Search results for: transcription regulation

Authors: W. Abu Rayyan, A. Singh, A. M. Al-Jaafreh, W. Abu Dayyih, M. Bustami, S. Salem, N. Seder, K. Schröppel

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Hyphal growth and the transcriptional regulation to the host environment are key issues during the pathogenesis of C. albicans. Tec1p is the C. albicans homolog of a TEA transcription factor family, which share a conserved DNA-binding TEA domain in their N-terminal. In order to define a structure-function relationship of the C. albicans Tec1p protein, we constructed several mutations on the N terminal, C terminal or in the TEA binding domain itself by homologous recombination technology. The modifications in the open reading frame of TEC1 were tested for reconstitution of the morphogenetic development of the tec1/tec1 mutant strain CaAS12. Mutation in the TEA consensus sequence did not confer transition to hyphae whereas the reconstitution of the full-length Tec1p has reconstituted hyphal development. A deletion in one of glutamine-rich regions either in the Tec1p N-terminal or the C-terminal in regions of 53-212 or 637–744 aa, respectively, did not restore morphological development in mutant CaAS12 strain. Whereas, the reconstitution with Tec1p mutants other than the glutamate-rich region has restored the morphogenetic switch. Additionally, the deletion of the glutamine-rich region has attenuated the invasive growth and the heat shock resistance of C. albicans. In conclusion, we show that a glutamine-rich region of Tec1p is essential for the hyphal development and mediating adaptation to the host environment of C. albicans.

Keywords: Candida albicans, morphogenetic development, TEA domain, hyphal formation, TEC1

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Authors: K. Julia Rose Mary, Victor Arokia Doss

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Electrical and chemical stimulations up-regulate phosphorylaion of CREB, a transcriptional factor that induces its target gene production for memory consolidation and Late Long-Term Potentiation (L-LTP) in CA1 region of the hippocampus. L-LTP requires complex interactions among second-messenger signaling cascade molecules such as cAMP, CAMKII, CAMKIV, MAPK, RSK, PKA, all of which converge to phosphorylate CREB which along with CBP induces the transcription of target genes involved in memory consolidation. A differential equation based model for L-LTP representing stimulus-mediated activation of downstream mediators which confirms the steep, supralinear stimulus-response effects of activation and inhibition was used. The same was extended to accommodate the inhibitory effect of the Inducible cAMP Early Repressor (ICER). ICER is the natural inducible CREB antagonist represses CRE-Mediated gene transcription involved in long-term plasticity for learning and memory. After verifying the sensitivity and robustness of the model, we had simulated it with various empirical levels of repressor concentration to analyse their effect on the gene induction. The model appears to predict the regulatory dynamics of repression on the L-LTP and agrees with the experimental values. The flux data obtained in the simulations demonstrate various aspects of equilibrium between the gene induction and repression.

Keywords: CREB, L-LTP, mathematical modeling, simulation

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Authors: Zhongyang Sun, Shu Zhang

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In osteoblasts, L-type voltage sensitive calcium channels (LTCCs), especially the Cav1.2 LTCCs, play fundamental roles in cellular responses to external stimuli including both mechanical forces and hormonal signals. Several lines of evidence have revealed that the density of bone is increased and the resorption of bone is decreased when these calcium channels in osteoblasts are activated. And numerous studies have shown that mechanical loading promotes bone formation in the modeling skeleton, whereas removal of this stimulus in microgravity results in a reduction in bone mass. However, the effect of microgravity on LTCCs in osteoblasts is still unknown. The aim of this study was to determine whether microgravity exerts influence on LTCCs in osteoblasts and the possible mechanisms underlying. In this study, we demonstrate that simulated microgravity substantially inhibits LTCCs in osteoblast by suppressing the expression of Cav1.2. Then we show that the up-regulation of miR-103 is involved in the down-regulation of Cav1.2 expression and inhibition of LTCCs by simulated microgravity in osteoblasts. Our study provides a novel mechanism of simulated microgravity-induced adverse effects on osteoblasts, offering a new avenue to further investigate the bone loss caused by microgravity.

Keywords: L-type voltage sensitive calcium channels, Cav1.2, osteoblasts, microgravity

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Authors: Jang-Hwan Jo

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The supply management of ecosystem services of local forests is an essential issue as it is linked to the ecological welfare of local residents. This study aims to estimate the supply, trade-offs, and synergies of local forest regulating ecosystem services using a land cover classification map (LCCM) and a forest types map (FTM). Rigorous literature reviews and Expert Delphi analysis were conducted using the detailed variables of 1:5,000 LCCM and FTM. Land-use scoring method and Getis-Ord Gi* Analysis were utilized on detailed variables to propose a method for estimating supply, trade-offs, and synergies of the local forest regulating ecosystem services. The analysis revealed that the rank order (1st to 5th) of supply of regulating ecosystem services was Erosion prevention, Air quality regulation, Heat island mitigation, Water quality regulation, and Carbon storage. When analyzing the correlation between defined services of the entire city, almost all services showed a synergistic effect. However, when analyzing locally, trade-off effects (Heat island mitigation – Air quality regulation, Water quality regulation – Air quality regulation) appeared in the eastern and northwestern forest areas. This suggests the need to consider not only the synergy and trade-offs of the entire forest between specific ecosystem services but also the synergy and trade-offs of local areas in managing the regulating ecosystem services of local forests. The study result can provide primary data for the stakeholders to determine the initial conditions of the planning stage when discussing the establishment of policies related to the adjustment of the supply of regulating ecosystem services of the forests with limited access. Moreover, the study result can also help refine the estimation of the supply of the regulating ecosystem services with the availability of other forms of data.

Keywords: ecosystem service, getis ord gi* analysis, land use scoring method, regional forest, regulating service, synergies, trade-offs

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Authors: Pankhudi Khandelwal

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The revenue models of digital giants such as Facebook and Google, use targeted advertising for revenues. Such a model requires huge amounts of consumer data. While the data protection law deals with the protection of personal data, however, this data is acquired by the companies on the basis of consent, performance of a contract, or legitimate interests. This paper analyses the role that competition law can play in evading these loopholes for the protection of data and privacy of online consumers. Digital markets have certain distinctive features such as network effects and feedback loop, which gives incumbents of these markets a first-mover advantage. This creates a situation where the winner takes it all, thus creating entry barriers and concentration in the market. It has been also seen that this dominant position is then used by the undertakings for leveraging in other markets. This can be harmful to the consumers in form of less privacy, less choice, and stifling innovation, as seen in the cases of Facebook Cambridge Analytica, Google Shopping, and Google Android. Therefore, the article aims to provide a legal framework wherein the data protection law and competition law can come together to provide a balance in regulating digital markets. The issue has become more relevant in light of the Facebook decision by German competition authority, where it was held that Facebook had abused its dominant position by not complying with data protection rules, which constituted an exploitative practice. The paper looks into the jurisdictional boundaries that the data protection and competition authorities can work from and suggests ex ante regulation through data protection law and ex post regulation through competition law. It further suggests a change in the consumer welfare standard where harm to privacy should be considered as an indicator of low quality.

Keywords: data protection, dominance, ex ante regulation, ex post regulation

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Authors: Cristina Costescu, Carmen David, Adrian Roșan

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Executive functions (EF) and emotion regulation strategies are processes that allow individuals to function in an adaptative way and to be goal-oriented, which is essential for success in daily living activities, at school, or in social contexts. The Emotion Regulation and Executive Functioning Scale for Children and Adolescents (REMEX) represents an empirically based tool (based on the model of EF developed by Diamond) for evaluating significant dimensions of child and adolescent EFs and emotion regulation strategies, mainly in school contexts. The instrument measures the following dimensions: working memory, inhibition, cognitive flexibility, executive attention, planning, emotional control, and emotion regulation strategies. Building the instrument involved not only a top-down process, as we selected the content in accordance with prominent models of FE, but also a bottom-up one, as we were able to identify valid contexts in which FE and ER are put to use. For the construction of the instrument, we implemented three focus groups with teachers and other professionals since the aim was to develop an accurate, objective, and ecological instrument. We used the focus group method in order to address each dimension and to yield a bank of items to be further tested. Each dimension is addressed through a task that the examiner will apply and through several items derived from the main task. For the validation of the instrument, we plan to use item response theory (IRT), also known as the latent response theory, that attempts to explain the relationship between latent traits (unobservable cognitive processes) and their manifestations (i.e., observed outcomes, responses, or performance). REMEX represents an ecological scale that integrates a current scientific understanding of emotion regulation and EF and is directly applicable to school contexts, and it can be very useful for developing intervention protocols. We plan to test his convergent validity with the Childhood Executive Functioning Inventory (CHEXI) and Emotion Dysregulation Inventory (EDI) and divergent validity between a group of typically developing children and children with neurodevelopmental disorders, aged between 6 and 9 years old. In a previous pilot study, we enrolled a sample of 40 children with autism spectrum disorders and attention-deficit/hyperactivity disorder aged 6 to 12 years old, and we applied the above-mentioned scales (CHEXI and EDI). Our results showed that deficits in planning, bebavior regulation, inhibition, and working memory predict high levels of emotional reactivity, leading to emotional and behavioural problems. Considering previous results, we expect our findings to provide support for the validity and reliability of the REMEX version as an ecological instrument for assessing emotion regulation and EF in children and for key features of its uses in intervention protocols.

Keywords: executive functions, emotion regulation, children, item response theory, focus group

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Authors: Tahmina Huq

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Action research equips teachers with the skills needed to work on a particular situation in their classroom. This paper aims to introduce a strategy, visual dialogue between student and teacher, used by the researcher to help autistic students with intellectual disabilities to regulate their immediate emotions to achieve their academic goals. This research has been conducted to determine whether teaching self-regulation strategies can be effective instead of segregating them. The researcher has identified that visual dialogue between the student and teacher is a helpful technique for teaching self-regulation. For this particular research, action research suits the purpose as the findings can be applied immediately in the classroom. Like many autistic students, the teacher had two 15 years old autistic students with intellectual disabilities in class who had difficulty in controlling their emotions and impulses. They expressed their emotions through aggressive behavior, such as shouting, screaming, biting teachers or any adult who was in their sight, and destroying school property. They needed two to four hours to recover from their meltdowns with the help of a psychologist. The students missed the classes as they were often isolated from the classroom and stayed in the calming room until they calmed down. This negatively affected their learning. Therefore, the researcher decided to implement a self-regulation strategy, a visual dialogue between students and teachers, instead of isolating them to recover from the meltdown. The data was collected through personal observations, a log sheet, personal reflections, and pictures. The result shows that the students can regulate their emotions shortly in the classroom (15 to 30 minutes). Through visual dialogue, they can express their feelings and needs in socially appropriate ways. The finding indicates that autistic students can regulate their emotions through visual dialogues and participate in activities by staying in the classroom. Thus it positively impacted their learning and social lives. In this paper, the researcher discussed the findings of exploring how teachers can successfully implement a self-regulation strategy for autistic students in classroom settings. The action research describes the strategy that has been found effective for managing the emotions of autistic students with intellectual disabilities.

Keywords: action research, self-regulation, autism, visual communication

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Authors: Chia-Chi Cheng

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After the implementation of “the internet plus,” several puzzles emerge as below: why does China impose more regulation and laws on economic development on the Internet? Why does China urge the importance of manufacturing industry? Why does China’s local government passively implement the policy imposed by the central government? What kind of factors can influence China’s local government’s economic preference? In the framework of neo-institutionalism, this research considers China’s local government as changing agents to analyze its preferences and behavior. In general, the interests urged by the local government will decide its preference and behaviors. They will change its counterpart to cooperate if the change will bring more benefits. Thus, they will change its preference and behavior while the external environment alters. While the local government has the same definition on political activity and economic interest, they will prefer to cooperate with the local enterprises in the way of laying symbiont, within the presumption that the institution remains. While the local government has the different positions on political activity and economic interest, they will re-define the existed regulation or create new regulation in the condition of institution vacuum. Sequentially, they will replace the targets, and the policy, which does not fit in the Central government’s policy, will emerge.

Keywords: China, institutional change, government enterprise relationship, e-commercial policy

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Authors: Eugene Mashapa

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The age of information has witnessed countless unprecedented technological developments, which signal the articulation of succinct technological capabilities that can match these cutting-edge technological trends. These changes have impacted patterns in the production, distribution, and consumption of media content, a space that the Film and Publication Board (FPB) is concerned with. Consequently, the FPB is keen to understand the nature and impact of these technological changes on media content regulation. This exploratory study sought to investigate how content regulators in high and middle-income economies have adapted to the changes in this space, seeking insights into innovations, technological and operational, that facilitate continued relevance during this fast-changing environment. The study is aimed at developing recommendations that could assist and inform the organisation in regulating media content as it evolves. Thus, the overall research strategy in this analysis is applied research, and the analytical model adopted is a mixed research design guided by both qualitative and quantitative research instruments. It was revealed in the study that the FPB was significantly impacted by the unprecedented technological advancements in the media regulation space. Additionally, there exists a need for the FPB to understand the current and future penetrations of 4IR technology in the industry and its impact on media governance and policy implementation. This will range from reskilling officials to align with the technological skills to developing technological innovations as well as adopting co-regulatory or self-regulatory arrangements together with content distributors, where more content is distributed in higher volumes and with increased frequency. Importantly, initiating an interactive learning process for both FPB employees and the general public can assist the regulator and improve FPB’s operational efficiency and effectiveness.

Keywords: media, regulation, technology, film and publications board

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Authors: Mei Teng Woo, Keith Davids, Jarmo Liukkonen, Jia Yi Chow, Timo Jaakkola

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Wearable garments such as tapes, compression garments, and braces could improve proprioception and reduced postural sway. The aim of this study was to examine the effects of wearable garments on postural regulation in a sample of community-dwelling elderly individuals, aged 65 years. It was hypothesized that wearable garments such as socks would provide stimulation to lower leg mechanoreceptors, and help participants achieve better postural regulation. Participants (N=63) performed a 30-s Romberg balance test protocol under four conditions (barefoot; wearing commercial socks; wearing clinical compression socks; wearing non-clinical compression socks), in a counterbalanced order, with four levels of performance difficulty: (1) standing on a stable surface with open eyes (SO); (2) a stable surface with closed eyes (SC); (3) a foam surface with open eyes (FO); and (4) a foam surface with closed eyes (FC). Centre of pressure (CoP) measurements included postural sway area (C90 area), trace length (TL) and sway velocity. Thirty-five participants (55.6%) showed positive effects of wearing the socks (responded group). In the responded group, it was revealed that socks showed significant differences in SO, SC and FO conditions for the two CoP measurements - TL and sway velocity (p < 0.05). In contrast, in the non-responded group, barefoot condition significantly decreased the TL and velocity in the SO condition. From the positive effects observed in the responded group, it is possible that wearable garments provide sensory cues that could interact with a biological cueing system to enhance performance in the postural regulation system. This study suggests that individuals respond to the socks treatments differently and future research should be undertaken to examine the factors that benefited the responded group of participants.

Keywords: community-dwelling, elderly adults, postural regulation, wearable garments

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Authors: Kyung Jin Kim, Jiwon Kwak, Jae-Hoon Lee, Soo Suk Lee

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We describe an innovative method for highly specific detection of miRNAs using a specially modified method of poly(A) adaptor RT-qPCR. We use uniquely designed specific extension sequence, which plays important role in providing an opportunity to affect high specificity of miRNA detection. This method involves two steps of reactions as like previously reported and which are poly(A) tailing and reverse-transcription followed by real-time PCR. Firstly, miRNAs are extended by a poly(A) tailing reaction and then converted into cDNA. Here, we remarkably reduced the reaction time by the application of short length of poly(T) adaptor. Next, cDNA is hybridized to the 3’-end of a specific extension sequence which contains miRNA sequence and results in producing a novel PCR template. Thereafter, the SYBR Green-based RT-qPCR progresses with a universal poly(T) adaptor forward primer and a universal reverse primer. The target miRNA, miR-106b in human brain total RNA, could be detected quantitatively in the range of seven orders of magnitude, which demonstrate that the assay displays a dynamic range of at least 7 logs. In addition, the better specificity of this novel extension-based assay against well known poly(A) tailing method for miRNA detection was confirmed by melt curve analysis of real-time PCR product, clear gel electrophoresis and sequence chromatogram images of amplified DNAs.

Keywords: microRNA(miRNA), specific extension sequence, RT-qPCR, poly(A) tailing assay, reverse transcription

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Authors: Ilya B. Tsyrlov, Dmitry Y. Oshchepkov

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A computational search for dioxin response elements (DREs) in genes of proteins comprising the Ah receptor (AhR) cytosolic core complex was performed by highly efficient tool SITECON. Eventually, the following number of new DREs in 5’flanking region was detected by SITECON: one in AHR gene, five in XAP2, eight in HSP90AA1, and three in HSP90AB1 genes. Numerous DREs found in genes of AhR and AhR cytosolic complex members would shed a light on potential mechanisms of expression, the stoichiometry of unliganded AhR core complex, and its degradation vs biosynthesis dynamics resulted from treatment of target cells with the AhR most potent ligand, 2,3,7,8-TCDD. With human viruses, reduced susceptibility to TCDD of geneencoding HIV-1 P247 was justified by the only potential DRE determined in gag gene encoding HIV-1 P24 protein, whereas the regulatory region of CMV genes encoding IE gp/UL37 has five potent DRE, 1.65 kb/UL36 – six DRE, pp65 and pp71 – each has seven DRE, and pp150 – ten DRE. Also, from six to eight DRE were determined with SITECON in the regulatory region of HSV-1 IE genes encoding tegument proteins, UL36 and UL37, and of UL19 gene encoding bindingglycoprotein C (gC). So, TCDD in the low picomolar range may activate in human cells AhR: Arnt transcription pathway that triggers CMV and HSV-1 reactivation by binding to numerous promoter DRE within immediate-early (IE) genes UL37 and UL36, thus committing virus to the lytic cycle.

Keywords: dioxin response elements, Ah receptor, AhR: Arnt transcription pathway, human and viral genes

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Authors: Felicia Segeth, Florian G. Klein, Lea Berger, Andreas Kolk, Per S. Holm

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The entry of oncolytic viruses (OVs) into clinical application opens groundbreaking changes in current and future treatment regimens. However, despite their potent anti-cancer activity in vitro, clinical studies revealed limitations of OVs as monotherapy. The same applies to CDK 4/6 inhibitors (CDK4/6i) targeting cell cycle as well as bromodomain and extra-terminal domain inhibitors (BETi) targeting gene expression. In this study, the anti-tumoral effect of XVir-N-31, an YB-1 dependent oncolytic adenovirus, was evaluated in combination with Ribociclib, a CDK4/6i, and JQ1, a BETi. The head and neck squamous cell carcinoma (HNSCC) cell lines Fadu, SAS, and Cal-33 were used. DNA replication and gene expression of XVir-N-31 was measured by RT-qPCR, protein expression by western blotting, and cell lysis by SRB assays. Treatment with CDK4/6i and BETi increased viral gene expression, viral DNA replication, and viral particle formation. The data show that the combination of oncolytic adenovirus XVir-N-31 with CDK4/6i & BETi acts highly synergistic in cancer cell lysis. Furthermore, additional molecular analyses on this subject demonstrate that the positive transcription elongation factor P-TEFb plays a decisive role in this regard, indicating an influence of the combinational therapy on gene transcription control. The combination of CDK4/6i & BETi and XVir-N-31 is an attractive strategy to achieve substantial cancer cell killing and is highly suitable for clinical testing.

Keywords: adenovirus, BET, CDK4/6, HNSCC, P-TEFb, YB-1

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Authors: Patsy Tan, Dana Baltutis

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This presentation demonstrates the effectiveness of music therapy in co-treatment with speech pathology and occupational therapy as an innovative way when working with children and adolescents with complex individual differences to facilitate communication, emotional, motor and social skills development. Each child with special needs and their carer has an individual profile which encompasses their visual-spatial, auditory, language, learning, mental health, family dynamic, sensory-motor, motor planning and sequencing profiles. The most common issues among children with special needs, especially those diagnosed with Autism Spectrum Disorder, are in the areas of regulation, communication, and social-emotional development. The ability of children living with challenges to communicate and use language and understand verbal and non-verbal information, as well as move their bodies to explore and interact with their environments in social situations, depends on the children being regulated both internally and externally and trusting their communication partners and understanding what is happening in the moment. For carers, it is about understanding the tempo, rhythm, pacing, and timing of their own individual profile, as well as the profile of the child they are interacting with, and how these can sync together. In this study, music therapy is used in co-treatment sessions with a speech pathologist and/or an occupational therapist using the DIRFloortime approach to facilitate the regulation, attention, engagement, reciprocity and social-emotional capacities of children presenting with complex individual differences. Documented changes in 10 domains of children’s development over a 12-month period using the Individual Music Therapy Assessment Profile (IMTAP) were observed. Children were assessed biannually, and results show significant improvements in the social-emotional, musicality and receptive language domains indicating that co-treatment with a music therapist using the DIRFloortime framework is highly effective. This presentation will highlight strategies that facilitate regulation, social-emotional and communication development for children and adolescents with complex individual profiles.

Keywords: communication, shared attention, regulation, social emotional

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Authors: Kerolis Samoul Zaghloul Noaman

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area law is the brand new access in the basket of worldwide law in the latter half of the 20 th Century. inside the last hundred and fifty years, courts and pupils advanced a consensus that, the custom is an vital supply of global law. Article 38(1) (b) of the statute of the international court of Justice identified global custom as a supply of global law. country practices and usages have a more role to play in formulating commonplace international regulation. This paper examines those country practices which may be certified to emerge as global standard law. due to the fact that, 1979 (after Moon Treaty) no hard law had been developed within the vicinity of space exploration. It attempts to link among country practices and custom in area exploration and development of standard global regulation in area activities. The paper makes use of doctrinal approach of felony research for inspecting the current questions of worldwide regulation. The paper explores exceptional worldwide prison files which include general meeting Resolutions, Treaty standards, working papers of UN, cases relating to commonplace global law and writing of jurists regarding area law and standard international law. it's far argued that, ideas such as common background of mankind, non-navy region, sovereign equality, nuclear weapon unfastened area and protection of outer area environment, etc. evolved nation practices a number of the worldwide community which can be certified to turn out to be international customary regulation.

Keywords: social networks privacy issues, social networks security issues, social networks privacy precautions measures, social networks security precautions measures

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Authors: Christos Konstantopoulos, Thomas Ussmueller

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Digital low drop-out regulators, in contrast to analog counterparts, provide an architecture of sub-1 V regulation with low power consumption, high power efficiency, and system integration. Towards an optimized integration in the ultra-low-power system-on-chip Internet of Things architecture that is operated through a radio frequency energy harvesting scheme, the D-LDO regulator should constitute the main regulator that operates the master-clock and rest loads of the SoC. In this context, we present a D-LDO with linear search coarse regulation and asynchronous fine regulation, which incorporates an in-regulator clock generation unit that provides an autonomous, self-start-up, and power-efficient D-LDO design. In contrast to contemporary D-LDO designs that employ ring-oscillator architecture which start-up time is dependent on the frequency, this work presents a fast start-up burst oscillator based on a high-gain stage with wake-up time independent of coarse regulation frequency. The design is implemented in a 55-nm Global Foundries CMOS process. With the purpose to validate the self-start-up capability of the presented D-LDO in the presence of ultra-low input power, an on-chip test-bench with an RF rectifier is implemented as well, which provides the RF to DC operation and feeds the D-LDO. Power efficiency and load regulation curves of the D-LDO are presented as extracted from the RF to regulated DC operation. The D-LDO regulator presents 83.6 % power efficiency during the RF to DC operation with a 3.65 uA load current and voltage regulator referred input power of -27 dBm. It succeeds 486 nA maximum quiescent current with CL 75 pF, the maximum current efficiency of 99.2%, and 1.16x power efficiency improvement compared to analog voltage regulator counterpart oriented to SoC IoT loads. Complementary, the transient performance of the D-LDO is evaluated under the transient droop test, and the achieved figure-of-merit is compared with state-of-art implementations.

Keywords: D-LDO, Internet of Things, RF energy harvesting, voltage regulators

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Authors: Huimin Zhao, Xiaoquan Liu, Haochen Liu

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The major challenge facing Alzheimer's Disease (AD) drug development is how to effectively improve cognitive function in clinical practice. Growing evidence indicates that stimulating hippocampal neurogenesis is a strategy for restoring cognition in animal models of AD. The mitogen-activated protein kinase (MAPK) pathway is a crucial factor in neurogenesis, which is negatively regulated by Dual-specificity phosphatase 16 (DUSP16). Transcriptome analysis of post-mortem brain tissue revealed up-regulation of DUSP16 expression in AD patients. Additionally, DUSP16 was involved in regulating the proliferation and neural differentiation of neural progenitor cells (NPCs). Nevertheless, whether the effect of DUSP16 on ameliorating cognitive disorders by influencing NPCs differentiation in AD mice remains unclear. Our study demonstrates an association between DUSP16 SNPs and clinical progression in individuals with mild cognitive impairment (MCI). Besides, we found that increased DUSP16 expression in both 3×Tg and SAMP8 models of AD led to NPC differentiation impairments. By silencing DUSP16, cognitive benefits, the induction of AHN and synaptic plasticity, were observed in AD mice. Furthermore, we found that DUSP16 is involved in the process of NPC differentiation by regulating c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, the increased DUSP16 may be regulated by the ETS transcription factor (ELK1), which binds to the promoter region of DUSP16. Loss of ELK1 resulted in decreased DUSP16 mRNA and protein levels. Our data uncover a potential regulatory role for DUSP16 in adult hippocampal neurogenesis and provide a possibility to find the target of AD intervention.

Keywords: alzheimer's disease, cognitive function, DUSP16, hippocampal neurogenesis

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Authors: Jialin Ma, Jia Meng

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Genomic features, the genome-based coordinates, are commonly used for the representation of biological features such as genes, RNA transcripts and transcription factor binding sites. For the analysis of RNA-related genomic features, such as RNA modification sites, a common task is to correlate these features with transcript components (5'UTR, CDS, 3'UTR) to explore their distribution characteristics in terms of transcriptomic coordinates, e.g., to examine whether a specific type of biological feature is enriched near transcription start sites. Existing approaches for performing these tasks involve the manipulation of a gene database, conversion from genome-based coordinate to transcript-based coordinate, and visualization methods that are capable of showing RNA transcript components and distribution of the features. These steps are complicated and time consuming, and this is especially true for researchers who are not familiar with relevant tools. To overcome this obstacle, we develop a dedicated web app TARF, which represents web toolkit for annotating RNA-related genomic features. TARF web tool intends to provide a web-based way to easily annotate and visualize RNA-related genomic features. Once a user has uploaded the features with BED format and specified a built-in transcript database or uploaded a customized gene database with GTF format, the tool could fulfill its three main functions. First, it adds annotation on gene and RNA transcript components. For every features provided by the user, the overlapping with RNA transcript components are identified, and the information is combined in one table which is available for copy and download. Summary statistics about ambiguous belongings are also carried out. Second, the tool provides a convenient visualization method of the features on single gene/transcript level. For the selected gene, the tool shows the features with gene model on genome-based view, and also maps the features to transcript-based coordinate and show the distribution against one single spliced RNA transcript. Third, a global transcriptomic view of the genomic features is generated utilizing the Guitar R/Bioconductor package. The distribution of features on RNA transcripts are normalized with respect to RNA transcript landmarks and the enrichment of the features on different RNA transcript components is demonstrated. We tested the newly developed TARF toolkit with 3 different types of genomics features related to chromatin H3K4me3, RNA N6-methyladenosine (m6A) and RNA 5-methylcytosine (m5C), which are obtained from ChIP-Seq, MeRIP-Seq and RNA BS-Seq data, respectively. TARF successfully revealed their respective distribution characteristics, i.e. H3K4me3, m6A and m5C are enriched near transcription starting sites, stop codons and 5’UTRs, respectively. Overall, TARF is a useful web toolkit for annotation and visualization of RNA-related genomic features, and should help simplify the analysis of various RNA-related genomic features, especially those related RNA modifications.

Keywords: RNA-related genomic features, annotation, visualization, web server

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Authors: Nafiseh Noormohammadi, Ahmad Sobhani Najafabadi

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Hypericins (hypericin and pseudohypericin) are natural napthodianthrone derivatives produced by Hypericum perforatum (St. John’s Wort), which have many medicinal properties such as antitumor, antineoplastic, antiviral, and antidepressant activities. Production and accumulation of hypericin in the plant are influenced by both genetic and environmental conditions. Despite the existence of different high-throughput data on the plant, genetic dimensions of hypericin biosynthesis have not yet been completely understood. In this research, 21 high-quality RNA-seq data on different parts of the plant were integrated into metabolic data to reconstruct a coexpression network. Results showed that a cluster of 30 transcripts was correlated with total hypericin. The identified transcripts were divided into three main groups based on their functions, including hypericin biosynthesis genes, transporters, detoxification genes, and transcription factors (TFs). In the biosynthetic group, different isoforms of polyketide synthase (PKSs) and phenolic oxidative coupling proteins (POCPs) were identified. Phylogenetic analysis of protein sequences integrated into gene expression analysis showed that some of the POCPs seem to be very important in the biosynthetic pathway of hypericin. In the TFs group, six TFs were correlated with total hypericin. qPCR analysis of these six TFs confirmed that three of them were highly correlated. The identified genes in this research are a rich resource for further studies on the molecular breeding of H. perforatum in order to obtain varieties with high hypericin production.

Keywords: hypericin, St. John’s Wort, data mining, transcription factors, secondary metabolites

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Authors: Michael Josef Schwerer

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Background: Analyzing any aircraft accident is mandatory based on the regulations of the International Civil Aviation Organization and the respective country’s criminal prosecution authorities. Legal medicine investigations are unavoidable when fatalities involve the flight crew or when doubts arise concerning the pilot’s aeromedical health status before the event. As a result of frequently tremendous blunt and sharp force trauma along with the impact of the aircraft to the ground, consecutive blast or fire exposition of the occupants or putrefaction of the dead bodies in cases of delayed recovery, relevant findings can be masked or destroyed and therefor being inaccessible in standard pathology practice comprising just forensic autopsy and histopathology. Such cases are of considerable risk of remaining unsolved without legal consequences for those responsible. Further, no lessons can be drawn from these scenarios to improve flight safety and prevent future mishaps. Aims and Methods: To learn from previously unsolved aircraft accidents, re-evaluations of the investigation files and modern molecular pathology studies were performed. Genetic testing involved predominantly PCR-based analysis of gene regulation, studying DNA promotor methylations, RNA transcription and posttranscriptional regulation. In addition, the presence or absence of infective agents, particularly DNA- and RNA-viruses, was studied. Technical adjustments of molecular genetic procedures when working with archived sample material were necessary. Standards for the proper interpretation of the respective findings had to be settled. Results and Discussion: Additional molecular genetic testing significantly contributes to the quality of forensic pathology assessment in aviation mishaps. Previously undetected cardiotropic viruses potentially explain e.g., a pilot’s sudden incapacitation resulting from cardiac failure or myocardial arrhythmia. In contrast, negative results for infective agents participate in ruling out concerns about an accident pilot’s fitness to fly and the aeromedical examiner’s precedent decision to issue him or her an aeromedical certificate. Care must be taken in the interpretation of genetic testing for pre-existing diseases such as hypertrophic cardiomyopathy or ischemic heart disease. Molecular markers such as mRNAs or miRNAs, which can establish these diagnoses in clinical patients, might be misleading in-flight crew members because of adaptive changes in their tissues resulting from repeated mild hypoxia during flight, for instance. Military pilots especially demonstrate significant physiological adjustments to their somatic burdens in flight, such as cardiocirculatory stress and air combat maneuvers. Their non-pathogenic alterations in gene regulation and expression will likely be misinterpreted for genuine disease by inexperienced investigators. Conclusions: The growing influence of molecular pathology on legal medicine practice has found its way into aircraft accident investigation. As appropriate quality standards for laboratory work and data interpretation are provided, forensic genetic testing supports the medico-legal analysis of aviation mishaps and potentially reduces the number of unsolved events in the future.

Keywords: aviation medicine, aircraft accident investigation, forensic pathology, molecular pathology

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Authors: Raphaël Weuts, Mykyta Petik, Anton Vedder

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Artificial Intelligence has the potential to create and already creates enormous value in healthcare. Prescriptive systems might be able to make the use of healthcare capacity more efficient. Such systems might entail interpretations that exclude the effect of confounders that brings risks with it. Those risks might be mitigated by regulation that prevents systems entailing such risks to come to market. One modality of regulation is that of legislation, and the European AI Act is an example of such a regulatory instrument that might mitigate these risks. To assess the risk mitigation potential of the AI Act for those risks, this research focusses on a case study of a hypothetical application of medical device software that entails the aforementioned risks. The AI Act refers to the harmonised norms for already existing legislation, here being the European medical device regulation. The issue at hand is a causal link between a confounder and the value the algorithm optimises for by proxy. The research identifies where the AI Act already looks at confounders (i.a. feedback loops in systems that continue to learn after being placed on the market). The research identifies where the current proposal by parliament leaves legal uncertainty on the necessity to check for confounders that do not influence the input of the system, when the system does not continue to learn after being placed on the market. The authors propose an amendment to article 15 of the AI Act that would require high-risk systems to be developed in such a way as to mitigate risks from those aforementioned confounders.

Keywords: AI Act, healthcare, confounders, risks

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Authors: Peter. M. Kusen, Georg Wandrey, Christopher Probst, Dietrich Kohlheyer, Jochen Buchs, Jorg Pietruszkau

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Light as a stimulus provides the capability to develop regulation techniques for customizable gene expression. A great advantage is the extremely flexible and accurate dosing that can be performed in a non invasive and sterile manner even for high throughput technologies. Therefore, light regulation in a multiwell microbioreactor system was realized providing the opportunity to control gene expression with outstanding complexity. A light-regulated gene expression system in Saccharomyces cerevisiae was designed applying the strategy of caged compounds. These compounds are photo-labile protected and therefore biologically inactive regulator molecules which can be reactivated by irradiation with certain light conditions. The “caging” of a repressor molecule which is consumed after deprotection was essential to create a flexible expression system. Thereby, gene expression could be temporally repressed by irradiation and subsequent release of the active repressor molecule. Afterwards, the repressor molecule is consumed by the yeast cells leading to reactivation of gene expression. A yeast strain harboring a construct with the corresponding repressible promoter in combination with a fluorescent marker protein was applied in a Photo-BioLector platform which allows individual irradiation as well as online fluorescence and growth detection. This device was used to precisely control the repression duration by adjusting the amount of released repressor via different irradiation times. With the presented screening platform the regulation of complex expression procedures was achieved by combination of several repression/derepression intervals. In particular, a stepwise increase of temporally-constant expression levels was demonstrated which could be used to study concentration dependent effects on cell functions. Also linear expression rates with variable slopes could be shown representing a possible solution for challenging protein productions, whereby excessive production rates lead to misfolding or intoxication. Finally, the very flexible regulation enabled accurate control over the expression induction, although we used a repressible promoter. Summing up, the continuous online regulation of gene expression has the potential to synchronize gene expression levels to optimize metabolic flux, artificial enzyme cascades, growth rates for co cultivations and many other applications addicted to complex expression regulation. The developed light-regulated expression platform represents an innovative screening approach to find optimization potential for production processes.

Keywords: caged-compounds, gene expression regulation, optogenetics, photo-labile protecting group

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Authors: Marco Morini, Nicolandrea Calabrese, Dario Chello

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Despite the international commitment of Algeria towards the development of energy efficiency and renewable energy in the country, the internal energy demand has been continuously growing during the last decade due to the substantial increase of population and of living conditions, which in turn has led to an unprecedented expansion of the residential building sector. The thermal building regulation is the technical document that establishes the calculation framework for the thermal performance of buildings in Algeria, setting up minimum obligatory targets for the thermal performance of new buildings. An update of this regulation is due in the coming years, and this paper discusses some proposals in this regard, with the aim to improve the energy efficiency of the building sector, particularly with regard to social housing. In particular, it proposes a methodology for drafting an energy performance label of new Algerian residential buildings, moving from the results of the thermal compliance verification and sizing of technical systems as defined in the RTB. Such an energy performance label – whose calculation method is briefly described in the paper – aims to raise citizens' awareness of the benefits of energy efficiency. It can represent the first step in a process of integrating technical installations into the calculation of the energy performance of buildings in Algeria.

Keywords: building, energy certification, energy efficiency, social housing, international cooperation, Mediterranean region

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Authors: Alvian R. E. Purnomo, K. Noni Srijati, Hernawan Adi

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Government regulation is a result of agreement on the struggle of ideas, interests, and ideologies among elites in state institution. The polemic about death penalty policy in Indonesia is still becoming an interesting discussion and also a complex issue. There are pros/ cons of whether the policy is humane or not. Indonesia becomes the concern of the world’s community because the policy of death penalty applied is considered not reflecting the values of Indonesian culture including tolerance, mutual cooperation, and love. This paper examines them using literature study on how public policy theories respond to humanity issues and how Indonesian government should take steps to the issue of the death penalty that has become polemic until now.

Keywords: government regulation, public policy, death penalty policy, humanity

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Authors: Cheng-Cao Sun, Shu-Jun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, De-Jia Li

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Hsa-miRNA-326 (miR-326) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-326 on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-326 on the development of NSCLC. The results indicated that miR-326 was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-326 in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4, and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-326 induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-326 inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene CCND1 was revealed to be a putative target of miR-326, which was inversely correlated with miR-326 expression in NSCLC. Taken together, our results demonstrated that miR-326 played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic CCND1.

Keywords: hsa-miRNA-326 (miR-326), cyclin D1, non-small cell lung cancer (NSCLC), proliferation, apoptosis

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Authors: Ilija Musa

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Positive legal regulation of juvenile privacy protection, current state of showing a child in BH media and possibilities of a child’s privacy protection by more adequate media legislature which should be arranged in accordance to recommendations of the UN Committee on the Rights of the Child for Bosnia and Herzegovina. Privacy of the minors in Bosnian-Herzegovinian media is insufficiently legally arranged. Due to the fact that there is no law on media area arrangement at the state level, electronic media are under jurisdiction of Communications regulatory agency, which at least partially, regulated the sector of radio and television broadcasting by adequate protection of child’s privacy. However, print and online media are under jurisdiction of non-governmental association Print and online media council in B&H which is not authorized to punish violators of this body’s Codex, what points out the necessity of passing the unique media law which would enable sanctioning the child’s privacy violation. The analysis of media content, which is a common violation of the child's privacy, analysis of positive legislation which regulates the media, confirmed the working hypothesis by which the minor’s protection policy in BH media is not protected at the appropriate level. Taking this into consideration, in the conclusion of this article the author gives recommendations for the regulation of legal protection of minor’s privacy in BH media.

Keywords: children, media, legislation, privacy protection, Bosnia Herzegovina

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Authors: Jafar Ahmadi, Zhohreh Asiaban, Sedigheh Fabriki Ourang

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Brassinosteroids (BRs) regulate cell elongation, vascular differentiation, senescence and stress responses. BRs signal through the BES1/BZR1 family of transcription factors, which regulate hundreds of target genes involved in this pathway. In this research a comprehensive genome-wide analysis was carried out in BES1/BZR1 gene family in Arabidopsis thaliana, Cucumis sativus, Vitis vinifera, Glycin max, and Brachypodium distachyon. Specifications of the desired sequences, dot plot and hydropathy plot were analyzed in the protein and genome sequences of five plant species. The maximum amino acid length was attributed to protein sequence Brdic3g with 374aa and the minimum amino acid length was attributed to protein sequence Gm7g with 163aa. The maximum Instability index was attributed to protein sequence AT1G19350 equal with 79.99 and the minimum Instability index was attributed to protein sequence Gm5g equal with 33.22. Aliphatic index of these protein sequences ranged from 47.82 to 78.79 in Arabidopsis thaliana, 49.91 to 57.50 in Vitis vinifera, 55.09 to 82.43 in Glycin max, 54.09 to 54.28 in Brachypodium distachyon 55.36 to 56.83 in Cucumis sativus. Overall, data obtained from our investigation contributes a better understanding of the complexity of the BES1/BZR1 gene family and provides the first step towards directing future experimental designs to perform systematic analysis of the functions of the BES1/BZR1 gene family.

Keywords: BES1/BZR1, brassinosteroids, phylogenetic analysis, transcription factor

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Authors: Wahyu Riawanti

Abstract:

Food safety is the one of a prominent issue for globalization era. The more concern is paid in international food and agriculture trade; the more consumers will consider raising the standard of food safety. For this reason, the role of the issue is not only in term of added value but since then also the main requirement in import export activity, including agriculture products. Unfortunately, Indonesia and other developing countries found it difficult to fulfill some of the technical issues and end it up with the lower export activity. In this case, the technical requirements of food safety become an obstacle rather than challenging. Furthermore for local farmers’ activity, food safety is more or less a threat. The study is aimed to reveal on how Indonesian government had dealt with the certification regulation to face problem on competitiveness of Indonesian products. Local government has conducted the regulation of food certification. The study used the case of Salak Pondoh fruit (Salacca zalacca) certification process on Sleman District- Yogyakarta. Triangulation method was used to analyze the effectiveness of the certification program. The quantitative data series taken from 7 farmer groups during the certification processes were used for the research main data. The supporting qualitative data was obtained from in-depth interview with the members of farmers group. The pre-research result has shown that the impact varied from different groups. Conclusively the certification regulation has partly failed to make a significant change in local farmers’ competitiveness. Even the profit was increased, the highly amount budget of the program did not significantly increase the economic incentives for local farmers.

Keywords: economic incentive, food security, government regulation, international trade, local commodity, Salacca zalacca

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Authors: Sara Vora (Hoxha)

Abstract:

An essential feature of any international lawsuit is the ability of the parties to pick the law that would apply in the event of a tort claim. This option to choose the law to use in tort cases is based on Article 14 and 4/3 of the Rome II Regulation. The purpose of this article is to examine the boundaries of this freedom, as well as its relevance in international legal disputes. The article opens with a brief introduction to the basics of tort law. After a short introduction, the article demonstrates why Article 14 and 4/3 of the Rome II Regulation are so crucial to the right to select appropriate law in tort cases. The notion of the right to select the law to use in tort cases is examined, along with its breadth and possible restrictions. The article presents case studies to demonstrate how the right to select relevant law in tort might be put into practise. Case results and the judges' rationales for their rulings are examined. The possible influence of the right to select applicable law in tort on the process of harmonisation is also explored in this study. The results are summarised and the primary research question is addressed in the last section of the paper. In conclusion, the parties' ability to pick the law that rules their dispute via the freedom to choose relevant law in tort is a crucial feature of cross-border litigation. Despite certain restrictions, this freedom is nevertheless an important part of the legal structure that governs international conflicts.

Keywords: applicable law, tort, Rome II regulation, freedom to choose, cross-border litigation, harmonization of tort law

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Authors: Juan C. Torrado, Javier Gomez, Guadalupe Montero, German Montoro, M. Dolores Villalba

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One of the most challenging aspects of the executive dysfunction of people with Autism Spectrum Disorders is the behavior control. This is related to a deficit in their ability to regulate, recognize and manage their own emotions. Some researchers have developed applications for tablets and smartphones to practice strategies of relaxation and emotion recognition. However, they cannot be applied to the very moment of temper outbursts, anger episodes or anxiety, since they require to carry the device, start the application and be helped by caretakers. Also, some of these systems are developed for either obsolete technologies (old versions of tablet devices, PDAs, outdated operative systems of smartphones) or specific devices (self-developed or proprietary ones) that create differentiation between the users and the rest of the individuals in their context. For this project we selected smartwatches. Focusing on emergent technologies ensures a wide lifespan of the developed products, because the derived products are intended to be available in the same moment the very technology gets popularized, not later. We also focused our research in commercial versions of smartwatches, since this way differentiation is easily avoided, so the users’ abandonment rate lowers. We have developed a smartwatch system along with a smartphone authoring tool to display self-regulation strategies. These micro-prompting strategies are conformed of pictograms, animations and temporizers, and they are designed by means of the authoring tool: When both devices synchronize their data, the smartwatch holds the self-regulation strategies, which are triggered when the smartwatch sensors detect a remarkable rise of heart rate and movement. The system is being currently tested in an educational center of people with ASD of Madrid, Spain.

Keywords: assistive technologies, emotion regulation, human-computer interaction, smartwatches

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