Search results for: expression of love

Authors: Yuanrui Xu, Zailin Yang, Yunqiu Song, Guanxixi Jiang

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It is an important subject of seismology on the influence of local topography on ground motion during earthquake. In mountainous areas with complex terrain, the construction of the tunnel is often the most effective transportation scheme. In these projects, the local terrain can be simplified into hills with different shapes, and the underground tunnel structure can be regarded as a subsurface cavity. The presence of the subsurface cavity affects the strength of the rock mass and changes the deformation and failure characteristics. Moreover, the scattering of the elastic waves by underground structures usually interacts with local terrains, which leads to a significant influence on the surface displacement of the terrains. Therefore, it is of great practical significance to study the surface displacement of local terrains with underground tunnels in earthquake engineering and seismology. In this work, the region is divided into three regions by the method of region matching. By using the fractional Bessel function and Hankel function, the complex function method, and the wave function expansion method, the wavefield expression of SH waves is introduced. With the help of a constitutive relation between the displacement and the stress components, the hoop stress and radial stress is obtained subsequently. Then, utilizing the continuous condition at different region boundaries, the undetermined coefficients in wave fields are solved by the Fourier series expansion and truncation of the finite term. Finally, the validity of the method is verified, and the surface displacement amplitude is calculated. The surface displacement amplitude curve is discussed in the numerical results. The results show that different parameters, such as radius and buried depth of the tunnel, wave number, and incident angle of the SH wave, have a significant influence on the amplitude of surface displacement. For the underground tunnel, the increase of buried depth will make the response of surface displacement amplitude increases at first and then decreases. However, the increase of radius leads the response of surface displacement amplitude to appear an opposite phenomenon. The increase of SH wave number can enlarge the amplitude of surface displacement, and the change of incident angle can obviously affect the amplitude fluctuation.

Keywords: method of region matching, scattering of SH wave, subsurface cavity, trapezoidal hill

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Authors: Don Anushka Sandaruwan Elvitigala, P. D. S. U. Wickramasinghe, Jehee Lee

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Cystatins are a large superfamily of proteins which act as reversible inhibitors of cysteine proteases. Papain proteases and cysteine cathepsins are predominant substrates of cystatins. Cystatin superfamily can be further clustered into three groups as Stefins, Cystatins, and Kininogens. Among them, stefines are also known as family 1 cystatins which harbors cystatin Bs and cystatin As. In this study, a homologue of family one cystatins more close to cystatin Bs was identified from Korean black rockfish (Sebastes schlegeli) using a prior constructed cDNA (complementary deoxyribonucleic acid) database and designated as RfCyt1. The full-length cDNA of RfCyt1 consisted of 573 bp, with a coding region of 294 bp. It comprised a 5´-untranslated region (UTR) of 55 bp, and 3´-UTR of 263 bp. The coding sequence encodes a polypeptide consisting of 97 amino acids with a predicted molecular weight of 11kDa and theoretical isoelectric point of 6.3. The RfCyt1 shared homology with other teleosts and vertebrate species and consisted conserved features of cystatin family signature including single cystatin-like domain, cysteine protease inhibitory signature of pentapeptide (QXVXG) consensus sequence and N-terminal two conserved neighboring glycine (⁸GG⁹) residues. As expected, phylogenetic reconstruction developed using the neighbor-joining method showed that RfCyt1 is clustered with the cystatin family 1 members, in which more closely with its teleostan orthologues. An SYBR Green qPCR (quantitative polymerase chain reaction) assay was performed to quantify the RfCytB transcripts in different tissues in healthy and immune stimulated fish. RfCyt1 was ubiquitously expressed in all tissue types of healthy animals with gill and spleen being the highest. Temporal expression of RfCyt1 displayed significant up-regulation upon infection with Aeromonas salmonicida. Recombinantly expressed RfCyt1 showed concentration-dependent papain inhibitory activity. Collectively these findings evidence for detectable protease inhibitory and immunity relevant roles of RfCyt1 in Sebastes schlegeli.

Keywords: Sebastes schlegeli, family 1 cystatin, immune stimulation, expressional modulation

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Authors: Mrinal Gupta, Mohammad Rumman, Babita Singh Abbas Ali Mahdi, Shivani Pandey

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Introduction: Berberine (BBR), a bioactive compound isolated from Coptidis Rhizoma, possesses diverse pharmacological activities, including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic, and anti-diabetic. However, its role as an anti-diabetic agent in animal models of dexamethasone (Dex)-induced diabetes remains unknown. Studies have shown that natural compounds, including aloe, caper, cinnamon, cocoa, green and black tea, and turmeric, can be used for treating Type 2 diabetes mellitus (DM). Compared to conventional drugs, natural compounds have fewer side effects and are easily available. Herein, we studied the anti-diabetic effects of BBR in a mice model of Dex-induced diabetes. Methods: HepG2 cell line was used for glucose release and glycogen synthesis studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. For animal studies, mice were treated with Dex (2 mg/kg, i.m.) for 30 days and the effect of BBR at the doses 100, 200, and 500 mg/kg (p.o.) was analyzed. Glucose, insulin, and pyruvate tests were performed to evaluate the development of the diabetic model. An echo MRI was performed to assess the fat mass. Further, to elucidate the mechanism of action of BBR, mRNA expression of genes regulating gluconeogenesis, glucose uptake, and glycolysis were analyzed. Results: In vitro BBR had no impact on cell viability up to a concentration of 50μM. Moreover, BBR suppressed the hepatic glucose release and improved glucose tolerance in HepG2 cells. In vivo, BBR improved glucose homeostasis in diabetic mice, as evidenced by enhanced glucose clearance, increased glycolysis, elevated glucose uptake, and decreased gluconeogenesis. Further, Dex treatment increased the total fat mass in mice, which was ameliorated by BBR treatment. Conclusion: BBR improves glucose tolerance by increasing glucose clearance, inhibiting hepatic glucose release, and decreasing obesity. Thus, BBR may become a potential therapeutic agent for treating glucocorticoid-induced diabetes and obesity in the future.

Keywords: glucocorticoid, hyperglycemia, berberine, HepG2 cells, insulin resistance, glucose

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Authors: Shveta Bathla, Preeti Rawat, Sudarshan Kumar, Rubina Baithalu, Jogender Singh Rana, Tushar Kumar Mohanty, Ashok Kumar Mohanty

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Pregnancy is a complex process which includes series of events such as fertilization, formation of blastocyst, implantation of embryo, placental formation and development of fetus. The success of these events depends on various interactions which are synchronized by endocrine interaction between a receptive dam and competent embryo. These interactions lead to change in expression of hormones and proteins. But till date no protein biomarker is available which can be used to detect successful completion of these events. We employed quantitative proteomics approach to develop putative serological biomarker which has diagnostic applicability for early detection of pregnancy in cows. For this study, sera were collected from control (non-pregnant, n=6) and pregnant animals on successive days of pregnancy (7, 19, 45, n=6). The sera were subjected to depletion for removal of albumin using Norgen depletion kit. The tryptic peptides were labeled with iTRAQ. The peptides were pooled and fractionated using bRPLC over 80 min gradient. Then 12 fractions were injected to nLC for identification and quantitation in DDA mode using ESI. Identification using Mascot search revealed 2056 proteins out of which 352 proteins were differentially expressed. Twenty proteins were upregulated and twelve proteins were down-regulated with fold change > 1.5 and < 0.6 respectively (p < 0.05). The gene ontology studies of DEPs using Panther software revealed that majority of proteins are actively involved in catalytic activities, binding and enzyme regulatory activities. The DEP'S such as NF2, MAPK, GRIPI, UGT1A1, PARP, CD68 were further subjected to pathway analysis using KEGG and Cytoscape plugin Cluego that showed involvement of proteins in successful implantation, maintenance of pluripotency, regulation of luteal function, differentiation of endometrial macrophages, protection from oxidative stress and developmental pathways such as Hippo. Further efforts are continuing for targeted proteomics, western blot to validate potential biomarkers and development of diagnostic kit for early pregnancy diagnosis in cows.

Keywords: bRPLC, Cluego, ESI, iTRAQ, KEGG, Panther

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Authors: Jianming Cai

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Exposure to ionizing radiation causes severe damage to human body and an safe and effective radioprotector is urgently required for alleviating radiation damage. In 2008, flagellin, an agonist of TLR5, was found to exert radioprotective effects on radiation injury through activating NF-kB signaling pathway. From then, the radioprotective effects of TLR ligands has shed new lights on radiation protection. CpG-ODN is an unmethylated oligonucleotide which activates TLR9 signaling pathway. In this study, we demonstrated that CpG-ODN has therapeutic effects on radiation injuries induced by γ ray and 12C6+ heavy ion particles. Our data showed that CpG-ODN increased the survival rate of mice after whole body irradiation and increased the number of leukocytes as well as the bone marrow cells. CpG-ODN also alleviated radiation damage on intestinal crypt through regulating apoptosis signaling pathway including bcl2, bax, and caspase 3 etc. By using a radiation-induced pulmonary fibrosis model, we found that CpG-ODN could alleviate structural damage, within 20 week after whole–thorax 15Gy irradiation. In this model, Th1/Th2 imbalance induced by irradiation was also reversed by CpG-ODN. We also found that TGFβ-Smad signaling pathway was regulated by CpG-ODN, which accounts for the therapeutic effects of CpG-ODN in radiation-induced pulmonary injury. On another hand, for high LET radiation protection, we investigated protective effects of CpG-ODN against 12C6+ heavy ion irradiation and found that after CpG-ODN treatment, the apoptosis and cell cycle arrest induced by 12C6+ irradiation was reduced. CpG-ODN also reduced the expression of Bax and caspase 3, while increased the level of bcl2. Then we detected the effect of CpG-ODN on heavy ion induced immune dysfunction. Our data showed that CpG-ODN increased the survival rate of mice and also the leukocytes after 12C6+ irradiation. Besides, the structural damage of immune organ such as thymus and spleen was also alleviated by CpG-ODN treatment. In conclusion, we found that TLR9 ligand, CpG-ODN reduced radiation injuries in response to γ ray and 12C6+ heavy ion irradiation. On one hand, CpG-ODN inhibited the activation of apoptosis induced by radiation through regulating bcl2, bax and caspase 3. On another hand, through activating TLR9, CpG-ODN recruit MyD88-IRAK-TRAF6 complex, activating TAK1, IRF5 and NF-kB pathway, and thus alleviates radiation damage. This study provides novel insights into protection and therapy of radiation damages.

Keywords: TLR9, CpG-ODN, radiation injury, high LET radiation

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Authors: Moin Uddin, M. Masroor A. Khan, Faisal Rasheed, Tariq Ahmad Dar, Akbar Ali, Lalit Varshney

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Oligomers, obtained by exposing the natural polysaccharides (alginate, carrageenan, chitosan, etc.) to cobalt-60 generated gamma radiation may prove as potent plant growth promoters when applied as foliar sprays to the plants. They function as endogenous growth elicitors, triggering the synthesis of different enzymes and modulating various plant responses by exploiting the gene expression. Exogenous application of Jasmonic acid or of its methyl ester, methyl jasmonate (MeJ) has been reported to increase the secondary metabolites production in medicinal and aromatic plants. Keeping this in mind, three pot experiments were conducted to test whether the foliar application of irradiated-chitosan (IC) and MeJ, applied alone or in combination, could augment the active constituents as well as growth, physiological and yield attributes of Catharanthus roseus, which carries anticancer alkaloids, viz. vincristine and vinblastine, in its leaves in addition to various other useful alkaloids. Totally, 5 spray treatments, comprising various aqueous solutions of IC [20, 40, 80 and 160 mg L-1 (Experiment 1)], MeJ (10, 20, 30 and 40 mg L-1 (Experiment 2)] and those of IC+MeJ [40+20, 40+30, 80+20, 80+30, 160+20 and 160+30 mg L-1 (Experiment 3)], were applied at seven days interval. Total leaf-alkaloids content as well as growth, physiological and yield parameters, evaluated at 120 days after sowing, were significantly enhanced by IC application. IC application could not increase the leaf-content of vincristine and vinblastine; nonetheless, it significantly augmented the yield of these alkaloids owing to enhancing the dry mass of leaves per plant. MeJ application, particularly at 30 mg L-1, increased both content (17%) and yield (48%) of total leaf-alkaloids as well as the content and yield of vincristine ( 29 and 63%, respectively) and vinblastine (14 and 44%, respectively) alkaloids, though it significantly decreased most other parameters studied, particularly at higher concentrations (30 and 40 mg L-1 of MeJ). As compared to the control (water-spray treatment), collective application of IC (80 mg L-1) and MeJ (20 mg L-1) resulted in the highest values of most of the parameters studied. However, 80 mg L-1 of IC applied with 30 mg L-1 of MeJ gave the best results for the content and yield of total as well as anticancer leaf-alkaloids (vincristine and vinblastine). Comparing the control, it increased the content and yield of total leaf-alkaloids (37 and 118%, respectively) and those of vincristine (65 and 163%, respectively) and vinblastine (31 and 107%, respectively). Conclusively, the applied technique significantly enhanced the production of total as well as anticancer alkaloids of Catharanthus roseus.

Keywords: anticancer alkaloids (vincristine and vinblastine), catharanthus roseus, irradiated chitosan, methyl jasmonate

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Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Liang Wang, Yongyong Xi, Dejia Li

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Backgrounds: Sulforaphane, one of the most important isothiocyanates in the human diet, is known to have chemopreventive and antioxidant activities in different tissues via activation of NF-E2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase II enzymes, such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). However, its effects on muscular dystrophy remain unknown. This work was undertaken to evaluate the effects of Sulforaphane on Duchenne muscular dystrophy (DMD). Methods: 4-week-old mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 8 weeks. Blood was collected from eye socket every week, and tibial anterior, extensor digitorum longus, gastrocnemius, soleus, triceps brachii muscles and heart samples were collected after 8-week gavage. Force measurements and mice exercise capacity assays were detected. GSH/GSSG ratio, TBARS, CK and LDH levels were analyzed by spectrophotometric methods. H&E staining was used to analyze histological and morphometric of skeletal muscles of mdx mice, and Evas blue dye staining was made to detect sarcolemmal integrity of mdx mice. Further, the role of Sulforaphane on Nrf2/ARE signaling pathway was analyzed by ELISA, western blot and qRT-PCR. Results: Our results demonstrated that SFN treatment increased the expression and activity of muscle phase II enzymes NQO1 and HO-1 with Nrf2 dependent manner. SFN significantly increased skeletal muscle mass, muscle force (~30%), running distance (~20%) and GSH/GSSG ratio (~3.2 folds) of mdx mice, and decreased the activities of plasma creatine phosphokinase (CK) (~45%) and lactate dehydrogenase (LDH) (~40%), gastrocnemius hypertrophy (~25%), myocardial hypertrophy (~20%) and MDA levels (~60%). Further, SFN treatment also reduced the central nucleation (~40%), fiber size variability, inflammation and improved the sarcolemmal integrity of mdx mice. Conclusions: Collectively, these results show that SFN can improve muscle function, pathology and protect dystrophic muscle from oxidative damage in mdx mice through Nrf2 signaling pathway, which indicate Nrf2 may have clinical implications for the treatment of patients with muscular dystrophy.

Keywords: sulforaphane, duchenne muscular dystrophy, Nrf2, oxidative stress

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Authors: Shaimaa Eltanani, Thangal Yumnamcha, Ahmed S. Ibrahim

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Purpose: Mitochondria dysfunction is central to breaking the barrier integrity of retinal endothelial cells (RECs) in various blinding eye diseases such as diabetic retinopathy and retinopathy of prematurity. Therefore, we aimed to dissect the role of different mitochondrial components, specifically, those of oxidative phosphorylation (OxPhos), in maintaining the barrier function of RECs. Methods: Electric cell-substrate impedance sensing (ECIS) technology was used to assess in real-time the role of different mitochondrial components in the total impedance (Z) of human RECs (HRECs) and its components; the capacitance (C) and the total resistance (R). HRECs were treated with specific mitochondrial inhibitors that target different steps in OxPhos: Rotenone for complex I; Oligomycin for ATP synthase; and FCCP for uncoupling OxPhos. Furthermore, data were modeled to investigate the effects of these inhibitors on the three parameters that govern the total resistance of cells: cell-cell interactions (Rb), cell-matrix interactions (α), and cell membrane permeability (Cm). Results: Rotenone (1 µM) produced the greatest reduction in the Z, followed by FCCP (1 µM), whereas no reduction in the Z was observed after the treatment with Oligomycin (1 µM). Following this further, we deconvoluted the effect of these inhibitors on Rb, α, and Cm. Firstly, rotenone (1 µM) completely abolished the resistance contribution of Rb, as the Rb became zero immediately after the treatment. Secondly, FCCP (1 µM) eliminated the resistance contribution of Rb only after 2.5 hours and increased Cm without considerable effect on α. Lastly, Oligomycin had the lowest impact among these inhibitors on Rb, which became similar to the control group at the end of the experiment without noticeable effects on Cm or α. Conclusion: These results demonstrate differential roles for complex I, complex V, and coupling of OxPhos in maintaining the barrier functionality of HRECs, in which complex I being the most important component in regulating the barrier functionality and the spreading behavior of HRECs. Such differences can be used in investigating gene expression as well as for screening selective agents that improve the functionality of complex I to be used in the therapeutic approach for treating REC-related retinal diseases.

Keywords: human retinal endothelial cells (hrecs), rotenone, oligomycin, fccp, oxidative phosphorylation, oxphos, capacitance, impedance, ecis modeling, rb resistance, α resistance, and barrier integrity

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Authors: Beloulou Mohamed Lamine, Fedili Benamar, Meliani Walid, Chaid Dalila, Lamara Abdelhak

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Introduction: Post-surgical chronic pain (PSCP) is a pathological condition with a rather complex etiopathogenesis that extensively involves sensitization processes and neuronal damage. The neuropathic component of these pains is almost always present, with variable expression depending on the type of surgery. Objective: To assess the presumed beneficial effect of Regional Anesthesia-Analgesia Techniques (RAAT) on the development of post-surgical chronic neuropathic pain (PSCNP) in various surgical procedures. Patients and Methods: A comparative study involving 510 patients distributed across five surgical models (mastectomy, thoracotomy, hernioplasty, cholecystectomy, and major abdominal-pelvic surgery) and randomized into two groups: Group A (240) receiving conventional postoperative analgesia and Group B (270) receiving balanced analgesia, including the implementation of a Regional Anesthesia-Analgesia Technique (RAAT). These patients were longitudinally followed over a 6-month period, with postsurgical chronic neuropathic pain (PSCNP) defined by a Neuropathic Pain Score DN2≥ 3. Comparative measurements through univariate and multivariable analyses were performed to identify associations between the development of PSCNP and certain predictive factors, including the presumed preventive impact (protective effect) of RAAT. Results: At the 6th month post-surgery, 419 patients were analyzed (Group A= 196 and Group B= 223). The incidence of PSCNP was 32.2% (n=135). Among these patients with chronic pain, the prevalence of neuropathic pain was 37.8% (95% CI: [29.6; 46.5]), with n=51/135. It was significantly lower in Group B compared to Group A, with respective percentages of 31.4% vs. 48.8% (p-value = 0.035). The most significant differences were observed in breast and thoracopulmonary surgeries. In a multiple regression analysis, two predictors of PSCNP were identified: the presence of preoperative pain at the surgical site as a risk factor (OR: 3.198; 95% CI [1.326; 7.714]) and RAAT as a protective factor (OR: 0.408; 95% CI [0.173; 0.961]). Conclusion: The neuropathic component of PSCNP can be observed in different types of surgeries. Regional analgesia included in a multimodal approach to postoperative pain management has proven to be effective for acute pain and seems to have a preventive impact on the development of PSCNP and its neuropathic nature, particularly in surgeries that are more prone to chronicization.

Keywords: post-surgical chronic pain, post-surgical chronic neuropathic pain, regional anesthesia-analgesia techniques, neuropathic pain score DN2, preventive impact

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Authors: Elisabetta Baldassini

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Responses to atrocities are always unique and context-dependent. They cannot be foretold nor easily prompted. However, the events of the twentieth century had set the scene for the international community to explore new and more robust systems in response to war atrocities, with the ultimate goal being the restoration and maintenance of peace and security. The outlawry of war and the attribution of individual liability for international crimes were two major landmarks that set the roots for the development of international criminal law. From the London Conference (1945) for the establishment of the first international military tribunal in Nuremberg to Rome at the inauguration of the first permanent international criminal court, the development of international criminal law has shaped in itself a fluctuating degree of tensions between justice and maintenance of international peace and security, the cardinal dichotomy of this article. The adoption of judicial measures to achieve peace indeed set justice as an essential feature at the heart of the new international system. Blackhole of this dichotomy is the crime of aggression. Aggression was at first the key component of a wide body of peace projects prosecuted under the charges of crimes against peace. However, the wide array of controversies around aggression mostly related to its definition, determination and the involvement of the Security Council silenced, partly, a degree of efforts and agreements. Notwithstanding the establishment of the International Criminal Court (ICC), jurisdiction over the crime of aggression was suspended until an agreement over the definition and the conditions for the Court’s exercise of jurisdiction was reached. Compromised over the crime was achieved in Kampala in 2010 and the Court’s jurisdiction over the crime of aggression was eventually activated on 17 July 2018. China has steadily supported the advancement of international criminal justice together with the establishment of a permanent international judicial body to prosecute grave crimes and has proactively participated at the various stages of the codification and development of the crime of aggression. However, China has also expressed systematic reservations and setbacks. With the use of primary and secondary sources, including semi-structured interviews, this research aims at analyzing the role that China has played throughout the substantive historical development of the crime of aggression, demonstrating a sharp inclination in the maintenance of international peace and security. Such state behavior seems to reflect national and international political mechanisms that gravitate around a distinct rationale that involves a share of culture and tradition.

Keywords: maintenance of peace and security, cultural expression of justice, crime of aggression, China

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Authors: Adhithy Menon E., Biju C. A.

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In the 1960s, the concept of preserving heritage monuments was first introduced. During the 1990s, the concept of cultural landscapes gained importance, highlighting the importance of culture and heritage. Throughout this paper, we examine the second category of the cultural landscape, which is an organically evolving landscape as it represents a web of tangible, intangible, and ecological heritage and the ways in which they can be rejuvenated. Cultural landscapes in various regions, such as the Chettinad Village clusters, are in serious decline, which is identified through the Heritage Passport program of this area (2007). For this reason, it is necessary to conduct a detailed analysis of the factors that contribute to this degradation to ensure its protection in the future. An analysis of the cultural landscape of the Chettinad Village clusters and its impact on the community is presented in this paper. The paper follows the first objective, which is to understand cultural landscapes and their different criteria and categories. It is preceded by the study of various methods for protecting cultural landscapes. To identify a core area of intervention based on the parameters of Cultural Landscapes and Community Based Tourism, a study and analysis of the regional context of Chettinad village clusters considering tourism development must first be conducted. Lastly, planning interventions for integrating community-based tourism in Chettinad villages for the purpose of rejuvenating the cultural landscapes of the villages as well as their communities. The major findings include the importance of the local community in protecting cultural landscapes. The parameters identified to have an impact on Chettinad Village clusters are a community (community well-being, local maintenance, and enhancement, demand, alternative income for community, public participation, awareness), tourism (location and physical access, journey time, tourist attractions), integrity (natural factors, natural disasters, demolition of structures, deterioration of materials) authenticity (sense of place, living elements, building techniques, artistic expression, religious context) disaster management (natural disasters) and environmental impact (pollution). This area can be restored to its former glory and preserved as part of the cultural landscape for future generations by focusing on and addressing these parameters within the identified core area of the Chettinad Villages cluster (Kanadukathan TP, Kothamangalam, Kottaiyur, Athangudi, Karikudi, and Palathur).

Keywords: Chettinad village clusters, community, cultural landscapes, organically evolved.

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Authors: Hoda M. Eid, Abir Nachar, Farah Thong, Gary Sweeney, Pierre S. Haddad

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Caffeic acid methyl ester (CAME) and caffeic ethyl esters (CAEE) were previously reported to potently stimulate glucose uptake in cultured C2C12 skeletal muscle cells via insulin-independent mechanisms involving the activation of adenosine monophosphate-activated protein kinase (AMPK). In the present study, we investigated the effect of the two compounds on the translocation of glucose transporter GLUT4 in L6 skeletal muscle cells. The cells were treated with the optimum non-toxic concentration (50 µM) of either CAME or CAEE for 18 h. Levels of GLUT4myc at the cell surface were measured by O-phenylenediamine dihydrochloride (OPD) assay. The effects of CAME and CAEE on GLUT1 and GLUT4 protein content were also measured by western immunoblot. Our results show that CAME and CAEE significantly increased glucose uptake, GLUT4 translocation and GLUT4 protein content. Furthermore, the effect of the two CA esters on two insulin-sensitive cell lines: H4IIE rat hepatoma and 3T3-L1 adipocytes were investigated. CAME and CAEE reduced the enzymatic activity of the key hepatic gluconeogenic enzyme glucose-6-phosphatase in a concentration-dependent manner. In addition, they exerted a concentration-dependent antiadipogenic effect on 3T3-L1 cells. Mitotic clonal expansion (MCE), a prerequisite for adipocytes differentiation was also concentration-dependently inhibited. The two compounds abrogated lipid droplet accumulation, blocked MCE and maintained cells in fibroblast-like state when applied at the maximum non-toxic concentration (100 µM). In addition, the expression of the early key adipogenic transcription factors CCAAT enhancer-binding protein beta (C/EBP-β) and the master regulator of adipogenesis peroxisome-proliferator-activated receptor gamma (PPAR-γ) were inhibited. We, therefore, conclude that CAME and CAEE exert pleiotropic benefits in several insulin-sensitive cell lines through insulin-independent mechanisms involving AMPK, hence they may treat obesity, diabetes and other metabolic diseases.

Keywords: type 2 diabetes mellitus, insulin resistance, GLUT4, Akt, AMPK.

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Authors: Alsulami H., Alghamdi N., Alasker A., Almohen N., Shome D.

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Most conventional chemotherapeutic agents which are used for the treatment of cancers not only eradicate cancer cells but also affect normal hematopoietic Stem cells (HSCs) that leads to severe pancytopenia during treatment. Therefore, a need exists for novel approaches to treat cancer without or with minimum effect on normal HSCs. Parthenolide (PTL), a herbal product occurring naturally in the plant Feverfew, is a potential new chemotherapeutic agent for the treatment of many cancers such as acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). In this study we investigated the effect of different PTL concentrations on the viability of normal HSCs and also on the ability of these cells to form colonies after they have been treated with PTL in vitro. Methods: In this study, 24 samples of bone marrow and cord blood were collected with consent, and mononuclear cells were separated using density gradient separation. These cells were then exposed to various concentrations of PTL for 24 hours. Cell viability after culture was determined using 7ADD in a flow cytometry test. Additionally, the impact of PTL on hematopoietic stem cells (HSCs) was evaluated using a colony forming unit assay (CFU). Furthermore, the levels of NFҝB expression were assessed by using a PE-labelled anti-pNFκBP65 antibody. Results: this study showed that there was no statistically significant difference in the percentage of cell death between untreated and PTL treated cells with 5 μM PTL (p = 0.7), 10 μM PTL (p = 0.4) and 25 μM (p = 0.09) respectively. However, at higher doses, PTL caused significant increase in the percentage of cell death. These results were significant when compared to untreated control (p < 0.001). The response of cord blood cells (n=4) on the other hand was slightly different from that for bone marrow cells in that the percentage of cell death was significant at 100 μM PTL. Therefore, cord blood cells seemed more resistant than bone marrow cells. Discussion &Conclusion: At concentrations ≤25 μM PTL has a minimum or no effect on HSCs in vitro. Cord blood HSCs are more resistant to PTL compared to bone marrow HSCs. This could be due to the higher percentage of T-lymphocytes, which are resistant to PTL, in CB samples (85% in CB vs. 56% in BM. Additionally, CB samples contained a higher proportion of CD34+ cells, with 14.5% of brightly CD34+ cells compared to only 1% in normal BM. These bright CD34+ cells in CB were mostly negative for early-stage stem cell maturation antigens, making them young and resilient to oxidative stress and high concentrations of PTL.

Keywords: stem cell, parthenolide, NFKB, CLL

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Authors: Nigatu Tadesse, Ying Liu, Juan Li, Hong Ming Liu

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Gastric carcinogenesis is a lengthy process of histopathological transition from normal to atrophic gastritis (AG) to intestinal metaplasia (GIM), dysplasia toward gastric cancer (GC). The stage of GIM identified as precancerous lesions with resistance to H-pylori eradication and recurrence after endoscopic surgical resection therapies. GIM divided in to two morphologically distinct phenotypes such as complete GIM bearing intestinal type morphology whereas the incomplete type has colonic type morphology. The incomplete type GIM considered to be the greatest risk factor for the development of GC. Studies indicated the expression of the caudal type homeobox 2 (CDX2) gene is responsible for the development of complete GIM but its progressive downregulation from incomplete metaplasia toward advanced GC identified as the risk for IM progression and neoplastic transformation. The downregulation of CDX2 gene have promoted cell growth and proliferation in gastric and colon cancers and ascribed in chemo-treatment inefficacies. CDX2 downregulated through promoter region hypermethylation in which the methylation frequency positively correlated with the dietary history of the patients, suggesting the role of diet as methyl carbon donor sources such as methionine. However, the metabolism of exogenous methionine is yet unclear. Targeting exogenous methionine metabolism has become a promising approach to limits tumor cell growth, proliferation and progression and increase treatment outcome. This review article discusses molecular alterations that could shed light on the potential of exogenous methionine metabolisms, such as gut microbiota alteration as sources of methionine to host cells, metabolic pathway signaling via PI3K/AKt/mTORC1-c-MYC to rewire exogenous methionine and signature of increased gene methylation index, cell growth and proliferation in GIM, with insights to new treatment avenue via targeting methionine metabolism, and the need for future integrated studies on molecular alterations and metabolomics to uncover altered methionine metabolism and characterization of CDX2 methylation in gastric intestinal metaplasia for potential therapeutic exploitation.

Keywords: altered methionine metabolism, Intestinal metaplesia, CDX2 gene, gastric cancer

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Authors: Franco Bruno Castaldo

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Aim: The term bioethics is a term coined by VanPotter R ., who in 1970 thought of a discipline, capable of contributing to a better quality of human life and the cosmos. At first he intended bioethics as a wisdom capable of creating a bridge between bios and ethos and between bio-experimental science and ethical-anthropological sciences.Similarly, the modern sport is presented as a polysemic phenomenon, multidisciplinary, pluris value. From the beginning, the sport is included in the discussion of bioethical problems with doping. Today, the ethical problems of the sport are not only ascribable to doping, the medicalization of society, Techniques for enhancement, violence, Fraud, corruption, even the acceptance of anthropological transhumanist theories. Our purpose is to shed light on these issues so that there is a discernment, a fine-tuning also in educational programs, for the protection of all the sport from a scientist adrift, which would lead to an imbalance of values. Method: Reading, textual and documentary analysis, evaluation of critical examples. Results: Harold VanderZwaag, (1929-2011) in ancient times, asked: how many athletic directors have read works of sport philosophy or humanities? Along with E.A. Zeigler (North American Society for Sport Management) are recognized as pioneers of educational Sport Management. Comes the need to leave the confines of a scientific field, In order to deal with other than itself. Conclusion: The quantitative sciences attracts more funds than qualitative ones, the philosopher M. Nussbaum, has relaunched the idea that the training of students will have to be more disinterested than utilitarian, Offering arguments against the choice of anti-classical, analyzing and comparing different educational systems. schools, universities must assign a prominent place in the program of study to the humanistic, literary and artistic subjects, cultivating a participation that can activate and improve the ability to see the world through the eyes of another person. In order to form citizens who play their role in society, science and technology alone are not enough, we need disciplines that are able to cultivate critical thinking, respect for diversity, solidarity, the judgment, the freedom of expression. According to A. Camelli, the humanities faculties prepare for that life-long learning, which will characterize tomorrow's jobs.

Keywords: bioethics, management, sport, transhumanist, medicalization

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Authors: Khushboo Shah

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Categorical bans on the death penalty and life-without-parole sentences for juvenile offenders in a growing number of countries have established a new era in juvenile jurisprudence. This has been brought about by integration of the growing knowledge in cognitive neuroscience and appreciation of the inherent differences between adults and adolescents over the last ten years. This evolving understanding of being a child in the criminal system can be aptly reflected through policies that incorporate the mitigating traits of youth. First, the presentation will delineate the structures in cognitive neuroscience and in particular, focus on the prefrontal cortex, the amygdala, and the basal ganglia. These key anatomical structures in the brain are linked to three mitigating adolescent traits—an underdeveloped sense of responsibility, an increased vulnerability to negative influences, and transitory personality traits—that establish why juveniles have a lessened culpability. The discussion will delve into the details depicting how an underdeveloped prefrontal cortex results in the heightened emotional angst, high-energy and risky behavior characteristic of the adolescent time period or how the amygdala, the emotional center of the brain, governs different emotional expression resulting in why teens are susceptible to negative influences. Based on this greater understanding, it is incumbent that policies adequately reflect the adolescent physiology and psychology in the criminal system. However, it is important to ensure that these views are appropriately weighted while considering the jurisprudence for the treatment of children in the law. To ensure this balance is appropriately stricken, policies must incorporate the distinctive traits of youth in sentencing and legal considerations and yet refrain from the potential fallacies of absolving a juvenile offender of guilt and culpability. Accordingly, three policies will demonstrate how these results can be achieved: (1) eliminate housing of juvenile offenders in the adult prison system, (2) mandate fitness hearings for all transfers of juveniles to adult criminal court, and (3) use the post-disposition review as a type of rehabilitation method for juvenile offenders. Ultimately, this interdisciplinary approach of science and law allows for a better understanding of adolescent psychological and social functioning and can effectuate better legal outcomes for juveniles tried as adults.

Keywords: criminal law, Juvenile Justice, interdisciplinary, neuroscience

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Authors: Aleksandra Tomic

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According to reliable sources, 4% of all websites is devoted to pornographic material, yet these estimates are often reported to be much higher. The largest internet pornography streaming website reports 21.2 billion visits in 2015 only. Considering the ubiquity of online pornography and the frequency of use, it is necessary to examine its potential influence on the construal of the sexual act and the roles of participants. Apart from the verbal and physical interactions in the pornographic movies themselves, the language in the titles of movies has the power to frame the sexual intercourse. In this study, Critical Discourse Analysis and corpus linguistics approaches will be used to examine the way the sexual intercourse and the roles of the participants are ideologically construed and perpetuated in the Internet pornography discourse. To this end, the study will explore the association between the specific morphosyntactic aspects of the references to performers of both genders, the person and the thematic role, and the gender of referred performer in the corpus of online pornographic movie titles. Distinctive collexeme analysis will be conducted to uncover possible associations between for gender of the performer denoted by the linguistic expression, and the person and thematic role assigned to it in the titles of online pornography movies. Initial results of the chi-square procedure performed on a sample of 295 online pornography movie titles on the largest pornography streaming website ‘Pornhub’ yielded significant results. The use of the three person categories was not equally distributed between genders, X2 (2, N = 106) = 32.52, p < 0.001, with female performers being referred to in the third person in 71.7% of the instances, and speaking in the first person 20.8% of the time, whereas male performers spoke in the first person 68% of the time, and were referred to in the third person in 17% of the instances. Moreover, there was a gender disparity in the assignment of thematic roles, with linguistic expressions for women being assigned the Patient role and men the Agent role in 58.8% of the cases, whereas the roles were reversed in 41.2% of the instances, X2 (1, N = 262) = 8.07633, p < 0.005. The results are discussed in terms of the ideologies surrounding female and male sexuality in the pornography discourse. Potential patterns of power imbalance, objectification, and discrimination are highlighted. Finally, the evidence from psycholinguistic studies on the influence of the language structure on event construal is related to the results of the study.

Keywords: corpus linguistics, gender studies, pornography, thematic roles

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Authors: Jihane Mossalim

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This study proposes a methodological framework that combines Participatory Action Research (PAR) with Arts-Based Research (ABR) to explore the potential of generative AI in elementary art education. By integrating PAR, this framework emphasizes elementary school students’ active participation as co-researchers, engaging with AI technologies and reflecting on their creative journeys. PAR’s iterative cycles of planning, action, observation, and reflection provide a solid structure for involving children in the research process, ensuring that the study is inclusive and reflective of the children’s perspectives. Arts-Based Research, on the other hand, allows for the exploration of AI not just as a tool but as a medium of creative expression. ABR’s emphasis on visual, performative, and creative outputs complements PAR’s inclusive approach, offering a dynamic and flexible way of studying the intersection of technology and art in educational contexts. This combination is particularly valuable as it encourages students to express their ideas and emotions through art, making the learning process more engaging and personally meaningful. Despite the recognized benefits of both PAR and ABR, there remains a notable gap in research that applies these methodologies in combination with elementary school students, particularly in the context of emerging technologies like generative AI. Addressing this gap is crucial, as integrating these approaches can lead to more inclusive and innovative educational practices that cater to the diverse needs of young learners. This chapter seeks to demonstrate how integrating PAR and ABR can empower young learners, giving them a voice in the research process while enriching their creative and critical thinking skills. This chapter will develop a methodology that integrates both theoretical and practical aspects of PAR and ABR, highlighting the challenges and opportunities that emerge when these approaches are integrated. It will also discuss how to adapt these methods for research in the elementary art education, providing a foundation for future inquiry. Further, the chapter will focus on situating these methodological developments in relation to a study that seeks to understand the potential of generative AI in fostering creativity, collaboration, and critical thinking among young learners. Ultimately, this work aims to provide a pioneering example that inspires further exploration and development of educational practices in the digital age.

Keywords: participatory action research, arts-based research, generative AI, elementary art education

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Authors: Chan Yan Nok

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The present study is a qualitative study based on the coping experiences of six Hong Kong Chinese mothers who had childhood trauma from their first-person perspective. Expanding the perspective beyond the dominant discourse of “inter-generation transmission of trauma”, this study explores the experiences and meanings of child trauma embedded in their narratives through the process of thematic analysis and narrative analysis. The interviewees painted a nuanced picture of their process of coping and trauma resolution. First, acknowledgement; second, feel safe and start to tell the story of trauma; third, feel the feelings and expression of emotions; fourth, clarifying and coping with the impacts of trauma; fifth, integration and transformation; and sixth, using their new understanding of experience to have a better life. It was seen that there was no “end” within the process of trauma resolution. Instead, this is an ongoing process with positive healing trajectory. Analysis of the stories of the mothers revealed recurrent themes around continuous self-reflective awareness in the process of trauma coping. Rather than being necessarily negative and detrimental, childhood trauma could highlight the meanings of being a mother and reveal opportunities for continuous personal growth and self-enhancement. Utilizing the sense of inadequacy as a core driver in the trauma recovery process while developing a heightened awareness of the unfinished business embedded in their “automatic pattern” of behaviors, emotions, and thoughts can help these mothers become more flexible to formulate new methods in facing future predicaments. Future social work and parent education practices should help mothers deal with unresolved trauma, make sense of their impacts of childhood trauma and discover the growth embedded in the past traumatic experience. They should be facilitated in “acknowledging the reality of the trauma”, including understanding their complicated emotions arising from the traumatic experiences and voicing their struggles. In addition, helping these mothers to be aware of short-term and long-term trauma impacts (i.e., secondary responses to the trauma) and explore their effective coping strategies in “overcoming secondary responses to the trauma” are crucial for their future positive adjustment and transformation. Through affirming their coping abilities and lessons learnt from past experiences, mothers can reduce feelings of shame and powerlessness and enhance their parental capacity.

Keywords: childhood trauma, coping, mothers, self-awareness, self-reflection, trauma resolution

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Authors: Christopher Benedikt Jakob

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In our current society, there is no need to take a look at the wristwatch to know the exact time. Smartphones, the watch in the car or the computer watch, inform us about the time too. Over hundreds of years, luxury watches have held a fascination for human beings. Consumers buy watches that cost thousands of euros, although they could buy much cheaper watches which also fulfill the function to indicate the correct time. This shows that the functional value has got a minor meaning with reference to the buying-reasons as regards luxury watches. For a few years, people have an increased demand to track data like their walking distance per day or to track their sleep for example. Smart watches enable consumers to get information about these data. There exists a trend that people intend to optimise parts of their social life, and thus they get the impression that they are able to optimise themselves as human beings. With the help of smart watches, they are able to optimise parts of their productivity and to realise their targets at the same time. These smart watches are also offered as luxury models, and the question is: how will customers of traditional luxury watches react? Therefore this study has the intention to give answers to the question why people are willing to spend an enormous amount of money on the consumption of luxury watches. The self-expression model, the relationship basis model, the functional benefit representation model and the means-end-theory are chosen as an appropriate methodology to find reasons why human beings purchase specific luxury watches and luxury smart watches. This evaluative approach further discusses these strategies concerning for example if consumers buy luxury watches/smart watches to express the current self or the ideal self and if human beings make decisions on expected results. The research critically evaluates that relationships are compared on the basis of their advantages. Luxury brands offer socio-emotional advantages like social functions of identification and that the strong brand personality of luxury watches and luxury smart watches helps customers to structure and retrieve brand awareness which simplifies the process of decision-making. One of the goals is to identify if customers know why they like specific luxury watches and dislike others although they are produced in the same country and cost comparable prices. It is very obvious that the market for luxury watches especially for luxury smart watches is changing way faster than it has been in the past. Therefore the research examines the market changing parameters in detail.

Keywords: buying-behaviour, brand management, consumer, luxury watch, smart watch

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Authors: Gobinathan Devathasan, Kezia Devathasan

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Objective: To improve the current modified Broca-Wernicke-Lichtheim-Kussmaul speech schema and provide insight into autism. Methods: We reviewed the pertinent literature. Current findings, involving Brodmann areas 22, 46, 9,44,45,6,4 are based on neuropathology and functional MRI studies. However, in primary autism, there is no lucid explanation and changes described, whether neuropathology or functional MRI, appear consequential. Findings: We forward an enhanced model which may explain the enigma related to autism. Vowel output is subcortical and does need cortical representation whereas consonant speech is cortical in origin. Left lateralization is needed to commence the circuitry spin as our life have evolved with L-amino acids and left spin of electrons. A fundamental species difference is we are capable of three syllable-consonants and bi-syllable expression whereas cetaceans and songbirds are confined to single or dual consonants. The 4 key sites for speech are superior auditory cortex, Broca’s two areas, and the supplementary motor cortex. Using the Argand’s diagram and Reimann’s projection, we theorize that the Euclidean three dimensional synaptic neuronal circuits of speech are quantized to coherent waves, and then decoherence takes place at area 6 (spherical representation). In this quantum state complex, 3-consonant languages are instantaneously integrated and multiple languages can be learned, verbalized and differentiated. Conclusion: We postulate that evolutionary human speech is elevated to quantum interaction unlike cetaceans and birds to achieve the three consonants/bi-syllable speech. In classical primary autism, the sudden speech switches off and on noted in several cases could now be explained not by any anatomical lesion but failure of coherence. Area 6 projects directly into prefrontal saccadic area (8); and this further explains the second primary feature in autism: lack of eye contact. The third feature which is repetitive finger gestures, located adjacent to the speech/motor areas, are actual attempts to communicate with the autistic child akin to sign language for the deaf.

Keywords: quantum neuronal paradigm, cetaceans and human speech, autism and rapid magnetic stimulation, coherence and decoherence of speech

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Authors: Anne Öman

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Today in Sweden and in other countries, a variety of digital artefacts, such as laptops, tablets, interactive whiteboards, are being used at all school levels. From an educational perspective, digital artefacts challenge traditional teaching because they provide a range of modes for expression and communication and are not limited to the traditional medium of paper. Digital technologies offer new opportunities for representations and physical interactions with objects, which put forward the role of the body in interaction and learning. From a multimodal perspective the emphasis is on the use of multiple semiotic resources for meaning- making and the study presented here has examined the differential use of semiotic resources by pupils interacting in a digitally designed task in a primary school context. The instances analyzed in this paper come from a case study where the learning task was to create an advertising film in a film-software. The study in focus involves the analysis of a single case with the emphasis on the examination of the classroom setting. The research design used in this paper was based on a micro ethnographic perspective and the empirical material was collected through video recordings of small-group work in order to explore pupils’ communication within the group activity. The designed task described here allowed students to build, share, collaborate upon and publish the redesigned products. The analysis illustrates the variety of communicative modes such as body position, gestures, visualizations, speech and the interaction between these modes and the representations made by the pupils. The findings pointed out the importance of embodied communication during the small- group processes from a learning perspective as well as a pedagogical understanding of pupils’ representations, which were similar from a cultural literacy perspective. These findings open up for discussions with further implications for the school practice concerning the small- group processes as well as the redesigned products. Wider, the findings could point out how multimodal interactions shape the learning experience in the meaning-making processes taking into account that language in a globalized society is more than reading and writing skills.

Keywords: communicative learning, interactive learning environments, pedagogical issues, primary school education

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Authors: Nandhakumar Elumalai, Purushothaman Ayyakannu, Sachidanandam T. Panchanatham

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Background: Understanding the basic mechanisms and factors underlying the tumor growth and invasion has gained attention in recent times. The processes of angiogenesis and apoptosis are known to play a vital role in various stages of cancer. The vascular endothelial growth factor (VEGF) is well established as one of the key regulators of tumor angiogenesis while MMPs are known for their exclusive ability to degrade ECM. Objective: The present study was designed to evaluate the pro apoptotic and anti angiogenic activity of the herbal formulation Shemamruthaa. The anticancer activity of Shemamruthaa was tested in breast cancer cell line (MCF-7). Results of MTT, trypan blue and flow cytometric analysis of apoptotis suggested that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration- and time dependent manner and induce apoptosis. With these results, we further evaluated the antiangiogenic and pro-apoptotic activities of Shemamruthaa in DMBA induced mammary carcinoma in Sprague Dawley rats. Flavono tumour was induced in 8-week-old Sprague-Dawley rats by gastric intubation of 25 mg DMBA in 1ml olive oil. After 90 days of induction period, the rats were orally administered with Shemamruthaa (400 mg/kg body wt) for 45 days. Treatment with the drug SM significantly modulated the expression of p53, MMP-2, MMP-3, MMP-9 and VEGF by means of its anti angiogenic and protease inhibiting activity. Conclusion: Based on these results, it might be concluded that the formulation, Shemamruthaa, constituted of dried flowers of Hibiscus rosa-sinensis, fruits of Emblica officinalis, and honey has been found to exhibit pronounced antiproliferative and apoptotic effects. This enhanced anticancer effect of Shemamruthaa might be attributed to the synergistic action of polyphenols such as flavonoids, tannins, alkaloids, glycosides, saponins, steroids, terpenoids, vitamin C, niacin, pyrogallol, hydroxymethylfurfural, trilinolein, and other compounds present in the formulation. Collectively, these results demonstrate that Shemamruthaa holds potential to be developed as a potent chemotherapeutic agent against mammary carcinoma.

Keywords: Shemamruthaa, flavonoids, MCF-7 cell line, mammary cancer

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Authors: Kinnsley Travis, Camerron M. Crowder

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Mapk8ip3 (Mitogen-Activated Protein Kinase 8 Interacting Protein 3) is a gene that codes for the JIP3 protein, which is a part of the JIP scaffolding protein family. This protein is involved in axonal vesicle transport, elongation and regeneration. Variants in the Mapk8ip3 gene are associated with a rare-genetic condition that results in a neurodevelopmental disorder that can cause a range of phenotypes including global developmental delay and intellectual disability. Currently, there are 18 known individuals diagnosed to have sequenced confirmed Mapk8ip3 genetic disorders. This project focuses on examining the impact of a subset of missense patient variants on the Jip3 protein function by overexpressing the mRNA of these variants in a zebrafish knockout model for Jip3. Plasmids containing cDNA with individual missense variants were reverse transcribed, purified, and injected into single-cell zebrafish embryos (Wild Type, Jip3 -/+, and Jip3 -/-). At 6-days post mRNA microinjection, morphological, behavioral, and microscopic phenotypes were examined in zebrafish larvae. Morphologically, we compared the size and shape of the zebrafish during their development over a 5-day period. Total locomotive activity was assessed using the Microtracker assay and patterns of movement over time were examined using the DanioVision assay. Lastly, we used confocal microscopy to examine sensory axons for swelling and shortened length, which are phenotypes observed in the loss-of-function knockout Jip3 zebrafish model. Using these assays during embryonic development, we determined the impact of various missense variants on Jip3 protein function, compared to knockout and wild-type zebrafish embryo models. Variants in the gene Mapk8ip3 cause rare-neurodevelopmental disorders due to an essential role in axonal vesicle transport, elongation and regeneration. A subset of missense variants was examined by overexpressing the mRNA of these variants in a Jip3 knock-out zebrafish. Morphological, behavioral, and microscopic phenotypes were examined in zebrafish larvae. Using these assays, the spectrum of disorders can be phenotypically determined and the impact of variant location can be compared to knockout and wild-type zebrafish embryo models.

Keywords: rare disease, neurodevelopmental disorders, mrna overexpression, zebrafish research

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Authors: Chukwuka Justus Iwegbu, Monye Christopher Prayer

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Propeller aircraft engines, and more generally engines with a large rotating part (turboprops, high bypass ratio turbojets, etc.) are widely used in the industry and are subject to numerous developments in order to reduce their fuel consumption. In this context, unconventional architectures such as open rotors or distributed propulsion appear, and it is necessary to consider the influence of these systems on the aircraft's stability in flight. Indeed, the tendency to lengthen the blades and wings on which these propulsion devices are fixed increases their flexibility and accentuates the risk of whirl flutter. This phenomenon of aeroelastic instability is due to the precession movement of the axis of rotation of the propeller, which changes the angle of attack of the flow on the blades and creates unsteady aerodynamic forces and moments that can amplify the motion and make it unstable. The whirl flutter instability can ultimately lead to the destruction of the engine. We note the existence of a critical speed of the incident flow. If the flow velocity is lower than this value, the motion is damped and the system is stable, whereas beyond this value, the flow provides energy to the system (negative damping) and the motion becomes unstable. A simple model of whirl flutter is based on the work of Houbolt & Reed who proposed an analytical expression of the aerodynamic load on a rigid blade propeller whose axis orientation suffers small perturbations. Their work considered a propeller subjected to pitch and yaw movements, a flow undisturbed by the blades and a propeller not generating any thrust in the absence of precession. The unsteady aerodynamic forces were then obtained using the thin airfoil theory and the strip theory. In the present study, the unsteady aerodynamic loads are expressed for a general movement of the propeller (not only pitch and yaw). The acceleration and rotation of the flow by the propeller are modeled using a Blade Element Momentum Theory (BEMT) approach, which also enable to take into account the thrust generated by the blades. It appears that the thrust has a stabilizing effect. The aerodynamic model is further developed using Theodorsen theory. A reduced order model of the aerodynamic load is finally constructed in order to perform linear stability analysis.

Keywords: advancing, entrepreneurial, knowledge, industralization

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Authors: Varsha Salian, Shama Rao, N. Narendra, B. Mohana Kumar

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Evolving evidence proposes the existence of a highly tumorigenic subpopulation of undifferentiated, self-renewing cancer stem cells, responsible for exhibiting resistance to conventional anti-cancer therapy, recurrence, metastasis and heterogeneous tumor formation. Importantly, the mechanisms exploited by cancer stem cells to resist chemotherapy are very less understood. Oral squamous cell carcinoma (OSCC) is one of the most regularly diagnosed cancer types in India and is associated commonly with alcohol and tobacco use. Therefore, the isolation and in vitro characterization of cancer stem-like cells from patients with OSCC is a critical step to advance the understanding of the chemoresistance processes and for designing therapeutic strategies. With this, the present study aimed to establish and characterize cancer stem-like cells in vitro from OSCC. The primary cultures of cancer stem-like cell lines were established from the tissue biopsies of patients with clinical evidence of an ulceroproliferative lesion and histopathological confirmation of OSCC. The viability of cells assessed by trypan blue exclusion assay showed more than 95% at passage 1 (P1), P2 and P3. Replication rate was performed by plating cells in 12-well plate and counting them at various time points of culture. Cells had a more marked proliferative activity and the average doubling time was less than 20 hrs. After being cultured for 10 to 14 days, cancer stem-like cells gradually aggregated and formed sphere-like bodies. More spheroid bodies were observed when cultured in DMEM/F-12 under low serum conditions. Interestingly, cells with higher proliferative activity had a tendency to form more sphere-like bodies. Expression of specific markers, including membrane proteins or cell enzymes, such as CD24, CD29, CD44, CD133, and aldehyde dehydrogenase 1 (ALDH1) is being explored for further characterization of cancer stem-like cells. To summarize the findings, the establishment of OSCC derived cancer stem-like cells may provide scope for better understanding the cause for recurrence and metastasis in oral epithelial malignancies. Particularly, identification and characterization studies on cancer stem-like cells in Indian population seem to be lacking thus provoking the need for such studies in a population where alcohol consumption and tobacco chewing are major risk habits.

Keywords: cancer stem-like cells, characterization, in vitro, oral squamous cell carcinoma

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Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

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Klebsiella pneumoniae bacteria is a global threat to human health due to an increase in multi-drug resistance among strains. The hypervirulent strains of Klebsiella pneumoniae is a major trouble due to their association with life-threatening infections in a healthy population. One of the major virulence factors of hyper virulent strains of Klebsiella pneumoniae is the T6SS (Type six secretary system) which is majorly involved in microbial antagonism and causes interaction with the host eukaryotic cells during infections. T6SS mediates some of the crucial factors for establishing infection by the bacteria, such as cell adherence, invasion, and subsequent in vivo colonisation. The antibacterial activity and the cell invasion property of the T6SS system is a major requirement for the establishment of K. pneumoniae infections within the gut. The T6SS can be an appropriate target for developing therapeutics. The T6SS consists of an inner tube comprising hexamers of Hcp (Haemolysin -regulated protein) protein, and at the top of this tube sits VgrG (Valine glycine repeat protein G); the tip of the machinery consists of PAAR domain containing proteins which act as a delivery system for bacterial effectors. For this study, immune response to recombinant VgrG protein was generated to establish this protein as a potential immunogen for the development of therapeutic leads. The immunogenicity of the selected protein was determined by predicting the B cell epitopes by the BCEP analysis tool. The gene sequence for multiple domains of VgrG protein (phage_base_V, T6SS_Vgr, DUF2345) was selected and cloned in pMAL vector in E. coli. The construct was subcloned and expressed as a fusion protein of 203 residue protein with mannose binding protein tag (MBP) to enhance solubility and purification of this protein. The purified recombinant VgrG fusion protein was used for mice immunisation. The antiserum showed reactivity with the recombinant VgrG in ELISA and western blot. The immunised mice were challenged with K. pneumoniae bacteria and showed bacterial clearance in immunised mice. The recombinant VgrG protein can further be used for studying downstream signalling of VgrG protein in mice during infection and for therapeutic MAb development to eradicate K. pneumoniae infections.

Keywords: immune response, Klebsiella pneumoniae, multi-drug resistance, recombinant protein expression, T6SS, VgrG

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Authors: Theo Heyns Veldsman, Dieter Veldsman

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Organisational Identity (OI) refers to who and what the organisation is, what it stands for and does, and what it aspires to become. OI explores the perspectives of how we see ourselves, are seen by others and aspire to be seen. It provides as rationale the ‘why’ for the organisation’s continued existence. The most widely accepted differentiating features of OI are encapsulated in the organisation’s core, distinctive, differentiating, and enduring attributes. OI finds its concrete expression in the organisation’s Purpose, Vision, Strategy, Core Ideology, and Legacy. In the emerging new order infused by hyper-turbulence and hyper-fluidity, the VICCAS world, OI provides a secure anchor and steady reference point for the organisation, particularly the growing widespread focus on Purpose, which is indicative of the organisation’s sense of social citizenship. However, the transforming world of work (TWOW) - particularly the potent mix of ongoing disruptive innovation, the 4th Industrial Revolution, and the gig economy with the totally unpredicted COVID19 pandemic - has resulted in the consequential adoption of different workplace strategies by organisations in terms of how, where, and when work takes place. Different employment relations (transient to permanent); work locations (on-site to remote); work time arrangements (full-time at work to flexible work schedules); and technology enablement (face-to-face to virtual) now form the basis of the employer/employee relationship. The different workplace strategies, fueled by the demands of TWOW, pose a substantive challenge to organisations of doing durable OI work, able to fulfill OI’s critical attributes of core, distinctive, differentiating, and enduring. OI work is contained in the ongoing, reciprocally interdependent stages of sense-breaking, sense-giving, internalisation, enactment, and affirmation. The objective of our paper is to explore how to do durable OI work relative to different workplace strategies in the TWOW. Using a conceptual-theoretical approach from a practice-based orientation, the paper addresses the following topics: distinguishes different workplace strategies based upon a time/place continuum; explicates stage-wise the differential organisational content and process consequences of these strategies for durable OI work; indicates the critical success factors of durable OI work under these differential conditions; recommends guidelines for OI work relative to TWOW; and points out ethical implications of all of the above.

Keywords: organisational identity, workplace strategies, new world of work, durable organisational identity work

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Authors: Nadzeya Marozkina, Joe Zein, Benjamin Gaston

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Introduction: We have observed that many patients with Primary Ciliary Dyskinesia (PCD) benefit from asthma medications. In healthy airways, the ciliary function is normal. Antigens and irritants are rapidly cleared, and NO enters the gas phase normally to be exhaled. In the PCD airways, however, antigens, such as Dermatophagoides, are not as well cleared. This defect leads to oxidative stress, marked by increased DUOX1 expression and decreased superoxide dismutase [SOD] activity (manuscript under revision). H₂O₂, in high concentrations in the PCD airway, injures the airway. NO is oxidized rather than being exhaled, forming cytotoxic peroxynitrous acid. Thus, antigen stasis on PCD airway epithelium leads to airway injury and may predispose PCD patients to asthma. Indeed, recent population genetics suggest that PCD genes may be associated with asthma. We therefore hypothesized that PCD patients would be predisposed to having asthma. Methods. We analyzed our database of 18 million individual electronic medical records (EMRs) in the Indiana Network for Patient Care research database (INPCR). There is not an ICD10 code for PCD itself; code Q34.8 is most commonly used clinically. To validate analysis of this code, we queried patients who had an ICD10 code for both bronchiectasis and situs inversus totalis in INPCR. We also studied a validation cohort using the IBM Explorys® database (over 80 million individuals). Analyses were adjusted for age, sex and race using a 1 PCD: 3 controls matching method in INPCR and multivariable logistic regression in the IBM Explorys® database. Results. The prevalence of asthma ICD10 codes in subjects with a code Q34.8 was 67% vs 19% in controls (P < 0.0001) (Regenstrief Institute). Similarly, in IBM*Explorys, the OR [95% CI] for having asthma if a patient also had ICD10 code 34.8, relative to controls, was =4.04 [3.99; 4.09]. For situs inversus alone the OR [95% CI] was 4.42 [4.14; 4.71]; and bronchiectasis alone the OR [95% CI] =10.68 (10.56; 10.79). For both bronchiectasis and situs inversus together, the OR [95% CI] =28.80 (23.17; 35.81). Conclusions: PCD causes antigen stasis in the human airway (under review), likely predisposing to asthma in addition to oxidative and nitrosative stress and to airway injury. Here, we show that, by several different population-based metrics, and using two large databases, patients with PCD appear to have between a three- and 28-fold increased risk of having asthma. These data suggest that additional studies should be undertaken to understand the role of ciliary dysfunction in the pathogenesis and genetics of asthma. Decreased antigen clearance caused by ciliary dysfunction may be a risk factor for asthma development.

Keywords: antigen, PCD, asthma, nitric oxide

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Authors: Adhithy Menon E., Biju C. A.

Abstract:

Heritage monuments were first introduced to the public in the 1960s when the concept of preserving them was introduced. As a result of the 1990s, the concept of cultural landscapes gained importance, emphasizing the importance of culture and heritage in the context of the landscape. It is important to note that this paper is primarily concerned with the second category of ecological landscapes, which is organically evolving landscapes, as they represent a complex network of tangible, intangible, and environment, and the connections they share with the communities in which they are situated. The United Nations Educational, Scientific, and Cultural Organization has identified 39 cultural sites as being in danger, including the Iranian city of Bam and the historic city of Zabid in Yemen. To ensure its protection in the future, it is necessary to conduct a detailed analysis of the factors contributing to this degradation. An analysis of selected cultural landscapes from around the world is conducted to determine which parameters cause their degradation. The paper follows the objectives of understanding cultural landscapes and their importance for development, followed by examining various criteria for identifying cultural landscapes, their various classifications, as well as agencies that focus on their protection. To identify and analyze the parameters contributing to the deterioration of cultural landscapes based on literature and case studies (cultural landscape of Sintra, Rio de Janeiro, and Varanasi). As a final step, strategies should be developed to enhance deteriorating cultural landscapes based on these parameters. The major findings of the study are the impact of community in the parameters derived - integrity (natural factors, natural disasters, demolition of structures, deterioration of materials), authenticity (living elements, sense of place, building techniques, religious context, artistic expression) public participation (revenue, dependence on locale), awareness (demolition of structures, resource management) disaster management, environmental impact, maintenance of cultural landscape (linkages with other sites, dependence on locale, revenue, resource management). The parameters of authenticity, public participation, awareness, and maintenance of the cultural landscape are directly related to the community in which the cultural landscape is located. Therefore, by focusing on the community and addressing the parameters identified, the deterioration curve of cultural landscapes can be altered.

Keywords: community, cultural landscapes, heritage, organically evolved, public participation

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