Search results for: resistivity induced polarization

Authors: A. V. Shrirao, N. I. Kochar, A. V. Chandewar

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The flower extract of Butea monosperma herb has been used traditionally in India for medicinal purposes. The plant has been reported to treat hyperglycemia and associated hyperlipidemia. Hyperlipidemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. The present work was undertaken to investigate the possible antihyperlipidemic and antioxidative effect of Butea monosperma flowers on hyperlipidemic rats. Hyperlipidemia was induced in rats by a single intraperitonial (i.p.) injection of Triton WR 1339 (400 mg/kg) and it showed sustained elevated levels of serum cholesterol and triglyceride. Ethanolic extract of Butea monosperma flowers (Et-BM) (250 and 500 mg/kg/day) was administered to normal and hyperlipidemic rats for 14 days. Serum and liver tissue were analyzed at three different time intervals for lipid profile and antioxidants enzymes and the activity were compared to the cholesterol-lowering drug, Atorvastatin (10 mg/kg). Parameters were altered during hyperlipidemia and reverted back to near normal values after Et-BM treatment or standard drug Atorvastatin. Lipid peroxidation decreased whereas the activities of superoxide dismutase, glutathione peroxidase and catalase increased in Et-BM treated rats. Pronounced changes were observed at 500 mg/kg of Et-BM for 2 weeks and it was comparable to the standard drug Atorvastatin. The current study provides strong evidence that Et-BM has a remarkable beneficial effect in treating hyperlipidemia and ROS without any side effects at the dosage and duration studied.

Keywords: antioxidant, butea monopserma, hyperlipidemia, triton WR 1339

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Authors: The Nan Chang, Ping-Tang Yu, Jyun-Ming Lin

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A triple band circularly polarized antenna covering 1.17, 1.22, and 1.57 GHz is presented. To extend to the triple-band operation, we need to add one more ring while maintaining the mechanism to independently control each ring. The inset-part in the feeding scheme is used to excite the band at 1.22 GHz, while the proximate-part of the feeding scheme is used to excite not only the band at 1.57 GHz but also the band at 1.17 GHz. This is achieved by up-vertically coupled with one ring to radiate at 1.57 GHz and down-vertically coupled another ring to radiate at 1.17 GHz. It is also noted that the inset-part in our feeding scheme is by horizontal coupling. Furthermore, to increase the gain at all three bands, three air-layers are added to make the total height of the antenna be 7.8 mm. The total thickness of the three air-layers is 3 mm. The gains of the three bands are all greater than 5 dBiC after adding the air-layers.

Keywords: circular polarization, global position system, high gain, triband antenna

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Authors: Shwu-Ling Peng, Chiung-Man Tsai, Chia-Jui Weng

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Chronic micro-inflammation is a hallmark of many aging-related neurodegenerative and metabolic syndrome-driven diseases. In high glucose (HG) environment, reactive oxygen species (ROS) is generated and the ROS induced inflammation, cytokines secretion, DNA damage, and cell cycle arrest to lead to cellular senescence. Water chestnut shell (WCS) is a plant hull which containing polyphenolic compounds and showed antioxidant and anticancer activities. Orchid, which containing a natural polysaccharide compound, possesses many physiological activities including anti-inflammatory and neuroprotective effects. These agricultural plants might be able to reduce oxidative stress and inflammation. This study was used HG-induced human normal dermal fibroblasts (HG-HNDFs) as an in vitro model to disclose the effects of water extract of Phalaenopsis orchid flower (WEPF) and ethanol extract of water chestnut shell (EEWCS) on the anti-aging and their underlying molecular mechanisms. The toxicity of extracts on human normal dermal fibroblasts (HNDFs) was determined by MTT method. The senescence of cells was assayed by β-galactosidase (SA-β-gal) kit. ROS and nitrate production was analyzed by Intracellular ROS contents and ELISA, respectively. Western blotting was used to detect the proteins in cells. The results showed that the exposure of HNDFs to HG (30 mM) for 72 h were caused cellular senescence and arrested cells at G0/G1 phase. Indeed, the treatment of HG-HNDFs with WEPF (200 μg/ml) and EEWCS (10 μg/ml) significantly released cell cycle arrest and promoted cell proliferation. The G1/S phase transition regulatory proteins such as protein retinoblastoma (pRb), p53, and p16ᴵᴺᴷ⁴ᵃ depressed by WEPF and EEWCS were also observed. Additionally, the treatment of WEPF and EEWCS increased the activity of HO-1 through upregulating Nrf2 as well as decreased the ROS and NO of HG-HNDFs. Therefore, the senescence marker protein-30 (SMP30) in cells was diminished. In conclusion, the WEPF and EEWCS might inhibit HG-induced aging of HNDFs by reducing oxidative stress and free radicals.

Keywords: agricultural plant extract, anti-aging, high glucose, Phalaenopsis orchid flower, water chestnut shell

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Authors: S. Nigri, R. Oumeddour, F. Djazi

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The inhibition of the corrosion of copper in 1 M HNO3 solution by oleic acid was investigated by weight loss measurement, potentiodynamic polarization and scanning electron microscope (SEM) studies. The experimental results have showed that this compound revealed a good corrosion inhibition and the inhibition efficiency is increased with the inhibitor concentration to reach 98%. The results obtained revealed that the adsorption of the inhibitor molecule onto metal surface is found to obey Langmuir adsorption isotherm. The temperature effect on the corrosion behavior of copper in 1 M HNO3 without and with inhibitor at different concentration was studied in the temperature range from 303 to 333 K and the kinetic parameters activation such as Ea, ∆Ha and ∆Sa were evaluated. Tafel plot analysis revealed that oleic acid acts as a mixed type inhibitor. SEM analysis substantiated the formation of protective layer over the copper surface.

Keywords: oleic acid, weight loss, electrochemical measurement, SEM analysis

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Authors: Aman Upaganlawar, Chandrasekhar Upasani

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The present study was designed to screen the neuroprotective and antioxidant activity of corosolic acid in painful diabetic neuropathy (DN). Diabetes was induced in rats by single dose of STZ (60mg/kg, i.p). Diabetic rats were tested every week for the development of pain, at 5th week rats showed sensation of pain. At 6th week the rats developed significant neuropathic pain. They were divided into different groups and treated with Corosolic acid (2 and 4 mg/kg, p.o) for further two weeks. Pain was assessed in the diabetic rats by mechano-tactil allodynia, mechanical hyperalgesia and cold allodynia. At the end of treatment period rats were scarified and biochemical changes such as plasma glucose level, endogenous antioxidants (Lipid peroxidation, reduced glutathione, superoxide dismutase and catalase) in sciatic nerve were evaluated. Further Na+/K+ ATPase and nitric oxide content was also evaluated. Treatment with corosolic acid for two weeks restored the altered body weight and elevated blood sugar level. Further corosolic acid showed dose dependent reduction in pain in neuropathic animals. The level of endogenous antioxidants enzymes, Na+/K+ ATPase and nitric oxide were significantly prevented. In conclusion, the result of the present study suggests the antidiabetic, antioxidant and neuroprotectieve property of corosolic acid in diabetic rats with neuropathic pain.

Keywords: neuropathic pain, diabetes, corosolic acid, antioxidant

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Authors: Gehan ElAkabawy

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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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Authors: Mohammad Khan, Arnaud Castel

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Concrete viscoelastic properties such as shrinkage, creep, and associated relaxation are important in assessing the risk of cracking during the first few days after placement. This paper investigates the early-age mechanical and viscoelastic properties, restrained shrinkage-induced cracking and time to cracking of concrete incorporating ferronickel slag (FNS) as supplementary cementitious material. Compressive strength, indirect tensile strength and elastic modulus were measured. Tensile creep and drying shrinkage was measured on dog-bone shaped specimens. Restrained shrinkage induced stresses and concrete cracking age were assessed by using the ring test. Results revealed that early-age strength development of FNS blended concrete is lower than that of the corresponding ordinary Portland cement (OPC) concrete. FNS blended concrete showed significantly higher tensile creep. The risk of early-age cracking for the restrained specimens depends on the development of concrete tensile stress considering both restrained shrinkage and tensile creep and the development of the tensile strength. FNS blended concrete showed only 20% reduction in time to cracking compared to reference OPC concrete, and this reduction is significantly lower compared to fly ash and ground granulated blast furnace slag blended concretes at similar replacement level.

Keywords: ferronickel slag, restraint shrinkage, tensile creep, time to cracking

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Authors: Venencia Albert, Arulselvi Subramanian, Hara Prasad Pati, Asok K. Mukhophadhyay

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Acute traumatic coagulopathy in an endogenous dysregulation of the intrinsic coagulation system in response to the injury, associated with three-fold risk of poor outcome, and is more amenable to corrective interventions, subsequent to early identification and management. Multiple definitions for stratification of the patients' risk for early acute coagulopathy have been proposed, with considerable variations in the defining criteria, including several trauma-scoring systems based on prehospital data. We aimed to develop a clinically relevant definition for acute coagulopathy of trauma based on conventional coagulation assays and to assess its efficacy in comparison to recently established prehospital prediction models. Methodology: Retrospective data of all trauma patients (n = 490) presented to our level I trauma center, in 2014, was extracted. Receiver operating characteristic curve analysis was done to establish cut-offs for conventional coagulation assays for identification of patients with acute traumatic coagulopathy was done. Prospectively data of (n = 100) adult trauma patients was collected and cohort was stratified by the established definition and classified as "coagulopathic" or "non-coagulopathic" and correlated with the Prediction of acute coagulopathy of trauma score and Trauma-Induced Coagulopathy Clinical Score for identifying trauma coagulopathy and subsequent risk for mortality. Results: Data of 490 trauma patients (average age 31.85±9.04; 86.7% males) was extracted. 53.3% had head injury, 26.6% had fractures, 7.5% had chest and abdominal injury. Acute traumatic coagulopathy was defined as international normalized ratio ≥ 1.19; prothrombin time ≥ 15.5 s; activated partial thromboplastin time ≥ 29 s. Of the 100 adult trauma patients (average age 36.5±14.2; 94% males), 63% had early coagulopathy based on our conventional coagulation assay definition. Overall prediction of acute coagulopathy of trauma score was 118.7±58.5 and trauma-induced coagulopathy clinical score was 3(0-8). Both the scores were higher in coagulopathic than non-coagulopathic patients (prediction of acute coagulopathy of trauma score 123.2±8.3 vs. 110.9±6.8, p-value = 0.31; trauma-induced coagulopathy clinical score 4(3-8) vs. 3(0-8), p-value = 0.89), but not statistically significant. Overall mortality was 41%. Mortality rate was significantly higher in coagulopathic than non-coagulopathic patients (75.5% vs. 54.2%, p-value = 0.04). High prediction of acute coagulopathy of trauma score also significantly associated with mortality (134.2±9.95 vs. 107.8±6.82, p-value = 0.02), whereas trauma-induced coagulopathy clinical score did not vary be survivors and non-survivors. Conclusion: Early coagulopathy was seen in 63% of trauma patients, which was significantly associated with mortality. Acute traumatic coagulopathy defined by conventional coagulation assays (international normalized ratio ≥ 1.19; prothrombin time ≥ 15.5 s; activated partial thromboplastin time ≥ 29 s) demonstrated good ability to identify coagulopathy and subsequent mortality, in comparison to the prehospital parameter-based scoring systems. Prediction of acute coagulopathy of trauma score may be more suited for predicting mortality rather than early coagulopathy. In emergency trauma situations, where immediate corrective measures need to be taken, complex multivariable scoring algorithms may cause delay, whereas coagulation parameters and conventional coagulation tests will give highly specific results.

Keywords: trauma, coagulopathy, prediction, model

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Authors: Khodzhaberdi Allaberdiev

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Substituted phenols are widely used for the synthesis of advanced polycondensation polymers. In terms of the structure regularity and practical value of obtained polymers are of special interest the p-substituted phenols. The lanthanide induced shifts (LIS) of the aromatic ring and the OH protons by addition Eu(fod)3 to various p-substituted phenols in CDCL3 solvent were measured Nuclear Magnetic Resonance spectroscopy. A linear relationship has been observed between the LIS of protons (∆=δcomplex –δsubstrate) and Eu(fod)3/substrate molar ratios. The LIS protons of the investigated phenols decreases in the following order: ОН > ortho > meta. The LIS of these protons also depends on both steric and electronic effects of p-substituents. The effect on the LIS of protons steric hindrance of substituents by way of example p-substituted alkyl phenols was studied. Alkyl phenols exhibit pronounced europium- induced shifts, their sensitivity increasing in the order: CH3 > C2H5 > sym-C5H11 > tert-C5H11 > tert-C4H9, i.e. in parallel with decreasing steric hindrance. The influence steric hindrance p-substituents of phenols on the LIS of protons in sequence following decreases: OH> meta >ortho. Contrary to the expectations, it is found that the LIS of the ortho protons an excellent linear correlation with meta-substituent constants, σm for 14 p-substituted phenols: ∆H2, 6=8.165-9.896 σm (r2=0,999). Moreover, a linear correlation between the LIS of the ortho protons and ionization constants, РКa of p-substituted phenols has been revealed. Similarly, the linear relationships for the LIS of the meta and the OH protons were obtained. Use the LIS of the phenolic hydroxyl groups for linear relationships is necessary with care, because of the signal broadening of the OH protons. New constants may be determinate with unusual case by this approach.

Keywords: novel correlations, NMR spectroscopy, phenols, shift reagent

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Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

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Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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Authors: Ezgi Yurdakul, Klaus-Alexander Rieder, Richard Sibbick

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Most of the shotcrete projects require compliance with meeting a specified early-age strength target (e.g., reaching 1 MPa in 1 hour) that is selected based on the underground conditions. To meet the desired early-age performance characteristics, accelerators are commonly used as they increase early-age strength development rate and accelerate the setting thereby reducing sagging and rebound. The selection of accelerator type and its dosage is made by the setting time and strength required for the shotcrete application. While alkaline and alkali-free accelerators are the two main types used in wet-mix shotcrete; alkali-free admixtures increasingly substitute the alkaline accelerators to improve the performance and working safety. This paper aims to evaluate the impact of alkali-free accelerators in wet-mix on various tests including set time, early and later-age compressive strength, boiled absorption, and electrical resistivity. Furthermore, the comparison between accelerated and non-accelerated samples will be made to demonstrate the interaction between cement and accelerators. Scanning electron microscopy (SEM), fluorescent resin impregnated thin section and cut and polished surface images will be used to understand the microstructure characterization of mixes in the presence of accelerators.

Keywords: accelerators, chemical admixtures, shotcrete, sprayed concrete

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Authors: Jing Hu, Xiaoping Ouyang

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We develop an optical readout gas chamber based on avalanche-induced scintillation for energetic charged particles track. The gas chamber is equipped with a Single Anode Wires (SAW) structure to produce intensive electric field when the measured particles are of low yield or even single. In the presence of an intensive electric field around the single anode, primary electrons, resulting from the incident charged particles when depositing the energy along the track, accelerate to the anode effectively and rapidly. For scintillation gasses, this avalanche of electrons induces multiplying photons comparing with the primary scintillation excited directly from particle energy loss. The electric field distribution for different shape of the SAW structure is analyzed, and finally, an optimal one is used to study the optical readout performance. Using CF4 gas and its mixture with the noble gas, the results indicate that the optical readout characteristics of the chamber are attractive for imaging. Moreover, images of particles track including single particle track from 5.485MeV alpha particles are successfully acquired. The track resolution is quite well for the reason that the electrons undergo less diffusion in the intensive electric field. With the simple and ingenious design, the optical readout gas chamber has a high sensitivity. Since neutrons can be converted to charged particles when scattering, this optical readout gas chamber can be applied to neutron measurement for dark matter, fusion research, and others.

Keywords: optical readout, gas chamber, charged particle track, avalanche-induced scintillation, neutron measurement

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Authors: Chao Hsing Yeh, Wei Chun Lin

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Background: Current management of aromatase inhibitor-induced arthralgia (AIA) in postmenopausal breast cancer survivors (PBCS) has limited effect. Method: In this prospective randomized clinical trial (RCT), a 4-week APA treatment was used to manage AIA. Twenty PBCS participated. After baseline data was collected, participants were waited for a month before they receive APA at a convenient time once a week for 4 weeks. Blood samples from participants in both groups were collected at baseline and after 4 weeks of treatment. The primary outcomes included: pain intensity, pain interference, stiffness, and physical function. Results: After the 4-week APA treatment, the pro-inflammatory cytokines and chemokines display a trend of mean percentage reduction (i.e., -22% in IL-1α, -4% in IL-1β, -1% in IL-2, -3% in IL-6, -19% in IL-12, -9% in Eotaxin, and -2% in MCP-1). The anti-inflammatory cytokine IL-10 and IL-13 (i.e., 5% in IL-10 and 29% in IL-13) increased from pre- to post-APA treatment. Significant positive correlation of percentage mean change was observed between symptom severity and eotaxin (ρ = 0.56; p < 0.01) & MCP-1 (ρ = 0.65; p < 0.01). Interference and chemokines (eotaxin & MIP-1) also shows positive correlation (ρ = 0.48; p < 0.01 & ρ = 0.39; p < 0.05). Another positive correlation was found between worst pain and chemokines (eotaxin, ρ = 0.48; p < 0.01 & MIP-1, ρ = 0.39; p < 0.05). Additionally, interference also shows positive correlation among IL-1α (ρ = 0.36; p < 0.05) and IL-β (ρ = 0.33; p < 0.05). Conclusion: These findings suggest that APA intervention may inhibit inflammation of AIA patients and chemokine could be one of the key factors of AIA symptom improvement.

Keywords: acupressure, cytokine, pain management, breast cancer survivors

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Authors: T. N. M. El Sebai, A. A. Khattab, Wafaa M. Abd-El Rahim, H. Moawad

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Fungal mutant strains have produced cellulase and xylanase enzymes, and have induced high hydrolysis with enhanced of rice straw. The mutants were obtained by exposing Penicillium strain to UV-light treatments. Screening and selection after treatment with UV-light were carried out using cellulolytic and xylanolytic clear zones method to select the hypercellulolytic and hyperxylanolytic mutants. These mutants were evaluated for their cellulase and xylanase enzyme production as well as their abilities for biodegradation of rice straw. The mutant 12 UV/1 produced 306.21% and 209.91% cellulase and xylanase, respectively, as compared with the original wild type strain. This mutant showed high capacity of rice straw degradation. The effectiveness of tested mutant strain and that of wild strain was compared in relation to enhancing the composting process of rice straw and animal manures mixture. The results obtained showed that the compost product of inoculated mixture with mutant strain (12 UV/1) was the best compared to the wild strain and un-inoculated mixture. Analysis of the composted materials showed that the characteristics of the produced compost were close to those of the high quality standard compost. The results obtained in the present work suggest that the combination between rice straw and animal manure could be used for enhancing the composting process of rice straw and particularly when applied with fungal decomposer accelerating the composting process.

Keywords: rice straw, composting, UV mutants, Penicillium

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Authors: Shazia Naheed Akhter, Rekha Kumari

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An estimated 70 million population are exposed to arsenic poisoning in India in recent times. Arsenic contamination in the groundwater has caused serious health hazards among the exposed population. In Bihar, the first district was Bhojpur, where arsenic causing health issues were reported in 2002. Presently, there are 18 districts that are reported arsenic poisoning in the groundwater. The exposed population is firstly diseased with various symptoms such as skin manifestations, loss of appetite, constipation, hormonal disorders, etc. The long duration exposure has led to cause infertility in the male subjects. The present study thus aims to develop the antidote against arsenic-induced male reproductive toxicity in animal models. The study was carried out on Charles Foster Rats after the approval from Institutional Animal Ethics Committee. A total of n=18 rats (12 weeks old) of an average weight of 160 ± 20 g were used for the study. The study group included n=6 control and n= 12 treated with sodium arsenite orally at the dose of 8mg/Kg b.w daily for 40 days. The n= 6 animals were dissected and the rest n=6 was administered orally with Curcuma longa rhizome ethanolic extract at the dose of 600mg/Kg b.w per day for 40 days. At the end of the entire experiment, all the animals were dissected out and their reproductive organs were taken out, especially epididymis for sperm counts, sperm motility, sperm mortality, sperm morphology. The blood samples were collected for the hormonal assay (testosterone and luteinizing hormone), as well as for hematological and biochemical analysis. The study showed a high magnitude of degeneration in the reproductive organs of the rats in the arsenic-treated group. There were degenerative fluctuations in the sperm counts, sperm motility, sperm mortality, sperm morphology and in the hormonal parameters, as well as in the hematological and biochemical parameters in the arsenic-treated rats. But, after the administration of Curcuma longa, there was significant amelioration in all these parameters. Therefore, the present study shows that Curcuma longa plays a vital role to combat arsenic-induced male reproductive toxicity.

Keywords: sodium arsenite, Charles foster rats, ethanolic rhizome extract of curcuma longa, male reproductive toxicity, amelioration

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Authors: J. A. N. Sandamali, R. P. Hewawasam, K. A. P. W. Jayatilaka, L. K. B. Mudduwa

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Introduction: Doxorubicin is widely used in the treatment of solid organ tumors and hematological malignancies, but the dose-dependent cardiotoxicity due to free radical formation compromises its clinical utility. Therapeutic strategies which enhance cellular endogenous defense systems have been identified as promising approaches to combat oxidative stress-associated conditions. Cinnamomum zeylanicum (Ceylon cinnamon) has a number antioxidant compounds, which can effectively scavenge reactive oxygen including superoxide anions, hydroxyl radicals and as well as other free radicals. Therefore, the objective of the study was to elucidate the most effective dose of Cinnamomum bark extract which ameliorates doxorubicin-induced cardiotoxicity. Materials and methods: Wistar rats were divided into seven groups of 10 animals in each. Group 1: normal control (distilled water, orally, for 14 days, 10 mL/kg saline, ip, after 16 hours fast on the 11th day); Group 2: doxorubicin control (distilled water, orally, for 14 days, 18 mg/kg doxorubicin, ip, after 16 hour fast on the 11th day); Groups 3-7: five doses of freeze dried aqueous bark extracts (0.125, 0.25, 0.5, 1.0, 2.0g/kg, orally, daily for 14 days, 18 mg/kg doxorubicin, ip, after 16 hours fast on the 11th day). Animals were sacrificed on the 15th day and blood was collected for the estimation of cardiac troponin I (cTnI), AST and LDH concentrations and myocardial tissues were collected for histopathological assessment of myocardial damage and irreversible changes were graded by developing a score. Results: cTnI concentration of groups 1-7 were 0, 161.9, 128.6, 95.9, 38, 19.41 & 12.36 pg/mL showing significant differences (p<0.05) between group 2 and groups 4-7. In groups 1-7, serum AST concentration were 26.82, 68.1, 37.18, 36.23, 26.8, 26.62 & 22.43U/L and LDH concentrations were 1166.13, 2428.84, 1658.35, 1474.34, 1277.58, 1110.21 & 974.40U/L and a significant difference (p<0.05) was observed between group 2 and groups 3-7. The maximum score for myocardial necrosis was observed in group 2. Parallel to the increase of the dosage of plant extract, a gradual reduction of the score for myocardial necrosis was observed in groups 3-7. Reversible histological changes such as vacuolation, congestion were observed in group 2 and all plant treated groups. Haemorrhages, inflammatory cell infiltrations, and interstitial oedema were observed in group 2, but absent in groups treated with higher doses of the plant extract. Discussion & Conclusion: According to the in vitro antioxidant assays performed, Cinnamomum zeylanicum (Ceylon cinnamon) bark possesses high amounts of polyphenolic substances and high antioxidant activity. The present study showed that Cinnamomum zeylanicum extract at 2.0 g/kg possesses the most significant cardioprotective effect against doxorubicin-induced cardiotoxicity. It can be postulated that pretreatment with Cinnamomum bark extract may replenish the cardiomyocytes with antioxidants that are needed for the defense against oxidative stress induced by doxorubicin.

Keywords: cardioprotection, Cinnamomum zeylanicum, doxorubicin, free radicals

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Authors: Adil Murtaza, Muhammad Tahir Khan, Awais Ghani, Chao Zhou, Sen Yang, Xiaoping Song

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The morphotropic phase boundary (MPB); a boundary between two different crystallographic symmetries in the composition–temperature phase diagram has been widely studied in ferroelectrics and recently has drawn interest in ferromagnets for obtaining enhanced large field-induced strain. At MPB, the system gets a compressed free energy state, which allows the polarization to freely rotate and hence results in a high magnetoelastic response (e.g., high magnetization, low coercivity, and large magnetostriction). Based on the same mechanism, we designed MPB in a ferromagnetic Tb₁₋ₓNdₓCo₂ system. The temperature-dependent magnetization curves showed spin reorientation (SR); which can be explained by a two-sublattice model. Contrary to previously reported MPB involved ferromagnetic systems, the MPB composition of Tb₀.₃₅Nd₀.₆₅Co₂ exhibits a low saturation magnetization (MS), indicating a compensation of the Tb and Nd magnetic moments at MPB. The coercive field (HC) under a low magnetic field and first anisotropy constant (K₁) shows a minimum value at MPB composition of x=0.65. A detailed spin configuration diagram is provided for the Tb₁₋ₓNdₓCo₂ around the composition for the anisotropy compensation; this can guide the development of novel magnetostrictive materials. The anisotropic magnetostriction (λS) first decreased until x=0.8 and then continuously increased in the negative direction with further increase of Nd concentration. In addition, the large ratio between magnetostriction and the absolute values of the first anisotropy constant (λS/K₁) appears at MPB, indicating that Tb₀.₃₅Nd₀.₆₅Co₂ has good magnetostrictive properties. Present work shows an anomalous type of MPB in ferromagnetic materials, revealing that MPB can also lead to a weakening of magnetoelastic behavior as shown in the ferromagnetic Tb₁₋ₓNdₓCo₂ system. Our work shows the universal presence of MPB in ferromagnetic materials and suggests the differences between different ferromagnetic MPB systems that are important for substantial improvement of magnetic and magnetostrictive properties. Based on the results of this study, similar MPB effects might be achieved in other ferroic systems that can be used for technological applications. The finding of magnetic MPB in the ferromagnetic system leads to some important significances. First, it provides a better understanding of the fundamental concept of spin reorientation transitions (SRT) like ferro-ferro transitions are not only reorientation of magnetization but also crystal symmetry change upon magnetic ordering. Second, the flattened free energy corresponding to a low energy barrier for magnetization rotation and enhanced magnetoelastic response near MPB. Third, to attain large magnetostriction with MPB approach two terminal compounds have different easy magnetization directions below Curie temperature Tc in order to accomplish the weakening of magnetization anisotropy at MPB (as in ferroelectrics), thus easing the magnetic domain switching and the lattice distortion difference between two terminal compounds should be large enough, e.g., lattice distortion of R symmetry ˃˃ lattice distortion of T symmetry). So that the MPB composition agrees to a nearly isotropic state along with large ‘net’ lattice distortion, which is revealed in a higher value of magnetostriction.

Keywords: magnetization, magnetostriction, morphotropic phase boundary (MPB), phase transition

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Authors: Rodchares Hanrinth, Theerapong Srisil, Peeraya Sriphong, Pawich Paktipat

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The trigger tool is the low-cost, low-tech method to detect adverse events through clues called triggers. The Institute for Healthcare Improvement (IHI) has developed the Global Trigger Tool for measuring and preventing adverse events. However, this tool is not specific for detecting adverse drug events. The pharmacy-based trigger tool is needed to detect adverse drug events (ADEs). Group concept mapping is an effective method for conceptualizing various ideas from diverse stakeholders. This technique was used to identify a pharmacy-based trigger to detect adverse drug events (ADEs). The aim of this study was to involve the pharmacists in conceptualizing, developing, and prioritizing a feasible trigger tool to detect adverse drug events in a provincial hospital, the northeastern part of Thailand. The study was conducted during the 6-month period between April 1 and September 30, 2017. Study participants involved 20 pharmacists (17 hospital pharmacists and 3 pharmacy lecturers) engaging in three concept mapping workshops. In this meeting, the concept mapping technique created by Trochim, a highly constructed qualitative group technic for idea generating and sharing, was used to produce and construct participants' views on what triggers were potential to detect ADEs. During the workshops, participants (n = 20) were asked to individually rate the feasibility and potentiality of each trigger and to group them into relevant categories to enable multidimensional scaling and hierarchical cluster analysis. The outputs of analysis included the trigger list, cluster list, point map, point rating map, cluster map, and cluster rating map. The three workshops together resulted in 21 different triggers that were structured in a framework forming 5 clusters: drug allergy, drugs induced diseases, dosage adjustment in renal diseases, potassium concerning, and drug overdose. The first cluster is drug allergy such as the doctor’s orders for dexamethasone injection combined with chlorpheniramine injection. Later, the diagnosis of drug-induced hepatitis in a patient taking anti-tuberculosis drugs is one trigger in the ‘drugs induced diseases’ cluster. Then, for the third cluster, the doctor’s orders for enalapril combined with ibuprofen in a patient with chronic kidney disease is the example of a trigger. The doctor’s orders for digoxin in a patient with hypokalemia is a trigger in a cluster. Finally, the doctor’s orders for naloxone with narcotic overdose was classified as a trigger in a cluster. This study generated triggers that are similar to some of IHI Global trigger tool, especially in the medication module such as drug allergy and drug overdose. However, there are some specific aspects of this tool, including drug-induced diseases, dosage adjustment in renal diseases, and potassium concerning which do not contain in any trigger tools. The pharmacy-based trigger tool is suitable for pharmacists in hospitals to detect potential adverse drug events using clues of triggers.

Keywords: adverse drug events, concept mapping, hospital, pharmacy-based trigger tool

Procedia PDF Downloads 149

Authors: Lishuang Ma

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Charge transfer (CT) complex, also known as Electron donor-acceptor (EDA) complex, has received attentions increasingly in the field of synthetic chemistry community, due to the CT complex can absorb the visible light through the intermolecular charge transfer excited states, various of catalyst-free photochemical transformations under mild visible-light conditions. However, a number of fundamental questions are still ambiguous, such as the origin of visible light absorption, the photochemical and photophysical properties of the CT complex, as well as the detailed mechanism of the radical coupling pathways mediated by CT complex. Since these are critical factors for target-specific design and synthesis of more new-type CT complexes. To this end, theoretical investigations were performed in our group to answer these questions based on multiconfigurational perturbation theory. The photo-induced fluoroalkylation reactions are mediated by CT complexes, which are formed by the association of an acceptor of perfluoroalkyl halides RF−X (X = Br, I) and a suitable donor molecule such as β-naphtholate anion, were chosen as a paradigm example in this work. First, spectrum simulations were carried out by both CASPT2//CASSCF/PCM and TD-DFT/PCM methods. The computational results showed that the broadening spectra in visible light range (360-550nm) of the CT complexes originate from the 1(σπ*) excitation, accompanied by an intermolecular electron transfer, which was also found closely related to the aggregate states of the donor and acceptor. Moreover, from charge translocation analysis, the CT complex that showed larger charge transfer in the round state would exhibit smaller charge transfer in excited stated of 1(σπ*), causing blue shift relatively. Then, the excited-state potential energy surface (PES) was calculated at CASPT2//CASSCF(12,10)/ PCM level of theory to explore the photophysical properties of the CT complexes. The photo-induced C-X (X=I, Br) bond cleavage was found to occur in the triplet state, which is accessible through a fast intersystem crossing (ISC) process that is controlled by the strong spin-orbit coupling resulting from the heavy iodine and bromine atoms. Importantly, this rapid fragmentation process can compete and suppress the backward electron transfer (BET) event, facilitating the subsequent effective photochemical transformations. Finally, the reaction pathways of the radical coupling were also inspected, which showed that the radical chain propagation pathway could easy to accomplish with a small energy barrier no more than 3.0 kcal/mol, which is the key factor that promote the efficiency of the photochemical reactions induced by CT complexes. In conclusion, theoretical investigations were performed to explore the photophysical and photochemical properties of the CT complexes, as well as the mechanism of radical coupling reactions mediated by CT complex. The computational results and findings in this work can provide some critical insights into mechanism-based design for more new-type EDA complexes

Keywords: charge transfer complex, electron transfer, multiconfigurational perturbation theory, radical coupling

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Authors: Vishal D. Bharud, B. J. Patil, S. S. Dahiwale, V. N. Bhoraskar, S. D. Dhole

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Photon induced average reaction cross section of ¹¹¹Cd (γ, γ`) ¹¹¹ᵐCd reaction was experimentally determined for the bremsstrahlung energy spectrum of 6 MeV by utilizing the activation and offline γ-ray spectrometric techniques. The 6 MeV electron accelerator Racetrack Microtron of Savitribai Phule Pune University, Pune was used for the experimental work. The bremsstrahlung spectrum generated by bombarding 6 MeV electrons on lead target was theoretically estimated by FLUKA code. Bremsstrahlung radiation can have energies exceeding the threshold of the particle emission, which is normally above 6 MeV. Photons of energies below the particle emission threshold undergo absorption into discrete energy levels, with possibility of exciting nuclei to excited state including metastable state. The ¹¹¹Cd (γ, γ`) ¹¹¹ᵐCd reaction cross sections were calculated at different energies of bombarding Photon by using the TALYS 1.8 computer code with a default parameter. The focus of the present work was to study the (γ,γ’) reaction for exciting ¹¹¹Cd nuclei to metastable states which have threshold energy below 3 MeV. The flux weighted average cross section was obtained from the theoretical values of TALYS 1.8 and TENDL 2017 and is found to be in good agreement with the present experimental cross section.

Keywords: bremsstrahlung, cross section, FLUKA, TALYS-1.8

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Authors: Cherry Dhiman, Ayushi Paliwal, Mohd. Shahid Khan, M. N. Reddy, Vinay Gupta, Monika Tomar

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The laser based high resolution spectroscopic experimental techniques such as Laser Induced Breakdown Spectroscopy (LIBS), Rotating Disk Electrode Optical Emission spectroscopy (RDE-OES) and Surface Plasmon Resonance (SPR) have been used for the study of composition and degradation analysis of used engine oils. Engine oils are mainly composed of aliphatic and aromatics compounds and its soot contains hazardous components in the form of fine, coarse and ultrafine particles consisting of wear metal elements. Such coarse particulates matter (PM) and toxic elements are extremely dangerous for human health that can cause respiratory and genetic disorder in humans. The combustible soot from thermal power plants, industry, aircrafts, ships and vehicles can lead to the environmental and climate destabilization. It contributes towards global pollution for land, water, air and global warming for environment. The detection of such toxicants in the form of elemental analysis is a very serious issue for the waste material management of various organic, inorganic hydrocarbons and radioactive waste elements. In view of such important points, the current study on used engine oils was performed. The fundamental characterization of engine oils was conducted by measuring water content and kinematic viscosity test that proves the crude analysis of the degradation of used engine oils samples. The microscopic quantitative and qualitative analysis was presented by RDE-OES technique which confirms the presence of elemental impurities of Pb, Al, Cu, Si, Fe, Cr, Na and Ba lines for used waste engine oil samples in few ppm. The presence of such elemental impurities was confirmed by LIBS spectral analysis at various transition levels of atomic line. The recorded transition line of Pb confirms the maximum degradation which was found in used engine oil sample no. 3 and 4. Apart from the basic tests, the calculations for dielectric constants and refractive index of the engine oils were performed via SPR analysis.

Keywords: surface plasmon resonance, laser-induced breakdown spectroscopy, ICCD spectrometer, engine oil

Procedia PDF Downloads 128

Authors: Karina Marie G. Nicolas, Kimberly M. Visaya, Emmanuel R. Cauinian

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A comparative study on the antihyperglycemic activity of aqueous extracts of Serpentina (Andrographis paniculata) and Papait (Mollugo oppositifolia linn) administered at 400mg/kg body weight per orem twice daily for 14 days was investigated using 24 alloxan-induced diabetic male, 6-8 weeks old ICR mice and Metformin as standard control. The blood glucose levels of all the animals in the treatment groups were not reduced to < 200mg/dl so as to consider them as non-diabetic but Papait showed a consistent blood glucose lowering effect from day 0 to 14 causing 36.07% reduction as compared to Serpentina which was observed to cause a fluctuating effect on blood glucose levels and a reduction of only 22.53% while the Metformin treated animals exhibited the highest reduction at 45.29%. The blood glucose levels at day 14 of animals treated with Papait (322.93 mg/dl) had comparable blood glucose levels (p<0.05) with the Metformin treated groups (284.50 mg/dl). Also, all the animals in the three treatment groups were still hypercholesterolemic with an observed consistent weight loss and a decrease in feed intake except for Serpentina which recorded a slight increase. Results of the study showed a superior antihyperglycemic activity of Papait compared with Serpentina.

Keywords: antihyperglycemic, diabetes, hypercholesterolemic, papait, serpentina

Procedia PDF Downloads 346

Authors: Seyedahmad Hosseini, Mohammadjavad Sotoudeheian

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Introduction: Allergic asthma is a heterogeneous immuno-inflammatory disease based on Th-2-mediated inflammation. Histopathologic abnormalities of the airways characteristic of asthma include epithelial damage and subepithelial collagen deposition. Objectives: Human bronchial epithelial cell genome expression of TNF‑α, IL‑6, ICAM‑1, VCAM‑1, nuclear factor (NF)‑κB signaling pathways up-regulate during inflammatory cascades. Moreover, immunofluorescence assays confirmed the nuclear translocation of NF‑κB p65 during inflammatory responses. An absolute LDH leakage assays suggestedLPS-inducedcells injury, and the associated mechanisms are co-incident events. LPS-induced phosphorylation of ERKand JNK causes inflammation in epithelial cells through inhibition of ERK and JNK activation and NF-κB signaling pathway. Furthermore, the inhibition of NF-κB mRNA expression and the nuclear translocation of NF-κB lead to anti-inflammatory events. Likewise, activation of SUMF2 which inhibits IL-13 and reduces Th2-cytokines, NF-κB, and IgE levels to ameliorate asthma. On the other hand, TNFα-induced mucus production reduced NF-κB activation through inhibition of the activation status of Rac1 and IκBα phosphorylation. In addition, bradykinin B2 receptor (B2R), which mediates airway remodeling, regulates through NF-κB. Bronchial B2R expression is constitutively elevated in allergic asthma. In addition, certain NF-κB -dependent chemokines function to recruit eosinophils in the airway. Besides, bromodomain containing 4 (BRD4) plays a significant role in mediating innate immune response in human small airway epithelial cells as well as transglutaminase 2 (TG2), which is detectable in saliva. So, the guanine nucleotide-binding regulatory protein α-subunit, Gα16, expresses a κB-driven luciferase reporter. This response was accompanied by phosphorylation of IκBα. Furthermore, expression of Gα16 in saliva markedly enhanced TNF-α-induced κB reporter activity. Methods: The applied method to form NF-κB activation is the electromobility shift assay (EMSA). Also, B2R-BRD4-TG2 complex detection by immunoassay method within saliva with EMSA of NF-κB activation may be a novel biomarker for asthma diagnosis and follow up. Conclusion: This concept introduces NF-κB signaling pathway as potential asthma biomarkers and promising targets for the development of new therapeutic strategies against asthma.

Keywords: NF-κB, asthma, saliva, T-helper

Procedia PDF Downloads 82

Authors: Kevin Molina, Daniel Ortega, Manuel Martinez, Andres Gonzalez-Estrada, William Pinto

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Due to the increasing environmental impact, the wind energy is getting strong. This research studied the relationship between the power produced by a horizontal axis wind turbine (HAWT) and the aerodynamic profiles used for its construction. The analysis is studied using the Computational Fluid Dynamic (CFD), presenting the parallel between the energy generated by a turbine designed with selected profiles and another one optimized. For the study, a selection process was carried out from profile NACA 6 digits recommended by the National Renewable Energy Laboratory (NREL) for the construction of this type of turbines. The selection was taken into account different characteristics of the wind (speed and density) and the profiles (aerodynamic coefficients Cl and Cd to different Reynolds and incidence angles). From the selected profiles, was carried out a sensitivity analysis optimization process between its geometry and the aerodynamic forces that are induced on it. The 3D model of the turbines was realized using the Blade Element Momentum method (BEM) and both profiles. The flow fields on the turbines were simulated, obtaining the forces induced on the blade, the torques produced and an increase of 3% in power due to the optimized profiles. Therefore, the results show that the sensitivity analysis optimization process can assist to increment the wind turbine power.

Keywords: blade element momentum, blade, fluid structure interaction, horizontal axis wind turbine, profile design

Procedia PDF Downloads 246

Authors: Muhammad Tarmidzi, Reza M. G. Gani, Andri Luthfi

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The purpose of this study is to identify rock zone containing hydrocarbons with calculating rock property includes volume shale, total porosity, effective porosity and water saturation. Identification method rock property based on GR log, resistivity log, neutron log and density rock. Zoning is based on sequence stratigraphic markers that are sequence boundary (SB), transgressive surface (TS) and flooding surface (FS) which correlating ten well log in blok “M”. The results of sequence stratigraphic correlation consist of eight zone that are two LST zone, three TST zone and three HST zone. The result of rock property calculation in each zone is showing two LST zone containing hydrocarbons. LST-1 zone has average volume shale (Vsh) 25%, average total porosity (PHIT) 14%, average effective porosity (PHIE) 11% and average water saturation 0,83. LST-2 zone has average volume shale (Vsh) 19%, average total porosity (PHIT) 21%, average effective porosity (PHIE) 17% and average water saturation 0,82.

Keywords: hydrocarbons zone, petrophysic, rock property, sequence stratigraphic

Procedia PDF Downloads 298

Authors: Jaspal Rana, Varinder Singh

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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 were also determined. Treatment with ACE significantly ameliorated IR mediated deterioration of memory and sensorimotor functions and rose 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: allium cepa, cerebral ischemia, memory, sensorimotor

Procedia PDF Downloads 97

Authors: Layla Farhat, Mathieu Bardoux, Stéphane Longuemart, Ziad Herro, Abdelhak Hadj Sahraoui

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Electrocaloric (EC) effect refers to the isothermal entropy or adiabatic temperature changes of a dielectric material induced by an external electric field. This phenomenon has been largely ignored for application because only modest EC effects (2.6

Keywords: electrocaloric effect, thermoreflectance, ferroelectricity, cooling system

Procedia PDF Downloads 164

Authors: S. Delpeux-Ouldriane, M. Gineys, S. Masson, N. Cohaut, L. Reinert, L. Duclaux, F. Béguin

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Nowadays, a wide variety of organic contaminants are present at trace concentrations in wastewater effluents. In order to face these pollution problems, the implementation of the REACH European regulation has defined lists of targeted pollutants to be eliminated selectively in water. It therefore implies the development of innovative and more efficient remediation techniques. In this sense, adsorption processes can be successfully used to achieve the removal of organic compounds in waste water treatment processes, especially at low pollutant concentration. Especially, activated carbons possessing a highly developed porosity demonstrate high adsorption capacities. More specifically, carbon cloths show high adsorption rates, an easily handling, a good mechanical integrity and regeneration potentialities. When loaded with pollutants, these materials can be indeed regenerated using an electrochemical polarization.

Keywords: nanoporous carbons, activated carbon cloths, adsorption, micropollutants, emerging contaminants, regeneration, electrochemistry

Procedia PDF Downloads 387

Authors: Narine Ghazaryan, Joana Catarina Macedo, Sara Vaz, Naira Ayvazyan, Elsa Logarinho

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Macrovipera lebetina obtusa (MLO) is a poisonous snake in Armenia. Obtustatin represents the shortest known monomeric disintegrin, isolated from the snake venom of MLO, and is known to specifically inhibit α1β1 integrin. Its oncostatic effect is due to the inhibition of angiogenesis, which likely arises from α1β1 integrin inhibition in the endothelial cells. To explore the therapeutic potential of the MLO snake venom and obtustatin, we studied activity of obtustatin and MLO venom in vitro, by testing their efficacy in human dermal microvascular endothelial cells (HMVEC-D) and in vivo, using chick embryo chorioallantoic membrane assay (CAM assay). Our in vitro results showed that obtustatin in comparison with MLO venom did not exhibit cytotoxic activity in HMVEC-D cells in comparison to MLO venom. But in vivo results have shown that 4µg /embryo (90 µM) of obtustatin inhibited angiogenesis induced by FGF2 by 17% while MLO snake venom induced 22% reduction of the angiogenic index. The concentration of obtustatin in the crude MLO venom was 0.3 nM, which is 300.000 times less than the concentration of the obtustatin itself. Given this enormous difference in concentration, it is likely that some components of the crude venom contribute to the observed anti-angiogenic effect. Hypotheses will be ascertained to justify this action: components in the MLO venom may increase obtustatin efficacy or have independent but synergic anti-angiogenic activities.

Keywords: angiogenesis, alpa1 beta 1 integrin, Macrovipera lebetina obtusa, obtustatin

Procedia PDF Downloads 172

Authors: Marcel Verwey, Anna M. Joubert, Elsie M. Nolte, Wolfgang Dohle, Barry V. L. Potter, Anne E. Theron

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A tetrahydroisoquinolinone (THIQ) core can be used to mimic the A,B-ring of colchicine site-binding microtubule disruptors such as 2-methoxyestradiol in the design of anti-cancer agents. Steroidomimeric microtubule disruptors were synthesized by introducing C'2 and C'3 of the steroidal A-ring to C'6 and C'7 of the THIQ core and by introducing a decorated hydrogen bond acceptor motif projecting from the steroidal D-ring to N'2. For this in vitro study, four non-steroidal THIQ-based analogues were investigated and comparative studies were done between the non-sulphamoylated compound STX 3450 and the sulphamoylated compounds STX 2895, STX 3329 and STX 3451. The objective of this study was to investigate the modes of cell death induced by these four THIQ-based analogues in A549 lung carcinoma epithelial cells and metastatic breast adenocarcinoma MDA-MB-231 cells. Cytotoxicity studies to determine the half maximal growth inhibitory concentrations were done using spectrophotometric quantification via crystal violet staining and lactate dehydrogenase (LDH) assays. Microtubule integrity and morphologic changes of exposed cells were investigated using polarization-optical transmitted light differential interference contrast microscopy, transmission electron microscopy and confocal microscopy. Flow cytometric quantification was used to determine apoptosis induction and the effect that THIQ-based analogues have on cell cycle progression. Signal transduction pathways were elucidated by quantification of the mitochondrial membrane integrity, cytochrome c release and caspase 3, -6 and -8 activation. Induction of autophagic cell death by the THIQ-based analogues was investigated by morphological assessment of fluorescent monodansylcadaverine (MDC) staining of acidic vacuoles and by quantifying aggresome formation via flow cytometry. Results revealed that these non-steroidal microtubule disrupting analogues inhibited 50% of cell growth at nanomolar concentrations. Immunofluorescence microscopy indicated microtubule depolarization and the resultant mitotic arrest was further confirmed through cell cycle analysis. Apoptosis induction via the intrinsic pathway was observed due to depolarization of the mitochondrial membrane, induction of cytochrome c release as well as, caspase 3 activation. Potential involvement of programmed cell death type II was observed due to the presence of acidic vacuoles and aggresome formation. Necrotic cell death did not contribute significantly, indicated by stable LDH levels. This in vitro study revealed the induction of the intrinsic apoptotic pathway as well as possible involvement of autophagy after exposure to these THIQ-based analogues in both MDA-MB-231- and A549 cells. Further investigation of this series of anticancer drugs still needs to be conducted to elucidate the temporal, mechanistic and functional crosstalk mechanisms between the two observed programmed cell deaths pathways.

Keywords: apoptosis, autophagy, cancer, microtubule disruptor

Procedia PDF Downloads 233