Search results for: inhibition of cancer cells

Authors: Azza T. Tahera, Eman M. Ahmeda, Nadia A. Khalila, Yassin M. Nissanb

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New 3-(pyridin-4-yl)-[1,2,4] triazolo [4,3-b] pyridazine derivatives 2a-i, 4a,b and 6a,b were designed, synthesized and evaluated as cytotoxic agents. All compounds were investigated for their in vitro cytotoxicity at a single dose 10-5M concentration towards 60 cancer cell lines according to USA NCI protocol. The preliminary screening results showed that the majority of tested compounds exhibited remarkable activity against SR (leukemia) cell panel. Molecular docking for all synthesized compounds was performed on the active site of c-Met kinase. The most active compounds, 2f and 4a were further evaluated at a seven dose level screening and their IC50 as a c-Met kinase inhibitors were determined in vitro.

Keywords: triazolopyridazines, pyridazines, cytotoxic activity, cell panel

Procedia PDF Downloads 537

Authors: S. Pathak, R. Lazarus

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A 25-year-old male HIV patient (CD4 cells 20/µL and HIV viral load 14200000 copies/ml) with a past medical history of duodenal ulcer, pneumocystis carinii pneumonia, oesophageal candidiasis presented with fever and a seizure to hospital. The only recent travel had been a religious pilgrimage from Singapore to Malaysia 5 days prior; during the trip he sustained skin abrasions. The patient had recently started highly active antiretroviral therapy 2 months prior. Clinical examination was unremarkable other than a temperature of 38.8°C and perianal warts. Laboratory tests showed a leukocyte count 12.5x109 cells/L, haemoglobin 9.4 g/dL, normal biochemistry and a C-reactive protein 121 mg/L. CT head and MRI head were unremarkable and cerebrospinal fluid analysis performed after a delay (due to technical difficulties) of 11 days was unremarkable. Blood cultures (three sets) taken on admission showed Gram-negative rods in the anaerobic bottles only at the end of incubation with culture result confirmed by molecular sequencing showing Helicobacter cinaedi. The patient was treated empirically with ceftriaxone for seven days and this was converted to oral co-amoxiclav for a further seven days after the blood cultures became positive. A Transthoracic echocardiogram was unremarkable. The patient made a full recovery. Helicobacter cinaedi is a gram-negative anaerobic fastidious organism affecting patients with comorbidity. Infection may manifest as cellulitius, colitis or as in this case as bloodstream infection – the latter is often attributed to faeco-oral infection. Laboratory identification requires prolonged culture. Therapeutic options may be limited by resistance to macrolides and fluoroquinolones. The likely pathogen inoculation routes in the case described include gastrointestinal translocation due to proctitis at the site of perianal warts, or breach of the skin via abrasions occurring during the pilgrimage. Such organisms are increasing in prevalence as our patient population ages and patients have multiple comorbidities including HIV. It may be necessary in patients with unexplained fever to prolong incubation of sterile sites including blood in order to identify this unusual fastidious organism.

Keywords: fastidious, Helicobacter cinaedi, HIV, immunocompromised

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Authors: Agburuga Obi, Madumere Akuego Jane

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This paper explores the important role sports can play in the promotion of good health and prevention of diseases. Technological advancements in today’s world has come along with some difficulties to man. This is because work formally done by man has been taken over by machines, thus, man has become sedentary. This has created a lot of health problems to man such as cardiovascular diseases, diabetes, cancer, obesity, and osteoporosis. To nip this ugly situation in the bud, the following recommendations are made: specific measures should be taken to raise the awareness within the government, key sectors and the population of the diverse benefits or physical activity and sports and the risk and costs of inactivity, provision of equipment, facilities for sports and recreational activities in every community, participation in physical activities in sports if not on daily basis at least thrice a week.

Keywords: physical activities, sport, good health, prevention, diseases

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Authors: Rufai Yakubu And Suleiman Kabiru

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Triterpenoids are a diverse class of secondary metabolites with potential antimicrobial properties. In this study, the crude extracts from ethyl acetate was obtained with ultrasonic extraction method. Using a combined chromatographic separation method to isolate squalene (1) stigmasterol (2), stigmasta-5,22-diene-3-ol acetate (3), γ-sitosterol (4), lupeol (5), taraxasterol (6), and betulinic acid (7) from ethyl acetate extracts. Ethyl acetate crude extracts and isolated compounds were both screened for antimicrobial activity and minimum inhibitory concentration (MIC). For ethyl acetate crude extracts with concentrations of (1.5, 0.75, 0.35, & 0.168 mg/mL) indicated marginal antibacterial activity with a range of 17, 20 and 14 mm zone of inhibition for Staphylococcus aureus, Escherichia coli and Candida albicans and lower minimum inhibitory concentrations ranges from 18.75 µg/ml to 150 µg/mL. Butulinic acid showed the highest activity against E. coli and C. albicans at 15 mm and 15 mm followed by Lupeol against S. aureus, E. coli and C. albicans at 13, 12, 12 mm. Moreso, no antimicrobial activity for both S. aureus and C. albicans with squalene except for E. coli which showed activity at 11 mm with 300 µg/mL (MIC). Thus, abundant triterpenoids in Deinbollia pinnata will be another centered area for antimicrobial drug discovery.

Keywords: triterpenoid, antimicrobial potentials, deinbollia pinnata, aerial parts

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Authors: Mateusz Hermyt, Pawel Kaczmarek, Weronika Rupik

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The egg tooth is a crucial structure during hatching of lizards and snakes. In contrast to birds, turtles, crocodiles, and monotremes, egg tooth of squamate reptiles is a true tooth sharing common features of structure and development with all the other teeth of vertebrates. The egg tooth; however, due to its function, exhibits structural differences in relation to regular teeth. External morphology seems to be important in the context of phylogenetic relationships within Squamata but up to date, there is scarce information concerning structure and development of the egg tooth at the submicroscopical level. In presented studies detailed analysis of the egg tooth development in grass snake has been performed with the usage of light (including fluorescent), transmission and scanning electron microscopy. Grass snake embryo’s heads have been used in our studies. Grass snake is common snake species occurring in most of Europe including Poland. The grass snake is characterized by the presence of single unpaired egg tooth (as in most squamates) in contrast to geckos and dibamids possessing paired egg teeth. Studies show changes occurring on the external morphology, tissue and cellular levels of differentiating egg tooth. The egg tooth during its development changes its curvature. Initially, faces directly downward and in the course of its differentiation, it gradually changes to rostro-ventral orientation. Additionally, it forms conical dentinal protrusions on the sides. Histological analysis showed that egg tooth development occurs in similar steps in relation to regular teeth. It undergoes initiation, bud, cap and bell morphological stages. Analyses focused on describing morphological changes in hard tissues (mainly dentin and predentin) of egg tooth and in cells which enamel organ consists of. It included: outer enamel epithelium, stratum intermedium, inner enamel epithelium, odontoblasts, and cells of dental pulp. All specimens used in the study were captured according to the Polish regulations concerning the protection of wild species. Permission was granted by the Local Ethics Commission in Katowice (41/2010; 87/2015) and the Regional Directorate for Environmental Protection in Katowice (WPN.6401.257.2015.DC).

Keywords: hatching, organogenesis, reptile, Squamata

Procedia PDF Downloads 180

Authors: Natalie Riley, Anita Quigley, Robert M. I. Kapsa, George W. Greene

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As the fields of medicine and bionics grow rapidly in technological advancement, the future and success of it depends on the ability to effectively interface between the artificial and the biological worlds. The biggest obstacle when it comes to implantable, electronic medical devices, is maintaining a ‘clean’, low noise electrical connection that allows for efficient sharing of electrical information between the artificial and biological systems. Implant fouling occurs with the adhesion and accumulation of proteins and various cell types as a result of the immune response to protect itself from the foreign object, essentially forming an electrical insulation barrier that often leads to implant failure over time. Lubricin (LUB) functions as a major boundary lubricant in articular joints, a unique glycoprotein with impressive anti-adhesive properties that self-assembles to virtually any substrate to form a highly ordered, ‘telechelic’ polymer brush. LUB does not passivate electroactive surfaces which makes it ideal, along with its innate biocompatibility, as a coating for implantable bionic electrodes. It is the aim of the study to investigate LUB’s anti-fouling properties and its potential as a safe, bioinspired material for coating applications to enhance the performance and longevity of implantable medical devices as well as reducing the frequency of implant replacement surgeries. Native, bovine-derived LUB (N-LUB) and recombinant LUB (R-LUB) were applied to gold-coated mylar surfaces. Fibroblast, chondrocyte and neural cell types were cultured and grown on the coatings under both passive and electrically stimulated conditions to test the stability and anti-adhesive property of the LUB coating in the presence of an electric field. Lactate dehydrogenase (LDH) assays were conducted as a directly proportional cell population count on each surface along with immunofluorescent microscopy to visualize cells. One-way analysis of variance (ANOVA) with post-hoc Tukey’s test was used to test for statistical significance. Under both passive and electrically stimulated conditions, LUB significantly reduced cell attachment compared to bare gold. Comparing the two coating types, R-LUB reduced cell attachment significantly compared to its native counterpart. Immunofluorescent micrographs visually confirmed LUB’s antiadhesive property, R-LUB consistently demonstrating significantly less attached cells for both fibroblasts and chondrocytes. Preliminary results investigating neural cells have so far demonstrated that R-LUB has little effect on reducing neural cell attachment; the study is ongoing. Recombinant LUB coatings demonstrated impressive anti-adhesive properties, reducing cell attachment in fibroblasts and chondrocytes. These findings and the availability of recombinant LUB brings into question the results of previous experiments conducted using native-derived LUB, its potential not adequately represented nor realized due to unknown factors and impurities that warrant further study. R-LUB is stable and maintains its anti-fouling property under electrical stimulation, making it suitable for electroactive surfaces.

Keywords: anti-fouling, bioinspired, cell attachment, lubricin

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Authors: Tim Bolle, Franziska Kreimendahl, Thomas Gries, Stefan Jockenhoevel

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The therapeutic treatment of extensive, deep wounds is limited. Autologous split-skin grafts are used as a so-called ‘gold standard’. Most common deficits are the defects at the donor site, the risk of scarring as well as the limited availability and quality of the autologous grafts. The aim of this project is a tissue engineered dermal-epidermal skin replacement to overcome the limitations of the gold standard. A key requirement for the development of such a three-dimensional implant is the formation of a functional capillary-like network inside the implant to ensure a sufficient nutrient and gas supply. Tailored three-dimensional warp knitted spacer fabrics are used to reinforce the mechanically week fibrin gel-based scaffold and further to create a directed in vitro pre-vascularization along the parallel-oriented pile yarns within a co-culture. In this study various three-dimensional warp knitted spacer fabrics were developed in a factorial design to analyze the influence of the machine parameters such as the stitch density and the pattern of the fabric on the scaffold performance and further to determine suitable parameters for a successful fibrin gel-incorporation and a physiological performance of the scaffold. The fabrics were manufactured on a Karl Mayer double-bar raschel machine DR 16 EEC/EAC. A fine machine gauge of E30 was used to ensure a high pile yarn density for sufficient nutrient, gas and waste exchange. In order to ensure a high mechanical stability of the graft, the fabrics were made of biocompatible PVDF yarns. Key parameters such as the pore size, porosity and stress/strain behavior were investigated under standardized, controlled climate conditions. The influence of the input parameters on the mechanical and morphological properties as well as the ability of fibrin gel incorporation into the spacer fabric was analyzed. Subsequently, the pile yarns of the spacer fabrics were colonized with Human Umbilical Vein Endothelial Cells (HUVEC) to analyze the ability of the fabric to further function as a guiding structure for a directed vascularization. The cells were stained with DAPI and investigated using fluorescence microscopy. The analysis revealed that the stitch density and the binding pattern have a strong influence on both the mechanical and morphological properties of the fabric. As expected, the incorporation of the fibrin gel was significantly improved with higher pore sizes and porosities, whereas the mechanical strength decreases. Furthermore, the colonization trials revealed a high cell distribution and density on the pile yarns of the spacer fabrics. For a tailored reinforcing structure, the minimum porosity and pore size needs to be evaluated which still ensures a complete incorporation of the reinforcing structure into the fibrin gel matrix. That will enable a mechanically stable dermal graft with a dense vascular network for a sufficient nutrient and oxygen supply of the cells. The results are promising for subsequent research in the field of reinforcing mechanically weak biological scaffolds and develop functional three-dimensional scaffolds with an oriented pre-vascularization.

Keywords: fibrin-gel, skin replacement, spacer fabric, pre-vascularization

Procedia PDF Downloads 257

Authors: Sushil Kumar Saraswat, K. K. Pant

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Co metal supported on SiO2 and Al2O3 catalysts with a metal loading varied from 30 of 70 wt.% were evaluated for decomposition of methane to CO/CO2 free hydrogen and carbon nano materials. The catalytic runs were carried out from 550-800 oC under atmospheric pressure using fixed bed vertical flow reactor. The fresh and spent catalysts were characterized by BET surface area analyzer, TPR, XRD, SEM, TEM, and TG analysis. The data showed that 50% Co/Al2O3 catalyst exhibited remarkable higher activity and stability up to 10 h time-on-stream at 750 oC with respect to H2 production compared to rest of the catalysts. However, the catalytic activity and durability was greatly declined at a higher temperature. The main reason for the catalytic inhibition of Co containing SiO2 catalysts is the higher reduction temperature of Co2SiO4. TEM images illustrate that the carbon materials with various morphologies, carbon nanofibers (CNFs), helical-shaped CNFs, and branched CNFs depending on the catalyst composition and reaction temperature, were obtained. The TG data showed that a higher yield of MWCNTs was achieved over 50% Co/Al2O3 catalyst compared to other catalysts.

Keywords: carbon nanotubes, cobalt, hydrogen production, methane decomposition

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Authors: Sergio D’Ambrosioa, Azza Dobousa, Chiara Schiraldia, Donatella Ciminib

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Probiotics are living microorganisms that give beneficial effects while consumed. Lactic acid bacteria and bifidobacteria are among the most representative strains assessed as probiotics and exploited as food supplements. Numerous studies demonstrated their potential as a therapeutic candidate for a variety of diseases (restoring gut flora, lowering cholesterol, immune response-enhancing, anti-inflammation and anti-oxidation activities). These beneficial actions are also due to biomolecules produced by probiotics, such as exopolysaccharides (EPSs), that demonstrate plenty of beneficial properties such as antimicrobial, antitumor, anti-biofilm, antiviral and immunomodulatory activities. Limosilactobacillus fermentum is a widely studied member of probiotics; however, few data are available on the development of fermentation and downstream processes for the production of viable biomasses for potential industrial applications. However, few data are available on the development of fermentation processes for the large-scale production of probiotics biomass for industrial applications and for purification processes of EPSs at an industrial scale. For this purpose, L. fermentum strain was isolated from buffalo milk and used as a test example for biotechnological process development. The strain was able to produce up to 109 CFU/mL on a (glucose-based) semi-defined medium deprived of animal-derived raw materials up to the pilot scale (150 L), demonstrating improved results compared to commonly used, although industrially not suitable, media-rich of casein and beef extract. Biomass concentration via microfiltration on hollow fibers, and subsequent spray-drying allowed to recover of about 5.7 × 1010CFU/gpowder of viable cells, indicating strain resistance to harsh processing conditions. Overall, these data demonstrate the possibility of obtaining and maintaining adequate levels of viable L. fermentum cells by using a simple approach that is potentially suitable for industrial development. A downstream EPS purification protocol based on ultrafiltration, precipitation and activated charcoal treatments showed a purity of the recovered polysaccharides of about 70-80%.

Keywords: probiotics, fermentation, exopolysaccharides (EPSs), purification

Procedia PDF Downloads 83

Authors: Ruth Diego, Luis M. Romeo, Antonio Morán

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In the present work, a study of the coupling of a Bioelectrochemical System together with an oxy-combustion boiler is carried out; specifically, it proposes to connect the combustion gas outlet of a boiler with a microbial electrolysis cell (MEC) where the CO2 from the gases are transformed into methane in the cathode chamber, and the oxygen produced in the anode chamber is recirculated to the oxy-combustion boiler. The MEC mainly consists of two electrodes (anode and cathode) immersed in an aqueous electrolyte; these electrodes are separated by a proton exchange membrane (PEM). In this case, the anode is abiotic (where oxygen is produced), and it is at the cathode that an electroactive biofilm is formed with microorganisms that catalyze the CO2 reduction reactions. Real data from an oxy-combustion process in a boiler of around 20 thermal MW have been used for this study and are combined with data obtained on a smaller scale (laboratory-pilot scale) to determine the yields that could be obtained considering the system as environmentally sustainable energy storage. In this way, an attempt is made to integrate a relatively conventional energy production system (oxy-combustion) with a biological system (microbial electrolysis cell), which is a challenge to be addressed in this type of new hybrid scheme. In this way, a novel concept is presented with the basic dimensioning of the necessary equipment and the efficiency of the global process. In this work, it has been calculated that the efficiency of this power-to-gas system based on MEC cells when coupled to industrial processes is of the same order of magnitude as the most promising equivalent routes. The proposed process has two main limitations, the overpotentials in the electrodes that penalize the overall efficiency and the need for storage tanks for the process gases. The results of the calculations carried out in this work show that certain real potentials achieve an acceptable performance. Regarding the tanks, with adequate dimensioning, it is possible to achieve complete autonomy. The proposed system called OxyMES provides energy storage without energetically penalizing the process when compared to an oxy-combustion plant with conventional CO2 capture. According to the results obtained, this system can be applied as a measure to decarbonize an industry, changing the original fuel of the oxy-combustion boiler to the biogas generated in the MEC cell. It could also be used to neutralize CO2 emissions from industry by converting it to methane and then injecting it into the natural gas grid.

Keywords: microbial electrolysis cells, oxy-combustion, co2, power-to-gas

Procedia PDF Downloads 108

Authors: Deborah Zelinsky

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The retina filters millions of incoming signals into a smaller amount of exiting optic nerve fibers that travel to different portions of the brain. Most of the signals are for eyesight (called "image-forming" signals). However, there are other faster signals that travel "elsewhere" and are not directly involved with eyesight (called "non-image-forming" signals). This article centers on the neurons of the optic nerve connecting to parts of the limbic system. Eye care providers are currently looking at parvocellular and magnocellular processing pathways without realizing that those are part of an enormous "galaxy" of all the body systems. Lenses are modifying both non-image and image-forming pathways, taking A.M. Skeffington's seminal work one step further. Almost 100 years ago, he described the Where am I (orientation), Where is It (localization), and What is It (identification) pathways. Now, among others, there is a How am I (animation) and a Who am I (inclination, motivation, imagination) pathway. Classic eye testing considers pupils and often assesses posture and motion awareness, but classical prescriptions often overlook limbic involvement in visual processing. The limbic system is composed of the hippocampus, amygdala, hypothalamus, and anterior nuclei of the thalamus. The optic nerve's limbic connections arise from the intrinsically photosensitive retinal ganglion cells (ipRGC) through the "retinohypothalamic tract" (RHT). There are two main hypothalamic nuclei with direct photic inputs. These are the suprachiasmatic nucleus and the paraventricular nucleus. Other hypothalamic nuclei connected with retinal function, including mood regulation, appetite, and glucose regulation, are the supraoptic nucleus and the arcuate nucleus. The retino-hypothalamic tract is often overlooked when we prescribe eyeglasses. Each person is different, but the lenses we choose are influencing this fast processing, which affects each patient's aiming and focusing abilities. These signals arise from the ipRGC cells that were only discovered 20+ years ago and do not address the campana retinal interneurons that were only discovered 2 years ago. As eyecare providers, we are unknowingly altering such factors as lymph flow, glucose metabolism, appetite, and sleep cycles in our patients. It is important to know what we are prescribing as the visual processing evaluations expand past the 20/20 central eyesight.

Keywords: neuromodulation, retinal processing, retinohypothalamic tract, limbic system, visual processing

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Authors: Gokhan Zengin, Cengiz Sarikurkcu, Abdurrahman Aktumsek, Ramazan Ceylan

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The present study was designated to characterize the essential oil from S. galatica (SGEOs) and evaluate its antioxidant and enzyme inhibitory activities. Antioxidant capacity were tested different methods including free radical scavenging (DPPH, ABTS and NO), reducing power (FRAP and CUPRAC), metal chelating and phosphomolybdenum. Inhibitory activities were analyzed on acetylcholiesterase, butrylcholinesterase, α-amylase and α-glucosidase. SGEOs were chemically analyzed and identified by gas chromatography (GC) and gas chromatography/mass spectrophotometry (GC/MS). 23 components, representing 98.1% of SGEOs were identified. Monoterpene hydrocarbons (74.1%), especially α- (23.0%) and β-pinene (32.2%), were the main constituents in SGEOs. The main sesquiterpene hydrocarbons were β-caryophyllene (16.9%), Germacrene-D (1.2%) and Caryophyllene oxide (1.2%), respectively. Generally, SGEOs has shown moderate free radical, reducing power, metal chelating and enzyme inhibitory activities. These activities related to chemical profile in SGEOs. Our findings supported that the possible utility of SGEOs is a source of natural agents for food, cosmetics or pharmaceutical industries.

Keywords: sideritis galatica, antioxidant, monoterpenes, cholinesterase, anti-diabetic

Procedia PDF Downloads 439

Authors: Anuschka Curran, Sandra Barnard

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Coral reefs are of the most diverse and productive ecosystems on the planet, but due to the impact of climate change, these infrastructures are dying off primarily through coral bleaching. Coral bleaching can be described as the process by which zooxanthellae (algal endosymbionts) are expelled from the gastrodermal cavity of the respective coral host, causing increased coral whitening. The general consensus is that mass coral bleaching is due to the dysfunction of photosynthetic processes in the zooxanthellae as a result of the combined action of elevated temperature and light-stress. The question then is, do zooxanthellae have the potential to play a key role in the future of coral reef restoration through genetic engineering? The aim of this study is firstly to review the different zooxanthellae taxa and their traits with respect to environmental stress, and secondly, to review the information available on the protective mechanisms present in zooxanthellae cells when experiencing temperature fluctuations, specifically concentrating on heat shock proteins and the antioxidant stress response of zooxanthellae. The eight clades (A-H) previously recognized were redefined into seven genera. Different zooxanthellae taxa exhibit different traits, such as their photosynthetic stress responses to light and temperature. Zooxanthellae have the ability to determine the amount and type of heat shock proteins (hsps) present during a heat response. The zooxanthellae can regulate both the host’s respective hsps as well as their own. Hsps, generally found in genotype C3 zooxanthellae, such as Hsp70 and Hsp90, contribute to the thermal stress response of the respective coral host. Antioxidant activity found both within exposed coral tissue, and the zooxanthellae cells can prevent coral hosts from expelling their endosymbionts. The up-regulation of gene expression, which may mitigate thermal stress induction of any of the physiological aspects discussed, can ensure stable coral-zooxanthellae symbiosis in the future. It presents a viable alternative strategy to preserve reefs amidst climate change. In conclusion, despite their unusual molecular design, genetic engineering poses as a useful tool in understanding and manipulating variables and systems within zooxanthellae and therefore presents a solution that can ensure stable coral-zooxanthellae symbiosis in the future.

Keywords: antioxidant enzymes, genetic engineering, heat-shock proteins, Symbiodinium

Procedia PDF Downloads 189

Authors: Reham H. Soliman, Noha Noufal, Howayda AbdelAal

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Calcium/calmodulin-dependent serine protein kinase (CASK) belongs to the membrane-associated guanylate kinase (MAGUK) family and has been proposed as a mediator of cell-cell adhesion and proliferation, which can contribute to tumorogenesis. CASK has been linked as a good prognostic factor with some tumor subtypes, while considered as a poor prognostic marker in others. To our knowledge, no sufficient evidence of CASK role in colorectal cancer is available. The aim of this study is to evaluate the expression of Calcium/calmodulin-dependent serine protein kinase (CASK) in non-mucinous colorectal adenocarcinoma and adenomatous polyps as precursor lesions and assess its prognostic significance. The study included 42 cases of conventional colorectal adenocarcinoma and 15 biopsies of adenomatous polyps with variable degrees of dysplasia. They were reviewed for clinicopathological prognostic factors and stained by CASK; mouse, monoclonal antibody using heat-induced antigen retrieval immunohistochemical techniques. The results showed that CASK protein was significantly overexpressed (p <0.05) in CRC compared with adenoma samples. The CASK protein was overexpressed in the majority of CRC samples with 85.7% of cases showing moderate to strong expression, while 46.7% of adenomas were positive. CASK overexpression was significantly correlated with both TNM stage and grade of differentiation (p <0.05). There was a significantly higher expression in tumor samples with early stages (I/II) rather than advanced stage (III/IV) and with low grade (59.5%) rather than high grade (40.5%). Another interesting finding was found among the adenomas group, where the stronger intensity of staining was observed in samples with high grade dysplasia (33.3%) than those of lower grades (13.3%). In conclusion, this study shows that there is significant overexpression of CASK protein in CRC as well as in adenomas with high grade dysplasia. This indicates that CASK is involved in the process of carcinogenesis and functions as a potential trigger of the adenoma-carcinoma cascade. CASK was significantly overexpressed in early stage and low-grade tumors rather than tumors with advanced stage and higher histological grades. This suggests that CASK protein is a good prognostic factor. We suggest that CASK affects CRC in two different ways derived from its physiology. CASK as part of MAGUK family can stimulate proliferation and through its cell membrane localization and as a mediator of cell-cell adhesion might contribute in tumor confinement and localization.

Keywords: CASK, colorectal cancer, overexpression, prognosis

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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: A. Bouaouiche, M. S. Boulakoud

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The functioning of the pineal gland, the transducer body of environmental information to the neuroendocrine system is subject to a circadian rhythm. Melatonin is the main neuro-hormone expressing this operation. It is synthesized in the pinealocytes after conversion serotonin via N-acetyl-transferase enzyme, itself subject to a photoperiodic modulation (activation dark inhibition by light). Some authors have suggested that melatonin is involved in diabetic disease and found that it could have a diabetogenic effect. To this study the effect of this hormone on glucose metabolism has long been subject to controversy. Agreeing in effect and hyperinsulinemic hypoglycemic effect. In order to illustrate the level of interaction of melatonin with neuro-immune- corticotropin axis and its impact on carbohydrate metabolism, we studied the impact homeostatic (glucose) through the solicitation of two control systems (gland pineal and corticotropin axis). We then found that melatonin could have an indirect influence on insulin control (glucose metabolism) to the levels of the growth hormone axis (somatostatin) and adrenocorticotropic (corticotropin). In addition, we have suggested that melatonin might limit the hyperglycemic action of corticosteroids by direct action at peripheral level.

Keywords: pinéal gland, melatonin, neuro-immuno-corticotrop, metabolism

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Authors: Jeremy Moloney

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A major oil and gas operator in western Canada producing approximately 50,000 BOE per day of sour fluids was experiencing increased water production along with decreased oil production over several years. The higher water volumes being produced meant an increase in the operator’s incumbent corrosion inhibitor (CI) chemical requirements but with reduced oil production revenues. Thus, a cost-effective corrosion inhibitor solution was sought to deliver enhanced corrosion mitigation of the carbon steel pipeline infrastructure but at reduced chemical injection dose rates. This paper presents the laboratory work conducted on the development of a corrosion inhibitor under the operator’s simulated sour operating conditions and then subsequent field testing of the product. The new CI not only provided extremely good levels of general and localized corrosion inhibition and outperformed the incumbent CI under the laboratory test conditions but did so at vastly lower concentrations. In turn, the novel CI product facilitated field chemical injection rates to be optimized and reduced by 40% compared with the incumbent whilst maintaining superior corrosion protection resulting in significant cost savings and associated sustainability benefits for the operator.

Keywords: carbon steel, sour gas, hydrogen sulphide, localized corrosion, pitting, corrosion inhibitor

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Authors: Shuang Chen, Zongqian Shi, Jiajia Sun, Mingjia Li

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Microfluidics is a technology that small amounts of fluids are manipulated using channels with dimensions of tens to hundreds of micrometers. At present, this significant technology is required for several applications in some fields, including disease diagnostics, genetic engineering, and environmental monitoring, etc. Among these fields, manipulation of microparticles and cells in microfluidic device, especially separation, have aroused general concern. In magnetic field, the separation methods include positive and negative magnetophoresis. By comparison, negative magnetophoresis is a label-free technology. It has many advantages, e.g., easy operation, low cost, and simple design. Before the separation of particles or cells, focusing them into a single tight stream is usually a necessary upstream operation. In this work, the focusing of diamagnetic particles in ferrofluid microflows with a single set of overhead permanent magnets is investigated numerically. The geometric model of the simulation is based on the configuration of previous experiments. The straight microchannel is 24mm long and has a rectangular cross-section of 100μm in width and 50μm in depth. The spherical diamagnetic particles of 10μm in diameter are suspended into ferrofluid. The initial concentration of the ferrofluid c₀ is 0.096%, and the flow rate of the ferrofluid is 1.8mL/h. The magnetic field is induced by five identical rectangular neodymium−iron− boron permanent magnets (1/8 × 1/8 × 1/8 in.), and it is calculated by equivalent charge source (ECS) method. The flow of the ferrofluid is governed by the Navier–Stokes equations. The trajectories of particles are solved by the discrete phase model (DPM) in the ANSYS FLUENT program. The positions of diamagnetic particles are recorded by transient simulation. Compared with the results of the mentioned experiments, our simulation shows consistent results that diamagnetic particles are gradually focused in ferrofluid under magnetic field. Besides, the diamagnetic particle focusing is studied by varying the flow rate of the ferrofluid. It is in agreement with the experiment that the diamagnetic particle focusing is better with the increase of the flow rate. Furthermore, it is investigated that the diamagnetic particle focusing is affected by other factors, e.g., the width and depth of the microchannel, the concentration of the ferrofluid and the diameter of diamagnetic particles.

Keywords: diamagnetic particle, focusing, microfluidics, permanent magnet

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Faezeh Zaefarian1, Sajedeh Golmohammadzadeh, Mohammad Rezvani

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Weed management decisions for weed species can be derived from knowledge of seed germination biology. Experiments were conducted in laboratory and greenhouse to determine the effects of light, temperature, salt and water stress, seed burial depth on seed germination and seedling emergence of Papaver rhoeas and P.dubium and to assay the response of these species to commonly available POST herbicides. Germination of the Papaver seeds was influenced by the tested temperatures (day/night temperatures of 20 and 25 °C) and light. The concentrations of sodium chloride, ranging from 0 to 80 mM, influence germination of seeds. The osmotic potential required for 50% inhibition of maximum germination of P. rhoeas was -0.27 MPa and for P. dubium species was 0.25 MPa. Seedling emergence was greatest for the seeds placed at 1 cm and emergence declined with increased burial depth in the soil. No seedlings emerged from a burial depth of 6 cm. The herbicide 2,4-D at 400 g ai ha-1 provided excellent control of both species when applied at the four-leaf and six-leaf stages. However, at the six-leaf stage, percent control was reduced. The information gained from this study could contribute to developing components of integrated weed management strategies for Papaver species.

Keywords: germination, papaver species, planting depth, POST herbicides

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Authors: Yung-Gi Chen, Pei-Leun Kang, Yu-Hsin Lin, Shwu-Jen Chang

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Myocardial tissue has limited self-repair ability due to its loss of differentiation characteristic for most mature cardiomyocytes. Therefore, the effective use of stem cell technology in regenerative medicine is an important development to alleviate the current difficulties in cardiac disease treatment. The main purpose of this project was to develop a 3-D hydrogel electrical stimulating system for promoting the differentiation of stem cells into myocardial cells, and the patch will be used to repair damaged myocardial tissue. This project was focused on the preparation of the electrical stimulation system with carbon/CaCl₂ electrodes covered with carbon nanotube-hydrogel. In this study, we utilized screen imprinting techniques and used Poly(lactic-co-glycolic acid)(PLGA) membranes as printing substrates to fabricate a carbon/CaCl₂ interdigitated electrode that covered with alginate/carbon nanotube hydrogels. The single-walled carbon nanotube was added in the hydrogel to enhance the mechanical strength and conductivity of hydrogel. In this study, we used PLGA (85:15) as electrode preparing substrate. The CaCl₂/ EtOH solution (80% w/v) was mixed into carbon paste to prepare various concentration calcium-containing carbon paste (2.5%, 5%, 7.5%, 10% v/v). Different concentrations of alginate (1%, 1.5%, 2% v/v) and SWCNT(Diameter < 2nm, length between 5-15μm) (1, 1.5, 3 mg/ml) are gently immobilized on the electrode by cross-linking with calcium chloride. The three-dimensional hydrogel electrode was tested for its redox efficiency by cyclic voltammetry to determine the optimal parameters for the hydrogel electrode preparation. From the result of the final electrodes, it indicated that the electrode was not easy to maintain the pattern of the interdigitated electrode when the concentration of calcium of chloride was more than 10%. According to the gel rate test and cyclic voltammetry experiment results showed the SWCNT could increase the electron conduction of hydrogel electrodes significantly. So far the 3D electrode system has been completed, 2% alginate mixed with 3mg SWCNT is the optimal condition to construct the most complete structure for the hydrogel preparation.

Keywords: myocardial tissue engineering, screen printing technology, poly (lactic-co-glycolic acid), alginate, single walled carbon nanotube

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Authors: P. Renjitha, P. Hari Prakash

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Auditory neuropathy spectrum disorder (ANSD) is an auditory disorder with normal cochlear outer hair cell function and disrupted auditory nerve function. It results in unique clinical characteristic with absent auditory brainstem response (ABR), absent acoustic reflex and the presence of otoacoustic emissions (OAE) and cochlear microphonics. The lesion site could be at cochlear inner hair cells, the synapse between the inner hair cells and type I auditory nerve fibers, and/or the auditory nerve itself. But the literatures on synchrony at higher auditory system are sporadic and are less understood. It might be interesting to see if there is a recovery of neural synchrony at higher auditory centers. Also, does the level at which the auditory system recovers with adequate synchrony to the extent of observable evoke response potentials (ERPs) can predict speech perception? In the current study, eight ANSD participants and healthy controls underwent detailed audiological assessment including ABR, auditory middle latency response (AMLR), and auditory late latency response (ALLR). AMLR was recorded for clicks and ALLR was evoked using 500Hz and 2 kHz tone bursts. Analysis revealed that the participant could be categorized into three groups. Group I (2/8) where ALLR was present only for 2kHz tone burst. Group II (4/8), where AMLR was absent and ALLR was seen for both the stimuli. Group III (2/8) consisted individuals with identifiable AMLR and ALLR for all the stimuli. The highest speech identification sore observed in ANSD group was 30% and hence considered having poor speech perception. Overall test result indicates that the site of neural synchrony recovery could be varying across individuals with ANSD. Some individuals show recovery of neural synchrony at the thalamocortical level while others show the same only at the cortical level. Within ALLR itself there could be variation across stimuli again could be related to neural synchrony. Nevertheless, none of these patterns could possible explain the speech perception ability of the individuals. Hence, it could be concluded that neural synchrony as measured by evoked potentials could not be a good clinical predictor speech perception.

Keywords: auditory late latency response, auditory middle latency response, auditory neuropathy spectrum disorder, correlation with speech identification score

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Authors: Samantha Meyerholz

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MSKCC offers patients cutting edge cancer care with the highest quality standards. However, many patients and industry members do not realize that the operations of the Immunology Histology Lab (IHC) are the backbone for carrying out this mission. The IHC lab manufactures blocks and slides containing critical tissue samples that will be read by a Pathologist to diagnose and dictate a patient’s treatment course. The lab processes 200 requests daily, leading to the generation of approximately 2,000 slides and 1,100 blocks each day. Lab material is transported through labeling, cutting, staining and sorting manufacturing stations, while being managed by multiple techs throughout the space. The quality of the stain as well as wait times associated with processing requests, is directly associated with patients receiving rapid treatments and having a wider range of care options. This project aims to improve slide request turnaround time for rush and non-rush cases, while increasing the quality of each request filled (no missing slides or poorly stained items). Rush cases are to be filled in less than 24 hours, while standard cases are allotted a 48 hour time period. Reducing turnaround times enable patients to communicate sooner with their clinical team regarding their diagnosis, ultimately leading faster treatments and potentially better outcomes. Additional project goals included streamlining tech and material workflow, while reducing waste and increasing efficiency. This project followed a DMAIC structure with emphasis on lean and ergonomic principles that could be integrated into an evolving lab culture. Load times and batching processes were analyzed using process mapping, FMEA analysis, waste analysis, engineering observation, 5S and spaghetti diagramming. Reduction of lab technician movement as well as their body position at each workstation was of top concern to pathology leadership. With new equipment being brought into the lab to carry out workflow improvements, screen and tool placement was discussed with the techs in focus groups, to reduce variation and increase comfort throughout the workspace. 5S analysis was completed in two phases in the IHC lab, helping to drive solutions that reduced rework and tech motion. The IHC lab plans to continue utilizing these techniques to further reduce the time gap between tissue analysis and cancer care.

Keywords: engineering, ergonomics, healthcare, lean

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Authors: Anis Al-Yakhiri

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Introduction: The World Health Organization (WHO) classifies malignant epithelial thyroid tumors into four major groups (papillary, follicular, medullar and undifferentiated) . Papillary thyroid carcinoma (PTC) is the most common type, for about eight out of ten thyroid cancers belong to this histological type. Radioactive iodine (RAI) is considered effective for patients with total or nearly total thyroidectomy, but the beneficial effects of RAI are still controversial. War conditions forced us to study alternative methods of using radioactive iodine in the treatment of patients with PTC. Material and methods: Between January 2014 and June 2021, in Al-Yakhiri hospital, 57 Total Thyroidectomy with Radical BilateralNeckDissection (RBND) were performed, 50 for malignant disease,7 for false positive cytology.RBND involves surgical clearance of Levels II-VI. Mean age was 40.7 years old and 92% of the patients were female. 7(14%) patients had hypothyroidism which required preoperative thyroid hormone treatment. The Thyroid Stimulating Hormone- Suppression Therapy (TSH-ST) immediately started after RBND for mostpatients on the first day. It consisted in reducing the level of TSH< 0.1 mIU/L. Results: The Apron flap was used on most operations (40)80% and with lateral extensions had 10(20%). RBND involves surgical clearance of Levels II-VI performed in all operated patients, besides that, 4(8%) of them had resection of sternocleidomastoid muscle (SCM) and accessory nerve (XIn) and internal jugular vein (IJV) withclearance of Levels IB. The PTC was the most common 80.9% (38 patients from 47)by histopathological report. and 4(8%) patients of 50 had resection of sternocleidomastoid muscle (SCM) and accessory nerve (XIn) and internal jugular vein (IJV). The postoperative mortality rate not observed (0%). The postoperative morbidity rate was 22.8% (n =13).Seroma(8.7%),Hypocalcimia(7%), Wound infection(5.3%), Bleeding(1.8%). To suppress TSH and growth of any residual thyroid theTSH-ST (levothyroxine150 – 600mcg)was performed in all patients 57(100%) on the first day afterRBND. We tracked the results of treatment for two years in 30 patients with PTC, only 3 of them received radioactive iodine abroad. Biennial Recurrence rate for PTC appeared in one woman (2%), who had RAI postoperatively in the form of neck lymph nodes metastasis. Conclusion: For patients with PTC, thyroidectomy plus prophylacticRBND is a safe and efficient procedure and it results in lower recurrence rate. Postoperative treatment with exogenous thyroid hormone in doses sufficient to suppress TSH (not less than 150mcg), decreases incidence of recurrence. Total Thyroidectomy with RBND followed by TSH-ST, in our opinion, applicable optimal treatment scheme care for this patient population.

Keywords: thyroid cancer, Yemen war, absence of radioactive iodine, neck dissection, surgery results

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Authors: Brahim Aissa

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Transparent conductive oxides (TCOs) used as front electrodes in solar cells must feature simultaneously high electrical conductivity, low contact resistance with the adjacent layers, and an appropriate refractive index for maximal light in-coupling into the device. However, these properties may conflict with each other, motivating thereby the search for TCOs with high performance. Additionally, due to the presence of temperature sensitive layers in many solar cell designs (for example, in thin-film silicon and silicon heterojunction (SHJ)), low-temperature deposition processes are more suitable. Several deposition techniques have been already explored to fabricate high-mobility TCOs at low temperatures, including sputter deposition, chemical vapor deposition, and atomic layer deposition. Among this variety of methods, to the best of our knowledge, magnetron sputtering deposition is the most established technique, despite the fact that it can lead to damage of underlying layers. The Sn doped In₂O₃ (ITO) is the most commonly used transparent electrode-contact in SHJ technology. In this work, we studied the properties of ITO thin films grown by RF sputtering. Using different oxygen fraction in the argon/oxygen plasma, we prepared ITO films deposited on glass substrates, on one hand, and on a-Si (p and n-types):H/intrinsic a-Si/glass substrates, on the other hand. Hall Effect measurements were systematically conducted together with total-transmittance (TT) and total-reflectance (TR) spectrometry. The electrical properties were drastically affected whereas the TT and TR were found to be slightly impacted by the oxygen variation. Furthermore, the time of flight-secondary ion mass spectrometry (TOF-SIMS) technique was used to determine the distribution of various species throughout the thickness of the ITO and at various interfaces. The depth profiling of indium, oxygen, tin, silicon, phosphorous, boron and hydrogen was investigated throughout the various thicknesses and interfaces, and obtained results are discussed accordingly. Finally, the extreme conditions were selected to fabricate rear emitter SHJ devices, and the photovoltaic performance was evaluated; the lower oxygen flow ratio was found to yield the best performance attributed to lower series resistance.

Keywords: solar cell, silicon heterojunction, oxygen content, optoelectronic properties

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Authors: Bensaid Fatiha

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The objective of our present work is the description of the antagonistic capacities of one strain of Pseudomonas fluorescens and the nonpathogenic fungic isolate Fusarium oxysporum against phytopathogenic agent Fusarium oxysporum F. Sp. lycopersici. This work has been achieved in two main parts: the first is interested on the in vitro antagonistic activities; the second was interested to study the soil receptiveness of fusarium wilt tomato. The use of strain of fluorescent Pseudomonas and a non-pathogenic strain of F. oxysporum in the different antagonism tests, has allowed assuring a certain bio-protection from the plants of tomatoes opposite to F. oxysporum F. Sp. lycopersici, agent of a wilt of tomato. These antagonistic have shown a substantial in vitro antagonistic activity on the three mediums (KB, PDA, KB+PDA) against F. oxysporum F. Sp. lycopersici, by inhibiting its growth mycelium with rate of inhibition going until 80 % with non-pathogen of Fusarium oxysporum and 60 % with strain of fluorescens Pseudomonas. Soil microbial balance, between the antagonistic population and that of pathogenic, can be modulated through microbiological variations or abiotic additives influencing directly or indirectly the metabolic behavior microbial. In this experiment, addition of glucose or EDTA, could increase or decrease the resistance of soil by activation of pathogenic or antagonists, as a result of modification and modulation in their metabolic activities.

Keywords: fluorescents, nonpathogenic, fusarium oxysporum, fusarium wilt, antagonism, biological control, soil receptivity

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Authors: Meksem Nabila, Bordjiba Ouahiba, Meraghni Messaouda, Meksem Amara Leila, Djebar Mohhamed Reda

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The problems of protection of the cultures are being more and more important that they interest great number of farmers and scientists because of the excessive use of the organic phytosanitary products of synthesis that causes fatal damages on the environment. To reduce the inconveniences produced by these pesticides, the use of "biopesticides" originated from plants could be an alternative. The aim of this work is the valuation of a botanical species: Eucalyptus camaldulensis from Northeastern Algeria which extracts are supposed to have an antimicrobial activity, similar to pesticides. The extraction of secondary metabolites from the leaves of E. camaldulensis was realized using methanol and water, and measurements of total polyphenols were made by spectrometric method. Determination of the antimicrobial activity of the extracts at issue was realized in vitro on phyto-pathogenic fungal and bacterial stumps. Tests of comparison were included in the essays by using the chemical pesticidal products of synthesis. The obtained results show that the plant contains polyphenols with an efficiency mattering of the order of 22 %. These polyphenols have a strong fungicidal and bactericidal pesticidal activity against various microbial stumps and the values of the zones of inhibition are more important compared with that obtained in the presence of the chemicals of synthesis (fungicide).

Keywords: eucalyptus camaldulensis, biopesticide, polyphenols, antimicrobial activity

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Authors: Alemu Tadesse Feroche

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In this study, some 2, 3 distributed quinazoline -4 (3H) - one derivative were synthesized using a three-step synthetic route. They were obtained in a good yield (59.5-85%) by applying different chemical reactions like cyclization and condensation reactions. The chemical structure of the final compounds was also verified by spectroscopic methods (IR, ¹HNMR) and elemental microanalysis. The in vivo antimalarial activity of these compounds on P. berghei infected mice was found to be moderate to high at an oral dose of 0.04846 mmol/kg /day. This is equal to 25 mg/kg of chloroquine phosphate, which causes 100% inhibition of the parasite. It is worth mentioning that most active compounds (E) -3 Phenyl -2- [2- (pyridine -4- yl) vinyl] -4 (3H) -quinazolinone IVa (64.02%, (E)-2-[2-(4 - Hydroxy-3 - methoxystyryl) - vinyl) -3 - phenyl -4 (3H ) - quinazolinone IVc (77.25%) and (E)-2 –[2 –(Pyridin -4-yl) –vinyl] -3 phenenylamine -4(3H) quinazolinone IVe (73.54%) showed a dose-dependent increase in present suppression in antimalarial activities. Furthermore, the synthesized compounds were screened for their in vitro antileishmanial activity against L. aethiopica isolate (CL/039/09). All tested compounds (IVa (0.03766 ug/ml), IVb (0.00538 ug/ml, IVc (0.00412 ug/ml, IVd (0.00110 ug/ml), IVe (0.03017 ug/ml) and IVf (0.03894 ug/ml)) showed excellent potency that is much better than amphotericin B (IC50 = 0,04359 ug/ml). The results of acute toxicity indicated that all test compounds (IVa –IVf) proved to be nontoxic and well tolerated by the experimental animals up to 300 mg/kg in oral and 140 mg/kg in parental studies.

Keywords: 4(3H)-quinazolinone, in vivo antimalarial activity, in vitro antileishmanial activity, acute toxicity

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Authors: Ririn Lestari Sri Rahayu, Mustofa Ahda

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The use of synthetic antioxidants often causes a negative effect on health and increases the incidence of carcinogenesis. Development of the natural antioxidants should be investigated. However, natural antioxidants have a low toxicity and are safe for human consumption. Ethanol extract of mangosteen rind (Garcinia mangostana) contains natural antioxidant compounds that have various pharmacological activities. Antioxidants from the ethanol extract of mangosteen rind have free radicals scavenging activities. The scavenging activity of ethanol extract of mangosteen rind was determined by DPPH method. The phenolic compound from the ethanol extract of mangosteen rind is determined with Folin-Ciocalteu method. The results showed that the absolute ethanol extract of mangosteen rind has IC₅₀ of 40.072 ug/mL. The correlation of total phenols content with free radical scavenging activity has an equation y: 5.207x + 205.51 and determination value (R²) of 0.9329. Total phenols content from the ethanol extract of mangosteen rind has a good correlation with free radicals scavenging activity of DPPH.

Keywords: Antioxidant, Garcinia mangostana, Inhibition concentration 50%, Phenolic.

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Authors: Giorgi Goguadze, Jakub Zajączkowski

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This paper is written due to overview the connection between fragile states and non-state actors, we should take into account that fragile states may vary from weak, failing and failed. In this paper we will discuss about two countries, one of them is weak (Colombia/ second one is already failed- Somalia. We will try to understand what feeds ill non-state actors such as: terrorist organizations, criminal entities and other cells in these countries, what threats are they representing and how to eliminate these dangers in both national and international scope. This paper is mainly based on literature overview and personal attitude and doesn’t claim to be in scientific chain.

Keywords: fragile States, terrorism, tribalism, Somalia

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