Search results for: oxidative capacity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4597

Search results for: oxidative capacity

4237 Human Dental Pulp Stem Cells Attenuate Streptozotocin-Induced Parotid Gland Injury in Rats

Authors: Gehan ElAkabawy

Abstract:

Background: Diabetes mellitus causes severe deteriorations of almost all the organs and systems of the body, as well as significant damage to the oral cavity. The oral changes are mainly related to salivary glands dysfunction characterized by hyposalivation and xerostomia, which significantly reduce diabetic patients’ quality of life. Human dental pulp stem cells represent a promising source for cell-based therapies, owing to their easy, minimally invasive surgical access, and high proliferative capacity. It was reported that the trophic support mediated by dental pulp stem cells can rescue the functional and structural alterations of damaged salivary glands. However, potential differentiation and paracrine effects of human dental pulp stem cells in diabetic-induced parotid gland damage have not been previously investigated. Our study aimed to investigate the therapeutic effects of intravenous transplantation of human dental pulp stem cells (hDPSCs) on parotid gland injury in a rat model of streptozotocin (STZ)-induced type 1 diabetes. Methods: Thirty Sprague-Dawley male rats were randomly categorised into three groups: control, diabetic (STZ), and transplanted (STZ+hDPSCs). hDPSCs or vehicle was injected into the tail vein 7 days after STZ injection. The fasting blood glucose levels were monitored weekly. A glucose tolerance test was performed, and the parotid gland weight, salivary flow rate, oxidative stress indices, parotid gland histology, and caspase-3, vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) expression in parotid tissues were assessed 28 days post-transplantation. Results: Transplantation of hDPSCs downregulated blood glucose, improved the salivary flow rate, and reduced oxidative stress. The cells migrated to, survived, and differentiated into acinar, ductal, and myoepithelial cells in the STZ-injured parotid gland. Moreover, they downregulated the expression of caspase-3 and upregulated the expression of VEGF and PCNA, likely exerting pro-angiogenetic and antiapoptotic effects and promoting endogenous regeneration. In addition, the transplanted cells enhanced the parotid nitric oxide (NO) -tetrahydrobiopterin (BH4) pathway. Conclusions: Our results show that hDPSCs can migrate to and survive within the STZ-injured parotid gland, where they prevent its functional and morphological damage by restoring normal glucose levels, differentiating into parotid cell populations, and stimulating paracrine-mediated regeneration. Thus, hDPSCs may have therapeutic potential in the treatment of diabetes-induced parotid gland injury.

Keywords: dental pulp stem cells, diabetes, streptozotocin, parotid gland

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4236 The Impact of Alkaline Water Supplemented with Sodium Ascorbate on Glucose and Cortisol Levels in the Blood Serum During Acute Hyperthermic Exposure of White Laboratory Rats

Authors: Valdrina Ajeti, Icko Gjorgoski

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Stress can be a reason for some physiological and biological disorders in the body. The antioxidative defense system is necessary for the maintenance of redox homeostasis in organisms. Because of its antioxidant effect, alkaline water (AW) is the focus of scientific interest. Adding AW and co-treatment with sodium ascorbate (SA) is expected for the organism to act preventively to hyperthermic stress. To investigate the effect of AW and SA on glucose and cortisol levels during acute hyperthermic stress, white female Wistar laboratory rats, divided into three groups of 10 individuals, were exposed to heat for 80 min, for 21 days. Acute hyperthermic exposure at 41˚C was a cause for oxidative stress. The first group is the control group, the second group is treated with AW, and the third group with AW and SA. Plasma glucose levels were determined by colorimetric method and cortisol was measured using the enzyme-linked immunosorbent assay method. The comparison of the means was made using the Tukey test. Differences were considered significant at a level of p < 0.05. Our results show that levels of glucose and cortisol have been increased in the group treated with AW on the 21st day after treatment (p < 0.0001), but not on the 7th and 14th day as compared to the control group. Also, co-treatment of animals with AW and SA significantly increased the levels of glucose and cortisol on the 21st day after treatment showing a synergistic effect. The individual action of AW, as well as synergism with SA, caused a high protective effect on oxidative damage.

Keywords: alkaline water, sodium ascorbate, hyperthermic stress, glucose, cortisol

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4235 Ramification of Pemphigus Vulgaris Sera and the Monoclonal Antibody Against Desmoglein-3 on Nrf2 Expression in Keratinocyte Cultures

Authors: Faris Mohsin Alabeedi

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Pemphigus Vulgaris (PV) is a life-threatening autoimmune blistering disease characterized by the presence of autoantibodies directed against the epidermis's surface proteins. There are two forms of PV, mucocutaneous and mucosal-dominant PV. Disruption of the cell junctions is a hallmark of PV due to the autoantibodies targeting the desmosomal cadherins, desmoglein-3 (Dsg3) and desmoglein-1, leading to acantholysis in the skin and mucous membrane. Although the pathogenesis of PV is known, the detailed molecular events remain not fully understood. Our recent study has shown that both the PV sera and pathogenic anti-Dsg3 antibody AK23 can induce ROS and cause oxidative stress in cultured keratinocytes. In line with our finding, other independent studies also demonstrate oxidative stress in PV. Since Nrf2 plays a crucial role in cellular anti-oxidative stress response, we hypothesize that the expression of Nrf2 may alter in PV. Thus, treatment of cells with PV sera or AK23 may cause changes in Nrf2 expression and distribution. The purpose of this study was to examine the effect of AK23 and PV sera on Nrf2 in a normal human keratinocyte cell line, such as NTERT cells. Both a time-course and dose-dependent experiments with AK23, alongside the matched isotype control IgG, were performed in keratinocyte cultures and analysed by immunofluorescence for Nrf2 and Dsg3. Additionally, the same approach was conducted with the sera from PV patients and healthy individuals that served as a control in this study. All the fluorescent images were analysed using ImageJ software. Each experiment was repeated twice. In general, variations were observed throughout this study. In the dose-response experiments, although enhanced Dsg3 expression was consistently detected in AK23 treated cells, the expression of Nrf2 showed no consistent findings between the experiments, although changes in its expression were noticeable in cells treated with AK23. In the time-course study, a trend with induction of Nrf2 over time was shown in control cells treated with mouse isotype IgG. Treatment with AK23 showed a reduction of Nrf2 in a time-dependent manner, especially at the 24-hour time point. However, the earlier time points, such as 2 hours and 6 hours with AK23 treatments, detected somewhat variations. Finally, PV sera caused a decrease of Dsg3, but on the other hand, variations were observed in Nrf2 expression in PV sera treated cells. In general, PV sera seemed to cause a reduction of Nrf2 in the majority of PV sera treated samples. In addition, more pronounced cytoplasmic expression of Nrf2 has been observed in PV sera treated cells than those treated with AK23, suggesting that polyclonal and monoclonal IgG might induce a different effect on Nrf2 expression and distribution. Further experimental studies are crucial to obtain a more coincide global view of Nrf2-mediated gene regulation. In particular, Pemphigus Voulgaris studies assessing how the Nrf2-dependent network changes from a physiological to a pathological condition can provide insight into disease mechanisms and perhaps initiate further treatment approaches.

Keywords: pemphigus vulgaris, monoclonal antibody against desmoglein-3, Nrf2 oxidative stress, keratinocyte cultures

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4234 Effect of Temperature on the Water Retention Capacity of Liner Materials

Authors: Ahmed M. Al-Mahbashi, Mosleh A. Al-Shamrani, Muawia Dafalla

Abstract:

Mixtures of sand and clay are frequently used to serve for specific purposes in several engineering practices. In environmental engineering, liner layers and cover layers are common for controlling waste disposal facilities. These layers are exposed to moisture and temperature fluctuation specially when existing in unsaturated condition. The relationship between soil suction and water content for these materials is essential for understanding their unsaturated behavior and properties such as retention capacity and unsaturated follow (hydraulic conductivity). This study is aimed at investigating retention capacity for two sand-natural expansive clay mixtures (15% (C15) and 30% (C30) expansive clay) at two ambient temperatures within the range of 5 -50 °C. Soil water retention curves (SWRC) for these materials were determined at these two ambient temperatures using different salt solutions for a wide range of suction (up to 200MPa). The results indicate that retention capacity of C15 mixture underwent significant changes due to temperature variations. This effect tends to be less visible when the clay fraction is doubled (C30). In addition, the overall volume change is marginally affected by high temperature within the range considered in this study.

Keywords: soil water retention curve, sand-expansive clay liner, suction, temperature

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4233 Influences of Slope Inclination on the Storage Capacity and Stability of Municipal Solid Waste Landfills

Authors: Feten Chihi, Gabriella Varga

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The world's most prevalent waste management strategy is landfills. However, it grew more difficult due to a lack of acceptable waste sites. In order to develop larger landfills and extend their lifespan, the purpose of this article is to expand the capacity of the construction by varying the slope's inclination and to examine its effect on the safety factor. The capacity change with tilt is mathematically determined. Using a new probabilistic calculation method that takes into account the heterogeneity of waste layers, the safety factor for various slope angles is examined. To assess the effect of slope variation on the overall safety of landfills, over a hundred computations were performed for each angle. It has been shown that capacity increases significantly with increasing inclination. Passing from 1:3 to 2:3 slope angles and from 1:3 to 1:2 slope angles, the volume of garbage that can be deposited increases by 40 percent and 25 percent, respectively, of the initial volume. The results of the safety factor indicate that slopes of 1:3 and 1:2 are safe when the standard method (homogenous waste) is used for computation. Using the new approaches, a slope with an inclination of 2:3 can be deemed safe, despite the fact that the calculation does not account for the safety-enhancing effect of daily cover layers. Based on the study reported in this paper, the malty layered nonhomogeneous calculating technique better characterizes the safety factor. As it more closely resembles the actual state of landfills, the employed technique allows for more flexibility in design parameters. This work represents a substantial advance in limiting both safe and economical landfills.

Keywords: landfill, municipal solid waste, slope inclination, capacity, safety factor

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4232 Assessing Adaptive Capacity to Climate Change and Agricultural Productivity of Farming Households of Makueni County in Kenya

Authors: Lilian Mbinya Muasa

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Climate change is inevitable and a global challenge with long term implications to the sustainable development of many countries today. The negative impacts of climate change are creating far reaching social, economic and environmental problems threatening lives and livelihoods of millions of people in the world. Developing countries especially sub-Saharan countries are more vulnerable to climate change due to their weak ecosystem, low adaptive capacity and high dependency on rain fed agriculture. Countries in Sub-Saharan Africa are more vulnerable to climate change impacts due to their weak adaptive capacity and over-reliance on rain fed agriculture. In Kenya, 78% of the rural communities are poor farmers who heavily rely on rain fed agriculture thus are directly affected by climate change impacts.Currently, many parts of Kenya are experiencing successive droughts which are contributing to persistently unstable and declining agricultural productivity especially in semi arid eastern Kenya. As a result, thousands of rural communities repeatedly experience food insecurity which plunge them to an ever over-reliance on relief food from the government and Non-Governmental Organization In addition, they have adopted poverty coping strategies to diversify their income, for instance, deforestation to burn charcoal, sand harvesting and overgrazing which instead contribute to environmental degradation.This research was conducted in Makueni County which is classified as one of the most food insecure counties in Kenya and experiencing acute environmental degradation. The study aimed at analyzing the adaptive capacity to climate change across farming households of Makueni County in Kenya by, 1) analyzing adaptive capacity to climate change and agricultural productivity across farming households, 2) identifying factors that contribute to differences in adaptive capacity across farming households, and 3) understanding the relationship between climate change, agricultural productivity and adaptive capacity. Analytical Hierarchy Process (AHP) was applied to determine adaptive capacity and Total Factor Productivity (TFP) to determine Agricultural productivity per household. Increase in frequency of prolonged droughts and scanty rainfall. Preliminary findings indicate a magnanimous decline in agricultural production in the last 10 years in Makueni County. In addition, there is an over reliance of households on indigenous knowledge which is no longer reliable because of the unpredictability nature of climate change impacts. These findings on adaptive capacity across farming households provide the first step of developing and implementing action-oriented climate change policies in Makueni County and Kenya.

Keywords: adaptive capacity, agricultural productivity, climate change, vulnerability

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4231 Utilization of Fins to Improve the Response of Pile under Torsional Loads

Authors: Waseim Ragab Azzam Ahmed Mohamed Nasr, Aalaa Ibrahim Khater

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Torsional loads from offshore wind turbines, waves, wind, earthquakes, ship collisions in the maritime environment, and electrical transmission towers might affect the pile foundations. Torsional loads can also be caused by the axial load from the sustaining structures. The paper introduces the finned pile, an alternative method of pile modification. The effects of torsional loads were investigated through a series of experimental tests aimed at improving the torsional capacity of a single pile in the sand (where sand was utilized in a state of medium density (Dr = 50%), with or without fins. In these tests, the fins' length, width, form, and number were varied to see how these attributes affected the maximum torsional capacity of the piles. We have noticed the torsion-rotation reaction. The findings demonstrated that the fins improve the maximum torsional capacity of the piles. It was demonstrated that a length of 0.6 times the embedded pile's length and a width equivalent to the pile's diameter constitute the optimal fin geometry. For the conventional pile and the finned pile, the maximum torsional capacities were determined to be 4.12 N.m. and 7.36 N.m., respectively. When subjected to torsional loads, the fins' presence enhanced the piles' maximum torsional capacity by almost 79%.

Keywords: clean sand, finned piles, model tests, torsional load

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4230 Evaluation of Batch Splitting in the Context of Load Scattering

Authors: S. Wesebaum, S. Willeke

Abstract:

Production companies are faced with an increasingly turbulent business environment, which demands very high production volumes- and delivery date flexibility. If a decoupling by storage stages is not possible (e.g. at a contract manufacturing company) or undesirable from a logistical point of view, load scattering effects the production processes. ‘Load’ characterizes timing and quantity incidence of production orders (e.g. in work content hours) to workstations in the production, which results in specific capacity requirements. Insufficient coordination between load (demand capacity) and capacity supply results in heavy load scattering, which can be described by deviations and uncertainties in the input behavior of a capacity unit. In order to respond to fluctuating loads, companies try to implement consistent and realizable input behavior using the capacity supply available. For example, a uniform and high level of equipment capacity utilization keeps production costs down. In contrast, strong load scattering at workstations leads to performance loss or disproportionately fluctuating WIP, whereby the logistics objectives are affected negatively. Options for reducing load scattering are e.g. shifting the start and end dates of orders, batch splitting and outsourcing of operations or shifting to other workstations. This leads to an adjustment of load to capacity supply, and thus to a reduction of load scattering. If the adaptation of load to capacity cannot be satisfied completely, possibly flexible capacity must be used to ensure that the performance of a workstation does not decrease for a given load. Where the use of flexible capacities normally raises costs, an adjustment of load to capacity supply reduces load scattering and, in consequence, costs. In the literature you mostly find qualitative statements for describing load scattering. Quantitative evaluation methods that describe load mathematically are rare. In this article the authors discuss existing approaches for calculating load scattering and their various disadvantages such as lack of opportunity for normalization. These approaches are the basis for the development of our mathematical quantification approach for describing load scattering that compensates the disadvantages of the current quantification approaches. After presenting our mathematical quantification approach, the method of batch splitting will be described. Batch splitting allows the adaptation of load to capacity to reduce load scattering. After describing the method, it will be explicitly analyzed in the context of the logistic curve theory by Nyhuis using the stretch factor α1 in order to evaluate the impact of the method of batch splitting on load scattering and on logistic curves. The conclusion of this article will be to show how the methods and approaches presented can help companies in a turbulent environment to quantify the occurring work load scattering accurately and apply an efficient method for adjusting work load to capacity supply. In this way, the achievements of the logistical objectives are increased without causing additional costs.

Keywords: batch splitting, production logistics, production planning and control, quantification, load scattering

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4229 Finite Element Analysis of Reinforced Structural Walls

Authors: Mintesinot Teshome Mengsha

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Reinforced concrete structural walls are provided in structures to decrease horizontal displacements under seismic loads. The cyclic lateral load resistance capacity of a structural wall is controlled by two parameters, the strength and the ductility; it is better to have the shear strength somewhat greater than the compression to prevent shear failure, which is brittle, sudden and of serious consequence. Due to architectural and functional reasons, small openings are provided in this important structural part. The main objective of this study is to investigate the finite element of RC structural walls with small openings subjected to cyclic load using the finite element approach. The experimental results in terms of load capacity, failure mode, crack pattern, flexural strength, shear strength, and deformation capacity.

Keywords: ABAQUS, finite element method, small openings, reinforced concrete structural walls

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4228 Impact of Stress and Protein Malnutrition on the Potential Role of Epigallocatechin-3-Gallate in Providing Protection from Nephrotoxicity and Hepatotoxicity Induced by Aluminum in Rats

Authors: Azza A. Ali, Mona G. Khalil, Hemat A. Elariny, Shereen S. El Shaer

Abstract:

Background: Aluminium (Al) is very abundant metal in the earth’s crust. It is a constituent of cooking utensils, medicines, cosmetics, some foods and food additives. Salts of Al are widely used in the treatment of drinking water for purification purposes. Excessive and prolonged exposure to Al causes oxidative stress and impairment of many physiological functions. Its accumulation in liver and kidney causes hepatotoxicity and nephrotoxicity. Social isolation (SI) or Protein malnutrition (PM) also increases oxidative stress and may enhance the toxicity of Al as well as the degeneration in liver and kidney. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and has strong antioxidant as well as anti-inflammatory activities and can protect against oxidative stress-induced degenerations. Objective: To study the influence of stress or PM on Al-induced nephrotoxicity and hepatotoxicity in rats, as well as on the potential role of EGCG in providing protection. Methods: Rats received daily AlCl3 (70 mg/kg, IP) for three weeks (Al-toxicity groups) except one normal control group received saline. Al-toxicity groups were divided into four treated and four untreated groups; treated rats received EGCG (10 mg/kg, IP) together with AlCl3. One group of both treated and untreated rats served as control for each of them, and the others were subjected to either stress (mild using isolation or high using electric shock) or to PM (10% casein diet). Specimens of liver and kidney were used for assessment of levels of inflammatory mediators as TNF-α, IL6β, nuclear factor kappa B (NF-κB), oxidative stress (MDA, SOD, TAC, NO), Caspase-3 and for DNA fragmentation as well as for histopathological examinations. Biochemical changes were also measured in the serum as total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea as well as the level of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate deshydrogenase (LDH). Results: Nephrotoxicity and hepatotoxicity induced by Al were enhanced in rats exposed to stress and to PM. The influence of stress was more pronounced than PM. Al-toxicity was indicated by the increase in liver and kidney MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3, DNA fragmentation and in ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea levels, together with the decrease in total proteins, SOD, TAC. EGCG provided protection against hazards of Al as indicated by the decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation as well as in levels of ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea in liver and kidney, together with the increase in total proteins, SOD, TAC and confirmed by histopathological examinations. It provided more pronounced protection in high stressful conditions than in mild one than in PM. Conclusion: Stress have a bad impact on Al-induced nephrotoxicity and hepatotoxicity more than PM. Thus it can clarify and maximize the role of EGCG in providing protection. Consequently, administration of EGCG is advised with excessive Al-exposure to avoid nephrotoxicity and hepatotoxicity especially in populations more subjected to stress or PM.

Keywords: aluminum, stress, protein malnutrition, nephrotoxicity, hepatotoxicity, epigallocatechin-3-gallate, rats

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4227 A Comparison between Russian and Western Approach for Deep Foundation Design

Authors: Saeed Delara, Kendra MacKay

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Varying methodologies are considered for pile design for both Russian and Western approaches. Although both approaches rely on toe and side frictional resistances, different calculation methods are proposed to estimate pile capacity. The Western approach relies on compactness (internal friction angle) of soil for cohesionless soils and undrained shear strength for cohesive soils. The Russian approach relies on grain size for cohesionless soils and liquidity index for cohesive soils. Though most recommended methods in the Western approaches are relatively simple methods to predict pile settlement, the Russian approach provides a detailed method to estimate single pile and pile group settlement. Details to calculate pile axial capacity and settlement using the Russian and Western approaches are discussed and compared against field test results.

Keywords: pile capacity, pile settlement, Russian approach, western approach

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4226 Evaluation of Possible Application of Cold Energy in Liquefied Natural Gas Complexes

Authors: А. I. Dovgyalo, S. O. Nekrasova, D. V. Sarmin, A. A. Shimanov, D. A. Uglanov

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Usually liquefied natural gas (LNG) gasification is performed due to atmospheric heat. In order to produce a liquefied gas a sufficient amount of energy is to be consumed (about 1 kW∙h for 1 kg of LNG). This study offers a number of solutions, allowing using a cold energy of LNG. In this paper it is evaluated the application turbines installed behind the evaporator in LNG complex due to its work additional energy can be obtained and then converted into electricity. At the LNG consumption of G=1000kg/h the expansion work capacity of about 10 kW can be reached. Herewith-open Rankine cycle is realized, where a low capacity cryo-pump (about 500W) performs its normal function, providing the cycle pressure. Additionally discussed an application of Stirling engine within the LNG complex also gives a possibility to realize cold energy. Considering the fact, that efficiency coefficient of Stirling engine reaches 50 %, LNG consumption of G=1000 kg/h may result in getting a capacity of about 142 kW of such a thermal machine. The capacity of the pump, required to compensate pressure losses when LNG passes through the hydraulic channel, will make 500 W. Apart from the above-mentioned converters, it can be proposed to use thermoelectric generating packages (TGP), which are widely used now. At present, the modern thermoelectric generator line provides availability of electric capacity with coefficient of efficiency up to 15%. In the proposed complex, it is suggested to install the thermoelectric generator on the evaporator surface is such a way, that the cold end is contacted with the evaporator’s surface, and the hot one – with the atmosphere. At the LNG consumption of G=1000 kgг/h and specified coefficient of efficiency the capacity of the heat flow Qh will make about 32 kW. The derivable net electric power will be P=4,2 kW, and the number of packages will amount to about 104 pieces. The carried out calculations demonstrate the research perceptiveness in this field of propulsion plant development, as well as allow realizing the energy saving potential with the use of liquefied natural gas and other cryogenics technologies.

Keywords: cold energy, gasification, liquefied natural gas, electricity

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4225 Effect of Filter Paper Technique in Measuring Hydraulic Capacity of Unsaturated Expansive Soil

Authors: Kenechi Kurtis Onochie

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This paper shows the use of filter paper technique in the measurement of matric suction of unsaturated expansive soil around the Haspolat region of Lefkosa, North Cyprus in other to establish the soil water characteristics curve (SWCC) or soil water retention curve (SWRC). The dry filter paper approach which is standardized by ASTM, 2003, D 5298-03 in which the filter paper is initially dry was adopted. The whatman No. 42 filter paper was used in the matric suction measurement. The maximum dry density of the soil was obtained as 2.66kg/cm³ and the optimum moisture content as 21%. The soil was discovered to have high air entry value of 1847.46KPa indicating finer particles and 25% hydraulic capacity using filter paper technique. The filter paper technique proved to be very useful for measuring the hydraulic capacity of unsaturated expansive soil.

Keywords: SWCC, matric suction, filter paper, expansive soil

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4224 Comparative Appraisal of Polymeric Matrices Synthesis and Characterization Based on Maleic versus Itaconic Anhydride and 3,9-Divinyl-2,4,8,10-Tetraoxaspiro[5.5]-Undecane

Authors: Iordana Neamtu, Aurica P. Chiriac, Loredana E. Nita, Mihai Asandulesa, Elena Butnaru, Nita Tudorachi, Alina Diaconu

Abstract:

In the last decade, the attention of many researchers is focused on the synthesis of innovative “intelligent” copolymer structures with great potential for different uses. This considerable scientific interest is stimulated by possibility of the significant improvements in physical, mechanical, thermal and other important specific properties of these materials. Functionalization of polymer in synthesis by designing a suitable composition with the desired properties and applications is recognized as a valuable tool. In this work is presented a comparative study of the properties of the new copolymers poly(maleic anhydride maleic-co-3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5]undecane) and poly(itaconic-anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5]undecane) obtained by radical polymerization in dioxane, using 2,2′-azobis(2-methylpropionitrile) as free-radical initiator. The comonomers are able for generating special effects as for example network formation, biodegradability and biocompatibility, gel formation capacity, binding properties, amphiphilicity, good oxidative and thermal stability, good film formers, and temperature and pH sensitivity. Maleic anhydride (MA) and also the isostructural analog itaconic anhydride (ITA) as polyfunctional monomers are widely used in the synthesis of reactive macromolecules with linear, hyperbranched and self & assembled structures to prepare high performance engineering, bioengineering and nano engineering materials. The incorporation of spiroacetal groups in polymer structures improves the solubility and the adhesive properties, induce good oxidative and thermal stability, are formers of good fiber or films with good flexibility and tensile strength. Also, the spiroacetal rings induce interactions on ether oxygen such as hydrogen bonds or coordinate bonds with other functional groups determining bulkiness and stiffness. The synthesized copolymers are analyzed by DSC, oscillatory and rotational rheological measurements and dielectric spectroscopy with the aim of underlying the heating behavior, solution viscosity as a function of shear rate and temperature and to investigate the relaxation processes and the motion of functional groups present in side chain around the main chain or bonds of the side chain. Acknowledgments This work was financially supported by the grant of the Romanian National Authority for Scientific Research, CNCS-UEFISCDI, project number PN-II-132/2014 “Magnetic biomimetic supports as alternative strategy for bone tissue engineering and repair’’ (MAGBIOTISS).

Keywords: Poly(maleic anhydride-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5)undecane); Poly(itaconic anhydride-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5)undecane); DSC; oscillatory and rotational rheological analysis; dielectric spectroscopy

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4223 Reliability Based Performance Evaluation of Stone Column Improved Soft Ground

Authors: A. GuhaRay, C. V. S. P. Kiranmayi, S. Rudraraju

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The present study considers the effect of variation of different geotechnical random variables in the design of stone column-foundation systems for assessing the bearing capacity and consolidation settlement of highly compressible soil. The soil and stone column properties, spacing, diameter and arrangement of stone columns are considered as the random variables. Probability of failure (Pf) is computed for a target degree of consolidation and a target safe load by Monte Carlo Simulation (MCS). The study shows that the variation in coefficient of radial consolidation (cr) and cohesion of soil (cs) are two most important factors influencing Pf. If the coefficient of variation (COV) of cr exceeds 20%, Pf exceeds 0.001, which is unsafe following the guidelines of US Army Corps of Engineers. The bearing capacity also exceeds its safe value for COV of cs > 30%. It is also observed that as the spacing between the stone column increases, the probability of reaching a target degree of consolidation decreases. Accordingly, design guidelines, considering both consolidation and bearing capacity of improved ground, are proposed for different spacing and diameter of stone columns and geotechnical random variables.

Keywords: bearing capacity, consolidation, geotechnical random variables, probability of failure, stone columns

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4222 Comparison of Microwave-Assisted and Conventional Leaching for Extraction of Copper from Chalcopyrite Concentrate

Authors: Ayfer Kilicarslan, Kubra Onol, Sercan Basit, Muhlis Nezihi Saridede

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Chalcopyrite (CuFeS2) is the most common primary mineral used for the commercial production of copper. The low dissolution efficiency of chalcopyrite in sulfate media has prevented an efficient industrial leaching of this mineral in sulfate media. Ferric ions, bacteria, oxygen and other oxidants have been used as oxidizing agents in the leaching of chalcopyrite in sulfate and chloride media under atmospheric or pressure leaching conditions. Two leaching methods were studied to evaluate chalcopyrite (CuFeS2) dissolution in acid media. First, the conventional oxidative acid leaching method was carried out using sulfuric acid (H2SO4) and potassium dichromate (K2Cr2O7) as oxidant at atmospheric pressure. Second, microwave-assisted acid leaching was performed using the microwave accelerated reaction system (MARS) for same reaction media. Parameters affecting the copper extraction such as leaching time, leaching temperature, concentration of H2SO4 and concentration of K2Cr2O7 were investigated. The results of conventional acid leaching experiments were compared to the microwave leaching method. It was found that the copper extraction obtained under high temperature and high concentrations of oxidant with microwave leaching is higher than those obtained conventionally. 81% copper extraction was obtained by the conventional oxidative acid leaching method in 180 min, with the concentration of 0.3 mol/L K2Cr2O7 in 0.5M H2SO4 at 50 ºC, while 93.5% copper extraction was obtained in 60 min with microwave leaching method under same conditions.

Keywords: extraction, copper, microwave-assisted leaching, chalcopyrite, potassium dichromate

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4221 Circulating Oxidized LDL and Insulin Resistance among Obese School Students

Authors: Nayera E. Hassan, Sahar A. El-Masry, Mones M. Abu Shady, Rokia A. El Banna, Muhammad Al-Tohamy, Mehrevan M. Abd El-Moniem, Mona Anwar

Abstract:

Circulating oxidized LDL (ox-LDL) is associated with obesity, insulin resistance (HOMA), metabolic syndrome, and cardiovascular disease in adults. Little is known about relations in children. Aim: To assess association of ox-LDL with fat distribution and insulin resistance in a group of obese Egyptian children. Methods: Study is cross-sectional consisting of 68 obese children, with a mean age of 9.96 ± 1.32. Each underwent a complete physical examination; blood pressure (SBP, DBP) and anthropometric measurements (weight, height, BMI; waist, hip circumferences, waist/hip ratio), biochemical tests of fasting blood glucose (FBS), insulin levels; lipid profile (TC, LDL,HDL, TG) and ox-LDL; calculated HOMA. Sample was classified according to waist/hip ratio into: group I with and group II without central obesity. Results: ox-LDL showed significant positive correlation with LDL and TC in all groups of obesity. After adjustment for age and sex, significant positive correlation was detected between ox-LDL with SBP, DBP, TC, LDL, insulin, and HOMA in group II and with TC and FBS in group I. Insignificant association was detected between ox-LDL and other anthropometric parameters including BMI in any group of obese children (p > 0.05). Conclusions: ox-LDL, as a marker of oxidative stress is not correlated with BMI among all studied obese children (aged 6-12 years). Increased oxidative stress has causal effects on insulin resistance in obese children without central obesity and on fasting blood sugar in those with central obesity. These findings emphasize the importance of obesity during childhood and suggest that the metabolic complications of obesity and body fat distribution are detectable early in life.

Keywords: ox-LDL, obesity, insulin resistance, children

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4220 Effect of Visnagin on Altered Steroidogenesis and Spermatogenesis, and Testicular Injury Induced by the Heavy Metal Lead

Authors: Saleh N. Maodaa

Abstract:

Background: Lead (Pb) is an environmental pollutant causing serious health problems, including impairment of reproduction. Visnagin (VIS) is a furanochromone with promising antioxidant and anti-inflammatory effects; however, its protective efficacy against Pb toxicity has not been investigated. Objective: This study evaluated the protective effect of VIS on Pb reproductive toxicity, impaired steroidogenesis and spermatogenesis, oxidative stress and inflammation. Methods: Rats received VIS (30 or 60 mg/kg) and 50 mg/kg lead acetate for 3 weeks, and blood and testes samples were collected. Results: Pb intoxication impaired the pituitary-testicular axis (PTA), manifested by the decreased serum levels of gonadotropins and testosterone. Pb decreased sperm count, motility and viability, increased sperm abnormalities, and downregulated the steroidogenesis markers StAR, CYP17A1, 3β-HSD and 17β-HSD in the testis of rats. VIS significantly increased serum gonadotropins and testosterone, alleviated sperm parameters and upregulated steroidogenesis. In addition, VIS decreased pro-inflammatory cytokines, testicular lipid peroxidation and DNA fragmentation, downregulated Bax, and enhanced antioxidants and Bcl-2 Conclusion: These results demonstrate the protective effect of VIS against Pb reproductive toxicity in rats. VIS improved serum gonadotropins and testosterone, enhanced steroidogenesis and spermatogenesis, and attenuated oxidative injury, inflammation and apoptosis. Therefore, VIS is a promising candidate for the protection against Pb-induced reproduction impairment.

Keywords: pituitary-gonadal axis, cytokines, DNA damage, apoptosis

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4219 Effect of Electromagnetic Field on Capacitive Deionization Performance

Authors: Alibi Kilybay, Emad Alhseinat, Ibrahim Mustafa, Abdulfahim Arangadi, Pei Shui, Faisal Almarzooqi

Abstract:

In this work, the electromagnetic field has been used for improving the performance of the capacitive deionization process. The effect of electromagnetic fields on the efficiency of the capacitive deionization (CDI) process was investigated experimentally. The results showed that treating the feed stream of the CDI process using an electromagnetic field can enhance the electrosorption capacity from 20% up to 70%. The effect of the degree of time of exposure, concentration, and type of ions have been examined. The electromagnetic field enhanced the salt adsorption capacity (SAC) of the Ca²⁺ ions by 70%, while the SAC enhanced 20% to the Na⁺ ions. It is hypnotized that the electrometric field affects the hydration shell around the ions and thus reduces their effective size and enhances the mass transfer. This reduction in ion effective size and increase in mass transfer enhanced the electrosorption capacity and kinetics of the CDI process.

Keywords: capacitive deionization, desalination, electromagnetic treatment, water treatment

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4218 Analysis of Universal Mobile Telecommunications Service (UMTS) Planning Using High Altitude Platform Station (HAPS)

Authors: Yosika Dian Komala, Uke Kurniawan Usman, Yuyun Siti Rohmah

Abstract:

The enable technology fills up needs of high-speed data service is Universal Mobile Telecommunications Service (UMTS). UMTS has a data rate up to 2Mbps.UMTS terrestrial system has a coverage area about 1-2km. High Altitude Platform Station (HAPS) can be built by a macro cell that is able to serve the wider area. Design method of UMTS using HAPS is planning base on coverage and capacity. The planning method is simulated with 2.8.1 Atoll’s software. Determination of radius of the cell based on the coverage uses free space loss propagation model. While the capacity planning to determine the average cell through put is available with the Offered Bit Quantity (OBQ).

Keywords: UMTS, HAPS, coverage planning, capacity planning, signal level, Ec/Io, overlapping zone, throughput

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4217 Allium Cepa Extract Provides Neuroprotection Against Ischemia Reperfusion Induced Cognitive Dysfunction and Brain Damage in Mice

Authors: Jaspal Rana, Alkem Laboratories, Baddi, Himachal Pradesh, India Chitkara University, Punjab, India

Abstract:

Oxidative stress has been identified as an underlying cause of ischemia-reperfusion (IR) related cognitive dysfunction and brain damage. Therefore, antioxidant based therapies to treat IR injury are being investigated. Allium cepa L. (onion) is used as culinary medicine and is documented to have marked antioxidant effects. Hence, the present study was designed to evaluate the effect of A. cepa outer scale extract (ACE) against IR induced cognition and biochemical deficit in mice. ACE was prepared by maceration with 70% methanol and fractionated into ethylacetate and aqueous fractions. Bilateral common carotid artery occlusion for 10 min followed by 24 h reperfusion was used to induce cerebral IR injury. Following IR injury, ACE (100 and 200 mg/kg) was administered orally to animals for 7 days once daily. Behavioral outcomes (memory and sensorimotor functions) were evaluated using Morris water maze and neurological severity score. Cerebral infarct size, brain thiobarbituric acid reactive species, reduced glutathione, and superoxide dismutase activity was also determined. Treatment with ACE significantly ameliorated IR mediated deterioration of memory and sensorimotor functions and rise in brain oxidative stress in animals. The results of the present investigation revealed that ACE improved functional outcomes after cerebral IR injury, which may be attributed to its antioxidant properties.

Keywords: stroke, neuroprotection, ischemia reperfusion, herbal drugs

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4216 Application Research on Large Profiled Statues of Steel-Concrete Composite Shear Wall

Authors: Zhao Cai-qi, Ma Jun

Abstract:

Twin steel plates-concrete composite shear walls are composed of a pair of steel plate layers and a concrete layer sandwiched between them, which have the characteristics of both reinforced concrete shear walls and steel plate shear walls. Twin steel plates-composite shear walls contain very high ultimate bearing capacity and ductility, which have great potential to be applied in the super high-rise buildings and special structures. In this paper, we analyzed the basic characteristics and stress mechanism of the twin steel plates-composite shear walls. Specifically, we analyzed the effects of the steel plate thickness, wall thickness and concrete strength on the bearing capacity of the twin steel plates-composite shear walls. The analysis results indicate that:(1)the initial shear stiffness and ultimate shear-carrying capacity is not significantly affected by the thickness of concrete wall but by the class of concrete,(2)both factors significantly impact the shear distribution of the shear walls in ultimate shear-carrying capacity. The technique of twin steel plates-composite shear walls has been successfully applied in the construction of a 88-meter Huge Statue of Buddha located in Hunan Province, China. The analysis results and engineering experiences showed that the twin steel plates-composite shear walls have great potential for future research and applications.

Keywords: twin steel plates-concrete composite shear wall, huge statue of Buddha, shear capacity, initial lateral stiffness, overturning moment bearing

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4215 Renoprotective Effect of Alcoholic Extract of Bacopa monnieri via Inhibition of Advanced Glycation End Products and Oxidative Stress in Stz-Nicotinamide Induced Diabetic Nephropathy

Authors: Lalit Kishore, Randhir Singh

Abstract:

Diabetic nephropathy (DN) is the major cause of morbidity among diabetic patients. In this study, the effect of Bacopa monnieri Linn. (Brahmi, BM), was studied in a Streptozotocin (STZ)-induced experimental rat model of DN. Diabetic nephropathy was induced in Male Wistar rats (body weight- 300± 10 gms) by single intra-peritoneal injection of STZ (45mg/kg, i.p.) after 15 min of Nicotinamide (230 mg/kg) administration. Different doses of alcoholic extract i.e. 100, 200 and 400 mg/kg was given for 45 days by oral gavage after induction of DN. Blood glucose level, serum insulin, glycosylated haemoglobin, renal parameters (serum urea, uric acid, creatinine and BUN) and lipid profile (total cholesterol, triglycerides, HDL, LDL and VLDL levels) were measured. Concentration of thiobarbituric acid reactive species (TBARS) and levels of antioxidant enzymes of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were evaluated in the kidney, liver and pancreas. At the end of treatment period the alcoholic extract of BM reduced the elevated level of blood glucose, serum insulin, renal parameters, lipid levels, TBARS, AGE’s in kidney and significantly increased body weight, HDL and antioxidant enzymes in dose dependent manner as compared to diabetic control animals. These results suggested the BM possesses significant renoprotective activity.

Keywords: AGE's, lipid profile, oxidative stress, renal parameters

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4214 An Antidiabetic Dietary Defence Weapon: Oats and Milk Based Probiotic Fermented Product

Authors: Rameshwar Singh Seema

Abstract:

In today’s world where diabetes has become an epidemic, our aim was to potentiate the effect of probiotics by integrating probiotics with cereals to formulate composite foods using Lactobacillus rhamnosus GG (LGG) and Lactobacillus casei NCDC19 against type 2 diabetes. After optimizing the product by Response Surface Methodology, it was studied for their effect on induction and progression of type 2 diabetes in HFD-fed Wistar rats. After 9 weeks study, best results were shown by the group fed with oat and milk based product fermented with LGG and L. casei NCDC19 which resulted in a significant decrease in blood glucose, HBA1c, improved OGTT, oxidative stress, cholesterol and triglycerides level during progression study of type 2 diabetes. During induction study also, there was significant reduction in blood glucose level, oxidative stress, cholesterol level and triglycerides level but slightly less as compared to progression study. Real time PCR gene expression studies were done for 5 genes (GLUT-4, IRS-2, ppar-γ, TNF-α, IL-6) whose expression is directly related to type 2 diabetes. The relative fold change expression was increased in case of GLUT-4, IRS-2, ppar-γ and decreased in case of TNF-α and IL-6 during both induction and progression study of diabetes but more significantly during progression study. Hence it was concluded that oat and milk based probiotic fermented product showed the synergistic effect of probiotics and oats especially in case of progression of type 2 diabetes. The benefits of these probiotic formulations may be further validated by clinical trials.

Keywords: type 2 diabetes, LGG, L.casei NCDC19, food science

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4213 Ameliorative Effect of Martynia annua Linn. on Collagen-Induced Arthritis via Modulating Cytokines and Oxidative Stress in Mice

Authors: Alok Pal Jain, Santram Lodhi

Abstract:

Martynia annua Linn. (Martyniaccae) is traditionally used in inflammation and applied locally to tuberculosis glands of camel’s neck. The leaves used topically to bites of venomous insects and wounds of domestic animals. Chemical examination of Martynia annua leaves revealed the presence of glycosides, tannins, proteins, phenols and flavonoids. The present study was aimed to evaluate the anti-arthritic activity of methanolic extract of Martynia annua leaves. Methanolic extract of Martynia annua leaves was tested by using in vivo collagen-induced arthritis mouse model to investigate the anti-rheumatoid arthritis activity. In addition, antioxidant effect of methanolic extract was determined by the estimation of antioxidants level in joint tissues. The severity of arthritis was assessed by arthritis score and edema. Levels of cytokines TNF-α and IL-6, in the joint tissue homogenate were measured using ELISA. A high dose (250 mg/kg) of methanolic extract was significantly reduced the degree of inflammation in mice as compared with reference drug. Antioxidants level and malondialdehyde (MDA) in joint tissue homogenate found significantly (p < 0.05) higher. Methanolic extract at dose of 250 mg/kg modulated the cytokines production and suppressed the oxidative stress in the mice with collagen-induced arthritis. This study suggested that Martynia annua might be alternative herbal medicine for the management of rheumatoid arthritis.

Keywords: Martynia annua, collagen, rheumatoid arthritis, antioxidants

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4212 Study on the Effect Cabbage (Brassica oleracea) and Ginger (Zingiber officinale) Extracts on Rat Liver Injuries Induced by Carbon tetrachloride (CCl4)

Authors: Asmaa F. Hamouda, Randa M Shrourou

Abstract:

Cabbage (Brassica oleracea) and Ginger (Zingiber officinale) constitute apportion of regular human diet. The effect of Cabbage(CE) and Ginger extracts(GE) separately on liver nitric oxide (NO), malondialdehyde (MDA), as well as serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, total cholesterol(TC), triglyceride(T.G), high density lipoprotein(HDL cholesterol), low density lipoprotein (LDL cholesterol), thyroid-stimulating hormone (TSH), Triiodothyronine (T3), Thyroxine (T4) in rats treated and untreated with carbon tetrachloride (CCl4) was studied. The levels of NO, MDA, as well as serum AST, ALT, total bilirubin, TC, T.G, LDLand TSH showed an elevation and decline in HDL, T3, and T4 in rats treated with CCl4 as compared to control. Treatment of rats with GE pre, during, and post CCl4 administration improved NO, MDA, as well as serum AST, ALT, total bilirubin, TC, T.G, HDL, LDL, TSH, T3, T4 as compared to CCl4, indicates that GE improve thyroid function and reduced oxidative stress as well as injuries induced by CCl4. Treatment of rats with CE pre, during, and post CCl4 administration did not improved in the thyroid hormones and lipid profile levels as compared to CCl4. These findings suggest that ginger treatment exerts a protective effect on metabolic disorders by decreasing oxidative stress.

Keywords: liver injuries, carbon tetrachloride (CCl4), cabbage (Brassica oleracea), ginger (Zingiber officinale), thyroid function

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4211 Effect of CSL Tube Type on the Drilled Shaft Axial Load Carrying Capacity

Authors: Ali Motevalli, Shahin Nayyeri Amiri

Abstract:

Cross-Hole Sonic Logging (CSL) is a common type of Non-Destructive Testing (NDT) method, which is currently used to check the integrity of placed drilled shafts. CSL evaluates the integrity of the concrete inside the cage and between the access tubes based on propagation of ultrasonic waves between two or more access tubes. A number of access tubes are installed inside the reinforcing cage prior to concrete placement as guides for sensors. The access tubes can be PVC or steel galvanized based on ASTM6760. The type of the CSL tubes can affect the axial strength of the drilled shaft. The objective of this study is to compare the amount of axial load capacity of drilled shafts due to using a different type of CSL tubes inside the caging. To achieve this, three (3) large-scale drilled shaft samples were built and tested using a hydraulic actuator at the Florida International University’s (FIU) Titan America Structures and Construction Testing (TASCT) laboratory. During the static load test, load-displacement curves were recorded by the data acquisition system (MegaDAC). Three drilled shaft samples were built to evaluate the effect of the type of the CSL tube on the axial load capacity in drilled shaft foundations.

Keywords: drilled shaft foundations, axial load capacity, cage, PVC, galvanized tube, CSL tube

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4210 Evaluating the Durability and Safety of Lithium-Ion Batterie in High-Temperature Desert Climates

Authors: Kenza Maher, Yahya Zakaria, Noora S. Al-Jaidah

Abstract:

Temperature is a critical parameter for lithium-ion battery performance, life, and safety. In this study, four commercially available 18650 lithium-ion cells from four different manufacturers are subjected to accelerated cycle aging for up to 500 cycles at two different temperatures (25°C and 45°C). The cells are also calendar-aged at the same temperatures in both charged and discharged states for 6 months to investigate the effect of aging and temperature on capacity fade and state of health. The results showed that all battery cells demonstrated good cyclability and had a good state of health at both temperatures. However, the capacity loss and state of health of these cells are found to be dependent on the cell chemistry and aging conditions, including temperature. Specifically, the capacity loss is found to be higher at the higher aging temperature, indicating the significant impact of temperature on the aging of lithium-ion batteries.

Keywords: lithium-ion battery, aging mechanisms, cycle aging, calendar aging.

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4209 Protective Role of Autophagy Challenging the Stresses of Type 2 Diabetes and Dyslipidemia

Authors: Tanima Chatterjee, Maitree Bhattacharyya

Abstract:

The global challenge of type 2 diabetes mellitus is a major health concern in this millennium, and researchers are continuously exploring new targets to develop a novel therapeutic strategy. Type 2 diabetes mellitus (T2DM) is often coupled with dyslipidemia increasing the risks for cardiovascular (CVD) complications. Enhanced oxidative and nitrosative stresses appear to be the major risk factors underlying insulin resistance, dyslipidemia, β-cell dysfunction, and T2DM pathogenesis. Autophagy emerges to be a promising defense mechanism against stress-mediated cell damage regulating tissue homeostasis, cellular quality control, and energy production, promoting cell survival. In this study, we have attempted to explore the pivotal role of autophagy in T2DM subjects with or without dyslipidemia in peripheral blood mononuclear cells and insulin-resistant HepG2 cells utilizing flow cytometric platform, confocal microscopy, and molecular biology techniques like western blotting, immunofluorescence, and real-time polymerase chain reaction. In the case of T2DM with dyslipidemia higher population of autophagy, positive cells were detected compared to patients with the only T2DM, which might have resulted due to higher stress. Autophagy was observed to be triggered both by oxidative and nitrosative stress revealing a novel finding of our research. LC3 puncta was observed in peripheral blood mononuclear cells and periphery of HepG2 cells in the case of the diabetic and diabetic-dyslipidemic conditions. Increased expression of ATG5, LC3B, and Beclin supports the autophagic pathway in both PBMC and insulin-resistant Hep G2 cells. Upon blocking autophagy by 3-methyl adenine (3MA), the apoptotic cell population increased significantly, as observed by caspase‐3 cleavage and reduced expression of Bcl2. Autophagy has also been evidenced to control oxidative stress-mediated up-regulation of inflammatory markers like IL-6 and TNF-α. To conclude, this study elucidates autophagy to play a protective role in the case of diabetes mellitus with dyslipidemia. In the present scenario, this study demands to have a significant impact on developing a new therapeutic strategy for diabetic dyslipidemic subjects by enhancing autophagic activity.

Keywords: autophagy, apoptosis, dyslipidemia, reactive oxygen species, reactive nitrogen species, Type 2 diabetes

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4208 Dimethyl fumarate Alleviates Valproic Acid-Induced Autism in Wistar Rats via Activating NRF-2 and Inhibiting NF-κB Pathways

Authors: Sandy Elsayed, Aya Mohamed, Noha Nassar

Abstract:

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behavior. Multiple studies suggest that oxidative stress and neuroinflammation are key factors in the etiology of ASD and often associated with worsening of ASD-related behaviors. Nuclear factor erythroid 2-related factor 2 (NRF-2) is a transcription factor that promotes expression of antioxidant response element genes in oxidative stress. In ASD subjects, decreased expression of NRF-2 in frontal cortex shifted the redox homeostasis towards oxidative stress, and resulted in inflammation evidenced by elevation of nuclear factor kappa B (NF-κB) transcriptional activity. Dimethyl fumarate (DMF) is a NRF-2 activator that is used in the treatment of psoriasis and multiple sclerosis. It participates in the transcriptional control of inflammatory factors via inhibition of NF-κB and its downstream targets. This study aimed to investigate the role of DMF in alleviating the cognitive impairments and behavior deficits associated with ASD through mitigation of oxidative stress and inflammation in prenatal valproic acid (VPA) rat model of autism. Methods: Pregnant female Wistar rats received a single intraperitoneal injection of VPA (600 mg/kg) to induce autistic-like-behavioral and neurobiological alterations in their offspring. Chronic oral gavage of DMF (150mg/kg/day) started from postnatal day (PND) 24 till PND62 (39 days). Prenatal VPA exposure elicited autistic behaviors including decreased social interaction and stereotyped behavior. Social interaction was evaluated using three-chamber sociability test and calculation of sociability index (SI), while stereotyped repetitive behavior and anxiety associated with ASD were assessed using marble burying test (MBT). Biochemical analyses were done on prefrontal cortex homogenates including NRF-2, and NF-κB expression. Moreover, inducible nitric oxide synthase (iNOS) gene expression and tumor necrosis factor (TNF-) protein expression were evaluated as markers of inflammation. Results: Prenatal VPA elicited decreased social interaction shown by decreased SI compared to control group (p < 0.001) and DMF enhanced SI (p < 0.05). In MBT, prenatal injection of VPA manifested stereotyped behavior and enhanced number of buried marbles compared to control (p < 0.05) and DMF reduced the anxiety-related behavior in rats exhibiting ASD-like behaviors (p < 0.05). In prefrontal cortex, NRF-2 expression was downregulated in prenatal VPA model (p < 0.0001) and DMF reversed this effect (p < 0.0001). The inflammatory transcription factor NF-κB was elevated in prenatal VPA model (p < 0.0001) and reduced (p < 0.0001) upon NRF-2 activation by DMF. Prenatal VPA expressed higher levels of proinflammatory cytokine TNF- compared to control group (p < 0.0001) and DMF reduced it (p < 0.0001). Finally, the gene expression of iNOS was downregulated upon NRF-2 activation by DMF (p < 0.01). Conclusion: This study proposes that DMF is a potential agent that can be used to ameliorate autistic-like-changes through NRF-2 activation along with NF-κB downregulation and therefore, it is a promising novel therapy for ASD.

Keywords: autism spectrum disorders, dimethyl fumarate, neuroinflammation, NRF-2

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