Search results for: transitional cell carcinoma

Authors: Flavien Marteau, Pedro Affonso Nóbrega, Pascal Biwole, Nicolas Autrusson, Iona De Bievre, Christian Beauger

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Effective water management is essential for the optimal performance of fuel cells. For this reason, many vehicle systems use a membrane humidifier, a passive device that humidifies the air before the cathode inlet. Although they offer good performance, humidifiers are voluminous, costly, and fragile, hence the desire to find an alternative. Direct water injection could be an option, although this method lacks maturity. It consists of injecting liquid water as a spray in the dry heated air coming out from the compressor. This work focuses on the evaluation of direct water injection and its performance compared to the membrane humidifier selected as a reference. Two architectures were experimentally tested to humidify an industrial 2 kW short stack made up of 20 cells of 150 cm² each. For the reference architecture, the inlet air is humidified with a commercial membrane humidifier. For the direct water injection architecture, a pneumatic nozzle was selected to generate a fine spray in the air flow with a Sauter mean diameter of about 20 μm. Initial performance was compared over the entire range of current based on polarisation curves. Then, the influence of various parameters impacting water management was studied, such as the temperature, the gas stoichiometry, and the water injection flow rate. The experimental results obtained confirm the possibility of humidifying the fuel cell using direct water injection. This study, however shows the limits of this humidification method, the mean cell voltage being significantly lower in some operating conditions with direct water injection than with the membrane humidifier. The voltage drop reaches 30 mV per cell (4 %) at 1 A/cm² (1,8 bara, 80 °C) and increases in more demanding humidification conditions. It is noteworthy that the heat of compression available is not enough to evaporate all the injected liquid water in the case of DWI, resulting in a mix of liquid and vapour water entering the fuel cell, whereas only vapour is present with the humidifier. Variation of the injection flow rate shows that part of the injected water is useless for humidification and seems to cross channels without reaching the membrane. The stack was successfully humidified thanks to direct water injection. Nevertheless, our work shows that its implementation requires substantial adaptations and may reduce the fuel cell stack performance when compared to conventional membrane humidifiers, but opportunities for optimisation have been identified.

Keywords: cathode humidification, direct water injection, membrane humidifier, proton exchange membrane fuel cell

Procedia PDF Downloads 45

Authors: Gürkan Şakar, Fevzi Çakmak Bolat

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In this study free vibration analysis of aluminum honeycomb sandwich structures were carried out experimentally and numerically. The natural frequencies and mode shapes of sandwich structures fabricated with different configurations for clamped-free boundary condition were determined. The effects of lower and upper face sheet thickness, the core material thickness, cell diameter, cell angle and foil thickness on the vibration characteristics were examined. The numerical studies were performed with ANSYS package. While the sandwich structures were modeled in ANSYS the continuum model was used. Later, the numerical results were compared with the experimental findings.

Keywords: sandwich structure, free vibration, numeric analysis, 3D model, continuum model

Procedia PDF Downloads 417

Authors: Mohadeseh Salari Sardari

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As Muslims conquered Iran, their first impression was to show their power over others. They needed mosques for their multiple needs like prayer, tax collecting, law-making, hearing of law cases, and most important of all, as a seat of government. Sometimes they did not have time to build mosques and only began to build them after years of ruling. Many religious buildings with pre-Islamic past survived in Iran, most of the fire temples in cities were destroyed or changed radically, but some deserted temples outside of cities survived, and based on these surviving buildings, we can trace changes in fire temples inside cities and discover how they were adapted and expanded to be mosques. In addition, there are some other buildings with doubts about their date of construction. These buildings might be transitional buildings between two different historical eras or might be an old building with a slight change. One of these interesting buildings is Tarikhaneh, a small, simple yet striking building. By tracing Tarikhaneh’s roots in other buildings like fire temples and secular buildings existed before Arab invasion, it can be better understood how the original form of Tatikhaneh was.

Keywords: iranian architecture, early mosques, fire temples, adaptation and reuse

Procedia PDF Downloads 137

Authors: Chutamas Thepmalee, Aussara Panya, Mutita Junking, Jatuporn Sujjitjoon, Nunghathai Sawasdee, Pa-Thai Yenchitsomanus

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Cholangiocarcinoma (CCA) is an aggressive malignancy of bile duct epithelial cells in which the standard treatments, including surgery, radiotherapy, chemotherapy, and targeted therapy are partially effective. Many solid tumors including CCA escape host immune responses by creating tumor microenvironment and generating immunosuppressive cytokines such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). These cytokines can inhibit dendritic cell (DC) differentiation and function, leading to decreased activation and response of effector CD4+ and CD8+ T cells for cancer cell elimination. To overcome the effects of these immunosuppressive cytokines and to increase ability of DC to activate effector CD4+ and CD8+ T cells, we generated self-differentiated DCs (SD-DCs) with down-regulation of IL-10 and TGF-β receptors for activation of effector CD4+ and CD8+ T cells. Human peripheral blood monocytes were initially transduced with lentiviral particles containing the genes encoding GM-CSF and IL-4 and then secondly transduced with lentiviral particles containing short-hairpin RNAs (shRNAs) to knock-down mRNAs of IL-10 and TGF-β receptors. The generated SD-DCs showed up-regulation of MHC class II (HLA-DR) and co-stimulatory molecules (CD40 and CD86), comparable to those of DCs generated by convention method. Suppression of IL-10 and TGF-β receptors on SD-DCs by specific shRNAs significantly increased levels of IFN-γ and also increased cytolytic activity of DC-activated effector T cells against CCA cell lines (KKU-213 and KKU-100), but it had little effect to immortalized cholangiocytes (MMNK-1). Thus, SD-DCs with down-regulation of IL-10 and TGF-β receptors increased activation of effector T cells, which is a recommended method to improve DC function for the preparation of DC-activated effector T cells for adoptive T-cell therapy.

Keywords: cholangiocarcinoma, IL-10 receptor, self-differentiated dendritic cells, TGF-β receptor

Procedia PDF Downloads 142

Authors: Y. Cochet, A. Achim, Tom Flatman, J-C. Domec, J. Ogée, L. Wingate, Ram Oren

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It is accepted that atmospheric CO2 concentration will increase in the future. For the past 30 years, researchers have used FACE (Free-Air Carbon Dioxide Enrichment) facilities to study the development of terrestrial ecosystems under elevated CO2 (eCO2). Forest responses to eCO2 are likely to impact timber industries with potential feedbacks towards the atmosphere. The main objectives of this study were to examine whether eCO2 alone or in combination with N-fertilization alter wood properties and to identify changes in wood anatomy related to water transport. Wood disks were sampled at breast height from mature loblolly pine trees (Pinus taeda L.) harvested at the Duke FACE site (NC, USA). By measuring ring width and intra-ring changes in density (X-ray densitometry) and tracheid size (lumen and cell wall thickness) from pith to bark, the following hypotheses were tested: 1) eCO2 and N-fertilization interact positively to increase significantly above-ground primary productivity; 2) eCO2 and N-fertilization lead to a decrease in density; 3) eCO2 and N-fertilization increase lumen diameter and decrease cell wall thickness, thus affecting water transport capacity. Our results revealed a boost in earlywood tracheid production induced by eCO2 lasting a few years. The following decrease seemed to be buffered by N-fertilization. X-ray profiles did not show a marked decrease in wood density under eCO2 or N-fertilization, although there were changes in cell anatomical properties such as a reduction in cell-wall thickness and an increase in lumen diameter. If such effects of eCO2 are confirmed, forest management strategies for example N-fertilization should be redesigned.

Keywords: wood density, Duke FACE (free-air carbon dioxide enrichment), N fertilization, tree ring

Procedia PDF Downloads 336

Authors: Thais Cavalheri Santos, Pedro Jose Gabriel Ferreira, Alexandre Daliberto Frugoli, Lucio Leonardo, Pedro Americo Frugoli

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This paper presents a low cost education proposal to be used in engineering courses. The engineering education in universities of a developing country that is in need of an increasing number of engineers carried out with quality and affordably, pose a difficult problem to solve. In Brazil, the political and economic scenario requires academic managers able to reduce costs without compromising the quality of education. Within this context, the elaboration of a physics principles teaching method with the construction of an electronic balance is proposed. First, a method to develop and construct a load cell through which the students can understand the physical principle of strain gauges and bridge circuit will be proposed. The load cell structure was made with aluminum 6351T6, in dimensions of 80 mm x 13 mm x 13 mm and for its instrumentation, a complete Wheatstone Bridge was assembled with strain gauges of 350 ohms. Additionally, the process involves the use of a software tool to document the prototypes (design circuits), the conditioning of the signal, a microcontroller, C language programming as well as the development of the prototype. The project also intends to use an open-source I/O board (Arduino Microcontroller). To design the circuit, the Fritizing software will be used and, to program the controller, an open-source software named IDE®. A load cell was chosen because strain gauges have accuracy and their use has several applications in the industry. A prototype was developed for this study, and it confirmed the affordability of this educational idea. Furthermore, the goal of this proposal is to motivate the students to understand the several possible applications in high technology of the use of load cells and microcontroller.

Keywords: Arduino, load cell, low-cost education, strain gauge

Procedia PDF Downloads 303

Authors: Florge Francis A. Sy

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Acute pancreatitis (AP) is an inflammatory condition of the pancreas with local and systemic complications. Severe acute pancreatitis (SAP) has a higher mortality rate. Laboratory parameters like the neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), and mean platelet volume (MPV) have been associated with SAP but with conflicting results. This study aims to determine the predictive value of these parameters on the severity and in-hospital mortality of AP. This retrospective, cross-sectional study was done in a private hospital in Cebu City, Philippines. One-hundred five patients were classified according to severity based on the modified Marshall scoring. The admitting hemogram, including the NLR, RDW, and MPV, was obtained from the complete blood count (CBC). Cut-off values for severity and in-hospital mortality were derived from the ROC. Association between NLR, RDW, and MPV with SAP and mortality were determined with a p-value of < 0.05 considered significant. The mean age for AP was 47.6 years, with 50.5% being male. Most had an unknown cause (49.5%), followed by a biliary cause (37.1%). Of the 105 patients, 23 patients had SAP, and 4 died. Older age, longer in-hospital duration, congestive heart failure, elevated creatinine, urea nitrogen, and white blood cell count were seen in SAP. The NLR was associated with in-hospital mortality using a cut-off of > 10.6 (OR 1.133, 95% CI, p-value 0.003) with 100% sensitivity, 70.3% specificity, 11.76% PPV and 100% NPV (AUC 0.855). The NLR was not associated with SAP. The RDW and MPV were not associated with SAP and mortality. The admitting NLR is, therefore, an easily accessible parameter that can predict in-hospital mortality in acute pancreatitis. Although the present study did not show an association of NLR with SAP nor RDW and MPV with both SAP and mortality, further studies are suggested to establish their clinical value.

Keywords: acute pancreatitis, mean platelet volume, neutrophil-lymphocyte ratio, red cell distribution width

Procedia PDF Downloads 125

Authors: Yun-An Chen, Hung-Jun Lin, Tai-Horng Young, Der-Zen Liu

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Decellularized brain extracellular matrix had been shown that it has the ability to influence on cell proliferation, differentiation and associated cell phenotype. However, this scaffold is thought to have poor mechanical properties and rapid degradation, it is hard for cell recellularization. In this study, we used decellularized brain extracellular matrix combined with chitosan, which is naturally occurring polysaccharide and non-cytotoxic polymer, forming a 3-D scaffold for neural stem/precursor cells (NSPCs) regeneration. HE staining and DAPI fluorescence staining confirmed decellularized process could effectively vanish the cellular components from the brain. GAGs and collagen I, collagen IV were be showed a great preservation by Alcain staining and immunofluorescence staining respectively. Decellularized brain extracellular matrix was well mixed in chitosan to form a 3-D scaffold (DB-C scaffold). The pore size was approximately 50±10 μm examined by SEM images. Alamar blue results demonstrated NSPCs had great proliferation ability in DB-C scaffold. NSPCs that were cultured in this complex scaffold differentiated into neurons and astrocytes, as reveled by NSPCs expression of microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein (GFAP). In conclusion, DB-C scaffold may provide bioinformatics cues for NSPCs generation and aid for CNS injury functional recovery applications.

Keywords: brain, decellularization, chitosan, scaffold, neural stem/precursor cells

Procedia PDF Downloads 321

Authors: Galawezh Obaid Othman

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The present investigation was undertaken to evaluate the germ cell toxicity induced by ciprofloxacin antibiotic and the Protective effect of grape seed oil, Ciproflaxin uses include treatment of genitor-urinary and some reproductive tract bacterial infections. One of the most attractive approaches to disease prevention involves the use of natural antioxidants to protect tissue against toxic injury, the possible protective effect of grape seed oil, against ciprofloxacin induced reproductive toxicity on mouse .the animals were randomly divided into four groups consisting of five mice. Group (1) was orally given distilled water (solvent of the used drugs) and kept as a control. Group (2) was administered 6ml/kg. b.w of grape seed oil orally 15 days .Group (3) was administered 206mg/kg. b.w of ciprofloxacin orally for 15 days.. Last group was treated orally with Grape seed oil (6mg/kg b.w. /day) prior to an orally administered ciprofloxacin (CPX) at a dose of 206 mg⁄kg. b.w. by three hours for fifteen days. Ciproflaxin have ability to induce various types of sperm abnormalities such as (Sperm without head, sperm without tail, defective head spearm,swollen head sperm ), The results explored that Grape seed oil possesses statistically significant (p<0.05) protective potential against Ciproflaxin by decreasing sperm abnormalities frequency in mouse.

Keywords: antimutagen, ciprofloxacin, grape seed oil, germ cell

Procedia PDF Downloads 440

Authors: Xi Yu, Lili Gu, Huizhu Wang, Xiao Wei, Dandan Sheng, Xiaoyan Jiang, Min Hong

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Introduction: Hypersensitivity disease is difficult to cure completely because of its recurrence, yupingfengsan (YPFS) is used to treat the diseases with the advantage of reducing the recurrence,but the precise mechanism is not clear. Previous studies of our laboratory have shown that the extract of YPFS can inhibit Th2-type allergic contact dermatitis(ACD) induced by FITC.Besides, thymic stromal lymphopoietin(TSLP) have been proved to be a master switch for allergic inflammation. Based on these studies, we want to establish a mouse model of TSLP production based on Th2 cell-mediated allergic inflammation to explore the regulating mechanisms of YPFS on TSLP in Th2 cell-mediated allergic inflammation. Methods: Th2-type ACD mouse model: The mice were topically sensitized on the abdomens (induction phase) and elicited on its ears skin 6 day later (excitation phase) with FITC solution, and the ear swelling was measured to evaluate the allergic inflammation；A mouse model of TSLP production based on Th2 cell-mediated allergic inflammation (TSLP production model): the skin of the ear was sensitized on two consecutive days with FITC solution causing the production of TSLP；Mice were treated with YPFS extract，ELISA、Real-time PCR and Western-blotting were using to examine the mRNA and protein levels of TSLP\TSLPR and TLRs ect. Results: YPFS extract can attenuates Th2-type allergic inflammatory in mice；in TSLP production model, YPFS can inhibit the expression of TSLP、 TSLPR、TLRs and MyD88, So we deduce the possible mechanisms of YPFS to play a role of intervention is through TLRs- MyD88 dependent and independent pathway to reduce TSLP production.

Keywords: YPFS, TSLP, TLRs, Th2-type allergic contact dermatitis

Procedia PDF Downloads 423

Authors: Komal Vig, Syamala Soumyakrishnan, Yadav Baral

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Bypass surgery, using the autologous vein has been one of the most effective treatments for cardiovascular diseases (CVD). More recently tissue engineering including engineered vascular grafts to synthesize blood vessels is gaining usage. Dacron and ePTFE has been employed for vascular grafts, however, these does not work well for small diameter grafts (<6 mm) due to intimal hyperplasia and thrombosis. In the present study PTFE was treated with LTP to improve the endothelialization of intimal surface of graft. Scaffolds were also modified with polyvinylpyrrolidone coated silver nanoparticles (Ag-PVP) and the antimicrobial peptides, p753 and p359. Human umbilical vein endothelial cells (HUVEC) were plated on the developed scaffolds and cell proliferation was determined by the MTT assay. Cells attachment on scaffolds was visualized by microscopy. mRNA expressions levels of different cell markers were investigated using quantitative real-time PCR (qPCR). X ray photoelectron spectroscopic confirmed the introduction of oxygenated functionalities from LTP air plasma. Microscopic and MTT assays indicated increase in cell viability in LTP treated scaffolds. Gene expression studies shows enhanced expression of cell adhesion marker Integrin- α 5 gene after LTP treatment. The KB test displayed a zone of inhibition for Ag-PVP, p753 and p359 of 19mm, 14mm, and 12mm respectively. To determine toxicity of antimicrobial agents to cells, MTT Assay was performed using HEK293 cells. MTT Assay exhibited that Ag-PVP and the peptides were non-toxic to cells at 100μg/mL and 50μg/mL, respectively. Live/dead analysis and plate count of treated bacteria exhibited bacterial inhibition on develop scaffold compared to non-treated scaffold. SEM was performed to analyze the structural changes of bacteria after treatment with antimicrobial agents. Gene expression studies were conducted on RNA from bacteria treated with Ag-PVP and peptides using qRT-PCR. Based on our initial results, more scaffolds alternatives will be developed and investigated for cell growth and vascularization studies.

Keywords: low temperature plasma, vascular graft, HUVEC cells, antimicrobial

Procedia PDF Downloads 244

Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

Procedia PDF Downloads 282

Authors: Barzin Rajabloo, Martin Desilets

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First, an electrochemical model for the reduction of CO₂ into CH₃OH is developed in which mass and charge transfer, reactions at the surface of the electrodes and fluid flow of the electrolyte are considered. This mathematical model is developed in COMSOL Multiphysics® where both secondary and tertiary current distribution interfaces are coupled to consider concentrations and potentials inside different parts of the cell. Constant reaction rates are assumed as the fitted parameters to minimize the error between experimental data and modeling results. The model is validated through a comparison with experimental data in terms of faradaic efficiency for production of CH₃OH, the current density in different applied cathode potentials as well as current density in different electrolyte flow rates. The comparison between model outputs and experimental measurements shows a good agreement. The model indicates the higher hydrogen evolution in comparison with CH₃OH production as well as mass transfer limitation caused by CO₂ concentration, which are consistent with findings in the literature. After validating the model, in the second part of the study, some design parameters of the cell, such as cathode geometry and catholyte/anolyte channel widths, are modified to reach better performance and higher faradaic efficiency of methanol production.

Keywords: carbon dioxide, electrochemical reduction, methanol, modeling

Procedia PDF Downloads 109

Authors: Myoung-Jin Kim, Chang-Bin Ha, Yeong-Seop Ahn, Hyoung-Kyu Song

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This paper proposes a cooperative communication scheme for improve wireless communication performance. When the receiver is located in the edge of coverage, the signal from the transmitter is distorted for various reasons such as inter-cell interference (ICI), power reduction, incorrect channel estimation. In order to improve communication performance, the proposed scheme adds the relay. By the relay, the receiver has diversity gain. In this paper, two base stations, one relay and one destination are considered. The two base stations transmit same time to relay and destination. The relay forwarding to destination and the destination detects signals.

Keywords: cooperative communication, diversity gain, OFDM, MMSE

Procedia PDF Downloads 390

Authors: Stanley Dula, Oluwatosini A. Ijabadeniyi

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Biofilm formation is a major source of materials and foodstuffs contamination, contributing to occurrence of pathogenic and spoilage microbes in food processing resulting in food spoilage, transmission of diseases and significant food hygiene and safety issues. This study elucidates biofilm formation of E. coli O157:H7 and L. monocytogenes ATCC 7644 grown under food related environmental stress conditions of varying pH (5.0;7.0; and 8.5) and temperature (15, 25 and 37 ℃). Both strains showed confluent biofilm formation at 25 ℃ and 37 ℃, at pH 8.5 after 5 days. E. coli showed curli fimbriae production at various temperatures, while L. monocytogenes did not show pronounced expression. Swarm, swimming and twitching plate assays were used to determine strain motilities. Characterization of cell hydrophobicity was done using the microbial adhesion to hydrocarbons (MATH) assay using n-hexadecane. Both strains showed hydrophilic characteristics as they fell within a < 20 % interval. FT-IR revealed COOH at 1622 cm-1, and a strong absorption band at 3650 cm-1 – 3200 cm-1 indicating the presence of both -OH and -NH groups. Both strains were hydrophilic and could form biofilm at different combinations of temperature and pH. EPS produced in both species proved to be an acidic hetero-polysaccharide.

Keywords: biofilm, pathogens, hydrophobicity, motility

Procedia PDF Downloads 237

Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

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Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

Procedia PDF Downloads 208

Authors: Md. Mizanur Rahman, Anquan Liu, Anna Frostegård, Johan Frostegård

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The role of the human immune system is essential in cardiovascular diseases and atherosclerosis. Activated cells in atherosclerosis produce abundant amounts of cytokines, but the exact mechanisms involved in the effects of these inflammatory cytokines are not clear in atherosclerosis. In a large clinical cohort, we have previously determined that antibodies against phosphorylcholine (anti-PC) are negatively and independently associated with both development of atherosclerosis and also a low risk of cardiovascular disease. Further, we reported that rheumatoid arthritis patients who were non-responders to TNF-inhibitors, where those with low anti-PC levels. Upon anti-TNF treatment, anti-PC levels increased. We, therefore, hypothesised that proinflammatory cytokines such as TNF could play a role in anti-PC regulation. Peripheral blood mononuclear cells (PBMC) were cultured with or without TNF and anti-TNF. The cell supernatants were collected after six days for ELISA measurements. In separate experiments, cells were cultured for 24 hours in both polystyrene plates and ELISPOT plates under a similar condition for ELISA and ELISPOT assays respectively. Total RNA was extracted after 6 hours of cell culture to perform RT-qPCR. Cell viability was confirmed by trypan blue staining and MTT assays. ELISA measurements detected less than 40% of anti-PC in TNF-treated cells, in comparison to control cells, whereas anti-PC production was recovered by anti-TNF treatment. ELISPOT assays showed that TNF suppresses anti-PC production by inhibiting anti-PC producing B-cells. In addition, RT-qPCR and ELISA showed that TNF also has effects also on B-cell activation as BAFF expression was inhibited by TNF treatment. Atherosclerosis is a major cause of cardiovascular diseases, but anti-PC is a protection marker for atherosclerosis development. Our findings show that TNF is a negative regulator of anti-PC production. Immune modulation and rising of anti-PC could be of major significance for the patients.

Keywords: anti-PC, Anti-TNF, atherosclerosis, cardiovascular diseases, phosphorylecholine

Procedia PDF Downloads 244

Authors: Chih-Rong Shyr, Chi-Ping Huang

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Intravesical BCG is the gold-standard therapy for high risk non-muscle invasive bladder cancer (NMIBC) after TURBT, but if not responsive to BCG, these BCG unresponsive patients face cystectomy that causes morbidity and comes with a morality risk. To provide the bladder sparing options for patients with BCG-unresponsive NMIBC, several new treatments have been developed to salvage the bladders and prevent progression to muscle invasive or metastatic, but however, most approved or developed treatments still fail in a significant proportion of patients without long term success. Thus more treatment options and the combination of different therapeutic modalities are urgently needed to change the outcomes. Xenogeneic rejection has been proposed to a mechanism of action to induce anti-tumor immunity for the treatment of cancers due to the similarities between rejection mechanism to xenoantigens (proteins, glycans and lipids) and anti-tumor immunities to tumor specific antigens (neoantigens, tumor associated carbohydrates and lipids). Xenogeneic urothelial cells (XUC) of porcine origin have been shown to induce anti-tumor immune responses to inhibit bladder tumor progression in mouse bladder cancer models. To further demonstrate the efficacy of the distinct intravesical XUC treatment in NMIBC, and the combined effects with chemotherapy and immune checkpoint inhibitors (ICIs) as a alternate therapeutic option, this study investigated the therapeutic effects and mechanisms of intravesical XUC immunotherapy in an orthotopic mouse immune competent model of NMIBC, generated from a mouse bladder cancer cell line. We found that the tumor progression was inhibited by intravescial XUC treatment and there was a synergy between intravesical XUC with intravesical chemotherapeutic agent, gemcitabine or systemic ICI, anti-PD1 antibody treatment. The cancer cell proliferation was decreased but the cell death was increased by the intravecisal XUC treatment. Most importantly, the mechanisms of action of intravesical XUC immunotherapy were found to be linked to enhanced infiltration of CD4+ and CD8+ T-cell as well as NK cells, but decreased presence of myeloid immunosuppressive cells in XUC treated tumors. The increased stimulation of immune cells of XUC treated mice to xenogeneic urothelial cells and mouse bladder cancer cells in immune cell proliferation and cytokine secretion were observed both as a monotherapy and in combination with intravesical gemcitabine or systemic anti PD-L1 treatment. In sum, we identified the effects of intravesical XUC treatment in monotherapy and combined therapy on tumor progression and its cellular and molecular events related to immune activation to understand the anti-tumoral mechanisms behind intravesical XUC immunotherapy for NMIBC. These results contribute to the understanding of the mechanisms behind successful xenogeneic cell immunotherapy against NMIBC and characterize a novel therapeutic approach with a new xenogeneic cell modality for BCG-unresponsive NMIBC.

Keywords: xenoantigen, neoantigen, rejection, immunity

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Authors: Mariyah Poonawala, Selvan Ravindran, Anuradha Vaidya

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Despite much progress in understanding the regulatory factors and cytokines that support the maturation of the various cell lineages of the hematopoietic system, factors that govern the self-renewal and proliferation of hematopoietic stem cells (HSCs) is still a grey area of research. Hematopoietic stem cell transplantation (HSCT) has evolved over the years and gained tremendous importance in the treatment of both malignant and non-malignant diseases. However, factors such as graft rejection and multiple organ failure have challenged HSCT from time to time, underscoring the urgent need for development of milder processes for successful hematopoietic transplantation. An emerging concept in the field of stem cell biology states that the interactions between the bone-marrow micro-environment and the hematopoietic stem and progenitor cells is essential for regulation, maintenance, commitment and proliferation of stem cells. Understanding the role of mesenchymal stromal cells in modulating the functionality of HSCs is, therefore, an important area of research. Trans-resveratrol has been extensively studied for its various properties to combat and prevent cancer, diabetes and cardiovascular diseases etc. The aim of the present study was to understand the effect of trans-resveratrol on HSCs using single and co-culture systems. We have used KG1a cells since it is a well accepted hematopoietic stem cell model system. Our preliminary experiments showed that low concentrations of trans-resveratrol stimulated the HSCs to undergo proliferation whereas high concentrations of trans-resveratrol did not stimulate the cells to proliferate. We used a murine fibroblast cell line, M210B4, as a stromal feeder layer. On culturing the KG1a cells with M210B4 cells, we observed that the stimulatory as well as inhibitory effects of trans-resveratrol at low and high concentrations respectively, were enhanced. Our further experiments showed that low concentration of trans-resveratrol reduced the generation of reactive oxygen species (ROS) and nitric oxide (NO) whereas high concentrations increased the oxidative stress in KG1a cells. We speculated that perhaps the oxidative stress was imposing inhibitory effects at high concentration and the same was confirmed by performing an apoptotic assay. Furthermore, cell cycle analysis and growth kinetic experiments provided evidence that low concentration of trans-resveratrol reduced the doubling time of the cells. Our hypothesis is that perhaps at low concentration of trans-resveratrol the cells get pushed into the G0/G1 phase and re-enter the cell cycle resulting in their proliferation, whereas at high concentration the cells are perhaps arrested at G2/M phase or at cytokinesis and therefore undergo apoptosis. Liquid Chromatography-Quantitative-Time of Flight–Mass Spectroscopy (LC-Q-TOF MS) analyses indicated the presence of trans-resveratrol and its metabolite(s) in the supernatant of the co-cultured cells incubated with high concentration of trans-resveratrol. We conjecture that perhaps the metabolites of trans-resveratrol are responsible for the apoptosis observed at the high concentration. Our findings may shed light on the unsolved problems in the in vitro expansion of stem cells and may have implications in the ex vivo manipulation of HSCs for therapeutic purposes.

Keywords: co-culture system, hematopoietic micro-environment, KG1a cell line, M210B4 cell line, trans-resveratrol

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Authors: Na Li, Samuel Simon Araya, Søren Knudsen Kær

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This study investigates the effects of operating parameters of different current density, temperature and pressure on the performance of a proton exchange membrane (PEM) water electrolysis stack. A 7-cell PEM water electrolysis stack was assembled and tested under different operation modules. The voltage change and polarization curves under different test conditions, namely current density, temperature and pressure, were recorded. Results show that higher temperature has positive effect on overall stack performance, where temperature of 80 ℃ improved the cell performance greatly. However, the cathode pressure and current density has little effect on stack performance.

Keywords: PEM electrolysis stack, current density, temperature, pressure

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Authors: Abdullah Almatouq

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Understanding the impact of key operational variables on concurrent energy generation and phosphorus recovery in microbial fuel cell is required to improve the process and reduce the operational cost. In this study, full factorial design (FFD) and central composite designs (CCD) were employed to identify the effect of influent COD concentration and cathode aeration flow rate on energy generation and phosphorus (P) recovery and to optimise MFC power density and P recovery. Results showed that influent chemical oxygen demand (COD) concentration and cathode aeration flow rate had a significant effect on power density, coulombic efficiency, phosphorus precipitation efficiency and phosphorus precipitation rate at the cathode. P precipitation was negatively affected by the generated current during the batch duration. The generated energy was reduced due to struvite being precipitated on the cathode surface, which might obstruct the mass transfer of ions and oxygen. Response surface mathematical model was used to predict the optimum operating conditions that resulted in a maximum power density and phosphorus precipitation efficiency of 184 mW/m² and 84%, and this corresponds to COD= 1700 mg/L and aeration flow rate=210 mL/min. The findings highlight the importance of the operational conditions of energy generation and phosphorus recovery.

Keywords: energy, microbial fuel cell, phosphorus, struvite

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Authors: Ana Paula Soares, Alexandrina Lages, Helena Oliveira, Francisco-Javier Gutiérrez-Domínguez, Marisa Lousada

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From an early age, exposure to a spoken language allows us to implicitly capture the structure underlying the succession of the speech sounds in that language and to segment it into meaningful units (words). Statistical learning (SL), i.e., the ability to pick up patterns in the sensory environment even without intention or consciousness of doing it, is thus assumed to play a central role in the acquisition of the rule-governed aspects of language and possibly to lie behind the language difficulties exhibited by children with development language disorder (DLD). The research conducted so far has, however, led to inconsistent results, which might stem from the behavioral tasks used to test SL. In a classic SL experiment, participants are first exposed to a continuous stream (e.g., syllables) in which, unbeknownst to the participants, stimuli are grouped into triplets that always appear together in the stream (e.g., ‘tokibu’, ‘tipolu’), with no pauses between each other (e.g., ‘tokibutipolugopilatokibu’) and without any information regarding the task or the stimuli. Following exposure, SL is assessed by asking participants to discriminate between triplets previously presented (‘tokibu’) from new sequences never presented together during exposure (‘kipopi’), i.e., to perform a two-alternative-forced-choice (2-AFC) task. Despite the widespread use of the 2-AFC to test SL, it has come under increasing criticism as it is an offline post-learning task that only assesses the result of the learning that had occurred during the previous exposure phase and that might be affected by other factors beyond the computation of regularities embedded in the input, typically the likelihood two syllables occurring together, a statistic known as transitional probability (TP). One solution to overcome these limitations is to assess SL as exposure to the stream unfolds using online techniques such as event-related potentials (ERP) that is highly sensitive to the time-course of the learning in the brain. Here we collected ERPs to examine the neurofunctional correlates of SL in preschool children with DLD, and chronological-age typical language development (TLD) controls who were exposed to an auditory stream in which eight three-syllable nonsense words, four of which presenting high-TPs and the other four low-TPs, to further analyze whether the ability of DLD and TLD children to extract-word-like units from the steam was modulated by words’ predictability. Moreover, to ascertain if the previous knowledge of the to-be-learned-regularities affected the neural responses to high- and low-TP words, children performed the auditory SL task, firstly, under implicit, and, subsequently, under explicit conditions. Although behavioral evidence of SL was not obtained in either group, the neural responses elicited during the exposure phases of the SL tasks differentiated children with DLD from children with TLD. Specifically, the results indicated that only children from the TDL group showed neural evidence of SL, particularly in the SL task performed under explicit conditions, firstly, for the low-TP, and, subsequently, for the high-TP ‘words’. Taken together, these findings support the view that children with DLD showed deficits in the extraction of the regularities embedded in the auditory input which might underlie the language difficulties.

Keywords: development language disorder, statistical learning, transitional probabilities, word segmentation

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Authors: Husain S. Yawer, Vasim Raja Panwar, Nidhi Priya

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The objective of this study is to evaluate and compare the role of nano-gelatin and Bioengineered Scaffolds on the attachment, proliferation, and osteogenic differentiation of human dental pulp stem cells (DPSCs). Tooth decay and early fall have each been one of the most prevailing dental disorders which cause physical and emotional suffering and compromise the patient's quality of life. The design of novel scaffolding materials will be based on mimicking the architecture of natural dental extracellular matrix which may provide as in vivo environments for proper cell growth. This methodology will involve the combination of nano-fibred gelatin as well as biodegradable hydrogel based tooth scaffold. We have measured and optimized the Dental Pulp Stem Cells growth profile in cultures carried out on collagen-coated plastic surface, however, for tissue regeneration study, we aim to develop an enhanced microenvironment for stem cell growth and dental tissue regeneration. We believe biomimetic cell adhesion and scaffolds might provide a near in vivo growth environment for proper growth and differentiation of human DPSCs, which further help in dentin/pulp tissue regeneration.

Keywords: nano-gelatin, stem cells, dental pulp, scaffold

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Authors: Yunhui Chen, Damon Kent, Matthew Dargusch

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Synthetic scaffolds are a highly promising new approach to replace both autografts and allografts to repair and remodel damaged bone tissue. Biocompatible porous titanium scaffold was manufactured through a powder metallurgy approach. Magnesium powder was used as space holder material which was compacted with titanium powder and removed during sintering. Evaluation of the porosity and mechanical properties showed a high level of compatibility with human bone. Interconnectivity between pores is higher than 95% for porosity as low as 30%. The elastic moduli are 39 GPa, 16 GPa and 9 GPa for 30%, 40% and 50% porosity samples which match well to that of natural bone (4-30 GPa). The yield strengths for 30% and 40% porosity samples of 315 MPa and 175 MPa are superior to that of human bone (130-180 MPa). In-vitro cell culture tests on the scaffold samples using Human Mesenchymal Stem Cells (hMSCs) demonstrated their biocompatibility and indicated osseointegration potential. The scaffolds allowed cells to adhere and spread both on the surface and inside the pore structures. With increasing levels of porosity/interconnectivity, improved cell proliferation is obtained within the pores. It is concluded that samples with 30% porosity exhibit the best biocompatibility. The results suggest that porous titanium scaffolds generated using this manufacturing route have excellent potential for hard tissue engineering applications.

Keywords: scaffolds, MG-63 cell culture, titanium, space holder

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Authors: Saba Amreen Syeda, Summaiah Asim, Syeda, Hafsa, Essam Quraishi

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Mantle Cell Lymphoma (MCL) is a relatively uncommon type of lymphoma that comprises approximately 7 percent of non hodgkin's lymphomas (NHL), Classic MCL presents mostly in lymph nodes and occasionally in extranodal sites. About 26 % of MCL is present primarily in the Gastrointestinal tract. While both the upper GI tract and the lower GI tract could be involved, it is rare to present with concurrent upper and lower GI involvement with MCL. We present the case of a 51-year-old Asian Indian male that presented to our clinic with complaints of chronic diarrhea for the last one year, progressively worsening over the past three months. The Patient also reported black stool as well as bright red blood per rectum. Patient reported severe fatigue on minimal exertion. On a physical exam, the patient was noted to have matted lymphadenopathy in the neck. Patient was noted to be anemic with a hemoglobin to be 8 g/dl. Esophagogastroduodenoscopy and colonoscopy was performed. EGD showed a large 4 cm ulcer in the gastric antrum with thick heaped up edges. There was bleeding on contact. Colonoscopy showed a large 35 mm multilobulated polyp in the ascending colon, which was biopsied. The patient was also noted to have nodular proctitis in the mid rectum. This was localized and extended to about 5 cm. This area was biopsied as well. Biopsies from the stomach, colon, as well as the rectum, returned with findings of mantle cell lymphoma on pathology. Lymphoid cells in the biopsy were stained strongly positive for CD 20, cyclin D1, and CD 5. There was the absence of stain for CD 3 and CD 10. The IHC stain for CD 23 was negative. Biopsies from neck LAD were obtained and were also positive for MCL. The patient was referred to oncology for staging and treatment.

Keywords: mantle cell lymphoma, GI bleed, diarrhea, gastric ulcer, colon polyp

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Authors: Agung Rizki Perdana, Asrofi Mursalin, Adniwan Shubhi Banuzaki, M. Indra Novian

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The understanding about sediment-derived plastiglomerate has a wide-range of merit in the academic realm. It can cover discussions about the Anthropocene Epoch in the scope of geoscience knowledge to even provide a solution for the environmental problem of plastic waste. Albeit its importance, very few research has been done regarding this issue. This research aims to create a classification as a pioneer for the study of sediment-derived plastiglomerate. This research was done in Bantul Regency, Daerah Istimewa Yogyakarta Province as an analogue of plastic debris sedimentation process. Observation is carried out in five observation points that shows three different depositional environments, which are terrestrial, fluvial, and transitional environment. The resulting classification uses three parameters and forms in a taxonomical manner. These parameters are composition, degree of lithification, and abundance of matrix respectively in advancing order. There is also a compositional ternary diagram which should be followed before entering the plastiglomerate nomenclature classification.

Keywords: plastiglomerate, classification, sedimentary mechanism, microplastic

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Authors: Nima E. Gorji

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The performance and characteristics of a hybrid heterojunction single-walled carbon nanotube and GaAs solar cell is modelled and numerically simulated using AMPS-1D device simulation tool. The device physics and performance parameters with different junction parameters are analysed. The results suggest that the open-circuit voltage changes very slightly by changing the work function, acceptor and donor density while the other electrical parameters reach to an optimum value. Increasing the concentration of a discrete defect density in the absorber layer decreases the electrical parameters. The current-voltage characteristics, quantum efficiency, band gap and thickness variation of the photovoltaic response will be quantitatively considered.

Keywords: carbon nanotube, GaAs, hybrid solar cell, AMPS-1D modelling

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Authors: Ashish Shukla, K. P. Mishra, Pushplata Tripathi

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This paper investigates the production and optimization of β-galactosidase enzyme using synthetic medium by isolated wild strains (S1, S2) mutated strains (M1, M2) through SSF and SmF. Among the different cell disintegration methods used, the highest specific activity was obtained when the cells were permeabilized using isoamyl alcohol. Wet lab experiments were performed to investigate the effects of carbon and nitrogen substrates present in Vogel’s medium on β-galactosidase enzyme activity using S1, S2, and M1, M2 strains through SSF. SmF experiments were performed for effects of carbon and nitrogen sources in YLK2Mg medium on β-galactosidase enzyme activity using S1, S2 and M1, M2 strains. Effect of pH on β-galactosidase enzyme production was also done using S1, S2, and M1, M2 strains. Results were found to be very appreciable in all the cases.

Keywords: β-galactosidase, cell disintegration, permeabilized, SSF, SmF

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Authors: Svetlana Guryeva, Inna Kornienko, Elena Petersen

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At present, translational medicine is a rapidly developing branch of biomedicine. The main idea of translational medicine is a practical application of fundamental research. One of the possible applications for translational medicine is researching therapies that improve human age-related organism condition. To fill the gap between experiments and clinical practice, it is necessary to create the standardized system for the investigation of different effects on cellular aging models. In this study, primary human fibroblasts derived from patients of different ages were used as a cellular aging model. The senescence-associated β-galactosidase activity, lipofuscin, γ-H2AX, the reactive oxygen species level, and cell death markers (annexin V/propidium iodide) were used as biomarkers of the cell functional state. The effects of damaging exposures (oxidative stress and heat shock), potential positive factors (metformin and acetaminophen), and their combinations were investigated using the described biomarkers. Oxidative stress and heat shock caused the increase in the levels of all biomarkers, and only the cells from young patients partly coped with stress 3 days after the exposures. Metformin improved the state of pretreatment cells from young and old patients. The acetaminophen did not show significant changes in the biomarker levels compare to the action of metformin. This study proved the opportunity to develop a standardized screening system based on biomarkers of the cell functional state to identify potential positive or negative effects of some physical and chemical exposures. Moreover, such a system can be useful for the aims of regenerative medicine to determine the effect of cell pretreatment before transplantation.

Keywords: biomarkers, primary fibroblasts, regenerative medicine, senescence, test system, translational medicine

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Authors: Binbin Chen, Dennis Y. C. Leung

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Aluminium (Al) -air cell holds a high volumetric capacity density of 8.05 Ah cm-3, benefit from the trivalence of Al ions. Additional benefits of Al-air cell are low price and environmental friendliness. Furthermore, the Al energy conversion process is characterized of 100% recyclability in theory. Along with a large base of raw material reserve, Al attracts considerable attentions as a promising material to be integrated within the global energy system. However, despite the early successful applications in military services, several problems exist that prevent the Al-air cells from widely civilian use. The most serious issue is the parasitic corrosion of Al when contacts with electrolyte. To overcome this problem, super-pure Al alloyed with various traces of metal elements are used to increase the corrosion resistance. Nevertheless, high-purity Al alloys are costly and require high energy consumption during production process. An alternative approach is to add inexpensive inhibitors directly into the electrolyte. However, such additives would increase the internal ohmic resistance and hamper the cell performance. So far these methods have not provided satisfactory solutions for the problem within Al-air cells. For the operation of alkaline Al-air cell, there are still other minor problems. One of them is the formation of aluminium hydroxide in the electrolyte. This process decreases ionic conductivity of electrolyte. Another one is the carbonation process within the gas diffusion layer of cathode, blocking the porosity of gas diffusion. Both these would hinder the performance of cells. The present work optimizes the above problems by building an Al-air cell operation system, consisting of four components. A top electrolyte tank containing fresh electrolyte is located at a high level, so that it can drive the electrolyte flow by gravity force. A mechanical rechargeable Al-air cell is fabricated with low-cost materials including low grade Al, carbon paper, and PMMA plates. An electrolyte waste tank with elaborate channel is designed to separate the hydrogen generated from the corrosion, which would be collected by gas collection device. In the first section of the research work, we investigated the performance of the mechanical rechargeable Al-air cell with a constant flow rate of electrolyte, to ensure the repeatability experiments. Then the whole system was assembled together and the feasibility of operating was demonstrated. During experiment, pure hydrogen is collected by collection device, which holds potential for various applications. By collecting this by-product, high utilization efficiency of aluminum is achieved. Considering both electricity and hydrogen generated, an overall utilization efficiency of around 90 % or even higher under different working voltages are achieved. Fluidic electrolyte could remove aluminum hydroxide precipitate and solve the electrolyte deterioration problem. This operation system provides a low-cost strategy for harvesting energy from the abundant secondary Al. The system could also be applied into other metal-air cells and is suitable for emergency power supply, power plant and other applications. The low cost feature implies great potential for commercialization. Further optimization, such as scaling up and optimization of fabrication, will help to refine the technology into practical market offerings.

Keywords: aluminium-air cell, high efficiency, hydrogen, mechanical recharge

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