Search results for: inhibition effect

Authors: Zhongyang Sun, Shu Zhang

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In osteoblasts, L-type voltage sensitive calcium channels (LTCCs), especially the Cav1.2 LTCCs, play fundamental roles in cellular responses to external stimuli including both mechanical forces and hormonal signals. Several lines of evidence have revealed that the density of bone is increased and the resorption of bone is decreased when these calcium channels in osteoblasts are activated. And numerous studies have shown that mechanical loading promotes bone formation in the modeling skeleton, whereas removal of this stimulus in microgravity results in a reduction in bone mass. However, the effect of microgravity on LTCCs in osteoblasts is still unknown. The aim of this study was to determine whether microgravity exerts influence on LTCCs in osteoblasts and the possible mechanisms underlying. In this study, we demonstrate that simulated microgravity substantially inhibits LTCCs in osteoblast by suppressing the expression of Cav1.2. Then we show that the up-regulation of miR-103 is involved in the down-regulation of Cav1.2 expression and inhibition of LTCCs by simulated microgravity in osteoblasts. Our study provides a novel mechanism of simulated microgravity-induced adverse effects on osteoblasts, offering a new avenue to further investigate the bone loss caused by microgravity.

Keywords: L-type voltage sensitive calcium channels, Cav1.2, osteoblasts, microgravity

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Authors: Lidija Trandafilovic, Kirsten Leistner, Marie Stenfeldt, Louise Olsson

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Ammonia Selective Catalytic Reduction (NH3 SCR), is one of the most efficient post combustion abatement technologies for removing NOx from diesel engines. In order to remove soot, diesel particulate filters (DPF) are used. Recently, SCR coated filters have been introduced, which captures soot and simultaneously is active for ammonia SCR. There are large advantages with using SCR coated filters, such as decreased volume and also better light off characteristics, since both the SCR function as well as filter function is close to the engine. The objective of this work was to examine the effect of soot, produced using an engine bench, on Cu/SSZ-13 catalysts. The impact of soot on Cu/SSZ-13 in standard SCR, NH3 oxidation, NH3 temperature programmed desorption (TPD), as well as soot oxidation (with and without water) was examined using flow reactor measurements. In all experiments, prior to the soot loading, the fresh activity of Cu/SSZ-13 was recorded with stepwise increasing the temperature from 100°C till 600°C. Thereafter, the sample was loaded with soot and the experiment was repeated in the temperature range from 100°C till 700°C. The amount of CO and CO2 produced in each experiment is used to calculate the soot oxidized at each steady state temperature. The soot oxidized during the heating to next temperature step is included, e.g. the CO+CO2 produced when increasing the temperature to 600°C is added to the 600°C step. The influence of the two factors seem to be of the most importance to soot oxidation: ammonia and water. The influence of water on soot oxidation shift the maximum of CO2 and CO production towards lower temperatures, thus water increases the soot oxidation. Moreover, when adding ammonia to the system it is clear that the soot oxidation is lowered in the presence of ammonia, resulting in larger integrated COx at 500°C for O2+H2O, while opposite results at 600 °C was received where more was oxidised for O2+H2O+NH3 case. To conclude the presence of ammonia reduces the soot oxidation, which is in line with the ammonia TPD results where we found ammonia storage on the soot. Interestingly, during ammonia SCR conditions the activity for soot oxidation is regained at 500°C. At this high temperature the SCR zone is very short, thus the majority of the catalyst is not exposed to ammonia and therefore the inhibition effect of ammonia is not observed.

Keywords: NH3-SCR, Cu/SSZ-13, soot, zeolite

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Authors: Danni Cheng

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Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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Authors: Sushil Kumar Singh, Ashok Kumar, Ankit Ganeshpurkar, Ravi Singh, Devendra Kumar

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In spectrum of neurodegenerative diseases, Alzheimer’s disease (AD) is characterized by the presence of amyloid β plaques and neurofibrillary tangles in the brain. It results in cognitive and memory impairment due to loss of cholinergic neurons, which is considered to be one of the contributing factors. Donepezil, an acetylcholinesterase (AChE) inhibitor which also inhibits butyrylcholinesterase (BuChE) and improves the memory and brain’s cognitive functions, is the most successful and prescribed drug to treat the symptoms of AD. The present work is based on designing of the selective BuChE inhibitors using computational techniques. In this work, machine learning models were trained using classification algorithms followed by screening of diverse chemical library of compounds. The various molecular modelling and simulation techniques were used to obtain the virtual hits. The amide derivatives of 4-(phenylsulfonamido) benzoic acid were synthesized and characterized using 1H & 13C NMR, FTIR and mass spectrometry. The enzyme inhibition assays were performed on equine plasma BuChE and electric eel’s AChE by method developed by Ellman et al. Compounds 31, 34, 37, 42, 49, 52 and 54 were found to be active against equine BuChE. N-(2-chlorophenyl)-4-(phenylsulfonamido)benzamide and N-(2-bromophenyl)-4-(phenylsulfonamido)benzamide (compounds 34 and 37) displayed IC50 of 61.32 ± 7.21 and 42.64 ± 2.17 nM against equine plasma BuChE. Ortho-substituted derivatives were more active against BuChE. Further, the ortho-halogen and ortho-alkyl substituted derivatives were found to be most active among all with minimal AChE inhibition. The compounds were selective toward BuChE.

Keywords: Alzheimer disease, butyrylcholinesterase, machine learning, sulfonamides

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Authors: Sajjad Negahban, Ruihe Wang, Baojiang Sun

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Gas-lift dual gradient drilling is a solution for deepwater drilling challenges. As well, Continuous development of drilling technology leads to increase employment of mineral oil based drilling fluids and synthetic-based drilling fluids, which have adequate characteristics such as: high rate of penetration, lubricity, shale inhibition and low toxicity. The paper discusses utilization of nitrified mineral oil base drilling for deepwater drilling and for more accurate prediction of pressure in DGD at marine riser, solubility and bubble pressure were considered in steady state hydraulic model. The Standing bubble pressure and solubility correlations, and two models which were acquired from experimental determination were applied in hydraulic model. The effect of the black oil correlations, and new solubility and bubble pressure models was evaluated on the PVT parameters such as oil formation volume factor, density, viscosity, volumetric flow rate. Eventually, the consequent simulated pressure profile due to these models was presented.

Keywords: solubility, bubble pressure, gas-lift dual gradient drilling, steady state hydraulic model

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Authors: Pukhrambam Helena Chanu, Janardan Yadav

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This study investigates the potential of various fungal isolates to solubilize zinc and counteract rice pathogens, with the aim of mitigating zinc deficiency and disease prevalence in rice farming. Soil samples from the rhizosphere were collected, and zinc-solubilizing fungi were isolated and purified. Molecular analysis identified Talaromyces sp, Talaromyces versatilis, Talaromyces pinophilus, and Aspergillus terreus as effective zinc solubilizers. Through qualitative and quantitative assessments, it was observed that solubilization efficiencies varied among the isolates over time, with Talaromyces versatilis displaying the highest capacity for solubilization. This variability in solubilization rates may be attributed to differences in fungal metabolic activity and their ability to produce organic acids that facilitate zinc release from insoluble sources in the soil. In inhibition assays against rice pathogens, the fungal isolates exhibited antagonistic properties, with Talaromyces versatilis demonstrating the most significant inhibition rates. This antagonistic activity may be linked to the production of secondary metabolites, such as antibiotics or lytic enzymes by fungi, which inhibit the growth of rice pathogens. The ability of Talaromyces versatilis to outperform other isolates in both zinc solubilization and pathogen inhibition highlights its potential as a multifunctional biocontrol agent in rice cultivation systems. These findings emphasize the potential of fungi as natural solutions for enhancing zinc uptake and managing diseases in rice cultivation. Utilizing indigenous zinc-solubilizing fungi offers a sustainable and environmentally friendly approach to addressing zinc deficiency in soils, reducing the need for chemical fertilizers. Moreover, harnessing the antagonistic activity of these fungi can contribute to integrated disease management strategies, minimizing reliance on synthetic pesticides and promoting ecological balance in agroecosystems. Additionally, the study included the evaluation of dipping time under different concentrations, viz.,10 ppm, 20 ppm, and 30 ppm of biosynthesized nano ZnO on rice seedlings. This investigation aimed to optimize the application of nano ZnO for efficient zinc uptake by rice plants while minimizing potential risks associated with excessive nanoparticle exposure. Evaluating the effects of varying concentrations and dipping durations provides valuable insights into the safe and effective utilization of nano ZnO as a micronutrient supplement in rice farming practices.

Keywords: biosynthesized nano ZnO, rice, root dipping, zinc solubilizing fungi.

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Authors: Fitri Ayu, Nadia, Tanti, Putri, Fatkhan, Pasid Harlisa, Suparmi

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Acne is a skin abnormal conditions experienced by many teens, this is caused by various factors such as the climate is hot, humid and excessive sun exposure can aggravate acne because it will lead to excess oil production. Flavonoids form complex compounds against extracellular proteins that disrupt the integrity of bacterial cell membrane in a way denature bacterial cell proteins and bacterial cell membrane damage. This study aimed to test the antibacterial activity of corn silk extract with a concentration of 10 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 %, 90 % and 100 % in vitro by measuring the inhibition of the growth of bacteria Propionibacterium acne, Staphylococcus aureus and Staphylococcus epidermis then compared with the standard antibiotic clindamycin. Extracts tested by Disk Diffusion Method, in which the blank disc soaked with their respective corn silk extract concentration for 15-30 minutes and then the medium of bacteria that have been planted with Propionibacterium acne, Staphylococcus aureus and Staphylococcus epidermis in the given disk that already contains extracts with various concentration. Incubated for 24 hours and then measured the growth inhibition zone Propionibacterium acne, Staphylococcus aureus and Staphylococcus epidermidis. Corn silk contains flavonoids, is shown by the test of flavonoids in corn silk extract by using a tube heating and without heating. Flavonoid in corn silk potentially as anti acne by inhibiting the growth of bacteria that cause acne. Corn silk extract concentration which has the highest antibacterial activity is then performed in a cream formulation and evaluation test of physical and chemical properties of the resulting cream preparation.

Keywords: antibacterial, flavonoid, corn silk, acne

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Authors: Yu-Shan Hsu

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This paper studies a two-sector growth model with a technology of social constant returns and with a utility that features either a zero or a positive income effect on the demand for leisure. The purpose is to investigate how the existence of aggregate instability or equilibrium indeterminacy depends on both the intensity of the income effect on the demand for leisure and the value of the labor supply elasticity. The main finding is that when there is a factor intensity reversal between the private perspective and the social perspective, indeterminacy arises even if the utility has a positive income effect on leisure demand. Moreover, we find that a smaller value of the labor supply elasticity increases the range of the income effect on leisure demand and thus increases the possibility of equilibrium indeterminacy. JEL classification: E3; O41

Keywords: indeterminacy, non-separable preferences, income effect, labor supply elasticity

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Authors: A. Mulry, C. Kealey, D. B. Brady

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Planktonic bacteria can form biofilms which are microbial aggregates embedded within a matrix of extracellular polymeric substances (EPS). They can be found attached to abiotic or biotic surfaces. Biofilms are responsible for oral diseases such as dental caries, gingivitis and the progression of periodontal disease. Biofilms can resist 500 to 1000 times the concentration of biocides and antibiotics used to kill planktonic bacteria. Biofilm development on oral surfaces involves four stages, initial attachment, early development, maturation and dispersal of planktonic cells. The Minimum Inhibitory Concentration (MIC) was determined using a range of saturated and unsaturated fatty acids using the resazurin assay, followed by serial dilution and spot plating on BHI agar plates to establish the Minimum Bactericidal Concentration (MBC). Log reduction of bacteria was also evaluated for each fatty acid. The Minimum Biofilm Inhibition Concentration (MBIC) was determined using crystal violet assay in 96 well plates on forming and pre-formed S. mutans biofilms using BHI supplemented with 1% sucrose. Saturated medium-chain fatty acids Octanoic (C8.0), Decanoic (C10.0) and Undecanoic acid (C11.0) do not display strong antibiofilm properties; however, Lauric (C12.0) and Myristic (C14.0) display moderate antibiofilm properties with 97.83% and 97.5% biofilm inhibition with 1000 µM respectively. Monounsaturated, Oleic acid (C18.1) and polyunsaturated large chain fatty acids, Linoleic acid (C18.2) display potent antibiofilm properties with biofilm inhibition of 99.73% at 125 µM and 100% at 65.5 µM, respectively. Long-chain polyunsaturated Omega-3 fatty acids α-Linoleic (C18.3), Eicosapentaenoic Acid (EPA) (C20.5), Docosahexaenoic Acid (DHA) (C22.6) have displayed strong antibiofilm efficacy from concentrations ranging from 31.25-250µg/ml. DHA is the most promising antibiofilm agent with an MBIC of 99.73% with 15.625µg/ml. This may be due to the presence of six double bonds and the structural orientation of the fatty acid. To conclude, fatty acids displaying the most antimicrobial activity appear to be medium or long-chain unsaturated fatty acids containing one or more double bonds. Most promising agents include Omega-3-fatty acids Linoleic, α-Linoleic, EPA and DHA, as well as Omega-9 fatty acid Oleic acid. These results indicate that fatty acids have the potential to be used as antimicrobials and antibiofilm agents against S. mutans. Future work involves further screening of the most potent fatty acids against a range of bacteria, including Gram-positive and Gram-negative oral pathogens. Future work will involve incorporating the most effective fatty acids onto dental implant devices to prevent biofilm formation.

Keywords: antibiofilm, biofilm, fatty acids, S. mutans

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Authors: Mohammad K. Parvez, Ahmed H. Arbab, Mohammed S. Al-Dosari

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Cyperus rotendus rhizomes are used as traditional medicine, including Ayurveda in chronic liver diseases and hepatitis B. We investigated the in vitro hepatoprotective and anti-hepatitis B virus (HBV) potential of Cyperus rotundus rhizome organic and aqueous fractions. Of these, the n-butanol and aqueous fractions showed the most promising, dose-dependent hepatoprotection in DCFH-injured HepG2 cells at 48 h. DCFH-toxicated cells were recovered to about 88% and 96%, upon treatment with n-butanol and aqueous fractions (200 g/ml), respectively compared to DCFH-only treated cells. Further, C. rotundus fractions were tested for anti-HBV activities by measuring the expression levels of viral antigens (HBsAg and HBeAg) in the HepG2.2.15 culture supernatants. At 48 h post-treatment, the ethyl acetate, n-butanol and aqueous fractions showed dose-dependent inhibition wherein at a higher dose (100 g/ml), HBsAg production was reduced to 60.27%, 46.87 and 42.76%, respectively. In a time-course study, HBsAg production was inhibited up to 50% and 40% by ethyl acetate and n-butanol fractions (100 g/ml), respectively on day 5. Three three active fractions were further subjected to time-dependent inhibition of HBeAg expression, an indirect measure of HBV active DNA replication. At day 5 post-treatment, ethyl acetate and n-butanol fractions downregulated HBV replication by 44.14% and 24.70%, respectively. In conclusion, our results showed very promising hepatoprotective and anti-HBV potential of C. rotendus tubers fractions in vitro. Our data could, therefore, provide the basis for the claimed traditional use of C. rotendus for jaundice and hepatitis.

Keywords: anti-hepatitis B, cyperus rotundus, hepatitis B virus, hepatoprotection

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Authors: Nasiruddin Khan

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The action of (-)-epicatechin, a cocoa (Theobroma cacao) flavanol that modulates redox/oxidative stress are contributed mainly to their antioxidant properties. The present study investigates the concentration and time dependent effect of (-)-epicatechin metabolites 3MeEc, 4MeEc, and 4SulEc on the production of ROS on BAEC using L-012, Lucigenin as chemiluminescence dye and XO/HX system. Our result demonstrates that 3MeEc shows significant (P <0.05) lowering effect of ROS production in BAEC with increasing concentration of metabolite while L-012 was used as chemiluminescence dye but not in the case of Lucigenin. In XO/HX system, using L-012 as chemiluminescence dye, 3MeEc and 4MeEc showed significant lowering effect on ROS production with increasing concentration from 100-500nM as compared to the positive control (SOD). When Lucigenin was used as chemiluminescence dye, 3MeEc exerted significant lowering effect with increasing concentration when compared to the positive control (SOD) whereas 4MeEc showed significant lowering effect in ROS production from 250 nM on as compared to positive control. For 4SulEc, a significant lowering effect of ROS production was only observed at 100 and 250 nM. Overall, although each metabolite shows considerable effect, 3MeEc exhibited more pronounced effect on decreasing the production of ROS as compared to other two metabolites.

Keywords: epicatechin metabolites, HO-1, Nrf2, ROS

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Authors: W. J. Fan, B. S. Ma

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The many-body effect on band structure and optical gain of n+ doping tensile-strained Ge/GeSiSn quantum wells are investigated by using an 8-band k•p method. Phase diagram of Ge/GeSiSn quantum well is obtained. The E-k dispersion curves, band gap renormalization and optical gain spectra including many-body effect will be calculated and discussed. We find that the k.p method without many-body effect will overestimate the optical gain and transition energy.

Keywords: Si photonics, many-body effect, optical gain, Ge-on-Si, Quantum well

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Authors: N. A. Kazemi Sefat, M. M. Mohammadi, J. Hadjati, S. Talebi, M. Ajami, H. Daneshvar

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Colorectal cancer metastases result in a significant number of cancer related deaths. Histone deacetylase (HDAC) inhibitors induce growth arrest and apoptosis in a variety of human cancer cells. Sodium butyrate (SB) is a short chain fatty acid, belongs to HDAC inhibitors which is released in the colonic lumen as a consequence of fiber fermentation. In this study, we are about to assess the effect of sodium butyrate on HCT116 human colorectal carcinoma cell line. The viability of cells was measured by microscopic morphologic study and MTT assay. After 48 hours, treatments more than 10 mM lead to cell injury in HCT116 by increasing cell granulation and decreasing cell adhesion (p>0.05). After 72 hours, treatments at 10 mM and more lead to significant cell injury (p<0.05). Our results may suggest that the gene expression which is contributed in cell proliferation and apoptosis has been changed under pressure of HDAC inhibition.

Keywords: colorectal cancer, sodium butyrate, cytotoxicity, MTT

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Authors: Majid Omidikhankahdani, Maryam Omidikhankahdani

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Chabahar city located southeast of Iran and is one of strategic regional port in Oman sea aim of this study was measuring Chabahar city resident perceptions about tourism positive and negative effect. 322 participants selected via random sampling and fill questionnaire about their attitude toward tourism economic, social cultural and environment positive and negative impact. the result showed perspective of resident tourism have more positive effect than negative effect, also pair sample t test showed significant difference between positive and negative effect of tourism in favor positive effect.

Keywords: tourism economic effect, tourism environment, residents attitude, tourism social-cultural

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Authors: Qin Ou, Yanghui Xu, Xintu Wang, Kim Maren Lompe, Gang Liu, Jan Peter Van Der Hoek

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Microplastics (MPs) can undergo the photooxidation process under ultraviolet (UV) exposure, which determines their transformation and fate in environments. The presence of dissolved organic matter (DOM) can interact with MPs and take participate in the photo-degradation of MPs. As an important DOM component, dissolved black carbon (DBC), widely distributed in aquatic environments, can accelerate or inhibit the sunlight-driven photo-transformation of environmental pollutants. However, the role and underlying mechanism of DBC in the photooxidation of MPs are not clear. Herein, the DBC (< 0.45 µm) was extracted from wood biochar and fractionated by molecular weight (i.e., <3 KDa, 3 KDa−30 KDa, 30 KDa−0.45 µm). The effects of DBC chemical composition (i.e., molecular weight and chemical structure) in DBC-mediated photo-transformation of polystyrene (PS) MPs were investigated. The results showed that DBC initially inhibited the photo-degradation of MPs due to light shielding. Under UV exposure for 6−24 h, the presence of 5 mg/L DBC decreased the carbonyl index of MPs compared to the control. This inhibitory effect of DBC was found to decrease with increasing irradiation time. Notably, DBC initially decreased but then increased the hydroxyl index with aging time, suggesting that the role of DBC may shift from inhibition to acceleration. In terms of the different DBC fractions, the results showed that the smallest fraction of DBC (<3 KDa) significantly accelerated the photooxidation of PS MPs since it acted as reactive oxygen species (ROS) generators, especially in promoting the production of ¹O₂ and ³DBC* and •OH. With the increase in molecular weight, the acceleration effect of DBC on the degradation of MPs was decreased due to the increase of light shielding and possible decrease of photosensitization ability. This study thoroughly investigated the critical role of DBC chemical composition in the photooxidation process, which helps to assess the duration of aging and transformation of MPs during long-term weathering in natural waters.

Keywords: microplastics, photo-degradation, dissolved black carbon, molecular weight, photosensitization

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Authors: Olaitan Akanji, Cleophas Loto, Patricia Popoola, Andrei Kolesnikov

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Studies involving performance of corrosion inhibitors had been identified as one of the critical research needs for improving the durability of mild steel used in various industrial applications. This paper investigates the inhibiting effect of calcium gluconate against the corrosion of mild steel in 2.5M magnesium chloride using weight loss method and linear polarization technique, calculated corrosion rates from the obtained weight loss data, potentiodynamic polarization measurements are in good agreement. Results revealed calcium gluconate has strong inhibitory effects with inhibitor efficiency increasing with increase in inhibitor concentration at ambient temperature, the efficiency of the inhibitor increased in the following order of concentrations 2%g/vol,1.5%g/vol,1%g/vol,0.5%g/vol. Further results obtained from potentiodynamics experiments had good correlation with those of the gravimetric methods, the adsorption of the inhibitor on the mild steel surface from the chloride has been found to obey Langmuir, Frumkin and Freudlich adsorption isotherm. Scanning electron microscopy (SEM) observation confirmed the existence of an absorbed protective film on the metal surface.

Keywords: calcium gluconate, corrosion, magnesium chloride, mild steel

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Authors: Marwan Khalil Qader, Arshad Mohammad Abdullah

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Antimicrobial resistance is a major cause of significant morbidity and mortality globally. Seven plant extracts (Plantago mediastepposa, Quercusc infectoria, Punic granatum, Thymus lcotschyana, Ginger officeinals, Rhus angustifolia and Cinnamon) were collected from different regions of Kurdistan region of Iraq. These plants’ extracts were dissolved in absolute ethanol and distillate water, after which they were assayed in vitro as an antimicrobial activity against Candida tropicalis, Candida albicanus, Candida dublinensis, Candida krusei and Candida glabrata also against 2 Gram-positive (Bacillus subtilis and Staphylococcus aureus) and 3 Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa and Klebsilla pneumonia). The antimicrobial activity was determined in ethanol extracts and distilled water extracts of these plants. The ethanolic extracts of Q. infectoria showed the maximum activity against all species of Candida fungus. The minimum inhibition zone of the Punic granatum ethanol extracts was 0.2 mg/ml for all microorganisms tested. Klebsilla pneumonia was the most sensitive bacterial strain to Quercusc infectoria and Rhus angustifolia ethanol extracts. Among both Gram-positive and Gram-negative bacteria tested with MIC of 0.2 mg/ml, the minimum inhibition zone of Ginger officeinals D. W. extracts was 0.2 mg/mL against Pseudomonas aeruginosa and Klebsilla pneumonia. The most sensitive bacterial strain to Thymus lcotschyana and Plantago mediastepposa D.W. extracts was S. aureus and E. coli.

Keywords: antimicrobial activity, pathogenic bacteria, plant extracts, chemical systems engineering

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Authors: N. Behidj, K. Benyounes, T. Dahmane, A. Allem

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The aim of this study was to investigate the antimicrobial activity of flavonoids isolated from the aerial part of a medicinal plant which is Thymus inodorusby the middle agar diffusion method on following microorganisms. We have Staphylococcus aureus, Escherichia coli, Pseudomonas fluorescens, AspergillusNiger, Aspergillus fumigatus and Candida albicans. During this study, flavonoids extracted by stripping with steam are performed. The yields of flavonoids is 7.242% for the aqueous extract and 28.86% for butanol extract, 29.875% for the extract of ethyl acetate and 22.9% for the extract of di - ethyl. The evaluation of the antibacterial effect shows that the diameter of the zone of inhibition varies from one microorganism to another. The operation values obtained show that the bacterial strain P fluoresces, and 3 yeasts and molds; A. Niger, A. fumigatus and C. albicansare the most resistant. But it is noted that, S. aureus is shown more sensitive to crude extracts, the stock solution and the various dilutions. Finally for the minimum inhibitory concentration is estimated only with the crude extract of Thymus inodorus flavonoid.Indeed, these extracts inhibit the growth of Gram + bacteria at a concentration varying between 0.5% and 1%. While for bacteria to Gram -, it is limited to a concentration of 0.5%.

Keywords: antimicrobial activity, organic extracts, aqueous extracts, Thymus numidicus

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Authors: Mustafa Kirisci

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Arms embargoes have not been adequately examined in terms of their effects on conflict duration. Prior research on arms embargoes has generally investigated the effect of arms embargoes on arms import/export practices and violations in arms embargoes, but it says little about the effect on conflict duration. This paper attempts to fill this gap and aims to investigate the effect of arms embargoes on conflict duration throughout the world. More precisely, the purpose of the paper is to understand how arms embargoes affect the duration of both internal and interstate conflicts. Given the theoretical framework, the main hypothesis of the paper is arms embargoes will have no reduction effect on conflict duration when arms transfer and region are controlled. This hypothesis is tested by using OLS regression. Results indicate that arms embargoes have no effect on both internal and interstate conflict duration. Another crucial result is that both small and major arms transfers made by the embargoed countries during the internal conflict increase the duration of the conflict, but no effect on interstate conflict duration. The final part concludes and provide explanations on what these results imply for finishing the conflict and bringing the peace.

Keywords: arms embargo, arms transfer, internal conflict, international conflict

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Authors: Intanri Kurniati, Raja Iqbal Mulya Harahap, Agustyas Tjiptaningrum, Reni Zuraida

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Background: Diabetes mellitus is still increasing and has become a health and social burden in the world. It is known that glycation among various proteins is increased in diabetic patients compared with non-diabetic subjects. Some of these glycated proteins are suggested to be involved in the development and progression of chronic diabetic complications. Among these glycated proteins, glycated hemoglobin (HbA1C) is commonly used as the gold standard index of glycemic control in the clinical setting. HbA1C testing has some methods, and the most commonly used is immunoturbidimetry. This research aimed to compare the HbA1c level between immunoturbidimetry and HbA1C level in T2DM patients. Methods: This research involves 77 patients from Abd Muluk Hospital Bandar Lampung; the patient was asked for consent in this research, then underwent phlebotomy to be tested for HbA1C; the sample was then examined for HbA1C with Turbidimetric Inhibition Immunoassay (TINIA) and High-Performance Liquid Chromatography (HPLC) method. Result: Mean± SD of the samples with the TINIA method was 9.2±1,2; meanwhile, the level HbA1C with the HPLC method is 9.6±1,2. The t-test showed no significant difference between the group subjects. (p<0.05). It was proposed that the two methods have high suitability in testing, and both are eligibly used for the patient. Discussion: There was no significant difference among research subjects, indicating that the high conformity of the two methods is suitable to be used for monitoring patients clinically. Conclusion: There is increasing in HbA1C level in a patient with T2DM measured with HPLC and or Turbidimetric Inhibition Immunoassay (TINIA) method, and there were no significant differences among those methods.

Keywords: diabetes mellitus, glycated albumin, HbA1C, HPLC, immunoturbidimetry

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Authors: N. Saki, S. Nalbantoglu, M. Akin, G. Arabaci

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Walnut has a great range of phenolic profile and it is used in Asia and Africa for treatment of many diseases and cancer. Phenolic compounds play a number of crucial roles in complex metabolism of plants and of also fruit trees. Consumption of certain phenolics in the food is considered beneficial for human nutrition. Phenolic compounds known as anti-radical inactivators with their high antioxidant activities and these activities play an important role in inhibition of multi-metal corrosion. Many common corrosion inhibitors that are still in use today are health hazards. Therefore, there is still an increased attention directed towards the development of environmentally compatible, nonpolluting corrosion inhibitors. The present study reports the total phenols content, antioxidant potentials and tyrosinase inhibitory activity of the walnut (Juglans regia L.) produced in Turkey. The anti-tyrosinase activity was investigated for walnut at 2 h extraction time and all extracts exhibited tyrosinase activity. The results of this study suggested that walnut can be used as an excellent, easily accessible source of natural antioxidant.

Keywords: antioxidant activity, Juglans Regia, total phenols, tyrosinase activity

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Authors: Christopher Latella, Ashlee M. Hendy, Dan Vander Westhuizen, Wei-Peng Teo

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Introduction: Neural adaptations following resistance training interventions have been widely investigated, however the evidence regarding the mechanisms of early adaptation are less clear. Understanding neural responses from an acute resistance training session is pivotal in the prescription of frequency, intensity and volume in applied strength and conditioning practice. Therefore the primary aim of this study was to investigate the time course of neurophysiological mechanisms post training against current super compensation theory, and secondly, to examine whether these responses reflect neural adaptations observed with resistance training interventions. Methods: Participants (N=14) completed a randomised, counterbalanced crossover study comparing; control, strength and hypertrophy conditions. The strength condition involved 3 x 5RM leg extensions with 3min recovery, while the hypertrophy condition involved 3 x 12 RM with 60s recovery. Transcranial magnetic stimulation (TMS) and peripheral nerve stimulation were used to measure excitability of the central and peripheral neural pathways, and maximal voluntary contraction (MVC) to quantify strength changes. Measures were taken pre, immediately post, 10, 20 and 30 mins and 1, 2, 6, 24, 48, 72 and 96 hrs following training. Results: Significant decreases were observed at post, 10, 20, 30 min, 1 and 2 hrs for both training groups compared to control group for force, (p <.05), maximal compound wave; (p < .005), silent period; (p < .05). A significant increase in corticospinal excitability; (p < .005) was observed for both groups. Corticospinal excitability between strength and hypertrophy groups was near significance, with a large effect (η2= .202). All measures returned to baseline within 6 hrs post training. Discussion: Neurophysiological mechanisms appear to be significantly altered in the period 2 hrs post training, returning to homeostasis by 6 hrs. The evidence suggests that the time course of neural recovery post resistance training occurs 18-40 hours shorter than previous super compensation models. Strength and hypertrophy protocols showed similar response profiles with current findings suggesting greater post training corticospinal drive from hypertrophy training, despite previous evidence that strength training requires greater neural input. The increase in corticospinal drive and decrease inl inhibition appear to be a compensatory mechanism for decreases in peripheral nerve excitability and maximal voluntary force output. The changes in corticospinal excitability and inhibition are akin to adaptive processes observed with training interventions of 4 wks or longer. It appears that the 2 hr recovery period post training is the most influential for priming further neural adaptations with resistance training. Secondly, the frequency of prescribed resistance sessions can be scheduled closer than previous super compensation theory for optimal strength gains.

Keywords: neural responses, resistance training, super compensation, transcranial magnetic stimulation

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Authors: Tugba G. Isin Ozkan, Yoshiharu Fujii

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One of the most important constrains that decrease the crop yields are weeds. Increased amount and number of chemical herbicides are being utilized every day to control weeds. Chemical herbicides which cause environmental effects, and limitations on implementation of them have led to the nonchemical alternatives in the management of weeds. It is needed increasingly the application of allelopathy as a nonherbicidal innovation to control weed populations in integrated weed management. It is not only because of public concern about herbicide use, but also increased agricultural costs and herbicide resistance weeds. Allelopathy is defined as a common biological phenomenon, direct or indirect interaction which one plant or organism produces biochemicals influence the physiological processes of another neighboring plant or organism. Biochemicals involved in allelopathy are called allelochemicals that influence beneficially or detrimentally the growth, survival, development, and reproduction of other plant or organisms. All plant parts could have allelochemicals which are secondary plant metabolites. Allelochemicals are released to environment, influence the germination and seedling growth of neighbors' weeds; that is the way how allelopathy is applied for weed control. Crop cultivars have significantly different ability for inhibiting the growth of certain weeds. So, a high commercial value crop Corylus avellana L. and its byproducts were chosen to introduce for their allelopathic potential in this research. Edible nut of Corylus avellana L., commonly known as hazelnut is commercially valuable crop with byproducts; skin, hard shell, green leafy cover, and tree leaf. Research on allelopathic potential of a plant by using the sandwich bioassay method and investigation growth inhibitory activity is the first step to develop new and environmentally friendly alternatives for weed control. Thus, the objective of this research is to determine allelopathic potential of C. avellana L. and its byproducts by using sandwich method and to determine effective concentrations (EC) of their extracts for inducing half-maximum elongation inhibition on radicle of test plant, EC50. The sandwich method is reliable and fast bioassay, very useful for allelopathic screening under laboratory conditions. In experiments, lettuce (Lactuca sativa L.) seeds will be test plant, because of its high sensitivity to inhibition by allelochemicals and reliability for germination. In sandwich method, the radicle lengths of dry material treated lettuce seeds and control lettuce seeds will be measured and inhibition of radicle elongation will be determined. Lettuce seeds will also be treated by the methanol extracts of dry hazelnut parts to calculate EC₅₀ values, which are required to induce half-maximal inhibition of growth, as mg dry weight equivalent mL-1. Inhibitory activity of extracts against lettuce seedling elongation will be evaluated, like in sandwich method, by comparing the radicle lengths of treated seeds with that of control seeds and EC₅₀ values will be determined. Research samples are dry parts of Turkish hazelnut, C. avellana L. The results would suggest the opportunity for allelopathic potential of C. avellana L. with its byproducts in plant-plant interaction, might be utilized for further researches, could be beneficial in finding bioactive chemicals from natural products and developing of natural herbicides.

Keywords: allelopathy, Corylus avellana L., EC50, Lactuca sativa L., sandwich method, Turkish hazelnut

Procedia PDF Downloads 157

Authors: Fakhreia A. Al Sagheer, Enas I. Ibrahim, Khaled D. Khalil

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N-Acryloyl morpholine, NAM, was grafted onto chitosan utilizing homogeneous conditions with 1% acetic acid as the solvent, and potassium persulfate and sodium sulfite as the redox initiator. The effects of various reaction parameters, such as time, temperature, and monomer and initiator concentrations, on the percentage of grafting (G%) and the grafting efficiency (E%) were determined. The graft copolymer showed a remarkably improved crystallinity, as compared to the unmodified chitosan, based on the FESEM, XRD, and DSC results. Chitosan-g-poly(N-acryloyl morpholine) (Cs-PNAM), the copolymer obtained by using this procedure, was characterized by utilizing FTIR, FESEM, TGA, and XRD analysis. As expected, the results of an evaluation of antibacterial and antifungal activities show that the grafted chitosan copolymers exhibit stronger inhibitory effects against both types of microbes than does chitosan. Moreover, the size of the inhibition zone created by the graft copolymer was observed to be proportional to its G% corresponding to its morpholine content. Fortunately, the graft copolymer showed a marked growth inhibition against candidiasis (C.Albicans and C.Kefyr). We conclude that the graft copolymer may be highly effective in the prevention and treatment of candidiasis. In addition, the extent and pH dependence of uptake of different types of dyes (acidic: EBT, and MV; and basic: MB) by grafted chitosan in pH 6.5 aqueous solutions was determined. The results show that, the grafted copolymer exhibited a greater affinity to absorb the acid dyes more than the basic ones especially at relatively low temperature. Thus the modified chitosan can be used, in wastewater treatment, as efficient economic absorbent especially for anionic dyes from the industrial processing effluents.

Keywords: chitosan, N-Acryloyl morpholine, homogeneous grafting, antimicrobial activity, dye uptake

Procedia PDF Downloads 357

Authors: Hany M. Fayed, Rehab F. Abdel-Rahman, Alyaa F. Hessin, Hanan A. Ogaly, Gihan F. Asaad, Abeer A. A. Salama, Sahar Abdelrahman, Mahmoud S. Arbid, Marwan Abd Elbaset Mohamed

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Liver fibrosis is a serious global health problem that occurs as a result of a variety of chronic liver disorders. Apigenin, a flavonoid found in many plants, has several pharmacological properties. The aim of this study was to evaluate the antifibrotic efficacy of apigenin (APG) against experimentally induced hepatic fibrosis in rats via using thioacetamide (TAA) and to explore the possible underlying mechanisms. TAA (100 mg/kg, i.p.) was given three times each week for two weeks to induce liver fibrosis. After TAA injections, APG was given orally (5 and 10 mg/kg) daily for two weeks. Biochemical, molecular, histological and immunohistochemical analyses were performed on blood and liver tissue samples. The functioning of the liver, oxidative stress, inflammation, and liver fibrosis indicators were all evaluated. The findings showed that TAA markedly increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as the levels of malondialdehyde (MDA), focal adhesion kinase (FAK), hypoxia-inducible factor-1 (HIF-1), nuclear factor-κB (NF-κB), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) with a reduction in albumin, total protein, A/G ratio, GSH content and interleukin-10 (IL-10). Moreover, TAA elevated the content of collagen I, α -smooth muscle actin (α-SMA), and hydroxyproline in the liver. The treatment with APG in a dose-dependent manner has obviously prevented these alterations and amended the harmful effects induced by TAA. The histopathological and immunohistochemical observations supported this biochemical evidence. The higher dose of APG produced the most significant antifibrotic effect. As a result of these data, APG appears to be a promising antifibrotic drug and could be used as a new herbal medication or dietary supplement in the future for the treatment of liver fibrosis. This effect might be related to the inhibition of the HIF-1/FAK signaling pathway.

Keywords: apigenin, FAK, HIF-1, liver fibrosis, rat, thioacetamide

Procedia PDF Downloads 122

Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

Procedia PDF Downloads 272

Authors: Alireza Jalalvand, Maryam Saleh, Somayeh Behjat Khatouni, Zahra Bahri Najafi, Foroozan Fatahinia, Narges Ismailzadeh, Behrokh Farahmand

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Object: In the last two decades, the recent outbreak of Coronavirus (SARS-CoV-2) imposed a global pandemic in the world. Despite the increasing prevalence of the disease, there are no effective drugs to treat it. A suitable and rapid way to afford an effective drug and treat the global pandemic is a computational drug study. This study used molecular docking methods to examine the potential inhibition of over 50 antiviral drugs against three fundamental proteins of SARS-CoV-2. METHODS: Through a literature review, three important proteins (a key protease, RNA-dependent RNA polymerase (RdRp), and spike) were selected as drug targets. Three-dimensional (3D) structures of protease, spike, and RdRP proteins were obtained from the Protein Data Bank. Protein had minimal energy. Over 50 antiviral drugs were considered candidates for protein inhibition and their 3D structures were obtained from drug banks. The Autodock 4.2 software was used to define the molecular docking settings and run the algorithm. RESULTS: Five drugs, including indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, exhibited the highest inhibitory potency against all three proteins based on the binding energies and drug binding positions deduced from docking and hydrogen-bonding analysis. Conclusions: According to the results, among the drugs mentioned, saquinavir and lopinavir showed the highest inhibitory potency against all three proteins compared to other drugs. It may enter laboratory phase studies as a dual-drug treatment to inhibit SARS-CoV-2.

Keywords: covid-19, drug repositioning, molecular docking, lopinavir, saquinavir

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Authors: Konstantopoulos N., Samitas A., E. Vasileiou, Kinias I.

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This article introduces a new view on the month effect study. Applying a Markov Switching Regime model on data from the Greek Time Deposits (TDs) market for the time span January 2003 to October 2013, we examine if there is a month effect on the Greek banking industry. The empirical findings provide convincing evidence for a new king of monthly anomaly. The explanation for the specific abnormality may be the upward deposits window dressing. Further research should be done in order to examine if the specific calendar effect exists in other countries or it is only a Greek phenomenon.

Keywords: calendar anomalies, banking crisis, month effect, Greek banking industry

Procedia PDF Downloads 358

Authors: Michelle Belinda S. Weerawardana, Gobika Thiripuranathar, Priyani A. Paranagama

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Most of fresh vegetables and fruits available in the retail markets undergo a physiological disorder in its appearance and coloration, which indeed discourages consumer purchase. A loss of millions of dollars yearly to the food industry had been due to this pronounced color reaction called Enzymatic Browning which is driven due to the catalytic activity by an oxidoreductase enzyme, polyphenol oxidase (PPO). The enzyme oxidizes the phenolic compounds which are abundantly available in fruits and vegetables as substrates into quinones, which could react with proteins in its surrounding to generate black pigments, called melanins, which are highly UV-active compounds. Annona muricata (Katu anoda) and Musa acuminata (Ash plantains) is a fruit and a vegetable consumed by Sri Lankans widely due to their high nutritional values, medicinal properties and economical importance. The objective of the present study was to evaluate and determine the effective natural anti-browning inhibitors that could prevent PPO activity in the selected fruit and vegetable. Enzyme extracts from Annona muricata (Katu anoda) and Musa acuminata (Ash plantains), were prepared by homogenizing with analytical grade acetone, and pH of each enzyme extract was maintained at 7.0 using a phosphate buffer. The extracts of inhibitors were prepared using powdered ginger rhizomes and essential oil from the bark of Cinnamomum zeylanicum. Water extracts of ginger were prepared and the essential oil from Ceylon cinnamon bark was extracted using steam distillation method. Since the essential oil is not soluble in water, 0.1µl of cinnamon bark oil was mixed with 0.1µl of Triton X-100 emulsifier and 5.00 ml of water. The effect of each inhibitor on the PPO activity was investigated using catechol (0.1 mol dm-3) as the substrate and two samples of enzyme extracts prepared. The dosages of the prepared Cinnamon bark oil, and ginger (2 samples) which were used to measure the activity were 0.0035 g/ml, 0.091 g/ml and 0.087 g/ml respectively. The measurements of the inhibitory activity were obtained at a wavelength of 525 nm using the UV-visible spectrophotometer. The results evaluated thus revealed that % inhibition observed with cinnamon bark oil, and ginger for Annona muricata was 51.97%, and 60.90% respectively. The effects of cinnamon bark oil, and ginger extract on PPO activity of Musa acuminata were 49.51%, and 48.10%. The experimental findings thus revealed that Cinnamomum zeylanicum bark oil was a more effective inhibitor for PPO enzyme present in Musa acuminata and ginger was effective for PPO enzyme present in Annona muricata. Overall both the inhibitors were proven to be more effective towards the activities of PPO enzyme present in both samples. These inhibitors can thus be corroborated as effective, natural, non-toxic, anti-browning extracts, which when added to the above fruit and vegetable will increase the shelf life and also the acceptance of the product by the consumers.

Keywords: anti-browning agent, enzymatic browning, inhibitory activity, polyphenol oxidase

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Authors: Khaled M. Khleifat

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An extracellular methanol and ethanol tolerant lipase producing bacterial strain K5b4 was isolated from soil samples contaminated with hydrocarbon residues. It was identified by using morphological and biochemical characteristics and 16srRNA technique as Acinetobacter species. The immobilized lipase from Acinetobacter sp. K5b4 retained more than 98% of its residual activity after incubation with pure methanol and ethanol for 24 hours. The highest hydrolytic activity of the immobilized enzyme was obtained in the presence of 75% (v/v) methanol in the assay solution. In contrary, the enzyme was able to maintain its original activity up to only 25% (v/v) ethanol whereas at elevated concentrations of 50 and 75% (v/v) the enzyme activity was reduced to 10 and 40%, respectively. Maximum lipase activity of 31.5 mU/mL was achieved after 48 hr cultivation when the optimized medium (pH 7.0) that composed of 1.0% (w/v) olive oil, 0.2% (w/v) glycerol, 0.15% (w/v) yeast extract, and 0.05% (w/v) NaCl was inoculated with 0.4% (v/v) seed culture and incubated at 30°C and 150 rpm agitation speed. However, the presence of CaCl2 in the growth media did not show any inhibitory or stimulatory effect on the enzyme production as it compared to the control experiment. Meanwhile, the other mineral salts MgCl2, MnCl2, KCl and CoCl2 were negatively affected the production of lipase enzyme. The inhibition of lipase production from Acinetobacter sp. K5b4 in presence of glucose suggesting that lipase gene expression is prone to catabolic repression.

Keywords: K5B4, methanol and ethanol, acinetobacter, morphological

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