Search results for: gene expression

Authors: Tamar Khardziani, Violeta Berikashvili, Mariam Rusitashvili, Eva Kachlishvili, Vladimir Elisashvili, Mikheil Asatiani

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Last years, the search for natural sources of novel and effective antifungal substances became a scientific and technological challenge. In the present research, thirty basidiomycetes isolated from various ecological niches of Georgia and belonging to different taxonomic groups were screened for their antifungal activities against pathogenic fungi such as Aspergillus, Fusarium, and Guignardia bidwellii. Among mushroom tested, several potential producers of antifungal substances have been revealed, such as Schizophyllum commune, Lentinula edodes, Ganoderma abietinum, Fomes fomentarius, Hericium erinaceus, and Trametes versicolor. For mushroom cultivation and expression of antifungal potential, submerged and solid-state fermentations of different plant raw materials were performed and various approaches and strategies have been exploited. Sch. commune appeared as a most promising producer of antifungal compounds. It was established that among different agro-industrial wastes, the presence of mandarin juice production waste in a nutrient medium, causing the significant increase of antifungal activity Sch. commune (growth inhibition: Aspergillus – 59 %, Fusarium – 55 %, G. bidwellii – 78 %, after 3, 2 and 4 days of cultivation, respectively). Besides this, Sch. commune demonstrate similar antifungal activities in the presence of glucose, glycerol, maltose, mannitol, and xylose, and growth inhibition of Fusarium ranged in 41 % - 49 % during 6 days of cultivation. Inhibition of Aspergillus growth inhibition varied in 27 % - 36 %, and inhibition of G. bidwellii was in the range 49 % - 61 %, respectively. Sch. commune under solid-state fermentation of mandarin peels at 13 days of cultivation demonstrates powerful growth inhibition of pathogenic fungi (growth inhibition: Aspergillus – 50 %, Fusarium – 61 %, G. bidwellii – 68 %, after 3, 4, and 4 days of cultivation, respectively) as well as at 20 days old mushroom (growth inhibition: Aspergillus – 41 %, Fusarium – 54 %, G. bidwellii – 66 %, after 3 days of cultivation). It was established that Sch. commune was effective as a producer of antifungal compounds in submerged as well as in solid-state fermentation. Finally, performed study confirms that the higher basidiomycetes possess antifungal potential, which strongly depends on the physiological factors of growth. Acknowledgments: The work was implemented with the financial support of fundamental science project FR-19-3719 by the Shota Rustaveli National Science Foundation of Georgia.

Keywords: antifungal potential, higher basidiomycetes, pathogenic fungi, submerged and solid-state fermentation

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Authors: Mengfei Peng, Serajus Salaheen, Debabrata Biswas

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Lactobacillus casei found in the human intestine and mouth is commonly applied for dairy production. Recently, it was found that some byproducts produced by Lactobacillus exhibited antimicrobial activities against multiple bacteria. Meanwhile, introduction of prebiotic-like foods (e.g. cocoa) or probiotics or both of them as food supplements in human diets as well as in farm animal feeds is believed to be an effective ways in control/reduce the colonization of foodborne bacterial pathogens infection in the gut environment. We hypothesized that cocoa may stimulate the production antimicrobial components of Lactobacillus casei and may potentially inhibit/reduce the colonization and infection of foodborne bacterial pathogens in the gut. Mixed culture of L. casei (LC) with enterohemorrhagic E. coli EDL933 (EHEC), Salmonella Typhimurium LT2 (ST), or Listeria monocytogenes LM2 (LM) showed that LC could competitively exclude (100%) them within 72 h. Further, investigation of cell-free culture supernatant (CFCS) revealed that the antimicrobial effects of LC came from CFCS. CFCS of LC eliminated (100%) EHEC, ST, and LM within 72 h, and 2 h CFCS treatment increased the hydrophobicity of EHEC (5.10 folds), ST (8.48 folds), and LM (2.03 folds). In addition, LC cells exhibited more inhibitive effects than CFCS on cell adhesive and invasive activities of EHEC (52.14% & 90.45%), ST (66.89% & 93.83%), and LM (61.10% & 83.40%). Two clusters of poly-peptides in CFCS were identified by SDS-PAGE, the molecular weights of which are ≈5 KD and 40-45 KD. LC CFCS with overnight growth in the presence of 3% strengthened all of the antimicrobial activities (growth inhibition, outer membrane disruption, and cell infective ability reduction). Liquid chromatography/Mass spectrometry analysis detected 5 unique components in class of flavonoids in LC CFCS with overnight 3% cocoa supplement. Furthermore, qPCR results showed that CFCSs up-regulated the expression level of genes responsible for flagellin synthesis and motility, but down-regulated genes for specific binding and invasion-associated proteins synthesis. The stimulatory effects of cocoa in producing bioactive components of probiotics may aid prevention of foodborne illness caused by major foodborne enteric bacterial pathogens.

Keywords: foodborne pathogens, probiotics, prebiotics, pathogen exclusion

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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: 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: 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: 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: Irina M. Kolesnikova, Andrey M. Gaponov, Sergey A. Roumiantsev, Tatiana V. Grigoryeva, Dilyara R. Khusnutdinova, Dilyara R. Kamaldinova, Alexander V. Shestopalov

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Background. Obese patients have unequal risks of metabolic disorders. It is accepted to distinguish between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). MUHO patients have a high risk of metabolic disorders, insulin resistance, and diabetes mellitus. Among the other things, the gut microbiota also contributes to the development of metabolic disorders in obesity. Obesity is accompanied by significant changes in the gut microbial community. In turn, bacterial translocation from the intestine is the basis for the blood microbiome formation. The aim was to study the features of the blood microbiome in patients with various metabolic types of obesity. Patients, materials, methods. The study included 116 healthy donors and 101 obese patients. Depending on the metabolic type of obesity, the obese patients were divided into subgroups with MHO (n=36) and MUHO (n=53). Quantitative and qualitative assessment of the blood microbiome was based on metagenomic analysis. Blood samples were used to isolate DNA and perform sequencing of the variable v3-v4 region of the 16S rRNA gene. Alpha diversity indices (Simpson index, Shannon index, Chao1 index, phylogenetic diversity, the number of observed operational taxonomic units) were calculated. Moreover, we compared taxa (phyla, classes, orders, and families) in terms of isolation frequency and the taxon share in the total bacterial DNA pool between different patient groups. Results. In patients with MHO, the characteristics of the alpha-diversity of the blood microbiome were like those of healthy donors. However, MUHO was associated with an increase in all diversity indices. The main phyla of the blood microbiome were Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. Cyanobacteria, TM7, Thermi, Verrucomicrobia, Chloroflexi, Acidobacteria, Planctomycetes, Gemmatimonadetes, and Tenericutes were found to be less significant phyla of the blood microbiome. Phyla Acidobacteria, TM7, and Verrucomicrobia were more often isolated in blood samples of patients with MUHO compared with healthy donors. Obese patients had a decrease in some taxonomic ranks (Bacilli, Caulobacteraceae, Barnesiellaceae, Rikenellaceae, Williamsiaceae). These changes appear to be related to the increased diversity of the blood microbiome observed in obesity. An increase of Lachnospiraceae, Succinivibrionaceae, Prevotellaceae, and S24-7 was noted for MUHO patients, which, apparently, is explained by a magnification in intestinal permeability. Conclusion. Blood microbiome differs in obese patients and healthy donors at class, order, and family levels. Moreover, the nature of the changes is determined by the metabolic type of obesity. MUHO linked to increased diversity of the blood microbiome. This appears to be due to increased microbial translocation from the intestine and non-intestinal sources.

Keywords: blood microbiome, blood bacterial DNA, obesity, metabolically healthy obesity, metabolically unhealthy obesity

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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: 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: 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

Procedia PDF Downloads 174

Authors: B. Gonzalez-Yebra, H. Barajas, P. Palomares, M. Hernandez, O. Torres, M. Ayala, A. L. González, G. Vazquez-Ortiz, M. L. Guzman

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Leukemia arises by molecular alterations of the normal hematopoietic stem cell (HSC) transforming it into a leukemic stem cell (LSC) with high cell proliferation, self-renewal, and cell differentiation. Chronic myeloid leukemia (CML) originates from an LSC-leading to elevated proliferation of myeloid cells and acute lymphoblastic leukemia (ALL) originates from an LSC development leading to elevated proliferation of lymphoid cells. In both cases, LSC can be identified by multicolor flow cytometry using several antibodies. However, to date, LSC levels in peripheral blood (PB) are not established well enough in ALL and CML patients. On the other hand, the detection of the minimal residue disease (MRD) in leukemia is mainly based on the identification of the mRNA bcr-abl gene in CML patients and some other genes in ALL patients. There is no a properly biomarker to detect MDR in both types of leukemia. The objective of this study was to determine mRNA bcr-abl and the percentage of LSC in peripheral blood of patients with CML and ALL and identify a possible association between the amount of LSC in PB and clinical data. We included in this study 19 patients with Leukemia. A PB sample was collected per patient and leukocytes were obtained by Ficoll gradient. The immunophenotype for LSC CD34+ was done by flow cytometry analysis with CD33, CD2, CD14, CD16, CD64, HLA-DR, CD13, CD15, CD19, CD10, CD20, CD34, CD38, CD71, CD90, CD117, CD123 monoclonal antibodies. In addition, to identify the presence of the mRNA bcr-abl by RT-PCR, the RNA was isolated using TRIZOL reagent. Molecular (presence of mRNA bcr-abl and LSC CD34+) and clinical results were analyzed with descriptive statistics and a multiple regression analysis was performed to determine statistically significant association. In total, 19 patients (8 patients with ALL and 11 patients with CML) were analyzed, 9 patients with de novo leukemia (ALL = 6 and CML = 3) and 10 under treatment (ALL = 5 and CML = 5). The overall frequency of mRNA bcr-abl was 31% (6/19), and it was negative in ALL patients and positive in 80% in CML patients. On the other hand, LSC was determined in 16/19 leukemia patients (%LSC= 0.02-17.3). The Novo patients had higher percentage of LSC (0.26 to 17.3%) than patients under treatment (0 to 5.93%). The amount of LSC was significantly associated with the amount of LSC were: absence of treatment, the absence of splenomegaly, and a lower number of leukocytes, negative association for the clinical variables age, sex, blasts, and mRNA bcr-abl. In conclusion, patients with de novo leukemia had a higher percentage of circulating LSC than patients under treatment, and it was associated with clinical parameters as lack of treatment, absence of splenomegaly and a lower number of leukocytes. The mRNA bcr-abl detection was only possible in the series of patients with CML, and molecular detection of LSC could be identified in the peripheral blood of all leukemia patients, we believe the identification of circulating LSC may be used as biomarker for the detection of the MRD in leukemia patients.

Keywords: stem cells, leukemia, biomarkers, flow cytometry

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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: Nasser Y. Athamneh

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Muzaffar al-Nawwab (1934--) is a modern Iraqi poet, critic, and painter, well-known to Arab youth of the second half of the 20th century for his revolutionary spirit and political activism. For the greater part of his relatively long life, al-Nawwab was wanted 'dead or alive,' so to speak, by most of the Arab regimes and authorities due to his scathing, and at times unsparingly obscene attacks on them. Hence it is that the Arab masses found in his poetry the rebellious expression of their own anger and frustration, stifled by fear for their physical safety. Thus, al-Nawwab’s contemporary Arab audience loved and embraced him both as an Arab exile and as a poet. They memorized and celebrated his poems and transmitted them secretly by word of mouth and on compact cassette tapes. He himself recited his own poetry and had it recorded on compact cassette tapes for fans to smuggle from one Arab country to the other. The themes of al-Nawwab’s poems are varied, but the most predominant among them is political opposition. In most of his poems, al-Nawwab takes up politics as the major theme. Yet, he often represents it coupled with the leitmotifs of women and wine. Indeed he oscillates almost systematically between political commitment to the revolutionary cause of the masses of his nation and homeland on the one hand and love for women and wine on the other. For the persona in al-Nawwab’s poetry, love-longing for the woman and devotion to the cause of revolution and Pan-Arabism are interrelated; each of them readily evokes the other. In this paper, an attempt is made at investigating the treatment and representation of the theme of revolution and political opposition in some of al-Nawwab’s poems. This investigation will be conducted through close reading and textual analysis of representative sections of the poetic texts under consideration in the paper. The primary texts for the study are selected passages from two representative poems, namely, 'The Night Song of the Bow Strings' (Watariyyaat Layliyyah) and 'In Wine and Sorrow My Heart [Is Immersed]' (bil-khamri wa bil-huzni fu’aady). Other poems and extracts from al-Nawwab’s poetic works will be drawn upon as secondary texts to clarify the arguments in the paper and support its thesis. The discussions and textual analysis of the texts under consideration are meant to show that revolution and undaunted political opposition is a predominant theme in al-Nawwab’s poetry, often represented through the use of the leitmotifs of women and wine.

Keywords: Arabic poetry, Muzaffar al-Nawwab, politics, revolution

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Authors: Pakize Neslihan Taslı, Alev Cumbul, Gul Merve Yalcın, Fikrettin Sahin

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A key experimental trial in the regeneration of large oral and craniofacial defects is the neogenesis of osseous and ligamentous interfacial structures. Currently, oral regenerative medicine strategies are unpredictable for repair of tooth supporting tissues destroyed as a consequence of trauma, chronic infection or surgical resection. A different approach combining the gel-casting method with Hydroxy Apatite HA-based scaffold and different cell lineages as a hybrid system leads to successively mimic the early stage of tooth development, in vitro. HA is widely accepted as a bioactive material for guided bone and tooth regeneration. In this study, it was reported that, HA porous scaffold preparation, characterization and evaluation of structural and chemical properties. HA is the main factor that exists in tooth and it is in harmony with structural, biological, and mechanical characteristics. Here, this study shows mimicking immature tooth at the late bell stage design and construction of HA scaffolds for cell transplantation of human Adipose Stem Cells (hASCs), human Bone Marrow Stem Cells (hBMSCs) and Gingival Epitelial cells for the formation of human tooth dentin-pulp-enamel complexes in vitro. Scaffold characterization was demonstrated by SEM, FTIR and pore size and density measurements. The biological contraction of dental tissues against each other was demonstrated by mRNA gene expressions, histopatologic observations and protein release profile by ELISA tecnique. The tooth shaped constructs with a pore size ranging from 150 to 300 µm arranged by gathering right amounts of materials provide interconnected macro-porous structure. The newly formed tissue like structures that grow and integrate within the HA designed constructs forming tooth cementum like tissue, pulp and bone structures. These findings are important as they emphasize the potential biological effect of the hybrid scaffold system. In conclusion, this in vitro study clearly demonstrates that designed 3D scaffolds shaped as a immature tooth at the late bell stage were essential to form enamel-dentin-pulp interfaces with an appropriate cell and biodegradable material combination. The biomimetic architecture achieved here is providing a promising platform for dental tissue engineering.

Keywords: tooth regeneration, tissue engineering, adipose stem cells, hydroxyapatite tooth engineering, porous scaffold

Procedia PDF Downloads 206

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: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

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Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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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

Procedia PDF Downloads 65

Authors: José Maria, Vânia Laranjo, Luís Abrunhosa, António Inês

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The occurrence of mycotoxigenic moulds such as Aspergillus, Penicillium and Fusarium in food and feed has an important impact on public health, by the appearance of acute and chronic mycotoxicoses in humans and animals, which is more severe in the developing countries due to lack of food security, poverty and malnutrition. This mould contamination also constitutes a major economic problem due the lost of crop production. A great variety of filamentous fungi is able to produce highly toxic secondary metabolites known as mycotoxins. Most of the mycotoxins are carcinogenic, mutagenic, neurotoxic and immunosuppressive, being ochratoxin A (OTA) one of the most important. OTA is toxic to animals and humans, mainly due to its nephrotoxic properties. Several approaches have been developed for decontamination of mycotoxins in foods, such as, prevention of contamination, biodegradation of mycotoxins-containing food and feed with microorganisms or enzymes and inhibition or absorption of mycotoxin content of consumed food into the digestive tract. Some group of Gram-positive bacteria named lactic acid bacteria (LAB) are able to release some molecules that can influence the mould growth, improving the shelf life of many fermented products and reducing health risks due to exposure to mycotoxins. Some LAB are capable of mycotoxin detoxification. Recently our group was the first to describe the ability of LAB strains to biodegrade OTA, more specifically, Pediococcus parvulus strains isolated from Douro wines. The pathway of this biodegradation was identified previously in other microorganisms. OTA can be degraded through the hydrolysis of the amide bond that links the L-β-phenylalanine molecule to the ochratoxin alpha (OTα) a non toxic compound. It is known that some peptidases from different origins can mediate the hydrolysis reaction like, carboxypeptidase A an enzyme from the bovine pancreas, a commercial lipase and several commercial proteases. So, we wanted to have a better understanding of this OTA degradation process when LAB are involved and identify which molecules where present in this process. For achieving our aim we used some bioinformatics tools (BLAST, CLUSTALX2, CLC Sequence Viewer 7, Finch TV). We also designed specific primers and realized gene specific PCR. The template DNA used came from LAB strains samples of our previous work, and other DNA LAB strains isolated from elderberry fruit, silage, milk and sausages. Through the employment of bioinformatics tools it was possible to identify several proteins belonging to the carboxypeptidase family that participate in the process of OTA degradation, such as serine type D-Ala-D-Ala carboxypeptidase and membrane carboxypeptidase. In conclusions, this work has identified carboxypeptidase proteins being one of the molecules present in the OTA degradation process when LAB are involved.

Keywords: carboxypeptidase, lactic acid bacteria, mycotoxins, ochratoxin a.

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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: Dace Grauda, Gunta Cekstere, Inta Belogrudova, Andis Karlsons, Isaak Rashal

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Trifolium repens L. (white or Dutch clover) is a perennial herb, belongs to legume family (Leguminosae Juss.), spread extensively by stolons and seeds. The species is cultivated worldwide and was naturalized in many countries in meadows, yards, gardens, along roads and streets etc., especially in temperate regions. It is widespread also in grasslands throughout Riga, the capital of Latvia. The goal of this study was to investigate genetic structure of white clover population in Riga and to evaluate influence of different salt concentration on plants. For this purpose universal retrotranspozone based IRAP (Inter-Retrotransposon Amplified Polymorphism) method was used. The plant material was collected in different regions of Riga and in several urban areas of Latvia. Plant DNA was isolated from in silicogel dried leaves of using 1% CTAB (cetyltrimet-ammonium bromide) buffer DNA extraction procedure. Genetic structure of city population and wild populations were compared. Soil salinization is an important issue associated with low water resources and highly urbanized areas in aride and semi-aride climate conditions, as well as de-icing salt application to prevent ice formation on roads in winter. The T. repens variety ‘Daile’ (form giganteum), one of the often used component of urban greeneries, was studied in this investigation. Plants were grown from seeds and cultivated in the light conditions (18-25 C, 16h/8h of day/night, light intensity 3000 lx) in plastic pots (200 ml), filled with commercial neutralized (pH 5.9 ± 0.3) peat substrate with mineral nutrients. To analyse the impact of increased soil salinity treatments with gradually rising NaCl (0; 20; 40; 60; 80; 100 mM) levels were arranged. Plants were watered when necessary with deionised water to provide optimum substrate moisture 60-70%. The experiment was terminated six weeks after establishment. For analysis of mineral nutrients, dry plant material (above ground part and roots) was used. Decrease of Na content can be significant under elevated salinity till 20 mM NaCl. High NaCl concentrations in the substrate increase Na, Cl, Cu, Fe, and Mn accumulation, but reduce S, Mg, K content in the plant above ground parts. Abiotic stresses generally changes the levels of DNA metilation. Several candidate gene for salt tolerance will be analysed for DNA metilation level using Pyromark-Q24 advanced.

Keywords: DNA metilation, IRAP, soil salinization, white clover

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Authors: Lauren Schuldt Wilson

Abstract:

Felicia Hemans’ memorializing of the unwritten lives of women and the consequent allowance for marginalized voices to remember and be remembered has been considered by many critics in terms of ekphrasis and elegy, terms which privilege the question of whether Hemans’ poeticizing can represent lost voices of history or only her poetic expression. Amy Gates, Brian Elliott, and others point out Hemans’ acknowledgement of the self-projection necessary for imaginatively filling the absences of unrecorded histories. Yet, few have examined the complex temporal positioning Hemans inscribes in these moments of self-projection and imaginative historicizing. In poems like ‘The Image in Lava,’ Hemans maps not only a lost past, but also a lost potential future onto the image of a dead infant in its mother’s arms, the discovery and consideration of which moves the imagined viewer to recover and incorporate the ‘hope’ encapsulated in the figure of the infant into a reevaluation of national time embodied by the ‘relics / Left by the pomps of old.’ By examining Hemans’ acknowledgement and response to Percy Bysshe Shelley’s ‘Ozymandias,’ this essay explores how Hemans’ depictions of imaginative historicizing open new horizons of possibility and reevaluate temporal value structures by imagining previously undiscovered or unexplored potentialities of the past. Where Shelley’s poem mocks the futility of national power and time, this essay outlines Hemans’ suggestion of alternative threads of identity and temporal meaning-making which, regardless of historical veracity, exist outside of and against the structures Shelley challenges. Counter to previous readings of Hemans’ poem as celebration of either recovered or poetically constructed maternal love, this essay argues that Hemans offers a meditation on sites of reproduction—both of personal reproductive futurity and of national reproduction of power. This meditation culminates in Hemans’ gesturing towards a method of historicism by which the imagined viewer reinvigorates the sterile, ‘shattered visage’ of national time by forming temporal identity through the imagining of trans-historical hope inscribed on the infant body of the universal, individual subject rather than the broken monument of the king.

Keywords: futurity, national temporalities, reproduction, revisionary histories

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Authors: Theo Heyns Veldsman, Dieter Veldsman

Abstract:

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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