Search results for: small cells
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 7767

Search results for: small cells

6687 Vascularized Adipose Tissue Engineering by Using Adipose ECM/Fibroin Hydrogel

Authors: Alisan Kayabolen, Dilek Keskin, Ferit Avcu, Andac Aykan, Fatih Zor, Aysen Tezcaner

Abstract:

Adipose tissue engineering is a promising field for regeneration of soft tissue defects. However, only very thin implants can be used in vivo since vascularization is still a problem for thick implants. Another problem is finding a biocompatible scaffold with good mechanical properties. In this study, the aim is to develop a thick vascularized adipose tissue that will integrate with the host, and perform its in vitro and in vivo characterizations. For this purpose, a hydrogel of decellularized adipose tissue (DAT) and fibroin was produced, and both endothelial cells and adipocytes that were differentiated from adipose derived stem cells were encapsulated in this hydrogel. Mixing DAT with fibroin allowed rapid gel formation by vortexing. It also provided to adjust mechanical strength by changing fibroin to DAT ratio. Based on compression tests, gels of DAT/fibroin ratio with similar mechanical properties to adipose tissue was selected for cell culture experiments. In vitro characterizations showed that DAT is not cytotoxic; on the contrary, it has many natural ECM components which provide biocompatibility and bioactivity. Subcutaneous implantation of hydrogels resulted with no immunogenic reaction or infection. Moreover, localized empty hydrogels gelled successfully around host vessel with required shape. Implantations of cell encapsulated hydrogels and histological analyses are under study. It is expected that endothelial cells inside the hydrogel will form a capillary network and they will bind to the host vessel passing through hydrogel.

Keywords: adipose tissue engineering, decellularization, encapsulation, hydrogel, vascularization

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6686 Flywheel Energy Storage Control Using SVPWM for Small Satellites Application

Authors: Noha El-Gohary, Thanaa El-Shater, A. A. Mahfouz, M. M. Sakr

Abstract:

Searching for high power conversion efficiency and long lifetime are important goals when designing a power supply subsystem for satellite applications. To fulfill these goals, this paper presents a power supply subsystem for small satellites in which flywheel energy storage system is used as a secondary power source instead of chemical battery. In this paper, the model of flywheel energy storage system is introduced; a DC bus regulation control algorithm for charging and discharging of flywheel based on space vector pulse width modulation technique and motor current control is also introduced. Simulation results showed the operation of the flywheel for charging and discharging mode during illumination and shadowed period. The advantages of the proposed system are confirmed by the simulation results of the power supply system.

Keywords: small-satellites, flywheel energy storage system, space vector pulse width modulation, power conversion

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6685 Study of Aging Behavior of Parallel-Series Connection Batteries

Authors: David Chao, John Lai, Alvin Wu, Carl Wang

Abstract:

For lithium-ion batteries with multiple cell configurations, some use scenarios can cause uneven aging effects to each cell within the battery because of uneven current distribution. Hence the focus of the study is to explore the aging effect(s) on batteries with different construction designs. In order to systematically study the influence of various factors in some key battery configurations, a detailed analysis of three key battery construction factors is conducted. And those key factors are (1) terminal position; (2) cell alignment matrix; and (3) interconnect resistance between cells. In this study, the 2S2P circuitry has been set as a model multi-cell battery to set up different battery samples, and the aging behavior is studied by a cycling test to analyze the current distribution and recoverable capacity. According to the outcome of aging tests, some key findings are: (I) different cells alignment matrices can have an impact on the cycle life of the battery; (II) symmetrical structure has been identified as a critical factor that can influence the battery cycle life, and unbalanced resistance can lead to inconsistent cell aging status; (III) the terminal position has been found to contribute to the uneven current distribution, that can cause an accelerated battery aging effect; and (IV) the internal connection resistance increase can actually result in cycle life increase; however, it is noteworthy that such increase in cycle life is accompanied by a decline in battery performance. In summary, the key findings from the study can help to identify the key aging factor of multi-cell batteries, and it can be useful to effectively improve the accuracy of battery capacity predictions.

Keywords: multiple cells battery, current distribution, battery aging, cell connection

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6684 Degradation of EE2 by Different Consortium of Enriched Nitrifying Activated Sludge

Authors: Pantip Kayee

Abstract:

17α-ethinylestradiol (EE2) is a recalcitrant micropollutant which is found in small amounts in municipal wastewater. But these small amounts still adversely affect for the reproductive function of aquatic organisms. Evidence in the past suggested that full-scale WWTPs equipped with nitrification process enhanced the removal of EE2 in the municipal wastewater. EE2 has been proven to be able to be transformed by ammonia oxidizing bacteria (AOB) via co-metabolism. This research aims to clarify the EE2 degradation pattern by different consortium of ammonia oxidizing microorganism (AOM) including AOA (ammonia oxidizing archaea) and investigate contribution between the existing ammonia monooxygenase (AMO) and new synthesized AOM. The result showed that AOA or AOB of N. oligotropha cluster in enriched nitrifying activated sludge (NAS) from 2mM and 5mM, commonly found in municipal WWTPs, could degrade EE2 in wastewater via co-metabolism. Moreover, the investigation of the contribution between the existing ammonia monooxygenase (AMO) and new synthesized AOM demonstrated that the new synthesized AMO enzyme may perform ammonia oxidation rather than the existing AMO enzyme or the existing AMO enzyme may has a small amount to oxidize ammonia.

Keywords: 17α-ethinylestradiol, nitrification, ammonia oxidizing bacteria, ammonia oxidizing archaea

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6683 Angiogenic, Cytoprotective, and Immunosuppressive Properties of Human Amnion and Chorion-Derived Mesenchymal Stem Cells

Authors: Kenichi Yamahara, Makiko Ohshima, Shunsuke Ohnishi, Hidetoshi Tsuda, Akihiko Taguchi, Toshihiro Soma, Hiroyasu Ogawa, Jun Yoshimatsu, Tomoaki Ikeda

Abstract:

We have previously reported the therapeutic potential of rat fetal membrane(FM)-derived mesenchymal stem cells (MSCs) using various rat models including hindlimb ischemia, autoimmune myocarditis, glomerulonephritis, renal ischemia-reperfusion injury, and myocardial infarction. In this study, 1) we isolated and characterized MSCs from human amnion and chorion; 2) we examined their differences in the expression profile of growth factors and cytokines; and 3) we investigated the therapeutic potential and difference of these MSCs using murine hindlimb ischemia and acute graft-versus-host disease (GVHD) models. Isolated MSCs from both amnion and chorion layers of FM showed similar morphological appearance, multipotency, and cell-surface antigen expression. Conditioned media obtained from amnion- and chorion-derived MSCs inhibited cell death caused by serum starvation or hypoxia in endothelial cells and cardiomyocytes. Amnion and chorion MSCs secreted significant amounts of angiogenic factors including HGF, IGF-1, VEGF, and bFGF, although differences in the cellular expression profile of these soluble factors were observed. Transplantation of human amnion or chorion MSCs significantly increased blood flow and capillary density in a murine hindlimb ischemia model. In addition, compared to human chorion MSCs, human amnion MSCs markedly reduced T-lymphocyte proliferation with the enhanced secretion of PGE2, and improved the pathological situation of a mouse model of GVHD disease. Our results highlight that human amnionand chorion-derived MSCs, which showed differences in their soluble factor secretion and angiogenic/immuno-suppressive function, could be ideal cell sources for regenerative medicine.

Keywords: amnion, chorion, fetal membrane, mesenchymal stem cells

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6682 An Investigation on the Suitability of Dual Ion Beam Sputtered GMZO Thin Films: For All Sputtered Buffer-Less Solar Cells

Authors: Vivek Garg, Brajendra S. Sengar, Gaurav Siddharth, Nisheka Anadkat, Amitesh Kumar, Shailendra Kumar, Shaibal Mukherjee

Abstract:

CuInGaSe (CIGSe) is the dominant thin film solar cell technology. The band alignment of Buffer/CIGSe interface is one of the most crucial parameters for solar cell performance. In this article, the valence band offset (VBOff) and conduction band offset (CBOff) values of Cu(In0.70Ga0.30)Se/ 1 at.% Ga: Mg0.25Zn0.75O (GMZO) heterojunction, grown by dual ion beam sputtering system (DIBS), are calculated to understand the carrier transport mechanism at the heterojunction for the realization of all sputtered buffer-less solar cells. To determine the valence band offset (VBOff), ∆E_V at GMZO/CIGSe heterojunction interface, the standard method based on core-level photoemission is utilized. The value of ∆E_V can be evaluated by considering common core-level peaks. In our study, the values of (Valence band onset)VBOn, obtained by linear extrapolation method for GMZO and CIGSe films are calculated to be 2.86 and 0.76 eV. In the UPS spectra peak positions of Se 3d is observed in UPS spectra at 54.82 and 54.7 eV for CIGSe film and GMZO/CIGSe interface respectively, while the peak position of Mg 2p is observed at 50.09 and 50.12 eV for GMZO and GMZO/CIGSe interface respectively. The optical band gap of CIGSe and GMZO are obtained from absorption spectra procured from spectroscopic ellipsometry are 1.26 and 3.84 eV respectively. The calculated average values of ∆E_v and ∆E_C are estimated to be 2.37 and 0.21 eV, respectively, at room temperature. The calculated positive conduction band offset termed as a spike at the absorber junction is the required criterion for the high-efficiency solar cells for the efficient charge extraction from the junction. So we can conclude that the above study confirms GMZO thin films grown by the dual ion beam sputtering system are the suitable candidate for the CIGSe thin films based ultra-thin buffer-less solar cells. We investigated the band-offset properties at the GMZO/CIGSe heterojunction to verify the suitability of the GMZO for the realization of the buffer-less solar cells. The calculated average values of ∆E_V and ∆E_C are estimated to be 2.37 and 0.21 eV, respectively, at room temperature. The calculated positive conduction band offset termed as a spike at the absorber junction is the required criterion for the high-efficiency solar cells for the efficient charge extraction from the junction. So we can conclude that the above study confirms GMZO thin films grown by the dual ion beam sputtering system are the suitable candidate for the CIGSe thin films based ultra-thin buffer-less solar cells. Acknowledgment: We are thankful to DIBS, EDX, and XRD facility equipped at Sophisticated Instrument Centre (SIC) at IIT Indore. The authors B.S.S and A.K acknowledge CSIR and V.G acknowledge UGC, India for their fellowships. B.S.S is thankful to DST and IUSSTF for BASE Internship Award. Prof. Shaibal Mukherjee is thankful to DST and IUSSTF for BASE Fellowship and MEITY YFRF award. This work is partially supported by DAE BRNS, DST CERI, and DST-RFBR Project under India-Russia Programme of Cooperation in Science and Technology. We are thankful to Mukul Gupta for SIMS facility equipped at UGC-DAE Indore.

Keywords: CIGSe, DIBS, GMZO, solar cells, UPS

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6681 A Comparison of Bias Among Relaxed Divisor Methods Using 3 Bias Measurements

Authors: Sumachaya Harnsukworapanich, Tetsuo Ichimori

Abstract:

The apportionment method is used by many countries, to calculate the distribution of seats in political bodies. For example, this method is used in the United States (U.S.) to distribute house seats proportionally based on the population of the electoral district. Famous apportionment methods include the divisor methods called the Adams Method, Dean Method, Hill Method, Jefferson Method and Webster Method. Sometimes the results from the implementation of these divisor methods are unfair and include errors. Therefore, it is important to examine the optimization of this method by using a bias measurement to figure out precise and fair results. In this research we investigate the bias of divisor methods in the U.S. Houses of Representatives toward large and small states by applying the Stolarsky Mean Method. We compare the bias of the apportionment method by using two famous bias measurements: The Balinski and Young measurement and the Ernst measurement. Both measurements have a formula for large and small states. The Third measurement however, which was created by the researchers, did not factor in the element of large and small states into the formula. All three measurements are compared and the results show that our measurement produces similar results to the other two famous measurements.

Keywords: apportionment, bias, divisor, fair, measurement

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6680 Unsupervised Segmentation Technique for Acute Leukemia Cells Using Clustering Algorithms

Authors: N. H. Harun, A. S. Abdul Nasir, M. Y. Mashor, R. Hassan

Abstract:

Leukaemia is a blood cancer disease that contributes to the increment of mortality rate in Malaysia each year. There are two main categories for leukaemia, which are acute and chronic leukaemia. The production and development of acute leukaemia cells occurs rapidly and uncontrollable. Therefore, if the identification of acute leukaemia cells could be done fast and effectively, proper treatment and medicine could be delivered. Due to the requirement of prompt and accurate diagnosis of leukaemia, the current study has proposed unsupervised pixel segmentation based on clustering algorithm in order to obtain a fully segmented abnormal white blood cell (blast) in acute leukaemia image. In order to obtain the segmented blast, the current study proposed three clustering algorithms which are k-means, fuzzy c-means and moving k-means algorithms have been applied on the saturation component image. Then, median filter and seeded region growing area extraction algorithms have been applied, to smooth the region of segmented blast and to remove the large unwanted regions from the image, respectively. Comparisons among the three clustering algorithms are made in order to measure the performance of each clustering algorithm on segmenting the blast area. Based on the good sensitivity value that has been obtained, the results indicate that moving k-means clustering algorithm has successfully produced the fully segmented blast region in acute leukaemia image. Hence, indicating that the resultant images could be helpful to haematologists for further analysis of acute leukaemia.

Keywords: acute leukaemia images, clustering algorithms, image segmentation, moving k-means

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6679 Analytical Terahertz Characterization of In0.53Ga0.47As Transistors and Homogenous Diodes

Authors: Abdelmadjid Mammeri, Fatima Zohra Mahi, Luca Varani, H. Marinchoi

Abstract:

We propose an analytical model for the admittance and the noise calculations of the InGaAs transistor and diode. The development of the small-signal admittance takes into account the longitudinal and transverse electric fields through a pseudo two-dimensional approximation of the Poisson equation. The frequency-dependent of the small-signal admittance response is determined by the total currents and the potentials matrix relation between the gate and the drain terminals. The noise is evaluated by using the real part of the transistor/diode admittance under a small-signal perturbation. The analytical results show that the admittance spectrum exhibits a series of resonant peaks corresponding to the excitation of plasma waves. The appearance of the resonance is discussed and analyzed as functions of the channel length and the temperature. The model can be used, on one hand; to control the appearance of the plasma resonances, and on other hand; can give significant information about the noise frequency dependence in the InGaAs transistor and diode.

Keywords: InGaAs transistors, InGaAs diode, admittance, resonant peaks, plasma waves, analytical model

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6678 Microglia Activation in Animal Model of Schizophrenia

Authors: Esshili Awatef, Manitz Marie-Pierre, Eßlinger Manuela, Gerhardt Alexandra, Plümper Jennifer, Wachholz Simone, Friebe Astrid, Juckel Georg

Abstract:

Maternal immune activation (MIA) resulting from maternal viral infection during pregnancy is a known risk factor for schizophrenia. The neural mechanisms by which maternal infections increase the risk for schizophrenia remain unknown, although the prevailing hypothesis argues that an activation of the maternal immune system induces changes in the maternal-fetal environment that might interact with fetal brain development. It may lead to an activation of fetal microglia inducing long-lasting functional changes of these cells. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, we hypothesize that prenatal treatment with the inflammatory agent Poly(I:C) during embryogenesis at contributes to microglial activation in the offspring, which may, therefore, represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options. Pregnant rats were treated with intraperitoneal injections a single dose of Poly(I:C) or saline on gestation day 17. Brains of control and Poly(I:C) offspring, were removed and into 20-μm-thick coronal sections were cut by using a Cryostat. Brain slices were fixed and immunostained with ba1 antibody. Subsequently, Iba1-immunoreactivity was detected using a secondary antibody, goat anti-rabbit. The sections were viewed and photographed under microscope. The immunohistochemical analysis revealed increases in microglia cell number in the prefrontal cortex, in offspring of poly(I:C) treated-rats as compared to the controls injected with NaCl. However, no significant differences were observed in microglia activation in the cerebellum among the groups. Prenatal immune challenge with Poly(I:C) was able to induce long-lasting changes in the offspring brains. This lead to a higher activation of microglia cells in the prefrontal cortex, a brain region critical for many higher brain functions, including working memory and cognitive flexibility. which might be implicated in possible changes in cortical neuropil architecture in schizophrenia. Further studies will be needed to clarify the association between microglial cells activation and schizophrenia-related behavioral alterations.

Keywords: Microglia, neuroinflammation, PolyI:C, schizophrenia

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6677 Enhanced Performance of Perovskite Solar Cells by Modifying Interfacial Properties Using MoS2 Nanoflakes

Authors: Kusum Kumari, Ramesh Banoth, V. S. Reddy Channu

Abstract:

Organic-inorganic perovskite solar cells (PrSCs) have emerged as a promising solar photovoltaic technology in terms of realizing high power conversion efficiency (PCE). However, their limited lifetime and poor device stability limits their commercialization in future. In this regard, interface engineering of the electron transport layer (ETL) using 2D materials have been currently used owing to their high carrier mobility, high thermal stability and tunable work function, which in turn enormously impact the charge carrier dynamics. In this work, we report an easy and effective way of simultaneously enhancing the efficiency of PrSCs along with the long-term stability through interface engineering via the incorporation of 2D-Molybdenum disulfide (2D-MoS₂, few layered nanoflakes) in mesoporous-Titanium dioxide (mp-TiO₂)scaffold electron transport buffer layer, and using poly 3-hexytheophene (P3HT) as hole transport layers. The PSCs were fabricated in ambient air conditions in device configuration, FTO/c-TiO₂/mp-TiO₂:2D-MoS₂/CH3NH3PbI3/P3HT/Au, with an active area of 0.16 cm². The best device using c-TiO₂/mp-TiO₂:2D-MoS₂ (0.5wt.%) ETL exhibited a substantial increase in PCE ~13.04% as compared to PCE ~8.75% realized in reference device fabricated without incorporating MoS₂ in mp-TiO₂ buffer layer. The incorporation of MoS₂ nanoflakes in mp-TiO₂ ETL not only enhances the PCE to ~49% but also leads to better device stability in ambient air conditions without encapsulation (retaining PCE ~86% of its initial value up to 500 hrs), as compared to ETLs without MoS₂.

Keywords: perovskite solar cells, MoS₂, nanoflakes, electron transport layer

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6676 Human 3D Metastatic Melanoma Models for in vitro Evaluation of Targeted Therapy Efficiency

Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

Abstract:

Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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6675 Stem Cell Augmentation Therapy for Cardiovascular Risk in Ankylosing Spondylitis: STATIN-as Study

Authors: Ashit Syngle, Nidhi Garg, Pawan Krishan

Abstract:

Objective: Bone marrow derived stem cells, endothelial progenitor cells (EPCs), protect against atherosclerotic vascular damage. However, EPCs are depleted in AS and contribute to the enhanced cardiovascular risk. Statins have a protective effect in CAD and diabetes by enhancing the proliferation, migration and survival of EPCs. Therapeutic potential of augmenting EPCs to treat the heightened cardiovascular risk of AS has not yet been exploited. We aimed to investigate the effect of rosuvastatin on EPCs population and inflammation in AS. Methods: 30 AS patients were randomized to receive 6 months of treatment with rosuvastatin (10 mg/day, n=15) and placebo (n=15) as an adjunct to existing stable anti-rheumatic drugs. EPCs (CD34+/CD133+) were quantified by Flow Cytometry. Inflammatory measures (BASDAI, BASFI, CRP and ESR), pro-inflammatory cytokines (TNF-α, IL-6 and IL-1) and lipids were measured at baseline and after treatment. Results: At baseline, inflammatory measures and pro-inflammatory cytokines were elevated and EPCs depleted among both groups. EPCs increased significantly (p < 0.01) after treatment with rosuvastatin. At 6 months, BASDAI, BASFI, ESR, CRP, TNF-α, and IL-6 improved significantly in rosuvastatin group. Significant negative correlation was observed between EPCs and BASDAI, CRP and IL-6 after rosuvastatin treatment. Conclusion: First study to show that rosuvastatin augments EPCs population in AS. This defines a novel mechanism of rosuvastatin treatment in AS: the augmentation of EPCs with improvement in proinflammatory cytokines and inflammatory disease activity. The augmentation of EPCs by rosuvastatin may provide a novel strategy to prevent cardiovascular events in AS.

Keywords: ankylosing spondylitis, Endothelial Progenitor Cells, inflammation, pro-inflammatory cytokines, rosuvastatin

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6674 Investigation of the Effects of Quercetin on Oxidative Stress in Cells Infected with Infectious Pancreatic Necrosis Virus

Authors: Dilek Zorlu Kaya, Sena Çenesiz, Utku Duran

Abstract:

Infectious pancreatic necrosis virus is a disease of great concern in aquaculture, causing mortality of 80 - 90% of the stocks in salmonid production. We aimed to investigate the efficacy of quercetin on oxidant and antioxidant parameters of infectious pancreatic necrosis virus, which is important for fish farming and economy in vitro. Quercetin experimental model was used in the cell culture of Oncorhynchus mykiss infected with infectious pancreatic necrosis virus. Malondialdehyde, ceruloplasmin, total oxidant capacity, total antioxidant levels, and glutathione-peroxidase were measured in the samples. As a result of the study, it was observed that quercetin can minimize the damage caused by scavenging free radicals in cells infected with infectious pancreatic necrosis virus. Thus, we think that an important development can be achieved for fish farming and the economy.

Keywords: IPNV, oncorhynchus mykiss, TAS, TOS, quercetin

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6673 Factor Influencing the Certification to ISO 9000:2008 among SME in Malaysia

Authors: Dolhadi Bin Zainudin

Abstract:

The study attempts to predict the relationship between influencing factors in the adoption of ISO 9000:2008 and to identify which how these factors play the main role in achieving ISO 9000 standard. A survey using structured questionnaire was employed. A total of 255 respondents from 255 small and medium enterprises participated in this study. With regards to influencing factors, a discriminant analysis was conducted and the results showed that three out of nine critical success factors is statistically significant between ISO 9000:2008 and non-ISO 9000 certified companies which are communication for quality, information and analysis and organizational culture.

Keywords: ISO 9000, quality management, factors, small and medium enterprise, Malaysia, influencing factors

Procedia PDF Downloads 339
6672 Effect of Papaverine on Neurospheres

Authors: Noura Shehab-Eldeen, Mohamed Elsherbeeny, Hossam Elmetwally, Mohamed Salama, Ahmed Lotfy, Mohamed Elgamal, Hussein Sheashaa, Mohamed Sobh

Abstract:

Mitochondrial toxins including papaverine may be implicated in the etiology and pathogenesis of Parkinson's disease. The aim was to detect the effect of papaverine on the proliferation and viability of neural stem cells. Rat neural progenitor cells were isolated from embryos (E14) brains. The dispersed tissues were allowed to settle, then, The supernatant was centrifuged at 1,000 g for 5 min. The pellet was placed in Hank’s solution cultured as free-floating neurospheres Dulbecco’s modified Eagle medium (DMEM) and Hams F12 (3:1) supplemented with B27 (Invitrogen GmBH, Karlsruhe, Germany), 20 ng/mL epidermal growth factor (EGF; Biosource, Karlsruhe, Germany), 20 ng/mL recombinant human fibroblast growth factor (rhFGF; R&D Systems, Wiesbaden-Nordenstadt, Germany), and penicillin and streptomycin (1:100; Invitrogen) at 37°C with 7.5% CO2 . Differentiation was initiated by growth factor withdrawal and plating onto a poly-d-lysine/ laminin matrix. The neurospheres were fed every 2-3 days by replacing 50% of the culture media with fresh media. The culture suspension was transferred to a dish containing 16 wells. The wells were divided as follows: 4 wells received no papaverine (control), 4 wells 1 u, 4 wells 5 u and 4 wells 10 u of papaverine solution. In the next 2 weeks, photography (0,4,5,11days) and viability test were done. The photographs were analysed. Results : papaverine didn't affect proliferation of neurospheres, while it affected viability compared to control , this was dose related. Conclusion: This indicates the harmful effect of papaverine suggesting it to be a candidate neurotoxin causing Parkinsonism.

Keywords: neurospheres, neural stem cells, papaverine, Parkinsonism

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6671 Mitigating the Aggregation of Human Islet Amyloid Polypeptide with Nanomaterials

Authors: Ava Faridi, Pouya Faridi, Aleksandr Kakinen, Ibrahim Javed, Thomas P. Davis, Pu Chun Ke

Abstract:

Human islet amyloid polypeptide (IAPP) is a hormone associated with glycemic control and type 2 diabetes. Biophysically, the chirality of IAPP fibrils has been little explored with respect to the aggregation and toxicity of the peptide. Biochemically, it remains unclear as for how protein expression in pancreatic beta cells may be altered by cell exposure to the peptide, and how such changes may be mitigated by nanoparticle inhibitors for IAPP aggregation. In this study, we first demonstrated the elimination of the IAPP nucleation phase and shortening of its elongation phase by silica nanoribbons. This accelerated IAPP fibrillization translated to reduced toxicity, especially for the right-handed silica nanoribbons, as revealed by cell viability, helium ion microscopy, as well as zebrafish embryo survival, developmental and behavioral assays. We then examined the proteomes of βTC6 pancreatic beta cells exposed to the three main aggregation states of monomeric, oligomeric and amyloid fibrillar IAPP, and compared that with cellular protein expression modulated by graphene quantum dots (GQDs). A total of 29 proteins were significantly regulated by different forms of IAPP, and the majority of these proteins were nucleotide-binding proteins. A regulatory capacity of GQDs against aberrant protein expression was confirmed. These studies have demonstrated the great potential of employing nanomaterials targeting the mesoscopic enantioselectivity and protein expression dysregulation in pancreatic beta cells.

Keywords: graphene quantum dots, IAPP, silica nanoribbons, protein expression, toxicity

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6670 Modelling of Silicon Solar Cell with Anti-reflecting Coating

Authors: Ankita Gaur, Mouli Karmakar, Shyam

Abstract:

In this study, a silicon solar cell has been modeled and analyzed to enhance its electrical performance by improving the optical properties using an antireflecting coating (ARC). The dynamic optical reflectance, transmittance along with the net transmissivity absorptivity product of each layer are assessed as per the diurnal variation of the angle of incidence using MATLAB 2019. The model is tested with various Anti-Reflective coatings and the performance has also been compared with uncoated cells. ARC improves the optical transmittance of the photon. Higher transmittance of ⁓96.57% with lowest reflectance of ⁓ 1.74% at 12.00 hours was obtained with MgF₂ coated silicon cells. The electrical efficiency of the configured solar cell was evaluated for a composite climate of New Delhi, India, for all weather conditions. The annual electricity generation for Anti-reflective coated and uncoated crystalline silicon PV Module was observed to be 103.14 KWh and 99.51 KWh, respectively.

Keywords: antireflecting coating, electrical efficiency, reflectance, solar cell, transmittance

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6669 Exploring the Implementation of Building Information Modelling Level 2 in the UK Construction Industry: The Case of Small and Medium-Sized Enterprises

Authors: Khaled Abu Awwad, Abdussalam Shibani, Michel Ghostin

Abstract:

In the last few years, building information modelling (BIM) has been acknowledged as a new technology capable of transforming the construction sector to a collaborated industry. The implementation of BIM in the United Kingdom (UK) construction sector has increased significantly in the last decade, particularly after the UK government mandated the use of BIM in all public projects by 2016. Despite this, there are many indicators that BIM implementation is the main concern for large companies, while small and medium-sized enterprises (SMEs) are lagging behind in adopting and implementing this new technology. This slow adoption of BIM leads to an uncompetitive disadvantage in public projects and possible private projects. On the other hand, there is limited research focusing on the implementation of BIM Level 2 within SMEs. Therefore, the aim of this study is to bridge this gap and provide a conceptual framework to aid SMEs in implementing BIM Level 2. This framework is a result of interpreting qualitative data obtained by conducting semi-structured interviews with BIM experts in the UK construction industry.

Keywords: building information modelling, critical success factors, small and medium-sized enterprises, United Kingdom

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6668 Paramecuim as a Model for the Evaluation of Toxicity (Growth, Total Proteins, Respiratory and GSH Bio Marker Changes) Observed after Treatment with Essential Oils Isolated from Artemisia herba-alba Plant of Algeria

Authors: Bouchiha Hanene, Rouabhi Rachid, Bouchama Khaled, Djebar Berrebbah Houraya, Djebar Mohamed Reda

Abstract:

Recently, some natural products such as essentials oils (EOs) have been used in the fields as alternative to synthetic compounds, to minimize the negative impacts to the environment. This fact has led to questions about the possible impact of EOs on ecosystems. Currently in toxicology, the use of alternative models can help to understand the mechanisms of toxic action, at different levels of organization of ecosystems. Algae, protozoa and bacteria form the base of the food chain and protozoan cells are used as bioindicators often of pollution in environment. Unicellular organisms offer the possibility of direct study of independent cells with specific characteristics of individual cells and whole organisms at the same time. This unicellular facilitates the study of physiological processes, and effects of pollutants at the cellular level, which makes it widely used to assess the toxic effects of various xenobiotics. This study aimed to verify the effects of EOs of one famous plant used tremendously in our folk medicine, namely Artemisia herba alba in causing acute toxicity (24 hours) and chronic (15 days) toxicity for model cellular (Paramecium sp). To this end, cellular’s of paramecium were exposed to various concentrations (Three doses were chosen) of EOs extracted from plant (Artemisia herba alba). In the first experiment, the cellular s cultures were exposed for 48 hours to different concentrations to determine the median lethal concentration (DL50). We followed the evolution of physiological parameters (growth), biochemical (total proteins, respiratory metabolism), as well as the variations of a bio marker the GSH. Our results highlighted a light inhibition of the growth of the protozoa as well as a disturbance of the contents of total proteins and a reduction in the reduced rate of glutathione. The polarographic study revealed a stimulation of the consumption of O2 and this at the treated cells.

Keywords: essential oils, protozoa, bio indicators, toxicity, Growth, bio marker, proteins, polarographic

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6667 Characterization of High Phosphorus Gray Iron for the Stub- Anode Connection in the Aluminium Reduction Cells

Authors: Mohamed M. Ali, Adel Nofal, Amr Kandil, Mahmoud Agour

Abstract:

High phosphorus gray iron (HPGI) is used to connect the steel stub of an anode rod to a prebaked anode carbon block in the aluminium reduction cells. In this paper, a complete characterization for HPGI was done, includes studying the chemical composition of the HPGI collar, anodic voltage drop, collar temperature over 30 days anode life cycle, microstructure and mechanical properties. During anode life cycle, the carbon content in HPGI was lowed from 3.73 to 3.38%, and different changes in the anodic voltage drop at the stub- collar-anode connection were recorded. The collar temperature increases over the anode life cycle and reaches to 850°C in four weeks after anode changing. Significant changes in the HPGI microstructure were observed after 3 and 30 days from the anode changing. To simulate the actual operating conditions in the steel stub/collar/carbon anode connection, a bench-scale experimental set-up was designed and used for electrical resistance and resistivity respectively. The results showed the current HPGI properties needed to modify or producing new alloys with excellent electrical and mechanical properties. The steel stub and HPGI thermal expansion were measured and studied. Considerable permanent expansion was observed for the HPGI collar after the completion of the heating-cooling cycle.

Keywords: high phosphorus gray iron (HPGI), aluminium reduction cells, anodic voltage drop, microstructure, mechanical and electrical properties

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6666 Preparation, Characterization and Ionic Conductivity of (1‒x) (CdI2‒Ag2CrO4)‒(x) Al2O3 Composite Solid Electrolytes

Authors: Rafiuddin

Abstract:

Composite solid electrolyte of the salt and oxide type is an effective approach to improve the ionic conductivity in low and intermediate temperature regions. The conductivity enhancement in the composites occurs via interfaces. Because of their high ionic conduction, composite electrolytes have wide applications in different electrochemical devices such as solid-state batteries, solid oxide fuel cells, and electrochemical cells. In this work, a series of novel (1‒x) (CdI2‒Ag2CrO4)‒xAl2O3 composite solid electrolytes has been synthesized. The prepared materials were characterized by X‒ray diffraction, differential thermal analysis, and AC impedance spectroscopy. The impedance spectra show single semicircle representing the simultaneous contribution of grain and grain boundary. The conductivity increased with the increase of Al2O3 content and shows the maximum conductivity (σ= 0.0012 S cm‒1) for 30% of Al2O3 content at 30 ℃.

Keywords: composite solid electrolyte, X-ray diffraction, Impedance spectroscopy, ionic conductivity

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6665 An Original and Suitable Induction Method of Repeated Hypoxic Stress by Hydralazine to Investigate the Integrity of an in Vitro Contact Co-Culture Blood Brain Barrier Model

Authors: Morgane Chatard, Clémentine Puech, Nathalie Perek, Frédéric Roche

Abstract:

Several neurological disorders are linked to repeated hypoxia. The impact of such repeated hypoxic stress, on endothelial cells function of the blood-brain barrier (BBB) is little studied in the literature. Indeed, the study of hypoxic stress in cellular pathways is complex using hypoxia exposure because HIF 1α (factor induced by hypoxia) has a short half life. Our study presents an innovative induction method of repeated hypoxic stress, more reproducible, which allows us to study its impacts on an in vitro contact co-culture BBB model. Repeated hypoxic stress was induced by hydralazine (a mimetic agent of hypoxia pathway) during two hours and repeated during 24 hours. Then, BBB integrity was assessed by permeability measurements (transendothelial electrical resistance and membrane permeability), tight junction protein expressions (cell-ELISA and confocal microscopy) and by studying expression and activity of efflux transporters. First, this study showed that repeated hypoxic stress leads to a BBB’s dysfunction illustrated by a significant increase in permeability. This loss of membrane integrity was linked to a significant decrease of tight junctions’ protein expressions, facilitating a possible transfer of potential cytotoxic compounds in the brain. Secondly, we demonstrated that brain microvascular endothelial cells had set-up defence mechanism. These endothelial cells significantly increased the activity of their efflux transporters which was associated with a significant increase in their expression. In conclusion, repeated hypoxic stress lead to a loss of BBB integrity with a decrease of tight junction proteins. In contrast, endothelial cells increased the expression of their efflux transporters to fight against cytotoxic compounds brain crossing. Unfortunately, enhanced efflux activity could also lead to reducing pharmacological drugs delivering to the brain in such hypoxic conditions.

Keywords: BBB model, efflux transporters, repeated hypoxic stress, tigh junction proteins

Procedia PDF Downloads 294
6664 Direct Current Electric Field Stimulation against PC12 Cells in 3D Bio-Reactor to Enhance Axonal Extension

Authors: E. Nakamachi, S. Tanaka, K. Yamamoto, Y. Morita

Abstract:

In this study, we developed a three-dimensional (3D) direct current electric field (DCEF) stimulation bio-reactor for axonal outgrowth enhancement to generate the neural network of the central nervous system (CNS). By using our newly developed 3D DCEF stimulation bio-reactor, we cultured the rat pheochromocytoma cells (PC12) and investigated the effects on the axonal extension enhancement and network generation. Firstly, we designed and fabricated a 3D bio-reactor, which can load DCEF stimulation on PC12 cells embedded in the collagen gel as extracellular environment. The connection between the electrolyte and the medium using salt bridges for DCEF stimulation was introduced to avoid the cell death by the toxicity of metal ion. The distance between the salt bridges was adopted as the design variable to optimize a structure for uniform DCEF stimulation, where the finite element (FE) analyses results were used. Uniform DCEF strength and electric flux vector direction in the PC12 cells embedded in collagen gel were examined through measurements of the fabricated 3D bio-reactor chamber. Measurement results of DCEF strength in the bio-reactor showed a good agreement with FE results. In addition, the perfusion system was attached to maintain pH 7.2 ~ 7.6 of the medium because pH change was caused by DCEF stimulation loading. Secondly, we disseminated PC12 cells in collagen gel and carried out 3D culture. Finally, we measured the morphology of PC12 cell bodies and neurites by the multiphoton excitation fluorescence microscope (MPM). The effectiveness of DCEF stimulation to enhance the axonal outgrowth and the neural network generation was investigated. We confirmed that both an increase of mean axonal length and axogenesis rate of PC12, which have been exposed 5 mV/mm for 6 hours a day for 4 days in the bioreactor. We found following conclusions in our study. 1) Design and fabrication of DCEF stimulation bio-reactor capable of 3D culture nerve cell were completed. A uniform electric field strength of average value of 17 mV/mm within the 1.2% error range was confirmed by using FE analyses, after the structure determination through the optimization process. In addition, we attached a perfusion system capable of suppressing the pH change of the culture solution due to DCEF stimulation loading. 2) Evaluation of DCEF stimulation effects on PC12 cell activity was executed. The 3D culture of PC 12 was carried out adopting the embedding culture method using collagen gel as a scaffold for four days under the condition of 5.0 mV/mm and 10mV/mm. There was a significant effect on the enhancement of axonal extension, as 11.3% increase in an average length, and the increase of axogenesis rate. On the other hand, no effects on the orientation of axon against the DCEF flux direction was observed. Further, the network generation was enhanced to connect longer distance between the target neighbor cells by DCEF stimulation.

Keywords: PC12, DCEF stimulation, 3D bio-reactor, axonal extension, neural network generation

Procedia PDF Downloads 185
6663 Design Evaluation Tool for Small Wind Turbine Systems Based on the Simple Load Model

Authors: Jihane Bouabid

Abstract:

The urgency to transition towards sustainable energy sources has revealed itself imperative. Today, in the 21st Century, the intellectual society have imposed technological advancements and improvements, and anticipates expeditious outcomes as an integral component of its relentless pursuit of an elevated standard of living. As a part of empowering human development, driving economic growth and meeting social needs, the access to energy services has become a necessity. As a part of these improvements, we are introducing the project "Mywindturbine" - an interactive web user interface for design and analysis in the field of wind energy, with a particular adherence to the IEC (International Electrotechnical Commission) standard 61400-2 "Wind turbines – Part 2: Design requirements for small wind turbines". Wind turbines play a pivotal role in Morocco's renewable energy strategy, leveraging the nation's abundant wind resources. The IEC 61400-2 standard ensures the safety and design integrity of small wind turbines deployed in Morocco, providing guidelines for performance and safety protocols. The conformity with this standard ensures turbine reliability, facilitates standards alignment, and accelerates the integration of wind energy into Morocco's energy landscape. The aim of the GUI (Graphical User Interface) for engineers and professionals from the field of wind energy systems who would like to design a small wind turbine system following the safety requirements of the international standards IEC 61400-2. The interface provides an easy way to analyze the structure of the turbine machine under normal and extreme load conditions based on the specific inputs provided by the user. The platform introduces an overview to sustainability and renewable energy, with a focus on wind turbines. It features a cross-examination of the input parameters provided from the user for the SLM (Simple Load Model) of small wind turbines, and results in an analysis according to the IEC 61400-2 standard. The analysis of the simple load model encompasses calculations for fatigue loads on blades and rotor shaft, yaw error load on blades, etc. for the small wind turbine performance. Through its structured framework and adherence to the IEC standard, "Mywindturbine" aims to empower professionals, engineers, and intellectuals with the knowledge and tools necessary to contribute towards a sustainable energy future.

Keywords: small wind turbine, IEC 61400-2 standard, user interface., simple load model

Procedia PDF Downloads 63
6662 Statistical Manufacturing Cell/Process Qualification Sample Size Optimization

Authors: Angad Arora

Abstract:

In production operations/manufacturing, a cell or line is typically a bunch of similar machines (computer numerical control (CNCs), advanced cutting, 3D printing or special purpose machines. For qualifying a typical manufacturing line /cell / new process, Ideally, we need a sample of parts that can be flown through the process and then we make a judgment on the health of the line/cell. However, with huge volumes and mass production scope, such as in the mobile phone industry, for example, the actual cells or lines can go in thousands and to qualify each one of them with statistical confidence means utilizing samples that are very large and eventually add to product /manufacturing cost + huge waste if the parts are not intended to be customer shipped. To solve this, we come up with 2 steps statistical approach. We start with a small sample size and then objectively evaluate whether the process needs additional samples or not. For example, if a process is producing bad parts and we saw those samples early, then there is a high chance that the process will not meet the desired yield and there is no point in keeping adding more samples. We used this hypothesis and came up with 2 steps binomial testing approach. Further, we also prove through results that we can achieve an 18-25% reduction in samples while keeping the same statistical confidence.

Keywords: statistics, data science, manufacturing process qualification, production planning

Procedia PDF Downloads 98
6661 Polypeptide Modified Carbon Nanotubes – Mediated GFP Gene Transfection for H1299 Cells and Toxicity Assessment

Authors: Pei-Ying Lo, Jing-Hao Ciou, Kai-Cheng Yang, Jia-Huei Zheng, Shih-Hsiang Huang, Kuen-Chan Lee, Er-Chieh Cho

Abstract:

As-produced CNTs are insoluble in all organic solvents and aqueous solutions have imposed limitations to the use of CNTs. Therefore, how to debundle carbon nanotubes and to modify them for further uses is an important issue. There are several methods for the dispersion of CNTs in water using covalent attachment of hydrophilic groups to the surface of tubes. These methods, however, alter the electronic structure of the nanotubes by disrupting the network of sp2 hybridized carbons. In order to keep the nanotubes’ intrinsic mechanical and electrical properties intact, non-covalent interactions are increasingly being explored as an alternative route for dispersion. Apart from conventional surfactants such as sodium dodecylsulfate (SDS) or sodium dodecylbenzenesulfonate (SDBS) which are highly effective in dispersing CNTs, biopolymers have received much attention as dispersing agents due to the anticipated biocompatibility of the dispersed CNTs. Also, The pyrenyl group is known to interact strongly with the basal plane of graphene via π-stacking. In this study, a highly re-dispersible biopolymer is reported for the synthesis of pyrene-modified poly-L-lysine (PBPL) and poly(D-Glu, D-Lys) (PGLP). To provide the evidence of the safety of the PBPL/CNT & PGLP/CNT materials we use in this study, H1299 and HCT116 cells were incubated with PBPL/CNT & PGLP/CNT materials for toxicity analysis, MTS assays. The results from MTS assays indicated that no significant cellular toxicity was shown in H1299 and HCT116 cells. Furthermore, the fluorescence marker fluorescein isothiocyanate (FITC) was added to PBPL & PGLP dispersions. From the fluorescent measurements showed that the chemical functionalisation of the PBPL/CNT & PGLP/CNT conjugates with the fluorescence marker were successful. The fluorescent PBPL/CNT & PGLP/CNT conjugates could find application in medical imaging. In the next step, the GFP gene is immobilized onto PBPL/CNT conjugates by introducing electrostatic interaction. GFP-transfected cells that emitted fluorescence were imaged and counted under a fluorescence microscope. Due to the unique biocompatibility of PBPL modified CNTs, the GFP gene could be transported into H1299 cells without using antibodies. The applicability of such soluble and chemically functionalised polypeptide/CNT conjugates in biomedicine is currently investigated. We expect that this polypeptide/CNT system will be a safe and multi-functional nanomedical delivery platform and contribute to future medical therapy.

Keywords: carbon nanotube, nanotoxicology, GFP transfection, polypeptide/CNT hybrids

Procedia PDF Downloads 342
6660 One-Pot Facile Synthesis of N-Doped Graphene Synthesized from Paraphenylenediamine as Metal-Free Catalysts for the Oxygen Reduction Used for Alkaline Fuel Cells

Authors: Leila Samiee, Amir Yadegari, Saeedeh Tasharrofi

Abstract:

In the work presented here, nitrogen-doped graphene materials were synthesized and used as metal-free electrocatalysts for oxygen reduction reaction (ORR) under alkaline conditions. Paraphenylenediamine was used as N precursor. The N-doped graphene was synthesized under hydrothermal treatment at 200°C. All the materials have been characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Transmission electron microscopy (TEM) and X-ray photo-electron spectroscopy (XPS). Moreover, for electrochemical evaluation of samples, Rotating Disk electrode (RDE) and Cyclic Voltammetry techniques (CV) were employed. The resulting material exhibits an outstanding catalytic activity for the oxygen reduction reaction (ORR) as well as excellent resistance towards methanol crossover effects, indicating their promising potential as ORR electrocatalysts for alkaline fuel cells.

Keywords: alkaline fuel cell, graphene, metal-free catalyst, paraphenylen diamine

Procedia PDF Downloads 479
6659 An Investigation of Peptide Functionalized Gold Nanoparticles On Colon Cancer Cells For Biomedical Application

Authors: Rolivhuwa Bishop Ramagoma1*, Lynn Cairncross1, , Saartjie Roux1

Abstract:

According to the world health organisation, colon cancer is among the most common cancers diagnosed in both men and women. Specifically, it is the second leading cause of cancer related deaths accounting for over 860 000 deaths worldwide in 2018. Currently, chemotherapy has become an essential component of most cancer treatments. Despite progress in cancer drug development over the previous years, traditional chemotherapeutic drugs still have low selectivity for targeting tumour tissues and are frequently constrained by dose-limiting toxicity. The creation of nanoscale delivery vehicles capable of directly directing treatment into cancer cells has recently caught the interest of researchers. Herein, the development of peptide-functionalized polyethylene glycol gold nanoparticles (Peptide-PEG-AuNPs) as a cellular probe and delivery agent is described, with the higher aim to develop a specific diagnostic prototype and assess their specificity not only against cell lines but primary human cells as well. Gold nanoparticles (AuNPs) were synthesized and stabilized through chemical conjugation. The synthesized AuNPs were characterized, stability in physiological solutions was assessed, their cytotoxicity against colon carcinoma and non-carcinoma skin fibroblasts was also studied. Furthermore, genetic effect through real-time polymerase chain reaction (RT-PCR), localization and uptake, peptide specificity were also determined. In this study, different peptide-AuNPs were found to have preferential toxicity at higher concentrations, as revealed by cell viability assays, however, all AuNPs presented immaculate stability for over 3 months following the method of synthesis. The final obtained peptide-PEG-AuNP conjugates showed good biocompatibility in the presence of high ionic solutions and biological media and good cellular uptake. Formulation of colon cancer specific targeting peptide was successful, additionally, the genes/pathways affected by the treatments were determined through RT-PCR. Primary cells study is still on going with promising results thus far.

Keywords: nanotechnology, cancer, diagnosis, therapeutics, gold nanoparticles.

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6658 DPAGT1 Inhibitors: Discovery of Anti-Metastatic Drugs

Authors: Michio Kurosu

Abstract:

Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

Procedia PDF Downloads 76