Search results for: parental regulation

Authors: Akhil Raj Pushparajan, Ranjit Ramachandran, Jijimole Gopi Reji, Ajay Kumar Ramakrishnan

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the leading causes of death by an infectious disease. In spite of the availability of effective drugs and a vaccine, TB is a major health concern and was declared a global emergency by the World Health Organization (WHO). The success of intracellular pathogens like Mtb depends on its ability to overcome the challenging environment in the host. Gene regulation controlled by transcriptional regulators (TRs) plays a crucial role for the bacteria to adapt to the host environment. In vitro studies on gene regulatory mechanisms during dormancy and reactivation have provided insights into the adaptations employed by Mtb to survive in the host. Here we present our efforts to functionally characterize Rv1019, a putative TR of Mtb H37Rv which was found to be present at significantly varying levels during dormancy and reactivation in vitro. The expression of this protein in the dormancy-reactivation model was validated by qRT-PCR and western blot. By DNA- protein interaction studies and reporter assays we found that under normal laboratory conditions of growth this protein behaves as an auto-repressor and tetracycline was found to abrogate this repression by interfering with its ability to bind DNA. Further, by cDNA analysis, we found that this TR is co-transcribed with its downstream genes Rv1020 (mfd) and Rv1021 (mazG) which are involved in DNA damage response in Mtb. Constitutive expression of this regulator in the surrogate host M. smegmatis showed downregulation of the orthologues of downstream genes suggested that Rv1019 could negatively regulate these genes. Our finds also show that M. smegmatis expressing Rv1019 is sensitive to DNA damage suggests the role of this protein in regulating DNA damage response induced by oxidative stress. Because of its role in regulating DNA damage response which may help in the persistence of Mtb, Rv1019 could be used as a prospective target for therapeutic intervention to fight TB.

Keywords: auto-repressor, DNA repair, mycobacterium smegmatis, mycobacterium tuberculosis, tuberculosis

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Authors: Rohan M. Dalal, Elena Pirondini, Shanu Somvanshi

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Introduction: The current state of reproductive health outcomes in lower-income countries is poor, with inadequate knowledge and culture among adolescent boys. Moreover, boys have traditionally not been a priority target. To explore the opportunity to educate adolescent boys in the developing world regarding accurate reproductive health information, the purpose of this study is to investigate how adolescent boys in the developing world engage and use technology, utilizing cell phones. This electronic survey and video interview study were conducted to determine the feasibility of a mobile phone platform for an educational video game specifically designed for boys that will improve health knowledge, influence behavior, and change health outcomes, namely teen pregnancies. Methods: With the assistance of Plan India, a subsidiary of Plan International, informed consent was obtained from parents of adolescent males who participated in an electronic survey and video interviews via Microsoft Teams. An electronic survey was created with 27 questions, including topics of mobile phone usage, gaming preferences, and sexual and reproductive health, with a sample size of 181 adolescents, ages 11-25, near New Delhi, India. The interview questions were written to explore more in-depth topics after the completion of the electronic survey. Eight boys, aged 15, were interviewed for 40 minutes about gaming and usage of mobile phones as well as sexual and reproductive health. Data/Results. 154 boys and 27 girls completed the survey. They rated their English fluency as relatively high. 97% of boys (149/154) had access to mobile phones. The majority of phones were smartphones (97%, 143/148). 48% (71/149) of boys borrowed cell phones. The most popular phone platform was Samsung (22%, 33/148). 36% (54/148) of adolescent males looked at their phones 1-10 times per day for 1-2 hours. 55% (81/149) of the boys had parental restrictions. 51% (76/148) had 32 GB of storage on their phone. 78% (117/150) of the boys had wifi access. 80% (120/150) of respondents reported ease in downloading apps. 97% (145/150) of male adolescents had social media, including WhatsApp, Facebook, and YouTube. 58% (87/150) played video games. Favorite video games included Free Fire, PubG, and other shooting games. In the video interviews, the boys revealed what made games fun and engaging, including customized avatars, progression to higher levels, realistic interactive platforms, shooting/guns, the ability to perform multiple actions, and a variety of worlds/settings/adventures. Ideas to improve engagement in sexual and reproductive health classes included open discussions in the community, enhanced access to information, and posting on social media. Conclusion: This study involving an electronic survey and video interviews provides an initial foray into understanding mobile phone usage among adolescent males and understanding sexual and reproductive health education in New Delhi, India. The data gathered from this study support using mobile phone platforms, and this will be used to create a serious video game to educate adolescent males about sexual and reproductive health in an attempt to lower the rate of unwanted pregnancies in the world.

Keywords: adolescent males, India, mobile phone, sexual and reproductive health

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Authors: Bartosz Kedra, Robert Malkowski

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This paper provides description and presentation of laboratory test unit built basing on 150 kVA power frequency converter and Simulink RealTime platform. Assumptions, based on criteria which load and generator types may be simulated using discussed device, are presented, as well as control algorithm structure. As laboratory setup contains transformer with thyristor controlled tap changer, a wider scope of setup capabilities is presented. Information about used communication interface, data maintenance, and storage solution as well as used Simulink real-time features is presented. List and description of all measurements are provided. Potential of laboratory setup modifications is evaluated. For purposes of Rapid Control Prototyping, a dedicated environment was used Simulink RealTime. Therefore, load model Functional Unit Controller is based on a PC computer with I/O cards and Simulink RealTime software. Simulink RealTime was used to create real-time applications directly from Simulink models. In the next step, applications were loaded on a target computer connected to physical devices that provided opportunity to perform Hardware in the Loop (HIL) tests, as well as the mentioned Rapid Control Prototyping process. With Simulink RealTime, Simulink models were extended with I/O cards driver blocks that made automatic generation of real-time applications and performing interactive or automated runs on a dedicated target computer equipped with a real-time kernel, multicore CPU, and I/O cards possible. Results of performed laboratory tests are presented. Different load configurations are described and experimental results are presented. This includes simulation of under frequency load shedding, frequency and voltage dependent characteristics of groups of load units, time characteristics of group of different load units in a chosen area and arbitrary active and reactive power regulation basing on defined schedule.

Keywords: MATLAB, power converter, Simulink Real-Time, thyristor-controlled tap changer

Procedia PDF Downloads 323

Authors: Fanny Guay

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Building resilience, sustainable buildings, urbanization, climate change, resilient cities, are just a few examples of where the focus of research has been in the last few years. It is obvious that there is a need to rethink how we are building our cities and how we are renovating our existing buildings. However, the question remaining is how can we assure that we are building sustainable yet resilient cities? There are many aspects one can touch upon when discussing resilience in cities, but after the event of Grenfell in June 2017, it has become clear that fire resilience must be a priority. We define resilience as a holistic approach including communities, society and systems, focusing not only on resisting the effects of a disaster, but also how it will cope and recover from it. Cities are an example of such a system, where components such as buildings have an important role to play. A building on fire will have an impact on the community, the economy, the environment, and so the entire system. Therefore, we believe that fire and resilience go hand in hand when we discuss building resilient cities. This article aims at discussing the current state of the concept of fire resilience and suggests actions to support the built of more fire resilient buildings. Using the case of Grenfell and the fire safety regulations in the UK, we will briefly compare the fire regulations in other European countries, more precisely France, Germany and Denmark, to underline the difference and make some suggestions to increase fire resilience via regulation. For this research, we will also include other types of resilience such as technological resilience, discussing the structure of buildings itself, as well as community resilience, considering the role of communities in building resilience. Our findings demonstrate that to increase fire resilience, amending existing regulations might be necessary, for example, how we performed reaction to fire tests and how we classify building products. However, as we are looking at national regulations, we are only able to make general suggestions for improvement. Another finding of this research is that the capacity of the community to recover and adapt after a fire is also an essential factor. Fundamentally, fire resilience, technological resilience and community resilience are closely connected. Building resilient cities is not only about sustainable buildings or energy efficiency; it is about assuring that all the aspects of resilience are included when building or renovating buildings. We must ask ourselves questions as: Who are the users of this building? Where is the building located? What are the components of the building, how was it designed and which construction products have been used? If we want to have resilient cities, we must answer these basic questions and assure that basic factors such as fire resilience are included in our assessment.

Keywords: buildings, cities, fire, resilience

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Authors: Surini Duthika Fernandopulle, Kalamba Arachchige Pramodya Wijesinghe

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Macrocapsules containing phase change material (PCM) PEG4000 as core and Calcium Alginate as the shell was synthesized by in-situ polymerization process, and their suitability for textile applications was studied. PCM macro-capsules were sandwiched between two polyurethane foams at regular intervals, and the sandwiched foams were subsequently covered with 100% cotton woven fabrics. According to the mathematical modelling and calculations 46 capsules were required to provide cooling for a period of 2 hours at 56ºC, so a panel of 10 cm x 10 cm area with 25 parts (having 5 capsules in each for 9 parts are 16 parts spaced for air permeability) were effectively merged into one textile material without changing the textile's original properties. First, the available cooling techniques related to textiles were considered and the best cooling techniques suiting the Sri Lankan climatic conditions were selected using a survey conducted for Sri Lankan Public based on ASHRAE-55-2010 standard and it consisted of 19 questions under 3 sections categorized as general information, thermal comfort sensation and requirement of Personal Cooling Garments (PCG). The results indicated that during daytime, majority of respondents feel warm and during nighttime also majority have responded as slightly warm. The survey also revealed that around 85% of the respondents are willing to accept a PCG. The developed panels were characterized using Fourier-transform infrared spectroscopy (FTIR) and Thermogravimetric Analysis (TGA) tests and the findings from FTIR showed that the macrocapsules consisted of PEG 4000 as the core material and Calcium Alginate as the shell material and findings from TGA showed that the capsules had the average weight percentage for core with 61,9% and shell with 34,7%. After heating both control samples and samples incorporating PCM panels, it was discovered that only the temperature of the control sample increased after 56ºC, whereas the temperature of the sample incorporating PCM panels began to regulate the temperature at 56ºC, preventing a temperature increase beyond 56ºC.

Keywords: phase change materials, thermal regulation, textiles, macrocapsules

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Authors: Avitus A. Agbor

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Numerous incidents, ranging from trivial to catastrophic, do come to mind when one reflects on hate. The victims of these belong to specific identifiable groups within communities. These experiences evoke discussions on Islamophobia, xenophobia, homophobia, anti-Semitism, racism, ethnic hatred, atheism, and other brutal forms of bigotry. Common to all these is an invisible but portent force that drives all of them: hatred. Such hatred is usually fueled by a profound degree of intolerance (to diversity) and the zeal to impose on others their beliefs and practices which they consider to be the conventional norm. More importantly, the perpetuation of these hateful acts is the unfortunate outcome of an overplay of invectives and hate speech which, to a greater extent, cannot be divorced from hate. From a legal perspective, acknowledging the existence of an undeniable link between hate speech and hate is quite easy. However, both within and without legal scholarship, the notion of “hate speech” remains a conundrum: a phrase that is quite easily explained through experiences than propounding a watertight definition that captures the entire essence and nature of what it is. The problem is further compounded by a few factors: first, within the international human rights framework, the notion of hate speech is not used. In limiting the right to freedom of expression, the ICCPR simply excludes specific kinds of speeches (but does not refer to them as hate speech). Regional human rights instruments are not so different, except for the subsequent developments that took place in the European Union in which the notion has been carefully delineated, and now a much clearer picture of what constitutes hate speech is provided. The legal architecture in domestic legal systems clearly shows differences in approaches and regulation: making it more difficult. In short, what may be hate speech in one legal system may very well be acceptable legal speech in another legal system. Lastly, the cornucopia of academic voices on the issue of hate speech exude the divergence thereon. Yet, in the absence of a well-formulated and universally acceptable definition, it is important to consider how hate speech can be defined. Taking an evidence-based approach, this research looks into the issue of defining hate speech in legal scholarship and how and why such a formulation is of critical importance in the prohibition and prosecution of hate speech.

Keywords: hate speech, international human rights law, international criminal law, freedom of expression

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Authors: Omolola R. Ayepola, Nicole L. Brooks, Oluwafemi O. Oguntibeju

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The liver plays an important role in the regulation of blood glucose and is a target organ of hyperglycaemia. Hyperglycemia plays a crucial role in the onset of various liver diseases and may culminate into hepatopathy if untreated. Alteration in antioxidant defense and increase in oxidative stress that results in tissue injury is characteristic of diabetes. We evaluated the protective effects of kolaviron-a biflavonoid complex, on hepatic antioxidants, lipid peroxidation and apoptosis in the liver of diabetic rats. To induce type I diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 50 mg/kg. Oral treatment of diabetic rats with kolaviron (100 mg/kg) started on the 6th day after diabetes induction and continued for 6 weeks (5 times weekly). Diabetic rats exhibited a significant increase in the peroxidation of hepatic lipids as observed from the elevated level of malondialdehyde (MDA) estimated by High-Performance Liquid Chromatography. In addition, Oxygen Radical Absorbance Capacity (ORAC), ratio of reduced to oxidized glutathione (GSH/GSSG) and catalase (CAT) activity was decreased in the liver of diabetic rats. TUNEL assay revealed increased apoptotic cell death in the liver of diabetic rats. Examination of Pancreatic beta-cells by immunohistochemical methods revealed beta cell degeneration and reduction in beta cell/ islet area in the diabetic controls. Kolaviron-treatment increased the area of insulin immunoreactive beta-cells significantly. Kolaviron attenuated lipid peroxidation and apoptosis in the liver of diabetic rats, increased CAT activity GSH levels and the resultant GSH: GSSG. The ORAC of kolaviron-treated diabetic liver was restored to near-normal values. Kolaviron protects the liver against oxidative and apoptotic damage induced by hyperglycemia. The antidiabetic effect of kolaviron may also be related to its beneficial effects on beta-cell function.

Keywords: diabetes mellitus, kolaviron, oxidative stress, liver, apoptosis

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Authors: Sarocha Vivatvakin, Thanaporn Ratchataswan, Thiratest Leesutipornchai, Komkrit Ruangritchankul, Somboon Keelawat, Virachai Kerekhanjanarong, Patnarin Mahattanasakul, Saknan Bongsebandhu-Phubhakdi

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In this globalization era, much attention has been drawn to various molecular biomarkers, which may have the potential to predict the progression of cancer. Epidermal growth factor receptor (EGFR) is the classic member of the ErbB family of membrane-associated intrinsic tyrosine kinase receptors. EGFR expression was found in several organs throughout the body as its roles involve in the regulation of cell proliferation, survival, and differentiation in normal physiologic conditions. However, anomalous expression, whether over- or under-expression is believed to be the underlying mechanism of pathologic conditions, including carcinogenesis. Even though numerous discussions regarding the EGFR as a prognostic tool in head and neck cancer have been established, the consensus has not yet been met. The aims of the present study are to assess the correlation between the level of EGFR expression and demographic data as well as clinicopathological features and to evaluate the ability of EGFR as a reliable prognostic marker. Furthermore, another aim of this study is to investigate the probable pathophysiology that explains the finding results. This retrospective study included 30 squamous cell laryngeal carcinoma patients treated at King Chulalongkorn Memorial Hospital from January 1, 2000, to December 31, 2004. EGFR expression level was observed to be significantly downregulated with the progression of the laryngeal cancer stage. (one way ANOVA, p = 0.001) A statistically significant lower EGFR expression in the late stage of the disease compared to the early stage was recorded. (unpaired t-test, p = 0.041) EGFR overexpression also showed the tendency to increase recurrence of cancer (unpaired t-test, p = 0.128). A significant downregulation of EGFR expression was documented in advanced stage laryngeal cancer. The results indicated that EGFR level correlates to prognosis in term of stage progression. Thus, EGFR expression might be used as a prevailing biomarker for laryngeal squamous cell carcinoma prognostic prediction.

Keywords: downregulation, epidermal growth factor receptor, immunohistochemistry, laryngeal squamous cell carcinoma

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Authors: Mohammad-Ali Latifi, Harry Bouwman

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Changes in the business environment accelerated dramatically over the last decades as a result of changes in technology, regulation, market, and competitors’ behavior. Firms need to change the way they do business in order to survive or maintain their growth. Innovating business model (BM) can create competitive advantages and enhance firm performance. However, many companies fail to achieve expected outcomes in practice, mostly due to irreversible fundamental changes in key components of the company’s BM. This leads to more ambiguity, uncertainty, and risks associated with business performance. However, the relationship among BM Innovation, moderating factors, and the firm’s overall performance is by and large ignored in the current literature. In this study, we identified twenty moderating factors from our comprehensive literature review. We categorized these factors based on two criteria regarding the extent to which: the moderating factors can be controlled and managed by firms, and they are generic or specific changes to the firms. This leads to four moderation groups. The first group is BM implementation, which includes management support, employees’ commitment, employees’ skills, communication, detailed plan. The second group is called BM practices, which consists of BM tooling, BM experimentation, the scope of change, speed of change, degree of novelty. The third group is Firm characteristics, including firm size, age, and ownership. The last group is called Industry characteristics, which considers the industry sector, competitive intensity, industry life cycle, environmental dynamism, high-tech vs. low-tech industry. Through collecting data from 508 European small and medium-sized enterprises (SMEs) and using the structural equation modeling technique, the developed moderation model was examined. Results revealed that all factors highlighted through these four groups moderate the relation between BMI and firm performance significantly. Particularly, factors related to BM-Implementation and BM-Practices are more manageable and would potentially improve firm overall performance. We believe that this result is more important for researchers and practitioners since the possibility of working on factors in Firm characteristics and Industry characteristics groups are limited, and the firm can hardly control and manage them to improve the performance of BMI efforts.

Keywords: business model innovation, firm performance, implementation, moderation

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Authors: María Dolores Caro, Eugenio M. Fedriani, Ángel F. Tenorio

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When lorries transport dangerous goods, there exist some legal stipulations in the European Union for assuring the security of the rest of road users as well as of those goods being transported. At this respect, lorry drivers cannot park in usual parking areas, because they must use parking areas with special conditions, including permanent supervision of security personnel. Moreover, drivers are compelled to satisfy additional regulations about resting and driving times, which involve in the practical possibility of reaching the suitable parking areas under these time parameters. The “European Agreement concerning the International Carriage of Dangerous Goods by Road” (ADR) is the basic regulation on transportation of dangerous goods imposed under the recommendations of the United Nations Economic Commission for Europe. Indeed, nowadays there are no enough parking areas adapted for dangerous goods and no complete study have suggested the best locations to build new areas or to adapt others already existing to provide the areas being necessary so that lorry drivers can follow all the regulations. The goal of this paper is to show how many additional parking areas should be built in the Iberian Peninsula to allow that lorry drivers may park in such areas under their restrictions in resting and driving time. To do so, we have modeled the problem via graph theory and we have applied a new efficient algorithm which determines an optimal solution for the problem of locating new parking areas to complement those already existing in the ADR for the Iberian Peninsula. The solution can be considered minimal since the number of additional parking areas returned by the algorithm is minimal in quantity. Obviously, graph theory is a natural way to model and solve the problem here proposed because we have considered as nodes: the already-existing parking areas, the loading-and-unloading locations and the bifurcations of roads; while each edge between two nodes represents the existence of a road between both nodes (the distance between nodes is the edge's weight). Except for bifurcations, all the nodes correspond to parking areas already existing and, hence, the problem corresponds to determining the additional nodes in the graph such that there are less up to 100 km between two nodes representing parking areas. (maximal distance allowed by the European regulations).

Keywords: dangerous goods, parking areas, Iberian peninsula, graph-based modeling

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Authors: Seong Gu Hwang, Young Kyoon Oh, Joseph F. dela Cruz

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Marbling, or intramuscular fat, has been consistently identified as one of the top beef quality problems. Intramuscular adipocytes distribute throughout the perimysial connective tissue of skeletal muscle and are the major site for the deposition of intramuscular fat, which is essential for the eating quality of meat. The stromal vascular fraction of the skeletal muscle contains progenitor cells that can be enhanced to differentiate to adipocytes and increase intramuscular fat. Primary cultures of bovine intramuscular stromal vascular cells were used in this study to elucidate the effects of extracellular calcium and retinoic acid concentration on adipocyte differentiation. Cell viability assay revealed that even at different concentrations of calcium and retinoic acid, there was no significant difference on cell viability. Monitoring of the adipocyte differentiation showed that bovine intramuscular stromal vascular cells cultured in a low concentration of extracellular calcium and retinoic acid had a better degree of fat accumulation. The mRNA and protein expressions of PPARγ, C/EBPα, SREBP-1c and aP2 were analyzed and showed a significant upregulation upon the reduction in the level of extracellular calcium and retinoic acid. The upregulation of these adipogenic related genes means that the decreasing concentration of calcium and retinoic acid is able to stimulate the adipogenic differentiation of bovine intramuscular stromal vascular cells. To further elucidate the effect of calcium, the expression level of calreticulin was measured. Calreticulin which is known to be an inhibitor of PPARγ was down regulated by the decreased level of calcium and retinoic acid in the culture media. The same tendency was observed on retinoic acid receptors RARα and CRABP-II. These receptors are recognized as adipogenic inhibitors, and the downregulation of their expression allowed a better level of differentiation in bovine intramuscular stromal vascular cells. In conclusion, data show that decreasing the level of extracellular calcium and retinoic acid can significantly promote adipogenesis in intramuscular stromal vascular cells of Hanwoo beef cattle. These findings may provide new insights in enhancing intramuscular adipogenesis and marbling in beef cattle.

Keywords: calcium, calreticulin, hanwoo beef, retinoic acid

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Authors: Surbhi Surbhi, Andrea Erni, Gunter Meister, Harold Cremer, Christophe Beclin

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MicroRNAs (miRNAs) are short 20-23 nucleotide long non-coding RNAs; there are 2605 miRNA in humans and 1936 miRNA in mouse in total (miRBase). The nervous system expresses the most abundant miRNA and most diverse. MiRNAs play a role in many steps during neurogenesis, like cell proliferation, differentiation, neural patterning, axon pathfinding, etc. Moreover, in vitro studies suggested a role in the regulation of local translation at the synapse, thus controlling neuronal plasticity. However, due to the specific structure of miRNA molecules, an in-vivo confirmation of the general role of miRNAs in the control of neuronal plasticity is still pending. For example, their small size and their high level of sequence homology make difficult the analysis of their cellular and sub-cellular localization in-vivo by in-situ hybridization. Moreover, it was found that only 40% of the expressed miRNA molecules in a cell are included in RNA-Induced Silencing Complexes (RISC) and, therefore, involved in inhibitory interactions while the rest is silent. Definitively, the development of new tools is needed to have a better understanding of the cellular function of miRNAs, in particular their role in neuronal plasticity. Here we describe a new technique called in-vivo AGO-APP designed to investigate miRNA expression and function in-vivo. This technique is based on the expression of a small peptide derived from the human RISC-complex protein TNRC6B, called T6B, which binds all known Argonaute (Ago) proteins with high affinity allowing the efficient immunoprecipitation of AGO-bound miRNAs. We have generated two transgenic mouse lines conditionally expressing T6B either ubiquitously in the cell or targeted at the synapse. A comparison of the repertoire of miRNAs immuno-precipitated from mature neurons of both mouse lines will provide us with a list of miRNAs showing a specific activity at the synapse. The physiological role of these miRNAs will be subsequently addressed through gain and loss of function experiments.

Keywords: RNA-induced silencing complexes, TNRC6B, miRNA, argonaute, synapse, neuronal plasticity, neurogenesis

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Authors: Kan Yu, Khui Hung Lee, Eben Afrifa-Yamoah, Jing Guo, Katrina Harrison, Jack Goldblatt, Nicholas Pachter, Jitian Xiao, Guicheng Brad Zhang

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Background and Significance of the Study: Congenital Heart Defects (CHDs) are the most common malformation at birth and one of the leading causes of infant death. Although the exact etiology remains a significant challenge, epigenetic modifications, such as DNA methylation, are thought to contribute to the pathogenesis of congenital heart defects. At present, no existing DNA methylation biomarkers are used for early detection of CHDs. The existing CHD diagnostic techniques are time-consuming and costly and can only be used to diagnose CHDs after an infant was born. The present study employed a machine learning technique to analyse genome-wide methylation data in children with and without CHDs with the aim to find methylation biomarkers for CHDs. Methods: The Illumina Human Methylation EPIC BeadChip was used to screen the genome‐wide DNA methylation profiles of 24 infants diagnosed with congenital heart defects and 24 healthy infants without congenital heart defects. Primary pre-processing was conducted by using RnBeads and limma packages. The methylation levels of top 600 genes with the lowest p-value were selected and further investigated by using a random forest approach. ROC curves were used to analyse the sensitivity and specificity of each biomarker in both training and test sample sets. The functionalities of selected genes with high sensitivity and specificity were then assessed in molecular processes. Major Findings of the Study: Three genes (MIR663, FGF3, and FAM64A) were identified from both training and validating data by random forests with an average sensitivity and specificity of 85% and 95%. GO analyses for the top 600 genes showed that these putative differentially methylated genes were primarily associated with regulation of lipid metabolic process, protein-containing complex localization, and Notch signalling pathway. The present findings highlight that aberrant DNA methylation may play a significant role in the pathogenesis of congenital heart defects.

Keywords: biomarker, congenital heart defects, DNA methylation, random forest

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Authors: Hongliang Ding, Ziqu Ouyang

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Under the basic national conditions that the energy structure is dominated by coal, it is of great significance to realize deep and flexible peak shaving of boilers in pulverized coal power plants, and maximize the consumption of renewable energy in the power grid, to ensure China's energy security and scientifically achieve the goals of carbon peak and carbon neutrality. With the promising self-preheating combustion technology, which had the potential of broad-load regulation and rapid response to load changes, this study mainly investigated the different load operation and rapid load-change characteristics of pulverized coal combustion. Four effective load-stabilization bases were proposed according to preheating temperature, coal gas composition (calorific value), combustion temperature (spatial mean temperature and mean square temperature fluctuation coefficient), and flue gas emissions (CO and NOx concentrations), on the basis of which the load-change rates were calculated to assess the load response characteristics. Due to the improvement of the physicochemical properties of pulverized coal after preheating, stable ignition and combustion conditions could be obtained even at a low load of 25%, with a combustion efficiency of over 97.5%, and NOx emission reached the lowest at 50% load, with the concentration of 50.97 mg/Nm3 (@6%O2). Additionally, the load ramp-up stage displayed higher load-change rates than the load ramp-down stage, with maximum rates of 3.30 %/min and 3.01 %/min, respectively. Furthermore, the driving force formed by high step load was conducive to the increase of load-change rate. The rates based on the preheating indicator attained the highest value of 3.30 %/min, while the rates based on the combustion indicator peaked at 2.71 %/min. In comparison, the combustion indicator accurately described the system’s combustion state and load changes, whereas the preheating indicator was easier to acquire, with a higher load-change rate, hence the appropriate evaluation strategy should depend on the actual situation. This study verified a feasible method for deep and flexible peak shaving of coal-fired power units, further providing basic data and technical supports for future engineering applications.

Keywords: clean coal combustion, load-change rate, peak shaving, self-preheating

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Authors: Emmanuel Dele Balogun

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This paper analyzes, using descriptive statistics and econometrics data which span the period 1981 to 2014 to gauge the effects of trade policy incentives on economic growth in Nigeria. It argues that the provided incentives penalize economic growth during pre-trade liberalization eras, but stimulated a rapid increase in total factor productivity during the post-liberalization period of 2000 to 2014. The trend analysis shows that Nigeria maintained high tariff walls in economic regulation eras which became low in post liberalization era. The protections were in favor of infant industries, which were mainly appendages of multinationals but against imports of competing food and finished consumer products. The trade openness index confirms the undue exposure of Nigeria’s economy to the vagaries of international market shocks; while banking sector recapitalization and new listing of telecommunications companies deepened the financial markets in post-liberalization era. The structure of economic incentives was biased in favor of construction, trade and services, but against the real sector despite protectionist policies. Total Factor Productivity (TFP) estimates show that the Nigerian economy suffered stagnation in pre-liberalization eras, but experienced rapid growth rates in post-liberalization eras. The regression results relating trade policy incentives to TFP growth rate yielded a significant but negative intercept suggesting that a non-interventionist policy could be detrimental to economic progress, while protective tariff which limits imports of competing products could spur productivity gains in domestic import substitutes beyond factor growth with market liberalization. The main constraint to the effectiveness of trade policy incentives is the failure of benefiting industries to leverage on the domestic factor endowments of the nation. This paper concludes that there is the need to review the current economic transformation strategies urgently with a view to provide policymakers with a better understanding of the most viable options that could make for rapid success.

Keywords: economic growth, macroeconomic incentives, total factor productivity, trade policies

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Authors: Pelin Balcik Ercin

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Introduction: ZEB transcription factor family member ZEB2, has a role in epithelial to mesenchymal transition during development and metastasis. The altered circulating extracellular miRNAs expression is observed in diseases, and extracellular miRNAs have an important role in cancer cell microenvironment. In ChIP-Seq study, the expression of miR-2110 was found to be regulated by ZEB2. In this study, the effects of miR2110 on cell proliferation and migration of hepatocellular carcinoma (HCC) cells were examined. Material and Methods: SNU398 cells transfected with mimic miR2110 (20nM) (HMI0375, Sigma-Aldrich) and negative control miR (HMC0002, Sigma-Aldrich). MicroRNA isolation was accomplished with miRVANA isolation kit according to manufacturer instructions. cDNA synthesis was performed expression, respectively, and calibrated with Ct of controls. The real-time quantitative PCR (RT-qPCR) reaction was performed using the TaqMan Fast Advanced Master Mix (Thermo Sci.). Ct values of miR2110 were normalized to miR-186-5p and miR16-5p for the intracellular gene. Cell proliferation analysis was analyzed with the xCELLigence RTCA System. Wound healing assay was analyzed with the ImageJ program and relative fold change calculated. Results: The mimic-miR-2110 transfected SNU398 cells nearly nine-fold (log2) more miR-2110 expressed compared to negative control transfected cells. The mimic-miR-2110 transfected HCC cell proliferation significantly inhibited compared to the negative control cells. Furthermore, miR-2110-SNU398 cell migration capacity was relatively four-fold decreased compared to negative control-miR-SNU398 cells. Conclusion: Our results suggest the miR-2110 inhibited cell proliferation and also miR-2110 negatively affect cell migration compared to control groups in HCC cells. These data suggest the complexity of microRNA EMT transcription factors regulation. These initial results are pointed out the predictive biomarker capacity of miR-2110 in HCC.

Keywords: epithelial to mesenchymal transition, EMT, hepatocellular carcinoma cells, micro-RNA-2110, ZEB2

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Authors: Hung-Chieh Chen, Kuo-Hui Wang, Tsu-Lin Yeh

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Proteomics represent the performance of genomic complement proteins and the protein level on functional genomics. This study adopted proteomic strategies for comparing serum proteins among three groups: elite sprinter (sprint runner group, SR), long-distance runners (long-distance runner group, LDR), and the untrained control group (control group, CON). Purposes: This study aims to identify elite sprinters and long-distance runners’ serum protein and to provide a comparison of their serum proteome’ composition. Methods: Serum protein fractionations that separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed by a quantitative nano-LC-MS/MS-based proteomic profiling. The one-way analysis of variance (ANOVA) and Scheffe post hoc comparison (α= 0.05) was used to determine whether there is any significant difference in each protein level among the three groups. Results: (1) After analyzing the 307 identified proteins, there were 26 unique proteins in the SR group, and 18 unique proteins in the LDR group. (2) For the LDR group, 7 coagulation function-associated proteins’ expression levels were investigated: vitronectin, serum paraoxonase/arylesterase 1, fibulin-1, complement C3, vitamin K-dependent protein, inter-alpha-trypsin inhibitor heavy chain H3 and von Willebrand factor, and the findings show the seven coagulation function-associated proteins were significantly lower than the group of SR. (3) Comparing to the group of SR, this study found that the LDR group’s expression levels of the 2 antioxidant proteins (afamin and glutathione peroxidase 3) were also significantly lower. (4) The LDR group’s expression levels of seven immune function-related proteins (Ig gamma-3 chain C region, Ig lambda-like polypeptide 5, clusterin, complement C1s subcomponent, complement factor B, complement C4-A, complement C1q subcomponent subunit A) were also significantly lower than the group of SR. Conclusion: This study identified the potential serum protein markers for elite sprinters and long-distance runners. The changes in the regulation of coagulation, antioxidant, or immune function-specific proteins may also provide further clinical applications for these two different track athletes.

Keywords: biomarkers, coagulation, immune response, oxidative stress

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Authors: Ben Main Piotr Ozieranski

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State government spending on pharmaceuticals stands at 1 trillion USD globally, promoting criticism of the pharmaceutical industry's monetization of drug efficacy, product cost overvaluation, and health injustice. This paper elucidates the mechanisms behind a state-institutional response to this problem through the sociological lens of the strategic relational approach to state power. To do so, 30 expert interviews, legal and policy documents are drawn on to explain how state elites in New Zealand have successfully contested a 30-year “pharmaceutical spending containment policy”. Proceeding from Jessop's notion of strategic “selectivity”, encompassing analyses of the enabling features of state actors' ability to harness state structures, a theoretical explanation is advanced. First, a strategic context is described that consists of dynamics around pharmaceutical dealmaking between the state bureaucracy, pharmaceutical pricing strategies (and their effects), and the industry. Centrally, the pricing strategy of "bundling" -deals for packages of drugs that combine older and newer patented products- reflect how state managers have instigated an “incentivization game” that is played by state and industry actors, including HTA professionals, over pharmaceutical products (both current and in development). Second, a protective context is described that is comprised of successive legislative-judicial responses to the strategic context and characterized by the regulation and the societalisation of commercial law. Third, within the policy, the achievement of increased pharmaceutical coverage (pharmaceutical “mix”) alongside contained spending is conceptualized as a state defence of a "social profit". As such, in contrast to scholarly expectations that political and economic cultures of neo-liberalism drive pharmaceutical policy-making processes, New Zealand's state elites' approach is shown to be antipathetic to neo-liberals within an overall capitalist economy. The paper contributes an analysis of state pricing strategies and how they are embedded in state regulatory structures. Additionally, through an analysis of the interconnections of state power and pharmaceutical value Abrahams's neo-liberal corporate bias model for pharmaceutical policy analysis is problematised.

Keywords: pharmaceutical governance, pharmaceutical bureaucracy, pricing strategies, state power, value theory

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Authors: Anushtha Saxena

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This paper examines the process of data monetisation bye-commerce companies operating in India. Data monetisation is collecting, storing, and analysing consumers’ data to use further the data that is generated for profits, revenue, etc. Data monetisation enables e-commerce companies to get better businesses opportunities, innovative products and services, a competitive edge over others to the consumers, and generate millions of revenues. This paper analyses the issues and challenges that are faced due to the process of data monetisation. Some of the issues highlighted in the paper pertain to the right to privacy, protection of data of e-commerce consumers. At the same time, data monetisation cannot be prohibited, but it can be regulated and monitored by stringent laws and regulations. The right to privacy isa fundamental right guaranteed to the citizens of India through Article 21 of The Constitution of India. The Supreme Court of India recognized the Right to Privacy as a fundamental right in the landmark judgment of Justice K.S. Puttaswamy (Retd) and Another v. Union of India . This paper highlights the legal issue of how e-commerce businesses violate individuals’ right to privacy by using the data collected, stored by them for economic gains and monetisation and protection of data. The researcher has mainly focused on e-commerce companies like online shopping websitesto analyse the legal issue of data monetisation. In the Internet of Things and the digital age, people have shifted to online shopping as it is convenient, easy, flexible, comfortable, time-consuming, etc. But at the same time, the e-commerce companies store the data of their consumers and use it by selling to the third party or generating more data from the data stored with them. This violatesindividuals’ right to privacy because the consumers do not know anything while giving their data online. Many times, data is collected without the consent of individuals also. Data can be structured, unstructured, etc., that is used by analytics to monetise. The Indian legislation like The Information Technology Act, 2000, etc., does not effectively protect the e-consumers concerning their data and how it is used by e-commerce businesses to monetise and generate revenues from that data. The paper also examines the draft Data Protection Bill, 2021, pending in the Parliament of India, and how this Bill can make a huge impact on data monetisation. This paper also aims to study the European Union General Data Protection Regulation and how this legislation can be helpful in the Indian scenarioconcerning e-commerce businesses with respect to data monetisation.

Keywords: data monetization, e-commerce companies, regulatory framework, GDPR

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

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Plant hormones are long known to be tightly associated with fruit development and are involved in controlling various aspects of fruit ripening. For fleshy fruits, ripening is characterized for changes in texture, color, aroma and other parameters that markedly contribute to its quality. Ethylene is one of the major players regulating the ripening-related processes, but emerging evidences suggest that auxin is also part of this dynamic control. Thus, the aim of this study was providing new insights into the auxin role during ripening and the hormonal interplay between auxin and ethylene. For that, tomato fruits (Micro-Tom) were collected at mature green stage and separated in four groups: one for indole-3-acetic acid (IAA) treatment, one for ethylene, one for a combination of IAA and ethylene, and one for control. Hormone solution was injected through the stylar apex, while mock samples were injected with buffer only. For ethylene treatments, fruits were exposed to gaseous hormone. Then, fruits were left to ripen under standard conditions and to assess ripening development, hue angle was reported as color indicator and ethylene production was measured by gas chromatography. The transcript levels of three ripening-related ethylene receptors (LeETR3, LeETR4 and LeETR6) were evaluated by RT-qPCR. Results showed that ethylene treatment induced ripening, stimulated ethylene production, accelerated color changes and induced receptor expression, as expected. Nonetheless, auxin treatment showed the opposite effect once fruits remained green for longer time than control group and ethylene perception has changed, taking account the reduced levels of receptor transcripts. Further, treatment with both hormones revealed that auxin effect in delaying ripening was predominant, even with higher levels of ethylene. Altogether, the data suggest that auxin modulates several aspects of the tomato fruit ripening modifying the ethylene perception. The knowledge about hormonal control of fruit development will help design new strategies for effective manipulation of ripening regarding fruit quality and brings a new level of complexity on fruit ripening regulation.

Keywords: ethylene, auxin, fruit ripening, hormonal crosstalk

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Authors: Chin-Tsu Ma, Yi-Jhen Wu, Hsia Ying Cheng, Han Hsiang Huang, Shyh Ming Kuo

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The use of specific molecules including nutrients and pharmacological agents has been tried in modulation of stem cells differentiation (MSCs) to insulin producing cells. The aim of this study is to investigate the ability of nano collagen molecules (nutrient or scaffold) to enhance the MSCs differentiation into insulin-producing cells in combination with nicotinamide and exendin-4 (pharmacological agents) in vitro and in vivo. The results demonstrated that the cells exhibit morphologically islet-like clusters after treatment with nano collagen molecules, nicotinamide and exendin-4. MSCs extra treated with nano collagen molecules showed significant increases in Nkx6.1 and insulin mRNA expression at 14-d and 21-d culture compared with those merely treated with nicotinamide and exendin-4. Early 7-day elevation in PDX-1 mRNA expression was observed. Furthermore, the MSCs exposed to nano collagen molecules produced the highest secretion of insulin (p ＜ 0.05). Type-2 diabetes induced by high-fat diet and low dose of streptozotocin in rat model was built in this study. This rat exhibited higher food intake, water intake, lower glucose tolerance, lower-insulin tolerance, and higher HbA1C (significant increases, p ＜ 0.01) as compared with the normal rat that demonstrated the model of type-2 diabetes was successfully built. Biopsy examinations also showed that obvious destruction of islet. After injection of differentiated MSCs into the destructed pancreas of diabetes rat, more regenerated islet were observed at the rats that treated with nano collagen molecules and exhibited much lower HbA1C as compared with the normal rat and diabetes rat after 4 weeks (significant deceases, p ＜ 0.001). These results indicate that the culturing MSCs with nano collagen molecules, nicotinamide, and exendin-4 are beneficial for MSCs differentiation into islet-like cells. These nano collagen molecules may lead to alternations or up-regulation of gene expression and influence the differentiated outcomes induced by nicotinamide and exendin-4.

Keywords: nano collagen molecules, nicotinamide, MSCs, diabetes

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Authors: Peli̇n Yilmaz, Gi̇zemnur Yildiz Uysal, Emi̇ne Bi̇rci̇, Berk Özcan, Burak Koca, Ehsan Tuzcuoğlu, Fati̇h Kasap

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Development of Energy Efficient Programs (EEP) is one of the most significant trends in the wet appliance industry of the recent years. Thanks to the EEP, the energy consumption of a washing machine as one of the most energy-consuming home appliances can shrink considerably, while its washing performance and the textile hygiene should remain almost unchanged. Here in, the goal of the present study is to achieve an optimum EEP algorithm providing excellent textile hygiene results as well as cleaning performance in a domestic washing machine. In this regard, steam-pretreated cold wash approach with a combination of innovative algorithm solution in a relatively short washing cycle duration was implemented. For the parametric study, steam exposure time, washing load, total water consumption, main-washing time, and spinning rpm as the significant parameters affecting the textile hygiene and cleaning performance were investigated within a Design of Experiment study using Minitab 2021 statistical program. For the textile hygiene studies, specific loads containing the contaminated cotton carriers with Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa bacteria were washed. Then, the microbial removal performance of the designed programs was expressed as log reduction calculated as a difference of microbial count per ml of the liquids in which the cotton carriers before and after washing. For the cleaning performance studies, tests were carried out with various types of detergents and EMPA Standard Stain Strip. According to the results, the optimum EEP program provided an excellent hygiene performance of more than 2 log reduction of microorganism and a perfect Washing Efficiency Index (Iw) of 1.035, which is greater than the value specified by EU ecodesign regulation 2019/2023.

Keywords: washing machine, energy efficient programs, hygiene, washing efficiency index, microorganism, escherichia coli, staphylococcus aureus, pseudomonas aeruginosa, laundry

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Authors: H. Aljabiry, L. Bailey, S. Young

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Qatar is a desert with an average temperature 37⁰C, reaching over 40⁰C during summer. Precipitation is uncommon and mostly in winter. Qatar depends on desalination for drinking water and on groundwater and recycled water for irrigation. Water consumption and network leakage per capita in Qatar are amongst the highest in the world; re-use of treated wastewater is extremely limited with only 14% of treated wastewater being used for irrigation. This has led to the country disposing of unwanted water from various sources in lagoons situated around the country, causing concern over the possibility of environmental pollution. Accordingly, our hypothesis underpinning this research is that the quality and quantity of water in lagoons is having an impact on the groundwater reservoirs in Qatar. Lagoons (n = 14) and wells (n = 55) were sampled for both summer and winter in 2018 (summer and winter). Water, adjoining soil and plant samples were analysed for multiple elements by Inductively Coupled Plasma Mass Spectrometry. Organic and inorganic carbon were measured (CN analyser) and the major anions were determined by ion chromatography. Salinization in both the lagoon and the wells was seen with good correlations between Cl⁻, Na⁺, Li, SO₄, S, Sr, Ca, Ti (p-value < 0.05). Association of heavy metals was observed of Ni, Cu, Ag, and V, Cr, Mo, Cd which is due to contamination from anthropological activities such as wastewater disposal or spread of contaminated dust. However, looking at each elements none of them exceeds the Qatari regulation. Moreover, gypsum saturation in the system was observed in both the lagoon and wells water samples. Lagoons and the water of the well are found to be of a saline type as well as Ca²⁺, Cl⁻, SO₄²⁻ type evidencing both gypsum dissolution and salinization in the system. Moreover, Maps produced by Inverse distance weighting showed an increasing level of Nitrate in the groundwater in winter, and decrease chloride and sulphate level, indicating recharge effect after winter rain events. While E. coli and faecal bacteria were found in most of the lagoons, biological analysis for wells needs to be conducted to understand the biological contamination from lagoon water infiltration. As a conclusion, while both the lagoon and the well showed the same results, more sampling is needed to understand the impact of the lagoons on the groundwater.

Keywords: groundwater quality, lagoon, treated wastewater, water management, wastewater treatment, wetlands

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Authors: Maor Farid, Oleg Gendelman

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Equivalent mechanical model of liquid sloshing in partially-filled cylindrical vessel is treated in the cases of free oscillations and of horizontal base excitation. The model is designed to cover both the linear and essentially nonlinear sloshing regimes. The latter fluid behaviour might involve hydraulic impacts interacting with the inner walls of the tank. These impulsive interactions are often modeled by high-power potential and dissipation functions. For the sake of analytical description, we use the traditional approach by modeling the impacts with velocity-dependent restitution coefficient. This modelling is similar to vibro-impact nonlinear energy sink (VI NES) which was recently explored for its vibration mitigation performances and nonlinear response regimes. Steady-state periodic regimes and chaotic strongly modulated responses (CSMR) are detected. Those dynamical regimes were described by the system's slow motion on the slow invariant manifold (SIM). There is a good agreement between the analytical results and numerical simulations. Subsequently, Finite-Element (FE) method is used to determine and verify the model parameters and to identify dominant dynamical regimes, natural modes and frequencies. The tank failure modes are identified and critical locations are identified. Mathematical relation is found between degrees-of-freedom (DOFs) motion and the mechanical stress applied in the tank critical section. This is the prior attempt to take under consideration large-amplitude nonlinear sloshing and tank structure elasticity effects for design, regulation definition and resistance analysis purposes. Both linear (tuned mass damper, TMD) and nonlinear (nonlinear energy sink, NES) passive energy absorbers contribution to the overall system mitigation is firstly examined, in terms of both stress reduction and time for vibration decay.

Keywords: nonlinear energy sink (NES), reduced-order modelling, liquid sloshing, vibration mitigation, vibro-impact dynamics

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Authors: Bendes Ákos

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Digital evidence will be the most widely used type of evidence in the future. With the development of the modern world, more and more new types of crimes have evolved and transformed. For this reason, it is extremely important to examine these types of crimes in order to get a comprehensive picture of them, with which we can help the authorities work. In 1865, with early technologies, people were able to forge a picture of a quality that is not even recognized today. With the help of today's technology, authorities receive a lot of false evidence. Officials are not able to process such a large amount of data, nor do they have the necessary technical knowledge to get a real picture of the authenticity of the given evidence. The digital world has many dangers. Unfortunately, we live in an age where we must protect everything digitally: our phones, our computers, our cars, and all the smart devices that are present in our personal lives and this is not only a burden on us, since companies, state and public utilities institutions are also forced to do so. The training of specialists and experts is essential so that the authorities can manage the incoming digital evidence at some level. When analyzing evidence, it is important to be able to examine it from the moment it is created. Establishing authenticity is a very important issue during official procedures. After the proper acquisition of the evidence, it is essential to store it safely and use it professionally. After the proper acquisition of the evidence, it is essential to store it safely and use it professionally. Otherwise, they will not have sufficient probative value and in case of doubt, the court will always decide in favor of the defendant. One of the most common problems in the world of digital data and evidence is doubt, which is why it is extremely important to examine the above-mentioned problems. The most effective way to avoid digital crimes is to prevent them, for which proper education and knowledge are essential. The aim is to present the dangers inherent in the digital world and the new types of digital crimes. After the comparison of the Hungarian investigative techniques with international practice, modernizing proposals will be given. A sufficiently stable yet flexible legislation is needed that can monitor the rapid changes in the world and not regulate afterward but rather provide an appropriate framework. It is also important to be able to distinguish between digital and digitalized evidence, as the degree of probative force differs greatly. The aim of the research is to promote effective international cooperation and uniform legal regulation in the world of digital crimes.

Keywords: digital crime, digital law, cyber crime, international cooperation, new crimes, skepticism

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Authors: Hilly Moodrick-Even Khen

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This study analyzes the legal regulation of the use of force in international law in the context of three emerging Palestinian forms of struggle against Israeli occupation: the Knife Intifada, Gaza border disturbances, and the launching of incendiary kites. It discusses what legal paradigms or concepts should regulate the type and level of force used in each situation—a question that is complicated by various dilemmas—and appraises the Israel Defence Forces policies tailored in response. Methodologically, the study is based on analysis of scholarship on the conceptual legal issues as well as dicta of the courts. It evaluates the applicability of two legal paradigms regulating the use of force in military operations—(i) the conduct of hostilities and (ii) law enforcement—as well as the concept of self-defense in international law and the escalation of force procedure. While the “Knife Intifada” clearly falls under the law enforcement paradigm, the disturbances at the border and the launching of incendiary kites raise more difficult questions, as applying law enforcement, especially in the latter case, can have undesirable ramifications for safeguarding humanitarian interests. The use of force in the cases of the border disturbances and the incendiary kites should thus be regulated, mutatis mutandis, by the concept of self-defense and escalation of force procedures; and in the latter case, the hostilities paradigm can also be applied. The study provides a factual description and analysis of the background and nature of the forms of struggle in Gaza and the West Bank—in each case surveying the geo-political developments since operation Protective Edge, contextualizing how the organized and unorganized violent activities evolved, and analyzing them in terms of level of organization and intensity. It then presents the two paradigms of the use of force—law enforcement and conduct of hostilities—and the concept of self-defense. Lastly, it uses the factual findings as the basis for legally analyzing which paradigm or concept regulating the use of force applies for each form of struggle. The study concludes that in most cases, the concept of self-defense is preferable to the hostilities or the law enforcement paradigms, as it best safeguards humanitarian interests and ensures the least loss of civilian lives.

Keywords: Israeli-Palestinian conflict, self defense, terrorism, use of force

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Authors: Sonja Giese, Tess N. Peacock

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South African based Innovation Edge is experimenting with technology to drive positive behavior change, enable data-driven decision making, and scale quality early years services. This paper uses five case studies to illustrate how technology can be used in resource-constrained environments to first, encourage parenting practices that build early language development (using a stage-based mobile messaging pilot, ChildConnect), secondly, to improve the quality of ECD programs (using a mobile application, CareUp), thirdly, how to affordably scale services for the early detection of visual and hearing impairments (using a mobile tool, HearX), fourthly, how to build a transparent and accountable system for the registration and funding of ECD (using a blockchain enabled platform, Amply), and finally enable rapid data collection and feedback to facilitate quality enhancement of programs at scale (the Early Learning Outcomes Measure). ChildConnect and CareUp were both developed using a design based iterative research approach. The usage and uptake of ChildConnect and CareUp was evaluated with qualitative and quantitative methods. Actual child outcomes were not measured in the initial pilots. Although parents who used and engaged on either platform felt more supported and informed, parent engagement and usage remains a challenge. This is contrast to ECD practitioners whose usage and knowledge with CareUp showed both sustained engagement and knowledge improvement. HearX is an easy-to-use tool to identify hearing loss and visual impairment. The tool was tested with 10000 children in an informal settlement. The feasibility of cost-effectively decentralising screening services was demonstrated. Practical and financial barriers remain with respect to parental consent and for successful referrals. Amply uses mobile and blockchain technology to increase impact and accountability of public services. In the pilot project, Amply is being used to replace an existing paper-based system to register children for a government-funded pre-school subsidy in South Africa. Early Learning Outcomes Measure defines what it means for a child to be developmentally ‘on track’ at aged 50-69 months. ELOM administration is enabled via a tablet which allows for easy and accurate data collection, transfer, analysis, and feedback. ELOM is being used extensively to drive quality enhancement of ECD programs across multiple modalities. The nature of ECD services in South Africa is that they are in large part provided by disconnected private individuals or Non-Governmental Organizations (in contrast to basic education which is publicly provided by the government). It is a disparate sector which means that scaling successful interventions is that much harder. All five interventions show the potential of technology to support and enhance a range of ECD services, but pathways to scale are still being tested.

Keywords: assessment, behavior change, communication, data, disabilities, mobile, scale, technology, quality

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Authors: Rayhana Begum, Manju Sharma

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Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

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Authors: Shih-Ping Liu, Cheng-Hsuan Chang, Yu-Chuen Huang, Shih-Yin Chen, Woei-Cherng Shyu

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Embryonic stem cells (ES) and induced pluripotnet stem cells (iPS) are both pluripotent stem cells. For mouse stem cells culture technology, leukemia inhibitory factor (LIF) was used to maintain the pluripotency of stem cells in vitro. However, LIF is an expensive reagent. The goal of this study was to find out a pure compound extracted from Chinese herbal medicine that could maintain stem cells pluripotency to replace LIF and improve the iPS generation efficiency. From 20 candidates traditional Chinese medicine we found that Cordycepsmilitaris triggered the up-regulation of stem cells activating genes (Oct4 and Sox2) expression levels in MEF cells. Cordycepin, a major active component of Cordycepsmilitaris, also could up-regulate Oct4 and Sox2 gene expression. Furthermore, we used ES and iPS cells and treated them with different concentrations of Cordycepin (replaced LIF in the culture medium) to test whether it was useful to maintain the pluripotency. The results showed higher expression levels of several stem cells markers in 10 μM Cordycepin-treated ES and iPS cells compared to controls that did not contain LIF, including alkaline phosphatase, SSEA1, and Nanog. Embryonic body formation and differentiation confirmed that 10 μM Cordycepin-containing medium was capable to maintain stem cells pluripotency after four times passages. For mechanism analysis, microarray analysis indicated extracellular matrix and Jak/Stat signaling pathway as the top two deregulated pathways. In ECM pathway, we determined that the integrin αVβ5 expression levels and phosphorylated Src levels increased after Cordycepin treatment. In addition, the phosphorylated Jak2 and phosphorylated Sat3 protein levels were increased after Cordycepin treatment and suppressed with the Jak2 inhibitor, AG490. The expression of cytokines associated with Jak2/Stat3 signaling pathway were also up-regulated by Q-PCR and ELISA assay. Lastly, we used Oct4-GFP MEF cells to test iPS generation efficiency following Cordycepin treatment. We observed that 10 Μm Cordycepin significantly increased the iPS generation efficiency in day 21. In conclusion, we demonstrated Cordycepin could maintain the pluripotency of stem cells through both of ECM and Jak2/Stat3 signaling pathway and improved iPS generation efficiency.

Keywords: cordycepin, iPS cells, Jak2/Stat3 signaling pathway, molecular biology

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Authors: M. A. Stoian, D. M. Cocarta, A. Badea

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The main sources of soil pollution due to petroleum contaminants are industrial processes involve crude oil. Soil polluted with crude oil is toxic for plants, animals, and humans. Human exposure to the contaminated soil occurs through different exposure pathways: Soil ingestion, diet, inhalation, and dermal contact. The present study research is focused on soil contamination with heavy metals as a consequence of soil pollution with petroleum products. Human exposure pathways considered are: Accidentally ingestion of contaminated soil and dermal contact. The purpose of the paper is to identify the human health risk (carcinogenic risk) from soil contaminated with heavy metals. The human exposure and risk were evaluated for five contaminants of concern of the eleven which were identified in soil. Two soil samples were collected from a bioremediation platform from Muntenia Region of Romania. The soil deposited on the bioremediation platform was contaminated through extraction and oil processing. For the research work, two average soil samples from two different plots were analyzed: The first one was slightly contaminated with petroleum products (Total Petroleum Hydrocarbons (TPH) in soil was 1420 mg/kg_d.w.), while the second one was highly contaminated (TPH in soil was 24306 mg/kg_d.w.). In order to evaluate risks posed by heavy metals due soil pollution with petroleum products, five metals known as carcinogenic were investigated: Arsenic (As), Cadmium (Cd), Chromium^VI (Cr^VI), Nickel (Ni), and Lead (Pb). Results of the chemical analysis performed on samples collected from the contaminated soil evidence soil contamination with heavy metals as following: As in Site 1 = 6.96 mg/kg_d.w; As in Site 2 = 11.62 mg/kg_d.w, Cd in Site 1 = 0.9 mg/kg_d.w; Cd in Site 2 = 1 mg/kg_d.w; Cr^VI was 0.1 mg/kg_d.w for both sites; Ni in Site 1 = 37.00 mg/kg_d.w; Ni in Site 2 = 42.46 mg/kg_d.w; Pb in Site 1 = 34.67 mg/kg_d.w; Pb in Site 2 = 120.44 mg/kg_d.w. The concentrations for these metals exceed the normal values established in the Romanian regulation, but are smaller than the alert level for a less sensitive use of soil (industrial). Although, the concentrations do not exceed the thresholds, the next step was to assess the human health risk posed by soil contamination with these heavy metals. Results for risk were compared with the acceptable one (10^-6, according to World Human Organization). As, expected, the highest risk was identified for the soil with a higher degree of contamination: Individual Risk (IR) was 1.11×10^-5 compared with 8.61×10^-6. 

Keywords: carcinogenic risk, heavy metals, human health risk assessment, soil pollution

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