Search results for: vortex induced vibration
Commenced in January 2007
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Paper Count: 3554

Search results for: vortex induced vibration

494 Physics-Informed Neural Network for Predicting Strain Demand in Inelastic Pipes under Ground Movement with Geometric and Soil Resistance Nonlinearities

Authors: Pouya Taraghi, Yong Li, Nader Yoosef-Ghodsi, Muntaseer Kainat, Samer Adeeb

Abstract:

Buried pipelines play a crucial role in the transportation of energy products such as oil, gas, and various chemical fluids, ensuring their efficient and safe distribution. However, these pipelines are often susceptible to ground movements caused by geohazards like landslides, fault movements, lateral spreading, and more. Such ground movements can lead to strain-induced failures in pipes, resulting in leaks or explosions, leading to fires, financial losses, environmental contamination, and even loss of human life. Therefore, it is essential to study how buried pipelines respond when traversing geohazard-prone areas to assess the potential impact of ground movement on pipeline design. As such, this study introduces an approach called the Physics-Informed Neural Network (PINN) to predict the strain demand in inelastic pipes subjected to permanent ground displacement (PGD). This method uses a deep learning framework that does not require training data and makes it feasible to consider more realistic assumptions regarding existing nonlinearities. It leverages the underlying physics described by differential equations to approximate the solution. The study analyzes various scenarios involving different geohazard types, PGD values, and crossing angles, comparing the predictions with results obtained from finite element methods. The findings demonstrate a good agreement between the results of the proposed method and the finite element method, highlighting its potential as a simulation-free, data-free, and meshless alternative. This study paves the way for further advancements, such as the simulation-free reliability assessment of pipes subjected to PGD, as part of ongoing research that leverages the proposed method.

Keywords: strain demand, inelastic pipe, permanent ground displacement, machine learning, physics-informed neural network

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493 Role of Autophagic Lysosome Reformation for Cell Viability in an in vitro Infection Model

Authors: Muhammad Awais Afzal, Lorena Tuchscherr De Hauschopp, Christian Hübner

Abstract:

Introduction: Autophagy is an evolutionarily conserved lysosome-dependent degradation pathway, which can be induced by extrinsic and intrinsic stressors in living systems to adapt to fluctuating environmental conditions. In the context of inflammatory stress, autophagy contributes to the elimination of invading pathogens, the regulation of innate and adaptive immune mechanisms, and regulation of inflammasome activity as well as tissue damage repair. Lysosomes can be recycled from autolysosomes by the process of autophagic lysosome reformation (ALR), which depends on the presence of several proteins including Spatacsin. Thus ALR contributes to the replenishment of lysosomes that are available for fusion with autophagosomes in situations of increased autophagic turnover, e.g., during bacterial infections, inflammatory stress or sepsis. Objectives: We aimed to assess whether ALR plays a role for cell survival in an in-vitro bacterial infection model. Methods: Mouse embryonic fibroblasts (MEFs) were isolated from wild-type mice and Spatacsin (Spg11-/-) knockout mice. Wild-type MEFs and Spg11-/- MEFs were infected with Staphylococcus aureus (multiplication of infection (MOI) used was 10). After 8 and 16 hours of infection, cell viability was assessed on BD flow cytometer through propidium iodide intake. Bacterial intake by cells was also calculated by plating cell lysates on blood agar plates. Results: in-vitro infection of MEFs with Staphylococcus aureus showed a marked decrease of cell viability in ALR deficient Spatacsin knockout (Spg11-/-) MEFs after 16 hours of infection as compared to wild-type MEFs (n=3 independent experiments; p < 0.0001) although no difference was observed for bacterial intake by both genotypes. Conclusion: Suggesting that ALR is important for the defense of invading pathogens e.g. S. aureus, we observed a marked increase of cell death in an in-vitro infection model in cells with compromised ALR.

Keywords: autophagy, autophagic lysosome reformation, bacterial infections, Staphylococcus aureus

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492 Malignant Ovarian Cancer Ascites Confers Platinum Chemoresistance to Ovarian Cancer Cells: A Combination Treatment with Crizotinib and 2 Hydroxyestradiol Restore Platinum Sensitivity

Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna

Abstract:

Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.

Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib

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491 Ph-Triggered Cationic Solid Lipid Nanoparticles Mitigated Colitis in Mice

Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

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In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

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490 Raising Antibodies against Epoxyscillirosidine, the Toxic Principle Contained in Moraea pallida Bak. in Rabbits

Authors: Hamza I. Isa, Gezina C. H. Ferreira, Jan E. Crafford, Christoffel J. Botha

Abstract:

Moraea pallida Bak. (yellow tulip) poisoning is the most important plant-induced cardiac glycoside toxicosis in South Africa. Cardiac glycoside poisonings collectively account for about 33 and 10 % mortalities due to plants, in large and small stock respectively, in South Africa. The toxic principle is 1α, 2α-epoxyscillirosidine, a bufadienolide. The aim of the study was to investigate the potential to develop a vaccine against epoxyscillirosidine. Epoxyscillirosidine and the related bufadienolides proscillaridin and bufalin, which are commercially available, were conjugated to the carrier proteins [Hen ovalbumin (OVA), bovine serum albumin (BSA) and keyhole limpet haemocyanin (KLH)], rendering them immunogenic. Adult male New Zealand White rabbits were immunized. In Trials 1 and 2, rabbits (n=6) were, each assigned to two groups. Experimental animals (n=3; n=4) were vaccinated with epoxyscillirosidine-OVA conjugate, while the control (n=3; n=2) were vaccinated with OVA, using Freund’s complete and incomplete and Montanide adjuvants, for Trials 1 and 2, respectively. In Trial 3, rabbits (n=15), randomly allocated to 5 equal groups (I, II, III, IV and V), were vaccinated with proscillaridin-BSA, bufalin-BSA, epoxyscillirosidine-KLH, epoxyscillirosidine-BSA conjugates, and BSA respectively, using Montanide as adjuvant. Vaccination was on Days 0, 21 and 42. Additional vaccinations were done on Day 56 and 63 for Trial 1. Vaccination was by intradermal injection of 0.4 ml of the immunogen (4 mg/ml [Trial 1] and 8 mg/ml for Trials 2 and Trial 3, respectively). Blood was collected pre-vaccination and at 3 week intervals following each vaccination. Antibody response was determined using an indirect ELISA. There was poor immune response associated with the dose (0.4 mg per rabbit) and adjuvant used in Trial 1. Antibodies were synthesized against the conjugate administered in Trial 2. For Trail 3, antibodies against the immunogens were successfully raised in rabbits with epoxyscillirosidine-KLH inducing the highest immune response. The antibodies raised against proscillaridin and bufalin cross-reacted with epoxyscillirosidine when used as antigen in the ELISA. The study successfully demonstrated the synthesis of antibodies against the bufadienolide conjugates administered. The cross-reactivity of proscillaridin and bufalin with epoxyscillirosidine could potentially be utilized as alternative to epoxyscillirosidine in future studies to prevent yellow tulp poisoning by vaccination.

Keywords: antibodies , bufadienolides, cross-reactivity, epoxyscillirosidine, Moraea pallida, poisoning

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489 Fly-Ash/Borosilicate Glass Based Geopolymers: A Mechanical and Microstructural Investigation

Authors: Gianmarco Taveri, Ivo Dlouhy

Abstract:

Geopolymers are well-suited materials to abate CO2 emission coming from the Portland cement production, and then replace them, in the near future, in building and other applications. The cost of production of geopolymers may be seen the only weakness, but the use of wastes as raw materials could provide a valid solution to this problem, as demonstrated by the successful incorporation of fly-ash, a by-product of thermal power plants, and waste glasses. Recycled glass in waste-derived geopolymers was lately employed as a further silica source. In this work we present, for the first time, the introduction of recycled borosilicate glass (BSG). BSG is actually a waste glass, since it derives from dismantled pharmaceutical vials and cannot be reused in the manufacturing of the original articles. Owing to the specific chemical composition (BSG is an ‘alumino-boro-silicate’), it was conceived to provide the key components of zeolitic networks, such as amorphous silica and alumina, as well as boria (B2O3), which may replace Al2O3 and contribute to the polycondensation process. The solid–state MAS NMR spectroscopy was used to assess the extent of boron oxide incorporation in the structure of geopolymers, and to define the degree of networking. FTIR spectroscopy was utilized to define the degree of polymerization and to detect boron bond vibration into the structure. Mechanical performance was tested by means of 3 point bending (flexural strength), chevron notch test (fracture toughness), compression test (compressive strength), micro-indentation test (Vicker’s hardness). Spectroscopy (SEM and Confocal spectroscopy) was performed on the specimens conducted to failure. FTIR showed a characteristic absorption band attributed to the stretching modes of tetrahedral boron ions, whose tetrahedral configuration is compatible to the reaction product of geopolymerization. 27Al NMR and 29Si NMR spectra were instrumental in understanding the extent of the reaction. 11B NMR spectroscopies evidenced a change of the trigonal boron (BO3) inside the BSG in favor of a quasi-total tetrahedral boron configuration (BO4). Thanks to these results, it was inferred that boron is part of the geopolymeric structure, replacing the Si in the network, similarly to the aluminum, and therefore improving the quality of the microstructure, in favor of a more cross-linked network. As expected, the material gained as much as 25% in compressive strength (45 MPa) compared to the literature, whereas no improvements were detected in flexural strength (~ 5 MPa) and superficial hardness (~ 78 HV). The material also exhibited a low fracture toughness (0.35 MPa*m1/2), with a tangible brittleness. SEM micrographies corroborated this behavior, showing a ragged surface, along with several cracks, due to the high presence of porosity and impurities, acting as preferential points for crack initiation. The 3D pattern of the surface fracture, following the confocal spectroscopy, evidenced an irregular crack propagation, whose proclivity was mainly, but not always, to follow the porosity. Hence, the crack initiation and propagation are largely unpredictable.

Keywords: borosilicate glass, characterization, fly-ash, geopolymerization

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488 Evaluation of Natural Frequency of Single and Grouped Helical Piles

Authors: Maryam Shahbazi, Amy B. Cerato

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The importance of a systems’ natural frequency (fn) emerges when the vibration force frequency is equivalent to foundation's fn which causes response amplitude (resonance) that may cause irreversible damage to the structure. Several factors such as pile geometry (e.g., length and diameter), soil density, load magnitude, pile condition, and physical structure affect the fn of a soil-pile system; some of these parameters are evaluated in this study. Although experimental and analytical studies have assessed the fn of a soil-pile system, few have included individual and grouped helical piles. Thus, the current study aims to provide quantitative data on dynamic characteristics of helical pile-soil systems from full-scale shake table tests that will allow engineers to predict more realistic dynamic response under motions with variable frequency ranges. To evaluate the fn of single and grouped helical piles in dry dense sand, full-scale shake table tests were conducted in a laminar box (6.7 m x 3.0 m with 4.6 m high). Two different diameters (8.8 cm and 14 cm) helical piles were embedded in the soil box with corresponding lengths of 3.66m (excluding one pile with length of 3.96) and 4.27m. Different configurations were implemented to evaluate conditions such as fixed and pinned connections. In the group configuration, all four piles with similar geometry were tied together. Simulated real earthquake motions, in addition to white noise, were applied to evaluate the wide range of soil-pile system behavior. The Fast Fourier Transform (FFT) of measured time history responses using installed strain gages and accelerometers were used to evaluate fn. Both time-history records using accelerometer or strain gages were found to be acceptable for calculating fn. In this study, the existence of a pile reduced the fn of the soil slightly. Greater fn occurred on single piles with larger l/d ratios (higher slenderness ratio). Also, regardless of the connection type, the more slender pile group which is obviously surrounded by more soil, yielded higher natural frequencies under white noise, which may be due to exhibiting more passive soil resistance around it. Relatively speaking, within both pile groups, a pinned connection led to a lower fn than a fixed connection (e.g., for the same pile group the fn’s are 5.23Hz and 4.65Hz for fixed and pinned connections, respectively). Generally speaking, a stronger motion causes nonlinear behavior and degrades stiffness which reduces a pile’s fn; even more, reduction occurs in soil with a lower density. Moreover, fn of dense sand under white noise signal was obtained 5.03 which is reduced by 44% when an earthquake with the acceleration of 0.5g was applied. By knowing the factors affecting fn, the designer can effectively match the properties of the soil to a type of pile and structure to attempt to avoid resonance. The quantitative results in this study assist engineers in predicting a probable range of fn for helical pile foundations under potential future earthquake, and machine loading applied forces.

Keywords: helical pile, natural frequency, pile group, shake table, stiffness

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487 Oxidative Dehydrogenation and Hydrogenation of Malic Acid over Transition Metal Oxides

Authors: Gheorghiţa Mitran, Adriana Urdă, Mihaela Florea, Octavian Dumitru Pavel, Florentina Neaţu

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Oxidative dehydrogenation and hydrogenation reactions of L-malic acid are interesting ways for its transformation into valuable products, including oxaloacetic, pyruvic and malonic acids but also 1,4-butanediol and 1,2,4-butanetriol. Keto acids have a range of applicationsin many chemical syntheses as pharmaceuticals, food additives and cosmetics. 3-Hydroxybutyrolactone and 1,2,4-butanetriol are used for the synthesis of chiral pharmaceuticals and other fine chemicals, while 1,4-butanediol can be used for organic syntheses, such as polybutylene succinate (PBS), polybutylene terephthalate (PBT), and for production of tetrahydrofuran (THF). L-malic acid is a non-toxic and natural organic acid present in fruits, and it is the main component of wine alongside tartaric acid representing about 90% of the wine total acidity. Iron oxides dopped with cobalt (CoxFe3-xO4; x= 0; 0.05; 0.1; 0.15) were studied as catalysts in these reactions. There is no mention in the literature of non-noble transition metal catalysts for these reactions. The method used for catalysts preparation was coprecipitation, whileBET XRD, XPS, FTIR and UV-VIS spectroscopy were used for the physicochemical properties evaluation.TheXRD patterns revealed the presence of α-Fe2O3 rhombohedral hematite structure, with cobalt atoms well dispersed and embedded in this structure. The studied samples are highly crystalline, with a crystallite size ranged from 58 to 65 nm. The optical absorption properties were investigated using UV-Vis spectroscopy, emphasizing the presence of bands that correspond with the reported hematite nanoparticle. Likewise, the presence of bands corresponding to lattice vibration of hexagonal hematite structurehas been evidenced in DRIFT spectra. Oxidative dehydrogenation of malic acid was studied using as solvents for malic acid ethanol or water(2, 5 and 10% malic acid in 5 mL solvent)at room temperature, while the hydrogenation reaction was evaluated in water as solvent (5%), in the presence of 1% catalyst. The oxidation of malic acid into oxaloacetic acid is the first step, after that, oxaloacetic acid is rapidly decarboxylated to malonic acid or pyruvic acid, depending on the active site. The concentration of malic acid in solution, it, in turn, has an influence on conversionthis decreases when the concentration of malic acid in the solution is high. The spent catalysts after the oxidative dehydrogenation of malic acid in ethanol were characterized by DRIFT spectroscopy and the presence of oxaloacetic, pyruvic and malonicacids, along with unreacted malic acidwere observed on the surface. The increase of the ratio of Co/Fe on the surface has an influence on the malic acid conversion and on the pyruvic acid yield, while the yield of malonic acid is influenced by the percentage of iron on the surface (determined from XPS). Oxaloacetic acid yield reaches a maximumat one hour of reaction, being higher when ethanol is used as a solvent, after which it suddenly decreases. The hydrogenation of malic acid occurs by consecutive reactions with the production of 3-hydroxy-butyrolactone, 1,2,4-butanetriol and 1,4-butanediol. Malic acid conversion increases with cobalt loading increasing up to Co/Fe ratio of 0.1, after which it has a slight decrease, while the yield in 1,4-butanediol is directly proportional to the cobalt content.

Keywords: malic acid, oxidative dehydrogenation, hydrogenation, oxaloacetic acid

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486 Lung Icams and Vcam-1 in Innate and Adaptive Immunity to Influenza Infections: Implications for Vaccination Strategies

Authors: S. Kozlovski, S.W. Feigelson, R. Alon

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The b2 integrin ligands ICAM-1 ICAM-2 and the endothelial VLA-4 integrin ligand VCAM-1 are constitutively expressed on different lung vessels and on high endothelial venules (HEVs), the main portal for lymphocyte entry from the blood into lung draining lymph nodes. ICAMs are also ubiquitously expressed by many antigen-presenting leukocytes and have been traditionally suggested as critical for the various antigen-specific immune synapses generated by these distinct leukocytes and specific naïve and effector T cells. Loss of both ICAM-1 and ICAM-2 on the lung vasculature reduces the ability to patrol monocytes and Tregs to patrol the lung vasculature at a steady state. Our new findings suggest, however, that in terms of innate leukocyte trafficking into the lung lamina propria, both constitutively expressed and virus-induced vascular VCAM-1 can functionally compensate for the loss of these ICAMs. In a mouse model for influenza infection, neutrophil and NK cell recruitment and clearance of influenza remained normal in mice deficient in both ICAMs. Strikingly, mice deficient in both ICAMs also mounted normal influenza-specific CD8 proliferation and differentiation. In addition, these mice normally combated secondary influenza infection, indicating that the presence of ICAMs on conventional dendritic cells (cDCs) that present viral antigens are not required for immune synapse formation between these APCs and naïve CD8 T cells as previously suggested. Furthermore, long-lasting humoral responses critical for protection from a secondary homosubtypic influenza infection were also normal in mice deficient in both ICAM-1 and ICAM-2. Collectively, our results suggest that the expression of ICAM-1 and ICAM-2 on lung endothelial and epithelial cells, as well as on DCs and B cells, is not critical for the generation of innate or adaptive anti-viral immunity in the lungs. Our findings also suggest that endothelial VCAM-1 can substitute for the functions of vascular ICAMs in leukocyte trafficking into various lung compartments.

Keywords: emigration, ICAM-1, lymph nodes, VCAM-1

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485 Tale of Massive Distressed Migration from Rural to Urban Areas: A Study of Mumbai City

Authors: Vidya Yadav

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Migration is the demographic process that links rural to urban areas, generating or spurring the growth of cities. Evidence shows the role of the city as a production processes. It looks the city as a power of centre, and a centre of change. It has been observed that not only the professionals want to settle down in an urban area but rural labourers are also coming to cities for employment. These are the people who are compelled to migrate to metropolises because of lack of employment opportunities in their place of residence. However, the cities also fail to provide adequate employment because of limited job opportunity creation and capital-intensive industrialization. So these masses of incoming migrants are force to take up whatever employment absorption is available to them particularly in urban informal activities. Ultimately with this informal job they are compelled to stay in the slum areas, which is another form of deprived housing colonies. The paper seeks to examine the evidences of poverty induced migration from rural to urban areas (particularly in urban agglomeration). The present paper utilizes an abundant rich source of census migration data (D-Series) of 1991-2001. Result shows that Mumbai remain as the most attractive place to migrate. The migrants are mainly from the major states like Uttar Pradesh, Bihar, West Bengal, Jharkhand, Odisha, and Rajasthan. Male dominated migration is related mostly for employment and females due to marriages. The picture of occupational absorption of migrants who moved for employment, cross classified with educational status. Result shows that illiterate males are primarily engaged in low grade production processing work. Illiterate’s females engaged in service sectors; but these are actually very low grade services in urban informal sectors in India like maid servants, domestic help, hawkers, vendors or vegetables sellers. Among the higher educational level, a small percentage of males and females got absorbed in professional or clerical work but the percentage has been increased in the period 1991-2001.

Keywords: informal, job, migration, urban

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484 Hepatoprotective and Immunostimulative Properties of Medicinal Plants against Tuberculosis

Authors: Anna-Mari Kok, Carel B. Oosthuizen, Namrita Lall

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Tuberculosis (TB) is a disease caused by the bacterial pathogen Mycobacterium tuberculosis. It is associated with high mortality rates in both developing and developed countries. Many higher plants are found that are medicinally associated with tuberculosis infection. Plants belonging to thirteen families were selected, based on their traditional usage for tuberculosis and its associated symptoms. Eight plants showed the best antimycobacterial activities (MIC-value ≤ 500.0 µg/ml) against M. tuberculosis H37Rv. LS was found to have a minimum inhibitory concentration (MIC) of 125 µg/ml whereas, Tulbaghia violacea, Heteromorpha arborescens, Sutherlandia frutescens, Eucalyptus deglupta, and Plectranthus neochilus were found to have a MIC value of 250 µg/ml against M. tuberculosis H37Rv. Cytotoxicity values on U937 and HepG2 cells were obtained and the IC50 values ranged between 40 ±4.30 and > 400 µg/ml for the U937 cell line and 72.4 ±1.50 and > 400 µg/ml for the HepG2 cell line. Heteromorpha arborescens had the lowest IC50 value in both cell lines and therefore showed moderate levels of toxicity. Of the 19 samples that underwent the 2, 2- diphenyl- 1- picrylhydrazyl (DPPH) antioxidant assay, Eucalyptus deglupta and Melianthus major showed significant free radical scavenging activities with concentrations of 1.33 and 1.32 µg/ml respectively for the inhibition of DPPH. Hepatotoxicity induced by acetaminophen identified Searsia lancea with hepatoprotective activity of 59.37% at a ¼ IC50 concentration. Out of the 7 samples that were investigated for their immunomodulatory capabilities, Eucalyptus deglupta produced the most IL-12 with Sutherlandia frutescens also showing positive results for IL-12 production. In the present study, Eucalyptus deglupta showed the most promising results with good activity against M. tuberculosis with an MIC-value of 250 µg/ml. It also has potent antioxidant activity with an IC50 value of 1.33 µg/ml. This sample also stimulated high production of the cytokine, IL-12. Searsia lancea showed moderate antimycobacterial acticvity with an MIC-value of 500 µg/ml. The antioxidant potential also showed promising results with an IC50 value of 4.50 µg/ml. The hepatoprotective capability of Searsia lancea was 59.34% at a ¼ IC50 concentration. Another sample Sutherlandia frutescens showed effective antimycobacterial activity with an MIC-value of 250 µg/ml. It also stimulated production of IL-12 with 13.43 pg/ml produced. These three samples can be considered for further studies for the consideration as adjuvants for current tuberculosis treatment.

Keywords: adjuvant, hepatoprotection, immunomodulation, tuberculosis

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483 The Use of Orthodontic Pacifiers to Prevent Pacifier Induced Malocclusion - A Literature Review

Authors: Maliha Ahmed Suleman, Sidra Ahmed Suleman

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Introduction: The use of pacifiers is common amongst infants and young children as a comforting behavior. These non-nutritive sucking habits can be detrimental to the developing occlusion should they persist while the permanent dentition is established. Orthodontic pacifiers have been recommended as an alternative to conventional pacifiers as they are considered to have less interference with orofacial development. However, there is a lack of consensus on whether this is true. Aim and objectives: To review the prevalence of malocclusion associated with the use of orthodontic pacifiers. Methodology: Literature was identified through a rigorous search of the Embase, Pubmed, CINAHL, and Cochrane Library databases. Articles published from 2000 onwards were included. In total, 5 suitable papers were identified. Results: One study showed that the use of orthodontic pacifiers increased the risk of malocclusion, as seen through a greater prevalence of accentuated overjet, posterior crossbites, and anterior open bites in comparison to individuals who did not use pacifiers. However, this study found that there was a clinically significant reduction in the prevalence of anterior open bites amongst orthodontic pacifier users in comparison to conventional pacifier users. Another study found that both types of pacifiers lead to malocclusion; however, they found no difference in the mean overjet and prevalence of anterior open bites amongst conventional and orthodontic pacifier users. In contrast, one study suggested that orthodontic pacifiers do not seem to be related to the development of malocclusions in the primary dentitions, and using them between the ages of 0-3 months was actually beneficial as it prevents thumb-sucking habits. One of the systemic reviews concluded that orthodontic pacifiers do not seem to reduce the occurrence of posterior crossbites; however, they could reduce the development of open bites by virtue of their thin neck design. Whereas another systematic review concluded that there were no differences as to the effects on the stomatognathic system when comparing conventional and orthodontic pacifiers. Conclusion: There is limited and conflicting evidence to support the notion that orthodontic pacifiers can reduce the prevalence of malocclusion when compared to conventional pacifiers. Well-designed randomized controlled trials are required in the future in order to thoroughly assess the effects of orthodontic pacifiers on the developing occlusion and orofacial structures.

Keywords: orthodontics, pacifier, malocclusion, review

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482 An Attenuated Quadruple Gene Mutant of Mycobacterium tuberculosis Imparts Protection against Tuberculosis in Guinea Pigs

Authors: Shubhita Mathur, Ritika Kar Bahal, Priyanka Chauhan, Anil K. Tyagi

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Mycobacterium tuberculosis, the causative agent of human tuberculosis, is a major cause of mortality. Bacillus Calmette-Guérin (BCG), the only licensed vaccine available for protection against tuberculosis confers highly variable protection ranging from 0%-80%. Thus, novel vaccine strains need to be evaluated for their potential as a vaccine against tuberculosis. We had previously constructed a triple gene mutant of M. tuberculosis (MtbΔmms), having deletions in genes encoding for phosphatases mptpA, mptpB, and sapM that are involved in host-pathogen interaction. Though vaccination with Mtb∆mms strain induced protection in the lungs of guinea pigs, the mutant strain was not able to control the hematogenous spread of the challenge strain to the spleens. Additionally, inoculation with Mtb∆mms resulted in some pathological damage to the spleens in the early phase of infection. In order to overcome the pathology caused by MtbΔmms in the spleens of guinea pigs and also to control the dissemination of the challenge strain, MtbΔmms was genetically modified by disrupting bioA gene to generate MtbΔmmsb strain. Further, in vivo attenuation of MtbΔmmsb was evaluated, and its protective efficacy was assessed against virulent M. tuberculosis challenge in guinea pigs. Our study demonstrates that Mtb∆mmsb mutant was highly attenuated for growth and virulence in guinea pigs. Vaccination with Mtb∆mmsb mutant generated significant protection in comparison to sham-immunized animals at 4 and 12 weeks post-infection in lungs and spleens of the infected animals. Our findings provide evidence that deletion of genes involved in signal transduction and biotin biosynthesis severely attenuates the pathogen and the single immunization with the auxotroph was able to provide significant protection as compared to sham-immunized animals. The protection imparted by Mtb∆mmsb fell short in comparison to the protection observed in BCG-immunized animals. This study nevertheless indicates the importance of attenuated multiple gene deletion mutants of M. tuberculosis in generating protection against tuberculosis.

Keywords: Mycobacterium tuberculosis, BCG, MtbΔmmsb, bioA, guinea pigs

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481 Bayesian Networks Scoping the Climate Change Impact on Winter Wheat Freezing Injury Disasters in Hebei Province, China

Authors: Xiping Wang,Shuran Yao, Liqin Dai

Abstract:

Many studies report the winter is getting warmer and the minimum air temperature is obviously rising as the important climate warming evidences. The exacerbated air temperature fluctuation tending to bring more severe weather variation is another important consequence of recent climate change which induced more disasters to crop growth in quite a certain regions. Hebei Province is an important winter wheat growing province in North of China that recently endures more winter freezing injury influencing the local winter wheat crop management. A winter wheat freezing injury assessment Bayesian Network framework was established for the objectives of estimating, assessing and predicting winter wheat freezing disasters in Hebei Province. In this framework, the freezing disasters was classified as three severity degrees (SI) among all the three types of freezing, i.e., freezing caused by severe cold in anytime in the winter, long extremely cold duration in the winter and freeze-after-thaw in early season after winter. The factors influencing winter wheat freezing SI include time of freezing occurrence, growth status of seedlings, soil moisture, winter wheat variety, the longitude of target region and, the most variable climate factors. The climate factors included in this framework are daily mean and range of air temperature, extreme minimum temperature and number of days during a severe cold weather process, the number of days with the temperature lower than the critical temperature values, accumulated negative temperature in a potential freezing event. The Bayesian Network model was evaluated using actual weather data and crop records at selected sites in Hebei Province using real data. With the multi-stage influences from the various factors, the forecast and assessment of the event-based target variables, freezing injury occurrence and its damage to winter wheat production, were shown better scoped by Bayesian Network model.

Keywords: bayesian networks, climatic change, freezing Injury, winter wheat

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480 Numerical Solution of Steady Magnetohydrodynamic Boundary Layer Flow Due to Gyrotactic Microorganism for Williamson Nanofluid over Stretched Surface in the Presence of Exponential Internal Heat Generation

Authors: M. A. Talha, M. Osman Gani, M. Ferdows

Abstract:

This paper focuses on the study of two dimensional magnetohydrodynamic (MHD) steady incompressible viscous Williamson nanofluid with exponential internal heat generation containing gyrotactic microorganism over a stretching sheet. The governing equations and auxiliary conditions are reduced to a set of non-linear coupled differential equations with the appropriate boundary conditions using similarity transformation. The transformed equations are solved numerically through spectral relaxation method. The influences of various parameters such as Williamson parameter γ, power constant λ, Prandtl number Pr, magnetic field parameter M, Peclet number Pe, Lewis number Le, Bioconvection Lewis number Lb, Brownian motion parameter Nb, thermophoresis parameter Nt, and bioconvection constant σ are studied to obtain the momentum, heat, mass and microorganism distributions. Moment, heat, mass and gyrotactic microorganism profiles are explored through graphs and tables. We computed the heat transfer rate, mass flux rate and the density number of the motile microorganism near the surface. Our numerical results are in better agreement in comparison with existing calculations. The Residual error of our obtained solutions is determined in order to see the convergence rate against iteration. Faster convergence is achieved when internal heat generation is absent. The effect of magnetic parameter M decreases the momentum boundary layer thickness but increases the thermal boundary layer thickness. It is apparent that bioconvection Lewis number and bioconvection parameter has a pronounced effect on microorganism boundary. Increasing brownian motion parameter and Lewis number decreases the thermal boundary layer. Furthermore, magnetic field parameter and thermophoresis parameter has an induced effect on concentration profiles.

Keywords: convection flow, similarity, numerical analysis, spectral method, Williamson nanofluid, internal heat generation

Procedia PDF Downloads 150
479 Prevalence and Clinical Significance of Antiphospholipid Antibodies in COVID-19 Patients Admitted to Intensive Care Units

Authors: Mostafa Najim, Alaa Rahhal, Fadi Khir, Safae Abu Yousef, Amer Aljundi, Feryal Ibrahim, Aliaa Amer, Ahmed Soliman Mohamed, Samira Saleh, Dekra Alfaridi, Ahmed Mahfouz, Sumaya Al-Yafei, Faraj Howady, Mohamad Yahya Khatib, Samar Alemadi

Abstract:

Background: Coronavirus disease 2019 (COVID-19) increases the risk of coagulopathy among critically ill patients. Although the presence of antiphospholipid antibodies (aPLs) has been proposed as a possible mechanism of COVID-19 induced coagulopathy, their clinical significance among critically ill patients with COVID-19 remains uncertain. Methods: This prospective observational study included patients with COVID-19 admitted to intensive care units (ICU) to evaluate the prevalence and clinical significance of aPLs, including anticardiolipin IgG/IgM, anti-β2-glycoprotein IgG/IgM, and lupus anticoagulant. The study outcomes included the prevalence of aPLs, a primary composite outcome of all-cause mortality, and arterial or venous thrombosis among aPLs positive patients versus aPLs negative patients during their ICU stay. Multiple logistic regression was used to assess the influence of aPLs on the primary composite outcome of mortality and thrombosis. Results: A total of 60 critically ill patients were enrolled. Of whom, 57 (95%) were male, with a mean age of 52.8 ± 12.2 years, and the majority were from Asia (68%). Twenty-two patients (37%) were found to have positive aPLs; of whom 21 patients were positive for lupus anticoagulant, whereas one patient was positive for anti-β2-glycoprotein IgG/IgM. The composite outcome of mortality and thrombosis during ICU did not differ among patients with positive aPLs compared to those with negative aPLs (4 (18%) vs. 6 (16%), aOR= 0.98, 95% CI 0.1-6.7; p-value= 0.986). Likewise, the secondary outcomes, including all-cause mortality, venous thrombosis, arterial thrombosis, discharge from ICU, time to mortality, and time to discharge from ICU, did not differ between those with positive aPLs upon ICU admission in comparison to patients with negative aPLs. Conclusion: The presence of aPLs does not seem to affect the outcomes of critically ill patients with COVID-19 in terms of all-cause mortality and thrombosis. Therefore, clinicians may not screen critically ill patients with COVID-19 for aPLs unless deemed clinically appropriate.

Keywords: antiphospholipid antibodies, critically ill patients, coagulopathy, coronavirus

Procedia PDF Downloads 137
478 Production and Purification of Salmonella Typhimurium MisL Autotransporter Protein in Escherichia coli

Authors: Neslihan Taskale Karatug, Mustafa Akcelik

Abstract:

Some literature data show that misL protein play a role on host immune response formed against Salmonella Typhimurium. The aim of the present study is to learn the role of the protein in S. Typhimurium pathogenicity. To describe certain functions of the protein, primarily recombinant misL protein was produced and purified. PCR was performed using a primer set targeted to passenger domain of the misL gene on S. Typhimurium LT2 genome. Amplicon and pet28a vector were enzymatically cleaved with EcoRI and NheI. The digested DNA materials were purified with High Pure PCR Product Purification Kit. The ligation reaction was achieved with the pure products. After preparation of competent Escherichia coli Dh5α, ligation mix was transformed into the cell by electroporation. To confirm the existence of insert gene, recombinant plasmid DNA of Dh5α was isolated with high pure plasmid DNA kit. Proved the correctness of recombinant plasmid was electroporated to BL21. The cell was induced by IPTG. After induction, the presence of recombinant protein was checked by SDS-PAGE. The recombinant misL protein was purified using HisPur Ni-NTA spin colon. The pure protein was shown by SDS-PAGE and western blot immünoassay. The concentration of the protein was measured BCA Protein Assay kit. In the wake of ligation with digested products (2 kb misL and 5.4 kb pet28a) visualised on gel size of the band was about 7.4 kb and was named as pNT01. The pNT01 recombinant plasmid was transformed into Dh5α and colonies were chosen in selective medium. Plasmid DNA isolation from them was carried out. PCR was achieved on the pNT01 to check misL and 2 kb band was observed on the agarose gel. After electroporation of the plasmid and induction of the cell, 68 kDa misL protein was seen. Subsequent to the purification of the protein, only a band was observed on SDS-PAGE. Association of the pure protein with anti-his antibody was verified by the western blot assay. The concentration of the pure misL protein was determined as 345 μg/mL. Production of polyclonal antibody will be achieved by using the obtained pure recombinant misL protein as next step. The role of the protein will come out on the immune system together some assays.

Keywords: cloning, Escherichia coli, recombinant protein purification, Salmonella Typhimurium

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477 Activity of Resveratrol on the Influence of Aflatoxin B1 on the Testes of Sprague Dawley Rats

Authors: Ali D. Omur, Betul Apaydin Yildirim, Yavuz S. Saglam, Selim Comakli, Mustafa Ozkaraca

Abstract:

Twenty-eight male Sprague Dawley rats (aged 3 months) were used in the study. The animals were given feed and water as ad libitum. Sprague Dawley rats were randomly divided into 4 groups as 7 rats in each group. Aflatoxin B1 (7.5 μg/200 g), resveratrol (60 mg/kg) was administered to rats in groups other than the control group. At the end of the 16th day, blood, semen and tissue specimens were taken by decapitation under ether anesthesia. The effects of aflatoxin B1 and resveratrol on spermatological, pathological and biochemical parameters were determined in rats. When we evaluate the spermatological parameters, it is understood that resveratrol has a statistically significant difference in terms of sperm motility and viability (membrane integrity) compared to the control group and aflatoxin B1 administration groups, indicating a protective effect on spermatological parameters (groups: control, resveratrol, aflatoxin B1 and Afb1 + res; respectively, values of motility: 71,42 ± 0,52b, 72,85 ± 1, 48c , 60,71 ± 1,30a, 57,14 ± 2, 40a; values of viability: 63,85 ± 1,33b, 70,42 ± 2,61c, 55,00 ± 1,54a, 56,57 ± 0,89a. In terms of pathological parameters -histopathological examination- in the control and resveratrol groups, seminiferous tubules were observed to be in normal structure. In the group treated with aflatoxin, the regular structure of the spermatogenic cells deteriorated, and the seminiferous tubules became necrotic and degenerative. In the group treated with Afb1 + res, the decreasing of necrotic and degenerative changes were determined compared with in the group treated with aflatoxin. As immunohistochemical examination, cleaved caspase 3 expression was found to be very low in the control and resveratrol groups. Cleaved caspase 3 expression was severely exacerbated in seminiferous tubules in aflatoxin group but cleaved caspase 3 expression level decreased in Afb1 + res. In the biochemical direction, resveratrol has been shown to inhibit the adverse effects of aflatoxin on antioxidant levels (GSH-mmol/L, CAT-kU/L, GPx-U/mL, SOD-EU/mL) and to show a protective effect. For this purpose, the use of resveratrol with antioxidant activity was investigated in preventing or ameliorating damage to aflatoxin B1. It has been concluded that resveratrol effectively prevents the aflatoxin-induced testicular damage and lipid peroxidation. It has also been shown that resveratrol has protective effects on sperm motility and viability.

Keywords: Aflatoxin B1, rat, resveratrol, sperm

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476 Ramadan as a Model of Intermittent Fasting: Effects on Gut Hormones, Appetite and Body Composition in Diabetes vs. Controls

Authors: Turki J. Alharbi, Jencia Wong, Dennis Yue, Tania P. Markovic, Julie Hetherington, Ted Wu, Belinda Brooks, Radhika Seimon, Alice Gibson, Stephanie L. Silviera, Amanda Sainsbury, Tanya J. Little

Abstract:

Fasting has been practiced for centuries and is incorporated into the practices of different religions including Islam, whose followers intermittently fast throughout the month of Ramadan. Thus, Ramadan presents a unique model of prolonged intermittent fasting (IF). Despite a growing body of evidence for a cardio-metabolic and endocrine benefit of IF, detailed studies of the effects of IF on these indices in type 2 diabetes are scarce. We studied 5 subjects with type 2 diabetes (T2DM) and 7 healthy controls (C) at baseline (pre), and in the last week of Ramadan (post). Fasting circulating levels of glucose, HbA1c and lipids, as well as body composition (with DXA) and resting energy expenditure (REE) were measured. Plasma gut hormone levels and appetite responses to a mixed meal were also studied. Data are means±SEM. Ramadan decreased total fat mass (-907±92 g, p=0.001) and trunk fat (-778±190 g, p=0.014) in T2DM but not in controls, without any reductions in lean mass or REE. There was a trend towards a decline in plasma FFA in both groups. Ramadan had no effect on body weight, glycemia, blood pressure, or plasma lipids in either group. In T2DM only, the area under the curve for post-meal plasma ghrelin concentrations increased after Ramadan (pre:6632±1737 vs. post:9025±2518 pg/ml.min-1, p=0.045). Despite this increase in orexigenic ghrelin, subjective appetite scores were not altered by Ramadan. Meal-induced plasma concentrations of the satiety hormone pancreatic polypeptide did not change during Ramadan, but were higher in T2DM compared to controls (post: C: 23486±6677 vs. T2DM: 62193±6880 pg/ml.min-1, p=0.003. In conclusion, Ramadan, as a model for IF appears to have more favourable effects on body composition in T2DM, without adverse effects on metabolic control or subjective appetite. These data suggest that IF may be particularly beneficial in T2DM as a nutritional intervention. Larger studies are warranted.

Keywords: type 2 diabetes, obesity, intermittent fasting, appetite regulating hormones

Procedia PDF Downloads 288
475 Multiscale Process Modeling of Ceramic Matrix Composites

Authors: Marianna Maiaru, Gregory M. Odegard, Josh Kemppainen, Ivan Gallegos, Michael Olaya

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Ceramic matrix composites (CMCs) are typically used in applications that require long-term mechanical integrity at elevated temperatures. CMCs are usually fabricated using a polymer precursor that is initially polymerized in situ with fiber reinforcement, followed by a series of cycles of pyrolysis to transform the polymer matrix into a rigid glass or ceramic. The pyrolysis step typically generates volatile gasses, which creates porosity within the polymer matrix phase of the composite. Subsequent cycles of monomer infusion, polymerization, and pyrolysis are often used to reduce the porosity and thus increase the durability of the composite. Because of the significant expense of such iterative processing cycles, new generations of CMCs with improved durability and manufacturability are difficult and expensive to develop using standard Edisonian approaches. The goal of this research is to develop a computational process-modeling-based approach that can be used to design the next generation of CMC materials with optimized material and processing parameters for maximum strength and efficient manufacturing. The process modeling incorporates computational modeling tools, including molecular dynamics (MD), to simulate the material at multiple length scales. Results from MD simulation are used to inform the continuum-level models to link molecular-level characteristics (material structure, temperature) to bulk-level performance (strength, residual stresses). Processing parameters are optimized such that process-induced residual stresses are minimized and laminate strength is maximized. The multiscale process modeling method developed with this research can play a key role in the development of future CMCs for high-temperature and high-strength applications. By combining multiscale computational tools and process modeling, new manufacturing parameters can be established for optimal fabrication and performance of CMCs for a wide range of applications.

Keywords: digital engineering, finite elements, manufacturing, molecular dynamics

Procedia PDF Downloads 74
474 Combined Effect of Gender Differences and Fatiguing Task on Unipedal Postural Balance and Functional Mobility in Adults with Multiple Sclerosis

Authors: Sonda Jallouli, Omar Hammouda, Imen Ben Dhia, Salma Sakka, Chokri Mhiri, Mohamed Habib Elleuch, Abedlmoneem Yahia, Sameh Ghroubi

Abstract:

Multiple sclerosis (MS) is characterized by gender differences with affecting women two to four times more than men, but the disease progression is faster and more severe in men. Fatigue represents one of the most frequent and disabling symptoms related to MS. Results of previous studies regarding gender differences in fatigue perception in MS persons are contradictory. Besides, fatigue has been shown to affect negatively postural balance and functional mobility in MS persons. However, no study has taken into account gender differences in the response of these physical parameters to a fatiguing protocol in MS persons. Given the reduction of autonomy due to the alteration of these parameters induced by fatigue and the importance of gender differences in postural balance training programs in fatigued men and women with MS, the aim of this study was to investigate the effect of gender difference on unipedal postural balance and functional mobility after performing a fatiguing task in MS adults. Methods: Eleven women (30.29 ± 7.99 years) and seven men (30.91 ± 8.19 years) with relapsing-remitting MS performed a fatiguing protocol: three sets of the 5×sit to stand test (5-STST), six-minute walk test (6MWT) followed by three sets of the 5-STST. Unipedal balance, functional mobility, and fatigue perception were measured prefatigue (T0) and post fatigue (T3) using a clinical unipedal balance test, timed up and go test (TUGT), and analogic visual scale of fatigue (VASF), respectively. Heart rate (HR) and rate of perceived exertion (RPE) were recorded before, during and after the fatiguing task. Results: Compared to women, men showed an impairment of unipedal balance on the dominant leg (p<0.001, d=0.52) and mobility (p<0.001, d=3) via reducing unipedal stance time and increasing duration of TUGT execution, respectively. No gender differences were observed in 6MWT, 5-STST, HR, RPE and VASF scores. Conclusion: Fatiguing protocol negatively affected unipedal postural balance and mobility only in men. These gender differences were inconclusive but can be taken into account in postural balance rehabilitation programs for persons with MS.

Keywords: functional mobility, fatiguing exercises, multiple sclerosis, sex differences, unipedal balance

Procedia PDF Downloads 100
473 Reduction of the Cellular Infectivity of SARS-CoV-2 by a Mucoadhesive Nasal Spray

Authors: Adam M. Pitz, Gillian L. Phillipson, Jayant E. Khanolkar, Andrew M. Middleton

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New emerging evidence suggests that the nose is the predominant route for entry of the SARS-CoV-2 virus into the host. A virucidal suspension test (conforming in principle to the European Standard EN14476) was conducted to determine whether a commercial liquid gel intranasal spray containing 1% of the mucoadhesive hydroxypropyl methylcellulose (HPMC) could inhibit the cellular infectivity of the SARS-CoV-2 coronavirus. Virus was added to the test product samples and to controls in a 1:8 ratio and mixed with one part bovine serum albumin as an interfering substance. The test samples were pre-equilibrated to 34 ± 2°C (representing the temperature of the nasopharynx) with the temperature maintained at 34 ± 2°C for virus contact times of 1, 5 and 10 minutes. Neutralized aliquots were inoculated onto host cells (Vero E6 cells, ATCC CRL-1586). The host cells were then incubated at 36 ± 2°C for a period of 7 days. The residual infectious virus in both test and controls was detected by viral-induced cytopathic effect. The 50% tissue culture infective dose per mL (TCID50/mL) was determined using the Spearman-Karber method with results reported as the reduction of the virus titer due to treatment with test product, expressed as log10. The controls confirmed the validity of the results with no cytotoxicity or viral interference observed in the neutralized test product samples. The HPMC formulation reduced SARS-CoV-2 titer, expressed as log10TCID50, by 2.30 ( ± 0.17), 2.60 ( ± 0.19), and 3.88 ( ± 0.19) with the respective contact times of 1, 5 and 10 minutes. The results demonstrate that this 1% HPMC gel formulation can reduce the cellular infectivity of the SARS-CoV-2 virus with an increasing viral inhibition observed with increasing exposure time. This 1% HMPC gel is well tolerated and can reside, when delivered via nasal spray, for up to one hour in the nasal cavity. We conclude that this intranasal gel spray with 1% HPMC repeat-dosed every few hours may offer an effective preventive or early intervention solution to limit the transmission and impact of the SARS-CoV-2 coronavirus.

Keywords: hydroxypropyl methylcellulose, mucoadhesive nasal spray, respiratory viruses, SARS-CoV-2

Procedia PDF Downloads 109
472 Airborne Particulate Matter Passive Samplers for Indoor and Outdoor Exposure Monitoring: Development and Evaluation

Authors: Kholoud Abdulaziz, Kholoud Al-Najdi, Abdullah Kadri, Konstantinos E. Kakosimos

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The Middle East area is highly affected by air pollution induced by anthropogenic and natural phenomena. There is evidence that air pollution, especially particulates, greatly affects the population health. Many studies have raised a warning of the high concentration of particulates and their affect not just around industrial and construction areas but also in the immediate working and living environment. One of the methods to study air quality is continuous and periodic monitoring using active or passive samplers. Active monitoring and sampling are the default procedures per the European and US standards. However, in many cases they have been inefficient to accurately capture the spatial variability of air pollution due to the small number of installations; which eventually is attributed to the high cost of the equipment and the limited availability of users with expertise and scientific background. Another alternative has been found to account for the limitations of the active methods that is the passive sampling. It is inexpensive, requires no continuous power supply, and easy to assemble which makes it a more flexible option, though less accurate. This study aims to investigate and evaluate the use of passive sampling for particulate matter pollution monitoring in dry tropical climates, like in the Middle East. More specifically, a number of field measurements have be conducted, both indoors and outdoors, at Qatar and the results have been compared with active sampling equipment and the reference methods. The samples have been analyzed, that is to obtain particle size distribution, by applying existing laboratory techniques (optical microscopy) and by exploring new approaches like the white light interferometry to. Then the new parameters of the well-established model have been calculated in order to estimate the atmospheric concentration of particulates. Additionally, an extended literature review will investigate for new and better models. The outcome of this project is expected to have an impact on the public, as well, as it will raise awareness among people about the quality of life and about the importance of implementing research culture in the community.

Keywords: air pollution, passive samplers, interferometry, indoor, outdoor

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471 Importance of CT and Timed Barium Esophagogram in the Contemporary Treatment of Patients with Achalasia

Authors: Sanja Jovanovic, Aleksandar Simic, Ognjan Skrobic, Dragan Masulovic, Aleksandra Djuric-Stefanovic

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Introduction: Achalasia is an idiopathic primary esophageal motility disorder characterized by esophageal peristalsis and impaired swallow-induced relaxation of the lower esophageal sphincter (LES). It is a rare disease that affects both genders with an incidence of 1/100.000 and a prevalence rate of 10/100,000 per year. Objective: Laparoscopic Heller myotomy (LHM) represents a therapy of choice for patients with achalasia, providing excellent outcomes. The aim of this study was to evaluate the significance of computed tomography (CT) in analyzing achalasia subtypes and timed barium esophagogram (TBE) in evaluation of LHM success, as a part of standardized diagnostic protocol. Method: Fifty-one patients with achalasia, confirmed by manometric studies, in addition to standardized diagnostic methods, underwent CT and TBE. CT was done with multiplanar reconstruction, measuring the wall thickness above the esophago-gastric junction in the axial plane. TBE was performed preoperatively and two days postoperatively swallowing low-density barium sulfate, and plane upright frontal films were performed 1, 2 and 5 minutes after the ingestion. In all patients, LHM was done, and pre and postoperative height and weight of the barium column were compared. Results: According to CT findings we divided patients into 3 subtypes of achalasia according to wall thickness: < 4mm as subtype one, between 4 - 9mm as II, and > 10 mm as subtype 3. Correlation of manometric results, as a reference values, and CT findings indicated CT sensitivity of 90% and specificity of 70 % in establishing subtypes of achalasia. The preoperative values of TBE at 1, 2 and 5 minutes were: median barium column height 17.4 ± 7.4, 15.9 ± 6.2 and 13.9 ± 6.2 cm; median column width 5 ± 1.5, 4.7 ± 1.6 and 4.5 ± 1.8 cm respectively. LHM significantly reduced these values (height 7 ± 4.6, 5.8 ± 4.2, 3.7 ± 3.4 cm; width 2.9 ± 1.3, 2.6 ± 1.3 and 2.4 ± 1.4 cm), indicating the quantitative estimates of emptying as excellent (p value < 0.01). Conclusion: CT has high sensitivity and specificity in evaluation of achalasia subtypes, and can be introduced as an additional method for standardized evaluation of these patients. The quantitative assessment of TBE based on measurements of the barium column is an accurate and beneficial method, which adequately estimates esophageal emptying success of LHM.

Keywords: achalasia, computed tomography, esophagography, myotomy

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470 Coherent Optical Tomography Imaging of Epidermal Hyperplasia in Vivo in a Mouse Model of Oxazolone Induced Atopic Dermatitis

Authors: Eric Lacoste

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Laboratory animals are currently widely used as a model of human pathologies in dermatology such as atopic dermatitis (AD). These models provide a better understanding of the pathophysiology of this complex and multifactorial disease, the discovery of potential new therapeutic targets and the testing of the efficacy of new therapeutics. However, confirmation of the correct development of AD is mainly based on histology from skin biopsies requiring invasive surgery or euthanasia of the animals, plus slicing and staining protocols. However, there are currently accessible imaging technologies such as Optical Coherence Tomography (OCT), which allows non-invasive visualization of the main histological structures of the skin (like stratum corneum, epidermis, and dermis) and assessment of the dynamics of the pathology or efficacy of new treatments. Briefly, female immunocompetent hairless mice (SKH1 strain) were sensitized and challenged topically on back and ears for about 4 weeks. Back skin and ears thickness were measured using calliper at 3 occasions per week in complement to a macroscopic evaluation of atopic dermatitis lesions on back: erythema, scaling and excoriations scoring. In addition, OCT was performed on the back and ears of animals. OCT allows a virtual in-depth section (tomography) of the imaged organ to be made using a laser, a camera and image processing software allowing fast, non-contact and non-denaturing acquisitions of the explored tissues. To perform the imaging sessions, the animals were anesthetized with isoflurane, placed on a support under the OCT for a total examination time of 5 to 10 minutes. The results show a good correlation of the OCT technique with classical HES histology for skin lesions structures such as hyperkeratosis, epidermal hyperplasia, and dermis thickness. This OCT imaging technique can, therefore, be used in live animals at different times for longitudinal evaluation by repeated measurements of lesions in the same animals, in addition to the classical histological evaluation. Furthermore, this original imaging technique speeds up research protocols, reduces the number of animals and refines the use of the laboratory animal.

Keywords: atopic dermatitis, mouse model, oxzolone model, histology, imaging

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469 Therapeutic Effects of Guar Gum Nanoparticles in Oxazolone-Induced Atopic Dermatitis

Authors: Nandita Ghosh, Shinjini Mitra, Ena Ray Banerjee

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Atopic dermatitis (AD) is a chronic disease of the skin, involving itchy, reddish, and scaly lesions. It mainly affects children and has a high prevalence in developing countries. The AD may occur due to environmental or genetic factors. There is no permanent cure for the AD. Currently, all therapeutic strategies involve methods to simply alleviate the symptoms, and include lotions and corticosteroids, which have adverse effects. Use of phytochemicals and natural products has not yet been exploited fully. The particle used in this study is derived from Cyamopsis tetragonoloba, an edible polysaccharide with a galactomannan component. The mannose component mainly increases its specificity towards cellular uptake by mannose receptors, highly expressed by the macrophage. The aim of this study was to determine the therapeutic effect of guar gum nanoparticles (GN) in vitro and in vivo in the AD. To assess the wound healing capacity of the guar gum nanoparticle (GN), we first treated adherent NIH3T3 cells, with a scratch injury, with GN. GN successfully healed the wound caused by the scratch. In the in vivo experiment, Balb/c mice ear were topically treated with oxazolone (oxa) to induce AD and then were topically treated with GN. The ear thickness was increased significantly till day 28 on the treatment of Oxa. The GN application showed a significant decrease in the thickness as assessed on day 28. The total cell count of skin cells showed fold increase when treated with oxa, was again decreased on topical application of GN on the affected skin. The eosinophil count, as assessed by Giemsa staining was also increased when treated with oxa, GN application led to a significant decrease. The IgE level was assessed in the serum samples which showed that GN helped in restoring the alleviated IgE level. The T helper cells and the macrophage population showed increased percentage when treated with oxa, the GN application. This was examined by flow cytometry. The H&E staining of the ear tissue showed epidermal thickness in the oxa treated mice, GN application showed reduced cellular filtration followed by epidermal thickness. Thus our assays showed that GN was successful in alleviating the disease caused by Oxa when administered topically.

Keywords: allergen, inflammation, nanodrug, wound

Procedia PDF Downloads 218
468 Activation of NLRP3 Inflammasomes by Helicobacter pylori Infection in Innate Cellular Model and Its Correlation to IL-1β Production

Authors: Islam Nowisser, Noha Farag, Mohamed El Azizi

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Helicobacter pylori is a highly important human pathogen which inhabits about 50% of the population worldwide. Infection with this bacteria is very hard to treat, with high probability of recurrence. H. pylori causes severe gastric diseases, including peptic ulcer, gastritis, and gastric cancer, which has been linked to chronic inflammation. The infection has been reported to be associated with high levels of pro-inflammatory cytokines, especially IL-1β and TNF-α. The aim of the current study is to investigate the molecular mechanisms by which H. pylori activates NLRP3 inflammasome and its contribution to Il-1 β production in an innate cellular model. H. pylori PMSS1 and G27 standard strains, as well as the PMSS1 isogenic mutant strain PMSS1ΔVacA and G27ΔVacA, G27ΔCagA in addition to clinical isolates obtained from biopsy samples from the antrum and corpus mucosa of chronic gastritis patients, were used to establish infection in RAW-264.7 macrophages. The production levels of TNF-α and IL-1β was assessed using ELISA. Since expression of these cytokines is often regulated by the transcription factor complex, nuclear factor-kB (NF-kB), the activation of NF-κB in H. pylori infected cells was also evaluated by luciferase assay. Genomic DNA was extracted from bacterial cultures of H. pylori clinical isolates as well as the standard strains and their corresponding mutants, where they were evaluated for the cagA pathogenicity island and vacA expression. The correlation between these findings and expression of the cagA Pathogenicity Island and vacA in the bacteria was also investigated. The results showed IL-1β, and TNF-α production significantly increased in raw macrophages following H. pylori infection. The cagA+ and vacA+ H. pylori strains induced significant production of IL-1β compared to cagA- and vacA- strains. The activation pattern of NF-κB was correlated in the isolates to their cagA and vacA expression profiles. A similar finding could not be confirmed for TNF-α production. Our study shows the ability of H. pylori to activate NF-kB and induce significant IL-1β production as a possible mechanism for the augmented inflammatory response seen in subjects infected with cagA+ and vacA+ H. pylori strains that would lead to the progression to more severe form of the disease.

Keywords: Helicobacter pylori, IL-1β, inflammatory cytokines, nuclear factor KB, TNF-α

Procedia PDF Downloads 98
467 Impact of Fischer-Tropsch Wax on Ethylene Vinyl Acetate/Waste Crumb Rubber Modified Bitumen: An Energy-Sustainability Nexus

Authors: Keith D. Nare, Mohau J. Phiri, James Carson, Chris D. Woolard, Shanganyane P. Hlangothi

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In an energy-intensive world, minimizing energy consumption is paramount to cost saving and reducing the carbon footprint. Improving mixture procedures utilizing warm mix additive Fischer-Tropsch (FT) wax in ethylene vinyl acetate (EVA) and modified bitumen highlights a greener and sustainable approach to modified bitumen. In this study, the impact of FT wax on optimized EVA/waste crumb rubber modified bitumen is assayed with a maximum loading of 2.5%. The rationale of the FT wax loading is to maintain the original maximum loading of EVA in the optimized mixture. The phase change abilities of FT wax enable EVA co-crystallization with the support of the elastomeric backbone of crumb rubber. Less than 1% loading of FT wax worked in the EVA/crumb rubber modified bitumen energy-sustainability nexus. Response surface methodology approach to the mixture design is implemented amongst the different loadings of FT wax, EVA for a consistent amount of crumb rubber and bitumen. Rheological parameters (complex shear modulus, phase angle and rutting parameter) were the factors used as performance indicators of the different optimized mixtures. The low temperature chemistry of the optimized mixtures is analyzed using elementary beam theory and the elastic-viscoelastic correspondence principle. Master curves and black space diagrams are developed and used to predict age-induced cracking of the different long term aged mixtures. Modified binder rheology reveals that the strain response is not linear and that there is substantial re-arrangement of polymer chains as stress is increased, this is based on the age state of the mixture and the FT wax and EVA loadings. Dominance of individual effects is evident over effects of synergy in co-interaction of EVA and FT wax. All-inclusive FT wax and EVA formulations were best optimized in mixture 4 with mixture 7 reflecting increase in ease of workability. Findings show that interaction chemistry of bitumen, crumb rubber EVA, and FT wax is first and second order in all cases involving individual contributions and co-interaction amongst the components of the mixture.

Keywords: bitumen, crumb rubber, ethylene vinyl acetate, FT wax

Procedia PDF Downloads 144
466 Still Hepatocellular Carcinoma Risk Despite Proper Treatment of Chronic Viral Hepatitis

Authors: Sila Akhan, Muge Toygar, Murat Sayan, Simge Fidan

Abstract:

Chronic viral hepatitis B, C, and D can cause hepatocellular carcinoma (HCC), cirrhosis and death. The proper treatment reduce the risk of development of HCC importantly, but not to zero point. Materials and Methods: We analysed retrospectively our chronic viral hepatitis B, C and D patients who attended to our Infectious Diseases policlinic between 2004-2018. From 589 biopsy-proven chronic hepatitis patients 3 have hepatocellular carcinoma on our follow up. First case is 74 years old patient. His HCV infection diagnosis was made 8 years ago. First treatment was pegylated interferon plus ribavirin only 28 weeks, because of HCV RNA breakthrough under treatment. In 2013 he was retreated with telaprevir, pegylated interferon plus ribavirin 24 weeks. But at the end of the therapy HCV RNA was found 1.290.000 IU/mL. He has abdominal ultrasonography (US) controls and alpha-fetoprotein (AFP) at 6 months intervals. All seemed normal until 2015 then he has an abdominal magnetic resonance imaging (MRI) and found HCC by chance. His treatment began in Oncology Clinic after verified with biopsy of HCC. And then sofosbuvir/ledipasvir was given to him for HCV 24 weeks. Sustained virologic response (SVR) was obtained. He is on cure for HCV infection and under control of Oncology for HCC. Second patient is 36 years old man. He knows his HBV infection since 2008. HBsAg and HBeAg positive; HDV RNA negative. Liver biopsy revealed grade:4, stage 3-4 according modified Knodell scoring system. In 2010 tenofovir treatment was began. His abdominal US and AFP were normal. His controls took place at 6 months intervals and HBV DNA negative, US, and AFP were normal until 2016 continuously. AFP found 37 above the normal range and then HCC was found in MRI. Third patient is 57 years old man. As hepatitis B infection was first diagnosed; he has cirrhosis and was began tenofovir as treatment. In short time he has HCC despite normal AFP values. Conclusion: In Mediterranian countries including Turkey naturally occurring pre-S/S variants are more than 75% of all chronic hepatitis B patients. This variants may contribute to the development of progressive liver damage and hepatocarcinogenesis. HCV-induced development of HCC is a gradual process and is affected by the duration of disease and viral genotype. All the chronic viral hepatitis patients should be followed up in 6 months intervals not only with US and AFP for HCC. Despite they have proper treatment there is always the risk development of HCC. Chronic hepatitis patients cannot be dropped from follow up even treated well.

Keywords: HCC, HCV, HBV, DAA

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465 Multi-omics Integrative Analysis with Genome-Scale Metabolic Model Simulation Reveals Reaction Essentiality data in Human Astrocytes Under the Lipotoxic Effect of Palmitic Acid

Authors: Janneth Gonzalez, Andres Pinzon Velasco, Maria Angarita, Nicolas Mendoza

Abstract:

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-inflammatory pathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, there are few studies on the neuro-protective mechanisms of tibolone, especially at the systemic (omic) level. 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 use control theory to identify those reactions that control the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a change 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 in metabolic pathways that increase neurotoxicity and represent potential treatment targets. Finally, this study framework facilitates the understanding of metabolic regulation strategies, andit can be used for in silico exploring 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, control theory

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