Search results for: 7T SRAM cell
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3588

Search results for: 7T SRAM cell

2898 Synthesis of Erlotinib Analogues, Conjugation of BSA to Erlotinib Alcohol and Their Anti-Cancer Activity against NSCLC

Authors: Ramalingam Boobalan, Chinpiao Chen, Jui-I. Chiao

Abstract:

A series of erlotinib analogues that have structural modification at 6,7-alkoxyl positions is efficiently synthesized. The key reactions that involved in synthesis are one-pot oxime formation-dehydration for the formation of nitrile, quinazoline ring formation reaction between aniline and o-cyanoaniline via formamidine intermediate, Fe/NH4Cl catalyzed reduction-hetereocyclization-reductive ring opening reaction for the formation of o-aminobenzamide, high yielding seal tube reactions for O-demethylation, sodium iodide substitution, ammonia substitution. The in vitro anti-tumor activity of synthesized compounds is studied in two non-small cell lung cancer (NSCLC) cell lines (A549 and H1975). Among the synthesized compounds, the iodo compound 6 (ETN-6) exhibits higher anti-cancer activity compared to erlotinib. An efficient method is developed for the conjugation of erlotinib analogue-4, alcohol compound, with protein, bovine serum albumin (BSA), via succinic acid linker. The in vitro anti-tumor activity of the protein attached erlotinib analogue, 8 (ETN-4-Suc-BSA), showed stronger inhibitory activity in both A549 and H1975 NSCLC cell lines.

Keywords: anti-cancer, BSA, EGFR, Erlotinib

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2897 Quaternized PPO/PSF Anion Exchange Membranes Doped with ZnO-Nanoparticles for Fuel Cell Application

Authors: P. F. Msomi, P. T. Nonjola, P. G. Ndungu, J. Ramontja

Abstract:

In view of the projected global energy demand and increasing levels of greenhouse gases and pollutants issues have inspired an intense search for alternative new energy technologies, which will provide clean, low cost and environmentally friendly solutions to meet the end user requirements. Alkaline anion exchange membrane fuel cells (AAEMFC) have been recognized as ideal candidates for the generation of such clean energy for future stationary and mobile applications due to their many advantages. The key component of the AAEMFC is the anion exchange membrane (AEM). In this report, a series of quaternized poly (2.6 dimethyl – 1.4 phenylene oxide)/ polysulfone (QPPO/PSF) blend anionic exchange membranes (AEM) were successfully fabricated and characterized for alkaline fuel cell application. Zinc Oxide (ZnO) nanoparticles were introduced in the polymer matrix to enhance the intrinsic properties of the AEM. The characteristic properties of the QPPO/PSF and QPPO/PSF-ZnO blend membrane were investigated with X-ray diffraction (XRD), thermogravimetric analysis (TGA) scanning electron microscope (SEM) and contact angle (CA). To confirm successful quaternisation, FT-IR spectroscopy and proton nuclear magnetic resonance (1H NMR) were used. Other properties such as ion exchange capacity (IEC), water uptake, contact angle and ion conductivity (IC) were also undertaken to check if the prepared nanocomposite materials are suitable for fuel cell application. The membrane intrinsic properties were found to be enhanced by the addition of ZnO nanoparticles. The addition of ZnO nanoparticles resulted to a highest IEC of 3.72 mmol/g and a 30-fold IC increase of the nanocomposite due to its lower methanol permeability. The above results indicate that QPPO/PSF-ZnO is a good candidate for AAEMFC application.

Keywords: anion exchange membrane, fuel cell, zinc oxide nanoparticle, nanocomposite

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2896 Development of an Elastic Functionally Graded Interphase Model for the Micromechanics Response of Composites

Authors: Trevor Sabiston, Mohsen Mohammadi, Mohammed Cherkaoui, Kaan Inal

Abstract:

A new micromechanics framework is developed for long fibre reinforced composites using a single fibre surrounded by a functionally graded interphase and matrix as a representative unit cell. The unit cell is formulated to represent any number of aligned fibres by a single fibre. Using this model the elastic response of long fibre composites is predicted in all directions. The model is calibrated to experimental results and shows very good agreement in the elastic regime. The differences between the proposed model and existing models are discussed.

Keywords: computational mechanics, functionally graded interphase, long fibre composites, micromechanics

Procedia PDF Downloads 299
2895 Improved Qualitative Modeling of the Magnetization Curve B(H) of the Ferromagnetic Materials for a Transformer Used in the Power Supply for Magnetron

Authors: M. Bassoui, M. Ferfra, M. Chrayagne

Abstract:

This paper presents a qualitative modeling for the nonlinear B-H curve of the saturable magnetic materials for a transformer with shunts used in the power supply for the magnetron. This power supply is composed of a single phase leakage flux transformer supplying a cell composed of a capacitor and a diode, which double the voltage and stabilize the current, and a single magnetron at the output of the cell. A procedure consisting of a fuzzy clustering method and a rule processing algorithm is then employed for processing the constructed fuzzy modeling rules to extract the qualitative properties of the curve.

Keywords: B(H) curve, fuzzy clustering, magnetron, power supply

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2894 Optimized Dye-Sensitized Solar Cell Using Natural Dye and Counter Electrode from Robusta Coffee Beans Peel Waste

Authors: Tomi Setiawan, Wahyu Y. Subekti, Siti S. Nur'Adya, Khusnul Ilmiah

Abstract:

Dye-Sensitized Solar Cell (DSSC) is one type of solar cell, where solar cells function to convert light energy become the electrical energy. DSSC has two important parts of dye and counter electrode. Anthocyanin compounds in the coffee beans peel can be potential as natural dye and also counter electrodes as activated carbon in the DSSC system. The purpose of this research is to find out how to isolate Anthocyanin, manufacture of counter electrode, and to know the efficiency of counter electrode produced from the coffee pulp waste in DSSC prototype. In this research we used 2 x 2 cm FTO glass coated carbon paste with a thickness variation of 100 μL, 200 μL and 300 μL as counter electrode and other FTO glass coated with TiO₂ paste as work electrode, then two FTO glasses are connected to form a sandwich-liked structure and add Triiodide electrolyte solution in its gap, thus forming a DSSC prototype. The results showed that coffee pulp waste contains anthocyanin of 12.23 mL/80gr and it can produce activated carbon. The characterization performed shows that the UV-Vis Anthocyanin result is at wavelength of ultra violet area that is 219,50 nm with absorbance value equal to 1,469, and maximum wavelength at visible area is 720,00 nm with absorbance value equal to 0,013. The functional groups contained in the anthocyanin are O-H groups at wave numbers 3385.60 cm⁻¹, C = O groups at wave numbers 1618.63 cm⁻¹, and C-O-C groups at 1065.40 cm⁻¹ wave numbers. Morphological characterization using the SEM shows the activated carbon surface area becomes larger and evenly distributed. Voltage obtained on Counter Electrode 100 μL variation of 395mV, 200 μL of 334mV 100 μL of 254mV.

Keywords: DSSC, anthocyanin, counter electrode, solar cell, coffee pulp

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2893 Thermal Analysis of Photovoltaic Integrated Greenhouse Solar Dryer

Authors: Sumit Tiwari, Rohit Tripathi, G. N. Tiwari

Abstract:

Present study focused on the utilization of solar energy by the help of photovoltaic greenhouse solar dryer under forced mode. A single slope photovoltaic greenhouse solar dryer has been proposed and thermal modelling has been developed. Various parameters have been calculated by thermal modelling such as greenhouse room temperature, cell temperature, crop temperature and air temperature at exit of greenhouse. Further cell efficiency, thermal efficiency, and overall thermal efficiency have been calculated for a typical day of May and November. It was found that system can generate equivalent thermal energy up to 7.65 kW and 6.66 kW per day for clear day of May and November respectively.

Keywords: characteristics curve, photovoltaic, thermal modelling, thermal efficiency

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2892 Blue-Collar Workers’ Accidents and Close Call Situations Connected to the Use of Cell Phones among Finns Aged 18–65

Authors: L. Korpinen, R. Pääkkönen, F. Gobba

Abstract:

There has been discussion if the use of mobile phones causes accidents. We studied workers’ accidents and near accidents related to the use of phones. This study is part of a large cross-sectional study that was carried out on 15,000 working-age Finns. We noticed that there were 4–5 times more close call situations than accidents connected to mobile phones and also work related accidents were fewer than leisure related. There are confusing parameters like the use of mobile phones at work, differences in work content between women and men.

Keywords: blue-collar workers, accident, cell phone, close call situation

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2891 Comparison with Two Clinical Cases of Plasma Cell Neoplasm by Using the Method of Capillary Electrophoresis

Authors: Kai Pai Huang

Abstract:

Background: There are several types of plasma cell neoplasms including multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are found in our lab. Today, we want to compare with two cases using the method of capillary electrophoresis. Method: Serum is prepared and electrophoresis is performed at alkaline PH in a capillary using the Sebia® Capillary 2. Albumin and globulins are detected by the detector which is located in the cathode of the capillary and the signals are transformed to peaks. Serum was treated with beta-mercaptoethanol which reducing the polymerized immunoglobulin to monomer immunoglobulin to clarify two M-protein are secreted from the same plasma cell clone in bone marrow. Result: Case 1: A 78-year-old female presenting dysuria, oliguria and leg edema for several months. Laboratory data showed proteinuria, leukocytosis, results of high serum IgA and lambda light chain. A renal biopsy found amyloid fibrils in the glomerular mesangial area. Serum protein electrophoresis shows a major monoclonal peak in the β region and minor small peak in gamma region, and the immunotyping studies for serum showed two IgA/λ type. Case 2: A 55-year-old male presenting abdominal distension and low back pain for more than one month. Laboratory data showed T12 T8 compression fracture, results of high serum IgM and kappa light chain. Bone marrow aspiration showed the cells from the bone marrow are B cells with monotypic kappa chain expression. Bone marrow biopsy found this is lymphoplasmacytic lymphoma (Waldenstrom macroglobulin). Serum protein electrophoresis shows a monoclonal peak in the β region and the immunotyping studies for serum showed IgM/κ type. Conclusion: Plasma cell neoplasm can be diagnosed by many examinations. Among them, using capillary electrophoresis by a lab can separate several types of gammopathy and the quantification of a monoclonal peak can be used to evaluate the patients’ prognosis or treatment.

Keywords: plasma cell neoplasm, capillary electrophoresis, serum protein electrophoresis, immunotyping

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2890 Refractory T-Cell Prolymphocytic Leukemia with JAK3 Mutation: In Vitro and Clinical Synergy of Tofacitinib and Ruxolitinib

Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

Abstract:

T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

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2889 Control of Proton Exchange Membrane Fuel Cell Power System Using PI and Sliding Mode Controller

Authors: Mohamed Derbeli, Maissa Farhat, Oscar Barambones, Lassaad Sbita

Abstract:

Conventional controller (PI) applied to a DC/DC boost converter for the improvement and optimization of the Proton Exchange Membrane Fuel Cell (PEMFC) system efficiency, cannot attain a good performance effect. Thus, due to its advantages comparatively with the PI controller, this paper interest is focused on the use of the sliding mode controller (SMC), Stability of the closed loop system is analytically proved using Lyapunov approach for the proposed controller. The model and the controllers are implemented in the MATLAB and SIMULINK environment. A comparison of results indicates that the suggested approach has considerable advantages compared to the traditional controller.

Keywords: DC/DC boost converter, PEMFC, PI controller, sliding mode controller

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2888 Enhanced Cytotoxic Effect of Expanded NK Cells with IL12 and IL15 from Leukoreduction Filter on K562 Cell Line Exhibits Comparable Cytotoxicity to Whole Blood

Authors: Abdulbaset Mazarzaei

Abstract:

Natural killer (NK) cells are innate immune effectors that play a pivotal role in combating tumors and infected cells. In recent years, the therapeutic potential of NK cells has gained significant attention due to their remarkable cytotoxic ability. This study focuses on investigating the cytotoxic effect of expanded NK cells enriched with interleukin 12 (IL12) and interleukin 15 (IL15), derived from the leukoreduction filter, on the K562 cell line. Firstly, NK cells were isolated from whole blood samples obtained from healthy volunteers. These cells were subsequently expanded ex vivo using a combination of feeder cells, IL12, and IL15. The expanded NK cells were then harvested and assessed for their cytotoxicity against K562, a well-established human chronic myelogenous leukemia cell line. The cytotoxicity was evaluated using flow cytometry assay. Results demonstrate that the expanded NK cells significantly exhibited enhanced cytotoxicity against K562 cells compared to non-expanded NK cells. Interestingly, the expanded NK cells derived specifically from IL12 and IL15-enriched leukoreduction filters showed a robust cytotoxic effect similar to the whole blood-derived NK cells. These findings suggest that IL12 and IL15 in the leukoreduction filter are crucial in promoting NK cell cytotoxicity. Furthermore, the expanded NK cells displayed relatively similar cytotoxicity profiles to whole blood-derived NK cells, indicating their comparable capability in targeting and eliminating tumor cells. This observation is of significant relevance as expanded NK cells from the leukoreduction filter could potentially serve as a readily accessible and efficient source for adoptive immunotherapy. In conclusion, this study highlights the significant cytotoxic effect of expanded NK cells enriched with IL12 and IL15 obtained from the leukoreduction filter on the K562 cell line. Moreover, it emphasizes that these expanded NK cells exhibit comparable cytotoxicity to whole blood-derived NK cells. These findings reinforce the potential clinical utility of using expanded NK cells from the leukoreduction filter as an effective strategy in adoptive immunotherapy for the treatment of cancer. Further studies are warranted to explore the broader implications of this approach in clinical settings.

Keywords: natural killer (NK) cells, Cytotoxicity, Leukoreduction filter, IL-12 and IL-15 Cytokines

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2887 Epidemiological and Clinical Characteristics of Five Rare Pathological Subtypes of Hepatocellular Carcinoma

Authors: Xiaoyuan Chen

Abstract:

Background: This study aimed to characterize the epidemiological and clinical features of five rare subtypes of hepatocellular carcinoma (HCC) and to create a competing risk nomogram for predicting cancer-specific survival. Methods: This study used the Surveillance, Epidemiology, and End Results database to analyze the clinicopathological data of 50,218 patients with classic HCC and five rare subtypes (ICD-O-3 Histology Code=8170/3-8175/3) between 2004 and 2018. The annual percent change (APC) was calculated using Joinpoint regression, and a nomogram was developed based on multivariable competing risk survival analyses. The prognostic performance of the nomogram was evaluated using the Akaike information criterion, Bayesian information criterion, C-index, calibration curve, and area under the receiver operating characteristic curve. Decision curve analysis was used to assess the clinical value of the models. Results: The incidence of scirrhous carcinoma showed a decreasing trend (APC=-6.8%, P=0.025), while the morbidity of other rare subtypes remained stable from 2004 to 2018. The incidence-based mortality plateau in all subtypes during the period. Clear cell carcinoma was the most common subtype (n=551, 1.1%), followed by fibrolamellar (n=241, 0.5%), scirrhous (n=82, 0.2%), spindle cell (n=61, 0.1%), and pleomorphic (n=17, ~0%) carcinomas. Patients with fibrolamellar carcinoma were younger and more likely to have non-cirrhotic liver and better prognoses. Scirrhous carcinoma shared almost the same macro clinical characteristics and outcomes as classic HCC. Clear cell carcinoma tended to occur in the Asia-Pacific elderly male population, and more than half of them were large HCC (Size>5cm). Sarcomatoid (including spindle cell and pleomorphic) carcinoma was associated with larger tumor size, poorer differentiation, and more dismal prognoses. The pathological subtype, T stage, M stage, surgery, alpha-fetoprotein, and cancer history were identified as independent predictors in patients with rare subtypes. The nomogram showed good calibration, discrimination, and net benefits in clinical practice. Conclusion: The rare subtypes of HCC had distinct clinicopathological features and biological behaviors compared with classic HCC. Our findings could provide a valuable reference for clinicians. The constructed nomogram could accurately predict prognoses, which is beneficial for individualized management.

Keywords: hepatocellular carcinoma, pathological subtype, fibrolamellar carcinoma, scirrhous carcinoma, clear cell carcinoma, spindle cell carcinoma, pleomorphic carcinoma

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2886 Relative Entropy Used to Determine the Divergence of Cells in Single Cell RNA Sequence Data Analysis

Authors: An Chengrui, Yin Zi, Wu Bingbing, Ma Yuanzhu, Jin Kaixiu, Chen Xiao, Ouyang Hongwei

Abstract:

Single cell RNA sequence (scRNA-seq) is one of the effective tools to study transcriptomics of biological processes. Recently, similarity measurement of cells is Euclidian distance or its derivatives. However, the process of scRNA-seq is a multi-variate Bernoulli event model, thus we hypothesize that it would be more efficient when the divergence between cells is valued with relative entropy than Euclidian distance. In this study, we compared the performances of Euclidian distance, Spearman correlation distance and Relative Entropy using scRNA-seq data of the early, medial and late stage of limb development generated in our lab. Relative Entropy is better than other methods according to cluster potential test. Furthermore, we developed KL-SNE, an algorithm modifying t-SNE whose definition of divergence between cells Euclidian distance to Kullback–Leibler divergence. Results showed that KL-SNE was more effective to dissect cell heterogeneity than t-SNE, indicating the better performance of relative entropy than Euclidian distance. Specifically, the chondrocyte expressing Comp was clustered together with KL-SNE but not with t-SNE. Surprisingly, cells in early stage were surrounded by cells in medial stage in the processing of KL-SNE while medial cells neighbored to late stage with the process of t-SNE. This results parallel to Heatmap which showed cells in medial stage were more heterogenic than cells in other stages. In addition, we also found that results of KL-SNE tend to follow Gaussian distribution compared with those of the t-SNE, which could also be verified with the analysis of scRNA-seq data from another study on human embryo development. Therefore, it is also an effective way to convert non-Gaussian distribution to Gaussian distribution and facilitate the subsequent statistic possesses. Thus, relative entropy is potentially a better way to determine the divergence of cells in scRNA-seq data analysis.

Keywords: Single cell RNA sequence, Similarity measurement, Relative Entropy, KL-SNE, t-SNE

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2885 LncRNA NEAT1 Promotes NSCLC Progression through Acting as a ceRNA of miR-377-3p

Authors: Chengcao Sun, Shujun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, Dejia Li

Abstract:

Recently, the long non-coding RNA (lncRNA) NEAT1 has been identified as an oncogenic gene in multiple cancer types and elevated expression of NEAT1 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in progression of non-small cell lung cancer (NSCLC). In our studies, we identified NEAT1 was highly expressed in NSCLC patients and was a novel regulator of NSCLC progression. Patients whose tumors had high NEAT1 expression had a shorter overall survival than patients whose tumors had low NEAT1 expression. Further, NEAT1 significantly accelerates NSCLC cell growth and metastasis in vitro and tumor growth in vivo. Additionally, by using bioinformatics study and RNA pull down combined with luciferase reporter assays, we demonstrated that NEAT1 functioned as a competing endogenous RNA (ceRNA) for has-miR-377-3p, antagonized its functions and led to the de-repression of its endogenous targets E2F3, which was a core oncogene in promoting NSCLC progression. Taken together, these observations imply that the NEAT1 modulated the expression of E2F3 gene by acting as a competing endogenous RNA, which may build up the missing link between the regulatory miRNA network and NSCLC progression.

Keywords: long non-coding RNA NEAT1, hsa-miRNA-377-3p, E2F3, non-small cell lung cancer, tumorigenesis

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2884 A Comparison of Direct Water Injection with Membrane Humidifier for Proton Exchange Membrane Fuel Cells Humification

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

Abstract:

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

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2883 The Free Vibration Analysis of Honeycomb Sandwich Beam using 3D and Continuum Model

Authors: Gürkan Şakar, Fevzi Çakmak Bolat

Abstract:

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

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2882 Increased Cytolytic Activity of Effector T-Cells against Cholangiocarcinoma Cells by Self-Differentiated Dendritic Cells with Down-Regulation of Interleukin-10 and Transforming Growth Factor-β Receptors

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

Abstract:

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

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2881 Quantifying the Impacts of Elevated CO2 and N Fertilization on Wood Density in Loblolly Pine

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

Abstract:

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

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2880 A Low Cost Education Proposal Using Strain Gauges and Arduino to Develop a Balance

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

Abstract:

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

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2879 The Admitting Hemogram as a Predictor for Severity and in-Hospital Mortality in Acute Pancreatitis

Authors: Florge Francis A. Sy

Abstract:

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

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2878 Basal Cell Carcinoma: Epidemiological Analysis of a 5-Year Period in a Brazilian City with a High Level of Solar Radiation

Authors: Maria E. V. Amarante, Carolina L. Cerdeira, Julia V. Cortes, Fiorita G. L. Mundim

Abstract:

Basal cell carcinoma (BCC) is the most prevalent type of skin cancer in humans. It arises from the basal cells of the epidermis and cutaneous appendages. The role of sunlight exposure as a risk factor for BCC is very well defined due to its power to influence genetic mutations, in addition to having a suppressor effect on the skin immune system. Despite showing low metastasis and mortality rates, the tumor is locally infiltrative, aggressive, and destructive. Considering the high prevalence rate of this carcinoma and the importance of early detection, a retrospective study was carried out in order to correlate the clinical data available on BBC, characterize it epidemiologically, and thus enable effective prevention measures for the population. Data on the period from January 2015 to December 2019 were collected from the medical records of patients registered at one pathology service located in the southeast region of Brazil, known as SVO, which delivers skin biopsy results. The study was aimed at correlating the variables, sex, age, and subtypes found. Data analysis was performed using the chi-square test at a nominal significance level of 5% in order to verify the independence between the variables of interest. Fisher's exact test was applied in cases where the absolute frequency in the cells of the contingency table was less than or equal to five. The statistical analysis was performed using the R® software. Ninety-three basal cell carcinoma were analyzed, and its frequency in the 31-to 45-year-old age group was 5.8 times higher in men than in women, whereas, from 46 to 59 years, the frequency was found 2.4 times higher in women than in men. Between the ages of 46 to 59 years, it should be noted that the sclerodermiform subtype appears more than the solid one, with a difference of 7.26 percentage points. Reversely, the solid form appears more frequently in individuals aged 60 years or more, with a difference of 8.57 percentage points. Among women, the frequency of the solid subtype was 9.93 percentage points higher than the sclerodermiform frequency. In males, the same percentage difference is observed, but sclerodermiform is the most prevalent subtype. It is concluded in this study that, in general, there is a predominance of basal cell carcinoma in females and in individuals aged 60 years and over, which demonstrates the tendency of this tumor. However, when rarely found in younger individuals, the male gender prevailed. The most prevalent subtype was the solid one. It is worth mentioning that the sclerodermiform subtype, which is more aggressive, was seen more frequently in males and in the 46-to 59-year-old range.

Keywords: basal cell carcinoma, epidemiology, sclerodermiform basal cell carcinoma, skin cancer, solar radiation, solid basal cell carcinoma

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2877 Decellularized Brain-Chitosan Scaffold for Neural Tissue Engineering

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

Abstract:

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

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2876 The Protective Effect of Grape Seed Oil with Use of Ciprofloxacin Induced Germ Cell Toxicity in Male Albino Mice

Authors: Galawezh Obaid Othman

Abstract:

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

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2875 YPFS Attenuating TH2 Cell-Mediated Allergic Inflammation by Regulating the TSLP Pathway

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

Abstract:

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

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2874 Developing Customizable Scaffolds With Antimicrobial Properties for Vascular Tissue Regeneration Using Low Temperature Plasma

Authors: Komal Vig, Syamala Soumyakrishnan, Yadav Baral

Abstract:

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

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2873 Antiproliferative and Apoptotic Effects of an Enantiomerically Pure β-Dipeptide Derivative through PI3K/Akt-Dependent and -Independent Pathways in Human Hormone-Refractory Prostate Cancer Cells

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

Abstract:

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

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2872 Modeling and Optimization of a Microfluidic Electrochemical Cell for the Electro-Reduction of CO₂ to CH₃OH

Authors: Barzin Rajabloo, Martin Desilets

Abstract:

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

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2871 Cooperative AF Scheme for Multi Source and Terminal in Edge of Cell Coverage

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

Abstract:

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

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2870 Effect of Environmental Conditions on E. Coli o157:h7 Atcc 43888 and L. Monocytogenes Atcc 7644 Cell Surface Hydrophobicity, Motility and Cell Attachment on Food-Contact Surfaces

Authors: Stanley Dula, Oluwatosini A. Ijabadeniyi

Abstract:

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

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2869 Cellular Mechanisms Involved in the Radiosensitization of Breast- and Lung Cancer Cells by Agents Targeting Microtubule Dynamics

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

Abstract:

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

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