Search results for: constitutive expression

Authors: M. Nerantzaki, I. Koliakou, D. Bikiaris

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This study evaluates the hypothesis that the incorporation of fibrous hydroxyapatite nanoparticles (nHA) with high crystallinity and high aspect ratio, synthesized by hydrothermal method, into Poly(butylene succinate) (PBSu), improves the bioactivity of the aliphatic polyester and affects new bone growth inhibiting resorption and enhancing bone formation. Hydroxyapatite nanorods were synthesized using a simple hydrothermal procedure. First, the HPO42- -containing solution was added drop-wise into the Ca2+-containing solution, while the molar ratio of Ca/P was adjusted at 1.67. The HA precursor was then treated hydrothermally at 200°C for 72 h. The resulting powder was characterized using XRD, FT-IR, TEM, and EDXA. Afterwards, PBSu nanocomposites containing 2.5wt% (nHA) were prepared by in situ polymerization technique for the first time and were examined as potential scaffolds for bone engineering applications. For comparison purposes composites containing either 2.5wt% micro-Bioglass (mBG) or 2.5wt% mBG-nHA were prepared and studied, too. The composite scaffolds were characterized using SEM, FTIR, and XRD. Mechanical testing (Instron 3344) and Contact Angle measurements were also carried out. Enzymatic degradation was studied in an aqueous solution containing a mixture of R. Oryzae and P. Cepacia lipases at 37°C and pH=7.2. In vitro biomineralization test was performed by immersing all samples in simulated body fluid (SBF) for 21 days. Biocompatibility was assessed using rat Adipose Stem Cells (rASCs), genetically modified by nucleofection with DNA encoding SB100x transposase and pT2-Venus-neo transposon expression plasmids in order to attain fluorescence images. Cell proliferation and viability of cells on the scaffolds were evaluated using fluoresce microscopy and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay. Finally, osteogenic differentiation was assessed by staining rASCs with alizarine red using cetylpyridinium chloride (CPC) method. TEM image of the fibrous HAp nanoparticles, synthesized in the present study clearly showed the fibrous morphology of the synthesized powder. The addition of nHA decreased significantly the contact angle of the samples, indicating that the materials become more hydrophilic and hence they absorb more water and subsequently degrade more rapidly. In vitro biomineralization test confirmed that all samples were bioactive as mineral deposits were detected by X-ray diffractometry after incubation in SBF. Metabolic activity of rASCs on all PBSu composites was high and increased from day 1 of culture to day 14. On day 28 metabolic activity of rASCs cultured on samples enriched with bioceramics was significantly decreased due to possible differentiation of rASCs to osteoblasts. Staining rASCs with alizarin red after 28 days in culture confirmed our initial hypothesis as the presence of calcium was detected, suggesting osteogenic differentiation of rACS on PBSu/nHAp/mBG 2.5% and PBSu/mBG 2.5% composite scaffolds.

Keywords: biomaterials, hydroxyapatite nanorods, poly(butylene succinate), scaffolds

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Authors: Chung-Yuan Wang, Min Hsu, Bo-Ya Juan, Hsiv Ching Lin, Hsveh Min Lin, Hsiu-Fang Yeh

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The success of Taiwan's National Health Insurance (NHI) system attracts widespread praise from the international society. However, the availability of medical care in a emote area is limited. Without the convenient public transportation system and mature social welfare policy, these people are difficult to regain their health and prevent disability. Preterm children have more risk to get development delay. Preterm children in a remote area have the human right to get rehabilitation resources as those in the city area. Therefore, the aim of this study was to show the importance of development screening to preterm children in a remote area and a tract the government to notice the issue. In Pingtung, children who are suspected development delay would be suggested to take a skillful screening evaluation in our hospital. Those preterm children (within 1-year-old) visited our pediatric clinic would also be referred to take the development evaluation. After the physiatrist’s systemic evaluation, the subjects would be scheduled to take the development evaluation. Gross motor, fine motor, speech comprehension/expression and mental study were included. The evaluation was in-charged by a physical therapist, occupational therapy, speech therapist and pediatric psychologist. The tools were Peabody developmental scale, Bayley Scales of Infant and Toddler Development (Bayley-III) and Wechsler Preschool & Primary Scale of Intelligence-Revised (WPPSI-R). In 2013, 459 children received the service in our hospital. Among these children, fifty-seven were noted with preterm baby history (gestation within 37 weeks). Thirty-six of these preterm children, who had never receive development evaluation, were included in this study. Thirty-six subjects (twenty-six male and ten female) were included. Nineteen subjects were found development delay. Six subjects were found suspected development delay. In gross motor, six subjects were development delay and eight were suspected development delay. In fine motor, five subjects were development delay and three were suspected development delay. In speech, sixteen subjects were development delay and six were suspected development delay. In our study, through the provision of development evaluation service, 72.2% preterm baby were found their development delay or suspected delay. They need further early intervention rehabilitation service. We made their parents realize that when development delay was recognized at the early stage, they are often reversible. No only the patients but also their families were improved their health status. The number of the subjects was limited in our study. Further study might be needed. Compared with 770 physical therapist (PT) and 370 occupational therapy (OT) in Taipei, there are only 108 PT and 54 OT in Pingtung. Further, there are much fewer therapists working on the field of pediatric rehabilitation. Living healthy is a human's right, no matter where does he live. For those development delay children in remote area, particularly preterm children, early detection, and early intervention rehabilitation service could play an important role in decreasing their disability and improving their quality of life. Through this study, we suggest the government to add more national resources on the development evaluation to preterm children in a remote area.

Keywords: development, early intervention, preterm children, rehabilitation

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Authors: P. Asiabi, M. Shahhoseini, R. Favaedi, F. Hassani, N. Nassiri, B. Movaghar, L. Karimian, P. Eftekhariyazdi

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Introduction: Polycystic Ovary Syndrome is a common gynecologic disorder. Many factors including environment, metabolism, hormones and genetics are involved in etiopathogenesis of PCOS. Of genes that have altered expression in human reproductive system disorders are HOX family genes which act as transcription factors in regulation of cell proliferation, differentiation, adhesion and migration. Since recent evidences consider epigenetic factors as causative mechanisms of PCOS, evaluation of association between known epigenetic marks of acetylation/methylation of histone 3 (H3K9ac/me) with regulatory regions of these genes can represent better insight about PCOS. In the current study, cumulus cells (CCs) which have critical roles during folliculogenesis, oocyte maturation, ovulation and fertilization were aimed to monitor epigenetic alterations of HOX genes. Material and methods: CCs were collected from 20 PCOS patients and 20 fertile women (18-36 year) with male infertility problems referred to the Royan Institute to have ICSI under GnRH antagonist protocol. Informed consents were obtained from the participants. Thirty six hours after hCG injection, ovaries were punctured and cumulus oocyte complexes were dissected. Soluble chromatin were extracted from CCs and Chromatin Immune precipitation (ChIP) coupled with Real Time PCR was performed to quantify the epigenetic marks of histone H3K9 acetylation/methylation (H3K9ac/me) on regulatory regions of 15 members of HOX genes from A-D subfamily. Results: Obtained data showed significant increase of H3K9ac epigenetic mark on regulatory regions of HOXA1, HOXB2, HOXC4, HOXD1, HOXD3 and HOXD4 (P < 0.01) and HOXC5 (P < 0.05) and also significant decrease of H3K9ac into regulatory regions of HOXA2, HOXA4, HOXA5, HOXB1 and HOXB5 (P < 0.01) and HOXB3 (P<0.05) in PCOS patients vs. control group. On the other side, there was a significant decrease in incorporation of H3K9me level on regulatory region of HOXA2, HOXA3, HOXA4, HOXA5, HOXB3 and HOXC4 (P≤0.01) and HOXB5 (P < 0.05) in PCOS patients vs. control group. This epigenetic mark (H3K9me2) has significant increase on regulatory region of HOXB1, HOXB2, HOXC5, HOXD1, HOXD3 and HOXD4 (P ≤ 0.01) and HOXB4 (P < 0.05) in patients vs. control group. There were no significant changes in acetylation/methylation levels of H3K9 on regulatory regions of the other studied genes. Conclusion: Current study suggests that epigenetic alterations of HOX genes can be correlated with PCOS and consequently female infertility. This finding might offer additional definitions of PCOS, and eventually provides insight for novel treatments with epidrugs for this disease.

Keywords: epigenetic, HOX genes, PCOS, female infertility

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Authors: Jelena Kovačević Vorgučin, Sibila Petenji Arbutina

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The postmodern age brings a rapid development of technology which inevitably leads to man's need to adapt to modern lifestyle. On the one hand, technological achievements have made human life easier, but there are numerous risks involved. Moreover, man's awareness and perception is changing and adapting unconsciously to the world we live in, while communication in the 21st century is predominantly based on the consumption of images. This paper presents sociological aspects of a community which is confined due to turbulent political-economic circumstances and its impact on the development of media literacy in Serbia. Previous researches led to the conclusion that the media culture is on an extremely low level, and that it can have a strong influence on the general development of the society, starting from the youngest segment of the population. Our aim is to use the conceptual authorial photographs inspired by the obtained research results to emphasize the importance that the impact of visual art has in delivering the message, its role in education and in raising awareness of universal social problems. The paper presents a number of stages involved in the conceptual project which is designed to last over a longer period of time in order to facilitate dissemination of information. First, a survey was carried out in several preschool institutions. This resulted in obtaining the necessary information on the habitual use of the medium of television in children and their carers-parents. The second stage focused on the relationship between the parent and the child in TV consumption. Further, an overview of the visual part of the project was made, which consisted of photographs in various dimensions, ranging from miniature to large dimensions, and following various exhibition principles in both gallery and alternative spaces. This stage of the project placed particular emphasis on the non-standard exhibiting formats and alternative exhibition principles which are increasingly present in all kinds of visual art aimed at achieving a higher level of information noticing and memorizing. The motif on the authorial photographs is children's portraits taken while they are watching different television contents, with emphasis on their emotional response. The importance of the medium of TV is particularly emphasized due to the fact that its consumption is the highest, even though there are newer and more advanced information-technological achievements. The already realized part of the project was used for an analysis of the results in the last stage of the project, which led to the conclusion that the response to the entire visual expression campaign was extremely positive, and action as such very useful indeed. The results obtained speak in favour of widening and continuation of the project, both on a greater number of sites locally as well as in other communities in Serbia with the aim of guiding people towards meaningful consumption of the television medium.

Keywords: alternative space exhibiting, children and TV, conceptual portrait photography, media literacy

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Authors: Alak Kumar Patra, Nilanjan Mitra

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Higher strength to weight ratio is the main advantage of sandwich composite structures. Interfacial delamination between the face sheet and core is a major problem in these structures. Many research works are devoted to improve the interfacial fracture toughness of composites majorities of which are on nano and laminated composites. Work on influence of multiwalled carbon nano-tubes (MWCNT) dispersed resin system on interface fracture of glass-epoxy PVC core sandwich composite is extremely limited. Finite element study is followed by experimental investigation on interface fracture toughness of glass-epoxy (G/E) PVC core sandwich composite with and without MWCNT. Results demonstrate an improvement in interface fracture toughness values (Gc) of samples with a certain percentages of MWCNT. In addition, dispersion of MWCNT in epoxy resin through sonication followed by mixing of hardener and vacuum resin infusion (VRI) technology used in this study is an easy and cost effective methodology in comparison to previously adopted other methods limited to laminated composites. The study also identifies the optimum weight percentage of MWCNT addition in the resin system for maximum performance gain in interfacial fracture toughness. The results agree with finite element study, high-resolution transmission electron microscope (HRTEM) analysis and fracture micrograph of field emission scanning electron microscope (FESEM) investigation. Interface fracture toughness (GC) of the DCB sandwich samples is calculated using the compliance calibration (CC) method considering the modification due to shear. Compliance (C) vs. crack length (a) data of modified sandwich DCB specimen is fitted to a power function of crack length. The calculated mean value of the exponent n from the plots of experimental results is 2.22 and is different from the value (n=3) prescribed in ASTM D5528-01for mode 1 fracture toughness of laminate composites (which is the basis for modified compliance calibration method). Differentiating C with respect to crack length (a) and substituting it in the expression GC provides its value. The research demonstrates improvement of 14.4% in peak load carrying capacity and 34.34% in interface fracture toughness GC for samples with 1.5 wt% MWCNT (weight % being taken with respect to weight of resin) in comparison to samples without MWCNT. The paper focuses on significant improvement in experimentally determined interface fracture toughness of sandwich samples with MWCNT over the samples without MWCNT using much simpler method of sonication. Good dispersion of MWCNT was observed in HRTEM with 1.5 wt% MWCNT addition in comparison to other percentages of MWCNT. FESEM studies have also demonstrated good dispersion and fiber bridging of MWCNT in resin system. Ductility is also observed to be higher for samples with MWCNT in comparison to samples without.

Keywords: carbon nanotube, epoxy resin, foam, glass fibers, interfacial fracture, sandwich composite

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Authors: Michel Soto Chalhoub

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Building code-related literature provides recommendations on normalizing approaches to the calculation of the dynamic properties of structures. Most building codes make a distinction among types of structural systems, construction material, and configuration through a numerical coefficient in the expression for the fundamental period. The period is then used in normalized response spectra to compute base shear. The typical parameter used in simplified code formulas for the fundamental period is overall building height raised to a power determined from analytical and experimental results. However, reinforced concrete buildings which constitute the majority of built space in less developed countries pose additional challenges to the ones built with homogeneous material such as steel, or with concrete under stricter quality control. In the present paper, the particularities of reinforced concrete buildings are explored and related to current methods of equivalent static analysis. A comparative study is presented between the Uniform Building Code, commonly used for buildings within and outside the USA, and data from the Middle East used to model 151 reinforced concrete buildings of varying number of bays, number of floors, overall building height, and individual story height. The fundamental period was calculated using eigenvalue matrix computation. The results were also used in a separate regression analysis where the computed period serves as dependent variable, while five building properties serve as independent variables. The statistical analysis shed light on important parameters that simplified code formulas need to account for including individual story height, overall building height, floor plan, number of bays, and concrete properties. Such inclusions are important for reinforced concrete buildings of special conditions due to the level of concrete damage, aging, or materials quality control during construction. Overall results of the present analysis show that simplified code formulas for fundamental period and base shear may be applied but they require revisions to account for multiple parameters. The conclusion above is confirmed by the analytical model where fundamental periods were computed using numerical techniques and eigenvalue solutions. This recommendation is particularly relevant to code upgrades in less developed countries where it is customary to adopt, and mildly adapt international codes. We also note the necessity of further research using empirical data from buildings in Lebanon that were subjected to severe damage due to impulse loading or accelerated aging. However, we excluded this study from the present paper and left it for future research as it has its own peculiarities and requires a different type of analysis.

Keywords: seismic behaviour, reinforced concrete, simplified code formulas, equivalent static analysis, base shear, response spectra

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Authors: Cherng-Jye Jeng, Ming-Feng Hou, Hsing-Yuan Liu, Chuan-Feng Chang, Lih-Rong Wang, Yen-Chin Lin

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Introduction: The incidence of breast cancer has gradually increased in Taiwan, and the characteristic of younger ages impact these women in their middle age, and may also cause challenges in terms of family, work, and illness. Breasts are symbols of femininity, as well as of sex. For women, breasts are important organs for the female identity and sexual expression. Losing breasts not only affects the female role, but would also affect sexual attraction and sexual desire. Thus, women with breast cancer who have need for mastectomies experience physical incompletion, which affects women’s self-confidence, physical image, and self-orientation. Purposes: 1. To understand the physical experience of women with breast cancer. 2. To explore the issue of sexual issues on the health effects of women with breast cancer. 3. To construct a domestic sex life issue group model for domestic women with breast cancer. 4. To explore the accompaniment experiences and sexual relationship adjustments of spouses when women have breast cancer. Method: After the research plan passes IRB review, participants will be recruited at breast surgery clinic in the affiliated hospital, to screen suitable subjects for entry into the group. Between March and May 2015, two sexual health and sex life consultation groups were conducted, which were (1) 10 in postoperative groups for women with cancer; (2) 4 married couples group for postoperative women with cancer. After sharing experiences and dialogue, women can achieve mutual support and growth. Data organization and analysis underwent descriptive analysis in qualitative research, and the group process was transcribed into transcripts for overall-content and category-content analysis. Results: Ten women with breast cancer believed that participating in group can help them exchange experiences, and elevate sexual health. The main issues include: (1) after breast cancer surgery, patients generally received chemotherapy or estrogen suppressants, causing early menopause; in particular, vaginal dryness can cause pain or bleeding in intercourse, reducing their desire for sexual activity; (2) breast cancer accentuates original spousal or family and friend relationships; some people have support and care from their family, and spouses emphasize health over the appearance of breasts; however, some people do not have acceptance and support from their family, and some even hear spousal sarcasm about loss of breasts; (3) women with breast cancer have polarized expressions of optimism and pessimism in regards to their emotions, beliefs, and body image regarding cancer; this is related to the women’s original personalities, attribution of causes of cancer, and extent of worry about relapse. Conclusion: The research results can be provided as a reference to medical institutions or breast cancer volunteer teams, to pay attention to maintaining the health of women with breast cancer.

Keywords: women with breast cancer, experiences of objectifying the body, quality of sex life, sexual health

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Authors: Kirti Hira, A. Sajeli Begum, S. Mahibalan, Poorna Chandra Rao

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Introduction: Cancer is one of the leading causes of death worldwide. Although existing therapy effectively kills cancer cells, they do affect normal growing cells leading to many undesirable side effects. Hence there is need to develop effective as well as safe drug molecules to combat cancer, which is possible through phyto-research. The currently available plant-derived blockbuster drugs are the example for this. In view of this, an investigation was done to identify cytotoxic lead molecules from Hedyotis umbellata (Family Rubiaceae), a widely distributed weed in India. Materials and Methods: The methanolic extract of the whole plant of H. umbellata (MHU), prepared through Soxhlet extraction method was further fractionated with diethyl ether and n-butanol, successively. MHU, ether fraction (EMHU) and butanol fraction (BMHU) were lyophilized and were tested for the cytotoxic effect using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay against non-small cell lung cancer (NSCLC) A549 cell lines. The potentially active EMHU was subjected to chromatographic purification using normal-phase silica columns, in order to isolate the responsible bioactive compounds. The isolated pure compounds were tested for their cytotoxic effect by MTT assay against A549 cells. Compound-3, which was found to be most active, was characterized using IR, 1H- and 13C-NMR and MS analysis. The study was further extended to decipher the mechanism of action of cytotoxicity of compound-3 against A549 cells through various in vitro cellular models. Cell cycle analysis was done using flow cytometry following PI (Propidium Iodide) staining. Protein analysis was done using Western blot technique. Results: Among MHU, EMHU, and BMHU, the non-polar fraction EMHU demonstrated a significant dose-dependent cytotoxic effect with IC50 of 67.7μg/ml. Chromatography of EMHU yielded seven compounds. MTT assay of isolated compounds explored compound-3 as potentially active one, which inhibited the growth of A549 cells with IC50value of 14.2μM. Further, compound-3 was identified as cedrelopsin, a coumarin derivative having molecular weight of 260. Results of in vitro mechanistic studies explained that cedrelopsin induced cell cycle arrest at G2/M phase and down-regulated the expression of G2/M regulatory proteins such as cyclin B1, cdc2, and cdc25C, dose dependently. This is the first report that explores the cytotoxic mechanism of cedrelopsin. Conclusion: Thus a potential small lead molecule, cedrelopsin isolated from H. umbellata, showing antiproliferative effect mediated by G2/M arrest in A549 cells was discovered. The effect of cedrelopsin against other cancer cell lines followed by in vivo studies can be performed in future to develop a new drug candidate.

Keywords: A549, cedrelopsin, G2/M phase, Hedyotis umbellata

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Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

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Authors: Thauane Silva, Gabrielle do Vale, Andre Ferreira, Marilda Siqueira, Thiago Moreno L. Souza, Milene D. Miranda

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The exposure of A(H1N1)pdm09-infected epithelial cells (HeLa) to HIV-1 viral particles, or its gp120, enhanced interferon-induced transmembrane protein (IFITM3) content, a viral restriction factor (RF), resulting in a decrease in influenza replication. The gp120 binds to CCR5 (R5) or CXCR4 (X4) cell receptors during HIV-1 infection. Then, it is possible that the endogenous ligands of these receptors also modulate the expression of IFITM3 and other cellular factors that restrict influenza virus replication. Thus, the aim of this study is to analyze the role of cellular receptors R5 and X4 in modulating RFs in order to inhibit the replication of the influenza virus. A549 cells were treated with 2x effective dose (ED50) of endogenous R5 or X4 receptor agonists, CCL3 (20 ng/ml), CCL4 (10 ng/ml), CCL5 (10 ng/ml) and CXCL12 (100 ng/mL) or exogenous agonists, gp120 Bal-R5, gp120 IIIB-X4 and its mutants (5 µg/mL). The interferon α (10 ng/mL) and oseltamivir (60 nM) were used as a control. After 24 h post agonists exposure, the cells were infected with virus influenza A(H3N2) at 2 MOI (multiplicity of infection) for 1 h. Then, 24 h post infection, the supernatant was harvested and, the viral titre was evaluated by qRT-PCR. To evaluate IFITM3 and SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) protein levels, A549 were exposed to agonists for 24 h, and the monolayer was lysed with Laemmli buffer for western blot (WB) assay or fixed for indirect immunofluorescence (IFI) assay. In addition to this, we analyzed other RFs modulation in A549, after 24 h post agonists exposure by customized RT² Profiler Polymerase Chain Reaction Array. We also performed a functional assay in which SAMHD1-knocked-down, by single-stranded RNA (siRNA), A549 cells were infected with A(H3N2). In addition, the cells were treated with guanosine to assess the regulatory role of dNTPs by SAMHD1. We found that R5 and X4 agonists inhibited influenza replication in 54 ± 9%. We observed a four-fold increase in SAMHD1 transcripts by RFs mRNA quantification panel. After 24 h post agonists exposure, we did not observe an increase in IFITM3 protein levels through WB or IFI assays, but we observed an upregulation up to three-fold in the protein content of SAMHD1, in A549 exposed to agonists. Besides this, influenza replication enhanced in 20% in cell cultures that SAMDH1 was knockdown. Guanosine treatment in cells exposed to R5 ligands further inhibited influenza virus replication, suggesting that the inhibitory mechanism may involve the activation of the SAMHD1 deoxynucleotide triphosphohydrolase activity. Thus, our data show for the first time a direct relationship of SAMHD1 and inhibition of influenza replication, and provides perspectives for new studies on the signaling modulation, through cellular receptors, to induce proteins of great importance in the control of relevant infections for public health.

Keywords: chemokine receptors, gp120, influenza, virus restriction factors

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Authors: Nur Rafeeda Daut

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The significance of this paper is to provide an insight on the role of social movement in building stronger ethnic relations in Malaysia. In particular, it focuses on how the BERSIH movement have been able to bring together the different ethnic groups in Malaysia to resist the present political administration that is seen to manipulate the electoral process and oppress the basic freedom of expression of Malaysians. Attention is given on how and why this group emerged and its mobilisation strategies. Malaysia which is a multi-ethnic and multi-religious society gained its independence from the British in 1957. Like many other new nations, it faces the challenges of nation building and governance. From economic issues to racial and religious tension, Malaysia is experiencing high level of corruption and income disparity among the different ethnic groups. The political parties in Malaysia are also divided along ethnic lines. BERSIH which is translated as ‘clean’ is a movement which seeks to reform the current electoral system in Malaysia to ensure equality, justice, free and fair elections. It was originally formed in 2007 as a joint committee that comprised leaders from political parties, civil society groups and NGOs. In April 2010, the coalition developed as an entirely civil society movement unaffiliated to any political party. BERSIH claimed that the electoral roll in Malaysia has been marred by fraud and other irregularities. In 2015, the BERSIH movement organised its biggest rally in Malaysia which also includes 38 other rallies held internationally. Supporters of BERSIH that participated in the demonstration were comprised of all the different ethnic groups in Malaysia. In this paper, two social movement theories are used: resource mobilization theory and political opportunity structure to explain the emergence and mobilization of the BERSIH movement in Malaysia. Based on these two theories, corruption which is believed to have contributed to the income disparity among Malaysians has generated the development of this movement. The rise of re-islamisation values propagated by certain groups in Malaysia and the shift in political leadership has also created political opportunities for this movement to emerge. In line with the political opportunity structure theory, the BERSIH movement will continue to create more opportunities for the empowerment of civil society and the unity of ethnic relations in Malaysia. Comparison is made on the degree of ethnic unity in the country before and after BERSIH was formed. This would include analysing the level of re-islamisation values and also the level of corruption in relation to economic income under the premiership of the former Prime Minister Mahathir and the present Prime Minister Najib Razak. The country has never seen such uprisings like BERSIH where ethnic groups which over the years have been divided by ethnic based political parties and economic disparity joined together with a common goal for equality and fair elections. As such, the BERSIH movement is a unique case where it illustrates the change of political landscape, ethnic relations and civil society in Malaysia.

Keywords: ethnic relations, Malaysia, political opportunity structure, resource mobilization theory and social movement

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Authors: Jeet Chakraborty, Sanjay Dutta

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Antibiotic resistance by bacteria has proved to be a severe threat to mankind in recent times, and this fortifies an urgency to design and develop potent antibacterial small molecules/compounds with nonconventional mechanisms than the conventional ones. DNA carries the genetic signature of any organism, and bacteria maintain their genomic DNA inside the cell in a well-regulated compact form with the help of various nucleoid associated proteins like HU, HNS, etc. These proteins control various fundamental processes like gene expression, replication, etc., inside the cell. Alteration of the native DNA structure of bacteria can lead to severe consequences in cellular processes inside the bacterial cell that ultimately result in the death of the organism. The change in the global DNA structure by small molecules initiates a plethora of cellular responses that have not been very well investigated. Echinomycin and Triostin-A are biologically active Quinoxaline small molecules that typically consist of a quinoxaline chromophore attached with an octadepsipeptide ring. They bind to double-stranded DNA in a sequence-specific way and have high activity against a wide variety of bacteria, mainly against Gram-positive ones. To date, few synthetic quinoxaline scaffolds were synthesized, displaying antibacterial potential against a broad scale of pathogenic bacteria. QNOs (Quinoxaline N-oxides) are known to target DNA and instigate reactive oxygen species (ROS) production in bacteria, thereby exhibiting antibacterial properties. The divergent role of Quinoxaline small molecules in medicinal research qualifies them for the evaluation of their antimicrobial properties as a potential candidate. The previous study from our lab has given new insights on a 6-nitroquinoxaline derivative 1d as an intercalator of DNA, which induces conformational changes in DNA upon binding.7 The binding event observed was dependent on the presence of a crucial benzyl substituent on the quinoxaline moiety. This was associated with a large induced CD (ICD) appearing in a sigmoidal pattern upon the interaction of 1d with dsDNA. The induction of DNA superstructures by 1d at high Drug:DNA ratios was observed that ultimately led to DNA condensation. Eviction of invitro-assembled nucleosome upon treatment with a high dose of 1d was also observed. In this work, monoquinoxaline derivatives of 1d were synthesized by various modifications of the 1d scaffold. The set of synthesized 6-nitroquinoxaline derivatives along with 1d were all subjected to antibacterial evaluation across five different bacteria species. Among the compound set, 3a displayed potent antibacterial activity against Staphylococcus aureus bacteria. 3a was further subjected to various biophysical studies to check whether the DNA structural alteration potential was still intact. The biological response of S. aureus cells upon treatment with 3a was studied using various cell biology processes, which led to the conclusion that 3d can initiate DNA damage in the S. aureus cells. Finally, the potential of 3a in disrupting preformed S.aureus and S.epidermidis biofilms was also studied.

Keywords: DNA structural change, antibacterial, intercalator, DNA superstructures, biofilms

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Authors: Sweta Agrawal, Sachin Chaugule, Gargi Rane, Shashank More, Madhavi Indap

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Angiogenesis and metastasis are two of the most important hallmarks of cancer. Hence, most of the cancer therapies nowadays are multi-targeted so as to reduce resistance and have better efficacy. As synthetic molecules arise with a burden of their toxicities and side-effects, more and more research is being focussed on exploiting the vast natural resources of drugs, in the form of plants and animals. Although, the idea of using marine organisms as a source of pharmaceuticals is not new, the pace at which marine drugs are being discovered, has definitely up surged! In the present study, we have assessed the anti-angiogenic and in vitro anti-metastatic activity of aqueous fraction from the extract of marine gastropod Euchelus asper. The soft body of Euchelus Asper was extracted with methanol and named EAME. Partition chromatography of EAME gave three fractions EAME I, II and III. Biochemical analysis revealed the presence of proteins in EAME III. Preliminary analysis had revealed the anti-angiogenic activity was exhibited by EAME III out of the three fractions. Hereafter, EAME III (concentration 25µg/ml-400µg/ml) was tested on chick chorioallantoic membrane (CAM) model for the detailed analysis of its potential anti-angiogenic effect. In vitro testing of the fraction (concentration 0.25µg/ml - 1µg/ml), involved cytotoxicity by SRB assay, cell cycle analysis by flow cytometry and anti-proliferative effect by scratch wound healing assay on A549 lung carcinoma cells. Apart from this, a portion of treated CAM as well as conditioned medium from treated A549 were subjected to gelatin zymography for assessment of matrix metalloproteinases MMP-2 and MMP-9 levels. Our results revealed that EAME III exhibited significant anti-angiogenic activity on CAM which was also supported by histological observations. During histological studies of CAM, it was found that EAME III caused reduction in angiogenesis by altering the extracellular matrix of the CAM membrane. In vitro analysis disclosed that EAME III exhibited moderate cytotoxic effect on A549 cells and its effect was not dose-dependent. The results of flow cytometry confirmed that EAME III caused cell cycle arrest in A549 cell line as almost all of the treated cells were found in G1 phase. Further, the migration and proliferation of A549 was significantly reduced by EAME III as observed from the scratch wound assay. Moreover, Gelatin zymography analysis revealed that EAME III caused suppression of MMP-2 in CAM membrane and reduced MMP-9 and MMP-2 expression in A549 cells. This verified that the anti-angiogenic and anti-metastatic effects of EAME III were correlated with the suppression of MMP-2 and -9. To conclude, EAME III shows dual anti-tumour action by reducing angiogenesis and exerting anti-metastatic effect on lung cancer cells, thus it has the potential to be used as an anti-cancer agent against lung carcinoma.

Keywords: angiogenesis, anti-cancer, marine drugs, matrix metalloproteinases

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Authors: Nurten Çelik

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Under the new developments in science, medicine, sociology, psychology and literary theories, body studies has gained huge importance and the body has become a debatable issue. There has emerged, among sociologists and literary theorists, an overwhelming consensus that body is socially, politically and culturally perceived and constructed and thus, the position of an individual in the society is determined in accordance with his/her body image. In this regard, the most complicated point is the theoretical views propounded upon disability studies, where the disabled body is considered to be a site upon which social and political restrictions as well as repressions are inscribed. There has been the widely-accepted view that no matter what kind of disability it is, those with physical, mental or learning impairments face varied social, political and environmental obstacles that prevent them from being an active citizen, worker, lover and even a family member. In parallel with these approaches, the matter of the sufferings of disabled individuals attains its place in cinema and literature as well as in theatre studies under the category of disability theatre. One of the prominent plays that deal with physical disability came from the contemporary British playwright Nina Raine. In her awarded play Tribes, which premiered at the Royal Court Theatre in 2010, Raine develops the social strata where her deaf protagonist, Billy, caught up between two tribes – namely his family and his lover Slyvia, a member of the deaf community– experiences personal and social hardships due to his hearing impairment. In the play, intransigent and self-opinionated family members foster no sense of empathy towards Billy, there are noisy talking and shouting, but no communication, love, compassion or mutual understanding, and language becomes just a tool for the expression of rage and oppression. In the disordered atmosphere of the family life, Billy experiences isolation and loneliness. Billy’s hopes for success and love are destroyed when Slyvia, troubled between hearing and deafness, rejects him because she does not utterly grasp what Billy is experiencing. Drawing upon the hardships, Billy undergoes in his relationships with his family and his girlfriend, Tribes problematizes the concept of deafness and explores to what extent a deaf person can find a place in the hearing world. Setting ‘the disabled’ bodies against ‘the abled’ bodies in a family, a microcosm of the society where bodies are socially shaped and constructed, Tribes dramatizes how the disabled bodies are disenfranchised, stigmatised, marginalized and othered on the grounds that they are socially misfit. Tribes, with a specific focus on the dysfunctional family, shows that the lack of communication and empathy numbs the characters to the feelings of each other and thereby, they become more disabled than Billy. In conclusion, this paper, with the reference to the embodiment of disability and social theories, aims to explore how disabled bodies are socially marked and segregated from family and society.

Keywords: body, deafness, disability, disability theatre, Nina Raine, tribes

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Authors: Shreeyam, Ranjan Kumar Sah, Shivangi

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Recognizing and solving handwritten mathematical expressions can be a challenging task, particularly when certain characters are segmented and classified. This project proposes a solution that uses Convolutional Neural Network (CNN) and image processing techniques to accurately solve various types of equations, including arithmetic, quadratic, and trigonometric equations, as well as logical operations like logical AND, OR, NOT, NAND, XOR, and NOR. The proposed solution also provides a graphical solution, allowing users to visualize equations and their solutions. In addition to equation solving, the platform, called CNNCalc, offers a comprehensive learning experience for students. It provides educational content, a quiz platform, and a coding platform for practicing programming skills in different languages like C, Python, and Java. This all-in-one solution makes the learning process engaging and enjoyable for students. The proposed methodology includes horizontal compact projection analysis and survey for segmentation and binarization, as well as connected component analysis and integrated connected component analysis for character classification. The compact projection algorithm compresses the horizontal projections to remove noise and obtain a clearer image, contributing to the accuracy of character segmentation. Experimental results demonstrate the effectiveness of the proposed solution in solving a wide range of mathematical equations. CNNCalc provides a powerful and user-friendly platform for solving equations, learning, and practicing programming skills. With its comprehensive features and accurate results, CNNCalc is poised to revolutionize the way students learn and solve mathematical equations. The platform utilizes a custom-designed Convolutional Neural Network (CNN) with image processing techniques to accurately recognize and classify symbols within handwritten equations. The compact projection algorithm effectively removes noise from horizontal projections, leading to clearer images and improved character segmentation. Experimental results demonstrate the accuracy and effectiveness of the proposed solution in solving a wide range of equations, including arithmetic, quadratic, trigonometric, and logical operations. CNNCalc features a user-friendly interface with a graphical representation of equations being solved, making it an interactive and engaging learning experience for users. The platform also includes tutorials, testing capabilities, and programming features in languages such as C, Python, and Java. Users can track their progress and work towards improving their skills. CNNCalc is poised to revolutionize the way students learn and solve mathematical equations with its comprehensive features and accurate results.

Keywords: AL, ML, hand written equation solver, maths, computer, CNNCalc, convolutional neural networks

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Authors: Jabulani Gilford Kheswa, Thembelihle Lobi

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From a cultural perspective, expression of hegemonic masculinity in South Africa continues to escalate among adolescent males who grow up in communities lacking in role models and recreational facilities. However, when the schools are constructive, and peer influence is positive, adolescent male can potentially express character strengths and lead a meaningful life. Drawing from Bronfenbrenner’s Ecological Model and Keyes and Ryff’s six dimensions of psychological well-being and mental health, such youth may exemplify positive self-esteem, problem- focused coping strategies, condom self-efficacy, good leadership skills, enhanced motivation and a positive emotional state, which buffer against risky sexual behaviors. This paper was aimed at investigating the relationships between adolescent males’ sexual behavior and psychological well-being. This study employed a quantitative research to collect data from 54 Xhosa-speaking adolescent males from one school high school in Fort Beaufort, Eastern Cape, South Africa. These learners were from grade nine, ten and eleven with their ages ranging from 14 to 20. Prior the research commenced, the school principal and caregivers of the learners who participated in the study, gave their informed consent. Self- administered closed-ended questionnaire with Section A (that is, biographical information) and Section B with each question rated on the 5–point Likert scale was used. The advantages of questionnaires include a high response rate as they require less time and offer anonymity because participants’ names are not identified. The SPSS version 18 was used for statistical data analysis. The mean age was 16.83 with a standard deviation of 1.611. 44.4% of the participants were from grade 9, 33.3% from grade 10 and 22.2% from grade 11. The Chronbach alpha of 0.79 was yielded, with respect to self- esteem of adolescent males. In this study, 76.9% reported to attend church services whilst 23% indicated not to attend church services. A further 96.2% of adolescent males indicated to have good relations with guardians while only 3.8% had poorer relations. A large proportion of adolescent males (72.9%) indicated to high-quality friendship as opposed to 27.1% who reported being receiving negative guidance from peers. Other findings revealed that 81.1% of the participants’ parents do not drink alcohol, and they cope at school as 79.6% reported protective factors as attributable towards non-engagement to risky sexual practices. As a result, 81.4% of participants reported not to participate in criminal activities although 85% of the participants indicated that in their school there are drugs. It could be speculated from this study that adolescent males whose caregivers are authoritative, find purpose in life and are most likely to be socially and academically competent. This paper leads to further research interest into mental health, coping strategies and sexual decision-making skills of the youth in South Africa.

Keywords: church, mental health, school, sexual behaviour

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Authors: Chien Yang Erdem

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This paper takes up the proliferating historical dramas and children’s programs featuring the Ottoman-Islamic legacy on Turkish television as a locus where the processes of subjectification take place. A critical analysis of this emergent cultural phenomenon reveals an alliance of neoliberal and neoconservative political rationalities based on which the Turkish media is restructured to transform society. The existing debates have focused on how the Ottoman historical dramas manifest the Justice and Development Party’s (Adalet ve Kalkınma Partisi) neo-Ottomanist ideology and foreign policy. However, this approach tends to overlook the more complex relationship between the media, government, and society. Employing Michel Foucault’s notion of 'technologies of the self,' this paper aims to examine the governing practices that are deployed to regulate the media and to transform individual citizens into governable subjects in contemporary Turkey. First, through a brief discussion of recent development of the Turkish media towards an authoritarian model, the paper suggests that the relation between the Ottoman television drama and the political subject in question cannot be adequately examined without taking into account the force of the market. Second, by focusing on the managerial restructuring of the Turkish Television and Radio Corporation (Türkiye Radyo ve Televizyon Kurumu), the paper aims to illustrate the rationale and process through which the Turkish media sector is transformed into an integral part of the free market where the government becomes a key actor. The paper contends that this new sphere of free market is organized in a way that enables direct interference of the government and divides media practitioners and consumers into opposing categories through their own participation in the media market. On the one hand, a 'free subject' is constituted based on the premise that the market is a sphere where individuals are obliged to exercise their right to freedom (of choice, lifestyle, and expression). On the other hand, this 'free subject' is increasingly subjugated to such disciplinary practices as censorship for being on the wrong side of the government. Finally, the paper examines the relation between the restructured Turkish media market and the proliferation of Ottoman television drama in the 2010s. The study maintains that the reorganization of the media market has produced a condition where private sector is encouraged to take an active role in reviving Turkey’s Ottoman-Islamic cultural heritage and promulgating moral-religious values. Paying specific attention to the controversial case of Magnificent Century (Muhteşem Yüzyıl) in contrast with TRT’s Ottoman historical drama and children’s programs, the paper aims to identify the ways in which individual citizens are directed to conduct themselves as a virtuous citizenry. It is through the double movement between the governing practices associated with the media market and those concerning the making of a 'conservative generation' that a subject of citizenry of new Turkey is constituted.

Keywords: neoconservatism, neoliberalism, ottoman historical drama, technologies of the self, Turkish television

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Authors: Tashwill Esterhuizen

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Throughout Africa, several countries continue to have laws which criminalise same-sex sexual activities, which increases the vulnerability of the LGBT community to stigma, discrimination, and persecution. These criminal provisions often form the basis upon which states deny LGBT activists the right to freely associate with other like-minded individuals and form organizations that protect their interests and advocate for the rights and aspirations of the LGBT community. Over the past year, however, there has been significant progress in the advancement of universal, fundamental rights of LGBT persons throughout Africa. In many instances, these advancements came about through the bravery of activists who have publically insisted (in environments where same-sex sexual practices are criminalised) that their rights should be respected. Where meaningful engagement with the State was fruitless, activists took their plight to the judiciary and have successfully sought to uphold the fundamental rights of LGBT persons, paving the way for a more inclusive and tolerant society. Litigation Progress: Botswana is a prime example. For several years, the State denied a group of LGBT activists their right to freely associate and form their organisation Lesbians, Gays, and Bisexuals of Botswana (LEGABIBO), which aimed to promote the interests of the LGBT community in Botswana. In March 2016, the Botswana Court of Appeal found that the government’s refusal to register LEGABIBO violated the activists’ right to associate freely. The Court held that the right freedom of association applies to all persons regardless of their sexual orientation or gender identity. It does not matter that the views of the organisation are unpopular or unacceptable amongst the majority. In particular, the Court rejected the government of Botswana’s contention that registering LEGABIBO would disturb public peace and is contrary to public morality. Quite remarkably, the Court of Appeal recognised that while LGBT individuals are a minority group within the country, they are nonetheless persons entitled to constitutional protections of their dignity, regardless of whether they are unacceptable to others on religious or any other grounds. Furthermore, the Court held that human rights and fundamental freedoms are granted to all, including criminals or social outcasts because the denial of an individual’s humanity is the denial of their human dignity. This is crucial observation by the Court of Appeal, as once it is accepted that human rights apply to all human beings, then it becomes much easier for vulnerable groups to assert their own rights. Conclusion: The Botswana Court of Appeal decision, therefore, represents significant progress in the promotion of the rights of lesbian, gay, bisexual and transgender persons. The judgment has broader implications for many other countries which do not provide recognition of sexual minorities. It highlights the State’s duty to uphold basic rights and to ensure dignity, tolerance, and acceptance for marginalised persons.

Keywords: acceptance, freedom of association, freedom of expression, fundamental rights and freedoms, gender identity, human rights are universal, inclusive, inherent human dignity, progress, sexual orientation, tolerance

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Authors: Kalyani Gandhi

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The eighteenth century in Britain saw a great burst of activity in writing (letters, journals, newspapers, essays); often these modes of writing had a public-spirited bent in-step with the prevailing intellectual atmosphere. Mary Wollstonecraft was one of the leading intellectuals of that period who utilized letter writing to convey her thoughts on the exciting political developments of the late eighteenth century. Fusing together her anxieties and concerns about humanity in general and herself in particular, Wollstonecraft’s views of the world around her are filtered through the lens of her subjectivity. Thus, Wollstonecraft’s letters covered a wide range of topics on both the personal and political level (for the two are often entwined in Wollstonecraft’s characteristic style of analysis) such as sentiment, gender, nature, peasantry, the class system, the legal system, political duties and rights of both rulers and subjects, death, immortality, religion, family and education. Therefore, this paper intends to examine the manner in which Wollstonecraft utilizes letter-writing to constitute and develop Romantic self-hood, understand the world around her and illustrate her ideas on the political and social happenings in Europe. The primary text analyzed will be Mary Wollstonecraft's Letters Written During a Short Stay in Sweden, Denmark and Norway (1796) and the analysis of this text will be supplemented by researching 18th-century British letter writing culture, with a special emphasis on the epistolary habits of women. Within this larger framework, this paper intends to examine the manner in which this hybrid of travel and epistolary writing aided Mary Wollstonecraft's expression on Romantic selfhood and how it was complicated by ideas of gender. This paper reveals Wollstonecraft's text to be wrought with anxiety about the world around her and within her; thus, the personal-public nature of the epistolary format particularly suits her characteristic point of view that looks within and without. That is to say, Wollstonecraft’s anxieties about gender and self, are as much about the women she sees in the world around her as much as they are about her young daughter and herself. Wollstonecraft constantly explores and examines this anxiety within the different but interconnected realms of politics, economics, history and society. In fact, it is her complex technique of entwining these aforementioned concerns with a closer look at interpersonal relationships among men and women (she often mentions specific anecdotes and instances) that make Wollstonecraft's Letters so engaging and insightful. Thus, Wollstonecraft’s Letters is an exemplar of British Romantic writing due to the manner in which it explores the bond between the individual and society. Mary Wollstonecraft's nuances this exploration by incorporating her concerns about women and the playing out of gender in society. Thus, Wollstonecraft’s Letters is an invaluable contribution to the field of British Romanticism, particularly as it offers crucial insight on female Romantic writing that can broaden and enrich the current academic understanding of the field.

Keywords: British romanticism, letters, feminism, travel writing

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Authors: Akanksha Bhatnagar, Sandhya Kortegare, Felice Elefant

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Context: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive cognitive decline and memory loss. The cause of AD is not fully understood, but it is thought to be caused by a combination of genetic, environmental, and lifestyle factors. One of the hallmarks of AD is the loss of neurons in the hippocampus, a brain region that is important for memory and learning. This loss of neurons is thought to be caused by a decrease in histone acetylation, which is a process that regulates gene expression. Research Aim: The research aim of the study was to develop mall molecule compounds that can enhance the activity of Tip60, a histone acetyltransferase that is important for memory and learning. Methodology/Analysis: The researchers used in silico structural modeling and a pharmacophore-based virtual screening approach to design and synthesize small molecule compounds strongly predicted to target and enhance Tip60’s HAT activity. The compounds were then tested in vitro and in vivo to assess their ability to enhance Tip60 activity and rescue cognitive deficits in AD models. Findings: The researchers found that several of the compounds were able to enhance Tip60 activity and rescue cognitive deficits in AD models. The compounds were also developed to cross the blood-brain barrier, which is an important factor for the development of potential AD therapeutics. Theoretical Importance: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Data Collection: The study collected data from a variety of sources, including in vitro assays and animal models. The in vitro assays assessed the ability of compounds to enhance Tip60 activity using histone acetyltransferase (HAT) enzyme assays and chromatin immunoprecipitation assays. Animal models were used to assess the ability of the compounds to rescue cognitive deficits in AD models using a variety of behavioral tests, including locomotor ability, sensory learning, and recognition tasks. The human clinical trials will be used to assess the safety and efficacy of the compounds in humans. Questions: The question addressed by this study was whether Tip60 HAT activators could be developed as therapeutic agents for AD. Conclusions: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Further research is needed to confirm the safety and efficacy of these compounds in humans.

Keywords: Alzheimer's disease, cognition, neuroepigenetics, drug discovery

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Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne

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Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging

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Authors: Shamini Dhana, G. Subrahmanya VRK Rao

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The fashion industry is advancing towards a mindset of zero waste, personalization, creativity, and circularity. The trend of upcycling clothing and materials into personalized fashion is being demanded by the next generation. There is a need for a digital tool to accelerate the process towards mass customization. Dhana’s D/Sphere fashion technology platform uses digital tools to accelerate upcycling. In essence, advanced fashion garments can be designed and developed via reuse, repurposing, recreating activities, and using existing fabric and circulating materials. The D/Sphere platform has the following objectives: to provide (1) An opportunity to develop modern fashion using existing, finished materials and clothing without chemicals or water consumption; (2) The potential for an everyday customer and designer to use the medium of fashion for creative expression; (3) A solution to address the global textile waste generated by pre- and post-consumer fashion; (4) A solution to reduce carbon emissions, water, and energy consumption with the participation of all stakeholders; (5) An opportunity for brands, manufacturers, retailers to work towards zero-waste designs and as an alternative revenue stream. Other benefits of this alternative approach include sustainability metrics, trend prediction, facilitation of disassembly and remanufacture deep learning, and hyperheuristics for high accuracy. A design tool for mass personalization and customization utilizing existing circulating materials and deadstock, targeted to fashion stakeholders will lower environmental costs, increase revenues through up to date upcycled apparel, produce less textile waste during the cut-sew-stitch process, and provide a real design solution for the end customer to be part of circular fashion. The broader impact of this technology will result in a different mindset to circular fashion, increase the value of the product through multiple life cycles, find alternatives towards zero waste, and reduce the textile waste that ends up in landfills. This technology platform will be of interest to brands and companies that have the responsibility to reduce their environmental impact and contribution to climate change as it pertains to the fashion and apparel industry. Today, over 70% of the $3 trillion fashion and apparel industry ends up in landfills. To this extent, the industry needs such alternative techniques to both address global textile waste as well as provide an opportunity to include all stakeholders and drive circular fashion with new personalized products. This type of modern systems thinking is currently being explored around the world by the private sector, organizations, research institutions, and governments. This technological innovation using digital tools has the potential to revolutionize the way we look at communication, capabilities, and collaborative opportunities amongst stakeholders in the development of new personalized and customized products, as well as its positive impacts on society, our environment, and global climate change.

Keywords: circular fashion, deep learning, digital technology platform, personalization

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Authors: Eszter Repasi, Akos Koller

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Our genetic information determines our look, physiology, sports performance and all our features. Maximizing the performances of athletes have adopted a science-based approach to the nutritional support. Nowadays genetics studies have blended with nutritional sciences, and a dynamically evolving, new research field have appeared. Nutritional genomics is needed to be used by nutritional experts. This is a recent field of nutritional science, which can provide a solution to reach the best sport performance using correlations between the athlete’s genome, nutritions, molecules, included human microbiome (links between food, microbiome and epigenetics), nutrigenomics and nutrigenetics. Nutritional genomics has a tremendous potential to change the future of dietary guidelines and personal recommendations. Experts need to use new technology to get information about the athletes, like nutritional genomics profile (included the determination of the oral and gut microbiome and DNA coded reaction for food components), which can modify the preparation term and sports performance. The influence of nutrients on the genes expression is called Nutrigenomics. The heterogeneous response of gene variants to nutrients, dietary components is called Nutrigenetics. The human microbiome plays a critical role in the state of health and well-being, and there are more links between food or nutrition and the human microbiome composition, which can develop diseases and epigenetic changes as well. A nutritional genomics-based profile of athletes can be the best technic for a dietitian to make a unique sports nutrition diet plan. Using functional food and the right food components can be effected on health state, thus sports performance. Scientists need to determine the best response, due to the effect of nutrients on health, through altering genome promote metabolites and result changes in physiology. Nutritional biochemistry explains why polymorphisms in genes for the absorption, circulation, or metabolism of essential nutrients (such as n-3 polyunsaturated fatty acids or epigallocatechin-3-gallate), would affect the efficacy of that nutrient. Controlled nutritional deficiencies and failures, prevented the change of health state or a newly discovered food intolerance are observed by a proper medical team, can support better sports performance. It is important that the dietetics profession informed on gene-diet interactions, that may be leading to optimal health, reduced risk of injury or disease. A special medical application for documentation and monitoring of data of health state and risk factors can uphold and warn the medical team for an early action and help to be able to do a proper health service in time. This model can set up a personalized nutrition advice from the status control, through the recovery, to the monitoring. But more studies are needed to understand the mechanisms and to be able to change the composition of the microbiome, environmental and genetic risk factors in cases of athletes.

Keywords: gene-diet interaction, multidisciplinary team, microbiome, diet plan

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Authors: Maria de Fátima Lambert

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Bernardo Soares is one of Fernando Pessoa' several heteronyms (and "half-heteronyms"). Perhaps the one that brought together the majority of his qualities and characters of self-identity within the famous inner-persona-alter-diversity. The Book of Disquiet by Bernardo Soares was released in 1983, consisting of ontological remarks caught by an obsessive inquiring about self-existence. The book became a highly valuable substance when focusing upon the philosophical grounds of Pessoa's aesthetics. For sure, we cannot consider a single aesthetic, admitting that each heteronym has its own particular one, developed after different principles and convictions. Regarding Bernardo Soares, his thought arises from sequenced self-clues expressing peculiar existential doubtless presented as certainties -and vice-versa. His written self-search-images are reported, molding the painful awareness of existence through the discredited tolerance of any conclusive dialogue with others. Given the nature of Soares’ [maybe] unfinished writings, it is obvious that he headed far from his self-insurance-capsule: the office, bedroom, or even the walkscapes through Lisbon. The idea of travel/journey is one of the most relevant when recognizing his profound - although undercover - anguish as melancholy and nostalgia. In Bernardo Soares, Aesthetics is taken agonizingly, grounded upon discreet poetic phraseology and terms. His poetical awareness developed compulsive titles such "Aesthetics of Indifference", "Aesthetics of Discouragement". Soares' Aesthetics emerges directly from oneself, understanding art as inner acts and living experienced issues. Art is not freed from the intellectual expression of oneself emotions. The Disquiet Book is an existential nightmare nourished by everyday life, single written thoughts, balanced by melancholia, nostalgia, and distress. One might wonder if it was dreams that guided his fictional literary persona or the narrow facts of life itself. Along with his endless disquiet writing, Pessoa’s semi-heteronymous traveled without physically going anywhere. The complexity of inner existence is fulfilled by lonely mental walks and travels, as in two texts titled The Never Accomplished Journey. Although we also can consider other fragments, these are the deepest reflections about travelling. Let’s recall that Fernando Pessoa’s ortonyms writings -poems and essays- also addressed this issue from a philosophical perspective. We believe that this theme is one of the meaningful concepts for featuring the main principles of his aesthetics. As we know, Fernando Pessoa did not travel to foreign countries (or in Portugal), except for the journey, with his family, from Lisbon to South Africa (as a child) and, some years later, the return back to Lisbon. One may wonder why the poet never undertook other journeys. Maybe due to a disbelief in moving away from his comfort zone or due to the fear of becoming addicted to endless travels and the loss of his convenient self-closeness. In The Book of Disquiet, the poet shared his internal visions of the outer world but mainly visualizing his deepest enigmas and experiences -so strongly incorporated into reality and fiction.

Keywords: aesthetic principles, Bernardo Soares, Fernando Pessoa , melancholia, nostalgia, non-accomplished travel, The Book of Disquiet

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Authors: Elena Filova, Ondrej Kaplan, Marie Markova, Helena Dragounova, Roman Matejka, Eduard Brynda, Lucie Bacakova

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Decellularized vessels have been evaluated as small-diameter vascular prostheses. Reseeding autologous cells onto decellularized tissue prior implantation should prolong prostheses function and make them living tissues. Suitable cell types for reseeding are both endothelial cells and bone marrow-derived stem cells, with a capacity for differentiation into smooth muscle cells upon mechanical loading. Endothelial cells assure antithrombogenicity of the vessels and MSCs produce growth factors and, after their differentiation into smooth muscle cells, they are contractile and produce extracellular matrix proteins as well. Fibrin is a natural scaffold, which allows direct cell adhesion based on integrin receptors. It can be prepared autologous. Fibrin can be modified with bound growth factors, such as basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF). These modifications in turn make the scaffold more attractive for cells ingrowth into the biological scaffold. The aim of the study was to prepare thin surface-attached fibrin assemblies with bound FGF-2 and VEGF, and to evaluate growth and differentiation of bone marrow-derived mesenchymal stem cells on the fibrin (Fb) assemblies. Following thin surface-attached fibrin assemblies were prepared: Fb, Fb+VEGF, Fb+FGF2, Fb+heparin, Fb+heparin+VEGF, Fb+heparin+FGF2, Fb+heparin+FGF2+VEGF. Cell culture poly-styrene and glass coverslips were used as controls. Human MSCs (passage 3) were seeded at the density of 8800 cells/1.5 mL alpha-MEM medium with 2.5% FS and 200 U/mL aprotinin per well of a 24-well cell culture. The cells have been cultured on the samples for 6 days. Cell densities on day 1, 3, and 6 were analyzed after staining with LIVE/DEAD cytotoxicity/viability assay kit. The differentiation of MSCs is being analyzed using qPCR. On day 1, the highest density of MSCs was observed on Fb+VEGF and Fb+FGF2. On days 3 and 6, there were similar densities on all samples. On day 1, cell morphology was polygonal and spread on all sample. On day 3 and 6, MSCs growing on Fb assemblies with FGF2 became apparently elongated. The evaluation of expression of genes for von Willebrand factor and CD31 (endothelial cells), for alpha-actin (smooth muscle cells), and for alkaline phosphatase (osteoblasts) is in progress. We prepared fibrin assemblies with bound VEGF and FGF-2 that supported attachment and growth of mesenchymal stem cells. The layers are promising for improving the ingrowth of MSCs into the biological scaffold. Supported by the Technology Agency of the Czech Republic TA04011345, and Ministry of Health NT11270-4/2010, and BIOCEV – Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University” project (CZ.1.05/1.1.00/02.0109), funded by the European Regional Development Fund for their financial supports.

Keywords: fibrin assemblies, FGF-2, mesenchymal stem cells, VEGF

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Authors: Alvyra Galkienė, Ona Monkevičienė

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The full participation of all pupils in the overall educational process is defined by the concept of inclusive education, which is gradually evolving in education policy and practice. It includes the full participation of all pupils in a shared learning experience and educational practices that address barriers to learning. Inclusive education applying the principles of Universal Design for Learning (UDL), which includes promoting students' involvement in learning processes, guaranteeing a deep understanding of the analysed phenomena, initiating self-directed learning, and using e-tools to create a barrier-free environment, is a prerequisite for the personal success of each pupil. However, the sustainability of quality education is affected by the transformation of education systems. This was particularly evident during the period of the forced transition from contact to distance education in the COVID-19 pandemic. Research Problem: The transformation of the educational environment from real to virtual one and the loss of traditional forms of educational support highlighted the need for new research, revealing the individual profiles of teachers using UDL-based learning and the pathways of sustainable transfer of successful practices to non-conventional learning environments. Research Methods: In order to identify individual latent teacher profiles that encompass the essential components of UDL-based inclusive teaching and direct leadership of students' learning, the quantitative analysis software Mplius was used for latent profile analysis (LPA). In order to reveal proven, i.e., sustainable, pathways for the transit of the components of UDL-based inclusive learning to distance learning, latent profile transit analysis (LPTA) via Mplius was used. An online self-reported questionnaire was used for data collection. It consisted of blocks of questions designed to reveal the experiences of subject teachers in contact and distance learning settings. 1432 Lithuanian, Latvian, and Estonian subject teachers took part in the survey. Research Results: The LPA analysis revealed eight latent teacher profiles with different characteristics of UDL-based inclusive education or traditional teaching in contact teaching conditions. Only 4.1% of the subject teachers had a profile characterised by a sustained UDL approach to teaching: promoting pupils' self-directed learning; empowering pupils' engagement, understanding, independent action, and expression; promoting pupils' e-inclusion; and reducing the teacher's direct supervision of the students. Other teacher profiles were characterised by limited UDL-based inclusive education either due to the lack of one or more of its components or to the predominance of direct teacher guidance. The LPTA analysis allowed us to highlight the following transit paths of teacher profiles in the extreme conditions of the transition from contact to distance education: teachers staying in the same profile of UDL-based inclusive education (sustainable transit) or jumping to other profiles (unsustainable transit in case of barriers), and teachers from other profiles moving to this profile (ongoing transit taking advantage of the changed new possibilities in the teaching process).

Keywords: distance education, latent teacher profiles, sustainable transit, UDL

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Authors: Archana Sharma, Vijayashree Nayak, Ashok Kumar

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Three-dimensional matrices were fabricated from blend of natural-natural polymers like carrageenan-gelatin and synthetic -natural polymers such as PEG- gelatin (PEG of different molecular weights (2,000 and 6,000) using two different crosslinkers; glutaraldehyde and EDC-NHS by cryogelation technique. Blends represented a feasible approach to design 3-D scaffolds with controllable mechanical, physical and biochemical properties without compromising biocompatibility and biodegradability. These matrices possessed interconnected porous structure, good mechanical strength, biodegradable nature, constant swelling kinetics, ability to withstand high temperature and visco-elastic behavior. Hemocompatibility of cryogel matrices was determined by coagulation assays and hemolytic activity assay which demonstrated that these cryogels have negligible effects on coagulation time and have excellent blood compatibility. In vitro biocompatibility (cell-matrix interaction) inferred good cell adhesion, proliferation, and secretion of ECM on matrices. These matrices provide a microenvironment for the growth, proliferation, differentiation and secretion of ECM of different cell types such as IMR-32, C2C12, Cos-7, rat bone marrow derived MSCs and human bone marrow MSCs. Hoechst 33342 and PI staining also confirmed that the cells were uniformly distributed, adhered and proliferated properly on the cryogel matrix. An ideal scaffold used for tissue engineering application should allow the cells to adhere, proliferate and maintain their functionality. Neurotransmitter analysis has been done which indicated that IMR-32 cells adhered, proliferated and secreted neurotransmitters when they interacted with these matrices which showed restoration of their functionality. The cell-matrix interaction up to molecular level was also evaluated so to check genotoxicity and protein expression profile which indicated that these cryogel matrices are non-genotoxic and maintained biofunctionality of cells growing on these matrices. All these cryogels, when implanted subcutaneously in balb/c mice, showed no adverse systemic or local toxicity effects at implantation site. There was no significant increase in inflammatory cell count has otherwise been observed after scaffold implantation. These cryogels are supermacroporous and this porous structure allows cell infiltration and proliferation of host cells. This showed the integration and presence of infiltrated cells into the cryogel implants. Histological analysis confirmed that the implanted cryogels do not have any adverse effect in spite of host immune system recognition at the site of implantation, on its surrounding tissues and other vital host organs. In vivo biocompatibility study after in vitro biocompatibility analysis has also concluded that these synthesized cryogels act as important biological substitutes, more adaptable and appropriate for transplantation. Thus, these cryogels showed their potential for soft tissue engineering applications.

Keywords: cryogelation, hemocompatibility, in vitro biocompatibility, in vivo biocompatibility, soft tissue engineering applications

Procedia PDF Downloads 224

Authors: Elyria Kemp, Kelly Cowart, My Bui

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According to the National Institute of Mental Health, an estimated 31.9% of adolescents have had an anxiety disorder. Several environmental factors may help to contribute to high levels of anxiety and depression in young people (i.e., Generation Z, Millennials). However, as young people negotiate life on social media, they may begin to evaluate themselves using excessively high standards and adopt self-perfectionism tendencies. Broadly defined, self-perfectionism involves very critical evaluations of the self. Perfectionism may also come from others and may manifest as socially prescribed perfectionism, and young adults are reporting higher levels of socially prescribed perfectionism than previous generations. This rising perfectionism is also associated with anxiety, greater physiological reactivity, and a sense of social disconnection. However, theories from psychology suggest that improvement in emotion regulation can contribute to enhanced psychological and emotional well-being. Emotion regulation refers to the ways people manage how and when they experience and express their emotions. Cognitive reappraisal and expressive suppression are common emotion regulation strategies. Cognitive reappraisal involves changing the meaning of a stimulus that involves construing a potentially emotion-eliciting situation in a way that changes its emotional impact. By contrast, expressive suppression involves inhibiting the behavioral expression of emotion. The purpose of this research is to examine the efficacy of social marketing initiatives which promote emotion regulation strategies to help young adults regulate their emotions. In Study 1 a single factor (emotional regulation strategy: a cognitive reappraisal, expressive, control) between-subjects design was conducted using an online, non-student consumer panel (n=96). Sixty-eight percent of participants were male, and 32% were female. Study participants belonged to the Millennial and Gen Z cohort, ranging in age from 22 to 35 (M=27). Participants were first told to spend at least three minutes writing about a public speaking appearance which made them anxious. The purpose of this exercise was to induce anxiety. Next, participants viewed one of three advertisements (randomly assigned) which promoted an emotion regulation strategy—cognitive reappraisal, expressive suppression, or an advertisement non-emotional in nature. After being exposed to one of the ads, participants responded to a measure composed of two items to access their emotional state and the efficacy of the messages in fostering emotion management. Findings indicated that individuals in the cognitive reappraisal condition (M=3.91) exhibited the most positive feelings and more effective emotion regulation than the expressive suppression (M=3.39) and control conditions (M=3.72, F(1,92) = 3.3, p<.05). Results from this research can be used by institutions (e.g., schools) in taking a leadership role in attacking anxiety and other mental health issues. Social stigmas regarding mental health can be removed and a more proactive stance can be taken in promoting healthy coping behaviors and strategies to manage negative emotions.

Keywords: emotion regulation, anxiety, social marketing, generation z

Procedia PDF Downloads 205

Authors: Georgios Samaras

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New media such as Facebook, YouTube and Twitter introduced the world to a new era of instant communication. An era where online interactions could replace a lot of offline actions. Technology can create a mediated environment in which participants can communicate (one-to-one, one-to-many, and many-to-many) both synchronously and asynchronously and participate in reciprocal message exchanges. Currently, social networks are attracting similar academic attention to that of the internet after its mainstream implementation into public life. Websites and platforms are seen as the forefront of a new political change. There is a significant backdrop of previous methodologies employed to research the effects of social networks. New approaches are being developed to be able to adapt to the growth of social networks and the invention of new platforms. Golden Dawn was the first openly neo-Nazi party post World War II to win seats in the parliament of a European country. Its racist rhetoric and violent tactics on social networks were rewarded by their supporters, who in the face of Golden Dawn’s leaders saw a ‘new dawn’ in Greek politics. Mainstream media banned its leaders and members of the party indefinitely after Ilias Kasidiaris attacked Liana Kanelli, a member of the Greek Communist Party, on live television. This media ban was seen as a treasonous move by a significant percentage of voters, who believed that the system was desperately trying to censor Golden Dawn to favor mainstream parties. The shocking attack on live television received international coverage and while European countries were condemning this newly emerged neo-Nazi rhetoric, almost 7 percent of the Greek population rewarded Golden Dawn with 18 seats in the Greek parliament. Many seem to think that Golden Dawn mobilised its voters online and this approach played a significant role in spreading their message and appealing to wider audiences. No strict online censorship existed back in 2012 and although Golden Dawn was openly used neo-Nazi symbolism, it was allowed to use social networks without serious restrictions until 2017. This paper used qualitative methods to investigate Golden Dawn’s rise in social networks from 2012 to 2019. The focus of the content analysis was set on three social networking platforms: Facebook, Twitter and YouTube, while the existence of Golden Dawn’s website, which was used as a news sharing hub, was also taken into account. The content analysis included text and visual analyses that sampled content from their social networking pages to translate their political messaging through an ideological lens focused on extreme-right populism. The absence of hate speech regulations on social network platforms in 2012 allowed the free expression of those heavily ultranationalist and populist views, as they were employed by Golden Dawn in the Greek political scene. On YouTube, Facebook and Twitter, the influence of their rhetoric was particularly strong. Official channels and MPs profiles were investigated to explore the messaging in-depth and understand its ideological elements.

Keywords: populism, far-right, social media, Greece, golden dawn

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Authors: Edite Kulmane, Mara Pilmane, Romans Lacis

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Introduction: Acquired heart diseases remain one of the leading health care problems in the world. Changes in myocardium of the diseased hearts are complex and pathogenesis is still not fully clear. The aim of this study was to identify appearance and distribution of apoptosis, homeostasis regulating factors, and innervation and ischemia markers in right atrial tissue in different acquired heart diseases. Methods: During elective open heart surgery were taken right atrial tissue fragments from 12 patients. All patients were operated because of acquired heart diseases- aortic valve stenosis (5 patients), coronary heart disease (5 patients), coronary heart disease and secondary mitral insufficiency (1 patient) and mitral disease (1 patient). The mean age was (mean±SD) 70,2±7,0 years (range 58-83 years). The tissues were stained with haematoxylin and eosin methods for routine light-microscopical examination and for immunohistochemical detection of protein gene peptide 9.5 (PGP 9.5), human atrial natriuretic peptide (hANUP), vascular endothelial growth factor (VEGF), chromogranin A and endothelin. Apoptosis was detected by TUNEL method. Results: All specimens showed degeneration of cardiomyocytes with lysis of myofibrils, diffuse vacuolization especially in perinuclear region, different size of cells and their nuclei. The severe invasion of connective tissue was observed in main part of all fragments. The apoptotic index ranged from 24 to 91%. One specimen showed region of newly performed microvessels with cube shaped endotheliocytes that were positive for PGP 9.5, endothelin, chromogranin A and VEGF. From all fragments, taken from patients with coronary heart disease, there were observed numerous PGP 9.5-containing nerve fibres, except in patient with secondary mitral insufficiency, who showed just few PGP 9.5 positive nerves. In majority of specimens there were regions observed with cube shaped mixed -VEGF immunoreactive endocardial and epicardial cells. Only VEGF positive endothelial cells were observed just in few specimens. There was no significant difference of hANUP secreting cells among all specimens. All patients operated due to the coronary heart disease moderate to numerous number of chromogranin A positive cells were seen while in patients with aortic valve stenosis tissue demonstrated just few factor positive cells. Conclusions: Complex detection of different factors may indicate selectively disordered morphopathogenetical event of heart disease: decrease of PGP 9.5 nerves suggests the decreased innervation of organ; increased apoptosis indicates the cell death without ingrowth of connective tissue; persistent presence of hANUP proves the unchanged homeostasis of cardiomyocytes probably supported by expression of chromogranins. Finally, decrease of VEGF detects the regions of affected blood vessels in heart affected by acquired heart disease.

Keywords: heart, apoptosis, protein-gene peptide 9.5, atrial natriuretic peptide, vascular endothelial growth factor, chromogranin A, endothelin

Procedia PDF Downloads 295