Search results for: genes expression

Authors: Fruzsina Luca Kézér, Viktor Jurkovich, Ottó Szenci, János Tőzsér, Levente Kovács

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Positive interaction between people and animals could have a favorable effect on the welfare and production by reducing stress levels. However, to the repeated contact with humans (e.g. farm staff, veterinarians or herdsmen), animals may respond with escape behavior or avoidance, which both have negative effects on the ease of handling, welfare and may lead to the expression of aggressive behaviors. Rough or aversive handling can impair health and the function of the cardiac autonomic activity due to fear and stress, which also can be determined by certain parameters of heart rate variability (HRV). Although the essential relationships between fear from humans and basal tone of the autonomic nervous system were described by the authors previously, several questions remained unclear in terms of the associations between different coping strategies (behavioral syndromes) of the animals and physiological responsiveness to humans. The main goal of this study was to find out whether human behavior and emotions to the animals have an impact on cardiac function and behavior of animals with different coping styles in response situations. Therefore, in the present study, special (fear, approaching, restraint, novel arena, novel object) tests were performed on healthy, 2-year old heifers (n = 104) differing in coping styles [reactive (passive) vs. proactive (active) coping]. Animals were categorized as reactive or proactive based on the following tests: 1) aggressive behavior at the feeding bunk, 2) avoidance from an approaching person, 3) immobility, and 4) daily activity (number of posture changes). Heart rate, the high frequency (HF) component of HRV as a measure of vagal activity and the ratio between the low frequency (LF) and HF components (LF/HF ratio) as a parameter of sympathetic nervous system activity were calculated for all individual during lying posture (baseline) and for response situations in novel object, novel arena, and unfamiliar person tests (both for 5 min), respectively. The differences between baseline and response were compared between groups. Higher sympathetic (higher heart rates and LF/HF ratios) and lower parasympathetic activity (lower HF) was found for proactive animals in response situations than for reactive (passive) animals either during the novel object, the novel arena and the unfamiliar person test. It suggests that animals with different behavioral traits differ in their immediate autonomic adaptation to novelty and people. Based on our preliminary results, it seems, that the analysis of HRV can help to understand the physiological manifestation of responsiveness to novelty and human presence in dairy cattle with different behavioral syndromes.

Keywords: behavioral syndromes, human-cattle interaction, novel arena test, physiological responsiveness, proactive coping, reactive coping

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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Authors: Sandra Christina Gressler

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Resting is essentially the physical and mental relaxation. So, can behaviors that go beyond the merely physical relaxation to some extent be understood as a behavior of restoration? Studies on restorative environments emphasize the physical, mental and social benefits that some environments can provide and suggest that activities in natural environments reduce the stress of daily lives, promoting recovery against the daily wear. These studies, though specific in their results, do not unify the different possibilities of restoration. Considering the importance of restorative environments by promoting well-being, this research aims to verify the applicability of the theory on restorative environments in a Brazilian context, inquiring about the environment/behavior of rest. The research sought to achieve its goals by; a) identifying daily ways of how participants interact/connect with nature; b) identifying the resting environments/behavior; c) verifying if rest strategies match the restorative environments suggested by restorative studies; and d) verifying different rest strategies related to time. Workers from different companies in which certain functions require focused attention, and high school students from different schools, participated in this study. An interview was used to collect data and information. The data obtained were compared with studies of attention restoration theory and stress recovery. The collected data were analyzed through the basic descriptive inductive statistics and the use of the software ALCESTE® (Analyse Lexicale par Contexte d'un Ensemble de Segments de Texte). The open questions investigate perception of nature on a daily basis – analysis using ALCESTE; rest periods – daily, weekends and holidays – analysis using ALCESTE with tri-croisé; and resting environments and activities – analysis using a simple descriptive statistics. According to the results, environments with natural characteristics that are compatible with personal desires (physical aspects and distance) and residential environments when they fulfill the characteristics of refuge, safety, and self-expression, characteristics of primary territory, meet the requirements of restoration. Analyzes suggest that the perception of nature has a wide range that goes beyond the objects nearby and possible to be touched, as well as observation and contemplation of details. The restoration processes described in the studies of attention restoration theory occur gradually (hierarchically), starting with being away, following compatibility, fascination, and extent. They are also associated with the time that is available for rest. The relation between rest behaviors and the bio-demographic characteristics of the participants are noted. It reinforces, in studies of restoration, the need to insert not only investigations regarding the physical characteristics of the environment but also behavior, social relationship, subjective reactions, distance and time available. The complexity of the theme indicates the necessity for multimethod studies. Practical contributions provide subsidies for developing strategies to promote the welfare of the population.

Keywords: attention restoration theory, environmental psychology, rest behavior, restorative environments

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Authors: Vaidehi Raipat

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A city is an expression of coexistence between its users and built environment. The way in which its spaces are animated signify the quality of this coexistence. Urban sustainability is the ability of a city to respond efficiently towards its people, culture, environment, visual image, history, visions and identity. The quality of built environment determines the quality of our lifestyles, but poor ability of the built environment to adapt and sustain itself through the changes leads to degradation of cities. Ranchi was created in November 2000, as the capital of the newly formed state Jharkhand, located on eastern side of India. Before this Ranchi was known as summer capital of Bihar and was a little larger than a town in terms of development. But since then it has been vigorously expanding in size, infrastructure as well as population. This sudden expansion has created a stress on existing built environment. The large forest covers, agricultural land, diverse culture and pleasant climatic conditions have degraded and decreased to a large extent. Narrow roads and old buildings are unable to bear the load of the changing requirements, fast improving technology and growing population. The built environment has hence been rendered unsustainable and unadaptable through fastidious changes of present era. Some of the common hazards that can be easily spotted in the built environment are half-finished built forms, pedestrians and vehicles moving on the same part of the road. Unpaved areas on street edges. Over-sized, bright and randomly placed hoardings. Negligible trees or green spaces. The old buildings have been poorly maintained and the new ones are being constructed over them. Roads are too narrow to cater to the increasing traffic, both pedestrian and vehicular. The streets have a large variety of activities taking place on them, but haphazardly. Trees are being cut down for road widening and new constructions. There is no space for greenery in the commercial as well as old residential areas. The old infrastructure is deteriorating because of poor maintenance and the economic limitations. Pseudo understanding of functionality as well as aesthetics drive the new infrastructure. It is hence necessary to evaluate the extent of sustainability of existing built environment of the city and create or regenerate the existing built environment into a more sustainable and adaptable one. For this purpose, research titled “Sustainability of the Built Environment of Ranchi District” has been carried out. In this research the condition of the built environment of Ranchi are explored so as to figure out the problems and shortcomings existing in the city and provide for design strategies that can make the existing built-environment sustainable. The built environment of Ranchi that include its outdoor spaces like streets, parks, other open areas, its built forms as well as its users, has been analyzed in terms of various urban design parameters. Based on which strategies have been suggested to make the city environmentally, socially, culturally and economically sustainable.

Keywords: adaptable, built-environment, sustainability, urban

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Authors: Shamim Mushtaq, Moazzam Shahid

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Breast cancer (BC) claims the lives of half a million women every year and is the most common cause of death in the developing world. In 2019, it was estimated that BC alone accounts for 15% of all cancer deaths in younger women (aged < 45 years old) with advanced-stage lung metastasis. According to the World Health Organization & International Union against Cancer, in Asia, a high number of cancer-related deaths will be observed in 2020, whereas the burden will be reduced in Western countries due to awareness about the disease, better health facilities and advanced treatments. In the last 15 years, it has been reported that the incidence of BC has increased by 1.1% among Asian compared to the US population from 2003 to 2012. To date, several BC biological subtypes have been reported so far, which are associated with different treatment responses. The heterogeneity and diversity of BC reflected these different subtypes, including Luminal A (23.7% prevalence) and B (38.8% prevalence) that have pathological estrogen receptor (ER+)-positive tumors, the human epidermal growth factor receptor 2 (HER2) (11.2% prevalence) and triple-negative breast cancer (TNBC) (25% prevalence). According to Shaukat Khanum Memorial Cancer Hospital and Research Centre – Pakistan, ten years of data showed that among 636 BC patients, 30.5% had TNBC who were <40 years of age, which is an extremely alarming situation. Therefore, there is a dire need to explore and develop therapeutic targets for the treatment of early TNBC. Since the last decade, unfortunately, there has been little success in understanding the complexity of TNBC and in discovering new biological therapeutic targets. However, conventional chemotherapy is the only choice of treatment for TNBC patients. Many investigators revealed advances in multi-omics (multiple "omes", e.g., genome, proteome, transcriptome, epigenome, and microbiome) which were later identified as actionable targets and increased prevalence in TNBC patients. However, various drugs have been identified so far which are related to a particular diagnostic and prognostic biomarker. For example, Epidermal growth factor receptor ( EGFR or ErbB-1), HER-2/neu (ErbB-2), HER-3 (ErbB-3), and HER-4 (ErbB-4). Protein Transglin-2 (TAGLN 2 ) and Profilins-1 (Pfn-1 ) are the ubiquitously expressed large family of proteins present in all eukaryotes, enabling actin cytoskeletal reorganization. It is known that the oncogenic transformation of cells is accompanied by alteration in the actin cytoskeleton. There are causal connections between altered expression of actin cytoskeletal regulators and cancer progression. Our case-control study identified TAGLN-2 and Pfn-1 proteins in TNBC blood by mass spectrometry. Both TAGLN-2 and Pfn-1 proteins are differentially expressed in early and advanced stages of TNBS patients, which could be potential predictors or therapeutic targets for TNBC.

Keywords: TNBC, blood biomarkers, mass spectrometry, qPCR, ELISA

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Authors: Sudipta Garai

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Films as a cultural, social practice remains a dominant space for creation and destruction of ideologies and practices which make the sociological viewing, analysis, and interpretation of the same a complex affair. It remains the doorway between the interpretations and understanding of the writer/director and the reader/viewer. India, being a multi-linguistic culture, the media plays a much intriguing role than that of newspaper, books, stories, novels or any other medium of expression. Known to be the largest democracy, the State seem to guarantee and safeguard people’s choices and life of dignity through its Fundamental Rights and Directives. However, the laws contradict themselves when it comes to IPC 377 criminalizing anything except penovaginal sexual intercourse restricting alternative sexual preferences and practices questioning its sense of ‘democracy.' In this context, the issue of homosexuality came up in bits and pieces through various representations in ‘popular’ cinema mostly with sudden references of mockery and laughter where the explicit narratives of ‘queer’ seemed missing. Rituparno Ghosh, an eminent film maker of Bengal, came up as the ‘queer’ face in Kolkata specifically through his ‘queer’ trilogy (Memories in March, 2010; Arekti Premer Golpo, 2010; Chitrangada: A Crowning Wish, 2012) coming out of his own closet and speaking about his own sexual choices not only through the explicit narratives in films but also in person which made these films an important point of departure in Bengali film history. A sociological reading of these films through a discourse analysis is being done with the critical questions of ‘choice,' ’freedom,' ‘love and marriage’ and most importantly the ‘change.' This study not only focuses on the films and its analysis of content but also to engage with its audience, queer and not in order to extend beyond the art form into the actual vulnerabilities of life and experiences through informal interviews, focused group discussions and engaging with the real life narratives. A research of this kind is always looked upon as a medium of change hoping for a better world wiping away the discrimination and ‘shame’ the ‘queer’ faces in their everyday life, but a social science research is limited but its ‘time’ and academic boundary where the hope of change might be initiated but not fulfilled. The experiences and reflections of the ‘queer’ not only redefined the narratives of the films but also me as a researcher. The perspectives of the ‘hetero-normative’ informants gave a broader picture of the study and the socio-cultural complications that are intrigued with the ideas of resistance and change. The issues on subjectivity, power, and position couldn’t be wiped out in a study of this kind as both politics and aesthetics become integrated with each other in the creation of any art form be it films or a study of research.

Keywords: cinema, alternative sexualities, narratives, sexual choices, state and society

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Authors: Drago Bratkovic, Curtis Gravance, David Ketteridge, Ravi Krishnan, Michael Imperiale

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The mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases that have a common defect in the catabolism of glycosaminoglycans (GAGs). MPS I is the most common of the MPS diseases. Manifestations of MPS I include coarsening of facial features, corneal clouding, developmental delay, short stature, skeletal manifestations, hearing loss, cardiac valve disease, hepatosplenomegaly, and umbilical and inguinal hernias. Treatments for MPS I restore or activate the missing or deficient enzyme in the case of enzyme replacement therapy (ERT) and haematopoietic stem cell transplantation (HSCT). Pentosan polysulfate sodium (PPS) is a potential treatment to improve bone and joint manifestations of MPS I. The mechanisms of action of PPS that are relevant to the treatment of MPS I are the ability to: (i) Reduce systemic and accumulated GAG, (ii) Reduce inflammatory effects via the inhibition of NF-kB, resulting in the reduction in pro-inflammatory mediators. (iii) Reduce the expression of the pain mediator nerve growth factor in osteocytes from degenerating joints. (iv) Inhibit the cartilage degrading enzymes related to joint dysfunction in MPS I. PPS is being evaluated as an adjunctive therapy to ERT and/or HSCT in an open-label, single-centre, phase 2 study. Patients are ≥ 5 years of age with a diagnosis of MPS I and previously received HSCT and/or ERT. Three white, female, patients with MPS I-Hurler, ages 14, 15, and 19 years, and one, white male patient aged 15 years are enrolled. All were diagnosed at ≤2 years of age. All patients received HSCT ≤ 6 months after diagnosis. Two of the patients were treated with ERT prior to HSCT, and 1 patient received ERT commencing 3 months prior to HSCT. Two patients received 0.75mg/kg and 2 patients received 1.5mg/kg of PPS. PPS was well tolerated at doses of 0.75 and 1.5 mg/kg to 47 weeks of continuous dosing. Of the 19 adverse events (AEs), 2 were related to PPS. One AE was moderate (pre-syncope) and 1 was mild (injection site bruising), experienced in the same patient. All AEs were reported as mild or moderate. There have been no SAEs. One subject experienced a COVID-19 infection and PPS was interrupted. The MPS I signature GAG fragments, sulfated disaccharide and UA-HNAc S, tended to decrease in 3 patients from baseline through Week 25. Week 25 GAG data are pending for the 4th patient. Overall, most biomarkers (inflammatory, cartilage degeneration, and bone turnover) evaluated in the 3 patients with 25-week assessments have indicated either no change or a reduction in levels compared to baseline. In 3 patients, there was a trend toward improvement in the 2MWT from baseline to Week 48 with > 100% increase in 1 patient (01-201). In the 3 patients that had Week 48 assessments, patients and proxies reported improvement in PGIC, including “worthwhile difference” (n=1), or “made all the difference” (n=2).

Keywords: MPS I, pentosan polysulfate sodium, clinical study, 2MWT, QoL

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Authors: Tomasz Lewinski

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The right to know becomes gradually recognised as an increasing number of states adopts national legislations regarding access to state-held information. Laws differ from each other in the scope of the right to information (hereinafter: RTI). In all regimes of RTI, there are exceptions from the general notion of the right. States’ authorities too often use exceptions to justify refusals to requests for state-held information. This paper sets out how states hamper RTI basing on the notion of exception and by not providing an effective procedure that could redress unlawful denials. This paper bases on two selected examples of RTI incorporation into the national legal regime, United Kingdom, and South Africa. It succinctly outlines the international standard given in Article 19 of the International Covenant on Civil and Political Rights (hereinafter: ICCPR) and its influence on the RTI in selected countries. It shortly demonstrates as a background to further analysis the Human Rights Committee’s jurisprudence and standards articulated by successive Special Rapporteurs on freedom of opinion and expression. Subsequently, it presents a brief comparison of these standards with the regional standards, namely the African Charter on Human and Peoples' Rights and the European Convention on Human Rights. It critically discusses the regimes of exceptions in RTI legislations in respective national laws. It shows how excessive these regimes are, what implications they have for the transparency in general. Also, the objective is to divide exceptions enumerated in legislations of selected states in relation to exceptions provided in Article 19 of the ICCPR. Basing on the established division of exceptions by its natures, it compares both regimes of exceptions related to the principle of national security. That is to compare jurisprudence of domestic courts, and overview practices of states’ authorities applied to RTI requests. The paper evaluates remedies available in legislations, including contexts of the length and costs of the subsequent proceedings. This provides a general assessment of the given mechanisms and present potential risks of its ineffectiveness. The paper relies on examination of the national legislations, comments of the credible non-governmental organisations (e.g. The Public's Right to Know Principles on Freedom of Information Legislation by the Article 19, The Tshwane Principles on National Security and the Right to Information), academics and also the research of the relevant judgements delivered by domestic and international courts. Conclusion assesses whether selected countries’ legislations go in line with international law and trends, whether the jurisprudence of the regional courts provide appropriate benchmarks for national courts to address RTI issues effectively. Furthermore, it identifies the largest disadvantages of current legislations and to what outcomes it leads in domestic courts jurisprudences. In the end, it provides recommendations and policy arguments for states to improve transparency and support local organisations in their endeavours to establish more transparent states and societies.

Keywords: access to information, freedom of information, national security, right to know, transparency

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Authors: Joseph Falzon, Margaret Nelson

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Background: Regeneration and re-use of abandoned historic buildings present a continuous challenge for policy makers and stakeholders in the tourism and leisure industry. Obsolete historic buildings provide great potential for tourism and leisure accommodation, presenting unique heritage experiences to travellers and host communities. Contemporary demands in the hospitality industry continuously require higher standards, some of which are in conflict with heritage conservation principles. Objective: The aim of this research paper is to critically discuss regeneration policies with stakeholders of the tourism and leisure industry and to examine current practices in policy development and the resultant impact of policies on the Maltese tourism and leisure industry. Research Design: Six semi-structured interviews with stakeholders involved in the tourism and leisure industry participated in the research. A number of measures were taken to reduce bias and thus improve trustworthiness. Clear statements of the purpose of the research study were provided at the start of each interview to reduce expectancy bias. The interviews were semi-structured to minimise interviewer bias. Interviewees were allowed to expand and elaborate as necessary, with only necessary probing questions, to allow free expression of opinion and practices. Interview guide was submitted to participants at least two weeks before the interview to allow participants to prepare for the interview and prevent recall bias during the interview as much as possible. Interview questions and probes contained both positive and negative aspects to prevent interviewer bias. Policy documents were available during the interview to prevent recall bias. Interview recordings were transcribed ‘intelligent’ verbatim. Analysis was carried out using thematic analysis with the coding frame developed independently by two researchers. All phases of the study were governed by research ethics. Findings: Findings were grouped in main themes: financing of regeneration, governance, legislation and policies. Other key issues included value of historic buildings and approaches for regeneration. Whist regeneration of historic buildings was noted, participants discussed a number of barriers that hindered regeneration. Stakeholders identified gaps in policies and gaps at policy implementation stages. European Union funding policies facilitated regeneration initiatives but funding criteria based on economic deliverables presented the intangible heritage gap. Stakeholders identified niche markets for heritage tourism accommodation. Lack of research-based policies was also identified. Conclusion: Potential of regeneration is hindered by inadequate legal framework that supports contemporary needs of the tourism industry. Policies should be developed by active stakeholder participation. Adequate funding schemes have to support the tangible and intangible components of the built heritage.

Keywords: governance, historic buildings, policy, tourism

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Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

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Authors: Smita Lahkar

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Sattriya, the youngest of the eight principal Classical Indian dance traditions, has undergone too many changes and modifications to arrive at its present stage of performing art form extracting itself from age-old religious confinement. Although some of the other traditions have been revived in the recent past, Sattriya has a living tradition since its inception in the 15th century by Srimanta Sankardeva, the great Vaishnavite saint, poet, playwright, lyricist, painter, singer and dancer of Assam, a primary north-eastern state of India. This living dance tradition from the Sattras, the Vaishnavite monasteries, has been practiced for over five hundred years by celibate male monks, as a powerful medium for propagating the Vaishnava religious faith. Sankardeva realised the potential of the vocalised word integrated with the visual image as a powerful medium of expression and communication. So he used this principal medium for propagating his newly found message of devotion among the people of his time. Earlier, Sattriya was performed by male monks alone in monasteries (Sattras) as a part of daily rituals. The females were not even allowed to learn this art form. But, in present time, Sattriya has come out from the Sattras to proscenium stage, performed mostly by female as well as few male dancers also. The technique of performing movements, costumes, ornaments, music and style of performance too have experienced too many changes and modifications. For example, earlier and even today in Sattra, the ‘Pataka’ hand gesture is depicted in conformity with the original context (religious) of creation of the dance form. But, today stage-performers prefer the instructions of the scripture ‘Srihastamuktavali’ and depict the ‘Pataka’ in a sophisticated manner affecting decontextualisation to a certain extent. This adds aesthetic beauty to the dance form as an art distancing it from its context of being a vehicle for propagating Vaishnava religion. The Sattriya dance today stands at the crossroads of past and future, tradition and modernity, devotion and display, spirituality and secularism. The traditional exponents trained under the tutelage of Sattra maestros and imbibing a devotionally inspired rigour of the religion, try to retain the traditional nuances; while the young artists being trained outside the monasteries are more interested in taking up the discipline purely from the perspective of ‘performing arts’ bereft of the philosophy of religion or its sacred associations. Hence, this paper will be an endeavor to establish the hypothesis that the Sattriya, whose origin was for propagating Vaishnava faith, has now entered the world of performing arts with highly aesthetical components. And as a transformed art form, Sattriya may be expected to carve a niche in world dance arena. This will be done with the help of historical evidences, observations from the recorded past and expert rendezvous.

Keywords: dance, performing art, religion, Sattriya

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Authors: Jesús Horacio, Alfredo Ollero, Víctor Bouzas-Blanco, Augusto Pérez-Alberti

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Rivers have traditionally been classified, assessed and managed in terms of hydrological, chemical and / or biological criteria. Geomorphological classifications had in the past a secondary role, although proposals like River Styles Framework, Catchment Baseline Survey or Stroud Rural Sustainable Drainage Project did incorporate geomorphology for management decision-making. In recent years many studies have been attracted to the geomorphological component. The geomorphological processes and their associated forms determine the structure of a river system. Understanding these processes and forms is a critical component of the sustainable rehabilitation of aquatic ecosystems. The fluvial auto-classification approach suggests that a river is a self-built natural system, with processes and forms designed to effectively preserve their ecological function (hydrologic, sedimentological and biological regime). Fluvial systems are formed by a wide range of elements with multiple non-linear interactions on different spatial and temporal scales. Besides, the fluvial auto-classification concept is built using data from the river itself, so that each classification developed is peculiar to the river studied. The variables used in the classification are specific stream power and mean grain size. A discriminant analysis showed that these variables are the best characterized processes and forms. The statistical technique applied allows to get an individual discriminant equation for each geomorphological type. The geomorphological classification was developed using sites with high naturalness. Each site is a control point of high ecological and geomorphological quality. The changes in the conditions of the control points will be quickly recognizable, and easy to apply a right management measures to recover the geomorphological type. The study focused on Galicia (NW Spain) and the mapping was made analyzing 122 control points (sites) distributed over eight river basins. In sum, this study provides a method for fluvial geomorphological classification that works as an open and flexible tool underlying the fluvial auto-classification concept. The hydrographic mapping is the visual expression of the results, such that each river has a particular map according to its geomorphological characteristics. Each geomorphological type is represented by a particular type of hydraulic geometry (channel width, width-depth ratio, hydraulic radius, etc.). An alteration of this geometry is indicative of a geomorphological disturbance (whether natural or anthropogenic). Hydrographic mapping is also dynamic because its meaning changes if there is a modification in the specific stream power and/or the mean grain size, that is, in the value of their equations. The researcher has to check annually some of the control points. This procedure allows to monitor the geomorphology quality of the rivers and to see if there are any alterations. The maps are useful to researchers and managers, especially for conservation work and river restoration.

Keywords: fluvial auto-classification concept, mapping, geomorphology, river

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Authors: Lucas Derks, Christine Beenhakker, Michiel Brandt, Gert Arts, Ruud van Langeveld

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Background: The method Depression in Awareness Space (DAS) is a psychotherapeutic intervention technique based on the principles of spatial cognition and imagination therapy with spatial components. The basic assumptions are: mental space is the primary organizing principle in the mind, and all psychological issues can be treated by first locating and by next relocating the conceptualizations involved. The most clinical experience was gathered over the last 20 years in the area of social issues (with the social panorama model). The latter work led to the conclusion that a mental object (image) gains emotional impact when it is placed more central, closer and higher in the visual field – and vice versa. Changing the locations of mental objects in space thus alters the (socio-) emotional meaning of the relationships. The experience of depression seems always associated with darkness. Psychologists tend to see the link between depression and darkness as a metaphor. However, clinical practice hints to the existence of more literal forms of darkness. Aims: The aim of the method Depression in Awareness Space is to reduce the distress of clients with depression in the clinical counseling practice, as a reliable alternative method of psychological therapy for the treatment of depression. The method Depression in Awareness Space aims at making dark areas smaller, lighter and more transparent in order to identify the problem or the cause of the depression which lies behind the darkness. It was hypothesized that the darkness is a subjective side-effect of the neurological process of repression. After reducing the dark clouds the real problem behind the depression becomes more visible, allowing the client to work on it and in that way reduce their feelings of depression. This makes repression of the issue obsolete. Results: Clients could easily get into their 'sadness' when asked to do so and finding the location of the dark zones proved pretty easy as well. In a recent pilot study with five participants with mild depressive symptoms (measured on two different scales and tested against an untreated control group with similar symptoms), the first results were also very promising. If the mental spatial approach to depression can be proven to be really effective, this would be very good news. The Society of Mental Space Psychology is now looking for sponsoring of an up scaled experiment. Conclusions: For spatial cognition and the research into spatial psychological phenomena, the discovery of dark areas can be a step forward. Beside out of pure scientific interest, it is great to know that this discovery has a clinical implication: when darkness can be connected to depression. Also, darkness seems to be more than metaphorical expression. Progress can be monitored over measurement tools that quantify the level of depressive symptoms and by reviewing the areas of darkness.

Keywords: depression, spatial cognition, spatial imagery, social panorama

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Authors: Rafael Santos, Clara Pimenta Do Vale, Barbara Bogoni, Poul Henning Kirkegaard

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In the last decades, the relevance of hand drawing has decreased in the scope of architectural education. However, some schools continue to recognize its decisive role, not only in the architectural design teaching, but in the whole of architectural training. With this paper it is intended to present the results of a research developed on the following problem: the practise of hand drawing as a premier form of representation in architectural design teaching. The research had as its object the educational model of the Faculty of Architecture of the University of Porto (FAUP) and was led by three main objectives: to identify the circumstance that promoted hand drawing as a form of representation in FAUP's model; to characterize the types of hand drawing and their role in that model; to determine the particularities of hand drawing as a premier form of representation in architectural design teaching. Methodologically, the research was conducted according to a qualitative embedded single-case study design. The object – i.e., the educational model – was approached in FAUP case considering its Context and three embedded unities of analysis: the educational Purposes, Principles and Practices. In order to guide the procedures of data collection and analysis, a Matrix for the Characterization (MCC) was developed. As a methodological tool, the MCC allowed to relate the three embedded unities of analysis with the three main sources of evidence where the object manifests itself: the professors, expressing how the model is Assumed; the architectural design classes, expressing how the model is Achieved; and the students, expressing how the model is Acquired. The main research methods used were the naturalistic and participatory observation, in-person-interview and documentary and bibliographic review. The results reveal that the educational model of FAUP – following the model of the former Porto School – was largely due to the methodological foundations created with the hand drawing teaching-learning processes. In the absence of a culture of explicit theoretical elaboration or systematic research, hand drawing was the support for the continuity of the school, an expression of a unified thought about what should be the reflection and practice of architecture. As a form of representation, hand drawing plays a transversal role in the entire educational model, since its purposes are not limited to the conception of architectural design – it is also a means for perception, analysis and synthesis. Regarding the architectural design teaching, there seems to be an understanding of three complementary dimensions of didactics: the instrumental, methodological and propositional dimension. At FAUP, hand drawing is recognized as the common denominator among these dimensions, according to the idea of "globality of drawing". It is expected that the knowledge base developed in this research may have three main contributions: to contribute to the maintenance and valorisation of FAUP’s model; through the precise description of the methodological procedures, to contribute by transferability to similar studies; through the critical and objective framework of the problem underlying the hand drawing in architectural design teaching, to contribute to the broader discussion concerning the contemporary challenges on architectural education.

Keywords: architectural design teaching, architectural education, forms of representation, hand drawing

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Authors: D. Cole, S. Mahootian, P. Medlock

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This research contributes to existing knowledge of the complexities surrounding women’s relationship to beauty standards by examining their lived experiences. While there is much academic work on the effects of culturally imposed and largely unattainable beauty standards, the arguments tend to fall into two paradigms. On the one hand is the radical feminist perspective that argues that women are subjected to absolute oppression within the patriarchal system in which beauty standards have been constructed. This position advocates for a complete restructuring of social institutions to liberate women from all types of oppression. On the other hand, there are liberal feminist arguments that focus on choice, arguing that women’s agency in how to present themselves is empowerment. These arguments center around what women do within the patriarchal system in order to liberate themselves. However, there is very little research on the lived experiences of women negotiating these two realms: the complex negotiation between the pressure to adhere to cultural beauty standards and the agency of self-expression and empowerment. By exploring beauty standards through the intersection of societal messages (including macro-level processes such as social media and advertising as well as smaller-scale interactions such as families and peers) and lived experiences, this study seeks to provide a nuanced understanding of how women navigate and negotiate their own presentation and sense of self-identity. Current research sees a rise in incidents of body dysmorphia, depression and anxiety since the advent of social media. Approximately 91% of women are unhappy with their bodies and resort to dieting to achieve their ideal body shape, but only 5% of women naturally possess the body type often portrayed by Americans in movies and media. It is, therefore, crucial we begin talking about the processes that are affecting self-image and mental health. A question that arises is that, given these negative effects, why do companies continue to advertise and target women with standards that very few could possibly attain? One obvious answer is that keeping beauty standards largely unattainable enables the beauty and fashion industries to make large profits by promising products and procedures that will bring one up to “standard”. The creation of dissatisfaction for some is profit for others. This research utilizes qualitative methods: interviews, questionnaires, and focus groups to investigate women’s relationships to beauty standards and empowerment. To this end, we reached out to potential participants through a video campaign on social media: short clips on Instagram, Facebook, and TikTok and a longer clip on YouTube inviting users to take part in the study. Participants are asked to react to images, videos, and other beauty-related texts. The findings of this research have implications for policy development, advocacy and interventions aimed at promoting healthy inclusivity and empowerment of women.

Keywords: women, beauty, consumerism, social media

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Authors: Daniel O. Kleinsman

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The 2019 terrorist attack on two masjidain in Christchurch, New Zealand, was a shocking demonstration of the harm that can be caused by hate crime. As legal and governmental responses to the attack struggle to provide effective remedies to its victims, restorative justice has emerged as a tool that can assist, in terms of both meeting victims’ needs and discharging the obligations of the state under the International Covenant on Civil and Political Rights (ICCPR), arts 2(3), 26, 27. Restorative justice is a model that emphasizes the repair of harm caused or revealed by unjust behavior. It also prioritises the facilitation of dialogue, the restoration of equitable relationships, and the prevention of future harm. Returning to the case study, in the remarks of the sentencing judge, the terrorist’s actions were described as a hate crime of vicious malevolence that the Court was required to decisively reject, as anathema to the values of acceptance, tolerance and mutual respect upon which New Zealand’s inclusive society is based and which the country strives to maintain. This was one of the reasons for which the terrorist received a life sentence with no possibility of parole. However, in the report of the Royal Commission of Inquiry into the Attack, it was found that victims felt the attack occurred within the context of widespread racism, discrimination and Islamophobia, where hostile behaviors, including hate-based threats and attacks, were rarely recorded, analysed or acted on. It was also found that the Government had inappropriately concentrated intelligence resources on the risk of ‘Islamist’ terrorism and had failed to adequately respond to concerns raised about threats against the Muslim community. In this light, the remarks of the sentencing judge can be seen to reflect a criminal justice system that, in the absence of other remedies, denies systemic accountability and renders hate crime an isolated incident rather than an expression of more widespread discrimination and hate to be holistically addressed. One of the recommendations of the Royal Commission was to explore with victims the desirability and design of restorative justice processes. This presents an opportunity for victims to meet with state representatives and pursue effective remedies (ICCPR art 2(3)) not only for the harm caused by the terrorist but the harm revealed by a system that has exposed the minority Muslim community in New Zealand to hate in all forms, including but not limited to violent extremism. In this sense, restorative justice can also assist the state in discharging its wider obligations to protect all persons from discrimination (art 26) and allow ethnic and religious minorities to enjoy their own culture and profess and practice their own religion (art 27). It can also help give effect to the law and its purpose as a remedy to hate crime, as expressed in this case study by the sentencing judge.

Keywords: hate crime, restorative justice, minorities, victims' rights

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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: 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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