Search results for: toehold mediated DNA switch

Authors: Catherine Harrison

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Faced with arrest, imprisonment and the denazification process in 1945, Tübingen University’s Professor of Theology, Gerhard Kittel, refused to abandon the “Christian” antisemitism which he had first expounded in his Die Judenfrage [The Jewish Question] (1933 and 1934). At the heart of this paper is a critical engagement with Die Judenfrage, the first in English. Putting Die Judenfrage into dialogue with Kittel’s 1946, Meine Verteidigung [My Defence] (1945-6) exposes the remarkable consistency of Kittel’s idiosyncratic but closely argued Christian theology of antisemitism. Girdling his career as a foremost theologian, antisemite and enthusiastic supporter of Hitler and the NSDAP, the consistency between Die Judenfrage and Meine Verteidigung attests Kittel’s consistent and authentic, intellectual position. In both texts, he claims to be advancing Christian, as opposed to “vulgar” or racial, antisemitism. Yet, in the thirteen years which divide them, Kittel had mediated contact with Nazi illuminati Rudolph Hess, Alfred Rosenberg, Winnifred Wagner, Josef Goebbels and Baldur von Schirach, through his publications in various antisemitic journals. The paper argues: Die Judenfrage, as both a text and as a theme, is axiomatic to Kittel’s defence statement; and that Die Judenfrage constitutes the template of Kittel’s arcane, personal “Christian” antisemitism of which Meine Verteidigung is a faithful impression. Both are constructed on the same theologically chimeric and abstruse hypotheses regarding Volk, Spätjudentum [late Judaism] and Heilgeschichte [salvation history]. Problematising these and other definitional vagaries that make up Kittel’s “Christian” antisemitism highlight the remarkable theoretical consistency between Die Judenfrage and Meine Verteidigung. It is concluded that a deadly synergy of Nazi racial antisemitism and the New Testament antisemitism shaped Kittel’s judgement to the degree that, despite the slipstream of concentration camp footage which was shaking the foundations of post-war German academia, Meine Verteidigung is a simple restatement of the antisemitsm conveyed in Die Judenfrage.

Keywords: Gerhard Kittel, Third Reich theology, the Jewish Question, Nazi antisemitism

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Authors: S. Pradhan, D. Pradhan, G. Tripathy

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Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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Authors: Seyhan Sahan-Firat, Meryem Temiz-Resitoglu, Demet Sinem Guden, Sefika Pinar Kucukkavruk, Bahar Tunctan, Ayse Nihal Sari, Zumrut Kocak

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We hypothesized that mTOR inhibition may prevent the multiple organ failures following severe multiple tissue injury associated with increased NADPH oxidase system activity occur in zymosan-induced systemic inflammation. Therefore, we investigated the role of mTOR in oxidative/nitrosative stress associated with increase in NADPH oxidase activity in zymosan-induced systemic inflammation model in rats. Male Wistar rats received saline (4 ml/kg, i.p.) and zymosan (500 mg/kg, i.p.) at time 0. Saline, or zymosan-treated rats were given rapamycin (1 mg/kg, i.p.) 1 h after saline or zymosan injections. Rats were sacrified 4 h after zymosan challenge and kidney, heart, thoracic aorta, and superior mesenteric artery were collected. NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels were measured in tissue samples. Zymosan administration caused an increase in NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels in kidney, heart, thoracic aorta, and superior mesenteric artery. These changes caused by zymosan reversed by rapamycin, a selective mTOR inhibitor. Rapamycin alone had no effect on the parameters measured. Our results demonstrated that zymosan-induced oxidative/nitrosative stress presumably due to enhanced activity of NADPH oxidase, expression of p22phox, gp91phox, and p47phox and production of peroxynitrite were mediated by mTOR. [This work was financially supported by Research Foundation of Mersin University (2016-2-AP3-1900)].

Keywords: oxidative stress, mTOR, nitrosative stress, zymosan

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Authors: Emineh Tsegahun Gedif

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Zinc oxide nanoparticles (ZnO NPs) have garnered significant attention due to their diverse applications encompassing catalytic, optical, photonic, and antibacterial properties. In this study, we successfully synthesized zinc oxide nanoparticles using a rapid, environmentally benign, and cost-effective method. Neem (Azadirachta indica) leaf extract served as the reducing agent for Zn (NO₃)₂.6H2O solution under optimized conditions (pH = 9). Qualitative screening techniques and FT-IR Spectroscopy confirmed the presence of active biomolecules such as flavonoids, phenolic groups, alkaloids, terpenoids, and tannins within the Neem leaf extract, both before and after reduction. The formation of ZnO NPs was visually evident through a distinct color change from colorless to light yellow. The biosynthesized nanoparticles underwent comprehensive characterization through UV-visible, FT-IR, and XRD spectroscopies. The reduction process proved to be straightforward and user-friendly, with UV-visible spectroscopy demonstrating a surface plasmon resonance (SPR) at 321 nm, unequivocally confirming the ZnO NP formation. X-ray diffraction analysis elucidated the crystal structure, revealing an average particle size of approximately 20 nm using Scherrer's equation based on the line width of the plane. Furthermore, the synthesized zinc oxide nanoparticles were evaluated for their antimicrobial properties against both Gram-positive and Gram-negative bacteria. The results showcased significant inhibitory activity, with the highest zone of inhibition observed against Escherichia coli (15 mm) and comparatively lower activity against Staphylococcus aureus. This research underscores the potential of Neem leaf extract-mediated synthesis of ZnO NPs as an eco-friendly and effective approach for various applications, including antibacterial agents.

Keywords: zinc oxide nanoparticles (ZnO NPs), bioreducing agent, green synthesis, antibacterial activity

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Authors: Shin-Pin Tseng

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Nowadays, numerous spectral amplitude coding (SAC) fiber-optic code-division-multiple-access (FO-CDMA) techniques were appealing due to their capable of providing moderate security and relieving the effects of multiuser interference (MUI). Nonetheless, the performance of the previous network is degraded due to fixed in-phase cross-correlation (IPCC) value. Based on the above problems, a new SAC FO-CDMA network using partial M-sequence (PMS) code is presented in this study. Because the proposed PMS code is originated from M-sequence code, the system using the PMS code could effectively suppress the effects of MUI. In addition, two-code keying (TCK) scheme can applied in the proposed SAC FO-CDMA network and enhance the whole network performance. According to the consideration of system flexibility, simple optical encoders/decoders (codecs) using fiber Bragg gratings (FBGs) were also developed. First, we constructed a diagram of the SAC FO-CDMA network, including (N/2-1) optical transmitters, (N/2-1) optical receivers, and one N×N star coupler for broadcasting transmitted optical signals to arrive at the input port of each optical receiver. Note that the parameter N for the PMS code was the code length. In addition, the proposed SAC network was using superluminescent diodes (SLDs) as light sources, which then can save a lot of system cost compared with the other FO-CDMA methods. For the design of each optical transmitter, it is composed of an SLD, one optical switch, and two optical encoders according to assigned PMS codewords. On the other hand, each optical receivers includes a 1 × 2 splitter, two optical decoders, and one balanced photodiode for mitigating the effect of MUI. In order to simplify the next analysis, the some assumptions were used. First, the unipolarized SLD has flat power spectral density (PSD). Second, the received optical power at the input port of each optical receiver is the same. Third, all photodiodes in the proposed network have the same electrical properties. Fourth, transmitting '1' and '0' has an equal probability. Subsequently, by taking the factors of phase‐induced intensity noise (PIIN) and thermal noise, the corresponding performance was displayed and compared with the performance of the previous SAC FO-CDMA networks. From the numerical result, it shows that the proposed network improved about 25% performance than that using other codes at BER=10-9. This is because the effect of PIIN was effectively mitigated and the received power was enhanced by two times. As a result, the SAC FO-CDMA network using PMS codes has an opportunity to apply in applications of the next-generation optical network.

Keywords: spectral amplitude coding, SAC, fiber-optic code-division multiple-access, FO-CDMA, partial M-sequence, PMS code, fiber Bragg grating, FBG

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Authors: Arfan Ali, Muhammad Shahzad Iqbal, Idrees Ahmad Nasir

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Potato (Solanum tuberosum L.) is ranked among the top leading staple foods in the world. Salinity adversely affects potato crop yield and quality. Therefore, increased level of salt tolerance is a key factor to ensure high yield. The present study focused on the Agrobacterium-mediated transformation of Atriplex canescens betaine aldehyde dehydrogenase (BADH) gene, using single, double and triple CAMV35s promoter to improve salt tolerance in potato. Detection of seven potato lines harboring BADH gene, followed by identification of T-DNA insertions, determination of transgenes copies no through Southern Hybridization and quantification of BADH protein through Enzyme Linked Immunosorbent Assay were considered in this study. The results clearly depict that the salt tolerance of potato was found to be promoter-dependent, as the potato transgenic lines with triple promoter showed 4.4 times more glycine betaine production which consequently leads towards high resistance to salt stress as compared to transgenic potato lines with single and double promoters having least production of glycine betaine. Moreover, triple promoter transgenic potato lines have also shown lower levels of H2O2, malondialdehyde (MDA), relative electrical conductivity, high proline and chlorophyll content as compared other two lines having a single and double promoter. Insilco analysis also confirmed that Atriplex canescens BADH has the tendency to interact with sodium ions and water molecules. Taken together these facts it can be concluded that over-expression of BADH under triple CAMV35s promoter with more glycine betaine, chlorophyll & MDA contents, high relative quantities of other metabolites results in an enhanced level of salt tolerance in potato.

Keywords: Atriplex canescens, BADH, CAMV35s promotor, potato, Solanum tubersum

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Authors: Gabriela Steffen

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Learning in a bilingual classroom not only implies learning in two languages or in an L2, it also means learning content subjects through the means of bilingual or plurilingual resources, which is of a qualitatively different nature than ‘monolingual’ learning. These resources form elements of a didactics of plurilingualism, aiming not only at the development of a plurilingual competence, but also at drawing on plurilingual resources for nonlinguistic subject learning. Applying a didactics of plurilingualism allows for taking account of the specificities of bilingual content subject learning in bilingual education classrooms. Bilingual education is used here as an umbrella term for different programs, such as bilingual education, immersion, CLIL, bilingual modules in which one or several non-linguistic subjects are taught partly or completely in an L2. This paper aims at discussing first results of a study on pupil group work in bilingual classrooms in several Swiss primary schools. For instance, it analyses two bilingual classes in two primary schools in a French-speaking region of Switzerland that follows a part of their school program through German in addition to French, the language of instruction in this region. More precisely, it analyses videotaped classroom interaction and in situ classroom practices of pupil group work in a mathematics lessons. The ethnographic observation of pupils’ group work and the analysis of their interaction (analytical tools of conversational analysis, discourse analysis and plurilingual interaction) enhance the description of whole-class interaction done in the same (and several other) classes. While the latter are teacher-student interactions, the former are student-student interactions giving more space to and insight into pupils’ talk. This study aims at the description of the linguistic and multimodal resources (in German L2 and/or French L1) pupils mobilize while carrying out a mathematical task. The analysis shows that the accomplishment of the mathematical task takes place in a bilingual mode, whether the whole-class interactions are conducted rather in a bilingual (German L2-French L1) or a monolingual mode in L2 (German). The pupils make plenty of use of German L2 in a setting that lends itself to use French L1 (peer groups with French as a dominant language, in absence of the teacher and a task with a mathematical aim). They switch from French to German and back ‘naturally’, which is regular for bilingual speakers. Their linguistic resources in German L2 are not sufficient to allow them to (inter-)act well enough to accomplish the task entirely in German L2, despite their efforts to do so. However, this does not stop them from carrying out the task in mathematics adequately, which is the main objective, by drawing on the bilingual resources at hand.

Keywords: bilingual content subject learning, bilingual primary education, bilingual pupil group work, bilingual teaching/learning resources, didactics of plurilingualism

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Authors: Cristian Moisa, Andreea Lupitu, Adriana Csakvari, Dana G. Radu, Leonard Marian Olariu, Georgeta Pop, Dorina Chambre, Lucian Copolovici, Dana Copolovici

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Green synthesis of nanoparticles (NPs) represents a promising, accessible, eco-friendly, and safe process with significant applications in biotechnology, pharmaceutical sciences, and farming. The aim of our study was to obtain silver nanoparticles, using plant wastes extracts resulted in the essential oils extraction process: Thymus vulgaris L., Origanum vulgare L., Lavandula angustifolia L., and in hemp processing for seed and fibre, Cannabis sativa. Firstly, we obtained aqueous extracts of thyme, oregano, lavender, and hemp (two monoicous and one dioicous varieties), all harvested in western part of Romania. Then, we determined the chemical composition of the extracts by liquid-chromatography coupled with diode array and mass spectrometer detectors. The compounds identified in the extracts were in agreement with earlier published data, and the determination of the antioxidant activity of the obtained extracts by DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assays confirmed their antioxidant activity due to their total polyphenolic content evaluated by Folin-Ciocalteu assay. Then, the silver nanoparticles (AgNPs) were successfully biosynthesised, as was demonstrated by UV-VIS, FT-IR spectroscopies, and SEM, by reacting AgNO₃ solution and plant extracts. AgNPs were spherical in shape, with less than 30 nm in diameter, and had a good bactericidal activity against Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Pseudomonas fluorescens).

Keywords: plant wastes extracts, chemical composition, high performance liquid chromatography mass spectrometer, HPLC-MS, scanning electron microscopy, SEM, silver nanoparticles

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Authors: Sarekha Woranuch, Rangrong Yoksan

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Chitosan is a derivative of chitin, which is a second most naturally abundant polysaccharide found in crab shells, shrimp shells, and squid pens. The applications of chitosan in pharmaceutical, cosmetics, food and packaging industries have been reported owing to its general recognition as safe, excellent biodegradability and biocompatibility, as well as ability to form films, membranes, gels, beads, fibers and particles. Nevertheless, chitosan is an amino polysaccharide consisting of strong inter- and intramolecular hydrogen bonds which limit its solubility in neutral pH water resulting in restricted utilization. Chemical modification is an alternative way to impede hydrogen bond formation. The objective of the present research is to improve water solubility and antioxidant activity of chitosan by grafting with ferulic acid. Ferulic acid was grafted onto chitosan at the C-2 position via a carbodiimide-mediated coupling reaction. Different mole ratios of chitosan to ferulic acid (i.e. 1.0:0.0, 1.0:0.5, 1.0:1.0, 1.0:1.5, 1.0:2.0, and 1.0:2.5) and various reaction temperatures (i.e. 40, 60, and 80 °C) were used. The reaction was performed at different times (i.e. 1.5, 3.0, 4.5, and 6.0 h). The obtained ferulic acid-grafted chitosan was characterized by FTIR and 1H NMR technique. The influences of ferulic acid on crystallinity, solubility and radical scavenging activity of chitosan were also investigated. Ferulic acid grafted chitosan was successfully synthesized as confirmed from (i) the appearance of FTIR absorption band at 1517 cm-1 belonging to C=C aromatic ring of ferulic acid and the increased C–H stretching band intensity and (ii) the appearance of proton signals at δ = 6.31-7.67 ppm ascribing to methine protons of ferulic acid. The condition in which the reaction temperature of 60°C, reaction time of 3 h and the mole ratio of chitosan to ferulic acid of 1:1 gave the highest ferulic acid substitution degree, i.e. 0.37. The resulting ferulic acid grafted chitosan was soluble in water (1.3 mg/mL) due to its reduced crystallinity as compared with chitosan and also exhibited 90% greater radical scavenging activity than chitosan. The result suggested the utilization of ferulic acid grafted chitosan as an antioxidant material.

Keywords: antioxidant property, chitosan, ferulic acid, grafting

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Authors: L. Mercier, D. Beladjine, K. Beddiar

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The digital transition of building in France brings many changes which some have been able to face very quickly, while others are struggling to find their place and the interest that BIM can bring in their profession. BIM today is already adopted or initiated by construction professionals. However, this change, which can be drastic for some, prevents them from integrating it definitively. This is the case with architects. The profession is shared on the practice of BIM in its exercise. The risk of not adopting this new working method now and of not wanting to switch to its new digital tools leads us to question the future of the profession in view of the gap that is likely to be created within project management. In order to deal with the subject efficiently, our work was based on a documentary watch on BIM and then on the profession of architect, which allowed us to establish links on these two subjects. The observation of the economic model towards which the agencies tend and the trend of the sought after profiles made it possible to develop the opportunities and the brakes likely to impact the future of the profession of architect. The centralization of research directs work towards the conclusion that the model implemented by companies does not allow to integrate BIM within their structure. A solution hypothesis was then issued, focusing on the development of agencies through the diversity of profiles, skills to be integrated internally with the aim of diversifying their skills, and their business practices. In order to address this hypothesis of a multidisciplinary agency model, we conducted a survey of architectural firms. It is built on the model of Anglo-Saxon countries, which do not have the same functioning in comparison to the French model. The results obtained showed a risk of gradual disappearance on the market from small agencies in favor of those who will have and could take this BIM working method. This is why the architectural profession must, first of all, look at what is happening within its training before absolutely wanting to diversify the profiles to integrate into its structure. This directs the study on the training of architects. The schools of French architects are generally behind schedule if we allow the comparison to the schools of engineers. The latter is currently experiencing a slight improvement with the emergence of masters and BIM options during the university course. If the training of architects develops towards learning BIM and the agencies have the desire to integrate different but complementary profiles, then they will develop their skills internally and therefore open their profession to new functions. The place of BIM Management on projects will allow the architect to remain in control of the project because of their overall vision of the project. In addition, the integration of BIM and more generally of the life cycle analysis of the structure will make it possible to guarantee eco-design or eco-construction by approaching the constraints of sustainable development omnipresent on the planet.

Keywords: building information modelling, BIM, BIM management, BIM manager, BIM architect

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Authors: Clotilde Guyon, Nada Jmari, Yen-Chin Li, Jean Denoyel, Noriyuki Fujikado, Christophe Blanchet, David Root, Matthieu Giraud

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Aire induces ectopic expression of a large repertoire of tissue-specific antigen (TSA) genes in thymic medullary epithelial cells (MECs), driving immunological self-tolerance in maturing T cells. Although important mechanisms of Aire-induced transcription have recently been disclosed through the identification and the study of Aire’s partners, the fine transcriptional functions underlied by a number of them and conferred to Aire are still unknown. Alternative cleavage and polyadenylation (APA) is an essential mRNA processing step regulated by the termination complex consisting of 85 proteins, 10 of them have been related to Aire. We evaluated APA in MECs in vivo by microarray analysis with mRNA-spanning probes and RNA deep sequencing. We uncovered the preference of Aire-dependent transcripts for short-3’UTR isoforms and for proximal poly(A) site selection marked by the increased binding of the cleavage factor Cstf-64. RNA interference of the 10 Aire-related proteins revealed that Clp1, a member of the core termination complex, exerts a profound effect on short 3’UTR isoform preference. Clp1 is also significantly upregulated in the MECs compared to 25 mouse tissues in which we found that TSA expression is associated with longer 3’UTR isoforms. Aire-dependent transcripts escape a global 3’UTR lengthening associated with MEC differentiation, thereby potentiating the repressive effect of microRNAs that are globally upregulated in mature MECs. Consistent with these findings, RNA deep sequencing of actinomycinD-treated MECs revealed the increased stability of short 3’UTR Aire-induced transcripts, resulting in TSA transcripts accumulation and contributing for their enrichment in the MECs.

Keywords: Aire, central tolerance, miRNAs, transcription termination

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Authors: Gabriele Ciasca, Tanya E. Sassun, Eleonora Minelli, Manila Antonelli, Massimiliano Papi, Antonio Santoro, Felice Giangaspero, Roberto Delfini, Marco De Spirito

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Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor, characterized by a diffuse infiltration of neoplastic cells into the brain parenchyma. Although rarely considered, mechanical cues play a key role in the infiltration process that is extensively mediated by the tumor microenvironment stiffness and, more in general, by the occurrence of aberrant interactions between neoplastic cells and the extracellular matrix (ECM). Here we provide a nano-mechanical characterization of the viscoelastic response of human GBM tissues by indentation-type atomic force microscopy. High-resolution elasticity maps show a large difference between the biomechanics of GBM tissues and the healthy peritumoral regions, opening possibilities to optimize the tumor resection area. Moreover, we unveil the nanomechanical signature of necrotic regions and anomalous vasculature, that are two major hallmarks useful for glioma staging. Actually, the morphological grading of GBM relies mainly on histopathological findings that make extensive use of qualitative parameters. Our findings have the potential to positively impact on the development of novel quantitative methods to assess the tumor grade, which can be used in combination with conventional histopathological examinations. In order to provide a more in-depth description of the role of mechanical cues in tumor progression, we compared the nano-mechanical fingerprint of GBM tissues with that of grade-I (WHO) meningioma, a benign lesion characterized by a completely different growth pathway with the respect to GBM, that, in turn hints at a completely different role of the biomechanical interactions.

Keywords: AFM, nano-mechanics, nanomedicine, brain tumors, glioblastoma

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Authors: Brahmanage S. Rangika, Dinithi C. Peiris

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Boiled Aqueous Flower Extract (AFE) of Nyctanthes arbor-tristis L. (Family: Oleaceae) is used in traditional Sri Lankan medicinal system to treat diabetes. However, this is not scientifically proven and the mechanisms by which the flowers reduce diabetes have not been investigated. The present study was carried out to examine the hypoglycemic potential and toxicity effects of aqueous flower extract of N. arbor-tristis. AFE was prepared and mice were treated orally either with 250, 500, and 750 mg/kg of AFE or distilled water (Control). Fasting and random blood glucose levels were determined. In addition, the toxicity of AFE was determined using chronic oral administration. In normoglycemic mice, mid dose (500mg/kg) of AFE significantly (p < 0.01) reduced fasting blood glucose levels by 49% at 4h post treatment. Further, 500mg/kg of AFE significantly (p < 0.01) lowered random blood glucose level of non-fasted normoglycemic mice. AFE significantly lowered total cholesterol and triglyceride levels while increasing the HDL levels in the serum. Further, AFE significantly inhibited the glucose absorption from the lumen of the intestine and it increases the diaphragm uptake of glucose. Alpha-amylase inhibitory activity was also evident. However, AFE did not induce any overt signs of toxicity or hepatotoxicity. There were no adverse effects on food and water intake and body weight of mice during the experimental period. It can be concluded that AFE of N. arbor-tristis posses safe oral anti diabetic potentials mediated via multiple mechanisms. Results of the present study scientifically proved the claims made about the uses of N. arbor-tristis in the treatment of diabetes mellitus in traditional Sri Lankan medicinal system. Further, flowers can also be used for as a remedy to improve blood lipid profile.

Keywords: aqueous extract, hypoglycemic hypolipidemic, Nyctanthes arbor-tristis flowers, hepatotoxicity

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Authors: Mengying Wang, Dongjing Liu, Holger Schwender, Ping Wang, Hongping Zhu, Tao Wu, Terri H Beaty

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Background: Maternal smoking is a recognized risk factor for nonsyndromic cleft lip with or without cleft palate (NSCL/P). It has been reported that the effect of maternal smoking on oral clefts is mediated through genes that influence nicotine dependence. The polymorphisms of cholinergic receptor nicotinic alpha (CHRNA) and beta (CHRNB) subunits genes have previously shown strong associations with nicotine dependence. Here, we attempted to investigate whether the above genes are associated with clefting risk through testing for potential gene-gene (G×G) and gene-environment (G×E) interaction. Methods: We selected 120 markers in 14 genes associated with nicotine dependence to conduct transmission disequilibrium tests among 806 Chinese NSCL/P case-parent trios ascertained in an international consortium which conducted a genome-wide association study (GWAS) of oral clefts. We applied Cordell’s method using “TRIO” package in R to explore G×G as well as G×E interaction involving environmental tobacco smoke (ETS) based on conditional logistic regression model. Results: while no SNP showed significant association with NSCL/P after Bonferroni correction, we found signals for G×G interaction between 10 pairs of SNPs in CHRNA3, CHRNA5, and CHRNB4 (p<10-8), among which the most significant interaction was found between RS3743077 (CHRNA3) and RS11636753 (CHRNB4, p<8.2×10-12). Linkage disequilibrium (LD) analysis revealed only low level of LD between these markers. However, there were no significant results for G×ETS interaction. Conclusion: This study fails to detect association between nicotine dependence genes and NSCL/P, but illustrates the importance of taking into account potential G×G interaction for genetic association analysis in NSCL/P. This study also suggests nicotine dependence genes should be considered as important candidate genes for NSCL/P in future studies.

Keywords: Gene-Gene Interaction, Maternal Smoking, Nicotine Dependence, Non-Syndromic Cleft Lip with or without Cleft Palate

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Authors: Alexandra-Monica Toma

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Internet memes are an element of computer mediated communication and an important part of online culture that combines text and image in order to generate meaning. This term coined by Richard Dawkings refers to more than a mere way to briefly communicate ideas or emotions, thus naming a complex and an intensely perpetuated phenomenon in the virtual environment. This paper approaches memes as a cultural artefact and a virtual trope that mirrors societal concerns and issues, and analyses the pragmatics of their use. Memes have to be analysed in series, usually relating to some image macros, which is proof of the interplay between imitation and creativity in the memes’ writing process. We believe that their potential to become viral relates to three key elements: adaptation to context, reference to a successful meme series, and humour (jokes, irony, sarcasm), with various pragmatic functions. The study also uses the concept of multimodality and stresses how the memes’ text interacts with the image, discussing three types of relations: symmetry, amplification, and contradiction. Moreover, the paper proves that memes could be employed as speech acts with illocutionary force, when the interaction between text and image is enriched through the connection to a specific situation. The features mentioned above are analysed in a corpus that consists of memes related to the COVID-19 pandemic. This corpus shows them to be highly adaptable to context, which helps build the feeling of connection and belonging in an otherwise tremendously fragmented world. Some of them are created based on well-known image macros, and their humour results from an intricate dialogue between texts and contexts. Memes created in relation to the COVID-19 pandemic can be considered speech acts and are often used as such, as proven in the paper. Consequently, this paper tackles the key features of memes, makes a thorough analysis of the memes sociocultural, linguistic, and situational context, and emphasizes their intertextuality, with special accent on their illocutionary potential.

Keywords: context, memes, multimodality, speech acts

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Authors: Paul E. Priester

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The Twelve Step approach to recovery from substance use and addictive disorders is considered an evidence-based model that assists many who recover from a chronic, progressive, fatal disease. Two key processes that contribute to the success of obtaining recovery from substance use disorders (SUD) are meeting engagement and the development of spiritual beliefs. Beyond establishing that there is a positive relationship between the development of spiritual beliefs in recovery from SUD’s, there has been a paucity of research exploring individual differences among individuals in this development of spiritual beliefs. One such personality variable that deserves exploration is that of the need for cognition. The need for cognition is a personality variable that explains the cognitive style of individuals. Individuals with a high need for cognition enjoy examining the complexities of a situation before coming to a conclusion. While individuals with a low need for cognition do not value or spend time cognitively dissecting a situation or decision. It is important to point out that a high need for cognition does not necessarily imply a high level of cognitive ability. Indeed, one could make the argument that a low need for cognition individual is not “wasting” cognitive energy in perseverating the multitude of aspects of a particular decision. This paper will present two case studies demonstrating the development of spiritual beliefs that enabled long-term recovery from SUD. The first case study presents an agnostic individual with a low need for cognition cognitive style in his development of spirituality in support of his recovery from alcoholism within the context of Alcoholics Anonymous. The second case study represents an adamant atheist with a high need for cognition cognitive style. This second individual is an intravenous cocaine addict and alcoholic who recovers through the development of spirituality within the contexts of Alcoholics Anonymous and Narcotics Anonymous. The two case studies will be contrasted with each other, noting how the individuals’ cognitive style mediated the development of spirituality that supported their long-term recovery from alcoholism and addiction.

Keywords: spirituality, twelve step recovery, need for cognition, individual differences in recovery from addictions

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Authors: Jeroen Rotteveel, Zeger De Groot

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The small satellite community is more and more aware of the need to start operating responsibly and sustainably in order to secure the use of outer space in the long run. On the technical side, many debris mitigation techniques have been investigated and demonstrated on board small satellites, showing that technically, a lot of things can be done to curb the growth of space debris and operate more responsible. However, in the absence of strict laws and constraints, one cannot help but wonder what the incentive is to incur significant costs (paying for debris mitigation systems and the launch mass of these systems) and to lose performance onboard resource limited small satellites (mass, volume, power)? Many small satellite developers are operating under tight budgets, either from their sponsors (in case of academic and research projects) or from their investors (in case of startups). As long as it is not mandatory to act more responsibly, we might need to consider the implementation of incentives to stimulate developers to accommodate deorbiting modules, etc. ISISPACE joined the NetZeroSpace initiative in 2021 with the aim to play its role in secure the use of low earth orbit for the next decades by facilitating more sustainable use of space. The company is in a good position as both a satellite builder, a rideshare launch provider, and a technology development company. ISISPACE operates under one of the stricter space laws in the world in terms of maximum orbital lifetime and has been active in various debris mitigation and debris removal in-orbit demonstration missions in the past 10 years. ISISPACE proposes to introduce together with launch partners and regulators an incentive scheme for CubeSat developers to baseline debris mitigation systems on board their CubeSats in such a way that is does not impose too many additional costs to the project. Much like incentives to switch to electric cars or install solar panels on your house, such an incentive can help to increase market uptake of behavior or solutions prior to legislation or bans of certain practices. This can be achieved by: Introducing an extended launch volume in CubeSat deployers to accommodate debris mitigation systems without compromising available payload space for the payload of the main mission Not charging the fee for the launch mass for the additional debris mitigation module Whenever possible, find ways to further co-fund the purchase price, or otherwise reduce the cost of flying debris mitigation modules onboard the CubeSats. The paper will outline the framework of such an incentive scheme and provides ISISPACE’s way forward to make this happen in the near future.

Keywords: netZerospace, cubesats, debris mitigation, small satellite community

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Authors: Gila Kurtz, Dan Kohen Vacs

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Social robots (SR) is an emerging field striving to deploy computers capable of resembling human shapes and mimicking human movements, gestures, and behaviors. The evolving capability of SR to interact with human offers groundbreaking ways for learning and training opportunities. Studies show that SR can offer instructional experiences for fostering creativity, entertainment, enjoyment, and curiosity. These added values are essential for empowering instructional opportunities as gamified learning experiences. We present our project focused on deploying an activity to be experienced in an escape room aimed at team-based learning scaffolded by an SR, NAO. An escape room is a well-known approach for gamified activities focused on a simulated scenario experienced by team-based participants. Usually, the simulation takes place in a physical environment where participants must complete a series of challenges in a limited amount of time. During this experience, players learn something about the assigned topic of the room. In the current learning simulation, students must "save the nation" by locating sensitive information stolen and stored in a vault of four locks. Team members have to look for hints and solve riddles mediated by NAO. Each solution provides a unique code for opening one of the four locks. NAO is also used to provide ongoing feedback on the team's performance. We captured the proceeding of our activity and used it to conduct an evaluation study among ten experts in related areas. The experts were interviewed on their overall assessment of the learning activity and their perception of the added value related to the robot. The results were very encouraging on the feasibility that NAO can serve as a motivational tutor in adults' collaborative game-based learning. We believe that this study marks the first step toward a template for developing innovative team-based training using escape rooms supported by a humanoid robot.

Keywords: social robot, NAO, learning, team based activity, escape room

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Authors: Chien Y. Lin, Jung Y. Huang, Leu-Wei Lo

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A growing body of data reveals that the membrane cholesterol molecules can alter the signaling pathways of living cells. However, the understanding about how membrane cholesterol modulates receptor proteins is still lacking. Single-molecule tracking can effectively probe into the microscopic environments and thermal fluctuations of receptor proteins in a living cell. In this study we applies single-molecule optical tracking on ligand-induced dimerization process of EGFRs in the plasma membranes of two cancer cell lines (HeLa and A431) and one normal endothelial cell line (MCF12A). We tracked individual EGFR and dual receptors, diffusing in a correlated manner in the plasma membranes of live cells. We developed an energetic model by integrating the generalized Langevin equation with the Cahn-Hilliard equation to help extracting important information from single-molecule trajectories. From the study, we discovered that ligand-bound EGFRs move from non-raft areas into lipid raft domains. This ligand-induced motion is a common behavior in both cancer and normal cells. By manipulating the total amount of membrane cholesterol with methyl-β-cyclodextrin and the local concentration of membrane cholesterol with nystatin, we further found that the amount of cholesterol can affect the stability of EGFR dimers. The EGFR dimers in the plasma membrane of normal cells are more sensitive to the local concentration changes of cholesterol than EGFR dimers in the cancer cells. Our method successfully captures dynamic interactions of receptors at the single-molecule level and provides insight into the functional architecture of both the diffusing EGFR molecules and their local cellular environment.

Keywords: membrane proteins, single-molecule tracking, Cahn-Hilliard equation, EGFR dimers

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Authors: Emmanuel Chinaguh, Kehinde Adeosun

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Nigerians die untimely, with 55.75 years of life expectancy, which is 17.45 below the world average of 73.2 (Worldometer, 2020). This is due, among other factors, to the country's limited access to high-quality healthcare. To increase access to good and affordable healthcare services, the National Health Insurance Authority (NHIA) Bill 2022 – which repealed the National Health Insurance Scheme Act 2004 – was passed into law. Applying Jacob Mey’s (2001) pragmatics act (pract) theory, this study explores how NHIA seeks to actualise these healthcare goals by characterising the general situational prototype or pragmemes and pragmatic acts in institutional communications. Data was sourced from the NHIA operational guidelines, which has 147 pages and four sections, and shared posters on NHIA Nigeria Twitter Handle with 14,200 followers. Digital humanities tools, like AntConc and Voyant, were engaged in the data analysis for text encoding and data visualisation. This study identifies these discourse tokens in the data: advertisement and programmes, standards and accreditation, records and information, and offences and penalties. Advertisement and programmes pract facilitating, propagating, prospecting, advising and informing; standards and accreditation, and records and information pract stating, informing and instructing; and offences and penalties pract stating and sanctioning. These practs combined to advance the goals of affordable care and universal accessibility to quality healthcare services. The pragmatic acts were marked by these pragmatic tools: shared situational knowledge (SSK), relevance (REL), reference (REF) and inference (INF). This paper adds to the understanding of health insurance discourse in Nigeria as a mediated social practice that promotes the health of Nigerians.

Keywords: affordable care, NHIA, Nigeria’s health insurance discourse, pragmatic acts.

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Authors: Sven Borén, Henrik Ny

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Ambitions within the EU for moving towards sustainable transport include major emission reductions for fossil fuel road vehicles, especially for buses, trucks, and cars. The electric driveline seems to be an attractive solution for such development. This study first applied the Framework for Strategic Sustainable Development to compare sustainability effects of today’s fossil fuel vehicles with electric vehicles that have batteries or hydrogen fuel cells. The study then addressed a scenario were electric vehicles might be in majority in Europe by 2050. The methodology called Strategic Lifecycle Assessment was first used, were each life cycle phase was assessed for violations against sustainability principles. This indicates where further analysis could be done in order to quantify the magnitude of each violation, and later to create alternative strategies and actions that lead towards sustainability. A Life Cycle Assessment of combustion engine cars, plug-in hybrid cars, battery electric cars and hydrogen fuel cell cars was then conducted to compare and quantify environmental impacts. The authors found major violations of sustainability principles like use of fossil fuels, which contribute to the increase of emission related impacts such as climate change, acidification, eutrophication, ozone depletion, and particulate matters. Other violations were found, such as use of scarce materials for batteries and fuel cells, and also for most life cycle phases for all vehicles when using fossil fuel vehicles for mining, production and transport. Still, the studied current battery and hydrogen fuel cell cars have less severe violations than fossil fuel cars. The life cycle assessment revealed that fossil fuel cars have overall considerably higher environmental impacts compared to electric cars as long as the latter are powered by renewable electricity. By 2050, there will likely be even more sustainable alternatives than the studied electric vehicles when the EU electricity mix mainly should stem from renewable sources, batteries should be recycled, fuel cells should be a mature technology for use in vehicles (containing no scarce materials), and electric drivelines should have replaced combustion engines in other sectors. An uncertainty for fuel cells in 2050 is whether the production of hydrogen will have had time to switch to renewable resources. If so, that would contribute even more to a sustainable development. Except for being adopted in the GreenCharge roadmap, the authors suggest that the results can contribute to planning in the upcoming decades for a sustainable increase of EVs in Europe, and potentially serve as an inspiration for other smaller or larger regions. Further studies could map the environmental effects in LCA further, and include other road vehicles to get a more precise perception of how much they could affect sustainable development.

Keywords: strategic, electric vehicles, sustainability, LCA

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Authors: Sruthi Ramagiri, Rajeev T.

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Free radical damage has been entailed as the major culprit in the ischemic stroke contributing for oxidative damage. Recent investigations on Hydroxy Safflower Yellow A (HSYA) suggested its role in cerebral ischemia and various neurodegenerative disorders with unidentified molecular mechanisms. The current study was designed to investigate putative therapeutic role and possible molecular mechanisms of HSYA administration during the onset of reperfusion in cerebral ischemia-reperfusion (I/R) injury in cerebral stroke. Cerebral stroke was achieved by focal ischemic model. HSYA (10 mg/kg) was injected intravenously via the tail vein 5 minutes before reperfusion. Losses of sensorimotor abilities were evaluated by neurological scoring, spontaneous locomotor activity, and rotarod performance. Extent of oxidative stress was evaluated by biochemical parameters i.e., malondialdehyde (MDA), Glutathione (GSH), Super Oxide Dismutase (SOD) and catalase levels. The infarct volume of brain was assessed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining technique. Increased cerebral injury (I/R) was evidenced by motor impairment, increased infarct volume and elevation of MDA levels along with significant reduction in antioxidant i.e.,MDA levels along with significant reduction in antioxidant i.e., GSH, SOD and catalase levels when compared to sham control. However, post conditioning with HSYA (10 mg/kg, i.v.) at the onset of reperfusion has significantly ameliorated sensorimotor abilities, attenuated MDA levels and reduced the infarct volume as compared with vehicle treated I/R injury group. Moreover, HSYA treatments improved antioxidant enzyme levels as compared with vehicle treated I/R-injury group. In conclusion, it may be suggested that HSYA post conditioning could be novel therapeutic approach against I/R injury in cerebral stroke possibly through its anti-oxidant mechanism.

Keywords: HSYA, Ischemia reperfusion injury, oxidative stress, stroke

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Authors: Elsa Marta Soares, Ana Rita Valente, Cristiana Rodrigues, Filipa Gonçalves

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Background: The assessment of feelings and attitudes of preschool children in relation to stuttering is crucial. Negative experiences can lead to anxiety, worry or frustration. To avoid the worsening of attitudes and feelings related to stuttering, it is important the early detection in order to intervene as soon as possible through an individualized intervention plan. Then it is important to have Portuguese instruments that allow this assessment. Aims: The aim of the present study is to realize the translation and adaptation of the Communication Attitude Test for Children in Preschool Age and Kindergarten (KiddyCat) for EP. Methodology: For the translation and adaptation process, a methodological study was carried out with the following steps: translation, back translation, assessment by a committee of experts and pre-test. This abstract describes the results of the first two phases of this process. The translation was accomplished by two bilingual individuals without experience in health and any knowledge about the instrument. One of them was an English teacher and the other one a Translator. The back-translation was conducted by two Senior Class Teachers that live in United Kingdom without any knowledge in health and about the instrument. Results and Discussion: In translation there were differences in semantic equivalences of various expressions and concepts. A discussion between the two translators, mediated by the researchers, allowed to achieve the consensus version of the translated instrument. Taking into account the original version of KiddyCAT the results demonstrated that back-translation versions were similar to the original version of this assessment instrument. Although the back-translators used different words, they were synonymous, maintaining semantic and idiomatic equivalences of the instrument’s items. Conclusion: This project contributes with an important resource that can be used in the assessment of feelings and attitudes of preschool children who stutter. This was the first phase of the research; expert panel and pretest are being developed. Therefore, it is expected that this instrument contributes to an holistic therapeutic intervention, taking into account the individual characteristics of each child.

Keywords: assessment, feelings and attitudes, preschool children, stuttering

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Authors: Ceyda Okudu, Secil Eroglu, Khandakar A. S. M. Saadat, Sibel O. Balci

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Ring Finger Protein 2 (RNF2) is a member of polycomb repressive complex 1 (PRC1), which is one of the epigenetic regulators in the genome. When RNF2 combines with other PRC1 members, it mediates the mono-ubiquitination of Histon2A (H2A). In breast cancer, RNF2 is commonly overexpressed, and also it promotes metastasis and invasion in other aggressive tumors like melanoma, prostate, and hepatocarcinoma. The role of RNF2 in the metastasis and invasion of breast cancer has not yet been elucidated. Our aim is to observe the role of RNF2 in metastasis and invasion in this study by miRNA mediated RNF2 gene silencing in breast cancer cell lines. We selected miRNAs, targeting to RNF2 by searching online databases. miR-17-5p, miR20a-5p, and miR-106b-5p were transfected to breast cancer cell lines (MCF-7, MDA-MB-231, SK-BR-3, and ZR-75-1), and also we used normal breast epithelial cell line (hTERT-HME1) to compare RNF2 gene expression level. After 48-72 hours post-transfection, mRNAs were isolated from the cells, and gene expressions were measured by RT-qPCR after from cDNA syntheses. We observed that RNF2 was highly expressed in SK-BR-3 and MDA-MB-231 cell lines opposite to MCF-7 and ZR-75-1 cell lines. RNF2 was downregulated 5, 5 and 7 fold by miR17-5p, miR20a-5p and miR106b-5p respectively in MCF-7. However, in SK-BR-3 and ZR-75-1 cell lines, miRNAs did not affect significantly RNF2 gene expression level. miR20a-5p decreased RNF2 3 fold and miR17-5p and miR106b-5p did not affect MDA-MB-231. After gene expression analysis, we performed metastasis and invasion assay in MCF-7 cells. For metastasis, we used both wound healing assay and Transwell Cell Migration Assay, and we used Transwell Cell Invasion Assay for invasion. The data of this assay showed that miR17-5p and miR20a-5p decreased both invasion and metastasis level, but miR106b-5p has no effect. We would like to conclude that RNF2 can be targeted by miR17-5p, miR20a-5p and miR106b-5p in MCF-7 cells and also RNF2, which is one of the upregulated genes in aggressive tumor, can be decreased by using these miRNAs. In future, we would like to confirm these results at the protein level and also whether these miRNAs are direct target of RNF2 or not.

Keywords: breast cancer, epigenetic, microRNAs, RNF2

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Authors: Ming-Hsiang Shih, Wen-Pei Sung, Shih-Heng Tung

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Semi-active control system for structure under excitation of earthquake provides with the characteristics of being adaptable and requiring low energy. DSHD (Displacement Semi-Active Hydraulic Damper) was developed by our research team. Shake table test results of this DSHD installed in full scale test structure demonstrated that this device brought its energy-dissipating performance into full play for test structure under excitation of earthquake. The objective of this research is to develop a new AIC (Active Interaction Control Device) and apply shake table test to perform its dissipation of energy capability. This new proposed AIC is converting an improved DSHD (Displacement Semi-Active Hydraulic Damper) to AIC with the addition of an accumulator. The main concept of this energy-dissipating AIC is to apply the interaction function of affiliated structure (sub-structure) and protected structure (main structure) to transfer the input seismic force into sub-structure to reduce the structural deformation of main structure. This concept is tested using full-scale multi-degree of freedoms test structure, installed with this proposed AIC subjected to external forces of various magnitudes, for examining the shock absorption influence of predictive control, stiffness of sub-structure, synchronous control, non-synchronous control and insufficient control position. The test results confirm: (1) this developed device is capable of diminishing the structural displacement and acceleration response effectively; (2) the shock absorption of low precision of semi-active control method did twice as much seismic proof efficacy as that of passive control method; (3) active control method may not exert a negative influence of amplifying acceleration response of structure; (4) this AIC comes into being time-delay problem. It is the same problem of ordinary active control method. The proposed predictive control method can overcome this defect; (5) condition switch is an important characteristics of control type. The test results show that synchronism control is very easy to control and avoid stirring high frequency response. This laboratory results confirm that the device developed in this research is capable of applying the mutual interaction between the subordinate structure and the main structure to be protected is capable of transforming the quake energy applied to the main structure to the subordinate structure so that the objective of minimizing the deformation of main structural can be achieved.

Keywords: DSHD (Displacement Semi-Active Hydraulic Damper), AIC (Active Interaction Control Device), shake table test, full scale structure test, sub-structure, main-structure

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Authors: Yanyan Wang

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This paper on second language teaching and learning uses conversation analysis (CA) approach and focuses on how second language learners of Chinese do repair when making clarification requests. In order to demonstrate their behavior in interaction, a comparison was made to study the differences between native speakers of Chinese with non-native speakers of Chinese. The significance of the research is to make second language teachers and learners aware of repair and how to seek clarification. Utilizing the methodology of CA, the research involved two sets of naturally occurring recordings, one of native speaker students and the other of non-native speaker students. Both sets of recording were telephone talks between students and teachers. There were 50 native speaker students and 50 non-native speaker students. From multiple listening to the recordings, the parts with repairs for clarification were selected for analysis which included the moments in the talk when students had problems in understanding or hearing the speaker and had to seek clarification. For example, ‘Sorry, I do not understand ‘and ‘Can you repeat the question? ‘were the parts as repair to make clarification requests. In the data, there were 43 such cases from native speaker students and 88 cases from non-native speaker students. The non-native speaker students were more likely to use repair to seek clarification. Analysis on how the students make clarification requests during their conversation was carried out by investigating how the students initiated problems and how the teachers repaired the problems. In CA term, it is called other-initiated self-repair (OISR), which refers to student-initiated teacher-repair in this research. The findings show that, in initiating repair, native speaker students pay more attention to mutual understanding (inter-subjectivity) while non-native speaker students, due to their lack of language proficiency, pay more attention to their status of knowledge (epistemic) switch. There are three major differences: 1, native Chinese students more often initiate closed-class OISR (seeking specific information in the request) such as repeating a word or phrases from the previous turn while non-native students more frequently initiate open-class OISR (not specifying clarification) such as ‘sorry, I don’t understand ‘. 2, native speakers’ clarification requests are treated by the teacher as understanding of the content while non-native learners’ clarification requests are treated by teacher as language proficiency problem. 3, native speakers don’t see repair as knowledge issue and there is no third position in the repair sequences to close repair while non-native learners take repair sequence as a time to adjust their knowledge. There is clear closing third position token such as ‘oh ‘ to close repair sequence so that the topic can go back. In conclusion, this paper uses conversation analysis approach to compare differences between native Chinese speakers and non-native Chinese learners in their ways of conducting repair when making clarification requests. The findings are useful in future Chinese language teaching and learning, especially in teaching pragmatics such as requests.

Keywords: conversation analysis (CA), clarification request, second language (L2), teaching implication

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Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, Ch. V. Rao

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Gastric ulcer is a major global health threat, and it is the leading cause of stomach cancer death worldwide. Helicobacter pylori bacteriumis the most important etiologic factor for gastric ulcer. This infection is highly pervasive in South Asian developing countries, especially in India, Nepal, Srilanka etc. due to diversification in geographic area. Pathophysiology of gastric mucosal damage associated with non-invasive bacterium has not justified in detail, but it leads to change in histopathology, immunochemistry of the gastric and duodenal reason of host. The mechanism responsible for bacteria tissue tropism and mucosal damage in stomach variance during the disease is not clearly described and understood scientifically in treatment and control of pathogenic organisms. Polyphenols are secondary metabolites of plants and are generally involved in defense against aggression by pathogens. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one and 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde are polyphenolic compound obtained from popular Indian medicinal plants ghavpatta (ArgeriaspeciosaLinn.f) andBael (Aeglemarmelos) have long been used in traditional Ayurvedic Indian medicine for various diseases. They have promising effects on ulcer, as detailed investigation has made in our laboratory. Therefore, the aim of present study is to explore membrane –dependent morphogenesis of H. pylori and associated apoptosis-mediated cell death. Based on this we analyzed immune gene expression in stomach of experimental animals with H. pylori, using quantitative reverse transcription polymerase chain reaction(q RT-PCR). This revealed rapid induction of prostaglandin, interferon I (INF-I), interferon II (INF-II) and INF-I associated genes in the infected animal. Ultrastructural changes associated with H. pylori will be taken for advanced studies. This investigation shows that the biomarkers eradicate H. pylori bacterium caused gastric ulcer which is a major risk factor for gastric cancer.

Keywords: gastric ulcer, Helicobacter pylori, immunochemistry, polyphenols

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Authors: Maria Karidakis, Barbara Kelly

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The challenges precipitated by the advent of COVID-19 have brought to the fore the task governments and key stakeholders are faced with; ensuring public health communication is readily accessible to vulnerable populations. COVID-19 has presented challenges for the provision and reception of timely, accessible, and accurate health information pertaining to vaccine health messaging to Aboriginal and Torres Strait Islander peoples. The aim of this qualitative study was to explore strategies used by Aboriginal-led organisations to improve communication about COVID-19 and vaccination for their communities and to explore how these mediation and outreach strategies were received by community members. We interviewed 6 Aboriginal-led organisations and 15 community members from several states across Australian, and these interviews were analysed thematically. The findings suggest that effective public health communication is enhanced when aFirst nations-led response defines the governance that happens in First Nations communities. Pro-active and self-determining Aboriginal leadership and decision-making helps drive the response to counter a growing trend towards vaccine hesitancy. Other strategies include establishing partnerships with government departments and relevant non-governmental organisations to ensure services are implemented and culturally appropriate. The outcomes of this research will afford policymakers, stakeholders in healthcare, and cultural mediators the capacity to identify strengths and potential problems associated with pandemic health information and to subsequently implement creative and culturally specific solutions that go beyond the provision of written documentation via translation or interpreting. It will also enable governing bodies to adjust multilingual polices and to adopt mediation strategies that will improve information delivery and intercultural services on a national and international level.

Keywords: intercultural communication, qualitative, public health communication, COVID-19, pandemic, mediated communication, first nations people

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Authors: Kadidiatou Toure

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Mali has started experimentation of teaching the national languages at school through the convergent pedagogy in 1987. Then, it is in 1994 that it will become widespread with eleven of the thirteen former national languages used at primary school. The aim was to improve the Malian educational system because the use of French as the only medium of instruction was considered a contributing factor to the significant number of student dropouts and the high rate of repetition. The Convergent pedagogy highlights the knowledge acquired by children at home, their vision of the world and especially the knowledge they have of their mother tongue. That pedagogy requires the use of a specific medium only during classroom practices and teachers have been trained in this sense. The specific medium depends on the learning content, which sometimes is French, other times, it is the national language. Research has shown that bilingual learners do not only use the required medium in their learning activities, but they code switch. It is part of their learning processes. Currently, many scholars agree on the importance of CS in bilingual classes, and teachers have been told about the necessity of integrating it into their classroom practices. One of the challenges of the Malian bilingual education curriculum is the question of ‘effective languages management’. Theoretically, depending on the classrooms, an average have been established for each of the involved language. Following that, teachers make use of CS differently, sometimes, it favors the learners, other times, it contributes to the development of some linguistic weaknesses. The present research tries to fill that gap through a tentative model of didactization of CS, which simply means the practical management of the languages involved in the bilingual classrooms. It is to know how to use CS for effective learning. Moreover, the didactization of CS tends to sensitize the teachers about the functional role of CS so that they may overcome their own weaknesses. The overall goal of this research is to make code switching a real tool for bilingual education. The specific objectives are: to identify the types of CS used during classroom activities to present the functional role of CS for the teachers as well as the pupils. to develop a tentative model of code-switching, which will help the teachers in transitional classes of bilingual schools to recognize the appropriate moment for making use of code switching in their classrooms. The methodology adopted is a qualitative one. The study is based on recorded videos of teachers of 3rd year of primary school during their classroom activities and interviews with the teachers in order to confirm the functional role of CS in bilingual classes. The theoretical framework adopted is the typology of CS proposed by Poplack (1980) to identify the types of CS used. The study reveals that teachers need to be trained on the types of CS and the different functions they assume and on the consequences of inappropriate use of language alternation.

Keywords: bilingual curriculum, code switching, didactization, national languages

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Authors: Saman Khan, Imrana Naseem

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Copper is an essential trace element required for pro-angiogenic co-factors including vascular endothelial growth factor (VEGF). Elevated levels of copper are found in various types of cancer including prostrate, colon, breast, lung and liver for angiogensis and metastasis. Therefore, targeting copper via copper-specific chelators in cancer cells can be developed as effective anticancer treatment strategy. In continuation of our pursuit to design and synthesize copper chelators, herein we opted for a reaction to incorporate di-(2-picolyl) amine in 3-(bromoacetyl) coumarin (parent backbone) for the synthesis of complex 1. We evaluated lipid peroxidation, protein carbonylation, ROS generation, DNA damage and consequent apoptosis by complex 1 in exogenously added Cu(II) in human peripheral lymphocytes (simulate malignancy condition). Results showed that Cu(II)-complex 1 interaction leads to cell proliferation inhibition, apoptosis, ROS generation and DNA damage in human lymphocytes, and these effects were abrogated by cuprous chelator neocuproine and ROS scavengers (thiourea, catalase, SOD). This indicates that complex 1 cytotoxicity is due to redox cycling of copper to generate ROS which leads to pro-oxidant cell death in cancer cells. To further confirm our hypothesis, using the rat model of diethylnitrosamine (DEN) induced hepatocellular carcinoma; we showed that complex 1 mediates DNA breakage and cell death in isolated carcinoma cells. Membrane permeant copper chelator, neocuproine, and ROS scavengers inhibited the complex 1-mediated cellular DNA degradation and apoptosis. In summary, complex 1 anticancer activity is due to its copper chelation capability. These results will provide copper chelation as an effective targeted cancer treatment strategy for selective cytotoxic action against malignant cells without affecting normal cells.

Keywords: cancer treatment, copper chelation, ROS generation, DNA damage, redox cycling, apoptosis

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