Search results for: transcription regulation

Authors: L. Kamandulytė-Merfeldienė

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The paper deals with the main issues of methodology of the Corpus of Spoken Lithuanian which was started to be developed in 2006. At present, the corpus consists of 300,000 grammatically annotated word forms. The creation of the corpus consists of three main stages: collecting the data, the transcription of the recorded data, and the grammatical annotation. Collecting the data was based on the principles of balance and naturality. The recorded speech was transcribed according to the CHAT requirements of CHILDES. The transcripts were double-checked and annotated grammatically using CHILDES. The development of the Corpus of Spoken Lithuanian has led to the constant increase in studies on spontaneous communication, and various papers have dealt with a distribution of parts of speech, use of different grammatical forms, variation of inflectional paradigms, distribution of fillers, syntactic functions of adjectives, the mean length of utterances.

Keywords: CHILDES, corpus of spoken Lithuanian, grammatical annotation, grammatical disambiguation, lexicon, Lithuanian

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Authors: Nazari Maryam, Gorji Saman

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For most competitions, athletes usually engage in a process called rapid weight loss (RWL) and subsequent rapid weight gain (RWG) in the days preceding the event. Besides the perfection of performance, weight regulation mediates a self-image of being “a real athlete” which is mentally important as a part of the pre-competition preparation. This feeling enhances the focus and commitment of the athlete. There is a large body of evidence that weight loss, particularly in combat sports, results in several health benefits. However, intentional weight loss beyond normal levels might have unknown negative special effects on the immune system. As the results show, a high prevalence (50%) of RWL is happening among combat athletes. It seems that energy deprivation and intense exercise to reach RWL results in altered blood cell distribution through modification of body composition that, in turn, changes B and T-Lymphocyte and/or CD4 T-Helper response. Moreover, it may diminish IgG antibody levels and modulate IgG glycosylation after this course. On the other hand, some studies show suppression of signaling and regulation of IgE antibody and chemokine production are responsible for immunodeficiency following a period of low-energy availability. Some researchers hypothesize that severe glutamine depletion, which occurs during exercise and calorie restriction, is responsible for this immune system weakness. However, supplementation by this amino acid is not prescribed yet. Therefore, weight loss is achieved not only through chronic strategies (body fat losses) but also through acute manipulations prior to competition should be supervised by a sports nutritionist to minimize side effects on the immune system and other body systems.

Keywords: athletes, immune system, rapid weight loss, weight loss strategies

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Authors: Inga Žukovaitė

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This paper aims to present postdoc research on remote criminal proceedings in court. In this period, when most countries have introduced the possibility of remote criminal proceedings in their procedural laws, it is not only possible to identify the weaknesses and strengths of the legal regulation but also assess the effectiveness of the instrument used and to develop an approach to the process. The example of some countries (for example, Italy) shows, on the one hand, that criminal procedure, based on orality and immediacy, does not lend itself to easy modifications that pose even a slight threat of devaluation of these principles in a society with well-established traditions of this procedure. On the other hand, such strong opposition and criticism make us ask whether we are facing the possibility of rethinking the traditional ways to understand the safeguards in order to preserve their essence without devaluing their traditional package but looking for new components to replace or compensate for the so-called “loss” of safeguards. The reflection on technological progress in the field of criminal procedural law indicates the need to rethink, on the basis of fundamental procedural principles, the safeguards that can replace or compensate for those that are in crisis as a result of the intervention of technological progress. Discussions in academic doctrine on the impact of technological interventions on the proceedings as such or on the limits of such interventions refer to the principles of criminal procedure as to a point of reference. In the context of the inferiority of technology, scholarly debate still addresses the issue of whether the court will not gradually become a mere site for the exercise of penal power with the resultant consequences – the deformation of the procedure itself as a physical ritual. In this context, this work seeks to illustrate the relationship between remote criminal proceedings in court and the principle of immediacy, the concept of which is based on the application of different models of criminal procedure (inquisitorial and adversarial), the aim is to assess the challenges posed for legal regulation by the interaction of technological progress with the principles of criminal procedure. The main hypothesis to be tested is that the adoption of remote proceedings is directly linked to the prevailing model of criminal procedure, arguing that the more principles of the inquisitorial model are applied to the criminal process, the more remote criminal trial is acceptable, and conversely, the more the criminal process is based on an adversarial model, more the remote criminal process is seen as incompatible with the principle of immediacy. In order to achieve this goal, the following tasks are set: to identify whether there is a difference in assessing remote proceedings with the immediacy principle between the adversarial model and the inquisitorial model, to analyse the main aspects of the regulation of remote criminal proceedings based on the examples of different countries (for example Lithuania, Italy, etc.).

Keywords: remote criminal proceedings, principle of orality, principle of immediacy, adversarial model inquisitorial model

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Authors: Avent Grange, Frederic Bertrand, Jean-Baptiste Droin, Amandine Marrel, Jean-Henry Ferrasse, Olivier Boutin

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CEA and its industrial partners are designing a gas Power Conversion System (PCS) based on a Brayton cycle for the ASTRID Sodium-cooled Fast Reactor. Investigations of control and regulation requirements to operate this PCS during operating, incidental and accidental transients are necessary to adapt core heat removal. To this aim, we developed a methodology to optimize the thermal-hydraulic behavior of the reactor during normal operations, incidents and accidents. This methodology consists of a multi-objective optimization for a specific sequence, whose aim is to increase component lifetime by reducing simultaneously several thermal stresses and to bring the reactor into a stable state. Furthermore, the multi-objective optimization complies with safety and operating constraints. Operating, incidental and accidental sequences use specific regulations to control the thermal-hydraulic reactor behavior, each of them is defined by a setpoint, a controller and an actuator. In the multi-objective problem, the parameters used to solve the optimization are the setpoints and the settings of the controllers associated with the regulations included in the sequence. In this way, the methodology allows designers to define an optimized and specific control strategy of the plant for the studied sequence and hence to adapt PCS piloting at its best. The multi-objective optimization is performed by evolutionary algorithms coupled to surrogate models built on variables computed by the thermal-hydraulic system code, CATHARE2. The methodology is applied to a loss of off-site power sequence. Three variables are controlled: the sodium outlet temperature of the sodium-gas heat exchanger, turbomachine rotational speed and water flow through the heat sink. These regulations are chosen in order to minimize thermal stresses on the gas-gas heat exchanger, on the sodium-gas heat exchanger and on the vessel. The main results of this work are optimal setpoints for the three regulations. Moreover, Proportional-Integral-Derivative (PID) control setting is considered and efficient actuators used in controls are chosen through sensitivity analysis results. Finally, the optimized regulation system and the reactor control procedure, provided by the optimization process, are verified through a direct CATHARE2 calculation.

Keywords: gas power conversion system, loss of off-site power, multi-objective optimization, regulation, sodium fast reactor, surrogate model

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Authors: Qi Liu, Jiqin Yao, Xiaohu Zhou, Bo Zheng

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The first artificial cell was produced by Thomas Chang in the 1950s when he was trying to make a mimic of red blood cells. Since then, many different types of artificial cells have been constructed from one of the two approaches: a so-called bottom-up approach, which aims to create a cell from scratch, and a top-down approach, in which genes are sequentially knocked out from organisms until only the minimal genome required for sustaining life remains. In this project, bottom-up approach was used to build a new cell-free expression system which mimics artificial cell that capable of protein expression and communicate with each other. The artificial cells constructed from the bottom-up approach are usually lipid vesicles, polymersomes, hydrogels or aqueous droplets containing the nucleic acids and transcription-translation machinery. However, lipid vesicles based artificial cells capable of communication present several issues in the cell communication research: (1) The lipid vesicles normally lose the important functions such as protein expression within a few hours. (2) The lipid membrane allows the permeation of only small molecules and limits the types of molecules that can be sensed and released to the surrounding environment for chemical communication; (3) The lipid vesicles are prone to rupture due to the imbalance of the osmotic pressure. To address these issues, the hydrogel-based artificial cells were constructed in this work. To construct the artificial cell, polyacrylamide hydrogel was functionalized with Acrylate PEG Succinimidyl Carboxymethyl Ester (ACLT-PEG2000-SCM) moiety on the polymer backbone. The proteinaceous factors can then be immobilized on the polymer backbone by the reaction between primary amines of proteins and N-hydroxysuccinimide esters (NHS esters) of ACLT-PEG2000-SCM, the plasmid template and ribosome were encapsulated inside the hydrogel particles. Because the artificial cell could continuously express protein with the supply of nutrients and energy, the artificial cell-artificial cell communication and artificial cell-natural cell communication could be achieved by combining the artificial cell vector with designed plasmids. The plasmids were designed referring to the quorum sensing (QS) system of bacteria, which largely relied on cognate acyl-homoserine lactone (AHL) / transcription pairs. In one communication pair, “sender” is the artificial cell or natural cell that can produce AHL signal molecule by synthesizing the corresponding signal synthase that catalyzed the conversion of S-adenosyl-L-methionine (SAM) into AHL, while the “receiver” is the artificial cell or natural cell that can sense the quorum sensing signaling molecule form “sender” and in turn express the gene of interest. In the experiment, GFP was first immobilized inside the hydrogel particle to prove that the functionalized hydrogel particles could be used for protein binding. After that, the successful communication between artificial cell-artificial cell and artificial cell-natural cell was demonstrated, the successful signal between artificial cell-artificial cell or artificial cell-natural cell could be observed by recording the fluorescence signal increase. The hydrogel-based artificial cell designed in this work can help to study the complex communication system in bacteria, it can also be further developed for therapeutic applications.

Keywords: artificial cell, cell-free system, gene circuit, synthetic biology

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Authors: Sema Cortoglu Koca

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Intellectual and industrial property rules, have a substantial effect on the sustainable development. Intellectual and industrial property rights, as temporary privileges over the products of intellectual activity, determine the supervision of information and technology. The level and scope of intellectual property protection thus influence the flow of technology between developed and developing countries. In addition, intellectual and industrial property rights are based on the notion of balance. Since they are time-limited rights, they reconcile private and public benefits. That is, intellectual and industrial property rights respond to both private interests and public interests by rewarding innovators and by promoting the dissemination of ideas, respectively. Intellectual and industrial property rights can, therefore, be a tool for sustainable development. If countries can balance their private and public interests according to their particular context and circumstances, they can ensure the intellectual and industrial property which promotes innovation and technology transfer relevant for them. People, enterprises and countries who need technology, can transfer developed technology which is acquired by people, enterprises and countries so as to decrease their technological necessity and improve their technology. Because of the significance of intellectual and industrial property rights on the technology transfer law as mentioned above, this paper is confined to intellectual and industrial property agreements especially technology transfer contracts. These are license contract, know-how contract, franchise agreement, joint venture agreement, management agreement, research and development agreement. In Turkey, technology transfer law is still a developing subject. For developing countries, technology transfer regulations are very important for their private international law because these countries do not know which technology transfer law is applicable when conflicts arise. In most technology transfer contracts having international elements, the parties choose a law to govern their contracts. Where the parties do not choose a law, either expressly or impliedly, and matters which is not excluded in party autonomy, the court has to determine the applicable law to contracts in a matter of capacity, material, the formal and essential validity of contracts. For determining the proper law of technology transfer contracts, it is tried to build a rule for applying all technology transfer contracts. This paper is confined to the applicable law to intellectual and industrial property agreements according to ‘5718 Turkish Act on Private International Law and Civil Procedure’ and ‘Regulation (EC) No 593/2008 of the European Parliament and of the Council of 17 June 2008 on the law applicable to contractual obligations (Rome I)’. Like these complex contracts, to find a rule can be really difficult. We can arrange technology transfer contracts in groups, and we can determine the rule and connecting factors to these groups. For the contracts which are not included in these groups, we can determine a special rule considering the characteristics of the contract.

Keywords: intellectual and industrial property agreements, Rome I regulation, technology transfer, Turkish act on private international law and civil procedure

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Authors: Renu Singh

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The caste system in Indian society plays an important role in subjugation of women. It creates divides and controls over women’s sexuality in various ways. This paper attempts to look into various modes in which the institution of caste makes some forms of sexuality as socially “acceptable” norms, while deems others as obscene, immoral and against social ethos. Based on a review of existing literature in this area this paper attempts to understand the notion of sexuality in Indian context. It tries to understand how the emergence of norms and values of sexual behaviour has been entwined with the evolution of caste system and the subjugation of many sections of Indian society. It also attempts to trace the internalisation of patriarchal values in Indian society, and the role played by the colonial rulers in creating and maintaining stringent division of space into public and private ones. It is argued here that brahmanical patriarchy, which is a unique phenomenon of the Indian Subcontinent, plays a crucial role in subjugating and controlling women in general and their sexuality in particular. It also creates a divide among women of different castes. Furthermore, the process of colonisation played an important role in shaping the discourse of sexuality in its present form. There were contradictions as well as consensus between the colonial rulers over the questions of regulation of the private domain, as in introducing reform legislation in the nineteenth century informed the debate on sexuality in postcolonial India. The process of emergence of the dichotomous notions of ‘good’ and ‘bad’ sexuality, and the resistance to any ‘deviation’ from the ‘normal’ sexuality is located, not merely in the ‘passive’ evolution of society, but in the actual politics of it.

Keywords: caste, control, sexuality, regulation, brahmanical patriarchy, India

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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: 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: Narin Salehiyan, Ramin Ghasemi Shayan

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In order to investigate coronavirus RNA replication, transcription, recombination, protein processing and transport, virion assembly, the identification of coronavirus-specific cell receptors, and polymerase processing, the manipulation of coronavirus clones and complementary DNAs (cDNAs) of defective-interfering (DI) RNAs is the subject of this chapter. The idea of the Covid genome is nonsegmented, single-abandoned, and positive-sense RNA. When compared to other RNA viruses, its size is significantly greater, ranging from 27 to 32 kb. The quality encoding the enormous surface glycoprotein depends on 4.4 kb, encoding a forcing trimeric, profoundly glycosylated protein. This takes off exactly 20 nm over the virion envelope, giving the infection the appearance-with a little creative mind of a crown or coronet. Covid research has added to the comprehension of numerous parts of atomic science as a general rule, like the component of RNA union, translational control, and protein transport and handling. It stays a fortune equipped for creating startling experiences.

Keywords: covid-19, corona, virus, genome, genetic

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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: Mark Berry

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A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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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: Alaa M. Badr Eldin, Mayar M. Shahen, Mohammed S. Sedeek, Marwa I. Ezzat, Sawsan M. ElSonbaty, Muhammed A. Saad, Manal S. Afifi, Omar M. Sabry

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Using HPLC-MS/MS technique, 133 polyphenolic compounds were identified in the methanol extract of pomegranate rind (Punica granatum L.). In-vitro cytotoxic activity against breast cancer cell line MCF-7 was investigated, with an IC50 of 54 ug/ml. In-silico molecular docking using ellagic acid, gallagic acid, and Punicalagin as model compounds identified in pomegranate rind extract confirmed the intriguing anti-estrogenic action of the key polyphenolic components in pomegranate rind extract. Surprisingly, taxol showed low activity compared to pomegranate compounds as ERα antagonist and ERβ agonist. Pomegranate rind extract enhanced apoptosis of breast cancer cells through upregulation of the caspase-3 expression and downregulation of NF-κB transcription factor.

Keywords: HPLC-MS/MS, pomegranate rind, cytotoxicity, MCF-7, ER, caspase-3, NF-kB

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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: 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: Sandy Elsayed, Aya Mohamed, Noha Nassar

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Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behavior. Multiple studies suggest that oxidative stress and neuroinflammation are key factors in the etiology of ASD and often associated with worsening of ASD-related behaviors. Nuclear factor erythroid 2-related factor 2 (NRF-2) is a transcription factor that promotes expression of antioxidant response element genes in oxidative stress. In ASD subjects, decreased expression of NRF-2 in frontal cortex shifted the redox homeostasis towards oxidative stress, and resulted in inflammation evidenced by elevation of nuclear factor kappa B (NF-κB) transcriptional activity. Dimethyl fumarate (DMF) is a NRF-2 activator that is used in the treatment of psoriasis and multiple sclerosis. It participates in the transcriptional control of inflammatory factors via inhibition of NF-κB and its downstream targets. This study aimed to investigate the role of DMF in alleviating the cognitive impairments and behavior deficits associated with ASD through mitigation of oxidative stress and inflammation in prenatal valproic acid (VPA) rat model of autism. Methods: Pregnant female Wistar rats received a single intraperitoneal injection of VPA (600 mg/kg) to induce autistic-like-behavioral and neurobiological alterations in their offspring. Chronic oral gavage of DMF (150mg/kg/day) started from postnatal day (PND) 24 till PND62 (39 days). Prenatal VPA exposure elicited autistic behaviors including decreased social interaction and stereotyped behavior. Social interaction was evaluated using three-chamber sociability test and calculation of sociability index (SI), while stereotyped repetitive behavior and anxiety associated with ASD were assessed using marble burying test (MBT). Biochemical analyses were done on prefrontal cortex homogenates including NRF-2, and NF-κB expression. Moreover, inducible nitric oxide synthase (iNOS) gene expression and tumor necrosis factor (TNF-) protein expression were evaluated as markers of inflammation. Results: Prenatal VPA elicited decreased social interaction shown by decreased SI compared to control group (p < 0.001) and DMF enhanced SI (p < 0.05). In MBT, prenatal injection of VPA manifested stereotyped behavior and enhanced number of buried marbles compared to control (p < 0.05) and DMF reduced the anxiety-related behavior in rats exhibiting ASD-like behaviors (p < 0.05). In prefrontal cortex, NRF-2 expression was downregulated in prenatal VPA model (p < 0.0001) and DMF reversed this effect (p < 0.0001). The inflammatory transcription factor NF-κB was elevated in prenatal VPA model (p < 0.0001) and reduced (p < 0.0001) upon NRF-2 activation by DMF. Prenatal VPA expressed higher levels of proinflammatory cytokine TNF- compared to control group (p < 0.0001) and DMF reduced it (p < 0.0001). Finally, the gene expression of iNOS was downregulated upon NRF-2 activation by DMF (p < 0.01). Conclusion: This study proposes that DMF is a potential agent that can be used to ameliorate autistic-like-changes through NRF-2 activation along with NF-κB downregulation and therefore, it is a promising novel therapy for ASD.

Keywords: autism spectrum disorders, dimethyl fumarate, neuroinflammation, NRF-2

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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: D. R. Apoorva

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Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome is a rare oculocutaneous disorder of genetic origin. This disorder results from mutations in the membrane-bound transcription factor protease site, two genes that impair cholesterol homeostasis, and the ability to cope with endoplasmic reticulum stress. We report a rare case of IFAP syndrome with an atypical presentation, and it was interesting to note that the child had patchy non-scarring alopecia over the scalp along with unilateral madarosis. To our best knowledge, this unique presentation has not been described earlier. The child presented with photophobia and unilateral ptosis. The child also had short stature and intellectual disability. Skin histopathology was nonspecific and consisted of dilated hair follicles with keratin plugs extending above the skin surface. This rare oculocutaneous disorder requires proper documentation so that identification of its variants may be possible in the future. Early recognition of atypical presentations can help in preventing cardiovascular complications, which remain the major cause of death.

Keywords: alopecia, photophobia, ichthyosis follicularis, IFAP syndrome

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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: Vasudev Das

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In a global survey of more than 5,000 participants in 99 territories, PwC found a loss of $42 billion through fraud in the last 24 months. The specific problem is that private and public organizational leaders often do not understand the importance of sonic therapeutic intervention in preventing financial fraud. The study aimed to explore sonic therapeutic intervention practitioners' lived experiences regarding the value of sonic therapeutic intervention in preventing financial fraud. The data collection methods were semi-structured interviews of purposeful samples and documentary reviews, which were analyzed thematically. Four themes emerged from the analysis of interview transcription data: Sonic therapeutic intervention enabled self-control, pro-spiritual values, consequentiality mindset, and post-conventional consciousness. The itemized four themes helped non-engagement in financial fraud. Implications for positive social change include enhanced financial fraud management, more significant financial leadership, and result-oriented decision-taking in the financial market. Also, the study results can improve the increased de-escalation of anxiety/stress associated with defrauding.

Keywords: consciousness, consequentiality, rehabilitation, reintegration

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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

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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: Louis Okon Akpan

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National Open University of Nigeria (NOUN) is an open and distance learning institution whose aim is to provide education for all and also promote lifelong learning in Nigeria. Before now, student-centred learning was adopted. In recent times, online facilitation has been introduced. Therefore, the study explores ways in which students are satisfied with online facilitation provided by NOUN lecturers. A qualitative approach was adopted. The interpretive paradigm was employed as a lens to interpret narratives from the participants. In order to gather information for the study, a semi-structured interview was developed for sixteen participants who were purposively selected from eight facilities of the university. After data gathering from the field, it was subjected to transcription and coding. The emergence of themes from the coded data was analysed using thematic analysis. Findings indicated that students found online learning, recently introduced by the university management, extremely fulfilling and rewarding.

Keywords: online facilitation, lecturer, students’ satisfaction, National Open University of Nigeria

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