Search results for: induced subgraph

Authors: F. Alaa Ali, S. A. Sherein Abdelgayed, S. Osama. EL-Tawil, M. Adel Bakeer

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Tartrazine is an organic azo dyes food additive widely used in foods, drugs, and cosmetics. The present study aimed to investigate the toxic effects of tartrazine on kidneys and liver biomarkers in addition to the investigation of oxidative stress and change of histopathological structure of liver and kidneys in 30 male rats. Tartrazine was orally administrated daily at dose 200 mg/ kg bw (1/ 10 LD₅₀) for sixty days. Serum and tissue samples were collected at the end of the experiment to investigate the underlying mechanism of tartrazine through assessment oxidative stress (Glutathione (GSH), Superoxide dismutase (SOD) and malondialdehyde (MDA) and biochemical markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), Total protein and Urea). Liver and kidneys tissue were collected and preserved in 10% formalin for histopathological examination. The obtained values were statistically analyzed by one way analysis of variance (ANOVA) followed by multiple comparison test. Biochemical analysis revealed that tartrazine induced significant increase in serum ALT, AST, total protein, urea level compared to control group. Tartrazine showed significant decrease in liver GSH and SOD where their values when compared to control group. Tartrazine induced increase in liver MDA compared to control group. Histopathology of the liver showed diffuse vacuolar degeneration in hepatic parenchyma, the portal area showed sever changes sever in hepatoportal blood vessels and in the bile ducts. The kidneys showed degenerated tubules at the cortex together with mononuclear leucocytes inflammatory cells infiltration. There is perivascular edema with inflammatory cell infiltration surrounding the congested and hyalinized vascular wall of blood vessel. The present study indicates that the subchronic effects of tartrazine have a toxic effect on the liver and kidneys together with induction of oxidative stress by formation of free radicals. Therefore, people should avoid the hazards of consuming tartrazine.

Keywords: albino rats, tartrazine, toxicity, pathology

Procedia PDF Downloads 359

Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche

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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.

Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells

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Authors: Jeremy Bost, Matthew Brett, Jacob Flynn, Weihui Li

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One response during anaphylaxis is reduced blood pressure due to blood vessels relaxing and dilating. Epinephrine causes the blood vessels to constrict, which raises blood pressure to counteract the symptoms. When going through an allergic reaction, an Epinephrine injector is used to administer a shot of epinephrine intramuscularly. Epinephrine injectors have become an integral part of day-to-day life for people with allergies. Current Epinephrine injectors (EpiPen) are completely mechanical and have no sensors to monitor the vital signs of patients or give suggestions the optimal time for the shot. The EpiPens are also large and inconvenient to carry daily. The current price of an EpiPen is roughly 600$ for a pack of two. This makes carrying an EpiPen very expensive, especially when they need to be switched out when the epinephrine expires. This new design is in the form of a bracelet, which has the ability to inject epinephrine. The bracelet will be equipped with vital signs monitors that can aid the patient to sense the allergic reaction. The vital signs that would be of interest are blood pressure, heart rate and Electrodermal activity (EDA). The heart rate of the patient will be tracked by a photoplethysmograph (PPG) that is incorporated into the sensors. The heart rate is expected to increase during anaphylaxis. Blood pressure will be monitored through a radar sensor, which monitors the phase changes in electromagnetic waves as they reflect off of the blood vessel. EDA is under autonomic control. Allergen-induced anaphylaxis is caused by a release of chemical mediators from mast cells and basophils, thus changes the autonomic activity of the patient. So by measuring EDA, it will give the wearer an alert on how their autonomic nervous system is reacting. After the vital signs are collected, they will be sent to an application on a smartphone to be analyzed, which can then alert an emergency contact if the epinephrine injector on the bracelet is activated. Overall, this design creates a safer system by aiding the user in keeping track of their epinephrine injector, while making it easier to track their vital signs. Also, our design will be more affordable and more convenient to replace. Rather than replacing the entire product, only the needle and drug will be switched out and not the entire design.

Keywords: allergy, anaphylaxis, epinephrine, injector, vital signs monitor

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Authors: Rayhana Begum, Manju Sharma

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Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

Procedia PDF Downloads 143

Authors: A. K. Tursunova, O. V. Chebonenko, A. Zh. Amirkulova, A. O. Abaildayev, O. A. Sapko, Y. M. Dyo, A. Sh. Utarbaeva

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Fusarium solani and its variants cause root and stem rot of plants. Dry rot is the most common disease of potato tubers during storage. The causative agents of fusariosis in contact with plants behave as antagonists, growth stimulants or parasites. The diversity of host-parasite relationships is explained by the parasite’s ability to produce a wide spectrum of biologically active compounds including toxins, enzymes, oligosaccharides, antibiotic substances, enniatins and gibberellins. Many of these metabolites contribute to the creation of compatible relations; others behave as elicitors, inducing various protective responses in plants. An important part of the strategy for developing plant resistance against pathogens is the activation of protein synthesis to produce protective ‘pathogenesis-related’ proteins. The family of PR-proteins known to confer the most protective response is chitinases (EC 3.2.1.14, Cht) and β-1,3-glucanases (EC 3.2.1.39, Glu). PR-proteins also include a large multigene family of peroxidases (EC 1.11.1.7, Pod), and increased activity of Pod and expression of the Pod genes leads to the development of resistance to a broad class of pathogens. Despite intensive research on the role of PR-proteins, the question of their participation in the mechanisms of formation of the F.solani–S.tuberosum pathosуstem is not sufficiently studied. Our aim was to investigate the effect of different classes of F. solani metabolites on the activity of chitinase, β-1,3-glucanases and peroxidases in tubers of Solanum tuberosum. Metabolite culture filtrate (CF) and cytoplasmic components were fractionated by extraction of the mycelium with organic solvents, salting out techniques, dialysis, column chromatography and ultrafiltration. Protein, lipid, carbohydrate and polyphenolic fractions of fungal metabolites were derived. Using enzymatic hydrolysis we obtained oligo glycans from fungal cell walls with different molecular weights. The activity of the metabolites was tested using potato tuber discs (d = 16mm, h = 5mm). The activity of PR-proteins of tubers was analyzed in a time course of 2–24 hours. The involvement of the analysed metabolites in the modulation of both early non-specific and late related to pathogenesis reactions was demonstrated. The most effective inducer was isolated from the CF (fraction of total phenolic compounds including naphtazarins). Induction of PR-activity by this fraction was: chitinase - 340-360%, glucanase - 435-450%, soluble forms of peroxidase - 400-560%, related forms of peroxidase - 215-237%. High-inducing activity was observed by the chloroform and acetonitrile extracts of the mycelium (induction of chitinase and glucanase activity was 176-240%, of soluble and bound forms of peroxidase - 190-400%). The fraction of oligo glycans mycelium cell walls of 1.2 kDa induced chitinase and β-1,3-glucanase to 239-320%; soluble forms and related peroxidase to 198-426%. Oligo glycans cell walls of 5-10 kDa had a weak suppressor effect - chitinase (21-25%) and glucanase (25-28%) activity; had no effect on soluble forms of peroxidase, but induced to 250-270% activity related forms. The CF polysaccharides of 8.5 kDa and 3.1 kDa inhibited synchronously the glucanase and chitinase specific response in step (after 24 hours at 42-50%) and the step response induced nonspecific peroxidase activity: soluble forms 4.8 -5.2 times, associated forms 1.4-1.6 times.

Keywords: fusarium solani, PR-proteins, peroxidase, solanum tuberosum

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Authors: E. A. Krasikov

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As a main barrier against radioactivity outlet reactor pressure vessel (RPV) is a key component in terms of NPP safety. Therefore, present-day demands in RPV reliability enhance have to be met by all possible actions for RPV in-service embrittlement mitigation. Annealing treatment is known to be the effective measure to restore the RPV metal properties deteriorated by neutron irradiation. There are two approaches to annealing. The first one is so-called ‘dry’ high temperature (~475°C) annealing. It allows obtaining practically complete recovery, but requires the removal of the reactor core and internals. External heat source (furnace) is required to carry out RPV heat treatment. The alternative approach is to anneal RPV at a maximum coolant temperature which can be obtained using the reactor core or primary circuit pumps while operating within the RPV design limits. This low temperature «wet» annealing, although it cannot be expected to produce complete recovery, is more attractive from the practical point of view especially in cases when the removal of the internals is impossible. The first RPV «wet» annealing was done using nuclear heat (US Army SM-1A reactor). The second one was done by means of primary pumps heat (Belgian BR-3 reactor). As a rule, there is no recovery effect up to annealing and irradiation temperature difference of 70°C. It is known, however, that along with radiation embrittlement neutron irradiation may mitigate the radiation damage in metals. Therefore, we have tried to test the possibility to use the effect of radiation-induced ductilization in ‘wet’ annealing technology by means of nuclear heat utilization as heat and neutron irradiation sources at once. In support of the above-mentioned conception the 3-year duration reactor experiment on 15Cr3NiMoV type steel with preliminary irradiation at operating PWR at 270°C and following extra irradiation (87 h at 330°C) at IR-8 test reactor was fulfilled. In fact, embrittlement was partly suppressed up to value equivalent to 1,5 fold neutron fluence decrease. The degree of recovery in case of radiation enhanced annealing is equal to 27% whereas furnace annealing results in zero effect under existing conditions. Mechanism of the radiation-induced damage mitigation is proposed. It is hoped that «wet » annealing technology will help provide a better management of the RPV degradation as a factor affecting the lifetime of nuclear power plants which, together with associated management methods, will help facilitate safe and economic long-term operation of PWRs.

Keywords: controlling, embrittlement, radiation, steel, wet annealing

Procedia PDF Downloads 380

Authors: Abubakar Maitama Yusuf Hotoro, Olokpo Israel Olofu, Yusuf U. Tarauni, Mudassir A. Umar, Aliyu A, Dahiru Garba Diso, Usman H. Jamoh, M. Sale

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The study assessed the impact of environmental pollution on groundwater potential at Tudun Murtala waste land fill using electrical resistivity, induced polarization and Physiochemical methods. The study area is located between latitude 12.023678N and longitude 8.573676 E. Geophysical data were collected at maximum length of 140m along twelve profiles using ABEM Terrameter SAS 1000. Results from the Geophysical analysis showed that the profiles were underlain by three lithological layers; the top layer consisting of Loamy and Sand soils, alluvium, granite, shale and sandstone. The second and third layers were predominantly made of weathered and fractured basements respectively. The potential groundwater water bearing zones of the study area occurred at VES2, VES4, VES5, VES6 and VES7. The thicknesses of the sounding points were found to be 20.8m at VES2; 25.2m at VES4; 13.2m at VES5; 50.8m at VES6 and 13.3m at VES7. The corresponding depths for the sounding points were 20.8m at VES2; 27.9m at VES4; 26.7m at VES5; 51.6m at VES6 and 24.9m at VES7 respectively. The Physiochemical study of selected groundwater samples assessed parameters such as the Electrical Conductivity, EC (288dS/m to 1365dS/m), TDS (170.8mg/L to 820mg/L) Pb (0.546mg/l to 0.629mg/l), Cu (-0.001mg/l to 0.004mg/l), and Cd (0.031mg/l to 0.092mg/l). The physiochemical results showed that the groundwater around the dumpsite may have been contaminated, especially in Dumpsite Hole 1 and Hole 2 at VES4 and VES6 respectively. There are indications for suspected leachate mitigation around the two VES points. Even though, the pH values of 6.4 and 6.2 at the two sounding points were considered to be within the permissible pH range (6.5 to 6.8). The values of other elements present in the groundwater for the samples at other VES points were found to be above permissible WHO and Nigerian Standards for Drinking Water.

Keywords: resistivity induced polarization, chargeability, landfill, leachate, contamination

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Authors: Luís R. Silva, Catarina Bento, Ana C. Gonçalves, Fábio Jesus, Branca M. Silva

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Nowadays, the general population is more and more concerned about nutrition and the health implications of an unbalanced diet. Current knowledge regarding the health benefits and antioxidant properties of certain foods such as fruits and vegetables has gained the interest of both the general public and scientific community. Peach (Prunus persica (L.) Batsch) is one of the most consumed fruits worldwide, with low sugar contents and a broad range of nutrients essential to the normal functioning of the body. Six different peach cultivars from the Fundão region in Portugal were evaluated regarding their phenolic composition by LC-DAD and biological activity. The prepared extracts’ capacity to scavenge free-radicals was tested through the stable free radical DPPH• and nitric oxide (•NO). Additionally, antidiabetic potential and protective effects against peroxyl radical (ROO•) induced damage to erythrocytes were also tested. LC-DAD analysis allowed the identification of 17 phenolic compounds, among which 5-O-caffeoylquinic acids and 3-O-caffeoylquinic acids are pointed out as the most abundant. Regarding the antioxidant activity, all cultivars displayed concentration-dependent free-radical scavenging activity against both nitrogen species and DPPH•. In respect to α-glucosidase inhibitory activity, Royal Magister and Royal Glory presented the highest inhibitory activity (IC50 = 11.7 ± 1.4 and 17.1 ± 1.7 μg/mL, respectively), nevertheless all six cultivars presented higher activity than the control acarbose. As for the protective effect of Royal Lu extract on the oxidative damage induced in erythrocytes by ROO•, the results were quite promising showing inhibition IC50 values of 110.0 ± 4.5 μg/mL and 83.8 ± 6.5 μg/mL for hemolysis and hemoglobin oxidation, respectively. The demonstrated activity is of course associated to the peaches’ phenolic profile, rich in phenolic acids and flavonoids with high hydrogen donating capacity. These compounds have great industrial interest for the manufacturing of natural products. The following step would naturally be the extraction and isolation from the plant tissues and large-scale production through biotechnology techniques.

Keywords: antioxidants, functional food, phenolic compounds, peach

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Authors: Cristina Núñez, Rufina Bastida, Elena Labisbal, Alejandro Macías, María T. Pereira, José M. Vila

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A highly selective quinoline-based fluorescent sensor L was designed in order to functionalize gold nanoparticles (GNPs@L). The cytotoxicity of compound L and GNPs@L on the MCF-7 breast cancer cells was explored and it was observed that L and GNPs@L compounds induced apoptosis in MCF-7 cancer cells. The cellular uptake of the hybrid system GNPs@L was studied using confocal laser scanning microscopy (CLSM).

Keywords: cytotoxicity, fluorescent probes, nanoparticles, quinoline

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Authors: Lina Liang, Kai Xu, Jing Zhang

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Purpose: Age-related macular degeneration (AMD) is a major leading cause of visual impairment and blindness with no cure currently established. Cell replacement is discussed as a potential therapy for AMD. Besides intravitreal injection and subretinal injection, intravenous administration has been explored as an alternative route. This study is to observe the effect of BSYJ, a traditional Chinese medicine on the homing and differentiation of mesenchymal stem cells transplanted via tail vein injection in an age-related macular degeneration mouse model. Methods: Four-week-old C57BL/6J mice were injected with 40 mg/kg NaIO₃ to induce age-related macular degeneration model. At the second day after NaIO₃ injection, 1×10⁷ GFP labeled bone marrow-derived mesenchymal stem cells (GFP-MSCs) were transplanted via tali vein injection into the experimental mice. Then the mice were randomly divided into two groups, gavaged with either BSYJ solution (BSYJ group, n=12) or distilled water (DW group, n=12). 12 age-matched healthy C57BL/6J mice were fed regularly as normal control. At day 7, day 14, and day 28 after treatment, retina flat mounting was used to detect the homing of mesenchymal stem cells at the retina. Double-labeling immunofluorescence was used to determine the differentiation of mesenchymal stem cells. Results: At 7, 14, 28 days after treatment, the numbers of GFP-MSCs detected by retina flatmount were 10.2 ± 2.5, 14.5 ± 3.4 and 18.7 ± 5.8, respectively in the distilled water group, while 15.7 ± 3.8, 32.3 ± 3.5 and 77.3 ± 6.4 in BSYJ group, the differences between the two groups were significant (p < 0.05). At 28 days after treatment, it was shown by double staining immunofluorescence that there were more GFP positive cells in the retina of BSYJ group than that of the DW group, but none of the cells expressed RPE specific genes such as RPE65 and CRALBP, or photoreceptor genes such as recoverin and rhodopsin either in BSYJ group or DW group. However, GFAP positive cells were found among the cells labeled with GFP, and the double labeling cells were much more in the BSYJ group than the distilled water group. Conclusion: BSYJ could promote homing of mesenchymal stem cells at the retina of age-related macular degeneration model mice induced by NaIO₃, and the differentiation towards to glial cells. Acknowledgement: National Natural Foundation of China (No: 81473736, 81674033,81973912).

Keywords: BSYJ, differentiation, homing, mesenchymal stem cells

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Authors: Hager Elsheikh, Juliane Glaubitz, Frank Ulrich Weiss, Matthias Sendler

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Aim: Acute pancreatitis (AP) and chronic pancreatitis (CP) are both accompanied by a prominent immune response which influences the course of disease. Whereas during AP the pro-inflammatory immune response dominates, during CP a fibroinflammatory response regulates organ remodeling. The transcription factor signal transducer and activator of transcription 6 (STAT6) is a crucial part of the Type 2 immune response. Here we investigate the role of STAT6 in a mouse model of AP and CP. Material and Methods: AP was induced by hourly repetitive i.p. injections of caerulein (50µg/kg/bodyweight) in C57Bl/6 J and STAT6-/- mice. CP was induced by repetitive caerulein injections 6 times a day, 3 days a week over 4 weeks. Disease severity was evaluated by serum amylase/lipase measurement, H&E staining of pancreas. Pancreatic infiltrate was characterized by immunofluorescent labeling of CD68, CD206, CCR2, CD4 and CD8. Pancreas fibrosis was evaluated by Azan blue staining. qRT-PCR was performed of Arg1, Nos2, Il6, Il1b, Col3a, Socs3 and Ym1. Affymetrix chip array analyses were done to illustrate the IL4/IL13/STAT6 signaling in bone marrow derived macrophages. Results: AP severity is mitigated in STAT6-/- mice, as shown by decreased serum amylase and lipase, as well as histological damage. CP mice surprisingly showed only slightly reduced fibrosis of the pancreas. Also staining of CD206 a classical marker of alternatively activated macrophages showed no decrease of M2-like polarization in the absence of STAT6. In contrast, transcription profile analysis in BMDM showed complete blockade of the IL4/IL13 pathway in STAT6-/- animals. Conclusion: STAT6 signaling pathway is protective during AP and mitigates the pancreatic damage. During chronic pancreatitis the IL4/IL13 – STAT6 axisis involved in organ fibrogenesis. Notably, fibrosis is not dependent on a single signaling pathway, and alternative macrophage activation is also complex and involves different subclasses (M2a, M2b, M2c and M2d) which could be independent of the IL4/IL13 STAT6 axis.

Keywords: chronic pancreatitis, macrophages, IL4/IL13, Type immune response

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Authors: Christina Williams, Mehari Weldemariam, Ann M. Farese, Thomas J. MacVittie, Maureen A. Kane

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Radiation exposure results in dose-dependent and time-dependent multi-organ damage. Drug development of medical countermeasures (MCM) for radiation-induced injury occurs under the FDA Animal Rule because human efficacy studies are not ethical or feasible. The FDA Animal Rule requires the representation of both sexes and describes several uses for biomarkers in MCM drug development studies. Currently, MCMs are limited and there is no FDA-approved biomarker for any radiation injury. Sex as a variable is essential to identifying biomarkers and developing effective MCMs for acute radiation exposure (ARS) and delayed effects of acute radiation exposure (DEARE). These studies aim to address the death of information on sex differences that have not been determined by studies that included only male, single-sex cohorts. Studies have reported differences in radiosensitivity according to sex. As such, biomarker discovery for radiation-induced damage must consider sex as a variable. This study evaluated the plasma proteomic profile of Rhesus macaque non-human primates after different exposures and doses, as well as time points after radiation. Exposures and doses included total body irradiation between 5-7.5 Gy and partial body irradiation with 5% bone marrow sparing at 9, 9.5 and 10 Gy. Timepoints after irradiation included days 1, 3, 60, and 180, which encompassed both acute radiation syndromes and delayed effects of acute radiation exposure. Bottom-up proteomic analyses of plasma included equal numbers of males and females. In the control animals, few proteomic differences are observed between the sexes. In the irradiated animals, there are a few sex differences, with changes mostly consisting of proteins upregulated in the female animals. Multiple canonical pathways were upregulated in irradiated animals relative to the control animals when subjected to pathway analysis, but differential responses between the sexes are limited. These data provide critical baseline differences according to sex and establish sex differences in non-human primate models relevant to drug development of MCM under the FDA Animal Rule.

Keywords: ionizing radiation, sex differences, plasma proteomics, biomarker discovery

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Authors: Fernanda Piculo, Giovana Vesentini, Gabriela Marini, Debora Cristina Damasceno, Angelica Mercia Pascon Barbosa, Marilza Vieira Cunha Rudge

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Introduction: Women with previous gestational diabetes mellitus (GDM) were significantly more likely to have urinary incontinence (UI) and pelvic floor muscle dysfunction compared to non-diabetic women two years after a cesarean section. Additional results demonstrated that induced diabetes causes detrimental effects on pregnant rat urethral muscle. These results indicate the need for exploration of the mechanistic role of a recovery factor in female UI. Chemokine ligand 7 (CCL7) was significantly over expressed in rat serum, urethral and vaginal tissues immediately following induction of stress UI in a rat model simulating birth trauma. CCL7 over expression has shown potency for stimulating targeted stem cell migration and provide a translational link (clinical measurement) which further provide opportunities for treatment. The aim of this study was to investigate the CCL7 levels profile in diabetic pregnant women with urinary incontinence during pregnancy over the first year postpartum. Methods: This study was conducted in the Perinatal Diabetes Research Center of the Botucatu Medical School/UNESP, and was approved by the Research Ethics Committee of the Institution (CAAE: 20639813.0.0000.5411). The diagnosis of GDM was established between 24th and 28th gestational weeks, by the 75 g-OGTT test according to ADA’s criteria. Urinary incontinence was defined according to the International Continence Society and the CCL7 levels was measured by ELISA (R&D Systems, Catalog Number DCC700). Two hundred twelve women were classified into four study groups: normoglycemic continent (NC), normoglycemic incontinent (NI), diabetic continent (DC) and diabetic incontinent (DI). They were evaluated at six-time-points: 12-18, 24-28 and 34-38 gestational weeks, 24-48 hours, 6 weeks and 6-12 months postpartum. Results: At 12-18 weeks, it was possible to consider only two groups, continent and incontinent, because at this early gestational period has not yet been the diagnosis of GDM. The group with GDM and UI (DI group) showed lower levels of CCL7 in all time points during pregnancy and postpartum, compared to normoglycemic groups (NC and NI), indicating that these women have not recovered from child birth induced UI during the 6-12 months postpartum compared to their controls, and that the progression of UI and/or lack of recovery throughout the first postpartum year can be related with lower levels of CCL7. Instead, serum CCL7 was significantly increased in the NC group. Taken together, these findings of overexpression of CCL7 in the NC group and decreased levels in the DI group, could confirm that diabetes delays the recovery from child birth induced UI, and that CCL7 could potentially be used as a serum marker of injury. Conclusion: This study demonstrates lower levels of CCL7 in the DI group during pregnancy and postpartum and suggests that the progression of UI in diabetic women and/or lack of recovery throughout the first postpartum year can be related with low levels of CCL7. This provides a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery. Successful controlled CCL7 mediated stem cell homing to the lower urinary tract could one day introduce the potential for non-operative treatment or prevention of stress urinary incontinence.

Keywords: CCL7, gestational diabetes, pregnancy, urinary incontinence

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Authors: Ananya Gupta, Sangeeta Bhaskar

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Mycobacterium indicus pranii (MIP) is a saprophytic mycobacterium. It is a predecessor of M. avium complex (MAC). Whole genome analysis and growth kinetics studies have placed MIP in between pathogenic and non-pathogenic species. It shares significant antigenic repertoire with M. tuberculosis and have unique immunomodulatory properties. MIP provides better protection than BCG against pulmonary tuberculosis in animal models. Immunization with MIP by aerosol route provides significantly higher protection as compared to immunization by subcutaneous (s.c.) route. However, mechanism behind differential protection has not been studied. In this study, using mice model we have evaluated and compared the M.tb specific immune response in lung compartments (airway lumen / lung interstitium) as well as spleen following MIP immunization via nasal (i.n.) and s.c. route. MIP i.n. vaccination resulted in increased seeding of memory T cells (CD4+ and CD8+ T-cells) in the airway lumen. Frequency of CD4+ T cells expressing Th1 migratory marker (CXCR3) and activation marker (CD69) were also high in airway lumen of MIP i.n. group. Significantly high ex vivo secretion of cytokines- IFN-, IL-12, IL-17 and TNF- from cells of airway luminal spaces provides evidence of antigen-specific lung immune response, besides generating systemic immunity comparable to MIP s.c. group. Analysis of T cell response on per cell basis revealed that antigen specific T-cells of MIP i.n. group were functionally superior as higher percentage of these cells simultaneously secreted IFN-gamma, IL-2 and TNF-alpha cytokines as compared to MIP s.c. group. T-cells secreting more than one of the cytokines simultaneously are believed to have robust effector response and crucial for protection, compared with single cytokine secreting T-cells. Adoptive transfer of airway luminal T-cells from MIP i.n. group into trachea of naive B6 mice revealed that MIP induced CD8 T-cells play crucial role in providing long term protection. Thus the study demonstrates that MIP intranasal vaccination induces M.tb specific memory T-cells in the airway lumen that results in an early and robust recall response against M.tb infection.

Keywords: airway lumen, Mycobacterium indicus pranii, Th1 migratory markers, vaccination

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Authors: Qing Liu, Jean-fabien Capsal, Claude Richard

Abstract:

In this current contribution, authors are dedicated to investigate influence of the crystal lamellae orientation on electromechanical behaviors of relaxor ferroelectric Poly (vinylidene fluoride –trifluoroethylene -chlorotrifluoroethylene) (P(VDF-TrFE-CTFE)) films by control of polymer microstructure, aiming to picture the full map of structure-property relationship. In order to define their crystal orientation films, terpolymer films were fabricated by solution-casting, stretching and hot-pressing process. Differential scanning calorimetry, impedance analyzer, and tensile strength techniques were employed to characterize crystallographic parameters, dielectric permittivity, and elastic Young’s modulus respectively. In addition, large electrical induced out-of-plane electrostrictive strain was obtained by cantilever beam mode. Consequently, as-casted pristine films exhibited surprisingly high electrostrictive strain 0.1774% due to considerably small value of elastic Young’s modulus although relatively low dielectric permittivity. Such reasons contributed to large mechanical elastic energy density. Instead, due to 2 folds increase of elastic Young’s modulus and less than 50% augmentation of dielectric constant, fully-crystallized film showed weak electrostrictive behavior and mechanical energy density as well. And subjected to mechanical stretching process, Film C exhibited stronger dielectric constant and out-performed electrostrictive strain over Film B because edge-on crystal lamellae orientation induced by uniaxially mechanical stretch. Hot-press films were compared in term of cooling rate. Rather large electrostrictive strain of 0.2788% for hot-pressed Film D in quenching process was observed although its dielectric permittivity equivalent to that of pristine as-casted Film A, showing highest mechanical elastic energy density value of 359.5 J/m^3. In hot-press cooling process, dielectric permittivity of Film E saw values at 48.8 concomitant with ca.100% increase of Young’s modulus. Films with intermediate mechanical energy density were obtained.

Keywords: crystal orientation, electrostroctive strain, mechanical energy density, permittivity, relaxor ferroelectric

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Authors: Simran Kaur, Paul J. Van Geel

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A coupled Thermal-Mechanical-Biological (TMB) model was developed for the analysis of impacts of temperatures on waste stabilization at a Municipal Solid Waste (MSW) landfill in Quebec, Canada using COMSOL Multiphysics, a finite element-based software. For waste placed in landfills in Northern climates during winter months, it can take months or even years before the waste approaches ideal temperatures for biodegradation to occur. Therefore, the proposed model links biodegradation induced strain in MSW to waste temperatures and corresponding heat generation rates as a result of anaerobic degradation. This provides a link between the thermal-biological and mechanical behavior of MSW. The thermal properties of MSW are further linked to density which is tracked and updated in the mechanical component of the model, providing a mechanical-thermal link. The settlement of MSW is modelled based on the concept of viscoelasticity. The specific viscoelastic model used is a single Kelvin – Voight viscoelastic body in which the finite element response is controlled by the elastic material parameters – Young’s Modulus and Poisson’s ratio. The numerical model was validated with 10 years of temperature and settlement data collected from a landfill in Ste. Sophie, Quebec. The coupled TMB modelling framework, which simulates placement of waste lifts as they are placed progressively in the landfill, allows for optimization of several thermal and mechanical parameters throughout the depth of the waste profile and helps in better understanding of temperature dependence of MSW stabilization. The model is able to illustrate how waste placed in the winter months can delay biodegradation-induced settlement and generation of landfill gas. A delay in waste stabilization will impact the utilization of the approved airspace prior to the placement of a final cover and impact post-closure maintenance. The model provides a valuable tool to assess different waste placement strategies in order to increase airspace utilization within landfills operating under different climates, in addition to understanding conditions for increased gas generation for recovery as a green and renewable energy source.

Keywords: coupled model, finite element modeling, landfill, municipal solid waste, waste stabilization

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Authors: Hossein Rassi, Marjan Moradi Fard, Samaneh Niko

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Human papillomavirus type 16 and 18 are closely associated with the development of human cervical carcinoma, which is one of the most common causes of cancer death in women worldwide. At present, HPV type 18 accounts for about 34 % of all HPV infections in Iran and the most promising vaccine against HPV infection is based on the L1 major capsid protein. The L1 protein of HPV18 has the capacity to self-assemble into capsomers or virus-like particles (VLPs) that are non-infectious, highly immunogenic and allowing their use in vaccine production. The methylotrophic yeast Pichia pastoris is an efficient and inexpensive expression system used to produce high levels of heterologous proteins. In this study we expressed HPV18 L1 VLPs in P. pastoris. The gene encoding the major capsid protein L1 of the high-risk HPV type 18 was isolated from Iranian patient by PCR and inserted into pTG19-T vector to obtain the recombinant expression vector pTG19-HPV18-L1. Then, the pTG19-HPV18-L1 was transformed into E. coli strain DH5α and the recombinant protein HPV18 L1 was expressed under IPTG induction in soluble form. The HPV18 L1 gene was excised from recombinant plasmid with XhoI and EcoRI enzymes and ligated into the yeast expression vector pPICZα linearized with the same enzymes, and transformed into P. pastoris. Induction and expression of HPV18 L1 protein was demonstrated by BMGY/BMMY and RT PCR. The parameters for induced cultivation for strain in P. pastoris KM71 with HPV16L1 were investigated in shaking flask cultures. After induced cultivation BMMY (pH 7.0) medium supplemented with methanol to a final concentration of 1.0% every 24 h at 37 degrees C for 96 h, the recombinant produced 78.6 mg/L of L1 protein. This work offers the possibility for the production of prophylactic vaccine for cervical carcinoma by P. pastoris for HPV-18 L1 gene. The VLP-based HPV vaccines can prevent persistent HPV18 infections and cervical cancer in Iran. The HPV-18 L1 gene was expressed successfully in E.coli, which provides necessary basis for preparing HPV-18 L1 vaccine in human. Also, HPV type 6 L1 proteins expressed in Pichia pastoris will facilitate the HPV vaccine development and structure-function study.

Keywords: Pichia pastoris, L1 virus-like particles, human papillomavirus type 18, biotechnology

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Authors: Janneth Gonzalez, Andrés Pinzon Velasco, Maria Angarita

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Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatorypathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, broad studies with a systemic point of view on the neurodegenerative role of PA and the neuro-protective mechanisms of tibolone are lacking. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also applied a control theory approach to identify those reactions that exert more control in the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a switch in energy source use through inhibition of folate cycle and fatty acid β‐oxidation and upregulation of ketone bodies formation. We found 25 metabolic switches under PA‐mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation of metabolic pathways that may increase neurotoxicity and represent potential treatment targets. Finally, the overall framework of our approach facilitates the understanding of complex metabolic regulation, and it can be used for in silico exploration of the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.

Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics

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Authors: Sebastian Töpfer, Marta Gilaberte Basset, Jorge Fuenzalida, Fabian Steinlechner, Juan P. Torres, Markus Gräfe

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This work introduces a combination of digital phase-shifting holography with a non-linear interferometer using undetected photons. Non-linear interferometers can be used in combination with a measurement scheme called quantum imaging with undetected photons, which allows for the separation of the wavelengths used for sampling an object and detecting it in the imaging sensor. This method recently faced increasing attention, as it allows to use of exotic wavelengths (e.g., mid-infrared, ultraviolet) for object interaction while at the same time keeping the detection in spectral areas with highly developed, comparable low-cost imaging sensors. The object information, including its transmission and phase influence, is recorded in the form of an interferometric pattern. To collect these, this work combines the method of quantum imaging with undetected photons with digital phase-shifting holography with a minimal sampling of the interference. With this, the quantum imaging scheme gets extended in its measurement capabilities and brings it one step closer to application. Quantum imaging with undetected photons uses correlated photons generated by spontaneous parametric down-conversion in a non-linear interferometer to create indistinguishable photon pairs, which leads to an effect called induced coherence without induced emission. Placing an object inside changes the interferometric pattern depending on the object’s properties. Digital phase-shifting holography records multiple images of the interference with determined phase shifts to reconstruct the complete interference shape, which can afterward be used to analyze the changes introduced by the object and conclude its properties. An extensive characterization of this method was done using a proof-of-principle setup. The measured spatial resolution, phase accuracy, and transmission accuracy are compared for different combinations of camera exposure times and the number of interference sampling steps. The current limits of this method are shown to allow further improvements. To summarize, this work presents an alternative holographic measurement method using non-linear interferometers in combination with quantum imaging to enable new ways of measuring and motivating continuing research.

Keywords: digital holography, quantum imaging, quantum holography, quantum metrology

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Authors: Gulnaz Khan, Meha F. Aftab, Munazza Murtaza, Rizwana S. Waraich

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Advanced glycation end products (AGEs) precursor and its abnormal accumulation cause damage to various tissues and organs. AGEs have pathogenic implication in several diseases including diabetes. Existing AGEs inhibitors are not in clinical use, and there is a need for development of novel inhibitors. The present investigation aimed at identifying the novel AGEs inhibitors and assessing their mechanism of action for treating insulin resistance in mice model of diabetes. Novel derivatives of benzylidene of indan-1,3-dione were synthesized. The compounds were selected to study their action mechanism in improving insulin resistance, in vitro, in human hepatocytes and murine adipocytes and then, in vivo, in mice genetic model of diabetes (db/db). Mice were treated with novel derivatives of benzylidene of indane 1,3-dione. AGEs mediated ROS production was measured by dihydroethidium fluorescence assay. AGEs level in the serum of treated mice was observed by ELISA. Gene expression of receptor for AGEs (RAGE), PPAR-gamma, TNF-alpha and GLUT-4 was evaluated by RT-PCR. Glucose uptake was measured by fluorescent method. Microscopy was used to analyze glycogen synthesis in muscle. Among several derivatives of benzylidene of indan-1,3-dione, IDD-24, demonstrated highest inhibition of AGESs. IDD-24 significantly reduced AGEs formation and expression of receptor for advanced glycation end products (RAGE) in fat, liver of db/db mice. Suppression of AGEs mediated ROS production was also observed in hepatocytes and fat cell, after treatment with IDD-24. Glycogen synthesis was increased in muscle tissue of mice treated with IDD-24. In adipocytes, IDD-24 prevented AGEs induced reduced glucose uptake. Mice treated with IDD-24 exhibited increased glucose tolerance, serum adiponectin levels and decreased insulin resistance. The result of present study suggested that IDD-24 can be a possible treatment target to address glycotoxins induced insulin resistance.

Keywords: advance glycation end product, hyperglycemia, indan-1, 3-dione, insulin resistance

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Authors: Homoud Bourisli, Haitham Safar

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Oil is one of main resources of energy in the world. As conventional oil is drying out, oil recovery is crucial to maintain the same level of oil production. Since water injection is one of the commonly used methods to increase and maintain pressure in oil wells, oil-water separation processes of the water associated with oil production for water injection oil recovery is very essential. Therefore, Gas Flotation Units are used for oil-water separation to be able to re-inject the treated water back into the wells to increase pressure.

Keywords: Kuwait oil company, dissolved gas flotation unit, induced gas flotation unit, oil-water separation

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Authors: Dugeree Otgongerel, Kyong Jin Cho, Yu-Han Kim, Sangmee Ahn Jo

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Excessive activation of glutamate receptor is thought to be involved in retinal ganglion cell (RGC) death after ischemia- reperfusion damage. Glutamate carboxypeptidase II (GCPII) is an enzyme responsible for the synthesis of glutamate. Several studies showed that inhibition of GCPII prevents or reduces cellular damage in brain diseases. Thus, in this study, we examined the expression of GCPII in rat retina and the role of GCPII in acute high IOP ischemia-reperfusion damage of eye by using a GCPII inhibitor, 2-(phosphonomethyl) pentanedioic acid (2-PMPA). Animal model of ischemia-reperfusion was induced by raising the intraocular pressure for 60 min and followed by reperfusion for 3 days. Rats were randomly divided into four groups: either intra-vitreous injection of 2-PMPA (11 or 110 ng per eye) or PBS after ischemia-reperfusion, 2-PMPA treatment without ischemia-reperfusion and sham-operated normal control. GCPII immunoreactivity in normal rat retina was detected weakly in retinal nerve fiber layer (RNFL) and retinal ganglionic cell layer (RGL) and also inner plexiform layer (IPL) and outer plexiform layer (OPL) strongly where are co-stained with an anti-GFAP antibody, suggesting that GCPII is expressed mostly in Muller and astrocytes. Immunostaining with anti-BRN antibody showed that ischemia- reperfusion caused RGC death (31.5 %) and decreased retinal thickness in all layers of damaged retina, but the treatment of 2-PMPA twice at 0 and 48 hour after reperfusion blocked these retinal damages. GCPII level in RNFL layer was enhanced after ischemia-reperfusion but was blocked by PMPA treatment. This result was confirmed by western blot analysis showing that the level of GCPII protein after ischemia- reperfusion increased by 2.2- fold compared to control, but this increase was blocked almost completely by 110 ng PMPA treatment. Interestingly, GFAP immunoreactivity in the retina after ischemia- reperfusion followed by treatment with PMPA showed similar pattern to GCPII, increase after ischemia-reperfusion but reduction to the normal level by PMPA treatment. Our data demonstrate that increase of GCPII protein level after ischemia-reperfusion injury is likely to cause glial activation and/or retinal cell death which are mediated by glutamate, and GCPII inhibitors may be useful in treatment of retinal disorders in which glutamate excitotoxicity is pathogenic.

Keywords: glutamate carboxypepptidase II, glutamate excitotoxicity, ischemia-reperfusion, retinal ganglion cell

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Authors: Y. Landkocz, C. Lepers, P.J. Martin, B. Fougère, F. Roy Saint-Georges. A. Verdin, F. Cazier, F. Ledoux, D. Courcot, F. Sichel, P. Gosset, P. Shirali, S. Billet

Abstract:

In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and fine particles as carcinogenic to humans. Causal relationships exist between elevated ambient levels of airborne particles and increase of mortality and morbidity including pulmonary diseases, like lung cancer. However, due to a double complexity of both physicochemical Particulate Matter (PM) properties and tumor mechanistic processes, mechanisms of action remain not fully elucidated. Furthermore, because of several common properties between air pollution PM and tobacco smoke, like the same route of exposure and chemical composition, potential mechanisms of synergy could exist. Therefore, smoking could be an aggravating factor of the particles toxicity. In order to identify some mechanisms of action of particles according to their size, two samples of PM were collected: PM0.03 2.5 and PM0.33 2.5 in the urban-industrial area of Dunkerque. The overall cytotoxicity of the fine particles was determined on human bronchial cells (BEAS-2B). Toxicological study focused then on the metabolic activation of the organic compounds coated onto PM and some genetic and epigenetic changes induced on a co-culture model of BEAS-2B and alveolar macrophages isolated from bronchoalveolar lavages performed in smokers and non-smokers. The results showed (i) the contribution of the ultrafine fraction of atmospheric particles to genotoxic (eg. DNA double-strand breaks) and epigenetic mechanisms (eg. promoter methylation) involved in tumor processes, and (ii) the influence of smoking on the cellular response. Three main conclusions can be discussed. First, our results showed the ability of the particles to induce deleterious effects potentially involved in the stages of initiation and promotion of carcinogenesis. The second conclusion is that smoking affects the nature of the induced genotoxic effects. Finally, the in vitro developed cell model, using bronchial epithelial cells and alveolar macrophages can take into account quite realistically, some of the existing cell interactions existing in the lung.

Keywords: air pollution, fine and ultrafine particles, genotoxic and epigenetic alterations, smoking

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Authors: A.N. Moulay Khatir, A. Guen-Bouazza, B. Bouazza

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SOI-Multifin-FET shows excellent transistor characteristics, ideal sub-threshold swing, low drain induced barrier lowering (DIBL) without pocket implantation and negligible body bias dependency. In this work, we analyzed this combination by a three-dimensional numerical device simulator to investigate the influence of fins number on corner effect by analyzing its electrical characteristics and potential distribution in the oxide and the silicon in the section perpendicular to the flow of the current for SOI-single-fin FET, three-fin and five-fin, and we provide a comparison with a Trigate SOI Multi-FinFET structure.

Keywords: SOI, FinFET, corner effect, dual-gate, tri-gate, Multi-Fin FET

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Authors: Michal Malik, Jiri Primas, Darina Jasikova, Michal Kotek, Vaclav Kopecky

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This paper is a case study dealing with the viability of using Electrical Impedance Tomography for measuring cavitation clouds in a pipe setup. The authors used a simple passive cavitation generator to cause a cavitation cloud, which was then recorded for multiple flow rates using electrodes in two measuring planes. The paper presents the results of the experiment, showing the used industrial grade tomography system ITS p2+ is able to measure the cavitation cloud and may be particularly useful for identifying the inception of cavitation in setups where other measuring tools may not be viable.

Keywords: cavitation cloud, conductivity measurement, electrical impedance tomography, mechanically induced cavitation

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Authors: Ludmila A. Gavriliuc, Jerry McLarty, Heather E. Kleiner, J. Michael Mathis

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Abstract -- Background: The citrus coumarine Auraptene (Aur) is an effective chemopreventive agent, as manifested in many models of diseases and cancer. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1, and peroxiredoxin 1, by activating the antioxidant response element (ARE). Genetic and biochemical evidence has demonstrated that glutathione (GSH) and glutathione-dependent enzymes, glutathione reductase (GR), glutathione peroxidases (GPs), glutathione S-transferases (GSTs) are responsible for the control of intracellular reduction-oxidation status and participate in cellular adaptation to oxidative stress. The effect of Aur on the activity of GR, GPs (Se-GP and Se-iGP), and content of GSH in the liver, kidney, and spleen is insufficiently explored. Aim: Our goal was the examination of the Aur influence on the redox-system of GSH in Nrf2 wild type and Nrf2 knockout mice via activation of Nrf2 and ARE. Methods: Twenty female mice, 10 Nrf2 wild-type (WT) and 10 Nrf2 (-/-) knockout (KO), were bred and genotyped for our study. The activity of GR, Se-GP, Se-iGP, GST, G6PD, CytP450 reductase, catalase (Cat), and content of GSH were analyzed in the liver, kidney, and spleen using Spectrophotometry methods. The results of the specific activity of enzymes and the amount of GSH were analyzed with ANOVA and Spearman statistical methods. Results: Aur (200 mg/kg) treatment induced hepatic GST, GR, Se-GP activity and inhibited their activity in the spleen of mice, most likely via activation of the ARE through Nrf2. Activation in kidney Se-GP and G6PD by Aur is also controlled, apparently through Nrf2. Results of the non-parametric Spearman correlation analysis indicated the strong positive correlation between GR and G6PD only in the liver in WT control mice (r=+0.972; p < 0.005) and in the kidney KO control mice (r=+0.958; p < 0.005). The observed low content of GSH in the liver of KO mice indicated an increase in its participation in the neutralization of toxic substances with the absence of induction of GSH-dependent enzymes, such as GST, GR, Se-GP, and Se-iGP. Activation of CytP450 in kidney and spleen and Cat in the liver in KO mice probably revealed another regulatory mechanism for these enzymes. Conclusion: Thereby, obtained results testify that Aur can modulate the activity of genes and antioxidant enzymatic redox-system of GSH, responsible for the control of intracellular reduction-oxidation status.

Keywords: auraptene, glutathione, GST, Nrf2

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Authors: I. V. Palamarchuk, N. V. Zaichko

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Background and Aims: Galectin-3 is a marker of subclinical cardiac injury and is elevated in individuals with type 2 diabetes mellitus; while hydrogen sulfide (H₂S), metabolite of sulfur-containing amino acids, is considered having antifibrogenic effects. This study was designed to investigate whether metformin and its combination with NaHS can influence plasma galectin-3 and cystathionine-γ-lyase/hydrogen sulfide (CSE/H₂S) system in diabetic rat’s heart. Methods: 32 healthy male rats (180-250 g) were divided into 4 groups. To induct diabetes, rats (group 2-4) were injected with streptozotocin (STZ, 40 mg/kg/i.p., 0.1 M citrate buffer (pH 4.5). Rats from 3d (STZ+Metf) and 4th (STZ+Metf+NaHS) groups were given metformin (500 mg/kg/day) orally, and rats from 4th (STZ+Metf+NaHS) group were injected sodium hydrosulfide (NaHS, 3 mg/kg/i.p.) once per day starting from 3 to 28 day after streptozotocin injection. Rats of first group (control) were administered the equivalent volumes of 0.9% NaCl. Plasma galectin-3 was measured by ELISA. Rats’ hearts were sampled for determination of H2S by reaction with N,N-Dimethyl-p-phenylenediamine. Determination of CSE gene expression was performed in real time using PCR in the presence of SYBR Green I, using DT-Light detecting amplifier ('DNA-technology', Russia). Results: Induction of streptozotocin diabetes (STZ-diabetes, group 2) was followed by low myocardial H2S concentration and CSE expression (by 35%, p < 0.05 and 60.5%, p < 0.001 respectively, than that in controls), while plasma galectin-3 in this group was significantly higher than in controls (by 3.8 times, p < 0.05). Administration of metformin (group 3) resulted in significantly higher H₂S concentration (by 28.5%, p < 0.05), whereas CSE expression was only by 6% more than that in STZ-diabetes, as well as plasma galectin-3 was only by 14.8% lower in comparison with untreated diabetic rats. The inhibition of H₂S generation and CSE activity by diabetes was greatly attenuated in STZ+Metf+NaHS group. The combination of metformin with NaHS significantly stimulated H₂S production (by 48%, p < 0.05 and 15%, p < 0.05 more than STZ-diabetes and STZ+Metf respectively) and CSE gene expression (by 64.8%, p < 0.05 compared to STZ-diabetes and by 55.4%,p < 0.05 compared to STZ+Metf). Besides, plasma galectin-3 in rats receiving metformin and NaHS was significantly lower by 42%, p < 0.05 and 32.5%, p < 0.05 compared to STZ-diabetes and STZ+Metf groups respectively. Conclusions: To summarize, dysfunction of CSE/H2S system and galectin-3 stimulation was found in streptozotocin-induced diabetic rats. Metformin and its combination with exogenous H2S effectively prevented the development of metabolic changes induced by diabetes. These findings suggest that CSE/H₂S system can be integrated into pathogenesis of diabetic complications through modulation of pro-inflammatory and pro-fibrogenic mediator galectin-3.

Keywords: cystathionine-γ-lyase, diabetic heart, galectin-3, hydrogen sulfide, metformin, sodium hydrosulfide

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Authors: Mina Iskander, Mina Melad, Mourad Yasser, Waleed Abdel Rahim, Amr Mosa, Mohamed El Lahamy, Ezzeldin Sayed-Ahmed, Mohamed Abou-Zeid

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Strengthening of reinforced concrete beams in flexure using externally bonded composite laminate of high tensile strength is easy and of the minimum cost compared to traditional methods such as increasing the concrete section depth or reinforcement that requires formwork and curing which affect the structure usability. One of the main limitations of this technique is debonding of the externally bonded laminate, either by end delamination or by mid-span flexural crack-induced debonding. ACI 440.2-08 suggests that using side-bonded FRP laminate in the flexural strengthening of RC beams may serve to limit the extent and width of flexural cracks. Consequently, this technique may decrease the effect of flexural cracks on initiating the mid-span debonding; i.e. delays the flexural crack-induced debonding. Furthermore, bonding the FRP strips to the side of the beam may offer an attractive, practical solution when the soffit of this beam is not accessible. This paper presents an experimental programme designed to investigate the effect of using externally bonded CFRP laminate on the sides of reinforced concrete beams and compares the results to those of bonding the CFRP laminate to the soffit of the beams. In addition, the paper discusses the effect of using end anchorage by U-wrapping the CFRP strips at their end zones with CFRP sheets for beams strengthened with soffit-bonded and side-bonded CFRP strips. Thus, ten rectangular reinforced concrete beams were tested to failure in order to study the effect of changing the location of the externally bonded laminate on the flexural capacity and ductility of the strengthened beams. Pultruded CFRP strips were bonded to the soffit of the beams or their sides to check the possibility of limiting the flexural cracking in mid-span region, which is the main reason for mid-span debonding. Pre-peg CFRP sheets were used near the support as U-wrap for the beam to act as an end-anchorage for the externally bonded strips in order to delay/prevent the end delamination. Strength gains of 38% and 43% were recorded for the soffit-bonded and the side-bonded composite strips with end U-wrapped sheets, respectively. Furthermore, beams with end sheets applied as an end anchorage showed higher ductility than those without these sheets.

Keywords: flexural strengthening, externally bonded CFRP, side-bonded CFRP, CFRP laminates

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Authors: Rong Li, Brian D. Wirth, Bing Liu

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Graphite is the matrix, and structural material in the high temperature gas-cooled reactor exhibits an irradiation response. It is of significant importance to analyze the defect production and evaluate the role of graphite under irradiation. A vast experimental literature exists for graphite on the dimensional change, mechanical properties, and thermal behavior. However, simulations have not been applied to the atomistic perspective. Remarkably few molecular dynamics simulations have been performed to study the irradiation response in graphite. In this paper, irradiation-induced damage cascades in graphite were investigated with molecular dynamics simulation. Statistical results of the graphite defects were obtained by sampling a wide energy range (1–30 KeV) and 10 different runs for every cascade simulation with different random number generator seeds to the velocity scaling thermostat function. The chemical bonding in carbon was described using the adaptive intermolecular reactive empirical bond-order potential (AIREBO) potential coupled with the standard Ziegler–Biersack–Littmack (ZBL) potential to describe close-range pair interactions. This study focused on analyzing the number of defects, the final cascade morphology and the distribution of defect clusters in space, the length-scale cascade properties such as the cascade length and the range of primary knock-on atom (PKA), and graphite mechanical properties’ variation. It can be concluded that the number of surviving Frenkel pairs increased remarkably with the increasing initial PKA energy but did not exhibit a thermal spike at slightly lower energies in this paper. The PKA range and cascade length approximately linearly with energy which indicated that increasing the PKA initial energy will come at expensive computation cost such as 30KeV in this study. The cascade morphology and the distribution of defect clusters in space mainly related to the PKA energy meanwhile the temperature effect was relatively negligible. The simulations are in agreement with known experimental results and the Kinchin-Pease model, which can help to understand the graphite damage cascades and lifetime span under irradiation and provide a direction to the designs of these kinds of structural materials in the future reactors.

Keywords: graphite damage cascade, molecular dynamics, cascade morphology, cascade distribution

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Authors: Mohammad Daud Ali

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For the past decade, marketing ethics has been a central point for academic researchers and practitioners. In particular, the development of frameworks and models to help in the analysis of marketing decisions are the focus of research. The current study aims at finding whether ethical decisions (honesty, fairness, responsibility, and respect) affect organizational marketing decisions. A selection of 250 respondents was purposely made from the telecommunication industry of Pakistan, out of which 204 responses were induced at an acceptable rate of 81.6%. A five-point Likert Scale, itemized with 12 items, was adopted from Taylor-Dunlop & Lester (2000) and used to draw responses regarding ethics.

Keywords: marketing, ethics, decisions making, telecommunication, Pakistan

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