Search results for: Rome II regulation

Authors: Nurliani, Ida Rosada

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The national rice consumption keeps increasing along with raising income of the households and the rapid growth of population. However, food availability, particularly rice, is limited. Impacts of rice-field conversion have run cumulatively, as we can see on potential losses of rice and crops production, as well as work opportunity that keeps increasing year-by-year. Therefore, it requires policy recommendation to control rice-field conversion through economic, social, and ecological approaches. The research was a survey method intended to: (1) Identify internal factors; quality and productivity of the land as the cause of land conversion, (2) Identify external factors of land conversion, value of the rice-field and the competitor’s land, workforce absorption, and regulation, as well as (3) Formulate strategies in controlling rice-field conversion. Population of the research was farmers who applied land conversion at Pangkep Regency, South Sulawesi. Samples were determined using the incidental sampling method. Data analysis used productivity analysis, land quality analysis, total economic value analysis, and SWOT analysis. Results of the research showed that the quality of rice-field was low as well as productivity of the grains (unhulled-rice). So that, average productivity of the grains and quality of rice-field were low as well. Total economic value of rice-field was lower than the economic value of the embankment. Workforce absorption value on rice-field was higher than on the embankment. Strategies in controlling such rice-field conversion can be done by increasing rice-field productivity, improving land quality, applying cultivation technique of specific location, improving the irrigation lines, and socializing regulation and sanction about the transfer of land use.

Keywords: land conversion, quality of rice-field, productivity, land economic value.

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Authors: David Abrahams

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In October 2016 South Africa deposited its ‘instrument of withdrawal’ from the Rome Statute of the International Criminal Court, with the Secretary-General of the United Nations. The Rome Statute is the founding document of the treaty-based International Criminal Court (ICC). The ICC has jurisdiction to hear cases where crimes against humanity, war crimes and genocide have been committed, on the basis of individual criminal responsibility. It is therefore not surprising that one of the ICCs mandates is to ensure that the sufferings, due to gross human rights violations towards the civilian population is, in principle, brought to an end by punishing those individuals responsible, thus providing justice to the victims. The ICC is unable to effectively fulfill its mandate and thus depends, in part on the willingness of states to assist the Court in its functions. This requires states to ratify the Statute and to domesticate its provisions, depending on whether it is a monist or dualist state. South Africa ratified the Statute in November 2000, and domesticated the Statute in 2002 by virtue of the Implementation of the Rome Statute of the International Criminal Court Act 27 of 2002. South Africa thus remains under an obligation to cooperate with the ICC until the final date of withdrawal, which is October 2017. An AU Summit was hosted by South Africa during June 2015. Omar Al-Bashir, whom the prosecutor of the ICC has indicted on two separate occasions, was invited to the summit. South Africa made an agreement with the AU that it will honour its obligations in terms of its Diplomatic and Immunities Privileges Act of 2001, by granting immunity to all heads of state, including that of Sudan. This decision by South Africa has raised a plethora of questions regarding the status and hierarchy of international laws versus regional laws versus domestic laws. In particular, this paper explores whether a state’s international law treaty obligations may be suspended in favour of, firstly, regional peace (thus safeguarding the security of the civilian population against further atrocities and other gross violations of human rights), and secondly, head of state immunity. This paper also reflects on the effectiveness of the trias politca in South Africa in relation the manner in which South African courts have confirmed South Africa’s failure in fulfilling its obligations in terms of the Rome Statute. A secondary question which will also be explored, is whether the Rome Statute is currently an effective tool in dealing with gross violations of human rights, particularly in a regional African context, given the desire by a number of African states currently party to the Statute, to engage in a mass exodus from the Statute. Finally, the paper concludes with a proposal that there can be no justice for victims of gross human rights violations unless states are serious in playing an instrumental role in bringing an end to impunity in Africa, and that withdrawing from the ICC without an alternative, effective system in place, will simply perpetuate impunity.

Keywords: African Union, diplomatic immunity, impunity, international criminal court, South Africa

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Authors: M. Sangeetha, D. Chamundeeswari, C. Saravanababu, C. Rose, V. Gopal

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Rheumatoid arthritis (RA) is a chronic, progressive, systemic inflammatory disorder affecting the synovial joints and typically producing symmetrical arthritis that leads to joint destruction, which is responsible for the deformity and disability. Despite improvements in the treatment of RA over the past decade, there still is a need for new therapeutic agents that are efficacious, less expensive, and free of severe adverse reactions. The present study aimed to investigate role of inflammatory markers in arthritic rats treated with ethanolic bark extract of Albizia procera. The protective effect of ethanolic bark extract of Albizia procera against complete Freund’s adjuvant (CFA) induced arthritis in rats. Arthritis was induced by an intradermal injection of 0.1 ml FCA in the foot pad of left hind limb of rats. ETBE (100 and 200 mg/kg b.wt./p.o) and the reference drug diclofenac (25 mg/kg b.wt./p.o) were administered to arthritic rats. Paw volume was measured for all the animals before inducing arthritis and thereafter once in seven days by using plethysmometer for 42 days. Gene expression of inflammatory markers such as IL-1β and IL-10 were investigated in paw tissues. Up regulation of IL-1β and Down regulation IL-10 were observed in CFA injected rats when compared to normal rats. ETBE attenuated these alterations dose dependently when compared to the vehicle treated rats. These results provide insights into the mechanism of anti-arthritic activity, and unravel potential therapeutic use of Albizia procera in arthritis.

Keywords: CFA-Complete Freund’s adjuvant, ETBE – ethanolic bark extract, IL- interleukins, RA-rheumatoid arthritis

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Authors: K. C. Ching

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There is growing public concern over the increasing prevalence of student suicide in Hong Kong. Some identify the problem with insufficient social support, while some attribute it to the vast fluctuations in emotional experience and the hindrances to emotion-regulation, both typical of adolescence and emerging adulthood. This study is thus designed to explore the respective effect of perceived social support and emotion self-confidence, on positive emotions and negative emotions. Fifty-seven Hong Kong higher-education students (17 males, 40 females) aged between 18 and 25 (M = 21.78) responded to an online questionnaire consisted of self-reported measures of perceived social support, emotional self-confidence, positive emotions, and negative emotions. Hierarchical regression analysis revealed that emotional self-confidence positively associated with positive emotions and negatively with negative emotions, while perceived social support positively associated with positive emotions but was not related to negative emotions. Perceived social support and emotional self-confidence both predicted positive emotions, but did not interact to predict any emotional outcome. It is concluded that students’ positive and negative emotional experiences are closely related to their emotion-regulation process. But for social support, its effect is merely protective, meaning that although perceived social support generally promotes positive emotions, it alone does not suffice to alleviate students’ negative emotions. These conclusions carry profound implications to suicide prevention practices, including that most existing suicide prevention campaigns should advance from merely fostering mutual support to directly promoting adaptive coping of emotional negativity.

Keywords: emerging adulthood, emotional self-confidence, hong kong, perceived social support, suicide prevention

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Authors: Yeimis Milton, Palomino Pichihua

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The city, like living organisms, originates from codes, structured information in the form of rules that condition the physical form and performance of urban space. Usually, the so-called urban codes clash with the spontaneous nature of the city, with the urban Kháos that contextualizes the free creation (poiesis) of human collectives. This contradiction is especially evident in Latin America, which, like other developing regions, lacks adequate instruments to guide urban growth. Thus constructing a hybrid between the formal and informal city, categories that are difficult to separate one from the other. This is a comparative study focusing on the urban codes created to address the pandemic. The objective is to build an overview of these innovations in the region. The sample is made up of official norms published in pandemic, directly linked to urban planning and building control (urban form). The countries analyzed are Brazil, Mexico, Argentina, Peru, Colombia, and Chile. The study uncovers a shared interest in facing future urban problems, in contrast to the inconsistency of proposed legal instruments. Factors such as the lack of articulation, validity time, and ambiguity, among others, accentuate this problem. Likewise, it evidences that the political situation of each country has a significant influence on the development of these norms and the possibility of their long-term impact. In summary, the global emergency has produced opportunities to transform urban systems from their internal rules; however, there are very few successful examples in this field. Therefore, Latin American cities have the task of learning from this defeat in order to lay the foundations for a more resilient and sustainable urban future.

Keywords: pandemic, regulation, urban planning, latin America

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Authors: Erika Yamaguchi, Sirawadee Arunyanrt, Shunichi Ohmori, Kazuho Yoshimoto

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In this paper, we suggest a simulation tool to make a decision of monthly production planning for maximizing a profit of Specialty store retailer of Private label Apparel (SPA) firms. Most of SPA firms are fabless and make outsourcing deals for productions with factories of their subcontractors. Every month, SPA firms make a booking for production lines and manpower in the factories. The booking is conducted a few months in advance based on a demand prediction and a monthly production planning at that time. However, the demand prediction is updated month by month, and the monthly production planning would change to meet the latest demand prediction. Then, SPA firms have to change the capacities initially booked within a certain range to suit to the monthly production planning. The booking system is called “capacity-booking”. These days, though it is an issue for SPA firms to make precise monthly production planning, many firms are still conducting the production planning by empirical rules. In addition, it is also a challenge for SPA firms to match their products and factories with considering their demand predictabilities and regulation abilities. In this paper, we suggest a model for considering these two issues. An objective is to maximize a total profit of certain periods, which is sales minus costs of production, inventory, and capacity-booking penalty. To make a better monthly production planning at SPA firms, these points should be considered: demand predictabilities by random trends, previous and next month’s production planning of the target month, and regulation abilities of the capacity-booking. To decide matching products and factories for outsourcing, it is important to consider seasonality, volume, and predictability of each product, production possibility, size, and regulation ability of each factory. SPA firms have to consider these constructions and decide orders with several factories per one product. We modeled these issues as a linear programming. To validate the model, an example of several computational experiments with a SPA firm is presented. We suppose four typical product groups: basic, seasonal (Spring / Summer), seasonal (Fall / Winter), and spot product. As a result of the experiments, a monthly production planning was provided. In the planning, demand predictabilities from random trend are reduced by producing products which are different product types. Moreover, priorities to produce are given to high-margin products. In conclusion, we developed a simulation tool to make a decision of monthly production planning which is useful when the production planning is set every month. We considered the features of capacity-booking, and matching of products and factories which have different features and conditions.

Keywords: capacity-booking, SPA, monthly production planning, linear programming

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

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

Keywords: black grass, herbicide, resistance, transporters

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

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

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

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Authors: Qingfang Guo

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

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

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Authors: Bhawna Chandravanshi, Ramesh Bhonde

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

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

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Authors: Ana Lambelho

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

Keywords: intern, internship contact, labour law, Portugal

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Authors: Sajedeh Salehi, Marco Giacalone

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

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

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

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

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

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Authors: Mónica Arroyo

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

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

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Authors: Linda Frazer

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

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

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Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

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

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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Authors: Anjali Suresh

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

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

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

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

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

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

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

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

Procedia PDF Downloads 295

Authors: Galuh Pramesti

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In Indonesia, the rise of the middle class and consumer purchasing power has created a trend of shifting the traditional into a modern retail market. Development of the creative economy as an impact of the global economy has invaded the traditional market, due to low rents and minimum innovation, raising the issue of sustainability and urban resilience for survival of the traditional market. The study aims to understand the current market conditions by examining the challenges, resiliency, and identify the relationship between the traditional market and creative market. Using a single-case study approach as the research methodology, Santa Market has been chosen as the case study. It is a pilot project of collaboration between a traditional market and creative economy in Jakarta, Indonesia. The research was conducted as a qualitative study through in-depth interviews with the market vendors and the market management, besides a desk-based study of the leasing data and spatial analysis. The findings indicate traffic fluctuation as the main challenge. It is related to the tenant’s presence, rental fluctuation, gentrification, infrastructure, and market competition. Thus, the findings on resilience show a different response for creative and traditional markets. The traditional market’s response remained stable with minimum innovation, whereas the creative market relies on technological development. Regarding the relationship, supply and demand have become the main relationship occurring in Santa Market. It is then developed into the context of society and regulation. The conclusion provides recommendations for more solid regulation to protect the market tenants from stakeholder interests that can disrupt market viability, and a critical discussion on the concept of collaboration between traditional and creative markets. There is also a suggestion for further study on relation with the surroundings, to create a holistic study on how the collaboration can work well in the traditional market.

Keywords: creative economy, market sustainability, traditional market, urban resilience

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Authors: Marina Chavleishvili

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Introduction: Today, the study of monopolies, including natural monopolies, is topical. In real life, pure monopolies are natural monopolies. Natural monopolies are used widely and are regulated by the state. In particular, the prices and rates are regulated. The paper considers the problems associated with the operation of natural monopolies in Georgia, in particular, their microeconomic analysis, pricing mechanisms, and legal mechanisms of their operation. The analysis was carried out on the example of the power industry. The rates of natural monopolies in Georgia are controlled by the Georgian National Energy and Water Supply Regulation Commission. The paper analyzes the positive role and importance of the regulatory body and the issues of improving the legislative base that will support the efficient operation of the branch. Methodology: In order to highlight natural monopolies market tendencies, the domestic and international markets are studied. An analysis of monopolies is carried out based on the endogenous and exogenous factors that determine the condition of companies, as well as the strategies chosen by firms to increase the market share. According to the productivity-based competitiveness assessment scheme, the segmentation opportunities, business environment, resources, and geographical location of monopolist companies are revealed. Main Findings: As a result of the analysis, certain assessments and conclusions were made. Natural monopolies are quite a complex and versatile economic element, and it is important to specify and duly control their frame conditions. It is important to determine the pricing policy of natural monopolies. The rates should be transparent, should show the level of life in the country, and should correspond to the incomes. The analysis confirmed the significance of the role of the Antimonopoly Service in the efficient management of natural monopolies. The law should adapt to reality and should be applied only to regulate the market. The present-day differential electricity tariffs varying depending on the consumed electrical power need revision. The effects of the electricity price discrimination are important, segmentation in different seasons in particular. Consumers use more electricity in winter than in summer, which is associated with extra capacities and maintenance costs. If the price of electricity in winter is higher than in summer, the electricity consumption will decrease in winter. The consumers will start to consume the electricity more economically, what will allow reducing extra capacities. Conclusion: Thus, the practical realization of the views given in the paper will contribute to the efficient operation of natural monopolies. Consequently, their activity will be oriented not on the reduction but on the increase of increments of the consumers or producers. Overall, the optimal management of the given fields will allow for improving the well-being throughout the country. In the article, conclusions are made, and the recommendations are developed to deliver effective policies and regulations toward the natural monopolies in Georgia.

Keywords: monopolies, natural monopolies, regulation, antimonopoly service

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Authors: Bei Zhang, Zhaoxin Zhang, Lidong Zhao

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Green infrastructures (GIs) for rainwater management can directly meet the multiple purposes of urban greening and non-point source pollution control. To reveal the overall layout law of GIs dominated by typical woody plants and their impact on urban environmental effects, we constructed a HYDRUS-1D and Stormwater management (SWMM) coupling model to simulate the response of typical root woody plant planting methods on urban hydrological. The results showed that the coupling model had high adaptability to the simulation of urban surface runoff control effect under different woody plant planting methods (NSE ≥0.64 and R² ≥ 0.71). The regulation effect on surface runoff showed that the average runoff reduction rate of GIs increased from 60 % to 71 % with the increase of planting area (5% to 25%) under the design rainfall event of the 2-year recurrence interval. Sophora japonica with tap roots was slightly higher than that of without plants (control) and Malus baccata (M. baccata) with fibrous roots. The comprehensive benefit evaluation system of rainwater utilization technology was constructed by using an analytic hierarchy process. The coupling model was used to evaluate the comprehensive benefits of woody plants with different planting areas in the study area in terms of environment, economy, and society. The comprehensive benefit value of planting 15% M. baccata was the highest, which was the first choice for the planting of woody plants in the study area. This study can provide a scientific basis for the decision-making of green facility layouts of woody plants.

Keywords: green infrastructure, comprehensive benefits, runoff regulation, woody plant layout, coupling model

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Authors: Lee Sunghyoun, Yu Byeongkee, Kim Hyuckjoo, Yun Namkyu, Jung Jongcheon

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Most of the recent on-sale oyster mushrooms are raised in a oyster mushroom house, in which the necessary adjustment of growing condition is feasible. The rationale for such artificial growing is the impossibility of successive cultivation in the case of a natural cultivation due to external weather conditions. A oyster mushroom house adopts an equipment called growing bed, laying one growing bed upon another in a multi-column fashion, growing and developing the mushrooms on the respective equipments. The indispensable environment management factors of mushroom cultivation are temperature, humidity, and CO2; on which an appropriate regulation of the three requisites is a necessitated condition for the sake of the total output’s increase. However, due to the multiple layers of growing bed’s disturbance on air circulation, a oyster mushroom house’s internal environmental uniformity meets with considerable instability. This research presents a technology which assures the facilitation of environment regulation over all the internal space of a oyster mushroom house, irrespective of its location. The research staff reinforced the oyster mushroom house’s insulation in order to minimize the external environment’s influence on the oyster mushroom house’s internal environment and installed circulation fan to improve the oyster mushroom house’s interior environmental uniformity. Also, the humidifier nozzle’s position was set to prevent dew condensation when humidifying. As a result, a highly sophisticated management over all the oyster mushroom house‘s internal space was realized with the temperature of 0.2~1.3℃, and the relative humidity of 2~7% at the cultivating stage of mushroom’s growth. Therefore, to maximize oyster mushroom house‘s internal environmental uniformity, it can be concluded that consideration of various factors such as insulation reinforcement, decision on the humidifier nozzle’s location, disposition of circulation fan’s installation and the direction of wind discharge is needed.

Keywords: mushroom growing facility, environmental uniformity, temperature, relative humidity, CO2 concentration

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Authors: A. Coetzee, C. F. Kelly, E. Even-Zahav

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Dominant approaches to livestock production are harmful to the environment, human health and animal welfare, yet global meat consumption is rising. Sustainable alternative production approaches are therefore urgently required, and ‘free range’ is the main alternative for chicken meat offered in South Africa (and globally). Although the South African Poultry Association provides non-binding guidelines, there is a lack of formal definition and regulation of free range chicken production, meaning it is unclear what this alternative entails and if it is consistently practised (a trend observed globally). The objective of this exploratory qualitative case study is therefore to investigate who and what determines free range chicken. The case study, conducted from a social constructivist worldview, uses semi-structured interviews, photographs and document analysis to collect data. Interviews are conducted with those involved with bringing free range chicken to the market - farmers, chefs, retailers, and regulators. Data is analysed using thematic analysis to establish dominant patterns in the data. The five major themes identified (based on prevalence in data and on achieving the research objective) are: 1) free range means a bird reared with good animal welfare in mind, 2) free range means quality meat, 3) free range means a profitable business, 4) free range is determined by decision makers or by access to markets, and 5) free range is coupled with concerns about the lack of regulation. Unpacking the findings in the context of the literature reveals who and what determines free range. The research uncovers wide-ranging interpretations of ‘free range’, driven by the absence of formal regulation for free range chicken practices and the lack of independent private certification. This means that the term ‘free range’ is socially constructed, thus varied and complex. The case study also shows that whether chicken meat is free range is generally determined by those who have access to markets. Large retailers claim adherence to the internationally recognised Five Freedoms, also include in the South African Poultry Association Code of Good Practice, which others in the sector say are too broad to be meaningful. Producers describe animal welfare concerns as the main driver for how they practice/view free range production, yet these interpretations vary. An additional driver is a focus on human health, which participants achieve mainly through the use of antibiotic-free feed, resulting in what participants regard as higher quality meat. The participants are also strongly driven by business imperatives, with most stating that free range chicken should carry a higher price than conventionally-reared chicken due to increased production costs. Recommendations from this study focus on, inter alia, a need to understand consumers’ perspectives on free range chicken, given that those in the sector claim they are responding to consumer demand, and conducting environmental research such as life cycle assessment studies to establish the true (environmental) sustainability of free range production. At present, it seems the sector mostly responds to social sustainability: human health and animal welfare.

Keywords: chicken meat production, free range, socially constructed, sustainability

Procedia PDF Downloads 157

Authors: Jessica Gonzalez

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Veganism, along with different types of vegetarianism, consists in the abstinence of animal products. Far from being only an alimentary regulation, it stands as a political posture against the food industry generating itself a set of beliefs, prohibitions, and attitudes that compel the individual to a reevaluation of his obligations towards the environment. Veganism defends animal rights and at the same time reinforces a different conception of natural resources embodying it in alimentary restrictions. These practices emerge in the context of alimentary modernity, which is characterized by bringing new concerns to the consumer. An increased skepticism towards the government ability to protect food supply; a notable distrust toward the market guaranties on providing safe food with sustainable techniques and the desire to react to the neoliberal forms of exploitation are some of its consequences of this phenomenon. This study aims to approach the concept of governmentality as a coproduced system of legitimized practices and knowledge, formed by the interaction of the different actors that are involved. In a scenario where the State seems to retreat from centralized regulation of food production giving up importance to citizens, dietary consultants, farmers, and stockbreeders, veganism plays its role on the conformation of distinctive forms of environmentalism, nature rights and responses to ecological crisis. The ethnographic method allows observing the mechanisms of interaction of consumers and discourses with the mainstream food system, providing evidence about the means of generation of new conceptions about nature and the environment. The paper focuses on how the dietary restrictions, consumption patterns and public discourses of vegans in Barcelona impact local consumption, demonstrating its relevance as a mechanism that associates particular concerns about food with political economy.

Keywords: animal rights, environmentalism, food system, governmentality, veganism

Procedia PDF Downloads 127

Authors: Scott A. Ochsner, Christopher M. Watkins, Apollo McOwiti, David L. Steffen Lauren B. Becnel, Neil J. McKenna

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Understanding signaling by nuclear receptors (NRs) requires an appreciation of their cognate ligand- and tissue-specific transcriptomes. While target gene regulation data are abundant in this field, they reside in hundreds of discrete publications in formats refractory to routine query and analysis and, accordingly, their full value to the NR signaling community has not been realized. One of the mandates of the Nuclear Receptor Signaling Atlas (NURSA) is to facilitate access of the community to existing public datasets. Pursuant to this mandate we are developing a freely-accessible community web resource, Transcriptomine, to bring together the sum total of available expression array and RNA-Seq data points generated by the field in a single location. Transcriptomine currently contains over 25,000,000 gene fold change datapoints from over 1200 contrasts relevant to over 100 NRs, ligands and coregulators in over 200 tissues and cell lines. Transcriptomine is designed to accommodate a spectrum of end users ranging from the bench researcher to those with advanced bioinformatic training. Visualization tools allow users to build custom charts to compare and contrast patterns of gene regulation across different tissues and in response to different ligands. Our resource affords an entirely new paradigm for leveraging gene expression data in the NR signaling field, empowering users to query gene fold changes across diverse regulatory molecules, tissues and cell lines, target genes, biological functions and disease associations, and that would otherwise be prohibitive in terms of time and effort. Transcriptomine will be regularly updated with gene lists from future genome-wide expression array and expression-sequencing datasets in the NR signaling field.

Keywords: target gene database, informatics, gene expression, transcriptomics

Procedia PDF Downloads 273

Authors: Gyoomi Kim, Jiyoung Bae

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In the field of language education research, there are not many tries to empirically examine learners’ acceptance behavior and related factors of mobile-assisted language learning (MALL). This study is one of the few attempts to propose an integrated theoretical framework that explains MALL users’ acceptance behavior and potential factors. Constructs from technology acceptance model (TAM) and MALL research are tested in the integrated framework. Based on previous studies, a hypothetical model was developed. Four external variables related to the MALL user’s acceptance behavior were selected: subjective norm, content reliability, interactivity, self-regulation. The model was also composed of four other constructs: two latent variables, perceived ease of use and perceived usefulness, were considered as cognitive constructs; attitude toward MALL as an affective construct; behavioral intention to use MALL as a behavioral construct. The participants were 438 undergraduate students who enrolled in an intensive English program at one university in Korea. This particular program was held in January 2018 using the vacation period. The students were given eight hours of English classes each day from Monday to Friday for four weeks and asked to complete MALL courses for practice outside the classroom. Therefore, all participants experienced blended MALL environment. The instrument was a self-response questionnaire, and each construct was measured by five questions. Once the questionnaire was developed, it was distributed to the participants at the final ceremony of the intensive program in order to collect the data from a large number of the participants at a time. The data showed significant evidence to support the hypothetical model. The results confirmed through structural equation modeling analysis are as follows: First, four external variables such as subjective norm, content reliability, interactivity, and self-regulation significantly affected perceived ease of use. Second, subjective norm, content reliability, self-regulation, perceived ease of use significantly affected perceived usefulness. Third, perceived usefulness and perceived ease of use significantly affected attitude toward MALL. Fourth, attitude toward MALL and perceived usefulness significantly affected behavioral intention to use MALL. These results implied that the integrated framework from TAM and MALL could be useful when adopting MALL environment to university students or adult English learners. Key constructs except interactivity showed significant relationships with one another and had direct and indirect impacts on MALL user’s acceptance behavior. Therefore, the constructs and validated metrics is valuable for language researchers and educators who are interested in MALL.

Keywords: blended MALL, learner factors/variables, mobile-assisted language learning, MALL, technology acceptance model, TAM, theoretical framework

Procedia PDF Downloads 238

Authors: Debatosh Das, Moxian Chen, Jianhua Zhang, Caroline Gutjahr

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Arbuscular mycorrhiza (AM) is a mutualistic symbiosis between plant roots and Glomeromycotina fungi, which is activated under low but inhibited by high phosphate. The effect of phosphate on AM development has been observed for many years, but mechanisms regulating it under contrasting phosphate levels remain unknown. Based on previous observations that promoters of several AM functional genes contain PHR binding motifs, we hypothesized that PHR2, a master regulator of phosphate starvation response in rice, was recruited to regulate AM symbiosis development. We observed a drastic reduction in root colonization and significant AM transcriptome modulation in phr2. PHR2 targets genes required for root colonization and AM signaling. The role of PHR2 in improving root colonization, mycorrhizal phosphate uptake, and growth response was confirmed in field soil. In conclusion, rice PHR2, which is considered a master regulator of phosphate starvation responses, acts as a positive regulator of AM symbiosis between Glomeromycotina fungi and rice roots. PHR2 directly targets the transcription of plant strigolactone and AM genes involved in the establishment of this symbiosis. Our work facilitates an understanding of ways to enhance AMF propagule populations introduced in field soils (as a biofertilizer) in order to restore the natural plant-AMF networks disrupted by modern agricultural practices. We show that PHR2 is required for AM-mediated improvement of rice yield in low phosphate paddy field soil. Thus, our work contributes knowledge for rational application of AM in sustainable agriculture. Our data provide important insights into the regulation of AM by the plant phosphate status, which has a broad significance in agriculture and terrestrial ecosystems.

Keywords: biofertilizer, phosphate, mycorrhiza, rice, sustainable, symbiosis

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Authors: Jiang Xu, Daoping Wang, Yinghong Pan

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The jointing-booting stage is a critical period of both vegetative growth and reproductive growth in rice. Therefore, the proteomic analysis of the mutant Osbri1, whose corresponding gene OsBRI1 encodes the putative BRs receptor OsBRI1, at jointing-booting stage is very important for understanding the effects of BRs on vegetative and reproductive growth. In this study, the proteomes of leaves from an allelic mutant of the DWARF 61 (D61, OsBRI1) gene, Fn189 (dwarf54, d54) and its wild-type variety T65 (Taichung 65) at jointing-booting stage were analysed by using a Q Exactive plus orbitrap mass spectrometer, and more than 3,100 proteins were identified in each sample. Ontology analysis showed that these proteins distribute in various space of the cells, such as the chloroplast, mitochondrion, and nucleus, they functioned as structural components and/or catalytic enzymes and involved in many physiological processes. Moreover, quantitative analysis displayed that 266 proteins were differentially expressed in two samples, among them, 77 proteins decreased and 189 increased more than two times in Fn189 compared with T65, the proteins whose content decreased in Fn189 including b5-like Heme/Steroid binding domain containing protein, putative retrotransposon protein, putative glutaminyl-tRNA synthetase, and higher content proteins such as mTERF, putative Oligopeptidase homologue, zinc knuckle protein, and so on. A former study founded that the transcription level of a mTERF was up-regulated in the leaves of maize seedling after EBR treatment. In our experiments, it was interesting that one mTERF protein increased, but another mTERF decreased in leaves of Fn189 at jointing-booting stage, which suggested that BRs may have differential regulation mechanisms on the expression of various mTERF proteins. The relationship between other differential proteins with BRs is still unclear, and the effects of BRs on rice protein contents and its regulation mechanisms still need further research.

Keywords: bri1 mutant, jointing-booting stage, proteomic analysis, rice

Procedia PDF Downloads 247

Authors: André Furtado, Rafael Mineiro, Isabel Gonçalves, Cecília Santos, Telma Quintela

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The development of therapies for central nervous system (CNS) disorders is one of the biggest challenges of current pharmacology, given the unique features of brain barriers, which limit drug delivery. Efflux transporters (ABC transporters) expressed at the blood-cerebrospinal fluid barrier (BCSFB), are the main obstacles for the delivery of therapeutic compounds into the CNS, compromising the effective treatment of brain cancer, brain metastasis from peripheral cancers, or even neurodegenerative disorders. It is thus extremely important to understand the regulation of these transporters for reducing their expression while treating a brain disorder or choosing the most appropriate conditions for drug administration. Based on the fact that the BCSFB have fine-tuned biological rhythms, studying the circadian variation of drug transport processes is critical for choosing the most appropriate time of the day for drug administration. In our study, using an in vitro model of the BCSFB, we characterized the circadian transport profile of methotrexate (MTX) and donepezil (DNPZ), two drugs involved in the treatment of cancer and Alzheimer’s Disease symptoms, respectively. We found that MTX is transported across the basal and apical membranes of the BCSFB in a circadian way. The circadian pattern of an ABC transporter, Abcc4, might be partially responsible for MTX circadian transport. Furthermore, regarding the DNPZ transport study, we observed that the regulation of Abcg2 expression by the circadian rhythm will impact the circadian-dependent transport of DNPZ across the BCSFB. Overall, our results will contribute to the current knowledge on brain pharmacoresistance at the BCSFB by disclosing how circadian rhythms control drug delivery to the brain, setting the grounds for a potential application of chronotherapy to brain diseases to enhance the efficacy of medications and minimize their side effects.

Keywords: blood-cerebrospinal fluid barrier, ABC transporters, drug transport, chronotherapy

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