Search results for: Molecular modeling of 17-picolyl and 17-picolinylidene androstane derivatives with anticancer activity

Authors: Marie Madeleine Sarzi Inacio, Ligiane Carolina Leite Dauzacker, Rodrigo Henriques Lopes Da Silva

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The climate changes resulting from human activity have increased interest in more sustainable production practices to reduce and offset pollutant emissions. Brazil, with its vast areas capable of carbon absorption, holds a significant advantage in this context. However, to optimize the country's sustainable potential, it is important to establish a robust carbon market with clear rules for the eligibility and validation of projects aimed at reducing and offsetting Greenhouse Gas (GHG) emissions. In this study, our objective is to conduct a feasibility analysis through a case study to evaluate the implementation of an urban forest credits standard in Brazil, using the Urban Forest Credits (UFC) model implemented in the United States as a reference. Thus, the city of Ribeirão Preto, located in Brazil, was selected to assess the availability of green areas. With the CO2 emissions value from the metalworking industry, it was possible to analyze information in the case study, considering the activity. The QGIS software was used to map potential urban forest areas, which can connect to various types of geospatial databases. Although the chosen municipality has little vegetative coverage, the mapping identified at least eight areas that fit the standard definitions within the delimited urban perimeter. The outlook was positive, and the implementation of projects like Urban Forest Credits (UFC) adapted to the Brazilian reality has great potential to benefit the country in the carbon market and contribute to achieving its Greenhouse Gas (GHG) emission reduction goals.

Keywords: carbon neutrality, metalworking industry, carbon credits, urban forestry credits

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Authors: Gajanan V. Mane, Rashmi More, Mahesh S. Sonawane, Tushar Lodha, Rohit Sharma

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The diversity of fungi isolated from two different termite species viz., Odontoterms assmuthi and O. abesus was investigated by dilution- plate method, combined with morphological characteristics and sequencing of internal transcribed spacer region. In total, ninety-six fungi were isolated and purified, out of which 69 isolates were obtained from O. assmuthi belonging to 18 genera and 31 species, whereas 27 isolates were obtained from O. abesus belonging to 15 genera and 17 species. The fungal strains were screened for laccase, amylase, cellulase and pectinase enzymes production. Twenty-seven strains were positive for laccase, 59 strains were positive for amylase, 71 strains were positive for cellulase and 72 strains were positive for pectinase enzymes. The antimicrobial activities of the isolated fungi were tested by the dual plate culture method against standard pathogens. Bioactive secondary metabolites were identified by HPLC and LCMS. Four isolates viz., Penicillium goetzii MG 57, Epicoccum sp. MG 39, Penicillium tanzanicum MG 30, Aspergillus polyporicola MG 54, showed positive antimicrobial activity against standard pathogens, Streptococcus pneumonia MCC 2425, Staphylococcus aureus MCC 2408, Pseudomonas aeruginosa MCC 2080, Escherichia coli MCC 2412, Enterococcus faecalis MCC 2409, Klebsiella pneumonia MCC 2451, Micrococcus luteus MCC 2155 and Candida albicans MCC 1151. In conclusion, the study showed that the insect gut harbor fungal diversity, which is futuristic with biotechnological potential and could be a good source of enzymes and antibiotics.

Keywords: termites, fungi, its, enzyme, antimicrobial activity

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Authors: Stephanie Remedios, Linda Veronica Rios

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Background. Pediatric obesity is a serious health problem linked to multiple physical diseases and ailments, including diabetes, heart disease, and joint issues. While research has shown pediatric obesity can bring about an array of physical illnesses, it is less known how such a condition can affect children’s cognitive development. With childhood overweight and obesity prevalence rates on the rise, it is essential to understand the scope of their cognitive consequences. The present review of the literature tested the hypothesis that poor physical health, such as childhood obesity or malnutrition, negatively impacts a child’s cognitive development. Methodology. A systematic review was conducted to determine the relationship between poor physical health and lower cognitive functioning in children ages 4-16. Electronic databases were searched for studies dating back to ten years. The following databases were used: Science Direct, FIU Libraries, and Google Scholar. Inclusion criteria consisted of peer-reviewed academic articles written in English from 2012 to 2022 that analyzed the relationship between childhood malnutrition and obesity on cognitive development. A total of 17,000 articles were obtained, of which 16,987 were excluded for not addressing the cognitive implications exclusively. Of the acquired articles, 13 were retained. Results. Research suggested a significant connection between diet and cognitive development. Both diet and physical activity are strongly correlated with higher cognitive functioning. Cognitive domains explored in this work included learning, memory, attention, inhibition, and impulsivity. IQ scores were also considered objective representations of overall cognitive performance. Studies showed physical activity benefits cognitive development, primarily for executive functioning and language development. Additionally, children suffering from pediatric obesity or malnutrition were found to score 3-10 points lower in IQ scores when compared to healthy, same-aged children. Conclusion. This review provides evidence that the presence of physical activity and overall physical health, including appropriate diet and nutritional intake, has beneficial effects on cognitive outcomes. The primary conclusion from this research is that childhood obesity and malnutrition show detrimental effects on cognitive development in children, primarily with learning outcomes. Assuming childhood obesity and malnutrition rates continue their current trade, it is essential to understand the complete physical and psychological implications of obesity and malnutrition in pediatric populations. Given the limitations encountered through our research, further studies are needed to evaluate the areas of cognition affected during childhood.

Keywords: childhood malnutrition, childhood obesity, cognitive development, cognitive functioning

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Authors: Konstantin S. Vainutis, Mark E. Andreev, Anastasia N. Voronova, Mikhail Yu. Shchelkanov

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Introduction: The trematodes from the family Cyclocoelidae (cyclocoelids) belong to the superfamily Echinostomatoidea infecting air sacs and trachea of wild birds. At present, the family Cyclocoelidae comprises nine valid genera in three subfamilies: Cyclocoelinae (type taxon), Haematotrephinae, and Typhlocoelinae. To our best knowledge, in this study, molecular genetic methods were used for the first time for studying cyclocoelids from the Russian Far East. Here we provide the data on the morphology and phylogeny of cyclocoelids from gadwall from the Russian Far East. The morphological and genetic data obtained for cyclocoelids indicated the necessity to revise the previously proposed classification within the family Cyclocoelidae. Objectives: The first objective was performing the morphological study of cyclocoelids found in M. strepera from the Russian Far East. The second objective is to reconstruct the phylogenetic relationships of the studied trematodes with other cyclocoelids using the 28S gene. Material and methods: During the field studies in the Khasansky district of the Primorsky region, 21 cyclocoelids were recovered from the air sacs of a single gadwall Mareca strepera. Seven samples of cyclocoelids were overstained in alum carmine, dehydrated in a graded ethanol series, cleared in clove oil, and mounted in Canada balsam. Genomic DNA was extracted from four cyclocoelids using the alkaline lysis method HotShot. The 28S rDNA fragment was amplified using the forward primer Digl2 and the reverse primer 1500R. Results: According to morphological features (ovary intratesticular, forming a triangle with the testes), the studied worms belong to the subfamily Cyclocoelinae Stossich, 1902. In particular, the highest morphological similarity was observed in relation to the trematodes of the genus Cyclocoelum Brandes, 1892 – genital pores are pharyngeal. However, the genetic analysis has shown significant discrepancies between the trematodes studied regarding the genus Cyclocoelum. On the phylogenetic tree, these trematodes took the sister position in relation to the genus Morishitium (previously considered in the subfamily Szidatitrematinae). Conclusion: Based on the results of the morphological and genetic studies, cyclocoelids isolated from Mareca strepera are suggested to be described in the previously unknown genus and differentiated from the type genus Cyclocoelum of the type subfamily Cyclocoelinae. Considering the available molecular data, including described cyclocoelids, the family Cyclocoelidae comprises ten valid genera in the three subfamilies mentioned above.

Keywords: new species, trematoda, phylogeny, cyclocoelidae

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Authors: Kamran Dastafkan, Chuan Zhao

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Improving surface chemistry is a promising approach in addition to the rational alteration in the catalyst composition to advance water electrolysis. Here, we demonstrate an evident enhancement of oxygen evolution on an iron-nickel vanadate catalyst synthesized by a facile successive ionic adsorption and reaction method. The vanadate-modified catalyst demonstrates a highly efficient oxygen evolution in 1 M KOH by requiring low overpotentials of 274 and 310 mV for delivering large current densities of 100 and 400 mA cm⁻², respectively where vigorous gas bubble evolution occurs. Vanadate modification augments the OER activity from three aspects. (i) Both the electrochemical surface area (47.1 cm²) and intrinsic activity (318 mV to deliver 10 mA cm⁻² per unit ECSA) of the catalytic sites are improved. (ii) The amorphous and roughened nanoparticle-comprised catalyst film exhibits a high surface wettability and a low-gas bubble-adhesion, which is beneficial for the accelerated mass transport and gas bubble dissipation at large current densities. The gas bubble dissipation behavior is studied by operando dynamic specific resistance measurements where a significant change in the variation of the interfacial resistance during the OER is detected for the vanadate-modified catalyst. (iii) The introduced vanadate poly-oxo-anions with high charge density have electronic interplay with Fe and Ni catalytic centers. Raman study reveals the structural evolution of β-NiOOH and γ-FeOOH phases during the OER through the vanadate-active site synergistic interactions. Achievement of a high catalytic turnover of 0.12 s⁻¹ put the developed FeNi vanadate among the best recent catalysts for water oxidation.

Keywords: gas bubble dissipation, iron-nickel vanadate, low-gas bubble-adhesion catalyst, oxygen evolution reaction

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Authors: Hanane Belayachi, Sarra Bourahla, Amel Belayachi, Fadela Nemchi, Mostefa Belhakem

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The most used techniques to remove pollutants from wastewater are adsorption onto activated carbon (AC) and oxidation using a photocatalyst slurry. The aim of this work is to eliminate such drawbacks by combining AC and titanium dioxide (TiO₂) in a photocatalytically Regenerative Activated Carbon. Anatase titania was deposited on powder-activated carbon made from grape seeds by the impregnation method, and then the composite photocatalyst was employed for the removal of reactive black 5, which is an anionic azo dye, from water. The AGS/TiO₂ was characterized by BET, MEB, RDX and optical absorption spectroscopy. The BET surface area and the pore structure of composite photocatalysts (AGS/TiO₂) and activated grape seeds (AGS) were evaluated from nitrogen adsorption data at 77 K in relation to process conditions. Our results indicate that the photocatalytic activity of AGS/TiO₂ was much higher than single-phase titania. The adsorption equilibrium of reactive black 5 from aqueous solutions on the examined materials was investigated. Langmuir, Freundlich, and Redlich–Petersen models were fitted to experimental equilibrium data, and their goodness of fit is compared. The degradation kinetics fitted well to the Langmuir-Hinselwood pseudo first order rate low. The photocatalytic activity of AGS/TiO₂ was much higher than virgin TiO₂. Chemical oxygen demand (COD) removal was measured at regular intervals to quantify the mineralization of the dye. Above 96% mineralization was observed. These results suggest that UV-irradiated TiO₂ immobilized on activated carbon may be considered an adequate process for the treatment of diluted colored textile wastewater.

Keywords: activated carbon, pollutant, catalysis, TiO₂

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Authors: Fahad Aljasass, Hamza Abu-Tarboush, Salah Aleid, Siddig Hamad

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The effects of different high hydrostatic pressure treatments on the shelf life of camel’s milk were studied. Treatments at 300 to 350 MPa for 5 minutes at 40°C reduced microbial contamination to levels that prolonged the shelf life of refrigerated (3° C) milk up to 28 days. The treatment resulted in a decrease in the proteolytic activity of the milk. The content of proteolytic enzymes in the untreated milk sample was 4.23 µM/ml. This content decreased significantly to 3.61 µM/ml when the sample was treated at 250 MPa. Treatment at 300 MPa decreased the content to 3.90 which was not significantly different from the content of the untreated sample. The content of the sample treated at 350 MPa dropped to 2.98 µM/ml which was significantly lower than the contents of all other treated and untreated samples. High pressure treatment caused a slight but statistically significant increase in the pH of camel’s milk. The pH of the untreated sample was 6.63, which increased significantly to 6.70, in the samples treated at 250 and 350 MPa, but insignificantly in the sample treated at 300 MPa. High pressure treatment resulted in some degree of milk fat oxidation. The thiobarbituric acid (TBA) value of the untreated sample was 0.86 mg malonaldehyde/kg milk. This value remained unchanged in the sample treated at 250 MPa, but then it increased significantly to 1.25 and 1.33 mg/kg in the samples treated at 300 and 350 MPa, respectively. High pressure treatment caused a small increase in the greenness (a* value) of camel’s milk. The value of a* was reduced from -1.17 for the untreated sample to -1.26, -1.21 and -1.30 for the samples treated at 250, 300 and 350 MPa, respectively. Δa* at the 250 MPa treatment was -0.09, which then decreased to -0.04 at the 300 MPa treatment to increase again to -0.13 at the 350 MPa treatment. The yellowness (b* value) of camel’s milk increased significantly as a result of high pressure treatment. The b* value of the untreated sample was 1.40, this value increased to 2.73, 2.31 and 2.18 after treatments at 250, 300 and 350 MPa, respectively. The Δb* value was +1.33 at the treatment 250 MPa, decreased to +0.91 at 300 MPa and further to +0.78 at 350 MPa. The pressure treatment caused slight effect on color, slight decrease in protease activity and a slight increase in the oxidation products of lipids.

Keywords: high hydrostatic pressure, camel’s milk, mesophilic aerobic bacteria, clotting, protease

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Authors: Dong Zhao

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Abstract—Extensive research on obtaining applicable room temperature superconductors meets the major barrier, and the record Tc of 135 K achieved via cuprate has been idling for decades. Even though, the accomplishment of higher Tc than the cuprate was made through pressurizing certain compounds composed of light elements, such as for the LaH10 and for the metallic hydrogen. Room temperature superconductivity under ambient pressure is still the preferred approach and is believed to be the ultimate solution for many applications. While racing to find the breakthrough method to achieve this room temperature Tc milestone in superconducting research, a report stated a discovery of a possible high-temperature superconductor, i.e., the thorium sulfide ThS. Apparently, ThS’s Tc can be at room temperature or even higher. This is because ThS revealed an unusual property of the ‘coexistence of high electrical conductivity and diamagnetism’. Noticed that this property of coexistence of high electrical conductivity and diamagnetism is in line with superconductors, meaning ThS is also at its superconducting state. Surprisingly, ThS owns the property of superconductivity at least at room temperature and under atmosphere pressure. Further study of the ThS’s electrical and magnetic properties in comparison with thorium di-iodide ThI2 concluded its molecular configuration as [Th4+(e-)2]S. This means the ThS’s cation is composed of a [Th4+(e-)2]2+ cation core. It is noticed that this cation core is built by an oxidation state +4 of thorium atom plus an electron pair on this thorium atom that resulted in an oxidation state +2 of this [Th4+(e-)2]2+ cation core. This special construction of [Th4+(e-)2]2+ cation core may lead to the ThS’s room temperature superconductivity because of this characteristic electron lone pair residing on the thorium atom. Since the study of thorium chemistry was carried out in the period of before 1970s. the exploration about ThS’s possible room temperature superconductivity would require resynthesizing ThS. This re-preparation of ThS will provide the sample and enable professionals to verify the ThS’s room temperature superconductivity. Regrettably, the current regulation prevents almost everyone from getting access to thorium metal or thorium compounds due to the radioactive nature of thorium-232 (Th-232), even though the radioactive level of Th-232 is extremely low with its half-life of 14.05 billion years. Consequently, further confirmation of ThS’s high-temperature superconductivity through experiments will be impossible unless the use of corresponding thorium metal and related thorium compounds can be deregulated. This deregulation would allow researchers to obtain the necessary starting materials for the study of ThS. Hopefully, the confirmation of ThS’s room temperature superconductivity can not only establish a method to obtain applicable superconductors but also to pave the way for fully understanding the mechanism of superconductivity.

Keywords: co-existence of high electrical conductivity and diamagnetism, electron pairing and electron lone pair, room temperature superconductivity, the special molecular configuration of thorium sulfide ThS

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Authors: Alok Kumar, Hari Ram, Lebin Thomas, Ved Pal Singh

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Organic solvent tolerant amylases and proteases of microbial origin are in great demand for their application in transglycosylation of water-insoluble flavanoids and in peptide synthesizing reaction in organic media. Most of the amylases and proteases are unstable in presence of organic solvent. In the present work two different bacterial strains M-11 and VP-07 were isolated from the soil sample of a dairy farm in Delhi, India, for the efficient production of extracellular amylase and protease through their screening on starch agar (SA) and skimmed milk agar (SMA) plates, respectively. Both the strains (M-11 and VP-07) were identified based on morphological, biochemical and 16S rRNA gene sequencing methods. After analysis through Ez-Taxon software, the strains M-11 and VP-07 were found to have maximum pairwise similarity of 98.63% and 100% with Bacillus subtilis subsp. inaquosorum BGSC 3A28 and Bacillus anthracis ATCC 14578 and were therefore identified as Bacillus sp. UKS1 and Bacillus sp. UKS2, respectively. Time course study of enzyme activity and bacterial growth has shown that both strains exhibited typical sigmoid growth behavior and maximum production of amylase (180 U/ml) and protease (78 U/ml) by these strains (UKS1 and UKS2) was commenced during stationary phase of growth at 24 and 20 h, respectively. Thereafter, both amylase and protease were tested for their tolerance towards organic solvents and were found to be active as well stable in p-xylene (130% and 115%), chloroform (110% and 112%), isooctane (119% and 107%), benzene (121% and 104%), n-hexane (116% and 103%) and toluene (112% and 101%, respectively). Owing to such properties, these enzymes can be exploited for their potential application in industries for organic synthesis.

Keywords: amylase, enzyme activity, industrial applications, organic solvent tolerant, protease

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Authors: Adela Diepoltova, Klara Konecna, Ondrej Jandourek, Petr Nachtigal

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A loss of control over antibiotic-resistant pathogens has become a global issue due to severe and often untreatable infections. This state is reflected in complicated treatment, health costs, and higher mortality. All these factors emphasize the urgent need for the discovery and development of new anti-infectives. One of the most common pathogens mentioned in the phenomenon of antibiotic resistance are bacteria of the genus Staphylococcus. These bacterial agents have developed several mechanisms against the effect of antibiotics. One of them is biofilm formation. In staphylococci, biofilms are associated with infections such as endocarditis, osteomyelitis, catheter-related bloodstream infections, etc. To author's best knowledge, no validated and standardized methodology evaluating candidate compound activity against staphylococcal biofilms exists. However, a variety of protocols for in vitro drug activity testing has been suggested, yet there are often fundamental differences. Based on our experience, a key methodological step that leads to credible results is to form a robust biofilm with appropriate attributes such as firm adherence to the substrate, a complex arrangement in layers, and the presence of extracellular polysaccharide matrix. At first, for the purpose of drug antibiofilm activity evaluation, the focus was put on various conditions (supplementation of cultivation media by human plasma/fetal bovine serum, shaking mode, the density of initial inoculum) that should lead to reproducible and robust in vitro staphylococcal biofilm formation in microtiter plate model. Three model staphylococcal reference strains were included in the study: Staphylococcus aureus (ATCC 29213), methicillin-resistant Staphylococcus aureus (ATCC 43300), and Staphylococcus epidermidis (ATCC 35983). The total biofilm biomass was quantified using the Christensen method with crystal violet, and results obtained from at least three independent experiments were statistically processed. Attention was also paid to the viability of the biofilm-forming staphylococcal cells and the presence of extracellular polysaccharide matrix. The conditions that led to robust biofilm biomass formation with attributes for biofilms mentioned above were then applied by introducing an alternative method analogous to the commercially available test system, the Calgary Biofilm Device. In this test system, biofilms are formed on pegs that are incorporated into the lid of the microtiter plate. This system provides several advantages (in situ detection and quantification of biofilm microbial cells that have retained their viability after drug exposure). Based on our preliminary studies, it was found that the attention to the peg surface and substrate on which the bacterial biofilms are formed should also be paid to. Therefore, further steps leading to the optimization were introduced. The surface of pegs was coated by human plasma, fetal bovine serum, and L-polylysine. Subsequently, the willingness of bacteria to adhere and form biofilm was monitored. In conclusion, suitable conditions were revealed, leading to the formation of reproducible, robust staphylococcal biofilms in vitro for the microtiter model and the system analogous to the Calgary biofilm device, as well. The robustness and typical slime texture could be detected visually. Likewise, an analysis by confocal laser scanning microscopy revealed a complex three-dimensional arrangement of biofilm forming organisms surrounded by an extracellular polysaccharide matrix.

Keywords: anti-biofilm drug activity screening, in vitro biofilm formation, microtiter plate model, the Calgary biofilm device, staphylococcal infections, substrate modification, surface coating

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Authors: Shih-Ching Wang, Mark Lang

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This paper examines the secondary effects and consequences of special displays on subsequent shopping behavior. Special displays are studied as a prominent form of in-store or shopper marketing activity. Two experiments are performed using special value and special quality-oriented displays in an online simulated store environment. The impact of exposure to special displays on mindsets and resulting product choices are tested in a shopping task. Impact on store image is also tested. The experiments find that special displays do trigger shopping mindsets that affect product choices and shopping basket composition and value. There are intended and unintended positive and negative effects found. Special value displays improve store price image but trigger a price sensitive shopping mindset that causes more lower-priced items to be purchased, lowering total basket dollar value. Special natural food displays improve store quality image and trigger a quality-oriented mindset that causes fewer lower-priced items to be purchased, increasing total basket dollar value. These findings extend the theories of product categorization, mind-sets, and price sensitivity found in communication research into the retail store environment. Findings also warn retailers to consider the total effects and consequences of special displays when designing and executing in-store or shopper marketing activity.

Keywords: special displays, mindset, shopping behavior, price consciousness, product categorization, store image

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Authors: Jinny Hong, Jeanne C. Watson

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Three types of autobiographical memory recall -specific, episodic, and generic- were examined in relation to the quality of descriptions and in-session levels of emotional arousal. Correlational analyses and general estimating equation were conducted to test the relationships between 1) quality of descriptions and type of memory, 2) type of memory and emotional arousal, and 3) quality of descriptions and emotional arousal. The data was transcripts drawn from an archival randomized-control study comparing cognitive-behavioral therapy and emotion-focused therapy in a 16-week treatment for depression. Autobiographical memory recall segments were identified and sorted into three categories: specific, episodic, and generic. Quality of descriptions of these segments was then operationalized and measured using the Referential Activity Scale, and each memory segment was rated on four dimensions: concreteness, specificity, clarity, and overall imagery. Clients’ level of emotional arousal for each recall was measured using the Client’s Expression Emotion Scale. Contrary to the predictions, generic memories are associated with higher emotional arousal ratings and descriptive language ratings compared to specific memories. However, a positive relationship emerged between the quality of descriptions and expressed emotional arousal, indicating that the quality of descriptions in which memories are described in sessions is more important than the type of memory recalled in predicting clients’ level of emotional arousal. The results from this study provide a clearer understanding of the role of memory recall types and use of language in activating emotional arousal in psychotherapy sessions in a depressed sample.

Keywords: autobiographical memory recall, emotional arousal, psychotherapy for depression, quality of descriptions, referential activity

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Authors: Anand Malik

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The Himalayas with high tectonic activities poses a great threat to human life and property. Climate change is another reason which triggering extreme events multiple fold effect on high mountain glacial environment, rock falls, landslides, debris flows, flash flood and snow avalanches. One such extreme event of cloud burst along with breach of moraine dammed Chorabri Lake occurred from June 14 to June 17, 2013, triggered flooding of Saraswati and Mandakini rivers in the Kedarnath Valley of Rudraprayag district of Uttrakhand state of India. As a result, huge volume of water with its high velocity created a catastrophe of the century, which resulted into loss of large number of human/animals, pilgrimage, tourism, agriculture and property. Thus a comprehensive assessment of debris flow hazards requires GIS-based modeling using numerical methods. The aim of present study is to focus on analysis and mapping of debris flow movements using geospatial data with flow-r (developed by team at IGAR, University of Lausanne). The model is based on combined probabilistic and energetic algorithms for the assessment of spreading of flow with maximum run out distances. Aster Digital Elevation Model (DEM) with 30m x 30m cell size (resolution) is used as main geospatial data for preparing the run out assessment, while Landsat data is used to analyze land use land cover change in the study area. The results of the study area show that model can be applied with great accuracy as the model is very useful in determining debris flow areas. The results are compared with existing available landslides/debris flow maps. ArcGIS software is used in preparing run out susceptibility maps which can be used in debris flow mitigation and future land use planning.

Keywords: debris flow, geospatial data, GIS based modeling, flow-R

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Authors: Suraj Muke, Vikas Mankumare, Sadhana Sathaye

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Osteoporosis is the most common metabolic bone disease which affects an estimated 25 million people worldwide, leading to 1 million fractures, 40,000 annual deaths and health costs of billions of dollars. It is estimated that about 80% of total osteoporosis patients are women, amongst which majority are above the age of 45 years. Postmenopausal osteoporosis is associated with lack of intestinal calcium absorption, increasing pro-oxidant and inflammatory mediators. Lawsonia inermis is a biennial dicotyledonous herbaceous shrub is reported to possess a high flavonoid, high phenolic and Inhibitors of osteoclastogenesis like Daphneside and Daphnorin. The present study aimed to screen osteoprotective effect of methanolic extract of Lawsonia inermis (LIM) in rat model along with its antioxidant activity. LIM shows phenolic content 146.3Milligrams of Gallic acid equivalent present per gram of extract and 19.8 Milligrams of rutin per gram of extract of Total flavonoid content with IC50 value 42.99μg/ml. bilateral ovariectomized rat model in which Healthy female wistar rats were used for screening. Treatment with LIM was carried out using graded doses of 25mg/kg, 50mg/kg and 100mg/kg for period of 28 days. The negative control group comprised of ovariectomized rats along with saline treatment for four weeks whereas sham operated rats were used as positive control.LIM showed a decrease in bone turnover by preventing loss of urinary calcium and phosphorous moreover it decreased the alkaline phosphatase levels and loss of bone density is prevented by LIM suggesting decrease in osteoclast activity.

Keywords: antioxidant, osteoclast, osteoporosis, ovariectomized

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Authors: Nuraisyah H. Zulkifley, Suriani Ismail, Rosliza Abdul Manaf, Poh Y. Lim

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Taking care of a person with dementia (PWD) is one of the most problematic and challenging caregiving situations. Without proper support, caregiver would need to deal with the impact of caregiving that would lead to caregiver burden. One of the most common tools used to measure caregiver burden among caregivers of PWD is Zarit Burden Interview (ZBI). A systematic review has been conducted through searching Medline, Science Direct, Cochrane Library, Embase, PsycINFO, ProQuest, and Scopus databases to identify relevant articles that elaborate on intervention and outcomes on ZBI among informal caregiver of PWD. The articles were searched in October 2019 with no restriction on language or publication status. Inclusion criteria are randomized control trial (RCT) studies, participants were informal caregivers of PWD, ZBI measured as outcomes, and intervention group was compared with no intervention control or usual care control. Two authors reviewed and extracted the data from the full-text articles. From a total of 344 records, nine studies were selected and included in this narrative review, and eight studies were included in the meta-analysis. The types of interventions that were implemented to ease caregiver burden are psychoeducation, physical activity, psychosocial, and computer-based intervention. The meta-analysis showed that there is a significant difference in the mean score of ZBI (p = 0.006) in the intervention group compared to the control group after implementation of intervention. In conclusion, interventions such as psychoeducation, psychosocial, and physical activity can help to reduce the burden experiencing by the caregivers of PWD.

Keywords: dementia, informal caregiver, randomized control trial, Zarit burden interview

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Authors: D. Mowla, N. Rasti, P. Keshavarz

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Reduction of fossil fuels sources, increasing of pollution gases emission, and global warming effects increase the demand of renewable fuels. One of the main candidates of alternative fuels is biodiesel. Biodiesel limits greenhouse gas effects due to the closed CO₂ cycle. Biodiesel has more biodegradability, lower combustion emissions such as CO, SO_x, HC, PM and lower toxicity than petro diesel. However, biodiesel has high production cost due to high price of plant oils as raw material. So, the utilization of waste cooking oils (WCOs) as feedstock, due to their low price and disposal problems reduce biodiesel production cost. In this study, production of biodiesel by transesterification of methanol and WCO using modified sodic potassic (SP) clinoptilolite zeolite and sodic potassic calcic (SPC) clinoptilolite zeolite as heterogeneous catalysts have been investigated. These natural clinoptilolite zeolites were modified by KOH solution to increase the site activity. The optimum biodiesel yields for SP clinoptilolite and SPC clinoptilolite were 95.8% and 94.8%, respectively. Produced biodiesel were analyzed and compared with petro diesel and ASTM limits. The properties of produced biodiesel confirm well with ASTM limits. The density, kinematic viscosity, cetane index, flash point, cloud point, and pour point of produced biodiesel were all higher than petro diesel but its acid value was lower than petro diesel. Finally, the reusability and regeneration of catalysts were investigated. The results indicated that the spent zeolites cannot be reused directly for the transesterification, but they can be regenerated easily and can obtain high activity.

Keywords: biodiesel, renewable fuel, transesterification, waste cooking oil

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Authors: Lancelot Boulet, Pierre Benard, Ghislain Lartigue, Vincent Moureau, Nicolas Chauvet, Sheddia Didorally

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International aeronautic standards demand a fire certification for engines that demonstrate their resistance. This demonstration relies on tests performed with prototype engines in the late stages of the development. Hardest tests require to place a kerosene standardized flame in front of the engine casing during a given time with imposed temperature and heat flux. The purpose of this work is to provide a better characterization of a kerosene/air certification burner in order to minimize the risks of test failure. A first Large-Eddy Simulation (LES) study of the certification burner permitted to model and simulate this burner, including both adiabatic and Conjugate Heat Transfer (CHT) computations. Carried out on unstructured grids with 40 million tetrahedral cells, using the finite-volume YALES2 code, spray combustion, forced convection on walls and conduction in the solid parts of the burner were coupled to achieve a detailed description of heat transfer. It highlighted the fact that conduction inside the solid has a real impact on the flame topology and the combustion regime. However, in the absence of radiative heat transfer, unrealistic temperature of the equipment was obtained. The aim of the present study is to include the radiative heat transfer in order to reach the same temperature given by experimental measurements. First, various test-cases are conducted to validate the coupling between the different heat solvers. Then, adiabatic case, CHT case, as well as CHT including radiative transfer are studied and compared. The LES model is finally applied to investigate the heat transfer in a flame impaction configuration. The aim is to progress on fire test modeling so as to reach a good confidence level as far as success of the certification test is concerned.

Keywords: conjugate heat transfer, fire resistance test, large-eddy simulation, radiative transfer, turbulent combustion

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Authors: Tarek Abdoun, Waleed Elsekelly

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Introduction: Liquefaction of soils during earthquakes can have significant consequences on the stability of structures and infrastructure. This study focuses on comparing two liquefaction case histories in California, namely the response of the Wildlife site in the Imperial Valley to the 2010 El-Mayor Cucapah earthquake (Mw = 7.2, amax = 0.15g) and the response of the Treasure Island Fire Station (F.S.) site in the San Francisco Bay area to the 1989 Loma Prieta Earthquake (Mw = 6.9, amax = 0.16g). Both case histories involve liquefiable layers of silty sand with non-plastic fines, similar shear wave velocities, low CPT cone penetration resistances, and groundwater tables at similar depths. The liquefaction charts based on shear wave velocity field predict liquefaction at both sites. However, a significant difference arises in their pore pressure responses during the earthquakes. The Wildlife site did not experience liquefaction, as evidenced by piezometer data, while the Treasure Island F.S. site did liquefy during the shaking. Objective: The primary objective of this study is to investigate and understand the reason for the contrasting pore pressure responses observed at the Wildlife site and the Treasure Island F.S. site despite their similar geological characteristics and predicted liquefaction potential. By conducting a detailed analysis of similarities and differences between the two case histories, the objective is to identify the factors that contributed to the higher liquefaction resistance exhibited by the Wildlife site. Methodology: To achieve this objective, the geological and seismic data available for both sites were gathered and analyzed. Then their soil profiles, seismic characteristics, and liquefaction potential as predicted by shear wave velocity-based liquefaction charts were analyzed. Furthermore, the seismic histories of both regions were examined. The number of previous earthquakes capable of generating significant excess pore pressures for each critical layer was assessed. This analysis involved estimating the total seismic activity that the Wildlife and Treasure Island F.S. critical layers experienced over time. In addition to historical data, centrifuge and large-scale experiments were conducted to explore the impact of prior seismic activity on liquefaction resistance. These findings served as supporting evidence for the investigation. Conclusions: The higher liquefaction resistance observed at the Wildlife site and other sites in the Imperial Valley can be attributed to preshaking by previous earthquakes. The Wildlife critical layer was subjected to a substantially greater number of seismic events capable of generating significant excess pore pressures over time compared to the Treasure Island F.S. layer. This crucial disparity arises from the difference in seismic activity between the two regions in the past century. In conclusion, this research sheds light on the complex interplay between geological characteristics, seismic history, and liquefaction behavior. It emphasizes the significant impact of past seismic activity on liquefaction resistance and can provide valuable insights for evaluating the stability of sandy sites in other seismic regions.

Keywords: liquefaction, case histories, centrifuge, preshaking

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Authors: H. H. Elewa, E. M. Ramadan, A. M. Nosair

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Rainfall water harvesting is considered as an important tool for overcoming water scarcity in arid and semi-arid region. Wadi Watir in the southeastern part of Sinai Peninsula is considered as one of the main and active basins in the Gulf of Aqaba drainage system. It is characterized by steep hills mainly consist of impermeable rocks, whereas the streambeds are covered by a highly permeable mixture of gravel and sand. A comprehensive approach involving the integration of geographic information systems, remote sensing and watershed modeling was followed to identify the RWH capability in this area. Eight thematic layers, viz volume of annual flood, overland flow distance, maximum flow distance, rock or soil infiltration, drainage frequency density, basin area, basin slope and basin length were used as a multi-parametric decision support system for conducting weighted spatial probability models (WSPMs) to determine the potential areas for the RWH. The WSPMs maps classified the area into five RWH potentiality classes ranging from the very low to very high. Three performed WSPMs' scenarios for W. Watir reflected identical results among their maps for the high and very high RWH potentiality classes, which are the most suitable ones for conducting surface water harvesting techniques. There is also a reasonable match with respect to the potentiality of runoff harvesting areas with a probability of moderate, low and very low among the three scenarios. WSPM results have shown that the high and very high classes, which are the most suitable for the RWH are representing approximately 40.23% of the total area of the basin. Accordingly, several locations were decided for the establishment of water harvesting dams and cisterns to improve the water conditions and living environment in the study area.

Keywords: Sinai, Wadi Watir, remote sensing, geographic information systems, watershed modeling, runoff water harvesting

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Authors: Sanjay Shukla

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Excessive use of antibiotics is a main problem in the treatment of wounds and other chronic infections and antibiotic treatment is frequently non-curative, thus alternative treatment is necessary. Phage therapy is considered one of the most effective approaches to treat multi-drug resistant bacterial pathogens. Infections caused by Staphylococcus aureus are very efficiently controlled with phage cocktails, containing a different individual phages lysate infecting a majority of known pathogenic S. aureus strains. The aim of current study was to investigate the efficiency of a purified phage cocktail for prophylactic as well as therapeutic application in mouse model and in large animals with chronic septic infection of wounds. A total of 150 sewage samples were collected from various livestock farms. These samples were subjected for the isolation of bacteriophage by double agar layer method. A total of 27 sewage samples showed plaque formation by producing lytic activity against S. aureus in double agar overlay method out of 150 sewage samples. In TEM recovered isolates of bacteriophages showed hexagonal structure with tail fiber. In the bacteriophage (ØVS) had an icosahedral symmetry with the head size 52.20 nm in diameter and long tail of 109 nm. Head and tail were held together by connector and can be classified as a member of the Myoviridae family under the order of Caudovirale. Recovered bacteriophage had shown the antibacterial activity against the S. aureus in vitro. Cocktail (ØVS1, ØVS5, ØVS9 and ØVS 27) of phage lysate were tested to know in vivo antibacterial activity as well as the safety profile. Result of mice experiment indicated that the bacteriophage lysate was very safe, did not show any appearance of abscess formation which indicates its safety in living system. The mice were also prophylactically protected against S. aureus when administered with cocktail of bacteriophage lysate just before the administration of S. aureus which indicates that they are good prophylactic agent. The S. aureus inoculated mice were completely recovered by bacteriophage administration with 100% recovery which was very good as compere to conventional therapy. In present study ten chronic cases of wound were treated with phage lysate and follow up of these cases was done regularly up to ten days (at 0, 5 and 10 d). Result indicated that the six cases out of ten showed complete recovery of wounds within 10 d. The efficacy of bacteriophage therapy was found to be 60% which was very good as compared to the conventional antibiotic therapy in chronic septic wounds infections. Thus, the application of lytic phage in single dose proved to be innovative and effective therapy for treatment of septic chronic wounds.

Keywords: phage therapy, phage lysate, antimicrobial resistance, S. aureus

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Authors: Young June Yoon

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We will present four different topics in estimating the mechanical properties of biological tissues. First we elucidate the viscoelastic behavior of collagen molecules whose diameter is a couple of nanometers. By using the molecular dynamics simulation, we observed the viscoelastic behavior in different pulling velocity. Second, the protein layer, so called ‘sheath’ in enamel microstructure reduces the stress concentration in enamel minerals. We examined the result by using the finite element methods. Third, the anisotropic elastic constants of dentin are estimated by micromechanical analysis and estimated results are close to the experimentally measured data. Last, new formulation between the fabric tensor and the wave velocity is established for calcaneus by employing the poroelasticity. This formulation can be simply used for future experiments.

Keywords: tissues, mechanics, mechanical properties, wave propagation

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Authors: Alan Ruiz-Padilla, Brando Villalobos-Villalobos, Yeniley Ruiz-Noa, Claudia Mendoza-Macías, Claudia Palafox-Sánchez, Miguel Marín-Rosales, Álvaro Cruz, Rubén Rangel-Salazar

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Introduction: In patients with rheumatoid arthritis, resistance or poor response to disease modifying antirheumatic drugs (DMARD) may be a reflection of the increase in g-P. The expression of g-P may be important in mediating the effluence of DMARD from the cell. In addition, P-glycoprotein is involved in the transport of cytokines, IL-1, IL-2 and IL-4, from normal lymphocytes activated to the surrounding extracellular matrix, thus influencing the activity of RA. The involvement of P-glycoprotein in the transmembrane transport of cytokines can serve as a modulator of the efficacy of DMARD. It was shown that a number of lymphocytes with glycoprotein P activity is increased in patients with RA; therefore, P-glycoprotein expression could be related to the activity of RA and could be a predictor of poor response to therapy. Objective: To evaluate in RA patients, if the G2677T/A MDR1 polymorphisms is associated with differences in the rate of therapeutic response to disease-modifying antirheumatic agents in patients with rheumatoid arthritis. Material and Methods: A prospective cohort study was conducted. Fifty seven patients with RA were included. They had an active disease according to DAS-28 (score >3.2). We excluded patients receiving biological agents. All the patients were followed during 6 months in order to identify the rate of therapeutic response according to the American College of Rheumatology (ACR) criteria. At the baseline peripheral blood samples were taken in order to identify the G2677T/A MDR1 polymorphisms using PCR- Specific allele. The fragment was identified by electrophoresis in polyacrylamide gels stained with ethidium bromide. For statistical analysis, the genotypic and allelic frequencies of MDR1 gene polymorphism between responders and non-responders were determined. Chi-square tests as well as, relative risks with 95% confidence intervals (95%CI) were computed to identify differences in the risk for achieving therapeutic response. Results: RA patients had a mean age of 47.33 ± 12.52 years, 87.7% were women with a mean for DAS-28 score of 6.45 ± 1.12. At the 6 months, the rate of therapeutic response was 68.7 %. The observed genotype frequencies were: for G/G 40%, T/T 32%, A/A 19%, G/T 7% and for A/A genotype 2%. Patients with G allele developed at 6 months of treatment, higher rate for therapeutic response assessed by ACR20 compared to patients with others alleles (p=0.039). Conclusions: Patients with G allele of the - G2677T/A MDR1 polymorphisms had a higher rate of therapeutic response at 6 months with DMARD. These preliminary data support the requirement for a deep evaluation of these and other genotypes as factors that may influence the therapeutic response in RA.

Keywords: pharmacogenetics, MDR1, P-glycoprotein, therapeutic response, rheumatoid arthritis

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Authors: Mrinalini Ranjan, Sudheesh Chethil

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Epilepsy is a common neurological disorder characterised by the recurrence of seizures. Electroencephalogram (EEG) signals are complex biomedical signals which exhibit nonlinear and nonstationary behavior. We use two methods 1) Detrended Fluctuation Analysis (DFA) and 2) Recurrence Plots (RP) to capture this complex behavior of EEG signals. DFA considers fluctuation from local linear trends. Scale invariance of these signals is well captured in the multifractal characterisation using detrended fluctuation analysis (DFA). Analysis of long-range correlations is vital for understanding the dynamics of EEG signals. Correlation properties in the EEG signal are quantified by the calculation of a scaling exponent. We report the existence of two scaling behaviours in the epileptic EEG signals which quantify short and long-range correlations. To illustrate this, we perform DFA on extant ictal (seizure) and interictal (seizure free) datasets of different patients in different channels. We compute the short term and long scaling exponents and report a decrease in short range scaling exponent during seizure as compared to pre-seizure and a subsequent increase during post-seizure period, while the long-term scaling exponent shows an increase during seizure activity. Our calculation of long-term scaling exponent yields a value between 0.5 and 1, thus pointing to power law behaviour of long-range temporal correlations (LRTC). We perform this analysis for multiple channels and report similar behaviour. We find an increase in the long-term scaling exponent during seizure in all channels, which we attribute to an increase in persistent LRTC during seizure. The magnitude of the scaling exponent and its distribution in different channels can help in better identification of areas in brain most affected during seizure activity. The nature of epileptic seizures varies from patient-to-patient. To illustrate this, we report an increase in long-term scaling exponent for some patients which is also complemented by the recurrence plots (RP). RP is a graph that shows the time index of recurrence of a dynamical state. We perform Recurrence Quantitative analysis (RQA) and calculate RQA parameters like diagonal length, entropy, recurrence, determinism, etc. for ictal and interictal datasets. We find that the RQA parameters increase during seizure activity, indicating a transition. We observe that RQA parameters are higher during seizure period as compared to post seizure values, whereas for some patients post seizure values exceeded those during seizure. We attribute this to varying nature of seizure in different patients indicating a different route or mechanism during the transition. Our results can help in better understanding of the characterisation of epileptic EEG signals from a nonlinear analysis.

Keywords: detrended fluctuation, epilepsy, long range correlations, recurrence plots

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Authors: Mbanzulu Kennedy, Zanga Josue, Wumba Roger

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Malaria and schistosomiasis remain life-threatening public health problems in sub-Saharan Africa. The infection pattern related to age indicates that preschool and school-age children are at the highest risk of malaria and schistosomiasis. Both parasitic infections, separately or combined, may have negative impacts on the haemoglobin concentration levels. The existing data revealed that artemisinin derivatives commonly used to cure malaria present also in antischistosomal activities. The current study investigated the impact of Artesunate-Amodiaquine (AS-AQ) on schistosomiasis when administered to treat malaria in rural area of Lemfu, DRC. A prospective longitudinal study including 171 coinfected children screened for anaemia, Schistosoma mansoni, and Plasmodium falciparum infections. The egg reduction rate and haemoglobin concentration were assessed four weeks after the treatment with AS-AQ, of all coinfected children of this series. One hundred and twenty-five (74.4%) out of 168 coinfected children treated and present during the assessment were found stool negative for S. mansoni eggs. Out of 43 (25.6%) children who remained positives, 37 (22%) showed a partial reduction of eggs amount, and no reduction was noted in 3.6% of coinfected. The mean of haemoglobin concentration and the prevalence of anaemia were, respectively, 10.74±1.5g/dl , 11.2±1.3g/dl, and 64.8%, 51.8%, respectively, before and after treatment, p<0.001. The AS-AQ commonly used against Plasmodium allowed curing S. mansoni in coinfected children and increasing the Hb level. For the future, the randomized and multicentric clinical trials are needed for a better understanding of the effectiveness of AS-AQ against Schistosoma spp. The trial registration number was 3487183.

Keywords: paludisme, schistosomiase, as-aq, enfants lemfu

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Authors: Ghadeer Jalloul, Nour Hijazi, Cassia Boyadjian, Hussein Awala, Mohammad N. Ahmad, ‎Ahmad Albadarin

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In this study, we applied Fe-sensitized TiO₂ supported over embryonic Beta zeolite (BEA) zeolite ‎for the photocatalytic degradation of Tetracycline (TC) antibiotic under visible light. Four different ‎samples having 20, 40, 60, and 100% w/w as a ratio of TiO₂/BEA were prepared. The ‎immobilization of solgel TiO₂ (33 m²/g) over BEA (390 m²/g) increased its surface area to (227 ‎m²/g) and enhanced its adsorption capacity from 8% to 19%. To expand the activity of TiO₂ ‎photocatalyst towards the visible light region (λ>380 nm), we explored two different metal ‎sensitization techniques with Iron ions (Fe³⁺). In the ion-exchange method, the substitutional cations ‎in the zeolite in TiO₂/BEA were exchanged with (Fe³⁺) in an aqueous solution of FeCl₃. In the ‎doping technique, solgel TiO₂ was doped with (Fe³⁺) from FeCl₃ precursor during its synthesis and ‎before its immobilization over BEA. (Fe-TiO₂/BEA) catalysts were characterized using SEM, XRD, ‎BET, UV-VIS DRS, and FTIR. After testing the performance of the various ion-exchanged catalysts ‎under blue and white lights, only (Fe-TiO₂/BEA 60%) showed better activity as compared to pure ‎TiO₂ under white light with 100 ppm initial catalyst concentration and 20 ppm TC concentration. As ‎compared to ion-exchanged (Fe-TiO₂/BEA), doped (Fe-TiO₂/BEA) resulted in higher photocatalytic ‎efficiencies under blue and white lights. The 3%-Fe-doped TiO₂/BEA removed 92% of TC ‎compared to 54% by TiO₂ under white light. The catalysts were also tested under real solar ‎irradiations. This improvement in the photocatalytic performance of TiO₂ was due to its higher ‎adsorption capacity due to BEA support combined with the presence of Iron ions that enhance the ‎visible light absorption and minimize the recombination effect by the charge carriers. ‎

Keywords: Tetracycline, photocatalytic degradation, immobilized TiO₂, zeolite, iron-doped TiO₂, ion-exchange

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Authors: Malki Fatima Zahra Nadia, Kellal Chaimaa, Brahimi Houria

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The following research aims to measure the impact of innovative marketing in achieving product quality in the Algerian Petroleum Company. In order to achieve the aim of the study, a random sample of 60 individuals was selected and the answers were analyzed using structural equation modeling to test the study hypotheses. The research concluded that there is a strong relationship between innovative marketing and the quality of petroleum products.

Keywords: marketing, innovation, quality, petroleum products

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Authors: Francesca Lombardi, Francesca Rosaria Augello, Benedetta Cinque, Maria Grazia Cifone, Paola Palumbo

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Glioblastoma multiforme (GBM) is a high-grade primary brain tumor refractory to current forms of treatment. The survival benefits of patients with GBM remain unsatisfactory due to the intrinsic or acquired resistance to temozolomide (TMZ), an alkylating agent, used as the first-line chemotherapeutic drug to treat GBM patients. Its cytotoxic effect is visualized by the induction of O6-methylguanine (O6MeG) within DNA. Cyclooxygenase-2 (COX-2), an inflammation-associated enzyme, has been implicated in tumorigenesis and progression of GBM, its inhibition shows anticancer activities. In the present study, it was verified if the combination of a COX-2 selective inhibitor, NS398, with TMZ could counteract the TMZ resistance. In particular, the effect of NS398 mixed with TMZ was investigated in the GBM TMZ-resistant cell line, T98G. Cells were pretreated with NS398 (100µM, 24 hours) and then exposed to TMZ alone (200µM), NS398 alone, or both for 72 hours, after which cell growth rate and cycle phases, as well as apoptosis level, were evaluated. Coadministration of NS398 and TMZ caused a significant decrease in cell growth and a progressive increase of dead cells detected by trypan blue staining. Moreover, a significant level of apoptotic cell percentage and alteration of cell cycle phases were observed in T98G treated with TMZ-NS398 combination when compared to untreated cells or TMZ-treated cells. TMZ-resistant tumors, as GBM, express elevated levels of DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). The mixture drastically reduced MGMT expression in the TMZ-resistant cell line T98G, known to express high levels of MGMT basically. Moreover, while TMZ alone did not influence the COX-2 protein expression, the combination successfully reduced it. In conclusion, these results demonstrated that NS398 enhanced the efficacy of TMZ through cell number reduction, apoptosis induction, and decreased MGMT levels, suggesting the ability of drug combination to reduce the chemoresistance. This drug combination deserves attention and could be considered as a promising therapeutic strategy for GBM patients.

Keywords: COX-2, COX-2 inhibitor, glioblastoma, NS398, T98G, temozolomide

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Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

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Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

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Authors: V. Nigam, V. Nambiar

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Aegle Marmelos leaf has been used as a remedy for various gastrointestinal infections and lowering blood sugar level in traditional system of medicine in India due to the presence of various constituents such as flavonoids, tannins and alkaloids (eg. Aegelin, Marmelosin, Luvangetin).The objective of the present study was to evaluate the total antioxidant activity, total and individual phenol content of the wild and cultivated variety of Aegle marmelos leaves to assess the role of this plant in ethanomedicine in India. The methanolic extracts of the leaves were screened for total antioxidant capacity through Ferric Reducing Antioxidant Potential (FRAP) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay; Total Phenol content (TPC) through spectrophotometric technique based on Folin Ciocalteau assay and for qualitative estimation of phenols, High performance Liquid Chromatography was used. The TPC of wild and cultivated variety was 7.6% and 6.5% respectively whereas HPLC analysis for quantification of individual polyphenol revealed the presence of gallic acid, chlorogenic acid and Ferullic acid in wild variety whereas gallic acid, Ferullic acid and pyrocatechol in cultivated variety. FRAP values and IC 50 value (DPPH) for wild and cultivated variety was 14.65 μmol/l and 11.80μmol/l; 437 μg/ml and 620μg/ml respectively and thus it can be used as potential inhibitor of free radicals. The wild variety was having more antioxidant capacity than the cultivated one it can be exploited further for its therapeutic application. As Aegle marmelos is rich in antioxidant, it can be used as food additives to delay the oxidative deterioration of foods and as nutraceutical in medicinal formulation against degenerative diseases like diabetes.

Keywords: antioxidant activity, aegle marmelos, antidiabetic, nutraceutical

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Authors: Mostafa Sefidgar, Sohrab Zendehboudi, Hossein Bazmara, Madjid Soltani

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Based on findings from clinical applications, most drug treatments fail to eliminate malignant tumors completely even though drug delivery through systemic administration may inhibit their growth. Therefore, better understanding of tumor formation is crucial in developing more effective therapeutics. For this purpose, nowadays, solid tumor modeling and simulation results are used to predict how therapeutic drugs are transported to tumor cells by blood flow through capillaries and tissues. A solid tumor is investigated as a porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multi scale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. In this work, the mathematical model in our previous studies is developed by considering two model of momentum equation for porous media: Darcy and Brinkman. The mathematical method involves processes such as fluid flow through solid tumor as porous media, extravasation of blood flow from vessels, blood flow through vessels and solute diffusion, convective transport in extracellular matrix. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model does.

Keywords: solid tumor, porous media, Darcy model, Brinkman model, drug delivery

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