere shortening process. Moreover, the hTERT-mediated telomere shortening is required its enzymatic activity, but telomerase RNA component hTR is not involved in it. Furthermore, shelterin protein TPP1 interacts with hTERT and recruits it on telomeres to mediate telomere shortening. In addition, telomere-associated proteins, DKC1 and TCAB1 also play roles in this process. This novel hTERT-mediated telomere shortening mechanism not only exists in cancer cells, but also in primary human cells. Thus, the hTERT-mediated telomere shortening is expected to shift the paradigm on current molecular models of telomere length maintenance, with wide-reaching consequences in cancer and aging fields.

Keywords: aging, hTERT, telomerase, telomeres, human cells

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1181 Changes in Forest Cover Regulate Streamflow in Central Nigerian Gallery Forests

Authors: Rahila Yilangai, Sonali Saha, Amartya Saha, Augustine Ezealor

Abstract:

Gallery forests in sub-Saharan Africa are drastically disappearing due to intensive anthropogenic activities thus reducing ecosystem services, one of which is water provisioning. The role played by forest cover in regulating streamflow and water yield is not well understood, especially in West Africa. This pioneering 2-year study investigated the interrelationships between plant cover and hydrology in protected and unprotected gallery forests. Rainfall, streamflow, and evapotranspiration (ET) measurements/estimates over 2015-2016 were obtained to form a water balance for both catchments. In addition, transpiration in the protected gallery forest with high vegetation cover was calculated from stomatal conductance readings of selected species chosen from plot level data of plant diversity and abundance. Results showed that annual streamflow was significantly higher in the unprotected site than the protected site, even when normalized by catchment area. However, streamflow commenced earlier and lasted longer in the protected site than the degraded unprotected site, suggesting regulation by the greater tree density in the protected site. Streamflow correlated strongly with rainfall with the highest peak in August. As expected, transpiration measurements were less than potential evapotranspiration estimates, while rainfall exceeded ET in the water cycle. The water balance partitioning suggests that the lower vegetation cover in the unprotected catchment leads to a larger runoff in the rainy season and less infiltration, thereby leading to streams drying up earlier, than in the protected catchment. This baseline information is important in understanding the contribution of plants in water cycle regulation, for modeling integrative water management in applied research and natural resource management in sustaining water resources with changing the land cover and climate uncertainties in this data-poor region.

Keywords: evapotranspiration, gallery forest, rainfall, streamflow, transpiration

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1180 Synergism in the Inquiry Lab: An Analysis of Time Targets and Achievement

Authors: John M. Basey, Clinton D. Francis, Maxwell B. Joseph

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After gathering data from experimental procedures, inquiry-oriented-science labs often allow students the freedom to stay and complete the write up in class or leave lab early and complete the write up later. Teachers must decide whether to allow students this freedom to self-regulate this time. Student interviews have indicated four time-target strategies that may influence how students utilize this time: grade-target-A, grade-target-C, time-limited, and proficiency. The hypothesis tested was that variability in class composition relative to the four grade-target strategies has an impact on when students leave class, which in turn may influence their overall learning as exemplified by grades. Students were divided into the four indicated groups with a survey. Class composition and the GTA teaching the class had significant impacts on how long students stayed in class with class composition having the greatest impact. A factor analysis identified two factors. Factor 1 included classes with percentages of grade-target students opposite time-limited/proficiency students and explained 43% of the variance. Factor 2 included classes with percentages of grade-target-A/proficiency students opposite grade-target-C students and explained 33% of the variance. Students who stayed longer received significantly higher grades (P = 0.008) with no significant relationships between grade and Factor 1 or Factor 2 (P > 0.05). The time students stayed in class was significantly positively related to Factor 1 (P = 0.006) and significantly negatively related to Factor 2 (P = 0.008). These results support the hypothesis and indicate that teachers may want to know the composition of student-target strategies before deciding on how to have students allocate study time at the end of inquiry-oriented labs. According to these results, ideal classes for self-regulation have a high proportion of proficiency and time-limited students and a low proportion of grade-target students, or a high proportion of grade-target-A and proficiency students and a low proportion of grade-target-C students. Non-ideal classes for self-regulation were comprised of the inverse proportions.

Keywords: grades, inquiry lab design, synergism in student motivation, class composition

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1179 Military Leadership: Emotion Culture and Emotion Coping in Morally Stressful Situations

Authors: Sofia Nilsson, Alicia Ohlsson, Linda-Marie Lundqvist, Aida Alvinius, Peder Hyllengren, Gerry Larsson

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In irregular warfare contexts, military personnel are often presented with morally ambiguous situations where they are aware of the morally correct choice but may feel prevented to follow through with it due to organizational demands. Moral stress and/or injury can be the outcome of the individual’s experienced dissonance. These types of challenges put a large demand on the individual to manage their own emotions and the emotions of others, particularly in the case of a leader. Both the ability and inability for emotional regulation can result in different combinations of short and long term reactions after morally stressful events, which can be either positive or negative. Our study analyzed the combination of these reactions based upon the types of morally challenging events that were described by the subjects. 1)What institutionalized norms concerning emotion regulation are favorable in short-and long-term perspectives after a morally stressful event? 2)What individual emotion-focused coping strategies are favorable in short-and long-perspectives after a morally stressful? To address these questions, we conducted a quantitative study in military contexts in Sweden and Norway on upcoming or current military officers (n=331). We tested a theoretical model built upon a recently developed qualitative study. The data was analyzed using factor analysis, multiple regression analysis and subgroup analyses. The results indicated that an individual’s restriction of emotion in order to achieve an organizational goal, which results in emotional dissonance, can be an effective short term strategy for both the individual and the organization; however, it appears to be unfavorable in a long-term perspective which can result in negative reactions. Our results are intriguing because they showed an increased percentage of reported negative long term reactions (13%), which indicated PTSD-related symptoms in comparison to previous Swedish studies which indicated lower PTSD symptomology.

Keywords: emotion culture, emotion coping, emotion management, military

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1178 Learning from the Positive to Encourage Compliance with Workplace Health and Safety

Authors: Amy Williamson, Kerry Armstrong, Jason Edwards, Patricia Obst

Abstract:

Australian national policy endorses a responsive approach to work health and safety (WHS) regulation, combining positive motivators (education and guidance), with compliance monitoring and enforcement to encourage and secure compliance with legislation. Despite theoretical support for responsive regulation, there is limited evidence regarding how to achieve best results in practice. Using positive psychology as a novel paradigm, this study aims to investigate how non-punitive regulatory interactions can be improved to further encourage regulatory compliance in the construction industry. As part of a larger project, semi-structured interviews were conducted with 35 inspectorate staff and 11 managers in the Australian (Queensland) construction industry. Using an inductive, grounded approach, an in-depth qualitative investigation was conducted to identify the positive psychological principles which underpin effective use of the non-punitive aspects of responsive regulation. Results highlighted the importance of effective engagement between inspectors and industry managers. This involved the need to interact cooperatively and encourage compliance with WHS legislation. Several strategies were identified that assisted regulatory interactions and the ability of inspectors to engage. The importance of communication and interpersonal skills was reported to be critical to any interaction, regardless of the nature of the visit and regulatory tools used. In particular, the use of clear and open communication fostered trust and rapport which facilitated more positive interactions. The importance of respect and empathy was also highlighted. The need for provision of guidance and direction on how to achieve compliance was also reported. This related to ensuring companies understand their WHS obligations, providing specific advice regarding how to rectify a breach and meet compliance requirements, and ensuring sufficient follow up to confirm that compliance is successfully achieved. In the absence of imminent risk, allowing companies the opportunity to comply before further action is taken was also highlighted. Increased proactive engagement with industry to educate and promote the vision of safety at work was also reported. Finally, provision of praise and positive feedback was reported to assist interactions and encourage the continuation of good practices. Evidence from positive psychology and organisational psychology was obtained to support the use of each strategy in practice. In particular, the area of positive leadership provided a useful framework to consider the factors and conditions that drive positive interactions within the context of work health and safety and the specific relationship between inspectors and industry managers. This study provides fresh insight into key psychological principles which support non-punitive regulatory interactions in the area of workplace health and safety. The findings of this research contribute to a better understanding of how inspectors can enhance the efficacy of their regulatory interactions to improve compliance with legislation. Encouraging and assisting compliance through effective non-punitive activity offers a sustainable pathway for promoting safety and preventing fatalities and injuries in the construction industry.

Keywords: engagement, non-punitive approaches to compliance, positive interactions in the workplace, work health and safety compliance

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1177 VIAN-DH: Computational Multimodal Conversation Analysis Software and Infrastructure

Authors: Teodora Vukovic, Christoph Hottiger, Noah Bubenhofer

Abstract:

The development of VIAN-DH aims at bridging two linguistic approaches: conversation analysis/interactional linguistics (IL), so far a dominantly qualitative field, and computational/corpus linguistics and its quantitative and automated methods. Contemporary IL investigates the systematic organization of conversations and interactions composed of speech, gaze, gestures, and body positioning, among others. These highly integrated multimodal behaviour is analysed based on video data aimed at uncovering so called “multimodal gestalts”, patterns of linguistic and embodied conduct that reoccur in specific sequential positions employed for specific purposes. Multimodal analyses (and other disciplines using videos) are so far dependent on time and resource intensive processes of manual transcription of each component from video materials. Automating these tasks requires advanced programming skills, which is often not in the scope of IL. Moreover, the use of different tools makes the integration and analysis of different formats challenging. Consequently, IL research often deals with relatively small samples of annotated data which are suitable for qualitative analysis but not enough for making generalized empirical claims derived quantitatively. VIAN-DH aims to create a workspace where many annotation layers required for the multimodal analysis of videos can be created, processed, and correlated in one platform. VIAN-DH will provide a graphical interface that operates state-of-the-art tools for automating parts of the data processing. The integration of tools that already exist in computational linguistics and computer vision, facilitates data processing for researchers lacking programming skills, speeds up the overall research process, and enables the processing of large amounts of data. The main features to be introduced are automatic speech recognition for the transcription of language, automatic image recognition for extraction of gestures and other visual cues, as well as grammatical annotation for adding morphological and syntactic information to the verbal content. In the ongoing instance of VIAN-DH, we focus on gesture extraction (pointing gestures, in particular), making use of existing models created for sign language and adapting them for this specific purpose. In order to view and search the data, VIAN-DH will provide a unified format and enable the import of the main existing formats of annotated video data and the export to other formats used in the field, while integrating different data source formats in a way that they can be combined in research. VIAN-DH will adapt querying methods from corpus linguistics to enable parallel search of many annotation levels, combining token-level and chronological search for various types of data. VIAN-DH strives to bring crucial and potentially revolutionary innovation to the field of IL, (that can also extend to other fields using video materials). It will allow the processing of large amounts of data automatically and, the implementation of quantitative analyses, combining it with the qualitative approach. It will facilitate the investigation of correlations between linguistic patterns (lexical or grammatical) with conversational aspects (turn-taking or gestures). Users will be able to automatically transcribe and annotate visual, spoken and grammatical information from videos, and to correlate those different levels and perform queries and analyses.

Keywords: multimodal analysis, corpus linguistics, computational linguistics, image recognition, speech recognition

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1176 Genetics, Law and Society: Regulating New Genetic Technologies

Authors: Aisling De Paor

Abstract:

Scientific and technological developments are driving genetics and genetic technologies into the public sphere. Scientists are making genetic discoveries as to the make up of the human body and the cause and effect of disease, diversity and disability amongst individuals. Technological innovation in the field of genetics is also advancing, with the development of genetic testing, and other emerging genetic technologies, including gene editing (which offers the potential for genetic modification). In addition to the benefits for medicine, health care and humanity, these genetic advances raise a range of ethical, legal and societal concerns. From an ethical perspective, such advances may, for example, change the concept of humans and what it means to be human. Science may take over in conceptualising human beings, which may push the boundaries of existing human rights. New genetic technologies, particularly gene editing techniques create the potential to stigmatise disability, by highlighting disability or genetic difference as something that should be eliminated or anticipated. From a disability perspective, use (and misuse) of genetic technologies raise concerns about discrimination and violations to the dignity and integrity of the individual. With an acknowledgement of the likely future orientation of genetic science, and in consideration of the intersection of genetics and disability, this paper highlights the main concerns raised as genetic science and technology advances (particularly with gene editing developments), and the consequences for disability and human rights. Through the use of traditional doctrinal legal methodologies, it investigates the use (and potential misuse) of gene editing as creating the potential for a unique form of discrimination and stigmatization to develop, as well as a potential gateway to a form of new, subtle eugenics. This article highlights the need to maintain caution as to the use, application and the consequences of genetic technologies. With a focus on the law and policy position in Europe, it examines the need to control and regulate these new technologies, particularly gene editing. In addition to considering the need for regulation, this paper highlights non-normative approaches to address this area, including awareness raising and education, public discussion and engagement with key stakeholders in the field and the development of a multifaceted genetics advisory network.

Keywords: disability, gene-editing, genetics, law, regulation

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1175 Trajectory Optimization for Autonomous Deep Space Missions

Authors: Anne Schattel, Mitja Echim, Christof Büskens

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Trajectory planning for deep space missions has become a recent topic of great interest. Flying to space objects like asteroids provides two main challenges. One is to find rare earth elements, the other to gain scientific knowledge of the origin of the world. Due to the enormous spatial distances such explorer missions have to be performed unmanned and autonomously. The mathematical field of optimization and optimal control can be used to realize autonomous missions while protecting recourses and making them safer. The resulting algorithms may be applied to other, earth-bound applications like e.g. deep sea navigation and autonomous driving as well. The project KaNaRiA ('Kognitionsbasierte, autonome Navigation am Beispiel des Ressourcenabbaus im All') investigates the possibilities of cognitive autonomous navigation on the example of an asteroid mining mission, including the cruise phase and approach as well as the asteroid rendezvous, landing and surface exploration. To verify and test all methods an interactive, real-time capable simulation using virtual reality is developed under KaNaRiA. This paper focuses on the specific challenge of the guidance during the cruise phase of the spacecraft, i.e. trajectory optimization and optimal control, including first solutions and results. In principle there exist two ways to solve optimal control problems (OCPs), the so called indirect and direct methods. The indirect methods are being studied since several decades and their usage needs advanced skills regarding optimal control theory. The main idea of direct approaches, also known as transcription techniques, is to transform the infinite-dimensional OCP into a finite-dimensional non-linear optimization problem (NLP) via discretization of states and controls. These direct methods are applied in this paper. The resulting high dimensional NLP with constraints can be solved efficiently by special NLP methods, e.g. sequential quadratic programming (SQP) or interior point methods (IP). The movement of the spacecraft due to gravitational influences of the sun and other planets, as well as the thrust commands, is described through ordinary differential equations (ODEs). The competitive mission aims like short flight times and low energy consumption are considered by using a multi-criteria objective function. The resulting non-linear high-dimensional optimization problems are solved by using the software package WORHP ('We Optimize Really Huge Problems'), a software routine combining SQP at an outer level and IP to solve underlying quadratic subproblems. An application-adapted model of impulsive thrusting, as well as a model of an electrically powered spacecraft propulsion system, is introduced. Different priorities and possibilities of a space mission regarding energy cost and flight time duration are investigated by choosing different weighting factors for the multi-criteria objective function. Varying mission trajectories are analyzed and compared, both aiming at different destination asteroids and using different propulsion systems. For the transcription, the robust method of full discretization is used. The results strengthen the need for trajectory optimization as a foundation for autonomous decision making during deep space missions. Simultaneously they show the enormous increase in possibilities for flight maneuvers by being able to consider different and opposite mission objectives.

Keywords: deep space navigation, guidance, multi-objective, non-linear optimization, optimal control, trajectory planning.

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1174 Expression of Micro-RNA268 in Zinc Deficient Rice

Authors: Sobia Shafqat, Saeed Ahmad Qaisrani

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MicroRNAs play an essential role in the regulation and development of all processes in most eukaryotes because of their prospective part as mediators controlling cell growth and differentiation towards the exact position of RNAs response in plants under biotic and abiotic factors or stressors. In a few cases, Zn is oblivious poisonous for plants due to its heavy metal status. Some other metals are extremely toxic, like Cd, Hg, and Pb, but these elements require in rice for the programming of genes under abiotic stress resembling Zn stress when micro RNAs268 was importantly introduced in rice. The micro RNAs overexpressed in transgenic plants with an accumulation of a large amount of melanin dialdehyde, hydrogen peroxide, and an excessive quantity of Zn in the seedlings stage. Let out results for rice pliability under Zn stress micro RNAs act as negative controllers. But the role of micro RNA268 act as a modulator in different ecological condition. It has been explained clearly with a long understanding of the role of micro RNA268 under stress conditions; pliability and practically showed outcome to increase plant sufferance under Zn stress because micro RNAs is an intervention technique for gene regulation in gene expression. The proposed study was experimented with by using genetic factors of Zn stress and toxicity effect on rice plants done at District Vehari, Pakistan. The trial was performed randomly with three replications in a complete block design (RCBD). These blocks were controlled with different concentrations of genetic factors. By overexpression of micro RNA268 rice, seedling growth was not stopped under Zn deficiency due to the accumulation of a large amount of melanin dialdehyde, hydrogen peroxide, and an excessive quantity of Zn in their seedlings. Results showed that micro RNA268 act as a negative controller under Zn stress. In the end, under stress conditions, micro RNA268 showed the necessary function in the tolerance of rice plants. The directorial work sketch gave out high agronomic applications and yield outcomes in rice with a specific amount of Zn application.

Keywords: micro RNA268, zinc, rice, agronomic approach

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1173 Integrative Omics-Portrayal Disentangles Molecular Heterogeneity and Progression Mechanisms of Cancer

Authors: Binder Hans

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Cancer is no longer seen as solely a genetic disease where genetic defects such as mutations and copy number variations affect gene regulation and eventually lead to aberrant cell functioning which can be monitored by transcriptome analysis. It has become obvious that epigenetic alterations represent a further important layer of (de-)regulation of gene activity. For example, aberrant DNA methylation is a hallmark of many cancer types, and methylation patterns were successfully used to subtype cancer heterogeneity. Hence, unraveling the interplay between different omics levels such as genome, transcriptome and epigenome is inevitable for a mechanistic understanding of molecular deregulation causing complex diseases such as cancer. This objective requires powerful downstream integrative bioinformatics methods as an essential prerequisite to discover the whole genome mutational, transcriptome and epigenome landscapes of cancer specimen and to discover cancer genesis, progression and heterogeneity. Basic challenges and tasks arise ‘beyond sequencing’ because of the big size of the data, their complexity, the need to search for hidden structures in the data, for knowledge mining to discover biological function and also systems biology conceptual models to deduce developmental interrelations between different cancer states. These tasks are tightly related to cancer biology as an (epi-)genetic disease giving rise to aberrant genomic regulation under micro-environmental control and clonal evolution which leads to heterogeneous cellular states. Machine learning algorithms such as self organizing maps (SOM) represent one interesting option to tackle these bioinformatics tasks. The SOMmethod enables recognizing complex patterns in large-scale data generated by highthroughput omics technologies. It portrays molecular phenotypes by generating individualized, easy to interpret images of the data landscape in combination with comprehensive analysis options. Our image-based, reductionist machine learning methods provide one interesting perspective how to deal with massive data in the discovery of complex diseases, gliomas, melanomas and colon cancer on molecular level. As an important new challenge, we address the combined portrayal of different omics data such as genome-wide genomic, transcriptomic and methylomic ones. The integrative-omics portrayal approach is based on the joint training of the data and it provides separate personalized data portraits for each patient and data type which can be analyzed by visual inspection as one option. The new method enables an integrative genome-wide view on the omics data types and the underlying regulatory modes. It is applied to high and low-grade gliomas and to melanomas where it disentangles transversal and longitudinal molecular heterogeneity in terms of distinct molecular subtypes and progression paths with prognostic impact.

Keywords: integrative bioinformatics, machine learning, molecular mechanisms of cancer, gliomas and melanomas

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1172 Autophagy Suppresses Tumorigenesis through Upregulation of MiR-449a in Colorectal Cancer

Authors: Sheng-Hui Lan, Shan-Ying Wu, Shu-Ching Lin, Wei-Chen Wang, Hsiao-Sheng Liu

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Autophagy is an essential mechanism to maintain cellular homeostasis through its degradation function, and the autophagy deficiency is related various diseases including tumorigenesis in several cancers. MicroRNAs (miRNAs) are small none coding RNAs, which regulate gene expression through degradation of mRNA or inhibition of translation. However, the relationship between autophagy deficiency and dysregulated miRNAs is still unclear. We revealed a mechanism that autophagy up-regulates miR-449a expression at the transcriptional level through activation of forkhead transcription factor family member FoxO1 and then suppresses tumorigenesis in CRC. Our data showed that the autophagic activity and miR-449a expression were lower in colorectal cancer (CRC) and has a positive correlation. We further reveal that autophagy degrades p300 expression and then suppresses acetylation of FoxO1. Under autophagic induction conditions, FoxO1 is transported from the cytoplasm to the nucleus and binds to the miR-449a promoter and then promotes miR-449a expression. In addition, either miR-449a overexpression or amiodarone-induced autophagy inhibits cell cycle progression, proliferation, colony formation migration, invasion, and tumor formation of SW480 cells. Our findings indicate that autophagy inducers may have the potential to be used for prevention and treatment of CRC through upregulation of miR-449a expression.

Keywords: autophagy, MiR-449a, FoxO1, colorectal cancer

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1171 Tax Criminal Case Settlement Through Obligative Justice Approach to Increase the State Revenue

Authors: Pujiyono, Reda Manthovani, Deny Tri Ardianto, Rabani Halawa, Isharyanto

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This research has background that the taxpayer (defendant) who has paid off the tax payable and the tax penalty payable after the tax case file has been transferred to the court, while the legality of stopping the prosecution of tax cases on the grounds that in the interest of state revenue is not regulated in the provisions of Law Number 8 of 1981 concerning The Criminal Procedure Code and Law Number 28 of 2007 concerning the Third Amendment to Law Number 6 of 1983 concerning General Provisions and Tax Procedures as amended several times, most recently by Law Number 16 of 2009 concerning Stipulation of Government Regulation in Lieu of Law Number 5 of 2008 concerning Fourth Amendment to Law Number 6 0f 1983 concerning General Provisions and Tax Procedures to become Law, even though at the investigation stage it regulates the mechanism for stopping the investigation for the sake of the interest of acceptance ne this is because before the case file is transferred to the court where at the request of the Minister of Finance of The Republic of Indonesia can stop the investigation in the interest of state revenue so that based on this phenomenon a legal vacuum is found. Therefore, a non-penal policy is needed from the public prosecutor to resolve tax crime cases without going through litigation in court through the penal mediation method using the Plea Bargaining System which adheres to the principles of restorative justice and obligative justice based on the ultimum remedium principle and the principle of opportunity in order to realize the principle of fast, simple and low cost justice (content principle). This research is a normative legal research, using a statutory approach, conceptual approach, and comparative law approach. Regulations that is used in many countries, include America, The Netherlands and Singapore. The results of this study indicate that there is a reformulation of the tax criminal justice system which regulates the mechanism, qualifications and authority to terminate the prosecution of tax cases in the interest of state revenues in order to achieve legal goals which are not only for legal certainty but more that, namely providing benefits and legal justice for people seeking justice.

Keywords: obligative justice, regulation, state reveneus, tax criminal

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1170 Lessons from Seven Years of Teaching Mindfulness to Children Living in a Context of Vulnerability

Authors: Annie Devault

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Mindfulness-based interventions (MBI) can be beneficial for the well-being of children. MBIs offered for children in contexts of vulnerability (poverty, neglect) report positive results in terms of emotion regulation and cognitive flexibility. Anxiety is a common issue for children living in a vulnerable context. It has a negative impact on children’s attention span, emotional regulation and self-esteem. The MBI (12 weeks) associated with this research has been developed for a total of 30 children suffering from anxiety (7 to 9 years old) and receiving services from a community center over the last seven years. The first objective is to describe in details the content of the mindfulness-based intervention. The second purpose is to document what helps and what hinders the practice of mindfulness for children living in a context of vulnerability. A special attention will be given to the importance of the way that the intervention is offered and the principles that are followed by the practitioners. Perceived effects of the intervention on children were collected through an individual semi-structured interview with each child at the end of the program. Parents were also interviewed to have their point of view on the effect of their children’s participation in the group. Anxiety was measure with the Beck youth pre-post and at follow up (2 months). Qualitative analysis of the interviews with children showed that most of them mentioned that the program helped them become calmer, more confident, less scared and more able to deal with difficult emotions. Almost all of them reported having used the material provided to them to practice at home. This result has been confirmed by parents. They reported that their child had gained confidence and were better at verbalizing emotions. Children also grew calmer, even though all anxiety was not gone. They would have liked more material to practice at home. The quantitative instrument used to measure anxiety did not corroborate the qualitative interviews about anxiety. Discussion will question the use of this questionnaire for children who have important cognitive limitations. Discussion will also report the importance of the personalized contact with children, along with other consideration, to enhance the adherence of children and parents. The MBI seems to have benefited children in different ways, which is corroborated by most parents. Since the sample was limited, we will need to continue documenting its effects with more children and parents. The major strength of this research is to have reported the subjective perspectives of children on their experience of mindfulness.

Keywords: anxiety, mindfulness, children, best practices

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1169 Promoting Effective Institutional Governance in Cameroon Higher Education: A Governance Equalizer Perspective

Authors: Jean Patrick Mve

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The increasing quest for efficiency, accountability, and transparency has led to the implementation of massive governance reforms among higher education systems worldwide. This is causing many changes in the governance of higher education institutions. Governments over the world are trying to adopt business-like organizational strategies to enhance the performance of higher education institutions. This study explores the changes that have taken place in the Cameroonian higher education sector. It also attempts to draw a picture of the likely future of higher education governance and the actions to be taken for the promotion of institutional effectiveness among higher education institutions. The “governance equalizer” is used as an analytical tool to this end. It covers the five dimensions of the New Public Management (NPM), namely: state regulation, stakeholder guidance, academic self-governance, managerial self-governance, and competition. Qualitative data are used, including semi-structured interviews with key informants at the organizational level and other academic stakeholders, documents and archival data from the university and from the ministry of higher education. It has been found that state regulation among higher education institutions in Cameroon is excessively high, causing the institutional autonomy to be very low, especially at the level of financial management, staffing and promotion, and other internal administrative affairs; at the level of stakeholder guidance there is a higher degree of stakeholders consideration in the academic and research activities among universities, though the government’s interest to keep its hands in most management activities is still high; academic self-governance is also very weak as the assignment of academics is done more on the basis of political considerations than competence; there is no real managerial self-governance among higher education institutions due to the lack of institutional capacity and insufficient autonomy at the level of decision making; there is a plan to promote competition among universities but a real competitive environment is not yet put into place. The study concludes that the government’s policy should make state control more relaxed and concentrate on steering and supervision. As well, real institutional autonomy, professional competence building for top management and stakeholder participation should be considered to guarantee competition and institutional effectiveness.

Keywords: Cameroon higher education, effective institutional governance, governance equalizer, institutional autonomy, institutional effectiveness

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1168 Iranian Sexual Health Needs in Viewpoint of Policy Makers: A Qualitative Study

Authors: Mahnaz Motamedi, Mohammad Shahbazi, Shahrzad Rahimi-Naghani, Mehrdad Salehi

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Introduction: Identifying sexual health needs, developing appropriate plans, and delivering services to meet those needs is an essential component of health programs for women, men, and children all over the world, especially in poor countries. Main Subject: The aim of this study was to describe the needs of sexual health from the viewpoint of health policymakers in Iran. Methods: A qualitative study using thematic content analysis was designed and conducted. Data gathering was conducted through semi-structured, in-depth interviews with 25 key informants within the healthcare system. Key informants were selected through both purposive and snowball sampling. MAXQUDA software (version 10) was used to facilitate transcription, classification of codes, and conversion of data into meaningful units, by the process of reduction and compression. Results: The analysis of narratives and information categorized sexual health needs into five categories: culturalization of sexual health discourse, sexual health care services, sexual health educational needs, sexual health research needs, and organizational needs. Conclusion: Identifying and explaining sexual health needs is an important factor in determining the priority of sexual health programs and identification of barriers to meet these needs. This can help other policymakers and health planners to develop appropriate programs to promote sexual and reproductive health.

Keywords: sexual health, sexual health needs, policy makers, health system, qualitative study

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1167 Potential Activities of Human Endogenous Retroviral kDNA in Melanoma Pathogenesis and HIV-1 Infection

Authors: Jianli Dong, Fangling Xu, Gengming Huang

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Human endogenous retroviral elements (HERVs) comprise approximately 8% of the human genome. They are thought to be germline-integrated genetic remnants of retroviral infections. Although HERV sequences are highly defective, some, especially the K type (HERV-K), have been shown to be expressed and may have biological activities in the pathogenesis of cancer, chronic inflammation and autoimmune diseases. We found that HERV-K GAG and ENV proteins were strongly expressed in pleomorphic melanoma cells. We also detected a critical role of HERV-K ENV in mediating intercellular fusion and colony formation of melanoma cells. Interestingly, we found that levels of HERV-K GAG and ENV expression correlated with the activation of ERK and loss of p16INK4A in melanoma cells, and inhibition of MEK or CDK4, especially in combination, reduced HERV-K expression in melanoma cells. We also performed a reverse transcription-polymerase chain reaction (RT-PCR) assay using DNase I digestion to remove “contaminating” HERV-K genomic DNA and examined HERV-K RNA expression in plasma samples from HIV-1 infected individuals. We found a covariation between HERV-K RNA expression and CD4 cell counts in HIV-1 positive samples. Although a causal link between HERV-K activation and melanoma development, and between HERV-K activation, HIV-1 infection and CD4 cell count have yet to be determined, existing data support the further research efforts in HERV-K.

Keywords: CD4 cell, HERV-K, HIV-1, melanoma

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1166 Pracademia in Irish Higher Education: The Only Solution to Contemporary Regulation in Professional Social Care Practice

Authors: Aoife Prendergast

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The synergy between theory and practice can be considered elusive, the touchstone for the development of successful undergraduate programmes particularly in allied health professions such as social care. A 'pracademic' is a person who spans both the somewhat ethereal world of academia as a scholar and the pragmatic world of practice. This paper examines the concept of 'pracademia' in relation to the role of the social care practitioner and continuing professional development. It also assists in the understanding of the synergy between social care professionals and higher education. A consideration of the identity and position in terms of approach to regulation is explored as well as an acknowledgement of the strengths and opportunities for sharing power in hierarchical positions. The world of practice serves as the centre point of the academic compass for most professional programs. Just as schools of engineering and law are disciplined by the marketplace, which seeks well-trained students, so our social care programmes must perennially find ways to address the fast changing needs of practitioners, whether they be government, not-for-profit organizations, consulting firms or contractors. We may not expect such traditional academic disciplines as history, sociology, or political science to cater to the needs of external audiences or practitioners— indeed, these disciplines' insulation from public concerns and issues is considered a strength by some. This paper aims to explore the integration of academic teaching and research with the communities of practice in social care. This appears to be a fundamental aspiration of the social care profession. While building and integrating an important body of academic theory and concepts from a variety of disciplines, social care as a field has embraced a professional orientation by seeking to be relevant to practitioners at various levels. While teaching theory, social care programmes, and faculty are often acutely aware that their academic content and credibility, in part, rest on a deep connection with practitioners. While theory can be self-contained, the impact of our research and teaching arguably finds its most compelling and highest audience when it addresses the agenda items and concerns of practitioners.

Keywords: social care, pracademia, supervision, practice education

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1165 The Rendering of Sex-Related Expressions by Court Interpreters in Hong Kong: A Corpus-Based Approach

Authors: Yee Yan Crystal Kwong

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The essence of rape is the absence of consent to sexual intercourse. Yet, the definition of consent is not absolute and allows for subjectivity. In this case, the accuracy of oral interpretation becomes very important as the narratives of events and situation, as well as the register and style of speakers would influence the juror decision making. This paper first adopts a corpus-based approach to investigate how court interpreters in Hong Kong handle expressions that refer to sexual activities. The data of this study will be based on online corpus :From legislation to translation, from translation to interpretation: The narrative of sexual offences. The corpus comprises the transcription of five separate rape trials and all of these trials were heard with the presence of an interpreter. Since there are plenty of sex-related expressions used by witnesses and defendants in the five cases, emphasis will be put on those which have an impact on the definition of rape. With an in-depth analysis of the interpreted utterances, different interpreting approaches will be identified to observe how interpreters retain the intended meanings. Interviews with experienced court interpreters will also be conducted to revisit the validity of the traditional verbatim standard. At the end of this research, various interpreting approaches will be compared and evaluated. A redefinition of interpreters' institutional role, as well as recommendations for interpreting learners will be provided.

Keywords: court interpreting, interpreters, legal translation, slangs

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1164 Legal Issues of Collecting and Processing Big Health Data in the Light of European Regulation 679/2016

Authors: Ioannis Iglezakis, Theodoros D. Trokanas, Panagiota Kiortsi

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This paper aims to explore major legal issues arising from the collection and processing of Health Big Data in the light of the new European secondary legislation for the protection of personal data of natural persons, placing emphasis on the General Data Protection Regulation 679/2016. Whether Big Health Data can be characterised as ‘personal data’ or not is really the crux of the matter. The legal ambiguity is compounded by the fact that, even though the processing of Big Health Data is premised on the de-identification of the data subject, the possibility of a combination of Big Health Data with other data circulating freely on the web or from other data files cannot be excluded. Another key point is that the application of some provisions of GPDR to Big Health Data may both absolve the data controller of his legal obligations and deprive the data subject of his rights (e.g., the right to be informed), ultimately undermining the fundamental right to the protection of personal data of natural persons. Moreover, data subject’s rights (e.g., the right not to be subject to a decision based solely on automated processing) are heavily impacted by the use of AI, algorithms, and technologies that reclaim health data for further use, resulting in sometimes ambiguous results that have a substantial impact on individuals. On the other hand, as the COVID-19 pandemic has revealed, Big Data analytics can offer crucial sources of information. In this respect, this paper identifies and systematises the legal provisions concerned, offering interpretative solutions that tackle dangers concerning data subject’s rights while embracing the opportunities that Big Health Data has to offer. In addition, particular attention is attached to the scope of ‘consent’ as a legal basis in the collection and processing of Big Health Data, as the application of data analytics in Big Health Data signals the construction of new data and subject’s profiles. Finally, the paper addresses the knotty problem of role assignment (i.e., distinguishing between controller and processor/joint controllers and joint processors) in an era of extensive Big Health data sharing. The findings are the fruit of a current research project conducted by a three-member research team at the Faculty of Law of the Aristotle University of Thessaloniki and funded by the Greek Ministry of Education and Religious Affairs.

Keywords: big health data, data subject rights, GDPR, pandemic

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1163 Mitigating Self-Regulation Issues in the Online Instruction of Math

Authors: Robert Vanderburg, Michael Cowling, Nicholas Gibson

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Mathematics is one of the core subjects taught in the Australian K-12 education system and is considered an important component for future studies in areas such as engineering and technology. In addition to this, Australia has been a world leader in distance education due to the vastness of its geographic landscape. Despite this, research is still needed on distance math instruction. Even though delivery of curriculum has given way to online studies, and there is a resultant push for computer-based (PC, tablet, smartphone) math instruction, much instruction still involves practice problems similar to those original curriculum packs, without the ability for students to self-regulate their learning using the full interactive capabilities of these devices. Given this need, this paper addresses issues students have during online instruction. This study consists of 32 students struggling with mathematics enrolled in a math tutorial conducted in an online setting. The study used a case study design to understand some of the blockades hindering the students’ success. Data was collected by tracking students practice and quizzes, tracking engagement of the site, recording one-on-one tutorials, and collecting data from interviews with the students. Results revealed that when students have cognitively straining tasks in an online instructional setting, the first thing to dissipate was their ability to self-regulate. The results also revealed that instructors could ameliorate the situation and provided useful data on strategies that could be used for designing future online tasks. Specifically, instructors could utilize cognitive dissonance strategies to reduce the cognitive drain of the tasks online. They could segment the instruction process to reduce the cognitive demands of the tasks and provide in-depth self-regulatory training, freeing mental capacity for the mathematics content. Finally, instructors could provide specific scheduling and assignment structure changes to reduce the amount of student centered self-regulatory tasks in the class. These findings will be discussed in more detail and summarized in a framework that can be used for future work.

Keywords: digital education, distance education, mathematics education, self-regulation

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1162 Characterization of Enterotoxigenic Escherichia coli CS6 Promoter

Authors: Mondal Indranil, Bhakat Debjyoti, Mukhopadayay Asish K., Chatterjee Nabendu S.

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CS6 is the prevalent CF in our region and deciphering its molecular regulators would play a pivotal role in reducing the burden of ETEC pathogenesis. In prokaryotes, most of the genes are under the control of one operon and the promoter present upstream of the gene regulates the transcription of that gene. Here the promoter of CS6 was characterized by computational method and further analyzed by β-galactosidase assay and sequencing. Promoter constructs and deletions were prepared as required to analyze promoter activity. The effect of different additives on the CS6 promoter was analysed by the β-galactosidase assay. Bioinformatics analysis done by Softberry/BPROM predicted fur, lrp, and crp boxes, -10 and -35 region upstream of the CS6 gene. The promoter construction in no promoter plasmid pTL61T showed that region -573 to +1 is actually the promoter region as predicted. Sequential deletion of the region upstream of CS6 revealed that promoter activity remains the same when -573bp to -350bp is deleted. But after the deletion of the upstream region -350 bp to -255bp, promoter expression decreases drastically to 26%. Further deletion also decreases promoter activity up to a little range. So the region -355bp to -255bp holds the promoter sequence for the CS6 gene. Additives like iron, NaCl, etc., modulate promoter activity in a dose-dependent manner. From the promoter analysis, it can be said that the minimum region lies between -254 and +1. Important region(s) lies between -350 bp to -255 bp upstream in the promoter, which might have important elements needed to control CS6 gene expression.

Keywords: microbiology, promoter, colonization factor, ETEC

Procedia PDF Downloads 159
1161 Role of Autophagic Lysosome Reformation for Cell Viability in an in vitro Infection Model

Authors: Muhammad Awais Afzal, Lorena Tuchscherr De Hauschopp, Christian Hübner

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Introduction: Autophagy is an evolutionarily conserved lysosome-dependent degradation pathway, which can be induced by extrinsic and intrinsic stressors in living systems to adapt to fluctuating environmental conditions. In the context of inflammatory stress, autophagy contributes to the elimination of invading pathogens, the regulation of innate and adaptive immune mechanisms, and regulation of inflammasome activity as well as tissue damage repair. Lysosomes can be recycled from autolysosomes by the process of autophagic lysosome reformation (ALR), which depends on the presence of several proteins including Spatacsin. Thus ALR contributes to the replenishment of lysosomes that are available for fusion with autophagosomes in situations of increased autophagic turnover, e.g., during bacterial infections, inflammatory stress or sepsis. Objectives: We aimed to assess whether ALR plays a role for cell survival in an in-vitro bacterial infection model. Methods: Mouse embryonic fibroblasts (MEFs) were isolated from wild-type mice and Spatacsin (Spg11-/-) knockout mice. Wild-type MEFs and Spg11-/- MEFs were infected with Staphylococcus aureus (multiplication of infection (MOI) used was 10). After 8 and 16 hours of infection, cell viability was assessed on BD flow cytometer through propidium iodide intake. Bacterial intake by cells was also calculated by plating cell lysates on blood agar plates. Results: in-vitro infection of MEFs with Staphylococcus aureus showed a marked decrease of cell viability in ALR deficient Spatacsin knockout (Spg11-/-) MEFs after 16 hours of infection as compared to wild-type MEFs (n=3 independent experiments; p < 0.0001) although no difference was observed for bacterial intake by both genotypes. Conclusion: Suggesting that ALR is important for the defense of invading pathogens e.g. S. aureus, we observed a marked increase of cell death in an in-vitro infection model in cells with compromised ALR.

Keywords: autophagy, autophagic lysosome reformation, bacterial infections, Staphylococcus aureus

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1160 The Impact of Animal-Assisted Pedagogy on Social Participation in Heterogenous Classrooms: A Survey Considering the Pupils Perspective on Animal-Assisted Teaching

Authors: Mona Maria Mombeck

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Social participation in heterogeneous classrooms is one of the main goals in inclusive education. Children with special educational needs (SEN) and children with learning difficulties, or behavioural problems not diagnosed as SEN, are more likely to be excluded by other children than others. It is proven that the presence of dogs, as well as contact with dogs, increases the likelihood of positive social behaviour between humans. Therefore, animal-assisted pedagogy may be presumed to be a constructive way of inclusive teaching and facing the challenges of social inclusion in school classes. This study investigates the presence of a friendly dog in heterogeneous groups of pupils in order to evaluate the influence of dogs on facets of social participation of children in school. 30 German pupils, aged from 10 to 14, in four classes were questioned about their social participation before and after they were educated for a year in school with animal-assisted-pedagogy, using the problem-concerned interview method. In addition, the post-interview includes some general questions about the putative differences or similarities of being educated with and without a dog. The interviews were analysed with the qualitative-content-analysis using QDA software. The results showed that a dog has a positive impact on the atmosphere, student relationships, and well-being in class. Regarding the atmosphere, the pupils mainly argued that the improvement was caused by taking into account the dog’s well-being, respecting the dog-related rules, and by emotional self-regulation. It can be supposed that children regard the rules concerning the dog as more relevant to them than rules, not concerning the dog even if they require the same behaviour and goal. Furthermore, a dog has a positive impact on emotional self-regulation and, therefore, on pupil’s behaviour in class and the atmosphere. In terms of the statements about relationships, the dog’s presence was mainly seen to provide both a unifying aim and a uniting topic to talk about. The improved well-being was described as a feeling of joy and peace of mind. Moreover, the teacher was evaluated as more friendly and trustworthy after animal-assisted teaching. Nevertheless, animal-assisted pedagogy can, rarely, cause problems as well, such as jealousy, distraction, or concerns about the well-being of the dog. The study could prove the relevance of animal-assisted pedagogy for facing the challenges of social participation in inclusive education.

Keywords: animal-assisted-pedagogy, inclusive education, human-animal-interactions, social participation

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1159 Regulation of Apoptosis in Human Lung Cancer NCI-H226 Cells through Caspase – Dependent Mechanism by Benjakul Extract

Authors: Pintusorn Hansakul, Ruchilak Rattarom, Arunporn Itharat

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Background: Benjakul, a Thai traditional herbal formulation, comprises of five plants: Piper chaba, Piper sarmentosum, Piper interruptum, Plumbago indica, and Zingiber officinale. It has been widely used to treat cancer patients in the context of folk medicine in Thailand. This study aimed to investigate the cytotoxic effect of the ethanol extract of Benjakul against three non-small cell lung cancer (NSCLC) cell lines (NCI-H226, A549, COR-L23), small cell lung cancer (SCLC) cell line NCI-H1688 and normal lung fibroblast cell line MRC-5. The study further examined the molecular mechanisms underlying its cytotoxicity via induction of apoptosis in NCI-H226 cells. Methods: The cytotoxic effect of Benjakul was determined by SRB assay. The effect of Benjakul on cell cycle distribution was assessed by flow cytometric analysis. The apoptotic effects of Benjakul were determined by sub-G1 quantitation and Annexin V-FITC/PI flow cytometric analyses as well as by changes in caspase-3 activity. Results: Benjakul exerted potent cytotoxicity on NCI-H226 and A549 cells but lower cytotoxicity on COR-L23 and NCI-H1688 cells without any cytotoxic effect on normal cells. Molecular studies showed that Benjakul extract induced G2/M phase arrest in human NCI-H226 cells in a dose-dependent manner. The highest concentration of Benjakul (150 μg/ml) led to the highest increase in the G2/M population at 12 h, followed by the highest increase in the sub-G1 population (apoptotic cells) at 60 h. Benjakul extract also induced early apoptosis (AnnexinV +/PI−) in NCI-H226 cells in a dose- and time- dependent manner. Moreover, treatment with 150 μg/ml Benjakul extract for 36 h markedly increased caspase-3 activity by 3.5-fold, and pretreatment with the general caspase inhibitor z-VAD-fmk completely abolished such activity. Conclusions: This study reveals for the first time the regulation of apoptosis in human lung cancer NCI-H226 cells through caspase-dependent mechanism by Benjakul extract.

Keywords: apoptosis, Benjakul, caspase activation, cytotoxicity

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1158 Inhibitory Effects of PPARγ Ligand, KR-62980, on Collagen-Stimulated Platelet Activation

Authors: Su Bin Wang, Jin Hee Ahn, Tong-Shin Chang

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The peroxisome proliferator-activated receptors (PPARs) are member of nuclear receptor superfamily that act as a ligand-activated transcription factors. Although platelets lack a nucleus, previous studies have shown that PPARγ agonists, rosiglitazone, inhibited platelet activation induced by collagen. In this study, we investigated the inhibitory effects of KR-62980, a newly synthesized PPARγ agonist, on collagen receptor-stimulated platelet activation. The specific tyrosine phosphorylations of key components (Syk, Vav1, Btk and PLCγ2) for collagen receptor signaling pathways were suppressed by KR-62980. KR-62980 also attenuated downstream responses including cytosolic calcium elevation, P-selectin surface exposure, and integrin αIIbβ3 activation. PPARγ was found to associate with multiple proteins within the LAT signaling complex in collagen-stimulated platelets. This association was prevented by KR-62980, indicating a potential mechanism for PPARγ function in collagen-stimulated platelet activation. Furthermore, KR-62980 inhibited platelet aggregation and adhesion in response to collagen in vitro and prolonged in vivo thrombotic response in carotid arteries of mice. Collectively, these data suggest that KR-62980 inhibits collagen-stimulated platelet activation and thrombus formation through modulating the collagen receptor signaling pathways.

Keywords: KR-62980, PPARγ, antiplatelet, thrombosis

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1157 PTOP Expression Correlates with Telomerase Activity and Grades of Malignancy in Human Glioma Tissues

Authors: F. Polito, M. Cucinotta, A. Conti, C. Lo Giudice, C. Tomasello, F. Angileri, D. La Torre, M. Aguennouz

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Glioblastoma multiforme (GBM) is the most aggressive form of brain tumors, with an extremely poor prognosis. Telomeres lenght is associated with tumor progression in several type of human cancers and telomere elongation is a common molecular feature of advanced malignancies. Among the telomeric shelterin proteins PTOP is required for telomeric protein complex assembly, telomerase recruitment and activity, and telomere length regulation through a PTOP-telomerase interaction. Previous studies suggest that PTOP upregulation is involved in radioresistance and telomere lengthening in colorectal cancer cells. Moreover, in human osteosarcoma cells PTOP deletion led to telomere shortening, increased apoptosis and radiation sensitivity enhancement. However, to date, little is known about the role of PTOP in progression of glioma cancers. In light of this background aim of the study is to investigate the expression of PTOP in different grades of human glioma and its correlation with the pathological grade of gliomas, grades of malignancy, proliferative activity and apoptosis. Fifteen Low Grade Astrocytomas (LGA), 18 Anaplastic Astrocytomas (AA) and 26 Glioblastoma Multiforme (GBM) samples were analyzed. Three samples of normal brain tissue (NBT) were used as controls. The expression levels of PTOP, h-TERT, BIRC1 and cyclin D1 were determined by real time PCR and/or western blot. Results obtained shows that PTOP expression in glioma tissues is tightly correlated with clinical grade ( p < 0.01 ). No correlation was found between PTOP expression and other clinicopathologic parameters. The expression of PTOP was positively correlated with the expression of hTERT and TERF1. Furthermore PTOP positively correlates with cyclin D1 and negatively correlates with the expression of BIRC1. Our findings indicate that PTOP might play key role in the progression of glioma regulating telomerase activity and likely through regulation of cell cycle and apoptosis. In conclusion results obtained prompted us to speculate that PTOP might represents a potential molecular bio marker and a therapeutic target for the treatment of glioblastoma tumors.

Keywords: glioblastoma, PTOP, telomere, brain tumors

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1156 Unravelling the Knot: Towards a Definition of ‘Digital Labor’

Authors: Marta D'Onofrio

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The debate on the digitalization of the economy has raised questions about how both labor and the regulation of work processes are changing due to the introduction of digital technologies in the productive system. Within the literature, the term ‘digital labor’ is commonly used to identify the impact of digitalization on labor. Despite the wide use of this term, it is still not available an unambiguous definition of it, and this could create confusion in the use of terminology and in the attempts of classification. As a consequence, the purpose of this paper is to provide for a definition and to propose a classification of ‘digital labor’, resorting to the theoretical approach of organizational studies.

Keywords: digital labor, digitalization, data-driven algorithms, big data, organizational studies

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1155 Roles of Lysine-63-Linked Ubiquitination in Cell Decision Fate between Cell Proliferation and Apoptosis

Authors: Chargui Abderrahman, Nehdi Afef , BelaïD Amine , Djerbi Nadir, Tauc Michel, Hofman Paul, Mograbi Baharia, El May MichèLe

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K63-linked ubiquitination — i.e. conjugation of a chain of ubiquitins (Ub) linked through lys63 — has emerged as a key mechanism regulating signalling transduction pathways. Although critical, very little information is currently available about how subversion of K63 ubiquitination might contribute to cancers and inflammatory diseases. The present study provides the first evidence that Cadmium (Cd), a widespread environmental carcinogen and toxicant, is a powerful activator of K63 ubiquitination. Indeed, Cd induces accumulation of K63 polyUb proteins. Importantly, Cd-induced ubiquitination does not stem on oxidative damage or proteasome impairment. Rather, we demonstrate that Cd not only activates K63 ubiquitination but also amplifies their accumulation by overloading the capacity of autophagy pathway. At molecular level, Cd-induced ubiquitination is correlated with stabilization of HIF-1 and the activation of NF-B, two transcription factors. Strikingly, prolonged cell exposure to high Cd concentrations induces an exaggerated K63 ubiquitination that fosters aggresome formation, thus precluding these proteins from interacting with their downstream nuclear targets. We therefore propose that the aberrant activation of K63 ubiquitination by the carcinogen Cadmium could promote cell proliferation and inflammation at low levels while high levels committed cell to death.

Keywords: cadmium, environmental exposure, Lysine-63-ubiquitination, kidney, apoptosis, proliferation, autophagy

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