Search results for: flux salts
7 Investigating Role of Autophagy in Cispaltin Induced Stemness and Chemoresistance in Oral Squamous Cell Carcinoma
Authors: Prajna Paramita Naik, Sujit Kumar Bhutia
Abstract:
Background: Regardless of the development multimodal treatment strategies, oral squamous cell carcinoma (OSCC) is often associated with a high rate of recurrence, metastasis and chemo- and radio- resistance. The present study inspected the relevance of CD44, ABCB1 and ADAM17 expression as a putative stem cell compartment in oral squamous cell carcinoma (OSCC) and deciphered the role of autophagy in regulating the expression of aforementioned proteins, stemness and chemoresistance. Methods: A retrospective analysis of CD44, ABCB1 and ADAM17 expression with respect to the various clinicopathological factors of sixty OSCC patients were determined via immunohistochemistry. The correlation among CD44, ABCB1 and ADAM17 expression was established. Sphere formation assay, flow cytometry and fluorescence microscopy were conducted to elucidate the stemness and chemoresistance nature of established cisplatin-resistant oral cancer cells (FaDu). The pattern of expression of CD44, ABCB1 and ADAM17 in parental (FaDu-P) and resistant FaDu cells (FaDu-CDDP-R) were investigated through fluorescence microscopy. Western blot analysis of autophagy marker proteins was performed to compare the status of autophagy in parental and resistant FaDu cell. To investigate the role of autophagy in chemoresistance and stemness, sphere formation assay, immunofluorescence and Western blot analysis was performed post transfection with siATG14 and the level of expression of autophagic proteins, mitochondrial protein and stemness-associated proteins were analyzed. The statistical analysis was performed by GraphPad Prism 4.0 software. p-value was defined as follows: not significant (n.s.): p > 0.05;*: p ≤ 0.05; **: p ≤ 0.01; ***: p ≤ 0.001; ****: p ≤ 0.0001 were considered statistically significant. Results: In OSCC, high CD44, ABCB1 and ADAM17 expression were significantly correlated with higher tumor grades and poor differentiation. However, the expression of these proteins was not related to the age and sex of OSCC patients. Moreover, the expression of CD44, ABCB1 and ADAM17 were positively correlated with each other. In vitro and OSCC tissue double labeling experiment data showed that CD44+ cells were highly associated with ABCB1 and ADAM17 expression. Further, FaDu-CDDP-R cells showed higher sphere forming capacity along with increased fraction of the CD44+ population and β-catenin expression FaDu-CDDP-R cells also showed accelerated expression of CD44, ABCB1 and ADAM17. A comparatively higher autophagic flux was observed in FaDu-CDDP-R against FaDu-P cells. The expression of mitochondrial proteins was noticeably reduced in resistant cells as compared to parental cells indicating the occurrence of autophagy-mediated mitochondrial degradation in oral cancer. Moreover, inhibition of autophagy was coupled with the decreased formation of orospheres suggesting autophagy-mediated stemness in oral cancer. Blockade of autophagy was also found to induce the restoration of mitochondrial proteins in FaDu-CDDP-R cells indicating the involvement of mitophagy in chemoresistance. Furthermore, a reduced expression of CD44, ABCB1 and ADAM17 was also observed in ATG14 deficient cells FaDu-P and FaDu-CDDP-R cells. Conclusion: The CD44+ ⁄ABCB1+ ⁄ADAM17+ expression in OSCC might be associated with chemoresistance and a putative CSC compartment. Further, the present study highlights the contribution of mitophagy in chemoresistance and confirms the potential involvement of autophagic regulation in acquisition of stem-like characteristics in OSCC.Keywords: ABCB1, ADAM17, autophagy, CD44, chemoresistance, mitophagy, OSCC, stemness
Procedia PDF Downloads 1896 Analysis of Short Counter-Flow Heat Exchanger (SCFHE) Using Non-Circular Micro-Tubes Operated on Water-CuO Nanofluid
Authors: Avdhesh K. Sharma
Abstract:
Key, in the development of energy-efficient micro-scale heat exchanger devices, is to select large heat transfer surface to volume ratio without much expanse on re-circulated pumps. The increased interest in short heat exchanger (SHE) is due to accessibility of advanced technologies for manufacturing of micro-tubes in range of 1 micron m - 1 mm. Such SHE using micro-tubes are highly effective for high flux heat transfer technologies. Nanofluids, are used to enhance the thermal conductivity of re-circulated coolant and thus enhances heat transfer rate further. Higher viscosity associated with nanofluid expands more pumping power. Thus, there is a trade-off between heat transfer rate and pressure drop with geometry of micro-tubes. Herein, a novel design of short counter flow heat exchanger (SCFHE) using non-circular micro-tubes flooded with CuO-water nanofluid is conceptualized by varying the ratio of surface area to cross-sectional area of micro-tubes. A framework for comparative analysis of SCFHE using micro-tubes non-circular shape flooded by CuO-water nanofluid is presented. In SCFHE concept, micro-tubes having various geometrical shapes (viz., triangular, rectangular and trapezoidal) has been arranged row-wise to facilitate two aspects: (1) allowing easy flow distribution for cold and hot stream, and (2) maximizing the thermal interactions with neighboring channels. Adequate distribution of rows for cold and hot flow streams enables above two aspects. For comparative analysis, a specific volume or cross-section area is assigned to each elemental cell (which includes flow area and area corresponds to half wall thickness). A specific volume or cross-section area is assumed to be constant for each elemental cell (which includes flow area and half wall thickness area) and variation in surface area is allowed by selecting different geometry of micro-tubes in SCFHE. Effective thermal conductivity model for CuO-water nanofluid has been adopted, while the viscosity values for water based nanofluids are obtained empirically. Correlations for Nusselt number (Nu) and Poiseuille number (Po) for micro-tubes have been derived or adopted. Entrance effect is accounted for. Thermal and hydrodynamic performances of SCFHE are defined in terms of effectiveness and pressure drop or pumping power, respectively. For defining the overall performance index of SCFHE, two links are employed. First one relates heat transfer between the fluid streams q and pumping power PP as (=qj/PPj); while another link relates effectiveness eff and pressure drop dP as (=effj/dPj). For analysis, the inlet temperatures of hot and cold streams are varied in usual range of 20dC-65dC. Fully turbulent regime is seldom encountered in micro-tubes and transition of flow regime occurs much early (i.e., ~Re=1000). Thus, Re is fixed at 900, however, the uncertainty in Re due to addition of nanoparticles in base fluid is quantified by averaging of Re. Moreover, for minimizing error, volumetric concentration is limited to range 0% to ≤4% only. Such framework may be helpful in utilizing maximum peripheral surface area of SCFHE without any serious severity on pumping power and towards developing advanced short heat exchangers.Keywords: CuO-water nanofluid, non-circular micro-tubes, performance index, short counter flow heat exchanger
Procedia PDF Downloads 2055 Microplastic Concentrations and Fluxes in Urban Compartments: A Systemic Approach at the Scale of the Paris Megacity
Authors: Rachid Dris, Robin Treilles, Max Beaurepaire, Minh Trang Nguyen, Sam Azimi, Vincent Rocher, Johnny Gasperi, Bruno Tassin
Abstract:
Microplastic sources and fluxes in urban catchments are only poorly studied. Most often, the approaches taken focus on a single source and only carry out a description of the contamination levels and type (shape, size, polymers). In order to gain an improved knowledge of microplastic inputs at urban scales, estimating and comparing various fluxes is necessary. The Laboratoire Eau, Environnement et Systèmes Urbains (LEESU), the Laboratoire Eau Environnement (LEE) and the SIAAP (Service public de l’assainissement francilien) initiated several projects to investigate different urban sources and flows of microplastics. A systemic approach is undertaken at the scale of Paris Megacity, and several compartments are considered, including atmospheric fallout, wastewater treatments plants, runoff and combined sewer overflows. These investigations are carried out within the Limnoplast and OPUR projects. Atmospheric fallout was sampled during consecutive periods ranging from 2 to 3 weeks with a stainless-steel funnel. Both wet and dry periods were considered. Different treatment steps were sampled in 2 wastewater treatment plants (Seine-Amont for activated sludge and Seine-Centre for biofiltration) of the SIAAP, including sludge samples. Microplastics were also investigated in combined sewer overflows as well as in stormwater at the outlet suburban catchment (Sucy-en-Brie, France) during four rain events. Samples are treated using hydroperoxide digestion (H₂O₂ 30 %) in order to reduce organic material. Microplastics are then extracted from the samples with a density separation step using NaI (d=1.6 g.cm⁻³). Samples are filtered on metallic filters with a porosity of 14 µm between steps to separate them from the solutions (H₂O₂ and NaI). The last filtration was carried out on alumina filters. Infrared mapping analysis (using a micro-FTIR with an MCT detector) is performed on each alumina filter. The resulting maps are analyzed using a microplastic analysis software simple, developed by Aalborg University, Denmark and Alfred Wegener Institute, Germany. Blanks were systematically carried out to consider sample contamination. This presentation aims at synthesizing the data found in the various projects. In order to carry out a systemic approach and compare the various inputs, all the data were converted into annual microplastic fluxes (number of microplastics per year), and extrapolated to the Parisian agglomeration. PP, PE and alkyd are the most prevalent polymers found in storm water samples. Rain intensity and microplastic concentrations did not show any clear correlation. Considering the runoff volumes and the impervious surface area of the studied catchment, a flux of 4*107–9*107 MPs.yr⁻¹.ha⁻¹ was estimated. Samples of wastewater treatment plants and atmospheric fallout are currently being analyzed in order to finalize this assessment. The representativeness of such samplings and uncertainties related to the extrapolations will be discussed and gaps in knowledge will be identified. The data provided by such an approach will help to prioritize future research as well as policy efforts.Keywords: microplastics, atmosphere, wastewater, urban runoff, Paris megacity, urban waters
Procedia PDF Downloads 1714 Unknown Groundwater Pollution Source Characterization in Contaminated Mine Sites Using Optimal Monitoring Network Design
Authors: H. K. Esfahani, B. Datta
Abstract:
Groundwater is one of the most important natural resources in many parts of the world; however it is widely polluted due to human activities. Currently, effective and reliable groundwater management and remediation strategies are obtained using characterization of groundwater pollution sources, where the measured data in monitoring locations are utilized to estimate the unknown pollutant source location and magnitude. However, accurately identifying characteristics of contaminant sources is a challenging task due to uncertainties in terms of predicting source flux injection, hydro-geological and geo-chemical parameters, and the concentration field measurement. Reactive transport of chemical species in contaminated groundwater systems, especially with multiple species, is a complex and highly non-linear geochemical process. Although sufficient concentration measurement data is essential to accurately identify sources characteristics, available data are often sparse and limited in quantity. Therefore, this inverse problem-solving method for characterizing unknown groundwater pollution sources is often considered ill-posed, complex and non- unique. Different methods have been utilized to identify pollution sources; however, the linked simulation-optimization approach is one effective method to obtain acceptable results under uncertainties in complex real life scenarios. With this approach, the numerical flow and contaminant transport simulation models are externally linked to an optimization algorithm, with the objective of minimizing the difference between measured concentration and estimated pollutant concentration at observation locations. Concentration measurement data are very important to accurately estimate pollution source properties; therefore, optimal design of the monitoring network is essential to gather adequate measured data at desired times and locations. Due to budget and physical restrictions, an efficient and effective approach for groundwater pollutant source characterization is to design an optimal monitoring network, especially when only inadequate and arbitrary concentration measurement data are initially available. In this approach, preliminary concentration observation data are utilized for preliminary source location, magnitude and duration of source activity identification, and these results are utilized for monitoring network design. Further, feedback information from the monitoring network is used as inputs for sequential monitoring network design, to improve the identification of unknown source characteristics. To design an effective monitoring network of observation wells, optimization and interpolation techniques are used. A simulation model should be utilized to accurately describe the aquifer properties in terms of hydro-geochemical parameters and boundary conditions. However, the simulation of the transport processes becomes complex when the pollutants are chemically reactive. Three dimensional transient flow and reactive contaminant transport process is considered. The proposed methodology uses HYDROGEOCHEM 5.0 (HGCH) as the simulation model for flow and transport processes with chemically multiple reactive species. Adaptive Simulated Annealing (ASA) is used as optimization algorithm in linked simulation-optimization methodology to identify the unknown source characteristics. Therefore, the aim of the present study is to develop a methodology to optimally design an effective monitoring network for pollution source characterization with reactive species in polluted aquifers. The performance of the developed methodology will be evaluated for an illustrative polluted aquifer sites, for example an abandoned mine site in Queensland, Australia.Keywords: monitoring network design, source characterization, chemical reactive transport process, contaminated mine site
Procedia PDF Downloads 2253 A Compact Standing-Wave Thermoacoustic Refrigerator Driven by a Rotary Drive Mechanism
Authors: Kareem Abdelwahed, Ahmed Salama, Ahmed Rabie, Ahmed Hamdy, Waleed Abdelfattah, Ahmed Abd El-Rahman
Abstract:
Conventional vapor-compression refrigeration systems rely on typical refrigerants, such as CFC, HCFC and ammonia. Despite of their suitable thermodynamic properties and their stability in the atmosphere, their corresponding global warming potential and ozone depletion potential raise concerns about their usage. Thus, the need for new refrigeration systems, which are environment-friendly, inexpensive and simple in construction, has strongly motivated the development of thermoacoustic energy conversion systems. A thermoacoustic refrigerator (TAR) is a device that is mainly consisting of a resonator, a stack and two heat exchangers. Typically, the resonator is a long circular tube, made of copper or steel and filled with Helium as a the working gas, while the stack has short and relatively low thermal conductivity ceramic parallel plates aligned with the direction of the prevailing resonant wave. Typically, the resonator of a standing-wave refrigerator has one end closed and is bounded by the acoustic driver at the other end enabling the propagation of half-wavelength acoustic excitation. The hot and cold heat exchangers are made of copper to allow for efficient heat transfer between the working gas and the external heat source and sink respectively. TARs are interesting because they have no moving parts, unlike conventional refrigerators, and almost no environmental impact exists as they rely on the conversion of acoustic and heat energies. Their fabrication process is rather simpler and sizes span wide variety of length scales. The viscous and thermal interactions between the stack plates, heat exchangers' plates and the working gas significantly affect the flow field within the plates' channels, and the energy flux density at the plates' surfaces, respectively. Here, the design, the manufacture and the testing of a compact refrigeration system that is based on the thermoacoustic energy-conversion technology is reported. A 1-D linear acoustic model is carefully and specifically developed, which is followed by building the hardware and testing procedures. The system consists of two harmonically-oscillating pistons driven by a simple 1-HP rotary drive mechanism operating at a frequency of 42Hz -hereby, replacing typical expensive linear motors and loudspeakers-, and a thermoacoustic stack within which the energy conversion of sound into heat is taken place. Air at ambient conditions is used as the working gas while the amplitude of the driver's displacement reaches 19 mm. The 30-cm-long stack is a simple porous ceramic material having 100 square channels per square inch. During operation, both oscillating-gas pressure and solid-stack temperature are recorded for further analysis. Measurements show a maximum temperature difference of about 27 degrees between the stack hot and cold ends with a Carnot coefficient of performance of 11 and estimated cooling capacity of five Watts, when operating at ambient conditions. A dynamic pressure of 7-kPa-amplitude is recorded, yielding a drive ratio of 7% approximately, and found in a good agreement with theoretical prediction. The system behavior is clearly non-linear and significant non-linear loss mechanisms are evident. This work helps understanding the operation principles of thermoacoustic refrigerators and presents a keystone towards developing commercial thermoacoustic refrigerator units.Keywords: refrigeration system, rotary drive mechanism, standing-wave, thermoacoustic refrigerator
Procedia PDF Downloads 3602 Cardiac Hypertrophy in Diabetes; The Role of Factor Forkhead Box Class O-Regulation by O-GlcNAcylation
Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian
Abstract:
Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin
Procedia PDF Downloads 1031 Extracellular Polymeric Substances Study in an MBR System for Fouling Control
Authors: Dimitra C. Banti, Gesthimani Liona, Petros Samaras, Manasis Mitrakas
Abstract:
Municipal and industrial wastewaters are often treated biologically, by the activated sludge process (ASP). The ASP not only requires large aeration and sedimentation tanks, but also generates large quantities of excess sludge. An alternative technology is the membrane bioreactor (MBR), which replaces two stages of the conventional ASP—clarification and settlement—with a single, integrated biotreatment and clarification step. The advantages offered by the MBR over conventional treatment include reduced footprint and sludge production through maintaining a high biomass concentration in the bioreactor. Notwithstanding these advantages, the widespread application of the MBR process is constrained by membrane fouling. Fouling leads to permeate flux decline, making more frequent membrane cleaning and replacement necessary and resulting to increased operating costs. In general, membrane fouling results from the interaction between the membrane material and the components in the activated sludge liquor. The latter includes substrate components, cells, cell debris and microbial metabolites, such as Extracellular Polymeric Substances (EPS) and Sludge Microbial Products (SMPs). The challenge for effective MBR operation is to minimize the rate of Transmembrane Pressure (TMP) increase. This can be achieved by several ways, one of which is the addition of specific additives, that enhance the coagulation and flocculation of compounds, which are responsible for fouling, hence reducing biofilm formation on the membrane surface and limiting the fouling rate. In this project the effectiveness of a non-commercial composite coagulant was studied as an agent for fouling control in a lab scale MBR system consisting in two aerated tanks. A flat sheet membrane module with 0.40 um pore size was submerged into the second tank. The system was fed by50 L/d of municipal wastewater collected from the effluent of the primary sedimentation basin. The TMP increase rate, which is directly related to fouling growth, was monitored by a PLC system. EPS, MLSS and MLVSS measurements were performed in samples of mixed liquor; in addition, influent and effluent samples were collected for the determination of physicochemical characteristics (COD, BOD5, NO3-N, NH4-N, Total N and PO4-P). The coagulant was added in concentrations 2, 5 and 10mg/L during a period of 2 weeks and the results were compared with the control system (without coagulant addition). EPS fractions were extracted by a three stages physical-thermal treatment allowing the identification of Soluble EPS (SEPS) or SMP, Loosely Bound EPS (LBEPS) and Tightly Bound EPS (TBEPS). Proteins and carbohydrates concentrations were measured in EPS fractions by the modified Lowry method and Dubois method, respectively. Addition of 2 mg/L coagulant concentration did not affect SEPS proteins in comparison with control process and their values varied between 32 to 38mg/g VSS. However a coagulant dosage of 5mg/L resulted in a slight increase of SEPS proteins at 35-40 mg/g VSS while 10mg/L coagulant further increased SEPS to 44-48mg/g VSS. Similar results were obtained for SEPS carbohydrates. Carbohydrates values without coagulant addition were similar to the corresponding values measured for 2mg/L coagulant; the addition of mg/L coagulant resulted to a slight increase of carbohydrates SEPS to 6-7mg/g VSS while a dose of 10 mg/L further increased carbohydrates content to 9-10mg/g VSS. Total LBEPS and TBEPS, consisted of proteins and carbohydrates of LBEPS and TBEPS respectively, presented similar variations by the addition of the coagulant. Total LBEPS at 2mg/L dose were almost equal to 17mg/g VSS, and their values increased to 22 and 29 mg/g VSS during the addition of 5 mg/L and 10 mg/L of coagulant respectively. Total TBEPS were almost 37 mg/g VSS at a coagulant dose of 2 mg/L and increased to 42 and 51 mg/g VSS at 5 mg/L and 10 mg/L doses, respectively. Therefore, it can be concluded that coagulant addition could potentially affect microorganisms activities, excreting EPS in greater amounts. Nevertheless, EPS increase, mainly SEPS increase, resulted to a higher membrane fouling rate, as justified by the corresponding TMP increase rate. However, the addition of the coagulant, although affected the EPS content in the reactor mixed liquor, did not change the filtration process: an effluent of high quality was produced, with COD values as low as 20-30 mg/L.Keywords: extracellular polymeric substances, MBR, membrane fouling, EPS
Procedia PDF Downloads 256