Search results for: signet ring cell cancer
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5371

Search results for: signet ring cell cancer

2761 Generalized π-Armendariz Authentication Cryptosystem

Authors: Areej M. Abduldaim, Nadia M. G. Al-Saidi

Abstract:

Algebra is one of the important fields of mathematics. It concerns with the study and manipulation of mathematical symbols. It also concerns with the study of abstractions such as groups, rings, and fields. Due to the development of these abstractions, it is extended to consider other structures, such as vectors, matrices, and polynomials, which are non-numerical objects. Computer algebra is the implementation of algebraic methods as algorithms and computer programs. Recently, many algebraic cryptosystem protocols are based on non-commutative algebraic structures, such as authentication, key exchange, and encryption-decryption processes are adopted. Cryptography is the science that aimed at sending the information through public channels in such a way that only an authorized recipient can read it. Ring theory is the most attractive category of algebra in the area of cryptography. In this paper, we employ the algebraic structure called skew -Armendariz rings to design a neoteric algorithm for zero knowledge proof. The proposed protocol is established and illustrated through numerical example, and its soundness and completeness are proved.

Keywords: cryptosystem, identification, skew π-Armendariz rings, skew polynomial rings, zero knowledge protocol

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2760 Bioremediation of Phenol in Wastewater Using Polymer-Supported Bacteria

Authors: Areej K. Al-Jwaid, Dmitiry Berllio, Andrew Cundy, Irina Savina, Jonathan L. Caplin

Abstract:

Phenol is a toxic compound that is widely distributed in the environment including the atmosphere, water and soil, due to the release of effluents from the petrochemical and pharmaceutical industries, coking plants and oil refineries. Moreover, a range of daily products, using phenol as a raw material, may find their way into the environment without prior treatment. The toxicity of phenol effects both human and environment health, and various physio-chemical methods to remediate phenol contamination have been used. While these techniques are effective, their complexity and high cost had led to search for alternative strategies to reduce and eliminate high concentrations of phenolic compounds in the environment. Biological treatments are preferable because they are environmentally friendly and cheaper than physico-chemical approaches. Some microorganisms such as Pseudomonas sp., Rhodococus sp., Acinetobacter sp. and Bacillus sp. have shown a high ability to degrade phenolic compounds to provide a sole source of energy. Immobilisation process utilising various materials have been used to protect and enhance the viability of cells, and to provide structural support for the bacterial cells. The aim of this study is to develop a new approach to the bioremediation of phenol based on an immobilisation strategy that can be used in wastewater. In this study, two bacterial species known to be phenol degrading bacteria (Pseudomonas mendocina and Rhodococus koreensis) were purchased from National Collection of Industrial, Food and Marine Bacteria (NCIMB). The two species and mixture of them were immobilised to produce macro porous crosslinked cell cryogels samples by using four types of cross-linker polymer solutions in a cryogelation process. The samples were used in a batch culture to degrade phenol at an initial concentration of 50mg/L at pH 7.5±0.3 and a temperature of 30°C. The four types of polymer solution - i. glutaraldehyde (GA), ii. Polyvinyl alcohol with glutaraldehyde (PVA+GA), iii. Polyvinyl alcohol–aldehyde (PVA-al) and iv. Polyetheleneimine–aldehyde (PEI-al), were used at different concentrations, ranging from 0.5 to 1.5% to crosslink the cells. The results of SEM and rheology analysis indicated that cell-cryogel samples crosslinked with the four cross-linker polymers formed monolithic macro porous cryogels. The samples were evaluated for their ability to degrade phenol. Macro porous cell–cryogels crosslinked with GA and PVA+GA showed an ability to degrade phenol for only one week, while the other samples crosslinked with a combination of PVA-al + PEI-al at two different concentrations have shown higher stability and viability to reuse to degrade phenol at concentration (50 mg/L) for five weeks. The initial results of using crosslinked cell cryogel samples to degrade phenol indicate that is a promising tool for bioremediation strategies especially to eliminate and remove the high concentration of phenol in wastewater.

Keywords: bioremediation, crosslinked cells, immobilisation, phenol degradation

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2759 Effect of Proteoliposome Concentration on Salt Rejection Rate of Polysulfone Membrane Prepared by Incorporation of Escherichia coli and Halomonas elongata Aquaporins

Authors: Aysenur Ozturk, Aysen Yildiz, Hilal Yilmaz, Pinar Ergenekon, Melek Ozkan

Abstract:

Water scarcity is one of the most important environmental problems of the World today. Desalination process is regarded as a promising solution to solve drinking water problem of the countries facing with water shortages. Reverse osmosis membranes are widely used for desalination processes. Nano structured biomimetic membrane production is one of the most challenging research subject for improving water filtration efficiency of the membranes and for reducing the cost of desalination processes. There are several researches in the literature on the development of novel biomimetic nanofiltration membranes by incorporation of aquaporin Z molecules. Aquaporins are cell membrane proteins that allow the passage of water molecules and reject all other dissolved solutes. They are present in cell membranes of most of the living organisms and provide high water passage capacity. In this study, GST (Glutathione S-transferas) tagged E. coli aquaporinZ and H. elongate aquaporin proteins, which were previously cloned and characterized, were purified from E. coli BL21 cells and used for fabrication of modified Polysulphone Membrane (PS). Aquaporins were incorporated on the surface of the membrane by using 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) phospolipids as carrier liposomes. Aquaporin containing proteoliposomes were immobilized on the surface of the membrane with m-phenylene-diamine (MPD) and trimesoyl chloride (TMC) rejection layer. Water flux, salt rejection and glucose rejection performances of the thin film composite membranes were tested by using Dead-End Reactor Cell. In this study, effect of proteoliposome concentration, and filtration pressure on water flux and salt rejection rate of membranes were investigated. Type of aquaporin used for membrane fabrication, flux and pressure applied for filtration were found to be important parameters affecting rejection rates. Results suggested that optimization of concentration of aquaporin carriers (proteoliposomes) on the membrane surface is necessary for fabrication of effective composite membranes used for different purposes.

Keywords: aquaporins, biomimmetic membranes, desalination, water treatment

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2758 Immunomodulatory Effect of Deer Antler Extract

Authors: Kang-Hyun Leem, Myung-Gyou Kim, Hye Kyung Kim

Abstract:

Velvet antler (VA), the immature antlers of male deer, is traditionally used for thousands of years in Asian countries, such as Korea, China, Taiwan, and Mongolia. It has been considered to improve immune system and physical strength. The goal of this study was to investigate the immunomodulatory effect of deer antler velvet using in vitro system. In the first step, the effects of VA (70% ethanol extract) on the proliferation of splenocytes, bone marrow cell, and macrophages were determined. Next, the effect of VA on the production of nitric oxide and phagocytic activity in macrophage were measured. The results showed that VA treatment increased concanavalin-A stimulated splenocyte, bone marrow cells, and macrophage proliferation in a dose dependent manner. VA at 50 and 100 ug/mL concentrations significantly enhanced the concanavalin-A stimulated splenocyte proliferation by 8.8% and 18.5%, respectively. The proliferation of bone marrow cells, isolated from 5wk-old ICR mice, were increased by 25.2% and 46.5% by 50 and 100 ug/mL VA treatment. RAW 264.7 cell proliferation reached peak value at 50 ug/mL of VA treatment exhibiting 108% of the basal value. Nitric oxide production by RAW 264.7 macrophage cells was slightly reduced by VA treatment but was not statistically significant. Moreover, the phagocytic activity of macrophages was enhanced by VA treatment. These results indicate that VA is effective in immune system.

Keywords: deer antler, splenocyte, bone marrow cells, macrophage proliferation, phagocytosis

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2757 Effect Indol Acetic Acid on Liver of Albino Rats

Authors: Ezaldin A. M. Mohammed, Youssef K. H. Abdalhafid, Masoud. M. Zatout

Abstract:

The study aims to clarify the toxic effect of plant hormones, which are widely used in agriculture. One of these is the plant hormones (indole acetic acid); has been ٳata hormone to rats at 100 ppm salt solution of 0.2 per day after day for a period of forty days before conception until the fourteenth day or sixteenth or childbirth. Treatment brought about a marked shortage in the rate of increase in the weight of mice., And a percentage of the weight of the liver there was a distinct increase in the relative weight of the liver. As well as the increase in pathological changes and increase the size of the nuclei and Kupffer cell, as noted widespread and dense clusters of inflammatory cells accompanied by about the erosion of liver tissue and blood ٳrchah. Biochemical analyzes showed a marked decrease of the liver in antioxidant enzymes and an increase in the rate of free radicals. It was also noted an increase in cases of abortion. The owner of so many birth defects. It was also noted the lack of body weight in fetuses and increase the absorption rate of embryos in fetuses of mothers treatment compared to the control group. Showed microscopic examinations of the liver of mice born in the transaction and the decay in the presence of hepatic cells and edema, blood vessels and increase the rate of cell death.

Keywords: indol acetic acid, liver, pathological changes, albino rats

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2756 A Comparative Time-Series Analysis and Deep Learning Projection of Innate Radon Gas Risk in Canadian and Swedish Residential Buildings

Authors: Selim M. Khan, Dustin D. Pearson, Tryggve Rönnqvist, Markus E. Nielsen, Joshua M. Taron, Aaron A. Goodarzi

Abstract:

Accumulation of radioactive radon gas in indoor air poses a serious risk to human health by increasing the lifetime risk of lung cancer and is classified by IARC as a category one carcinogen. Radon exposure risks are a function of geologic, geographic, design, and human behavioural variables and can change over time. Using time series and deep machine learning modelling, we analyzed long-term radon test outcomes as a function of building metrics from 25,489 Canadian and 38,596 Swedish residential properties constructed between 1945 to 2020. While Canadian and Swedish properties built between 1970 and 1980 are comparable (96–103 Bq/m³), innate radon risks subsequently diverge, rising in Canada and falling in Sweden such that 21st Century Canadian houses show 467% greater average radon (131 Bq/m³) relative to Swedish equivalents (28 Bq/m³). These trends are consistent across housing types and regions within each country. The introduction of energy efficiency measures within Canadian and Swedish building codes coincided with opposing radon level trajectories in each nation. Deep machine learning modelling predicts that, without intervention, average Canadian residential radon levels will increase to 176 Bq/m³ by 2050, emphasizing the importance and urgency of future building code intervention to achieve systemic radon reduction in Canada.

Keywords: radon health risk, time-series, deep machine learning, lung cancer, Canada, Sweden

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2755 Survival of Micro-Encapsulated Probiotic Lactic Acid Bacteria in Mutton Nuggets and Their Assessments in Simulated Gastro-Intestinal Conditions

Authors: Rehana Akhter, Sajad A. Rather, F. A. Masoodi, Adil Gani, S. M. Wani

Abstract:

During recent years probiotic food products receive market interest as health-promoting, functional foods, which are believed to contribute health benefits. In order to deliver the health benefits by probiotic bacteria, it has been recommended that they must be present at a minimum level of 106 CFU/g to 107 CFU/g at point of delivery or be eaten in sufficient amounts to yield a daily intake of 108 CFU. However a major challenge in relation to the application of probiotic cultures in food matrix is the maintenance of viability during processing which might lead to important losses in viability as probiotic cultures are very often thermally labile and sensitive to acidity, oxygen or other food constituents for example, salts. In this study Lactobacillus plantarum and Lactobacillus casei were encapsulated in calcium alginate beads with the objective of enhancing their survivability and preventing exposure to the adverse conditions of the gastrointestinal tract and where then inoculated in mutton nuggets. Micro encapsulated Lactobacillus plantarum and Lactobacillus casei were resistant to simulated gastric conditions (pH 2, 2h) and bile solution (3%, 2 h) resulting in significantly (p ≤ 0.05) improved survivability when compared with free cell counterparts. A high encapsulation yield was found due to the encapsulation procedure. After incubation at low pH-values, micro encapsulation yielded higher survival rates compared to non-encapsulated probiotic cells. The viable cell numbers of encapsulated Lactobacillus plantarum and Lactobacillus casei were 107-108 CFU/g higher compared to free cells after 90 min incubation at pH 2.5. The viable encapsulated cells were inoculated into mutton nuggets at the rate of 108 to 1010 CFU/g. The micro encapsulated Lactobacillus plantarum and Lactobacillus casei achieved higher survival counts (105-107 CFU/g) than the free cell counterparts (102-104 CFU/g). Thus micro encapsulation offers an effective means of delivery of viable probiotic bacterial cells to the colon and maintaining their survival during simulated gastric, intestinal juice and processing conditions during nugget preparation.

Keywords: survival, Lactobacillus plantarum, Lactobacillus casei, micro-encapsulation, nugget

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2754 Development of Nanoparticulate Based Chimeric Drug Delivery System Using Drug Bioconjugated Plant Virus Capsid on Biocompatible Nanoparticles

Authors: Indu Barwal, Shloka Thakur, Subhash C. Yadav

Abstract:

The plant virus capsid protein based nanoparticles are extensively studied for their application in biomedical research for development of nanomedicines and drug delivery systems. We have developed a chimeric drug delivery system by controlled in vitro assembly of separately bioconjugated fluorescent dye (as reporting molecule), folic acid (as receptor binding biomolecule for targeted delivery) and doxorubicin (as anticancer drug) using modified EDC NHS chemistry on heterologously overexpressed (E. coli) capsid proteins of cowpea chlorotic mottle virus (CCMV). This chimeric vehicle was further encapsidated on gold nanoparticles (20nm) coated with 5≠ thiolated DNA probe to neutralize the positive charge of capsid proteins. This facilitates the in vitro assembly of modified capsid subunits on the gold nanoparticles to develop chimeric GNPs encapsidated targeted drug delivery system. The bioconjugation of functionalities, number of functionality on capsid subunits as well as virus like nanoparticles, structural stability and in vitro assembly were confirmed by SDS PAGE, relative absorbance, MALDI TOF, ESI-MS, Circular dichroism, intrinsic tryptophan fluorescence, zeta particle size analyzer and TEM imaging. This vehicle was stable at pH 4.0 to 8.0 suitable for many organelles targeting. This in vitro assembled chimeric plant virus like particles could be suitable for ideal drug delivery vehicles for subcutaneous cancer treatment and could be further modified for other type of cancer treatment by conjugating other functionalities (targeting, drug) on capsids.

Keywords: chimeric drug delivery vehicles, bioconjugated plant, virus, capsid

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2753 A Case Study of Ontology-Based Sentiment Analysis for Fan Pages

Authors: C. -L. Huang, J. -H. Ho

Abstract:

Social media has become more and more important in our life. Many enterprises promote their services and products to fans via the social media. The positive or negative sentiment of feedbacks from fans is very important for enterprises to improve their products, services, and promotion activities. The purpose of this paper is to understand the sentiment of the fan’s responses by analyzing the responses posted by fans on Facebook. The entity and aspect of fan’s responses were analyzed based on a predefined ontology. The ontology for cell phone sentiment analysis consists of aspect categories on the top level as follows: overall, shape, hardware, brand, price, and service. Each category consists of several sub-categories. All aspects for a fan’s response were found based on the ontology, and their corresponding sentimental terms were found using lexicon-based approach. The sentimental scores for aspects of fan responses were obtained by summarizing the sentimental terms in responses. The frequency of 'like' was also weighted in the sentimental score calculation. Three famous cell phone fan pages on Facebook were selected as demonstration cases to evaluate performances of the proposed methodology. Human judgment by several domain experts was also built for performance comparison. The performances of proposed approach were as good as those of human judgment on precision, recall and F1-measure.

Keywords: opinion mining, ontology, sentiment analysis, text mining

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2752 Optimization of Poly-β-Hydroxybutyrate Recovery from Bacillus Subtilis Using Solvent Extraction Process by Response Surface Methodology

Authors: Jayprakash Yadav, Nivedita Patra

Abstract:

Polyhydroxybutyrate (PHB) is an interesting material in the field of medical science, pharmaceutical industries, and tissue engineering because of its properties such as biodegradability, biocompatibility, hydrophobicity, and elasticity. PHB is naturally accumulated by several microbes in their cytoplasm during the metabolic process as energy reserve material. PHB can be extracted from cell biomass using halogenated hydrocarbons, chemicals, and enzymes. In this study, a cheaper and non-toxic solvent, acetone, was used for the extraction process. The different parameters like acetone percentage, and solvent pH, process temperature, and incubation periods were optimized using the Response Surface Methodology (RSM). RSM was performed and the determination coefficient (R2) value was found to be 0.8833 from the quadratic regression model with no significant lack of fit. The designed RSM model results indicated that the fitness of the response variable was significant (P-value < 0.0006) and satisfactory to denote the relationship between the responses in terms of PHB recovery and purity with respect to the values of independent variables. Optimum conditions for the maximum PHB recovery and purity were found to be solvent pH 7, extraction temperature - 43 °C, incubation time - 70 minutes, and percentage acetone – 30 % from this study. The maximum predicted PHB recovery was found to be 0.845 g/g biomass dry cell weight and the purity was found to be 97.23 % using the optimized conditions.

Keywords: acetone, PHB, RSM, halogenated hydrocarbons, extraction, bacillus subtilis.

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2751 Heritage Value and Industrial Tourism Potential of the Urals, Russia

Authors: Anatoly V. Stepanov, Maria Y. Ilyushkina, Alexander S. Burnasov

Abstract:

Expansion of tourism, especially after WWII, has led to significant improvements in the regional infrastructure. The present study has revealed a lot of progress in the advancement of industrial heritage narrative in the Central Urals. The evidence comes from the general public’s increased fascination with some of Europe’s oldest mining and industrial sites, and the agreement of many stakeholders that the Urals industrial heritage should be preserved. The development of tourist sites in Nizhny Tagil and Nevyansk, gold-digging in Beryosovsky, gemstone search in Murzinka, and the progress with the Urals Gemstone Ring project are the examples showing the immense opportunities of industrial heritage tourism development in the region that are still to be realized. Regardless of the economic future of the Central Urals, whether it will remain an industrial region or experience a deeper deindustrialization, the sprouts of the industrial heritage tourism should be advanced and amplified for the benefit of local communities and the tourist community at large as it is hard to imagine a more suitable site for the discovery of industrial and mining heritage than the Central Urals Region of Russia.

Keywords: industrial heritage, mining heritage, Central Urals, Russia

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2750 Decreased Tricarboxylic Acid (TCA) Cycle Staphylococcus aureus Increases Survival to Innate Immunity

Authors: Trenten Theis, Trevor Daubert, Kennedy Kluthe, Austin Nuxoll

Abstract:

Staphylococcus aureus is a gram-positive bacterium responsible for an estimated 23,000 deaths in the United States and 25,000 deaths in the European Union annually. Recurring S. aureus bacteremia is associated with biofilm-mediated infections and can occur in 5 - 20% of cases, even with the use of antibiotics. Despite these infections being caused by drug-susceptible pathogens, they are surprisingly difficult to eradicate. One potential explanation for this is the presence of persister cells—a dormant type of cell that shows a high tolerance to antibiotic treatment. Recent studies have shown a connection between low intracellular ATP and persister cell formation. Specifically, this decrease in ATP, and therefore increase in persister cell formation, is due to an interrupted tricarboxylic acid (TCA) cycle. However, S. aureus persister cells’ role in pathogenesis remains unclear. Initial studies have shown that a fumC (TCA cycle gene) knockout survives challenge from aspects of the innate immune system better than wild-type S. aureus. Specifically, challenges from two antimicrobial peptides--LL-37 and hBD-3—show a log increase in survival of the fumC::N∑ strain compared to wild type S. aureus after 18 hours. Furthermore, preliminary studies show that the fumC knockout has a log more survival within a macrophage. These data lead us to hypothesize that the fumC knockout is better suited to other aspects of the innate immune system compared to wild-type S. aureus. To further investigate the mechanism for increased survival of fumC::N∑ within a macrophage, we tested bacterial growth in the presence of reactive oxygen species (ROS), reactive nitrogen species (RNS), and a low pH. Preliminary results suggest that the fumC knockout has increased growth compared to wild-type S. aureus in the presence of all three antimicrobial factors; however, no difference was observed in any single factor alone. To investigate survival within a host, a nine-day biofilm-associated catheter infection was performed on 6–8-week-old male and female C57Bl/6 mice. Although both sexes struggled to clear the infection, female mice were trending toward more frequently clearing the HG003 wild-type infection compared to the fumC::N∑ infection. One possible reason for the inability to reduce the bacterial burden is that biofilms are largely composed of persister cells. To test this hypothesis further, flow cytometry in conjunction with a persister cell marker was used to measure persister cells within a biofilm. Cap5A (a known persister cell marker) expression was found to be increased in a maturing biofilm, with the lowest levels of expression seen in immature biofilms and the highest expression exhibited by the 48-hour biofilm. Additionally, bacterial cells in a biofilm state closely resemble persister cells and exhibit reduced membrane potential compared to cells in planktonic culture, further suggesting biofilms are largely made up of persister cells. These data may provide an explanation as to why infections caused by antibiotic-susceptible strains remain difficult to treat.

Keywords: antibiotic tolerance, Staphylococcus aureus, host-pathogen interactions, microbial pathogenesis

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2749 Morphological Interaction of Porcine Oocyte and Cumulus Cells Study on in vitro Oocyte Maturation Using Electron Microscopy

Authors: M. Areekijseree, W. Pongsawat, M. Pumipaiboon, C. Thepsithar, S. Sengsai, T. Chuen-Im

Abstract:

Morphological interaction of porcine cumulus-oocyte complexes (pCOCs) was investigated on in vitro condition using electron microscope (SEM and TEM). The totals of 1,923 oocytes were round in shape, surrounded by zona pellucida with layer of cumulus cells ranging between 59.29-202.14 µm in size. They were classified into intact-, multi-, partial cumulus cell layer oocyte, and completely denuded oocyte, at the percentage composition of 22.80% 32.70%, 18.60%, and 25.90 % respectively. The pCOCs classified as intact- and multi cumulus cell layer oocytes were further culturing at 37°C with 5% CO2, 95% air atmosphere and high humidity for 44 h in M199 with Earle’s salts supplemented with 10% HTFCS, 2.2 mg/mL NaHCO3, 1 M Hepes, 0.25 mM pyruvate, 15 µg/mL porcine follicle-stimulating hormone, 1 µg/mL LH, 1µg/mL estradiol with ethanol, and 50 µg/mL gentamycin sulfate. On electron microscope study, cumulus cells were found to stick their processes to secrete substance from the sac-shape end into zona pellucida of the oocyte and also communicated with the neighboring cells through their microvilli on the beginning of incubation period. It is believed that the cumulus cells communicate with the oocyte by inserting the microvilli through this gap and embedded in the oocyte cytoplasm before secreting substance, through the sac-shape end of the microvilli, to inhibit primary oocyte development at the prophase I. Morphological changes of the complexes were observed after culturing for 24-44 h. One hundred percentages of the cumulus layers were expanded and cumulus cells were peeling off from the oocyte surface. In addition, the round-shape cumulus cells transformed themselves into either an elongate shape or a columnar shape, and no communication between cumulus neighboring cells. After 44 h of incubation time, diameter of oocytes surrounded by cumulus cells was larger than 0 h incubation. The effect of hormones in culture medium is exerted by their receptors present in porcine oocyte. It is likely that all morphological changes of the complexes after hormone treatment were to allow maturation of the oocyte. This study demonstrated that the association of hormones in M199 could promote porcine follicle activation in 44 h in vitro condition. This culture system should be useful for studying the regulation of early follicular growth and development, especially because these follicles represent a large source of oocytes that could be used in vitro for cell technology.

Keywords: cumulus cells, electron microscopy, in vitro, porcine oocyte

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2748 Application Difference between Cox and Logistic Regression Models

Authors: Idrissa Kayijuka

Abstract:

The logistic regression and Cox regression models (proportional hazard model) at present are being employed in the analysis of prospective epidemiologic research looking into risk factors in their application on chronic diseases. However, a theoretical relationship between the two models has been studied. By definition, Cox regression model also called Cox proportional hazard model is a procedure that is used in modeling data regarding time leading up to an event where censored cases exist. Whereas the Logistic regression model is mostly applicable in cases where the independent variables consist of numerical as well as nominal values while the resultant variable is binary (dichotomous). Arguments and findings of many researchers focused on the overview of Cox and Logistic regression models and their different applications in different areas. In this work, the analysis is done on secondary data whose source is SPSS exercise data on BREAST CANCER with a sample size of 1121 women where the main objective is to show the application difference between Cox regression model and logistic regression model based on factors that cause women to die due to breast cancer. Thus we did some analysis manually i.e. on lymph nodes status, and SPSS software helped to analyze the mentioned data. This study found out that there is an application difference between Cox and Logistic regression models which is Cox regression model is used if one wishes to analyze data which also include the follow-up time whereas Logistic regression model analyzes data without follow-up-time. Also, they have measurements of association which is different: hazard ratio and odds ratio for Cox and logistic regression models respectively. A similarity between the two models is that they are both applicable in the prediction of the upshot of a categorical variable i.e. a variable that can accommodate only a restricted number of categories. In conclusion, Cox regression model differs from logistic regression by assessing a rate instead of proportion. The two models can be applied in many other researches since they are suitable methods for analyzing data but the more recommended is the Cox, regression model.

Keywords: logistic regression model, Cox regression model, survival analysis, hazard ratio

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2747 A Study on FWD Deflection Bowl Parameters for Condition Assessment of Flexible Pavement

Authors: Ujjval J. Solanki, Prof.(Dr.) P.J. Gundaliya, Prof.M.D. Barasara

Abstract:

The application of Falling Weight Deflectometer is to evaluate structural performance of the flexible pavement. The exercise of back calculation is required to know the modulus of elasticity of existing in-service pavement. The process of back calculation needs in-depth field experience for the input of range of modulus of elasticity of bituminous, granular and subgrade layer, and its required number of trial to find such matching moduli with the observed FWD deflection on the field. The study carried out at Barnala-Mansa State Highway Punjab-India using FWD before and after overlay; the deflections obtained at 0 on the load cell, 300, 600, 900,1200, 1500 and 1800 mm interval from the load cell these seven deflection results used to calculate Surface Curvature Index (SCI), Base damage Index (BDI), Base curvature index (BCI). This SCI, BCI and BDI indices are useful to predict the structural performance of in-service pavement and also useful to identify homogeneous section for condition assessment. The SCI, BCI and BDI range are determined for before and after overlay the range of SCI 520 to 51 BDI 294 to 63 BCI 83 to 0.27 for old pavement and SCI 272 to 23 BDI 228 to 28, BCI 25.85 to 4.60 for new pavement. It also shows good correlation with back calculated modulus of elasticity of all the three layer.

Keywords: back calculation, base damage index, base curvature index, FWD (Falling Weight Deflectometer), surface curvature index

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2746 Computer-Aided Diagnosis System Based on Multiple Quantitative Magnetic Resonance Imaging Features in the Classification of Brain Tumor

Authors: Chih Jou Hsiao, Chung Ming Lo, Li Chun Hsieh

Abstract:

Brain tumor is not the cancer having high incidence rate, but its high mortality rate and poor prognosis still make it as a big concern. On clinical examination, the grading of brain tumors depends on pathological features. However, there are some weak points of histopathological analysis which can cause misgrading. For example, the interpretations can be various without a well-known definition. Furthermore, the heterogeneity of malignant tumors is a challenge to extract meaningful tissues under surgical biopsy. With the development of magnetic resonance imaging (MRI), tumor grading can be accomplished by a noninvasive procedure. To improve the diagnostic accuracy further, this study proposed a computer-aided diagnosis (CAD) system based on MRI features to provide suggestions of tumor grading. Gliomas are the most common type of malignant brain tumors (about 70%). This study collected 34 glioblastomas (GBMs) and 73 lower-grade gliomas (LGGs) from The Cancer Imaging Archive. After defining the region-of-interests in MRI images, multiple quantitative morphological features such as region perimeter, region area, compactness, the mean and standard deviation of the normalized radial length, and moment features were extracted from the tumors for classification. As results, two of five morphological features and three of four image moment features achieved p values of <0.001, and the remaining moment feature had p value <0.05. Performance of the CAD system using the combination of all features achieved the accuracy of 83.18% in classifying the gliomas into LGG and GBM. The sensitivity is 70.59% and the specificity is 89.04%. The proposed system can become a second viewer on clinical examinations for radiologists.

Keywords: brain tumor, computer-aided diagnosis, gliomas, magnetic resonance imaging

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2745 Efficacy of Umbilical Cord Lining Stem Cells For Wound Healing in Diabetic Murine Model

Authors: Fui Ping Lim, Wen Choong Chua, Toan Thang Phan

Abstract:

Aim: This study investigates the roles of Cord Lining Stem Cells (CLSCs) as potential therapeutic agents for diabetic wounds. Method: 20 genetically diabetic db/db mice were randomly assigned to two arms; (i) control group received placebo treatment (sham media or cells delivery material), and (ii) active comparator received CLSCs. Two full-thickness wounds, each sized 10mm X 10mm were created, one on each side of the midline on the back of the mice. Digital pictures were taken on day 1, 3, 7, 10, 14, 17, 21, 24, 28. Wound areas were analyzed with ImageJ TM software and calculated as percentage of the original wound. Time to closure was defined as the day the wound bed was completely epithelized and filled with new tissues. Results: The CLSCs-treated wounds, showed a significant increase in the percentage of wound closure and achieved 100% closure of the wound sooner than the control group by an average of 3.7 days. The mice treated with CLSCs have a shorter wound closure time (mean closure day: 19.8 days) as compared to the control group (mean closure day: 23.5 days). Conclusion: Our preliminary findings inferred that CLSCs treated wound achieved higher percentage of wound closure within a shorter duration of time.

Keywords: cord lining stem cell, diabetic wound, stem cell, wound

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2744 Cytotoxicity of Nano β–Tricalcium Phosphate (β-TCP) on Human Osteoblast (hFOB1.19)

Authors: Jer Ping Ooi, Shah Rizal Bin Kasim, Nor Aini Saidin

Abstract:

The objective of this study was to synthesize nano-sized β-tricalcium phosphate (β-TCP) powder and assess its cytotoxic effects on human osteoblast (hFOB1.19) by using four cytotoxicity assays, namely, lactose dehydrogenase (LDHe), tetrazolium hydroxide (XTT), neutral red (NR), and sulforhodamine B (SRB) assays. β-tricalcium phosphate (β-TCP) is a calcium phosphate compound commonly used as an implant material. To date, bulk-sized β-TCP is reported to be readily tolerated by the osteogenic cells and body based on in vitro, in vivo experiments and clinical studies. However, to what extent of nano-sized β-TCP will react in models as compared to bulk β-TCP is yet to be investigated. Thus, in this project, the cells were treated with nano β-TCP powder within a range of concentrations from 0 to 1000 μg/mL for 24, 48, and 72 h. The cytotoxicity tests showed that loss of cell viability ( > 50%) was high for hFOB1.19 cells in all assays. Cell cycle and apoptosis analysis of hFOB1.19 cells revealed that 50 μg/mL of the compound led to 30.5% of cells being apoptotic after 72 h of incubation, and the percentage was increased to 58.6% when the concentration was increased to 200 μg/mL. When the incubation time was increased from 24 to 72 h, the percentage of apoptotic cells increased from 17.3% to 58.6% when the hFOB1.19 were exposed with 200 μg/mL of nano β-TCP powder. Thus, both concentration and exposure duration affected the cytotoxicity effects of the nano β-TCP powder on hFOB1.19. We hypothesize that these cytotoxic effects on hFOB1.19 are related to the nano-scale size of the β-TCP.

Keywords: β-tricalcium phosphate, hFOB1.19, adipose-derived mesenchymal stem cells, cytotoxicity

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2743 Investigation of the Effects of Monoamine Oxidase Levels on the 20S Proteasome

Authors: Bhavini Patel, Aslihan Ugun-Klusek, Ellen Billet

Abstract:

The two main contributing factors to familial and idiopathic form of Parkinson’s disease (PD) are oxidative stress and altered proteolysis. Monoamine oxidase-A (MAO-A) plays a significant role in redox homeostasis by producing reactive oxygen species (ROS) via deamination of for example, dopamine. The ROS generated induces chemical modification of proteins resulting in altered biological function. The ubiquitin-proteasome system, which consists of three different types or proteolytic activity, namely “chymotrypsin-like” activity (CLA), “trypsin-like” activity (TLA) and “post acidic-like” activity (PLA), is responsible for the degradation of ubiquitinated proteins. Defects in UPS are known to be strongly correlated to PD. Herein, the effect of ROS generated by MAO-A on proteasome activity and the effects of proteasome inhibition on MAO-A protein levels in WT, mock and MAO-A overexpressed (MAO-A+) SHSY5Y neuroblastoma cell lines were investigated. The data in this study report increased proteolytic activity when MAO-A protein levels are significantly increased, in particular CLA and PLA. Additionally, 20S proteasome inhibition induced a decrease in MAO-A levels in WT and mock cells in comparison to MAO-A+ cells in which 20S proteasome inhibition induced increased MAO-A levels to be further increased at 48 hours of inhibition. This study supports the fact that MAO-A could be a potential pharmaceutical target for neuronal protection as data suggests that endogenous MAO-A levels may be essential for modulating cell death and survival.

Keywords: monoamine oxidase, neurodegeneration, Parkinson's disease, proteasome

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2742 A Computational Study of N–H…O Hydrogen Bonding to Investigate Cooperative Effects

Authors: Setareh Shekarsaraei, Marjan Moridi, Nasser L. Hadipour

Abstract:

In this study, nuclear magnetic resonance spectroscopy and nuclear quadrupole resonance spectroscopy parameters of 14N (Nitrogen in imidazole ring) in N–H…O hydrogen bonding for Histidine hydrochloride monohydrate were calculated via density functional theory. We considered a five-molecule model system of Histidine hydrochloride monohydrate. Also, we examined the trends of environmental effect on hydrogen bonds as well as cooperativity. The functional used in this research is M06-2X which is a good functional and the obtained results have shown good agreement with experimental data. This functional was applied to calculate the NMR and NQR parameters. Some correlations among NBO parameters, NMR, and NQR parameters have been studied which have shown the existence of strong correlations among them. Furthermore, the geometry optimization has been performed using M062X/6-31++G(d,p) method. In addition, in order to study cooperativity and changes in structural parameters, along with increase in cluster size, natural bond orbitals have been employed.

Keywords: hydrogen bonding, density functional theory (DFT), natural bond orbitals (NBO), cooperativity effect

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2741 IL-21 Production by CD4+ Effector T Cells and Frequency of Circulating Follicular Helper T Cells Are Increased in Type 1 Diabetes Patients

Authors: Ferreira RC, Simons HZ, Thompson WS, Cutler AJ, Dopico XC, Smyth DJ, Mashar M, Schuilenburg H, Walker NM, Dunger DB, Wallace C, Todd JA, Wicker LS, Pekalski ML

Abstract:

Type 1 diabetes is caused by autoimmune destruction of insulin-secreting beta cells in the pancreas. T cells are known to play an important role in this immune-mediated destruction; however, there is no general consensus regarding alterations in cytokine production or T cell subsets in peripheral blood of patients with type 1 diabetes. Using polychromatic flow cytometry of peripheral blood mononuclear cells (PBMCs), we assessed production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 by memory CD4 T effector (Teff) cells in 69 patients with type 1 diabetes and 61 healthy donors. We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). In a separate cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. Consistent with the increased production of IL-21, we also found a 14.9% increase in circulating Tfh cells in the patients with type 1 diabetes (95% CI 2.9, 26.9; p = 0.016). Analysis of IL-21 production by PBMCs from a subset of 46 of the 62 donors immunophenotyped for Tfh showed that frequency of Tfh cells was associated with the frequency of IL-21+ cells (r2 = 0.174, p = 0.004). These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target.

Keywords: T follicular helper cell, IL-21, IL-17, type 1 diabetes

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2740 Thermal, Chemical, and Mineralogical Properties of Soil Building Blocks Reinforced with Cement

Authors: Abdelmalek Ammari

Abstract:

This paper represents an experimental study to determine the effect between thermal conductivity of Compressed Earth Block Stabilized (CEBs) by cement and the mineralogical and chemical analyses of soil, all the samples of CEB in the dry state and with different content of cement, the samples made by soil stabilized by Portland Cement. The soil used collected from fez city in Morocco. That determination of the thermal conductivity of CEBs plays an important role when considering its suitability for energy saving insulation. The measurement technique used to determine thermal conductivity is called hot ring method, the thermal conductivity of the tested samples is strongly affected by the quantity of the cement added. The soil of Fez, mainly composed of calcite, quartz, and dolomite, improved the behaviour of the material by the addition of cement. The findings suggest that to manufacture lightweight samples with high thermal insulation properties, it is advisable to use clays that contain quartz. . In addition, quartz has high thermal conductivity.

Keywords: compressed earth blocks, thermal conductivity, mineralogical, chemical, temperature

Procedia PDF Downloads 136
2739 Endothelial Progenitor Cell Biology in Ankylosing Spondylitis

Authors: Ashit Syngle, Inderjit Verma, Pawan Krishan

Abstract:

Aim: Endothelial progenitor cells (EPCs) are unique populations which have reparative potential in overcoming the endothelial damage and reducing cardiovascular risk. Patients with ankylosing spondylitis (AS) have increased risk of cardiovascular morbidity and mortality. The aim of this study was to investigate the endothelial progenitor cell population in AS patients and its potential relationships with disease variables. Methods: Endothelial progenitor cells were measured in peripheral blood samples from 20 AS and 20 healthy controls by flow cytometry on the basis of CD34 and CD133 expression. Disease activity was evaluated by using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Functional ability was monitored by using Bath Ankylosing Spondylitis Functional Index (BASFI). Results: EPCs were depleted in AS patients as compared to the healthy controls (CD34+/CD133+: 0.027 ± 0.010 % vs. 0.044 ± 0.011 %, p<0.001). EPCs depletion were significantly associated with disease duration (r=-0.52, p=0.01) and BASDAI (r=-0.45, p=0.04). Conclusion: This is the first study to demonstrate endothelial progenitor cells depletion in AS patients. EPCs depletion inversely correlates with disease duration and disease activity, suggesting the pivotal role of inflammation in depletion of EPCs. EPC would possibly also serve as a therapeutic target for preventing cardiovascular disease in AS.

Keywords: ankylosing spondylitis, endothelial progenitor cells, inflammation, vascular damage

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2738 Mathematical Modelling of Blood Flow with Magnetic Nanoparticles as Carrier for Targeted Drug Delivery in a Stenosed Artery

Authors: Sreeparna Majee, G. C. Shit

Abstract:

A study on targeted drug delivery is carried out in an unsteady flow of blood infused with magnetic NPs (nanoparticles) with an aim to understand the flow pattern and nanoparticle aggregation in a diseased arterial segment having stenosis. The magnetic NPs are supervised by the magnetic field which is significant for therapeutic treatment of arterial diseases, tumor and cancer cells and removing blood clots. Coupled thermal energy have also been analyzed by considering dissipation of energy because of the application of the magnetic field and the viscosity of blood. Simulation technique used to solve the mathematical model is vorticity-stream function formulations in the diseased artery. An elevation in SLP (Specific loss power) is noted in the aortic bloodstream when the agglomeration of nanoparticles is higher. This phenomenon has potential application in the treatment of hyperthermia. The study focuses on the lowering of WSS (Wall Shear Stress) with increasing particle concentration at the downstream of the stenosis which depicts the vigorous flow circulation zone. These low shear stress regions prolong the residing time of the nanoparticles carrying drugs which soaks up the LDL (Low Density Lipoprotein) deposition. Moreover, an increase in NP concentration enhances the Nusselt number which marks the increase of heat transfer from the arterial wall to the surrounding tissues to destroy tumor and cancer cells without affecting the healthy cells. The results have a significant influence in the study of medicine, to treat arterial diseases such as atherosclerosis without the need for surgery which can minimize the expenditures on cardiovascular treatments.

Keywords: magnetic nanoparticles, blood flow, atherosclerosis, hyperthermia

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2737 A New Optimization Algorithm for Operation of a Microgrid

Authors: Sirus Mohammadi, Rohala Moghimi

Abstract:

The main advantages of microgrids are high energy efficiency through the application of Combined Heat and Power (CHP), high quality and reliability of the delivered electric energy and environmental and economic advantages. This study presents an energy management system (EMS) to optimize the operation of the microgrid (MG). In this paper an Adaptive Modified Firefly Algorithm (AMFA) is presented for optimal operation of a typical MG with renewable energy sources (RESs) accompanied by a back-up Micro-Turbine/Fuel Cell/Battery hybrid power source to level the power mismatch or to store the energy surplus when it’s needed. The problem is formulated as a nonlinear constraint problem to minimize the total operating cost. The management of Energy storage system (ESS), economic load dispatch and operation optimization of distributed generation (DG) are simplified into a single-object optimization problem in the EMS. The proposed algorithm is tested on a typical grid-connected MG including WT/PV/Micro Turbine/Fuel Cell and Energy Storage Devices (ESDs) then its superior performance is compared with those from other evolutionary algorithms such as Genetic Algorithm (GA), Particle Swarm Optimization (PSO), Fuzzy Self Adaptive PSO (FSAPSO), Chaotic Particle PSO (CPSO), Adaptive Modified PSO (AMPSO), and Firefly Algorithm (FA).

Keywords: microgrid, operation management, optimization, firefly algorithm (AMFA)

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2736 Laparoscopic Curative Resection for Right-Sided Colonic Tumours: Initial Experience from a Cancer Hospital of a Developing Country

Authors: Awais Naeem, Osama Shakeel, Aamir Ali Syed, Shahid Khattak

Abstract:

Introduction: Laparoscopic right hemicolectomy is an advanced cancer surgery in today's era. The aim of this study was to evaluate the surgical and initial oncological outcomes after curative, laparoscopic resection of right sided colonic tumors. Also to compare our results with those of previous randomized trials. Methods And Procedures: We retrospectively analyzed the medical record files of all the patients who presented to our hospital with the diagnosis of right sided colon carcinoma from January 2012 to December 2017 and underwent laparoscopic right hemicolectomy. Demographics, operative findings and histopathological reports were all recorded on a preformed data sheet. All the analysis was performed on SPSS 20. Results: Total of 48 patients were included. There were 37 male and 11 female patients with mean age of 49.7 (range from 25 – 82). Mean hospital stay was 8.25 ± 3.17 days. Blood loss was 80mls and operative mean time was 240 minutes. Eighteen patients had extended right hemicolectomy. Median length of the specimen retrieved was 31cm (range, 14-59cm). Mean size of tumor was 6.44cm + 2.53. Total number of lymph nodes removed was 20.5 + 8.3. All had R0 resection. Post-operatively 2 patients had pelvic collection and there was no 30 day mortality. In 33 patients there was T3 disease, 5 had T2 and 10 had T4 disease. There was distant recurrence in 4 patients with peritoneal metastasis in 3 and liver metastasis in 1 patient. Forty-six patients are still alive and 44 are disease free. The mean follow-up period was 25.31 (12 to 60) months. Conclusion: Our early experience with Laparascopic Right hemicolectomy as a safe and oncologically feasible surgical option. We attained comparable surgical results with curative intent.

Keywords: right hemicolectomy, right sided colonic tumors, laparoscopic, curative intent

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2735 Grid Based Traffic Vulnerability Model Using Betweenness Centrality for Urban Disaster Management Information

Authors: Okyu Kwon, Dongho Kang, Byungsik Kim, Seungkwon Jung

Abstract:

We propose a technique to measure the impact of loss of traffic function in a particular area to surrounding areas. The proposed method is applied to the city of Seoul, which is the capital of South Korea, with a population of about ten million. Based on the actual road network in Seoul, we construct an abstract road network between 1kmx1km grid cells. The link weight of the abstract road network is re-adjusted considering traffic volume measured at several survey points. On the modified abstract road network, we evaluate the traffic vulnerability by calculating a network measure of betweenness centrality (BC) for every single grid cells. This study analyzes traffic impacts caused by road dysfunction due to heavy rainfall in urban areas. We could see the change of the BC value in all other grid cells by calculating the BC value once again when the specific grid cell lost its traffic function, that is, when the node disappeared on the grid-based road network. The results show that it is appropriate to use the sum of the BC variation of other cells as the influence index of each lattice cell on traffic. This research was supported by a grant (2017-MOIS31-004) from Fundamental Technology Development Program for Extreme Disaster Response funded by Korean Ministry of Interior and Safety (MOIS).

Keywords: vulnerability, road network, beweenness centrality, heavy rainfall, road impact

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2734 Deformation of Particle-Laden Droplet in Viscous Liquid under DC Electric Fields

Authors: Khobaib Khobaib, Alexander Mikkelsen, Zbigniew Rozynek

Abstract:

Electric fields have proven useful for inducing droplet deformation and to structure particles adsorbed at droplet interfaces. In this experimental research, direct current electric fields were applied to deform particle-covered droplets made out of silicone oil and immersed in castor oil. The viscosity of the drop and surrounding fluid were changed by external heating. We designed an experimental system in such a way that electric field-induced electrohydrodynamic (EHD) flows were asymmetric and only present on one side of the drop, i.e., the droplet adjoined a washer and adhered to one of the electrodes constituting the sample cell. The study investigated the influence of viscosity on the steady-state deformation magnitude of particle-laden droplets, droplet compression, and relaxation, as well as particle arrangements at drop interfaces. Initially, before the application of an electric field, we changed the viscosity of the fluids by heating the sample cell at different temperatures. The viscosity of the fluids was varied by changing the temperature of the fluids from 25 to 50°C. Under the application of a uniform electric field of strength 290 Vmm⁻¹, electric stress was induced at the drop interface, yielding drop deformation. In our study, we found that by lowering the fluid viscosity, the velocity of the EHD flows was increased, which also increases the deformation of the drop.

Keywords: drop deformation and relaxation, electric field, electrohydrodynamic flow, particle assembly, viscosity

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2733 Preparation and Characterization of CO-Tolerant Electrocatalyst for PEM Fuel Cell

Authors: Ádám Vass, István Bakos, Irina Borbáth, Zoltán Pászti, István Sajó, András Tompos

Abstract:

Important requirements for the anode side electrocatalysts of polymer electrolyte membrane (PEM) fuel cells are CO-tolerance, stability and corrosion resistance. Carbon is still the most common material for electrocatalyst supports due to its low cost, high electrical conductivity and high surface area, which can ensure good dispersion of the Pt. However, carbon becomes degraded at higher potentials and it causes problem during application. Therefore it is important to explore alternative materials with improved stability. Molybdenum-oxide can improve the CO-tolerance of the Pt/C catalysts, but it is prone to leach in acidic electrolyte. The Mo was stabilized by isovalent substitution of molybdenum into the rutile phase titanium-dioxide lattice, achieved by a modified multistep sol-gel synthesis method optimized for preparation of Ti0.7Mo.3O2-C composite. High degree of Mo incorporation into the rutile lattice was developed. The conductivity and corrosion resistance across the anticipated potential/pH window was ensured by mixed oxide – activated carbon composite. Platinum loading was carried out using NaBH4 and ethylene glycol; platinum content was 40 wt%. The electrocatalyst was characterized by both material investigating methods (i.e. XRD, TEM, EDS, XPS techniques) and electrochemical methods (cyclic-voltammetry, COads stripping voltammetry, hydrogen oxidation reaction on rotating disc electrode). The electrochemical activity of the sample was compared to commercial 40 wt% Pt/C (Quintech) and PtRu/C (Quintech, Pt= 20 wt%, Ru= 10 wt%) references. Enhanced CO tolerance of the electrocatalyst prepared using the Ti0.7Mo.3O2-C composite material was evidenced by the appearance of a CO-oxidation related 'pre-peak' and by the pronounced shift of the maximum of the main CO oxidation peak towards less positive potential compared to Pt/C. Fuel cell polarization measurements were also carried out using Bio-Logic and Paxitech FCT-150S test device. All details on the design, preparation, characterization and testing by both electrochemical measurements and fuel cell test device of electrocatalyst supported on Ti0.7Mo.3O2-C composite material will be presented and discussed.

Keywords: anode electrocatalyst, composite material, CO-tolerance, TiMoOx

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2732 Structural Characterization of TIR Domains Interaction

Authors: Sara Przetocka, Krzysztof Żak, Grzegorz Dubin, Tadeusz Holak

Abstract:

Toll-like receptors (TLRs) play central role in the innate immune response and inflammation by recognizing pathogen-associated molecular patterns (PAMPs). A fundamental basis of TLR signalling is dependent upon the recruitment and association of adaptor molecules that contain the structurally conserved Toll/interleukin-1 receptor (TIR) domain. MyD88 (myeloid differentiation primary response gene 88) is the universal adaptor for TLRs and cooperates with Mal (MyD88 adapter-like protein, also known as TIRAP) in TLR4 response which is predominantly used in inflammation, host defence and carcinogenesis. Up to date two possible models of MyD88, Mal and TLR4 interactions have been proposed. The aim of our studies is to confirm or abolish presented models and accomplish the full structural characterisation of TIR domains interaction. Using molecular cloning methods we obtained several construct of MyD88 and Mal TIR domain with GST or 6xHis tag. Gel filtration method as well as pull-down analysis confirmed that recombinant TIR domains from MyD88 and Mal are binding in complexes. To examine whether obtained complexes are homo- or heterodimers we carried out cross-linking reaction of TIR domains with BS3 compound combined with mass spectrometry. To investigate which amino acid residues are involved in this interaction the NMR titration experiments were performed. 15N MyD88-TIR solution was complemented with non-labelled Mal-TIR. The results undoubtedly indicate that MyD88-TIR interact with Mal-TIR. Moreover 2D spectra demonstrated that simultaneously Mal-TIR self-dimerization occurs which is necessary to create proper scaffold for Mal-TIR and MyD88-TIR interaction. Final step of this study will be crystallization of MyD88 and Mal TIR domains complex. This crystal structure and characterisation of its interface will have an impact in understanding the TLR signalling pathway and possibly will be used in development of new anti-cancer treatment.

Keywords: cancer, MyD88, TIR domains, Toll-like receptors

Procedia PDF Downloads 277