Search results for: cannabis regulation proposal

Authors: F. M. El-Domyati, A. Atef, S. Edris, N. O. Gadalla, M. A. Al-Kordy, A. M. Ramadan, Y. M. Saad, H. S. Al-Zahrani, A. Bahieldin

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Transcriptome retrieved from SRA database of different tissues and treatments of C. roseus was assembled in order to detect tissue-specific transcription factors (TFs) and TFs possibly related to terpenoid indole alkaloids (TIA) pathway. A number of 290 TF-like transcripts along with 12 transcripts related to TIA biosynthetic pathway were divided in terms of co-expression in the different tissues, treatments and genotypes. Three transcripts encoding peroxidases 1 and 12 were downregulated in hairy root, while upregulated in mature leaf. Eight different transcripts of the TIA pathway co-expressed with TFs either functioning downstream tryptophan biosynthesis, e.g., tdc, str1 and sgd, or upstream vindoline biosynthesis, e.g., t16h, omt, nmt, d4h and dat. The results showed no differential expression of TF transcripts in hairy roots knocked down for tdc gene (TDCi) as compared to their wild type controls. There were several evidences of tissue-specific expression of TF transcripts in flower, mature leaf, root/hairy root, stem, seedling, hairy root and immature/mature leaves. Regulation included transcription factor families, e.g., bHLH, MYB and WRKY mostly induced by ABA and/or JA (or MeJA) and regulated during abiotic or biotic stress. The information of tissue-specific regulation and co-expression of TFs and genes in the TIA pathway can be utilized in manipulating alkaloid biosynthesis in C. roseus.

Keywords: SRA database, bHLH, MYB, WRKY, co-expression

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Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

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Authors: Razieh Zarei, Hassan zm, Abolghasem Ajami, Darush Moslemi, Narges Afsary, Amrollah Mostafa-zade

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Introduction: IL-23 is responsible for the differentiation and expansion of Th17/ThIL-17 cells from naive CD4+ T cells. Therefore, may be IL-23/IL17 axis involve in a variety of allergic and autoimmune diseases, such as RA, MS, inflammatory bowel disease (IBD), and asthma. TGF-β is also share for the differentiation Th17 producing IL-17 and CD4+CD25+Foxp3hiT regulatory cells from naïve CD4+ T cells which are involved in the regulation of immune response, maintaining immunological self-tolerance and immune homeostasis ,and the control of autoimmunity and cancer surveillance. Therefore, T regulatory cells play a key role in autoimmunity, allergy, cancer, infectious disease, and the induction of transplantation tolerance. Vitamin A and it's derivatives (retinoids) inhibit or reverse the carcinogenic process in some types of cancers in oral cavity,head and neck, breast, skin, liver, and blood cells. Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, in vitro. Our purpose is whether simultaneous oral treatment vitamin A and shark cartilage can modulate IL-23/IL-17 and CD4CD25Foxp3 T regulatory cell/TGF-β pathways and Th1/Th2 immunity in patients with gastric cancer. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23,IL-17,TGF-β,IL-4 and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: An imbalance between IL-17 secretion and TGF-β/Foxp3 t regulatory cell pathway and so, Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) was not seen in patients with gastric cancer treated by vitamin A and shark cartilage. But, the simultaneously presented down-regulation of IL-23 indicated, at least cytokine level. Conclusion: Il-23, as a pro-angiogenesis cytokine, probably, help to tumor growth. Hence, suggested that down-regulation of IL-23, at least cytokine level, is useful for anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4CD25Foxp3 T regulatory pathway, γ-IFN, IL-4, shark cartilage and gastric cancer

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Authors: Jinesh Kumar Jain, Faishal Pathan

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The concept of sustainable development and effective environmental regulation has led to the emergence of a new field of study and practise that is the Green Supply Chain Management. GSCM has become a subject of great importance for both the developed and developing countries to achieve the desired and much-awaited goals of the firm within the environmental and sustainable framework. Its merits are comprised of good financial pay off and competitiveness to the firms in a long lasting and sustainable manner. The purpose of the paper is to briefly review the recent literature of the GSCM and also determines the new direction area of this emerging field. A detailed study has helped to enlighten the minute details and develop the research direction of the study. The GSCM has gained popularity with both academic and practitioners. The items for the study were developed based on the extent literature. Here we found that the state of adoption of GSCM practices by Indian Firms was still in its infancy, the awareness of environmental sustainability was quite low among consumers and the regulatory frameworks were also lacking in terms promoting environmental sustainability. The present paper is an attempt to emphasize much attention on the above-mentioned issues and present a conclusive summary to make its use widespread and for reaching.

Keywords: environmental management, environmental performance, financial performance, green supply chain management

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Authors: Leila Anoosheh

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Aim: The aim of this study was to assess The effects of aerobic training on microRNA let-7a expression and levels of tumor tissue IL-6 in mice with breast cancer. Method: Twenty BALB/c c mice (4-5 weeks,17 gr mass) were cancerous by injection of estrogen-dependent receptor breast cancer cells MC4-L2 and divided into two groups: tumor-training(TT) and tumor-control(TC) group. Then TT group completed aerobic training for 6 weeks, 5 days per week (14-18 m/min). After tumor emersion, tumor width and length were measured by digital caliper every week. 48 hours after the last exercise subjects were killed. Tissue sampling were collected and stored in -70ᵒ. Tumor tissue was homogenized and let-7a expression and IL-6 levels were accounted with Real time-PCR and ELISA Kit respectively. Statistical analysis of let-7a was conducted by the REST software. Repeated measures and independent tests were used to assess tumor size and IL-6, respectively. Results: Tumor size and IL-6 levels were significantly decreased in TT group compare with TC group (p<0.05). microRNA let-7a was increased significantly in TT against control group respectively (p=0/000). Conclusion: Reduction in tumor size, followed by aerobic exercise can be attributed to the loss of inflammatory factors such as IL-6; It seems that regarding to up regulation effects of aerobic exercise training on let-7a and down regulation effects of that on IL-6 in mice with breast cancer, This type of training can be used as adjuvant therapy in conjunction with other therapies for breast cancer.

Keywords: breast cancer, aerobic training, microRNA let-7a, IL-6

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Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

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Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

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Authors: Sarra Haouala, Issam Doghri

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In this work, a multiscale computational strategy is proposed for the analysis of structures, which are described at a refined level both in space and in time. The proposal is applied to two-phase viscoelastic-viscoplastic (VE-VP) reinforced thermoplastics subjected to large numbers of cycles. The main aim is to predict the effective long time response while reducing the computational cost considerably. The proposed computational framework is a combination of the mean-field space homogenization based on the generalized incrementally affine formulation for VE-VP composites, and the asymptotic time homogenization approach for coupled isotropic VE-VP homogeneous solids under large numbers of cycles. The time homogenization method is based on the definition of micro and macro-chronological time scales, and on asymptotic expansions of the unknown variables. First, the original anisotropic VE-VP initial-boundary value problem of the composite material is decomposed into coupled micro-chronological (fast time scale) and macro-chronological (slow time-scale) problems. The former is purely VE, and solved once for each macro time step, whereas the latter problem is nonlinear and solved iteratively using fully implicit time integration. Second, mean-field space homogenization is used for both micro and macro-chronological problems to determine the micro and macro-chronological effective behavior of the composite material. The response of the matrix material is VE-VP with J2 flow theory assuming small strains. The formulation exploits the return-mapping algorithm for the J2 model, with its two steps: viscoelastic predictor and plastic corrections. The proposal is implemented for an extended Mori-Tanaka scheme, and verified against finite element simulations of representative volume elements, for a number of polymer composite materials subjected to large numbers of cycles.

Keywords: asymptotic expansions, cyclic loadings, inclusion-reinforced thermoplastics, mean-field homogenization, time homogenization

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Authors: Evans Iyamu

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Genes encoding hydrophobins play distinct roles at different stages of the life cycle of fungi, and they foster hyphal attachment to surfaces. The hydrophobin Sc4 is known to provide a hydrophobic membrane lining of the gas channels within Schizophyllum commune fruiting bodies. Here, we cultivated non-fruiting, monokaryotic S. commune 12-43 on glass surfaces that could be verified by micrography. Differential gene expression profiling of nine hydrophobin genes and the hydrophobin-like sc15 gene by quantitative PCR showed significant up-regulation of sc4 when S. commune was attached to glass surfaces, also confirmed with RNA-Seq data analysis. Another silicate, namely quartz sand, was investigated, and induction of sc4 was seen as well. The up-regulation of the hydrophobin gene sc4 may indicate involvement in S. commune hyphal attachment to glass as well as quartz surfaces. We propose that the covering of hyphae by Sc4 allows for direct interaction with the hydrophobic surfaces of silicates and that differential functions of specific hydrophobin genes depend on the surface interface involved. This study could help with the clarification of the biological functions of hydrophobins in natural surroundings, including hydrophobic surface attachment. Therefore, the analysis of growth on glass serves as a basis for understanding S. commune interaction with glass surfaces while providing the possibility to visualize the interaction microscopically.

Keywords: hydrophobin, structured glass surfaces, differential gene expression, quartz sand

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Authors: Laura Helena Caicedo Lopez, Luis Miguel Contreras Medina, Ramon Gerardo Guevara Gonzales, Juan E. Andrade

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In this study, we evaluated the effect of three different hydric stress conditions: Low (LHS), medium (MHS), and high (HHS) on capsaicinoid content and enzyme regulation of C. annuum plants. Five main peaks were detected using a 2 Hz resolution vibrometer laser (Polytec-B&K). These peaks or “characteristic frequencies” were used as acoustic emissions (AEs) treatment, transforming these signals into audible sound with the frequency (Hz) content of each hydric stress. Capsaicinoids (CAPs) are the main, secondary metabolites of chili pepper plants and are known to increase during hydric stress conditions or short drought-periods. The AEs treatments were applied in two plant stages: the first one was in the pre-anthesis stage to evaluate the genes that encode the transcription of enzymes responsible for diverse metabolic activities of C. annuum plants. For example, the antioxidant responses such as peroxidase (POD), superoxide dismutase (Mn-SOD). Also, phenyl-alanine ammonia-lyase (PAL) involved in the biosynthesis of the phenylpropanoid compounds. The chalcone synthase (CHS) related to the natural defense mechanisms and species-specific aquaporin (CAPIP-1) that regulate the flow of water into and out of cells. The second stage was at 40 days after flowering (DAF) to evaluate the biochemical effect of AEs related to hydric stress on capsaicinoids production. These two experiments were conducted to identify the molecular responses of C. annuum plants to AE. Moreover, to define AEs could elicit any increase in the capsaicinoids content after a one-week exposition to AEs treatments. The results show that all AEs treatment signals (LHS, MHS, and HHS) were significantly different compared to the non-acoustic emission control (NAE). Also, the AEs induced the up-regulation of POD (~2.8, 2.9, and 3.6, respectively). The gene expression of another antioxidant response was particularly treatment-dependent. The HHS induced and overexpression of Mn-SOD (~0.23) and PAL (~0.33). As well, the MHS only induced an up-regulation of the CHs gene (~0.63). On the other hand, CAPIP-1 gene gas down-regulated by all AEs treatments LHS, MHS, and HHS ~ (-2.4, -0.43 and -6.4, respectively). Likewise, the down-regulation showed particularities depending on the treatment. LHS and MHS induced downregulation of the SOD gene ~ (-1.26 and -1.20 respectively) and PAL (-4.36 and 2.05, respectively). Correspondingly, the LHS and HHS showed the same tendency in the CHs gene, respectively ~ (-1.12 and -1.02, respectively). Regarding the elicitation effect of AE on the capsaicinoids content, additional treatment controls were included. A white noise treatment (WN) to prove the frequency-selectiveness of signals and a hydric stressed group (HS) to compare the CAPs content. Our findings suggest that WN and NAE did not present differences statically. Conversely, HS and all AEs treatments induced a significant increase of capsaicin (Cap) and dihydrocapsaicin (Dcap) after one-week of a treatment. Specifically, the HS plants showed an increase of 8.33 times compared to the NAE and WN treatments and 1.4 times higher than the MHS, which was the AEs treatment with a larger induction of Capsaicinoids among treatments (5.88) and compared to the controls.

Keywords: acoustic emission, capsaicinoids, elicitors, hydric stress, plant signaling

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Authors: Dijana Sulejmanović

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Cognitive-behavioral modification (CBM) is a combination of cognitive and behavioral learning principles to shape and encourage the desired behaviors. A crucial element of cognitive-behavioral modification is that a change the behavior precedes awareness of how it affects others. CBM is oriented toward changing inner speech and learning to control behaviors through self-regulation techniques. It aims to teach individuals how to develop the ability to recognize, monitor and modify their thoughts, feelings, and behaviors. The review of literature emphasizes the efficiency the CBM approach in the treatment of children's hyperactivity and negative emotions such as anger. The results of earlier research show how impulsive and hyperactive behavior, agitation, and aggression may slow down and block the child from being able to actively monitor and participate in regular classes, resulting in the disruption of the classroom and the teaching process, and the children may feel rejected, isolated and develop long-term poor image of themselves and others. In this article, we will provide how the use of CBM, adapted to child's age, can incorporate measures of cognitive and emotional functioning which can help us to better understand the children’s cognitive processes, their cognitive strengths, and weaknesses, and to identify factors that may influence their behavioral and emotional regulation. Such a comprehensive evaluation can also help identify cognitive and emotional risk factors associated with aggressive behavior, specifically the processes involved in modulating and regulating cognition and emotions.

Keywords: aggressive behavior, cognitive behavioral modification, cognitive behavioral theory, modification

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Authors: Bozena Dohnalkova, Jakub Hodul, Rostislav Drochytka, Jana Kosikova

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This paper deals with a proposal of a new methodology for durability assessment of solidification product for its safe further use. The new methodology is based on a review of the current state of assessment of treated waste in Czech Republic and abroad. The aim of the paper is to propose an optimal evaluation methodology for verifying properties of solidification product to ensure its safe further use in building industry.

Keywords: solidification, stabilization, durability, waste

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Authors: Muhammed Gündoğan

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Permaculture is an important source of science and experience that can ensure the integration of sustainable architecture with nature. Since the past, many applications have been applied in rural areas for generations with the principle of benefiting from the self-renewal potential of nature. This culture, which has been transferred from generation to generation with architectural disciplines, has the potential to significantly improve the sustainability of the rural area and is an important guide with its nature-based solution proposals. Şanlıurfa has arid and semi-arid climate characteristics. Although it has substantial agricultural potential, water is limited, especially in rural areas. In the region, rainwater harvesting practices such as artificial water canals and cisterns have been used for a long time. However, these solutions remained mostly at the urban scale, and their reflections at the building scale were restricted and inadequate solutions. Impermeable surfaces are required for water harvesting, but water harvesting is not possible as rural buildings are mostly surrounded by cultivated land. Therefore, existing structures are important in terms of applicability. In this context, considering the typology of Traditional Şanlıurfa Houses, the aim of the project was to create a proposal for limited potable and utility water, which is a serious problem, especially for rural buildings in Şanlıurfa. In the project proposal, roof systems that can work integrated with the structural shape of Traditional Şanlıurfa Houses, rainwater collection systems in the inner courtyard, and greywater recycling were provided. While the average precipitation amount was 453.7 kg/m3 between 1929 and 2012, this value was measured as 622.7 kg/m3 in 2012. Greywater was used to produce natural fertilizers and compost for small-scale fruit and vegetable gardens, and it was combined with the principles of Permaculture to make it a lifestyle. As a result, it has been estimated that a total of 976.4 m3 kg of water can be saved, with an annual average of 158.8 m3 of rainwater recycling and 817.6 m3 of greywater recycling within the scope of the project.

Keywords: rural, traditional residential building, permaculture, rainwater harvesting, greywater recycling

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Authors: A. Alyami, S. Christmas, K. Neeltje, G. Pollakis, B. Paxton, Z. Al-Bayati

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The Human leukocyte antigen-G (HLA-G) molecule plays an important role in immunomodulation. To date, 16 untranslated regions (UTR) HLA-G haplotypes have been previously defined by sequenced SNPs in the coding region. From these, UTR-1, UTR-2, UTR-3, UTR-4, UTR-5, UTR-6 and UTR-7 are the most frequent 3’UTR haplotypes at the global level. UTR-1 is associated with higher levels of soluble HLA-G and HLA-G expression, whereas UTR-5 and UTR-7 are linked with low levels of soluble HLA-G and HLA-G expression. Human immunodeficiency virus type 1 (HIV-1) infection results in the progressive loss of immune function in infected individuals. The virus escape mechanism typically includes T lymphocytes and NK cell recognition and lyses by classical HLA-A and B down-regulation, which has been associated with non-classical HLA-G molecule up-regulation, respectively. We evaluated the haplotypes of the HLA-G 3′ untranslated region frequencies observed in three HIV-1 groups from the Netherlands and their susceptibility to develop infection. The three groups are made up of mainly men who have sex with men (MSM), injection drug users (IDU) and a high-risk-seronegative (HRSN) group. DNA samples were amplified with published primers prior sequencing. According to our results, the low expresser frequencies show higher in HRSN compared to other groups. This is indicating that 3’UTR polymorphisms may be identified as potential prognostic biomarkers to determine susceptibility to HIV.

Keywords: Human leukocyte antigen-G (HLA-G) , men who have sex with men (MSM), injection drug users (IDU), high-risk-seronegative (HRSN) group, high-untranslated region (UTR)

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Authors: Zhongyang Sun, Shu Zhang, Manjiang Xie

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Emerging evidence indicates that microRNAs (miRNAs) play important roles in modulating osteoblast function and bone formation. However, the influence of miRNA on osteoblast proliferation and the possible mechanisms underlying remain to be defined. In this study, we aimed to investigate whether miR-103 regulates osteoblast proliferation under simulated microgravity condition through regulating Cav1.2, the primary subunit of L-type voltage sensitive calcium channels (LTCCs). We first investigated the effect of simulated microgravity on osteoblast proliferation and the outcomes clearly demonstrated that the mechanical unloading inhibits MC3T3-E1 osteoblast-like cells proliferation. Using quantitative Real-Time PCR (qRT-PCR), we provided data showing that miR-103 was up-regulated in response to simulated microgravity. In addition, we observed that up-regulation of miR-103 inhibited and down-regulation of miR-103 promoted osteoblast proliferation under simulated microgravity condition. Furthermore, knocking-down or over-expressing miR-103, respectively, up- or down-regulated the level of Cav1.2 expression and LTCCs currents, suggesting that miR-103 acts as an endogenous attenuator of Cav1.2 in osteoblasts under the condition of simulated microgravity. More importantly, we showed that the effect of miR-103 on osteoblast proliferation was diminished in simulated microgravity, when co-transfecting miR-103 mimic or inhibitor with Cav1.2 siRNA. Taken together, our data suggest that miR-103 inhibits osteoblast proliferation mainly through suppression of Cav1.2 expression under simulated microgravity condition. This work may provide a novel mechanism of microgravity-induced detrimental effects on osteoblast, identifying miR-103 as a novel possible therapeutic target in bone remodeling disorders in this mechanical unloading.

Keywords: microRNA, osteoblasts, cell proliferation, Cav1.2, simulated microgravity

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Authors: Xiao Wen Xu

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There exists a challenge of accommodating/integrating people at risk and those from various backgrounds in urban areas. The success of interdependence as a tool for survival largely rests on the mutually beneficial relationships amongst individuals within a given society. One approach to meeting this challenge has been written by Ivan Illich in his book, Tools for Conviviality, where he defines 'conviviality' as interactions that help individuals. With the goal of helping the community and applying conviviality as a principle to actors in both natural and social realms of Moss Park in Toronto, the proposal involves redesigning the park and buildings as a series of different health care, extended learning, employment support, armoury, and recreation facilities that integrate the exterior landscape as treatment, teaching, military, and recreation areas; in other words, the proposal links services with access to park space. While buildings are traditionally known to physically provide shelter, parks embody shelter and act as service, as people often find comfort and relief from being in nature, and Moss Park, in particular, is home to many people at risk. This landscape is not only an important space for the homeless community but also the rest of the neighborhood. The thesis proposes that the federal government rebuilds the current armoury, as it is an obsolete building while acknowledging the extensive future developments proposed by developers and its impact on public space. The neighbourhood is an underserved area, and the new design develops not just a new armoury, but also a complex of interrelated services, which are completely integrated into the park. The armoury is redesigned as an integral component of the community that not only serves as training facilities for reservists but also serves as an emergency shelter in sub-zero temperatures for the homeless community. This paper proposes a new design for Moss Park through examining how 'park buildings', interconnected buildings and parks, can foster empowering relationships that create a supportive public realm.

Keywords: conviviality, natural, social, Ivan Illich

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Authors: Junichi Hosoi

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Epidermal Langerhans cells reside in upper layer of epidermis and play a role in immune surveillance. The finding of the close association of nerve endings to Langerhans cells triggered the research on systemic regulation of Langerhans cells. They disappear from epidermis after exposure to environmental and internal stimuli and reappear about a week later. Myeloid progenitor cells are assumed to be one of the sources of Langerhans cells. We examined the effects of cortisol on the reappearance of Langerhans cells in vitro. Cord-blood derived CD34-positive cells were cultured in the medium supplemented with stem cell factor/Flt3 ligand/granulocyte macrophage-colony stimulating factor/tumor necrosis factor alpha/bone morphologic protein 7/transforming growth factor beta in the presence or absence of cortisol. Cells were analyzed by flow cytometry for CD1a (cluster differentiation 1a), a marker of Langerhans cells and dermal dendritic cells, and CD39 (cluster differentiation factor 39), extracellular adenosine triphosphatase. Both CD1a-positive cells and CD39-positive cells were decreased by treatment with cortisol (suppression by 35% and 22% compared to no stress hormone, respectively). Differentiated Langerhans cells are attracted to epidermis by chemokines that are secreted from keratinocytes. Epidermal keratinocytes were cultured in the presence or absence of cortisol and analyzed for the expression of CCL2 (C-C motif chemokine ligand 2) and CCL20 (C-C motif chemokine ligand 20), which are typical attractants of Langerhans cells, by quantitative reverse transcriptase polymerase chain reaction. The expression of both chemokines, CCL2 and CCL20, were suppressed by treatment with cortisol (suppression by 38% and 48% compared to no stress hormone, respectively). We examined the possible regulation of the suppression by cortisol with plant extracts. The extracts of Ganoderma lucidum and Iris protected the suppression of the differentiation to CD39-positive cells and also the suppression of the gene expression of LC-chemoattractants. These results suggest that cortisol, which is either systemic or locally produced, blocks the supply of epidermal Langerhans cells at 2 steps, differentiation from the precursor and attraction to epidermis. The suppression is possibly blocked by some plant extracts.

Keywords: Langerhans cell, stress, CD39, chemokine

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Authors: Scott R. Butler

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Ontario, Canada’s largest province, is in the midst of an interesting experiment in mandated asset management planning for local governments. At the beginning of 2021, Ontario’s 444 municipalities were responsible for the management of 302,864 lane kilometers of roads that have a replacement cost of $97.545 billion CDN. Roadways are by far the most complex, expensive, and extensive assets that a municipality is responsible for overseeing. Since adopting Ontario Regulation 588/47: Asset Management Planning for Municipal Infrastructure in 2017, the provincial government has established prescriptions for local road authorities regarding asset category and levels of service being provided. This provincial regulation further stipulates that asset data such as extent, condition, and life cycle costing are to be captured in manner compliant with qualitative descriptions and technical metrics. The Ontario Good Roads Association undertook an exercise to aggregate the road-related data contained within the 444 asset management plans that municipalities have filed with the provincial government. This analysis concluded that collectively Ontario municipal roadways have a $34.7 billion CDN in deferred maintenance. The ill-state of repair of Ontario municipal roads has lasting implications for province’s economic competitiveness and has garnered considerable political attention. Municipal efforts to address the maintenance backlog are stymied by the extremely limited fiscal parameters municipalities must operate within in Ontario. Further exacerbating the program are provincially designed programs that are ineffective, administratively burdensome, and not necessarily aligned with local priorities or strategies. This paper addresses how municipal asset management plans – and more specifically, the data contained in these plans – can be used to design innovative policy frameworks, flexible funding programs, and new levels of service that respond to these funding challenges, as well as emerging issues such as local economic development and climate change. To fully unlock the potential that Ontario Regulation 588/17 has imposed will require a resolute commitment to data standardization and horizontal collaboration between municipalities within regions.

Keywords: transportation, municipal asset management, subnational policy design, subnational funding program design

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Authors: Mostafa Ahmed Shokshok

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Libyan industrial companies face many challenges in today's competitive market. Quality management culture approaches is one of these challenges which may furnish the road to the Libyan industrial companies to effectively empower their employees and improve their ability to respond to the international competition. The primary objective of this paper is to design a practical approach to guide Libyan industrial companies toward successful quality culture implementation.

Keywords: TQM, quality culture, Libyan manufacturing industries, quality framework

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Authors: Abdulrahman Fahim M. Alsulami

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The current research seeks to explore the regulation of vaccine-related IP rights in light of the areas of divergence between the Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement and investment treaties. The study is conducted in the context of the COVID-19 pandemic; therefore, it seems natural that a specific chapter is devoted to the examination of vaccine arrangements related to vaccine supplies. The chapter starts with the examination of a typical vaccine from the perspective of IP rights. It presents the distinctive features of vaccines as pharmaceutical products and investments, reviews the basics of their patent protection, reviews vaccines’ components, and discusses IPR protection of different components of vaccines. The subsection that focuses on vaccine development and licensing reviews vaccine development stages investigates differences between vaccine licensing in different countries and presents barriers to vaccine licensing. The third subsection, at the same time, introduces the existing arrangements related to COVID-19 vaccine supplies, including COVAX arrangements, international organizations’ assistance, and direct negotiations between governments and vaccine manufacturers.

Keywords: bilateral investment treaties, COVID-19 vaccine, IP rights, TRIPs agreement

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Authors: Alexandra Serra, Nadia Torrão, Rui G. Serôdio, José A. Lima

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The present study aimed to evaluate the incidence and the prevalence of domestic violence legitimatory beliefs, emotional regulation difficulties and, early maladaptive schemas regarding intimidate partner violence in a sample of 50 Portuguese inmates. As expected, results show high levels of legitimatory beliefs, significant difficulties of emotional regulation and a set of high levels of early maladaptive schemas that clearly compromise the inmates affective-cognitive functioning. The most prevalent set of maladaptive schemas are associated with depression, anxiety, hostility, reduced ability to empathize and, dependence on the approval of others, which, combined, may trigger aggressive responses towards the intimate’s partner. Being victimized in their childhood and having committing murder are not differentiating factors on the measures we analyzed, but alcohol consumption may be associated with an intensification of domestic violence legitimatory beliefs. In the discussion of our findings, we compare the pattern of the psychosocial measures we used with the equivalent results obtained with convicted individuals that attend a community compulsory program, specifically designed for domestic violence perpetrators. We also highlight the importance of implementing specialized interventions in prison settings focusing on an evidence-based-practice.

Keywords: affective-cognitive functioning, intimate partner offenders, psychological research with inmates

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Authors: Zsofia Patyi

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While empirical studies under socialism in Hungary focused on the lawyer society as a whole, current research deals with law students in specific. The change of regime and the mutation of legal education have influenced the motivation, efficiency, social background and self-concept of law students. This shift needs to be acknowledged, and the education system improved for students and together with students. A new law student society requires a different legal education system, different legal studies, or, at the minimum, a different approach to teaching law. This is to ensure that competitive lawyers be trained who understand the constantly changing nature of the law and, as a result, can potentially transform or create legislation themselves. A number of developments can affect law students’ awareness of legal relations in a democratic state. In today’s Hungary, these decisive factors are primarily the new regulation of the financing of law students, and secondly, the new Hungarian constitution (henceforth: Alaptörvény), which has modified the base of the Hungarian legal system. These circumstances necessitate a new, comprehensive, and empirical, investigation of law students. To this end, our research team (comprising a professor, a Ph.D. student, and two law students), is conducting a new type of study in February 2017. The first stage of the research project uses the desktop method to open up the research antecedents. Afterward, a structured questionnaire draft will be designed and sent to the Head of Department of Sociology and the Associate Professor of the Department of Constitutional Law at the University of Szeged to have the draft checked and amended. Next, an open workshop for students and teachers will be organized with the aim to discuss the draft and create the final questionnaire. The research team will then contact each Hungarian university with a Faculty of Law to reach all 1st- and 4th-year law students. 1st-year students have not yet studied the Alaptörvény, while 4th-year students have. All students will be asked to fill in the questionnaire (in February). Results are expected to be in at the end of February. In March, the research team will report the results and present the conclusions. In addition, the results will be compared to previous researches. The outcome will help us answer the following research question: How should legal studies and legal education in Hungary be reformed in accordance with law students and the future lawyer society? The aim of the research is to (1) help create a new student- and career-centered teaching method of legal studies, (2) offer a new perspective on legal education, and (3) create a helpful and useful de lege ferenda proposal for the attorney general as regards legal education as part of higher education.

Keywords: change, constitution, investigation, law students, lawyer society, legal education, legal studies, motivation, reform

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Authors: Musarat Ishaq, Tara Karnezis, Ramin Shayan

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Lipedema, a poorly understood chronic disease of adipose hyper-deposition, is often mistaken for obesity and causes significant impairment to mobility and quality-of-life. To identify molecular mechanisms underpinning lipedema, we employed comprehensive omics-based comparative analyses of whole tissue, adipocyte precursors (adipose-derived stem cells (ADSCs)), and adipocytes from patients with or without lipedema. Transcriptional profiling revealed significant differences in lipedema tissue, adipocytes, and ADSCs, with altered levels of mRNAs involved inproliferation and cell adhesion. One highly up-regulated gene in lipedema adipose tissue, adipocytes and ADSCs, ZIC4, encodes Zinc Finger Protein ZIC 4, a class of transcription factor which may be involved in regulating metabolism and adipogenesis. ZIC4 inhibition impaired the adipogenesis of ADSCs into mature adipocytes. Epigenetic regulation study revealed overexpression of ZIC4 is involved in decreased promoter DNA methylation and subsequent decrease in adipogenesis. These epigenetic modifications can alter adipocytes microenvironment and adipocytes differentiation. Our study show that epigenetic events regulate the ability of ADSCs to commit and differentiate into mature adipocytes by modulating ZIC4.

Keywords: lipedema, adipose-derived stem cells, adipose tisue, adipocytes, zinc finger protein, epigenetic

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Authors: Ian Kingsbury

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The rapid expansion of charter schools (public schools that receive government but do not face the same regulations as traditional public schools) over the preceding two decades has raised concerns over the potential for graft and fraud. These concerns are largely justified: Incidents of financial crime and mismanagement are not unheard of, and the charter sector has become a darling of hedge fund managers. In response, several states have strengthened their charter school regulatory regimes. Imposing regulations and attempting to increase accountability seem like sensible measures, and perhaps they are necessary. However, increased regulation may come at the cost of imposing barriers to entry. Specifically, increased regulation often entails evidence for a high likelihood of fiscal solvency. That should theoretically entail access to capital in the short-term, which may systematically preclude Black or Hispanic applicants from opening charter schools. Moreover, increased regulation necessarily entails more red tape. The institutional wherewithal and the number of hours required to complete an application to open a charter school might favor those who have partnered with an education service provider, specifically a charter management organization (CMO) or education management organization (EMO). These potential barriers to entry pose a significant policy concern. Just as policymakers hope to increase the share of minority teachers and principals, they should sensibly care whether individuals who open charter schools look like the students in that school. Moreover, they might be concerned if successful applications in states with stringent regulations are overwhelmingly affiliated with education service providers. One of the original missions of charter schools was to serve as a laboratory of innovation. Approving only those applications affiliated with education service providers (and in effect establishing a parallel network of schools rather than a diverse marketplace of schools) undermines that mission. Data and methods: The analysis examines more than 2,000 charter school applications from 15 states. It compares the outcomes of applications from states with a strong regulatory environment (those with high scores) from NACSA-the National Association of Charter School Authorizers- to applications from states with a weak regulatory environment (those with a low NACSA score). If the hypothesis is correct, applicants not affiliated with an ESP are more likely to be rejected in high-regulation states compared to those affiliated with an ESP, and minority candidates not affiliated with an education service provider (ESP) are particularly likely to be rejected. Initial returns indicate that the hypothesis holds. More applications in low NASCA-scoring Arizona come from individuals not associated with an ESP, and those individuals are as likely to be accepted as those affiliated with an ESP. On the other hand, applicants in high-NACSA scoring Indiana and Ohio are more than 20 percentage points more likely to be accepted if they are affiliated with an ESP, and the effect is particularly pronounced for minority candidates. These findings should spur policymakers to consider the drawbacks of charter school accountability and consider accountability regimes that do not impose barriers to entry.

Keywords: accountability, barriers to entry, charter schools, choice

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Authors: Liu Xiaohan

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Epstein–Barr virus (EBV) is a human herpesvirus and is closely related to many malignancies of lymphocyte and epithelial origins, such as gastric cancer, Burkitt’s lymphoma, and nasopharyngeal carcinoma (NPC). NPC is a malignant epithelial tumor which is 100% associated with EBV latent infection. Most of the NPC cases are densely populated in southern China, especially in Guangdong and Hong Kong. To our knowledge, overexpression of pro-inflammatory cytokines may result in a loss of balance of the immune system and cause damage to human bodies. Interleukin-6 (IL6) is a pro-inflammatory cytokine which plays an important role in tumor progression. In addition, gene expression is regulated by both transcriptional and post-transcriptional pathways, while post-transcriptional regulation is an important mechanism to modulate the mature mRNA level in mammalian cells. AU-rich element binding factor 1 (AUF1)/heterogeneous nuclear RNP D (hnRNP D) is known for its function in destabilizing mRNAs, including cytokines and cell cycle regulators. Previous studies have found that overexpression of hnRNP D would lead to tumorigenesis. In this project, our aim is to determine the role played by hnRNP D in EBV-infected cells and how our anti-EBV agents can affect the function of hnRNP D. The results of this study will provide a new insight into how the pro-inflammatory cytokine expression can be regulated by EBV.

Keywords: interleukin 6 (IL6), epstein-barr virus (EBV), nasopharyngeal carcinoma (NPC, epstein-barr nuclear antigen-1 (EBNA1)

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Authors: Tracie Catlett

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Students enrolled in high-achieving schools are under tremendous pressure to perform at high levels inside and outside the classroom. Achievement pressure is a prevalent source of stress for students enrolled in high-achieving schools, and female students, in particular, experience a higher frequency and higher levels of stress compared to their male peers. The practice of mindfulness in a school setting is one tool that has been linked to improved self-regulation of emotions, increased positive emotions, and stress reduction. A mixed methods randomized pretest-posttest no-treatment control trial evaluated the effects of a six-session mindfulness intervention taught during a regularly scheduled life skills period in an independent day school, one type of high-achieving school. Twenty-nine students in Grades 10 and 11 were randomized by class, where Grade 11 students were in the intervention group (n = 14) and Grade 10 students were in the control group (n = 15). Findings from the study produced mixed results. There was no evidence that the mindfulness program reduced participants’ stress levels and negative emotions. In fact, contrary to what was expected, students enrolled in the intervention group experienced higher levels of stress and increased negative emotions at posttreatment when compared to pretreatment. Neither the within-group nor the between-groups changes in stress level were statistically significant, p > .05, and the between-groups effect size was small, d = .2. The study found evidence that the mindfulness program may have had a positive impact on students’ ability to regulate their emotions. The within-group comparison and the between-groups comparison at posttreatment found that students in the mindfulness course experienced statistically significant improvement in the in their ability to regulate their emotions at posttreatment, p = .009 < .05 and p =. 034 < .05, respectively. The between-groups effect size was medium, d =.7, suggesting that the positive differences in emotion regulation difficulties were substantial and have practical implications. The analysis of gender differences, as they relate to stress and emotions, revealed that female students perceive higher levels of stress and report experiencing stress more often than males. There were no gender differences when analyzing sources of stress experienced by the student participants. Both females and males experience regular achievement pressures related to their school performance and worry about their future, college acceptance, grades, and parental expectations. Females reported an increased awareness of their stress and actively engaged in practicing mindfulness to manage their stress. Students in the treatment group expressed that the practice of mindfulness resulted in feelings of relaxation and calmness.

Keywords: achievement pressure, adolescents, emotion regulation, emotions, high-achieving schools, independent schools, mindfulness, negative affect, positive affect, stress

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Authors: Matthew Pleshaw, Caroline Lynch, Caleb Eaton, Ali Kiapour

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The problem addressed in this proposal is that of the lacking comfort and safety of inpatient rooms, specifically at Boston Children’s Hospital, with the implementation of a system that will allow inpatient children to feel more comfortable in the unfamiliar environment of a hospital. The focus is that of advancing and enhancing the healing process for children in a long-term inpatient stay at the hospital, though a combination of announcing a clinician or hospital staff’s arrival utilizing RFID (Fig. 1), and improving communication between clinicians, parents/guardians, patients, etc. by integrating a mobile application.

Keywords: Pediatrics, Hospital, RFID, Technology

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Authors: Cristian Andrei Nica

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The state of flow relies on cognitive elements that sustain openness for information processing in order to promote goal attainment. However, the need for closure may create mental constraints, which can impact affectivity levels. This study aims to observe the extent in which need for closure moderates the interaction between flow and affectivity, taking into account the mediating role of the mood repair motivation in the interaction process between need for closure and affectivity. Using a non-experimental, correlational design, n=73 participants n=18 men and n=55 women, ages between 19-64 years (m= 28.02) (SD=9.22), completed the Positive Affectivity-Negative Affectivity Schedule, the need for closure scale-revised, the mood repair items and an adapted version of the flow state scale 2, in order to assess the trait aspects of flow. Results show that need for closure significantly moderates the flow-affectivity process, while the tolerance of ambiguity sub-scale is positively associated with negative affectivity and negatively to positive affectivity. At the same time, mood repair motivation significantly mediates the interaction between need for closure and positive affectivity, whereas the mediation process for negative affectivity is insignificant. Need for closure needs to be considered when promoting the development of positive emotions. It has been found that the motivation to repair one’s mood mediates the interaction between need for closure and positive affectivity. According to this study, flow can trigger positive emotions when the person is willing to engage in mood regulation strategies and approach meaningful experiences with an open mind.

Keywords: flow, mood regulation, mood repair motivation, need for closure, negative affectivity, positive affectivity

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Authors: Emre Bayamlıoğlu

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This paper aims to provide an account of the legal and the regulative aspects of the algorithmic reputation systems with a special emphasis on the sharing economy (i.e., Uber, Airbnb, Lyft) business model. The first section starts with an analysis of the legal and commercial nature of the tripartite relationship among the parties, namely, the host platform, individual sharers/service providers and the consumers/users. The section further examines to what extent an algorithmic system of reputational information could serve as an alternative to legal regulation. Shortcomings are explained and analyzed with specific examples from Airbnb Platform which is a pioneering success in the sharing economy. The following section focuses on the issue of governance and control of the reputational information. The section first analyzes the legal consequences of algorithmic filtering systems to detect undesired comments and how a delicate balance could be struck between the competing interests such as freedom of speech, privacy and the integrity of the commercial reputation. The third section deals with the problem of manipulation by users. Indeed many sharing economy businesses employ certain techniques of data mining and natural language processing to verify consistency of the feedback. Software agents referred as "bots" are employed by the users to "produce" fake reputation values. Such automated techniques are deceptive with significant negative effects for undermining the trust upon which the reputational system is built. The third section is devoted to explore the concerns with regard to data mobility, data ownership, and the privacy. Reputational information provided by the consumers in the form of textual comment may be regarded as a writing which is eligible to copyright protection. Algorithmic reputational systems also contain personal data pertaining both the individual entrepreneurs and the consumers. The final section starts with an overview of the notion of reputation as a communitarian and collective form of referential trust and further provides an evaluation of the above legal arguments from the perspective of public interest in the integrity of reputational information. The paper concludes with certain guidelines and design principles for algorithmic reputation systems, to address the above raised legal implications.

Keywords: sharing economy, design principles of algorithmic regulation, reputational systems, personal data protection, privacy

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Authors: Amruta D. S. Pathare, Indira Hinduja, Kusum Zaveri

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Implantation failure (IF) even after the good-quality embryo transfer (ET) in the physiologically normal endometrium is the main obstacle in in vitro fertilization (IVF). Various microarray studies have been performed worldwide to elucidate the genes requisite for endometrial receptivity. These studies have included the population based on different phases of menstrual cycle during natural cycle and stimulated cycle in normal fertile women. Additionally, the literature is also available in recurrent implantation failure patients versus oocyte donors in natural cycle. However, for the first time, we aim to study the genomics of endometrial receptivity in IF patients under controlled ovarian stimulation (COS) during which ET is generally practised in IVF. Endometrial gene expression profiling in IF patients (n=10) and oocyte donors (n=8) were compared during window of implantation under COS by whole genome microarray (using Illumina platform). Enrichment analysis of microarray data was performed to determine dys-regulated biological functions and pathways using Database for Annotation, Visualization and Integrated Discovery, v6.8 (DAVID). The enrichment mapping was performed with the help of Cytoscape software. Microarray results were validated by real-time PCR. Localization of genes related to immune response (Progestagen-Associated Endometrial Protein (PAEP), Leukaemia Inhibitory Factor (LIF), Interleukin-6 Signal Transducer (IL6ST) was detected by immunohistochemistry. The study revealed 418 genes downregulated and 519 genes upregulated in IF patients compared to healthy fertile controls. The gene ontology, pathway analysis and enrichment mapping revealed significant downregulation in activation and regulation of immune and inflammation response in IF patients under COS. The lower expression of Progestagen Associated Endometrial Protein (PAEP), Leukemia Inhibitory Factor (LIF) and Interleukin 6 Signal Transducer (IL6ST) in cases compared to controls by real time and immunohistochemistry suggests the functional importance of these genes. The study was proved useful to uncover the probable reason of implantation failure being imbalance of immune and inflammatory regulation in our group of subjects. Based on the present study findings, a panel of significant dysregulated genes related to immune and inflammatory pathways needs to be further substantiated in larger cohort in natural as well as stimulated cycle. Upon which these genes could be screened in IF patients during window of implantation (WOI) before going for embryo transfer or any other immunological treatment. This would help to estimate the regulation of specific immune response during WOI in a patient. The appropriate treatment of either activation of immune response or suppression of immune response can be then attempted in IF patients to enhance the receptivity of endometrium.

Keywords: endometrial receptivity, immune and inflammatory response, gene expression microarray, window of implantation

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Authors: Mingxi Zhou, Jiří Kubásek, Iva Mozgová

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In Arabidopsis thaliana, histone 3 lysine 27 tri-methylation catalysed byPRC2 is playing essential functions in the regulation of plant development, growth, and reproduction[1-2]. Despite numerous studies related to the role of PRC2 in developmental control, how PRC2 works in the operational control in plants is unknown. In the present, the evidence that PRC2 probably participates in the regulation of retrograde singalling pathway in Arabidopsisis found. Firstly, we observed that the rosette size and biomass in PRC2-depletion mutants (clf-29 and swn-3) is significantly higher than WTunder medium light condition (ML: 125 µmol m⁻² s⁻²), while under medium high light condition (MHL: 300 µmol m⁻² s-2), the increase was reverse. Under ML condition, the photosynthesis related parameters determined by fluorCam did not show significant differences between WT and mutants, while the pigments concentration increased in the leaf of PRC2-depletion mutants, especially in swn. The dynamic of light-responsive genes and circadian clock genes expression by RT-qPCRwithin 24 hours in the mutants were comparable to WT. However, we observed upregulation of photosynthesis-associated nuclear genes in the PRC2-depletion mutants under chloroplast damaging condition (treated by lincomycin), corresponding to the so-called genome uncoupled (gun) phenotype. Here, we will present our results describing these phenotypes and our suggestion and outlook for studying the involvement of PRC2 in chloroplast-to-nucleus retrograde signalling.

Keywords: PRC2, retrograde signalling, light acclimation, photosyntheis

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