Search results for: transcription regulation

Authors: Aslanova Aida Ramiz

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One of the important aspects of rheophysical problems in oil and gas extraction is the regulation of thermohydrodynamic properties of liquid systems using physical and physicochemical methods. It is known that the constituent parts of real fluid systems in oil and gas production are practically non-conducting, non-magnetically active components. Real heterogeneous hydrocarbon systems, from the structural point of view, consist of an infinite number of microscopic local ion-electrostatic cores distributed in the volume of the dispersion medium. According to Cohen's rule, double electric layers are formed at the contact boundaries of components in contact (oil-gas, oil-water, water-condensate, etc.) in a heterogeneous system, and as a result, each real fluid system can be represented as a complex composition of a set of local electrostatic fields. The electrokinetic properties of this structure are characterized by a certain electrode potential. Prof. F.H. Valiyev called this potential the α-factor and came up with the idea that many natural and technological rheophysical processes (effects) are essentially electrokinetic in nature, and by changing the α-factor, it is possible to adjust the physical properties of real hydraulic systems, including thermohydrodynamic parameters. Based on this idea, extensive research work was conducted, and the possibility of reducing hydraulic resistances and improving rheological properties was experimentally discovered in real liquid systems by reducing the electrical potential with various physical and chemical methods.

Keywords: microcracked, electrode potential, hydraulic resistance, Newtonian fluid, rheophysical properties

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Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

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The family of phosphodiesterases (PDEs) plays a critical role in control of the level, localization, and duration of intracellular 3’-5’-cyclic adenosine monophosphate (cAMP) and 3’-5’-cyclic guanosine monophosphate (cGMP) signals by specifically hydrolyzing these cyclic nucleotides. As the involvement of cyclic nucleotide second messengers in cell signaling and homeostasis is established, the regulation of these pathways in the brain by various PDE isoforms is an area of considerable interest, as they are involved in nearly all brain functions and in the etiology of neuropsychiatric diseases. The PDE10A isoform, isolated from different species and characterized regarding structure and function, has received much attention in recent years, particularly in the context of schizophrenia and Huntington’s disease, which are both related to a role of PDE10A in the regulation of striatal dopaminergic neurotransmission. Quinazoline analogue 1-(4-methoxyphenyl)-6,7-dimethoxyquinazoline, was evaluated as specific PET marker for phosphodiesterase (PDE) 10A. Here, we report the radiosynthesis of [11C]2 and the in vitro and in vivo evaluation of [11C]2 as a potential positron emission tomography (PET) radiotracer for imaging PDE10A in the central nervous system (CNS). The radiosynthesis of [11C]2 was achieved by O-methylation of the corresponding des-methyl precursor with [11C]methyl iodide. [11C]2 was obtained with ∼50% radiochemical yield. PET imaging studies in rat brain displayed initial specific uptake with very rapid clearance of [11C]2 from brain. Though [11C]2 is not an ideal radioligand for clinical imaging of PDE10A in the CNS. Modified analogue of quinazoline having a higher potency for inhibiting PDE10A and improved pharmacokinetic properties will be necessary for imaging this enzyme with PET.

Keywords: PDE10A, PET, radiotracer, quinazoline

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Authors: Tamas Bezsenyi, Noemi Katona

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Fighting Human Trafficking is a highly important issue worldwide that states need to deal with in international politics. In the EU combatting human trafficking is emphasized in international policy making and also in the work of international law enforcement, thus in the work of the EUROPOL. While the EU Directive against Human Trafficking prescribes how states should fight this transnational crime and also how victims should be assisted, the EUROPOL focuses on the effective cooperation between national law enforcement agencies. However, despite the aims of the common fight, human trafficking is regulated differently in the punitive law of various nation states. This deeply defines the work and possibilities of national law enforcement organizations. Among the manifold differences in this paper, we focus on the role of regulating asset recovery. We highlight that money, and the regulation and practice how the law enforcement deals with income gained from criminal activities, play essential role in combatting human trafficking. While doing research on the investigation of transnational human trafficking by the Hungarian Law Enforcement Agencies, we have found that the unfortunate regulation of asset recovery determines the lower effectiveness of eliminating criminal organizations. While i.e. in the Netherlands confiscation of property takes place in an early stage of the criminal procedure, in Hungary it can be conducted only if money laundering is also assumed. Our presentation builds on the comparison of criminal procedures which we analyse based on criminal files and interviews with coworkers of the National Bureau of Investigation.

Keywords: human trafficking, law enforcement, asset recovery, organized crime

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Authors: Liya Abraham

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Eritrea is located along the Red Sea, north of the Horn of Africa, between Djibouti and Sudan and has a population of about 3.2 million as of 2010. It has six administrative regions; Anseba, Debub, Debubawi K’eyih Bahri, Gash-Barka, Ma'akel, and Semenawi K’eyih Bahri. Eritrea has got its independence in 1991 after 30 years war of liberation. The country is blessed with various medicinal flora and fauna, and marine and terrestrial biodiversity. Traditional Medicine (TM) has been an integral part of the Eritrean culture for centuries. So far, more than 19 TM modalities have been recognized, and are broadly categorized as; herbal, procedure-based and spiritual. Despite the availability of modern medicine to the majority of the population, TM is still widely practiced. The rationale behind widespread use is accessibility, affordability and cultural acceptability. Hence, TM is of great contribution to the Eritrean health care system. As a matter of fact, harnessing the potential contribution of effective and safe TM in order to attain Universal Health Coverage (UHC) has been emphasized in the WHO TM strategy 2014-2023. The Eritrean TM, however, was operating without regulation and reliable scientific justification behind its safety and efficacy. Thus, the Ministry of Health (MoH), in recognition of the role of TM in primary healthcare and safeguard public health, established a regulatory body for TM so-called as Traditional Medicine Unit (TMU) in 2012. The mission of the unit is to ensure rational TM use through an integrated health service delivery system and contribute to the country’s economic and social development. The unit has established its national TM policy in 2017. The activities of the unit are guided by the National TM Advisory Committee (TMAC), responsible for the provision of technical assistance and advisory role. Moreover, the Legal Framework and Code of Ethics and Practice which provide a legal basis for the regulation of TM have also been drafted. In recognition of the importance of TM research and development, the unit launched a nationwide TM survey in 2017 and had surveyed two zones (Gash-Barka and Debub). The findings of the survey were subjected to a research dissemination workshop and publication in international journals. Furthermore, TM-related adverse events reporting tool (Green Form) aiming to guide regulatory interventions and researches have been established by the unit, and ever since reports are flowing. The unit has also been offering training to THPs, pharmacy students and health care professionals regarding TM and its regulatory activities. In addition, as part of the establishment of the national medicinal plants' database and herbal monograph, more than 329 and 30 medicinal plants, have been compiled respectively. In conclusion, TM is still widely accepted and practiced in Eritrea. The TMU ever since its establishment is endeavoring to ensure the safety and efficacy of the TM, and its integration in the mainstream health service delivery system.

Keywords: efficacy, regulation, safety, traditional medicine, traditional medicine unit, universal health coverage

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Authors: Ana Tsokilauri

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The uppermost factor in the regulation of lignin-cellulose activity of decaying white rot or free rot are the substances serving as carbon and nitrogen nutrition of microorganisms and are considered as the most important factor of generative activity of white rot. The research object was Basidiomycete Fungi, peculiar and common in Georgia, and the separation of 10 of them as pure crops. The unidentified pure crops have tasted in order to be determined the potential of synthesis of lignin-degrading enzymes and the substrate of optimal lignocellulose growth. One of the most important aspects of the research conducted on Basidiomycetes was the use of specific lignocellulosic residues for selecting Fungi as a substrate of their growth. In order to increase lignocellulose with the help of substrate, crops were selected from the screening stage that showed good laccase activity. (Dusheti 1; Dusheti 10; Fshavi 5; Fshavi1; Fshavi 8; Fshavi 32; Manglisi 26; Sabaduri20; Dusheti 7; Sabaduri 1 ), Among the selected cultures, the crops with good laccase activity against the following substances, in particular: Dusheti 1- in this case, the rate of enzymatic activity on bran substrate was -105,6 u/ml, mandarin-96,4 u/ml. In case of corn - 102,9 u/ml. In case of Dusheti 7- the indicators were as follows: bananas-121,7 u/ml, mandarin-125,4 u/ml, corn - 117,1 u/ml. In the case of Sanaduri 32, the laccase activity was as follows: pomegranate- 101,2 u/ml. As a result of conducted experiments, the synthesis and activity rates of enzymes depending on plant substrates varied within a fairly wide range, which is still being under research.

Keywords: Lignocellulosic substrate, Basidiomycetes, white-rot basidiomycetes, Laccase

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Authors: Seok Woo Chang

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Aim: Capseal I and Capseal II are calcium silicate and calcium phosphate based experimental root canal sealer. The aim of this study was to evaluate the biocompatibility and mineralization potential of Capseal I and Capseal II. Materials and Methods: The biocompatibility and mineralization-related gene expression (alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN)) of Capseal I and Capseal II were compared using methylthiazol tetrazolium assay and reverse transcription-polymerization chain reaction analysis, respectively. The results were analyzed by Kruskal-Wallis test. P-value of < 0.05 was considered significant. Result: Both Capseal I and Capseal II were favorable in biocompatibility and influenced the messenger RNA expression of ALP and BSP. Conclusion: Within the limitation of this study, Capseal is biocompatible and have mineralization promoting potential, and thus could be a promising root canal sealer.

Keywords: biocompatibility, mineralization-related gene expression, Capseal I, Capseal II

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Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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Authors: Yuriko Takayama, Norihiro Kato

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Quorum sensing (QS) is a cell-to-cell communication system in bacteria to regulate expression of target genes. In gram-negative bacteria, activation on QS is controlled by a concentration increase of N-acylhomoserine lactone (AHL), which can diffuse in and out of the cell. Effective control of QS is expected to avoid virulence factor production in infectious pathogens, biofilm formation, and antibiotic production because various cell functions in gram-negative bacteria are controlled by AHL-mediated QS. In this research, we applied cyclodextrins (CDs) as artificial hosts for the AHL signal to reduce the AHL concentration in the culture broth below its threshold for QS activation. The AHL-receptor complex induced under the high AHL concentration activates transcription of the QS-target gene. Accordingly, artificial reduction of the AHL concentration is one of the effective strategies to inhibit the QS. A hydrophobic cavity of the CD can interact with the acyl-chain of the AHL due to hydrophobic interaction in aqueous media. We studied N-hexanoylhomoserine lactone (C6HSL)-mediated QS in Serratia marcescens; accumulation of C6HSL is responsible for regulation of the expression of pig cluster. Inhibitory effects of added CDs on QS were demonstrated by determination of prodigiosin amount inside cells after reaching stationary phase, because production of prodigiosin depends on the C6HSL-mediated QS. By adding approximately 6 wt% hydroxypropyl-β-CD (HP-β-CD) in Luria-Bertani (LB) medium prior to inoculation of S. maecescens AS-1, the intracellularly accumulated prodigiosin was drastically reduced to 7-10%, which was determined after the extraction of prodigiosin in acidified ethanol. The AHL retention ability of HP-β-CD was also demonstrated by Chromobacterium violacuem CV026 bioassay. The CV026 strain is an AHL-synthase defective mutant that activates QS solely by adding AHLs from outside of cells. A purple pigment violacein is induced by activation of the AHL-mediated QS. We demonstrated that the violacein production was effectively suppressed when the C6HSL standard solution was spotted on a LB agar plate dispersing CV026 cells and HP-β-CD. Physico-chemical analysis was performed to study the affinity between the immobilized CD and added C6HSL using a quartz crystal microbalance (QCM) sensor. The COOH-terminated self-assembled monolayer was prepared on a gold electrode of 27-MHz AT-cut quartz crystal. Mono(6-deoxy-6-N, N-diethylamino)-β-CD was immobilized on the electrode using water-soluble carbodiimide. The C6HSL interaction with the β-CD cavity was studied by injecting the C6HSL solution to a cup-type sensor cell filled with buffer solution. A decrement of resonant frequency (ΔFs) clearly showed the effective C6HSL complexation with immobilized β-CD and its stability constant for MBP-SpnR-C6HSL complex was on the order of 102 M-1. The CD has high potential for engineered control of QS because it is safe for human use.

Keywords: acylhomoserine lactone, cyclodextrin, intracellular signaling, quorum sensing

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Authors: Chin Ku, Han liang Lin

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The purpose of this study is to visualize how the rule related to urban design influences the building form by 3D modeling software CityEngine. In order to make the goal of urban design clearly connect to urban form, urban planner or designer should understand how the rule affects the form, especially the building form. In Taiwan, the rule pertained to urban design includes traditional zoning, urban design review and building codes. However, zoning cannot precisely expect the outcome of building form and lack of thinking about public realm and 3D form. In addition to that, urban design review is based on case by case, do not have a comprehensive regulation plan and the building code is just for general regulation. Therefore, rule cannot make the urban form reach the vision or goal of the urban design. Consequently, another kind of zoning called Form-based code (FBC) has arisen. This study uses the component of FBC which pertained to urban fabric such as street width, block and plot size, etc., to be the variants of building form, and find out the relationship between the rule and building form. There are three stages of this research, it will start from a field survey of Taichung City in Taiwan to induce the rule-building form relationship by using cluster analysis and descriptive Statistics. Second, visualize the relationship through the parameterized and codified process in CityEngine which is the procedural modeling, and can analyze, monitor and visualize the 3D world. Last, compare the CityEngine result with real world to examine how extent do this model represent the real world appearance.

Keywords: 3D visualization, CityEngine, form-based code, urban form

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Authors: Jian-Jun Shu

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The statistical properties of CRMs are explored by estimating similar-word set occurrence distribution. It is observed that CRMs tend to have a fat-tail distribution for similar-word set occurrence. Thus, the fat-tail test with two fatness coefficients is proposed to distinguish CRMs from non-CRMs, especially from exons. For the first fatness coefficient, the separation accuracy between CRMs and exons is increased as compared with the existing content-based CRM prediction method – fluffy-tail test. For the second fatness coefficient, the computing time is reduced as compared with fluffy-tail test, making it very suitable for long sequences and large data-base analysis in the post-genome time. Moreover, these indexes may be used to predict the CRMs which have not yet been observed experimentally. This can serve as a valuable filtering process for experiment.

Keywords: statistical approach, transcription factor binding sites, cis-regulatory modules, DNA sequences

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Authors: Kai Zhu, Shanhua He, Yujiao Chang

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This paper explores the virtual linguistic landscape of an emerging virtual language community in TikTok, a language community realizing immediate and non-immediate communication without a precise Spatio-temporal domain or a specific socio-cultural boundary or interpersonal network. This kind of language community generates a large number and various forms of virtual linguistic landscape, with which we conducted a virtual ethnographic survey together with telephone interviews to collect data from coping. We have been following two language communities in TikTok for several months so that we can illustrate the composition of the two language communities and some typical virtual language landscapes in both language communities first. Then we try to explore the reasons why and how they are formed through the organization, transcription, and analysis of the interviews. Our analysis reveals the richness and diversity of the virtual linguistic landscape, and finally, we summarize some of the characteristics of this language community.

Keywords: virtual linguistic landscape, virtual language community, virtual ethnographic survey, TikTok

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Authors: Arash Sepehri bonab

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One of the regions of critical development in medical devices has been the part of the software - as an indispensable component of a therapeutic device, as a standalone device, and more as of late, as applications on portable gadgets. The chance related to a breakdown of the standalone computer program utilized inside healthcare is in itself not a model for its capability or not as a medical device. It is, subsequently, fundamental to clarify a few criteria for the capability of a stand-alone computer program as a medical device. The number of computer program items and therapeutic apps is persistently expanding and so as well is used in wellbeing education (e. g., in clinics and doctors' surgeries) for determination and treatment. Within the last decade, the use of information innovation in healthcare has taken a developing part. In reality, the appropriation of an expanding number of computer devices has driven several benefits related to the method of quiet care and permitted simpler get to social and health care assets. At the same time, this drift gave rise to modern challenges related to the usage of these modern innovations. The program utilized in healthcare can be classified as therapeutic gadgets depending on the way they are utilized and on their useful characteristics. In the event that they are classified as therapeutic gadgets, they must fulfill particular directions. The point of this work is to show a computer program improvement system that can permit the generation of secure and tall, quality restorative gadget computer programs and to highlight the correspondence between each program advancement stage and the fitting standard and/or regulation.

Keywords: medical devices, regulation, software, development, healthcare

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Authors: Siqing Guan, Fumiyo Oshima, Eiji Shimizu, Nozomi Tomita, Toru Takahashi, Hiroaki Kumano

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Risk factors for social anxiety in autism spectrum conditions involve executive attention, emotion regulation, and thought regulation as processes of cognitive dysregulation. Social camouflaging behaviors as strategies used to mask and/or compensate for autism characteristics during social interactions in autism spectrum conditions have also been emphasized. However, the role of cognitive dysregulation and social camouflaging related to social anxiety in autism spectrum conditions has not been clarified. Whether these factors are specific to social anxiety in autism spectrum conditions or common to social anxiety independent of autism spectrum conditions needs to be clarified. Here, we explored risk factors specific to social anxiety in autism spectrum conditions and general risk factors for social anxiety independent of autism spectrum conditions. From the Japanese participants in early adulthood (age=18~39) of the online survey in Japan, those who exceeded the Japanese version Autism-Spectrum Quotient cutoff (33 points or more )were divided into the autism spectrum conditions group (ASC; N=255, mean age=32.08, SD age=5.16)and those who did not exceed the cutoff were divided into the non-autism spectrum conditions group (Non-ASC; N=255, mean age=31.70, SD age=5.09). Using the Japanese versions of the Social Phobia Scale, the Social Interaction Anxiety Scale, and the Short Fear of Negative Evaluation Scale, a composite score for social anxiety was calculated using a method of principal. We also measured emotional control difficulties using the Difficulties in Emotion Regulation Scale, executive attention using the Effortful Control Scale for Adults, rumination using the Rumination-Reflection Questionnaire, and worry using the Penn State Worry Questionnaire. This study was passed through the review of the Ethics Committee. No conflicts of interest. Multiple regression analysis with forced entry method was used to predict social anxiety in the ASC and non-ASC groups separately, based on executive attention, emotion dysregulation, worry, rumination, and social camouflage. In the ASC group, emotion dysregulation (β=.277, p<.001), worry (β=.162, p<.05), assimilation (β=.308, p<.001) and masking (β=.275, p<.001) were significant predictors of social anxiety (F (7,247) = 45.791, p <.001, R2=.565). In the non-ASC groups,emotion dysregulation (β=.171, p<.05), worry (β=.344，p <.001), assimilation (β=.366,p <.001) and executive attention (β=-.132,p <.05) were significant predictors of social anxiety (F (7,207) =47.333, p <.001, R2=.615).The findings suggest that masking was shown to be a risk factor for social anxiety specific to autism spectrum conditions, while emotion dysregulation, worry, and assimilation were shown to be common risk factors for social anxiety, regardless of autism spectrum conditions. In addition, executive attention is a risk factor for social anxiety without autism spectrum conditions.

Keywords: autism spectrum, cognitive control, social anxiety, social camouflaging

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Authors: G. C. Santini, C. Potrich, L. Lunelli, L. Vanzetti, S. Marasso, M. Cocuzza, C. Pederzolli

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The relevance of circulating miRNAs as non-invasive biomarkers for several pathologies is nowadays undoubtedly clear, as they have been found to have both diagnostic and prognostic value able to add fundamental information to patients’ clinical picture. The availability of these data, however, relies on a time-consuming process spanning from the sample collection and processing to the data analysis. In light of this, strategies which are able to ease this procedure are in high demand and considerable effort have been made in developing Lab-on-a-chip (LOC) devices able to speed up and standardise the bench work. In this context, a very promising polydimethylsiloxane (PDMS)-based microdevice which integrates the processing of the biological sample, i.e. purification of extracellular miRNAs, and reverse transcription was previously developed in our lab. In this study, we aimed at the improvement of the miRNA extraction performances of this micro device by increasing the ability of its surface to absorb extracellular miRNAs from biological samples. For this purpose, we focused on the modulation of two properties of the material: roughness and charge. PDMS surface roughness was modulated by casting with several templates (terminated with silicon oxide coated by a thin anti-adhesion aluminum layer), followed by a panel of curing conditions. Atomic force microscopy (AFM) was employed to estimate changes at the nanometric scale. To introduce modifications in surface charge we functionalized PDMS with different mixes of positively charged 3-aminopropyltrimethoxysilanes (APTMS) and neutral poly(ethylene glycol) silane (PEG). The surface chemical composition was characterized by X-ray photoelectron spectroscopy (XPS) and the number of exposed primary amines was quantified with the reagent sulfosuccinimidyl-4-o-(4,4-dimethoxytrityl) butyrate (s-SDTB). As our final end point, the adsorption rate of all these different conditions was assessed by fluorescence microscopy by incubating a synthetic fluorescently-labeled miRNA. Our preliminary analysis identified casting on thermally grown silicon oxide, followed by a curing step at 85°C for 1 hour, as the most efficient technique to obtain a PDMS surface roughness in the nanometric scaleable to trap miRNA. In addition, functionalisation with 0.1% APTMS and 0.9% PEG was found to be a necessary step to significantly increase the amount of microRNA adsorbed on the surface, therefore, available for further steps as on-chip reverse transcription. These findings show a substantial improvement in the extraction efficiency of our PDMS microdevice, ultimately leading to an important step forward in the development of an innovative, easy-to-use and integrated system for the direct purification of less abundant circulating microRNAs.

Keywords: circulating miRNAs, diagnostics, Lab-on-a-chip, polydimethylsiloxane (PDMS)

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Authors: Lu Yang, Keng Po Lai

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Metformin, a well-known clinical drug against diabetes, is found with potential anti-diabetic and anti-obese benefits, as reported in increasing evidences. However, the current clinical and experimental investigations are not to reveal the detailed mechanisms of metformin-anti-obesity/hypertension. We have used the bioinformatics strategy, including network pharmacology and molecular docking methodology, to uncover the key targets and pathways of bioactive compounds against clinical disorders, such as cancers, coronavirus disease. Thus, in this report, the in-silico approach was utilized to identify the hug targets, pharmacological function, and mechanism of metformin against obesity and hypertension. The networking analysis identified 154 differentially expressed genes of obesity and hypertension, 21 interaction genes, and 6 hug genes of metformin treating hypertensive obesity. As a result, the molecular docking findings indicated the potent binding capability of metformin with the key proteins, including interleukin 6 (IL-6) and chemokine (C-C motif) Ligand 2 (CCL2), in hypertensive obesity. The metformin-exerted anti-hypertensive obesity action involved in metabolic regulation, inflammatory reaction. And the anti-hypertensive obesity mechanisms of metformin were revealed, including regulation of inflammatory and immunological signaling pathways for metabolic homeostasis in tissue and microenvironmental melioration in blood pressure. In conclusion, our identified findings with bioinformatics analysis have demonstrated the detailed hug and pharmacological targets, biological functions, and signaling pathways of metformin treating hypertensive obesity.

Keywords: metformin, obesity, hypertension, bioinformatics findings

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Authors: Marin Mandić, Elis Sutlović, Tonći Modrić, Luka Stanić

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With the restructuring and deregulation of the power system, storage owners, generation companies or private producers can offer their multiple services on various power markets and earn income in different types of markets, such as the day-ahead, real-time, ancillary services market, etc. During the COVID-19 pandemic, electricity prices, as well as ancillary services prices, increased significantly. The optimization of the energy storage operation was performed using a suitable model for simulating the operation of a pumped storage hydropower plant under market conditions. The objective function maximizes the income earned through energy arbitration, regulation-up, regulation-down and spinning reserve services. The optimization technique used for solving the objective function is mixed integer linear programming (MILP). In numerical examples, the pumped storage hydropower plant operation has been optimized considering the already achieved hourly electricity market prices from Nord Pool for the pre-pandemic (2019) and the pandemic (2020 and 2021) years. The impact of the electricity market prices during the COVID-19 pandemic on energy storage operation is shown through the analysis of income, operating hours, reserved capacity and consumed energy for each service. The results indicate the role of energy storage during a significant fluctuation in electricity and services prices.

Keywords: electrical market prices, electricity market, energy storage optimization, mixed integer linear programming (MILP) optimization

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Authors: Nawal Yacoub Halim Abdelmasih

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The intersection between development and human rights has been the factor of scholarly debate for a long term. therefore, some of standards, which enlarge from the proper to development to the human rights-based totally method to development, had been adopted to apprehend the dynamics among the two standards. no matter these attempts, the exact relationship among improvement and human rights has not been completely determined but. however, the inevitable interdependence between the two notions and the idea that improvement efforts ought to be undertaken with the aid of giving due regard to human rights ensures has won momentum in recent years. then again, the emergence of sustainable development as a extensively common technique in development dreams and policies makes this unsettled convergence even extra complicated. The vicinity of sustainable improvement in human rights regulation discourse and the function of the latter in making sure the sustainability of development applications name for a scientific observe. as a result, this newsletter seeks to discover the relationship among development and human rights, particularly focusing at the location given to sustainable development principles in international human proper regulation. it'll similarly quest whether or not there is a proper to sustainable improvement diagnosed therein. as a result, the item asserts that the ideas of sustainable improvement are immediately or circuitously diagnosed in diverse human rights contraptions, which affords an affirmative response to the question raised hereinabove. This paintings, therefore, will make expeditions via international and regional human rights devices in addition to case legal guidelines and interpretative hints of human rights bodies to show this speculation.

Keywords: sustainable development, human rights, the right to development, the human rights-based approach to development, environmental rights, economic development, social sustainability human rights protection, human rights violations, workers’ rights, justice, security

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Authors: Jie Ding, Yingying Pan, Shammy Raj, Lindy Schaffrick, Jolene Wong, Antoinette Nguyen, Sharada Manchikanti, Larry Unsworth, Peter Kwan, Edward E. Tredget

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Background: Exosomes (EXOs) have been considered a new target that is thought to be involved in and treat wound healing. More research is needed to fully understand the EXO characteristics and mechanisms of EXO-mediated wound healing, especially wound healing after burn injury. Methods: Total EXOs were isolated from 85 serum samples of 29 burn patients and 13 healthy individuals. We characterized the EXOs for morphology and density, serum concentration, protein level, marker expression, size distribution, and cytokine content. After confirmation of EXO uptake by dermal fibroblasts, we also explored functional regulation of primary human normal skin and hypertrophic scar fibroblast cell lines by the EXOs in vitro, including cell proliferation and apoptosis. Results: EXOs dynamically changed their morphology, density, size, and cytokine level during wound healing in burn patients, which were correlated with burn severity and the stages of wound healing. EXOs from both burn patients and healthy individuals stimulated dermal fibroblast proliferation and apoptosis. Conclusion: EXO features may be important signals that influence wound healing after burn injury; however, to understand the mechanisms by which EXOs regulated the fibroblasts in healing wounds, further studies will be required in the future.

Keywords: exosome, burn, wound healing, hypertrophic scarring, cytokines

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Authors: Shuchi Bharti

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This article intends to analyse the transforming nature of state and corporate sector relationship in the light of evolving regulatory and institutional aspects pertaining to Corporate Social Responsibility (CSR) in India. The focus is on evaluating the accounts of law and decentred discourses, relevant within the changing regulatory and institutional paradigm that substantially goes ahead of formal legal control of state towards corporate actors. At this vantage point, it is important to understand the state’s posture towards a changing scenario particularly as the tone is set by regulatory parameters pertaining to CSR to drive process of engagement with the stakeholders. The tripartite framework of the article intends to focus on finding on the vital interconnected aspects of the CSR provisions (Section 135) of The Companies Act 2013 (The Act), rise of new institutions and the emergence of the decentred regulatory space. Thus is earmarked in a neo-liberal paradigm; state is witnessed to perform a responsive function in engendering enhanced public role for the corporate sector. In this overarching framework the aim is to undertake a causal, exploratory and relational analysis of aspects pertaining law, regulation and institutional transformations. Firstly, focus is drawn on to investigate the relational facets of the advent of law and regulatory framework of CSR. Secondly, in the light of the historical evolution, a causal connection is attempted between globalization, emergence of international soft law framework and the Indian case of CSR. Finally, I look into how the new Companies Act mandates CSR expenditure vis- a -vis multiple parameters and guidelines.

Keywords: corporate social responsibility, stakeholders, soft law, decentred regulation

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Authors: Hayyan ul Haq, Zainal Asikin

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This work aims to explore the appropriate solution in solving legal problems stemmed from managing and exploiting strategic natural resources in Indonesia. This discussion will be focused on the exploitation of gold mining, i.e. divestation process in the New Mont Corporation, West Nusa Tenggara. These legal problems relate to the deviation of the national budget regulation, UU. No. 19/2012, and the implementation of the divestastion process, which infringes PP. No. 50/2007 concerning the Impelementation Procedure of Regional Cooperation, which is an implementation regulation of UU No. 1/2004 on State’s Treasury. The cooperation model, have been developed by the Provincial Government, failed to create a permanent legal solution through normative approach. It has merely used practical approach that tends (instant solution), by using some loopholes in the divestation process. The above blunders have accumulated by other secondary legal blunders, i.e. good governance principles, particularly justice, transparency, efficiency, effective principles and competitiveness principle. To solve the above problems, this work offers constitutionalisation of contract that aimed at reviewing and coherencing all deviated contracts, rules and policies that have deprived the national and societies’ interest to optimize the strategic natural resources towards the greatest benefit for the greatest number of people..

Keywords: constitutionalisation of contract, strategic national resources, divestation, the greatest benefit for the greatest number of people, Indonesian Pancasila values

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Authors: Jacolien Barnard, Corlia Van Heerden

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Effective and accessible consensual dispute resolution and in particular alternative dispute resolution, are central to consumer protection legislation. In this regard, the Consumer Protection Act 68 of 2008 (CPA) of South Africa is no exception. Due to the nature of consumer disputes, alternative dispute resolution (in theory) is an effective vehicle for the adjudication of disputes in a timely manner avoiding overburdening of the courts. The CPA sets down as one of its core purposes the provision of ‘an accessible, consistent, harmonized, effective and efficient system of redress for consumers’ (section 3(1)(h) of the CPA). Section 69 of the Act provides for the enforcement of consumer rights and provides for the National Consumer Commission to be the Central Authority which streamlines, adjudicates and channels disputes to the appropriate forums which include Alternative Dispute Resolution Agents (ADR-agents). The purpose of this paper is to analyze the regulation of these enforcement and redress mechanisms with particular focus on the Central Authority as well as the ADR-agents and their crucial role in successful and efficient adjudication of disputes in South Africa. The South African position will be discussed comparatively with the European Union (EU) position. In this regard, the European Union (EU) Directive on Alternative Dispute Resolution for Consumer Disputes (2013/11/EU) will be discussed (The ADR Directive). The aim of the ADR Directive is to solve contractual disputes between consumers and traders (suppliers or businesses) regardless of whether the agreement was concluded offline or online or whether or not the trader is situated in another member state (Recitals 4-6). The ADR Directive provides for a set of quality requirements that an ADR body or entity tasked with resolving consumer disputes should adhere to in member states which include regulatory mechanisms for control. Transparency, effectiveness, fairness, liberty and legality are all requirements for a successful ADR body and discussed within this chapter III of the Directive. Chapters III and IV govern the importance of information and co-operation. This includes information between ADR bodies and the European Commission (EC) but also between ADR bodies or entities and national authorities enforcing legal acts on consumer protection and traders. (In South Africa the National Consumer Tribunal, Provincial Consumer Protectors and Industry ombuds come to mind). All of which have a responsibility to keep consumers informed. Ultimately the papers aims to provide recommendations as to the successfulness of the current South African position in light of the comparative position in Europe and the highlight the importance of proper regulation of these redress and enforcement institutions.

Keywords: alternative dispute resolution, consumer protection law, enforcement, redress

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Authors: Renata Hrecska

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This research seeks to fully examine the internal employment law of international organizations by comparing it with the characteristics of the national civil service. The aim of the research is to compare the legal system that has developed over many centuries and the relatively new internal staffing regulations to find out what solution schemes can help each other through mutual legal development in order to respond effectively to the social challenges of everyday life. Generally, the rules of civil service of any country or international entity have in common that they have, in their pragmatics inherently, the characteristic that makes them serving public interests. Though behind the common base there are many differences: there is the clear fragmentation of state regulation and the unity of organizational regulation. On the other hand, however, this difference disappears to some extent: the public service regulation of international organizations can be considered uniform until we examine it within, but not outside an organization. As soon as we compare the different organizations we may find many different solutions for staffing regulations. It is clear that the national civil service is a strong model for international organizations, but the question may be whether the staffing policy of international organizations can serve the national civil service as an example, too. In this respect, the easiest way to imagine a legislative environment would be to have a single comprehensive code, the general part of which is the Civil Service Act itself, and the specific part containing specific, necessarily differentiating rules for each layer of the civil service. Would it be advantageous to follow the footsteps of the leading international organizations, or is there any speciality in national level civil service that we cannot avoid during regulating processes? In addition to the above, the personal competencies of officials working in international organizations and public administrations also show a high degree of similarity, regardless of the type of employment. Thus, the whole public service system is characterized by the fundamental and special values that a person capable of holding a public office must be able to demonstrate, in some cases, even without special qualifications. It is also interesting how we can compare the two spheres of employment in light of the theory of Lawyer Louis Brandeis, a judge at the US Supreme Court, who formulated a complex theory of profession as distinguished from other occupations. From this point of view we can examine the continuous development of research and specialized knowledge at work; the community recognition and social status; that to what extent we can see a close-knit professional organization of altruistic philosophy; that how stability grows in the working conditions due to the stability of the profession; and that how the autonomy of the profession can prevail.

Keywords: civil service, comparative law, international organizations, regulatory systems

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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: Najib Khumaidillah

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A conversation needs skills to create the good flow of it. The skills also need to be paid attention by a host like Oprah Winfrey and Justin Bieber as an artist. This study is aimed at describing turn taking strategies and adjacency pairs used by the speakers. The data are from one segment of The Oprah Winfrey Show’s transcription with Justin Bieber. Those are analyzed by Stenstorm’s turn taking theories and adjacency pairs theories. From the analysis, it was found that both speakers use various turn taking strategies and adjacency pairs. These findings are hoped to be an example for non-native English speaker in doing English conversation and advance people’s comprehension of how to organize good conversation structure.

Keywords: adjacency pairs, conversation structure, the Oprah Winfrey show, turn taking

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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: 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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