Search results for: molecular simulations
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3786

Search results for: molecular simulations

636 Wind Generator Control in Isolated Site

Authors: Glaoui Hachemi

Abstract:

Wind has been proven as a cost effective and reliable energy source. Technological advancements over the last years have placed wind energy in a firm position to compete with conventional power generation technologies. Algeria has a vast uninhabited land area where the south (desert) represents the greatest part with considerable wind regime. In this paper, an analysis of wind energy utilization as a viable energy substitute in six selected sites widely distributed all over the south of Algeria is presented. In this presentation, wind speed frequency distributions data obtained from the Algerian Meteorological Office are used to calculate the average wind speed and the available wind power. The annual energy produced by the Fuhrlander FL 30 wind machine is obtained using two methods. The analysis shows that in the southern Algeria, at 10 m height, the available wind power was found to vary between 160 and 280 W/m2, except for Tamanrasset. The highest potential wind power was found at Adrar, with 88 % of the time the wind speed is above 3 m/s. Besides, it is found that the annual wind energy generated by that machine lie between 33 and 61 MWh, except for Tamanrasset, with only 17 MWh. Since the wind turbines are usually installed at a height greater than 10 m, an increased output of wind energy can be expected. However, the wind resource appears to be suitable for power production on the south and it could provide a viable substitute to diesel oil for irrigation pumps and electricity generation. In this paper, a model of the wind turbine (WT) with permanent magnet generator (PMSG) and its associated controllers is presented. The increase of wind power penetration in power systems has meant that conventional power plants are gradually being replaced by wind farms. In fact, today wind farms are required to actively participate in power system operation in the same way as conventional power plants. In fact, power system operators have revised the grid connection requirements for wind turbines and wind farms, and now demand that these installations be able to carry out more or less the same control tasks as conventional power plants. For dynamic power system simulations, the PMSG wind turbine model includes an aerodynamic rotor model, a lumped mass representation of the drive train system and generator model. In this paper, we propose a model with an implementation in MATLAB / Simulink, each of the system components off-grid small wind turbines.

Keywords: windgenerator systems, permanent magnet synchronous generator (PMSG), wind turbine (WT) modeling, MATLAB simulink environment

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635 Results of the Safety Evaluation of Cancer Vaccines Dealing with Novel Targets for Cancer Immunotherapy

Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

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Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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634 Production Optimization under Geological Uncertainty Using Distance-Based Clustering

Authors: Byeongcheol Kang, Junyi Kim, Hyungsik Jung, Hyungjun Yang, Jaewoo An, Jonggeun Choe

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It is important to figure out reservoir properties for better production management. Due to the limited information, there are geological uncertainties on very heterogeneous or channel reservoir. One of the solutions is to generate multiple equi-probable realizations using geostatistical methods. However, some models have wrong properties, which need to be excluded for simulation efficiency and reliability. We propose a novel method of model selection scheme, based on distance-based clustering for reliable application of production optimization algorithm. Distance is defined as a degree of dissimilarity between the data. We calculate Hausdorff distance to classify the models based on their similarity. Hausdorff distance is useful for shape matching of the reservoir models. We use multi-dimensional scaling (MDS) to describe the models on two dimensional space and group them by K-means clustering. Rather than simulating all models, we choose one representative model from each cluster and find out the best model, which has the similar production rates with the true values. From the process, we can select good reservoir models near the best model with high confidence. We make 100 channel reservoir models using single normal equation simulation (SNESIM). Since oil and gas prefer to flow through the sand facies, it is critical to characterize pattern and connectivity of the channels in the reservoir. After calculating Hausdorff distances and projecting the models by MDS, we can see that the models assemble depending on their channel patterns. These channel distributions affect operation controls of each production well so that the model selection scheme improves management optimization process. We use one of useful global search algorithms, particle swarm optimization (PSO), for our production optimization. PSO is good to find global optimum of objective function, but it takes too much time due to its usage of many particles and iterations. In addition, if we use multiple reservoir models, the simulation time for PSO will be soared. By using the proposed method, we can select good and reliable models that already matches production data. Considering geological uncertainty of the reservoir, we can get well-optimized production controls for maximum net present value. The proposed method shows one of novel solutions to select good cases among the various probabilities. The model selection schemes can be applied to not only production optimization but also history matching or other ensemble-based methods for efficient simulations.

Keywords: distance-based clustering, geological uncertainty, particle swarm optimization (PSO), production optimization

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633 Evaluation of Antimicrobial Efficacy of Nanofluid Containing Carbon Nanotubes Functionalized with Antibiotic on Urinary Tract Infection

Authors: Erfan Rahimi, Hadi Bahari Far, Mojgan Shikhpour

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Background: Urinary tract infection is one of the most common nosocomial infections, especially among women. E. coli is one of the main causes of urinary tract infections and one of the most common antibiotics to fight this bacterium is ampicillin. As conventional antibiotics led to bacterial antibiotic resistance, modification of the pure drugs can address this issue. The aim of this study was to prepare nanofluids containing carbon nanotubes conjugated with ampicillin to improve drug performance and reduce antibiotic resistance. Methods: Multi-walled carbon nanotubes (MWCNTs) were activated with thionyl chloride by reflux system and nanofluids containing antibiotics were prepared by ultrasonic method. The properties of the prepared nano-drug were investigated by general element analysis, infrared spectroscopy, Raman spectroscopy, scanning electron microscopy and transmission electron microscopy. After the treatment of the desired strain with nanofluid, microbial studies were performed to evaluate the antibacterial effects and molecular studies were carried out to measure the expression of the resistance gene AcrAB. Result: We have shown that the antimicrobial effect of ampicillin-functionalized MWCNTs at low concentrations performed better than that of the conventional drug in both resistant and ATCC strains. Also, a decrease in antibiotic resistance of bacteria treated with ampicillin-functionalized MWCNTs compared to the pure drug was observed. Also, ampicillin-functionalized MWCNTs downregulated the expression of AcrAB in treated bacteria. Conclusion: Because carbon nanotubes are capable of destroying the bacterial wall, which provides antibiotic resistance features in bacteria, their usage in the form of nanofluids can make lower dosages (about three times less) than that of the pure drug more effective. Additionally, the expression of the bacterial resistance gene AcrAB decreased, thereby reducing antibiotic resistance and improving drug performance against bacteria.

Keywords: urinary tract infection, antibiotic resistance, carbon nanotube, nanofluid

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632 CFD Modeling of Stripper Ash Cooler of Circulating Fluidized Bed

Authors: Ravi Inder Singh

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Due to high heat transfer rate, high carbon utilizing efficiency, fuel flexibilities and other advantages numerous circulating fluidized bed boilers have grown up in India in last decade. Many companies like BHEL, ISGEC, Thermax, Cethar Limited, Enmas GB Power Systems Projects Limited are making CFBC and installing the units throughout the India. Due to complexity many problems exists in CFBC units and only few have been reported. Agglomeration i.e clinker formation in riser, loop seal leg and stripper ash coolers is one of problem industry is facing. Proper documentation is rarely found in the literature. Circulating fluidized bed (CFB) boiler bottom ash contains large amounts of physical heat. While the boiler combusts the low-calorie fuel, the ash content is normally more than 40% and the physical heat loss is approximately 3% if the bottom ash is discharged without cooling. In addition, the red-hot bottom ash is bad for mechanized handling and transportation, as the upper limit temperature of the ash handling machinery is 200 °C. Therefore, a bottom ash cooler (BAC) is often used to treat the high temperature bottom ash to reclaim heat, and to have the ash easily handled and transported. As a key auxiliary device of CFB boilers, the BAC has a direct influence on the secure and economic operation of the boiler. There are many kinds of BACs equipped for large-scale CFB boilers with the continuous development and improvement of the CFB boiler. These ash coolers are water cooled ash cooling screw, rolling-cylinder ash cooler (RAC), fluidized bed ash cooler (FBAC).In this study prototype of a novel stripper ash cooler is studied. The Circulating Fluidized bed Ash Coolers (CFBAC) combined the major technical features of spouted bed and bubbling bed, and could achieve the selective discharge on the bottom ash. The novel stripper ash cooler is bubbling bed and it is visible cold test rig. The reason for choosing cold test is that high temperature is difficult to maintain and create in laboratory level. The aim of study to know the flow pattern inside the stripper ash cooler. The cold rig prototype is similar to stripper ash cooler used industry and it was made after scaling down to some parameter. The performance of a fluidized bed ash cooler is studied using a cold experiment bench. The air flow rate, particle size of the solids and air distributor type are considered to be the key parameters of the operation of a fluidized bed ash cooler (FBAC) are studied in this.

Keywords: CFD, Eulerian-Eulerian, Eulerian-Lagraingian model, parallel simulations

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631 Curative Role of Bromoenol Lactone, an Inhibitor of Phospholipase A2 Enzyme, during Cigarette Smoke Condensate Induced Anomalies in Lung Epithelium

Authors: Subodh Kumar, Sanjeev Kumar Sharma, Gaurav Kaushik, Pramod Avti, Phulen Sarma, Bikash Medhi, Krishan Lal Khanduja

Abstract:

Background: It is well known that cigarette smoke is one of the causative factors in various lung diseases especially cancer. Carcinogens and oxidant molecules present in cigarette smoke not only damage the cellular constituents (lipids, proteins, DNA) but may also regulate the molecular pathways involved in inflammation and cancer. Continuous oxidative stress caused by the constituents of cigarette smoke leads to higher PhospholipaseA₂ (PLA₂) activity, resulting in elevated levels of secondary metabolites whose role is well defined in cancer. To reduce the burden of chronic inflammation as well as oxidative stress, and higher levels of secondary metabolites, we checked the curative potential of PLA₂ inhibitor Bromoenol Lactone (BEL) during continuous exposure of cigarette smoke condensate (CSC). Aim: To check the therapeutic potential of Bromoenol Lactone (BEL), an inhibitor of PhospholipaseA₂s, in pathways of CSC-induced changes in type I and type II alveolar epithelial cells. Methods: Effect of BEL on CSC-induced PLA2 activity were checked using colorimetric assay, cellular toxicity using cell viability assay, membrane integrity using fluorescein di-acetate (FDA) uptake assay, reactive oxygen species (ROS) levels and apoptosis markers through flow cytometry, and cellular regulation using MAPKinases levels, in lung epithelium. Results: BEL significantly mimicked CSC-induced PLA₂ activity, ROS levels, apoptosis, and kinases level whereas improved cellular viability and membrane integrity. Conclusions: Current observations revealed that BEL may be a potential therapeutic agent during Cigarette smoke-induced anomalies in lung epithelium.

Keywords: cigarette smoke condensate, phospholipase A₂, oxidative stress, alveolar epithelium, bromoenol lactone

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630 Evolutions of Structural Properties of Native Phospho Casein (NPC) Powder during Storage

Authors: Sarah Nasser, Anne Moreau, Alain Hedoux, Romain Jeantet, Guillaume Delaplace

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Background: Spray dryed powders containing some caseins are commonly produced in dairy industry. It is widely admitted that the structure of casein evolves during powder storage, inducing a loss of solubility. However few studies evaluate accurately the destabilization mechanisms at molecular and mesoscopic level, in particular for Native Phospho Casein powder (NPC). Consequently, at the state of the art, it is very difficult to assess which secondary structure change or crosslinks initiate insolubility during storage. To address this issue, controlled ageing conditions have been applied to a NPC powder (which was obtained by spray drying a concentrate containing a higher content of casein (90%), whey protein (8%) and lactose (few %)). Evolution of structure and loss of solubility, with the effects of temperature and time of storage were systematically reported. Methods: FTIR spectroscopy, Raman and Circular Dichroism were used to monitor changes of secondary structure in dry powder and in solution after rehydration. Besides, proteomic tools and electrophoresis have been performed after varying storage conditions for evaluating aggregation and post translational modifications, like lactosylation or phosphorylation. Finally, Tof Sims and MEB were used to follow in parallel evolution of structure in surface and skin formation due to storage. Results + conclusion: These results highlight the important role of storage temperature in the stability of NPC. It is shown that this is not lactosylation at the heart of formation of aggregates, as advanced in others publications This is almost the rise of multitude post translational modifications (chemical cross link), added to disulphide bridges (physical cross link) wich contribute to the destabilisation of structure and aggregation of casein. A relative quantification of each kind of cross link, source of aggregates, is proposed. In addition, it has been proved that migration of lipids and formation of skin in surface during the ageing also explains the evolution of structure casein and thus the alterations of functional properties of NPC powder.

Keywords: casein, cross link, powder, storage

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629 Uncertainty Quantification of Fuel Compositions on Premixed Bio-Syngas Combustion at High-Pressure

Authors: Kai Zhang, Xi Jiang

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Effect of fuel variabilities on premixed combustion of bio-syngas mixtures is of great importance in bio-syngas utilisation. The uncertainties of concentrations of fuel constituents such as H2, CO and CH4 may lead to unpredictable combustion performances, combustion instabilities and hot spots which may deteriorate and damage the combustion hardware. Numerical modelling and simulations can assist in understanding the behaviour of bio-syngas combustion with pre-defined species concentrations, while the evaluation of variabilities of concentrations is expensive. To be more specific, questions such as ‘what is the burning velocity of bio-syngas at specific equivalence ratio?’ have been answered either experimentally or numerically, while questions such as ‘what is the likelihood of burning velocity when precise concentrations of bio-syngas compositions are unknown, but the concentration ranges are pre-described?’ have not yet been answered. Uncertainty quantification (UQ) methods can be used to tackle such questions and assess the effects of fuel compositions. An efficient probabilistic UQ method based on Polynomial Chaos Expansion (PCE) techniques is employed in this study. The method relies on representing random variables (combustion performances) with orthogonal polynomials such as Legendre or Gaussian polynomials. The constructed PCE via Galerkin Projection provides easy access to global sensitivities such as main, joint and total Sobol indices. In this study, impacts of fuel compositions on combustion (adiabatic flame temperature and laminar flame speed) of bio-syngas fuel mixtures are presented invoking this PCE technique at several equivalence ratios. High-pressure effects on bio-syngas combustion instability are obtained using detailed chemical mechanism - the San Diego Mechanism. Guidance on reducing combustion instability from upstream biomass gasification process is provided by quantifying the significant contributions of composition variations to variance of physicochemical properties of bio-syngas combustion. It was found that flame speed is very sensitive to hydrogen variability in bio-syngas, and reducing hydrogen uncertainty from upstream biomass gasification processes can greatly reduce bio-syngas combustion instability. Variation of methane concentration, although thought to be important, has limited impacts on laminar flame instabilities especially for lean combustion. Further studies on the UQ of percentage concentration of hydrogen in bio-syngas can be conducted to guide the safer use of bio-syngas.

Keywords: bio-syngas combustion, clean energy utilisation, fuel variability, PCE, targeted uncertainty reduction, uncertainty quantification

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628 The Pathology of Bovine Rotavirus Infection in Calves That Confirmed by Enzyme Linked Immunosorbant Assay, Reverse Transcription Polymerase Chain Reaction and Real-Time RT-PCR

Authors: Shama Ranjan Barua, Tofazzal M. Rakib, Mohammad Alamgir Hossain, Tania Ferdushy, Sharmin Chowdhury

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Rotavirus is one of the main etiologies of neonatal diarrhea in bovine calves that causes significant economic loss in Bangladesh. The present study was carried out to investigate the pathology of neonatal enteritis in calves due to bovine rotavirus infection in south-eastern part of Bangladesh. Rotavirus was identified by using ELISA, RT-PCR (Reverse Transcription Polymerase Chain Reaction), real-time RT-PCR. We examined 12 dead calves with history of diarrhea during necropsy. Among 12 dead calves, in gross examination, 6 were found with pathological changes in intestine, 5 calves had congestion of small intestine and rest one had no distinct pathological changes. Intestinal contents and/or faecal samples of all dead calves were collected and examined to confirm the presence of bovine rotavirus A using Enzyme linked immunosorbant assay (ELISA), RT-PCR and real-time RT-PCR. Out 12 samples, 5 (42%) samples revealed presence of bovine rotavirus A in three diagnostic tests. The histopathological changes were found almost exclusively limited in the small intestine. The lesions of rotaviral enteritis ranged from slight to moderate shortening (atrophy) of villi in the jejunum and ileum with necrotic crypts. The villi were blunt and covered by immature epithelial cells. Infected cells, stained with Haematoxylin and Eosin staining method, showed characteristic syncytia and eosinophilc intracytoplasmic inclusion body. The presence of intracytoplasmic inclusion bodies in enterocytes is the indication of viral etiology. The presence of rotavirus in the affected tissues and/or lesions was confirmed by three different immunological and molecular tests. The findings of histopathological changes will be helpful in future diagnosis of rotaviral infection in dead calves.

Keywords: calves, diarrhea, pathology, rotavirus

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627 Gene Expressions in Left Ventricle Heart Tissue of Rat after 150 Mev Proton Irradiation

Authors: R. Fardid, R. Coppes

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Introduction: In mediastinal radiotherapy and to a lesser extend also in total-body irradiation (TBI) radiation exposure may lead to development of cardiac diseases. Radiation-induced heart disease is dose-dependent and it is characterized by a loss of cardiac function, associated with progressive heart cells degeneration. We aimed to determine the in-vivo radiation effects on fibronectin, ColaA1, ColaA2, galectin and TGFb1 gene expression levels in left ventricle heart tissues of rats after irradiation. Material and method: Four non-treatment adult Wistar rats as control group (group A) were selected. In group B, 4 adult Wistar rats irradiated to 20 Gy single dose of 150 Mev proton beam locally in heart only. In heart plus lung irradiate group (group C) 4 adult rats was irradiated by 50% of lung laterally plus heart radiation that mentioned in before group. At 8 weeks after radiation animals sacrificed and left ventricle heart dropped in liquid nitrogen for RNA extraction by Absolutely RNA® Miniprep Kit (Stratagen, Cat no. 400800). cDNA was synthesized using M-MLV reverse transcriptase (Life Technologies, Cat no. 28025-013). We used Bio-Rad machine (Bio Rad iQ5 Real Time PCR) for QPCR testing by relative standard curve method. Results: We found that gene expression of fibronectin in group C significantly increased compared to control group, but it was not showed significant change in group B compared to group A. The levels of gene expressions of Cola1 and Cola2 in mRNA did not show any significant changes between normal and radiation groups. Changes of expression of galectin target significantly increased only in group C compared to group A. TGFb1 expressions in group C more than group B showed significant enhancement compared to group A. Conclusion: In summary we can say that 20 Gy of proton exposure of heart tissue may lead to detectable damages in heart cells and may distribute function of them as a component of heart tissue structure in molecular level.

Keywords: gene expression, heart damage, proton irradiation, radiotherapy

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626 Molecular Dissection of Late Flowering under a Photoperiod-Insensitive Genetic Background in Soybean

Authors: Fei Sun, Meilan Xu, Jianghui Zhu, Maria Stefanie Dwiyanti, Cheolwoo Park, Fanjiang Kong, Baohui Liu, Tetsuya Yamada, Jun Abe

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Reduced or lack of sensitivity to long daylengths is a key character for soybean, a short-day crop, to adapt to higher latitudinal environments. However, the photoperiod-insensitivity often results in a reduction of the duration of vegetative growth and final yield. To overcome this limitation, a photoperiod insensitive line (RIL16) was developed in this study that delayed flowering from the recombinant inbred population derived from a cross between a photoperiod-insensitive cultivar AGS292 and a late-flowering Thai cultivar K3. Expression analyses under SD and LD conditions revealed that the expression levels of FLOWERING LOCUS T (FT) orthologues, FT2a and FT5a, were lowered in RIL16 relative to AGS292, although the expression of E1, a soybean-specific suppressor for FTs, was inhibited in both conditions. A soybean orthologue of TARGET OF EAT1 (TOE1), another suppressor of FT, showed an upregulated expression in RIL16, which appeared to reflect a lower expression of miR172a. Our data suggest that the delayed flowering of RIL16 most likely is controlled by genes involved in an age-dependent pathway in flowering. The QTL analysis based on 1,125 SNPs obtained from Restriction Site Associated DNA Sequencing revealed two major QTLs for flowering dates in Chromosome 16 and two minor QTLs in Chromosome 4, all of which accounted for 55% and 48% of the whole variations observed in natural day length and artificially-induced long day length conditions, respectively. The intervals of the major QTLs harbored FT2a and FT5a, respectively, on the basis of annotated genes in the Williams 82 reference genome. Sequencing analysis further revealed a nonsynonymous mutation in FT2a and an SNP in the 3′ UTR region of FT5a. A further study may elucidate a detailed mechanism underlying the QTL for late flowering. The alleles from K3 at the two QTLs can be used singly or in combination to retain an appropriate duration of vegetative growth to maximize the final yield of photoperiod-insensitive soybeans.

Keywords: FT genes, miR72a, photoperiod-insensitive, soybean flowering

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625 Optimizing Cell Culture Performance in an Ambr15 Microbioreactor Using Dynamic Flux Balance and Computational Fluid Dynamic Modelling

Authors: William Kelly, Sorelle Veigne, Xianhua Li, Zuyi Huang, Shyamsundar Subramanian, Eugene Schaefer

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The ambr15™ bioreactor is a single-use microbioreactor for cell line development and process optimization. The ambr system offers fully automatic liquid handling with the possibility of fed-batch operation and automatic control of pH and oxygen delivery. With operating conditions for large scale biopharmaceutical production properly scaled down, micro bioreactors such as the ambr15™ can potentially be used to predict the effect of process changes such as modified media or different cell lines. In this study, gassing rates and dilution rates were varied for a semi-continuous cell culture system in the ambr15™ bioreactor. The corresponding changes to metabolite production and consumption, as well as cell growth rate and therapeutic protein production were measured. Conditions were identified in the ambr15™ bioreactor that produced metabolic shifts and specific metabolic and protein production rates also seen in the corresponding larger (5 liter) scale perfusion process. A Dynamic Flux Balance model was employed to understand and predict the metabolic changes observed. The DFB model-predicted trends observed experimentally, including lower specific glucose consumption when CO₂ was maintained at higher levels (i.e. 100 mm Hg) in the broth. A Computational Fluid Dynamic (CFD) model of the ambr15™ was also developed, to understand transfer of O₂ and CO₂ to the liquid. This CFD model predicted gas-liquid flow in the bioreactor using the ANSYS software. The two-phase flow equations were solved via an Eulerian method, with population balance equations tracking the size of the gas bubbles resulting from breakage and coalescence. Reasonable results were obtained in that the Carbon Dioxide mass transfer coefficient (kLa) and the air hold up increased with higher gas flow rate. Volume-averaged kLa values at 500 RPM increased as the gas flow rate was doubled and matched experimentally determined values. These results form a solid basis for optimizing the ambr15™, using both CFD and FBA modelling approaches together, for use in microscale simulations of larger scale cell culture processes.

Keywords: cell culture, computational fluid dynamics, dynamic flux balance analysis, microbioreactor

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624 Cytotoxicity of 13 South African Macrofungal Species and Mechanism/s of Action against Cancer Cell Lines

Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

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623 Dual Thermoresponsive Polyzwitterionic Core-Shell Microgels and Study of Their Anti-Fouling Effect

Authors: P. Saha, R. Ganguly, N. K .Singha, A. Pich

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Microgel, a smart class of material, has drawn attention in the past few years due to its response to external stimuli like temperature, pH, and ionic strength of the solution. Among them, one type of polymer becomes soluble, and the other becomes insoluble in water upon heating displaying upper critical solution temperature (UCST) (e.g., polysulfobetaine, PSB) and lower critical solution temperature (LCST) (e.g., poly(N-vinylcaprolactam, PVCL)) respectively. Polyzwitterions, electrically neutral polymers are biocompatible, biodegradable, and non-cytotoxic in nature, and presence of zwitterionic pendant group in the main backbone makes them stable against temperature and pH variations and strong hydration capability in salt solution promotes them to be used as interfacial bio-adhesion resistance material. Majority of zwitterionic microgels have been synthesized in mini- emulsion technique using free radical polymerization approach. Here, a new route to synthesize dual thermo-responsive PVCL microgels decorated with appreciable amount of zwitterionic PSB chains was developed by a purely water-based surfactant-free reversible addition–fragmentation chain transfer (RAFT) precipitation polymerization. PSB macro-RAFTs having different molecular weights were synthesized and utilized for surface-grafting with PVCL microgels varying the macro-RAFT concentration using N,N′-methylenebis(acrylamide) (BIS) as cross-linker. Increasing the PSB concentration in the PVCL microgels resulted in a linear increase in UCST but decrease in hydrodynamic radius due to strong intrachain coulombic attraction forces acting between the opposite charges present in the zwitterionic groups. Anti- fouling effect was observed on addition of BSA protein solution on the microgel-coated membrane surfaces as studied by fluorescence spectrophotoscopy.

Keywords: microgels, polyzwitterions, upper critical solution temperature-lower critical solution temperature, UCST-LCST, ionic crosslinking

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622 On the Optimality Assessment of Nano-Particle Size Spectrometry and Its Association to the Entropy Concept

Authors: A. Shaygani, R. Saifi, M. S. Saidi, M. Sani

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Particle size distribution, the most important characteristics of aerosols, is obtained through electrical characterization techniques. The dynamics of charged nano-particles under the influence of electric field in electrical mobility spectrometer (EMS) reveals the size distribution of these particles. The accuracy of this measurement is influenced by flow conditions, geometry, electric field and particle charging process, therefore by the transfer function (transfer matrix) of the instrument. In this work, a wire-cylinder corona charger was designed and the combined field-diffusion charging process of injected poly-disperse aerosol particles was numerically simulated as a prerequisite for the study of a multi-channel EMS. The result, a cloud of particles with non-uniform charge distribution, was introduced to the EMS. The flow pattern and electric field in the EMS were simulated using computational fluid dynamics (CFD) to obtain particle trajectories in the device and therefore to calculate the reported signal by each electrometer. According to the output signals (resulted from bombardment of particles and transferring their charges as currents), we proposed a modification to the size of detecting rings (which are connected to electrometers) in order to evaluate particle size distributions more accurately. Based on the capability of the system to transfer information contents about size distribution of the injected particles, we proposed a benchmark for the assessment of optimality of the design. This method applies the concept of Von Neumann entropy and borrows the definition of entropy from information theory (Shannon entropy) to measure optimality. Entropy, according to the Shannon entropy, is the ''average amount of information contained in an event, sample or character extracted from a data stream''. Evaluating the responses (signals) which were obtained via various configurations of detecting rings, the best configuration which gave the best predictions about the size distributions of injected particles, was the modified configuration. It was also the one that had the maximum amount of entropy. A reasonable consistency was also observed between the accuracy of the predictions and the entropy content of each configuration. In this method, entropy is extracted from the transfer matrix of the instrument for each configuration. Ultimately, various clouds of particles were introduced to the simulations and predicted size distributions were compared to the exact size distributions.

Keywords: aerosol nano-particle, CFD, electrical mobility spectrometer, von neumann entropy

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621 An Optimal Control Method for Reconstruction of Topography in Dam-Break Flows

Authors: Alia Alghosoun, Nabil El Moçayd, Mohammed Seaid

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Modeling dam-break flows over non-flat beds requires an accurate representation of the topography which is the main source of uncertainty in the model. Therefore, developing robust and accurate techniques for reconstructing topography in this class of problems would reduce the uncertainty in the flow system. In many hydraulic applications, experimental techniques have been widely used to measure the bed topography. In practice, experimental work in hydraulics may be very demanding in both time and cost. Meanwhile, computational hydraulics have served as an alternative for laboratory and field experiments. Unlike the forward problem, the inverse problem is used to identify the bed parameters from the given experimental data. In this case, the shallow water equations used for modeling the hydraulics need to be rearranged in a way that the model parameters can be evaluated from measured data. However, this approach is not always possible and it suffers from stability restrictions. In the present work, we propose an adaptive optimal control technique to numerically identify the underlying bed topography from a given set of free-surface observation data. In this approach, a minimization function is defined to iteratively determine the model parameters. The proposed technique can be interpreted as a fractional-stage scheme. In the first stage, the forward problem is solved to determine the measurable parameters from known data. In the second stage, the adaptive control Ensemble Kalman Filter is implemented to combine the optimality of observation data in order to obtain the accurate estimation of the topography. The main features of this method are on one hand, the ability to solve for different complex geometries with no need for any rearrangements in the original model to rewrite it in an explicit form. On the other hand, its achievement of strong stability for simulations of flows in different regimes containing shocks or discontinuities over any geometry. Numerical results are presented for a dam-break flow problem over non-flat bed using different solvers for the shallow water equations. The robustness of the proposed method is investigated using different numbers of loops, sensitivity parameters, initial samples and location of observations. The obtained results demonstrate high reliability and accuracy of the proposed techniques.

Keywords: erodible beds, finite element method, finite volume method, nonlinear elasticity, shallow water equations, stresses in soil

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620 Peptide-Gold Nanocluster as an Optical Biosensor for Glycoconjugate Secreted from Leishmania

Authors: Y. A. Prada, Fanny Guzman, Rafael Cabanzo, John J. Castillo, Enrique Mejia-Ospino

Abstract:

In this work, we show the important results about of synthesis of photoluminiscents gold nanoclusters using a small peptide as template for biosensing applications. Interestingly, we design one peptide (NBC2854) homologue to conservative domain from 215 250 residue of a galactolectin protein which can recognize the proteophosphoglycans (PPG) from Leishmania. Peptide was synthetized by multiple solid phase synthesis using FMoc group methodology in acid medium. Finally, the peptide was purified by High-Performance Liquid Chromatography using a Vydac C-18 preparative column and the detection was at 215 nm using a Photo Diode Array detector. Molecular mass of this peptide was confirmed by MALDI-TOF and to verify the α-helix structure we use Circular Dichroism. By means of the methodology used we obtained a novel fluorescents gold nanoclusters (AuNC) using NBC2854 as a template. In this work, we described an easy and fast microsonic method for the synthesis of AuNC with ≈ 3.0 nm of hydrodynamic size and photoemission at 630 nm. The presence of cysteine residue in the C-terminal of the peptide allows the formation of Au-S bond which confers stability to Peptide-based gold nanoclusters. Interactions between the peptide and gold nanoclusters were confirmed by X-ray Photoemission and Raman Spectroscopy. Notably, from the ultrafine spectra shown in the MALDI-TOF analysis which containing only 3-7 KDa species was assigned to Au₈-₁₈[NBC2854]₂ clusters. Finally, we evaluated the Peptide-gold nanocluster as an optical biosensor based on fluorescence spectroscopy and the fluorescence signal of PPG (0.1 µg-mL⁻¹ to 1000 µg-mL⁻¹) was amplified at the same wavelength emission (≈ 630 nm). This can suggest that there is a strong interaction between PPG and Pep@AuNC, therefore, the increase of the fluorescence intensity can be related to the association mechanism that take place when the target molecule is sensing by the Pep@AuNC conjugate. Further spectroscopic studies are necessary to evaluate the fluorescence mechanism involve in the sensing of the PPG by the Pep@AuNC. To our best knowledge the fabrication of an optical biosensor based on Pep@AuNC for sensing biomolecules such as Proteophosphoglycans which are secreted in abundance by parasites Leishmania.

Keywords: biosensing, fluorescence, Leishmania, peptide-gold nanoclusters, proteophosphoglycans

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619 Understanding the Information in Principal Component Analysis of Raman Spectroscopic Data during Healing of Subcritical Calvarial Defects

Authors: Rafay Ahmed, Condon Lau

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Bone healing is a complex and sequential process involving changes at the molecular level. Raman spectroscopy is a promising technique to study bone mineral and matrix environments simultaneously. In this study, subcritical calvarial defects are used to study bone composition during healing without discomposing the fracture. The model allowed to monitor the natural healing of bone avoiding mechanical harm to the callus. Calvarial defects were created using 1mm burr drill in the parietal bones of Sprague-Dawley rats (n=8) that served in vivo defects. After 7 days, their skulls were harvested after euthanizing. One additional defect per sample was created on the opposite parietal bone using same calvarial defect procedure to serve as control defect. Raman spectroscopy (785 nm) was established to investigate bone parameters of three different skull surfaces; in vivo defects, control defects and normal surface. Principal component analysis (PCA) was utilized for the data analysis and interpretation of Raman spectra and helped in the classification of groups. PCA was able to distinguish in vivo defects from normal surface and control defects. PC1 shows that the major variation at 958 cm⁻¹, which corresponds to ʋ1 phosphate mineral band. PC2 shows the major variation at 1448 cm⁻¹ which is the characteristic band of CH2 deformation and corresponds to collagens. Raman parameters, namely, mineral to matrix ratio and crystallinity was found significantly decreased in the in vivo defects compared to surface and controls. Scanning electron microscope and optical microscope images show the formation of newly generated matrix by means of bony bridges of collagens. Optical profiler shows that surface roughness increased by 30% from controls to in vivo defects after 7 days. These results agree with Raman assessment parameters and confirm the new collagen formation during healing.

Keywords: Raman spectroscopy, principal component analysis, calvarial defects, tissue characterization

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618 Characterization of Transcription Factors Involved in Early Defense Response during Interaction of Oil Palm Elaeis guineensis Jacq. with Ganoderma boninense

Authors: Sakeh N. Mohd, Bahari M. N. Abdul, Abdullah S. N. Akmar

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Oil palm production generates high export earnings to many countries especially in Southeast Asian region. Infection by necrotrophic fungus, Ganoderma boninense on oil palm results in basal stem rot which compromises oil palm production leading to significant economic loss. There are no reliable disease treatments nor promising resistant oil palm variety has been cultivated to eradicate the disease up to date. Thus, understanding molecular mechanisms underlying early interactions of oil palm with Ganoderma boninense may be vital to promote preventive or control measure of the disease. In the present study, four months old oil palm seedlings were infected via artificial inoculation of Ganoderma boninense on rubber wood blocks. Roots of six biological replicates of treated and untreated oil palm seedlings were harvested at 0, 3, 7 and 11 days post inoculation. Next-generation sequencing was performed to generate high-throughput RNA-Seq data and identify differentially expressed genes (DEGs) during early oil palm-Ganoderma boninense interaction. Based on de novo transcriptome assembly, a total of 427,122,605 paired-end clean reads were assembled into 30,654 unigenes. DEGs analysis revealed upregulation of 173 transcription factors on Ganoderma boninense-treated oil palm seedlings. Sixty-one transcription factors were categorized as DEGs according to stringent cut-off values of genes with log2 ratio [Number of treated oil palm seedlings/ Number of untreated oil palm seedlings] ≥ |1.0| (corresponding to 2-fold or more upregulation) and P-value ≤ 0.01. Transcription factors in response to biotic stress will be screened out from abiotic stress using reverse transcriptase polymerase chain reaction. Transcription factors unique to biotic stress will be verified using real-time polymerase chain reaction. The findings will help researchers to pinpoint defense response mechanism specific against Ganoderma boninense.

Keywords: Ganoderma boninense, necrotrophic, next-generation sequencing, transcription factors

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617 Demarcating Wetting States in Pressure-Driven Flows by Poiseuille Number

Authors: Anvesh Gaddam, Amit Agrawal, Suhas Joshi, Mark Thompson

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An increase in surface area to volume ratio with a decrease in characteristic length scale, leads to a rapid increase in pressure drop across the microchannel. Texturing the microchannel surfaces reduce the effective surface area, thereby decreasing the pressured drop. Surface texturing introduces two wetting states: a metastable Cassie-Baxter state and stable Wenzel state. Predicting wetting transition in textured microchannels is essential for identifying optimal parameters leading to maximum drag reduction. Optical methods allow visualization only in confined areas, therefore, obtaining whole-field information on wetting transition is challenging. In this work, we propose a non-invasive method to capture wetting transitions in textured microchannels under flow conditions. To this end, we tracked the behavior of the Poiseuille number Po = f.Re, (with f the friction factor and Re the Reynolds number), for a range of flow rates (5 < Re < 50), and different wetting states were qualitatively demarcated by observing the inflection points in the f.Re curve. Microchannels with both longitudinal and transverse ribs with a fixed gas fraction (δ, a ratio of shear-free area to total area) and at a different confinement ratios (ε, a ratio of rib height to channel height) were fabricated. The measured pressure drop values for all the flow rates across the textured microchannels were converted into Poiseuille number. Transient behavior of the pressure drop across the textured microchannels revealed the collapse of liquid-gas interface into the gas cavities. Three wetting states were observed at ε = 0.65 for both longitudinal and transverse ribs, whereas, an early transition occurred at Re ~ 35 for longitudinal ribs at ε = 0.5, due to spontaneous flooding of the gas cavities as the liquid-gas interface ruptured at the inlet. In addition, the pressure drop in the Wenzel state was found to be less than the Cassie-Baxter state. Three-dimensional numerical simulations confirmed the initiation of the completely wetted Wenzel state in the textured microchannels. Furthermore, laser confocal microscopy was employed to identify the location of the liquid-gas interface in the Cassie-Baxter state. In conclusion, the present method can overcome the limitations posed by existing techniques, to conveniently capture wetting transition in textured microchannels.

Keywords: drag reduction, Poiseuille number, textured surfaces, wetting transition

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616 Depth-Averaged Modelling of Erosion and Sediment Transport in Free-Surface Flows

Authors: Thomas Rowan, Mohammed Seaid

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A fast finite volume solver for multi-layered shallow water flows with mass exchange and an erodible bed is developed. This enables the user to solve a number of complex sediment-based problems including (but not limited to), dam-break over an erodible bed, recirculation currents and bed evolution as well as levy and dyke failure. This research develops methodologies crucial to the under-standing of multi-sediment fluvial mechanics and waterway design. In this model mass exchange between the layers is allowed and, in contrast to previous models, sediment and fluid are able to transfer between layers. In the current study we use a two-step finite volume method to avoid the solution of the Riemann problem. Entrainment and deposition rates are calculated for the first time in a model of this nature. In the first step the governing equations are rewritten in a non-conservative form and the intermediate solutions are calculated using the method of characteristics. In the second stage, the numerical fluxes are reconstructed in conservative form and are used to calculate a solution that satisfies the conservation property. This method is found to be considerably faster than other comparative finite volume methods, it also exhibits good shock capturing. For most entrainment and deposition equations a bed level concentration factor is used. This leads to inaccuracies in both near bed level concentration and total scour. To account for diffusion, as no vertical velocities are calculated, a capacity limited diffusion coefficient is used. The additional advantage of this multilayer approach is that there is a variation (from single layer models) in bottom layer fluid velocity: this dramatically reduces erosion, which is often overestimated in simulations of this nature using single layer flows. The model is used to simulate a standard dam break. In the dam break simulation, as expected, the number of fluid layers utilised creates variation in the resultant bed profile, with more layers offering a higher deviation in fluid velocity . These results showed a marked variation in erosion profiles from standard models. The overall the model provides new insight into the problems presented at minimal computational cost.

Keywords: erosion, finite volume method, sediment transport, shallow water equations

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615 A Double Ended AC Series Arc Fault Location Algorithm Based on Currents Estimation and a Fault Map Trace Generation

Authors: Edwin Calderon-Mendoza, Patrick Schweitzer, Serge Weber

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Series arc faults appear frequently and unpredictably in low voltage distribution systems. Many methods have been developed to detect this type of faults and commercial protection systems such AFCI (arc fault circuit interrupter) have been used successfully in electrical networks to prevent damage and catastrophic incidents like fires. However, these devices do not allow series arc faults to be located on the line in operating mode. This paper presents a location algorithm for series arc fault in a low-voltage indoor power line in an AC 230 V-50Hz home network. The method is validated through simulations using the MATLAB software. The fault location method uses electrical parameters (resistance, inductance, capacitance, and conductance) of a 49 m indoor power line. The mathematical model of a series arc fault is based on the analysis of the V-I characteristics of the arc and consists basically of two antiparallel diodes and DC voltage sources. In a first step, the arc fault model is inserted at some different positions across the line which is modeled using lumped parameters. At both ends of the line, currents and voltages are recorded for each arc fault generation at different distances. In the second step, a fault map trace is created by using signature coefficients obtained from Kirchhoff equations which allow a virtual decoupling of the line’s mutual capacitance. Each signature coefficient obtained from the subtraction of estimated currents is calculated taking into account the Discrete Fast Fourier Transform of currents and voltages and also the fault distance value. These parameters are then substituted into Kirchhoff equations. In a third step, the same procedure described previously to calculate signature coefficients is employed but this time by considering hypothetical fault distances where the fault can appear. In this step the fault distance is unknown. The iterative calculus from Kirchhoff equations considering stepped variations of the fault distance entails the obtaining of a curve with a linear trend. Finally, the fault distance location is estimated at the intersection of two curves obtained in steps 2 and 3. The series arc fault model is validated by comparing current registered from simulation with real recorded currents. The model of the complete circuit is obtained for a 49m line with a resistive load. Also, 11 different arc fault positions are considered for the map trace generation. By carrying out the complete simulation, the performance of the method and the perspectives of the work will be presented.

Keywords: indoor power line, fault location, fault map trace, series arc fault

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614 Series Connected GaN Resonant Tunneling Diodes for Multiple-Valued Logic

Authors: Fang Liu, JunShuai Xue, JiaJia Yao, XueYan Yang, ZuMao Li, GuanLin Wu, HePeng Zhang, ZhiPeng Sun

Abstract:

III-Nitride resonant tunneling diode (RTD) is one of the most promising candidates for multiple-valued logic (MVL) elements. Here, we report a monolithic integration of GaN resonant tunneling diodes to realize multiple negative differential resistance (NDR) regions for MVL application. GaN RTDs, composed of a 2 nm quantum well embedded in two 1 nm quantum barriers, are grown by plasma-assisted molecular beam epitaxy on free-standing c-plane GaN substrates. Negative differential resistance characteristic with a peak current density of 178 kA/cm² in conjunction with a peak-to-valley current ratio (PVCR) of 2.07 is observed. Statistical properties exhibit high consistency showing a peak current density standard deviation of almost 1%, laying the foundation for the monolithic integration. After complete electrical isolation, two diodes of the designed same area are connected in series. By solving the Poisson equation and Schrodinger equation in one dimension, the energy band structure is calculated to explain the transport mechanism of the differential negative resistance phenomenon. Resonant tunneling events in a sequence of the series-connected RTD pair (SCRTD) form multiple NDR regions with nearly equal peak current, obtaining three stable operating states corresponding to ternary logic. A frequency multiplier circuit achieved using this integration is demonstrated, attesting to the robustness of this multiple peaks feature. This article presents a monolithic integration of SCRTD with multiple NDR regions driven by the resonant tunneling mechanism, which can be applied to a multiple-valued logic field, promising a fast operation speed and a great reduction of circuit complexity and demonstrating a new solution for nitride devices to break through the limitations of binary logic.

Keywords: GaN resonant tunneling diode, multiple-valued logic system, frequency multiplier, negative differential resistance, peak-to-valley current ratio

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613 Model Reference Adaptive Approach for Power System Stabilizer for Damping of Power Oscillations

Authors: Jožef Ritonja, Bojan Grčar, Boštjan Polajžer

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In recent years, electricity trade between neighboring countries has become increasingly intense. Increasing power transmission over long distances has resulted in an increase in the oscillations of the transmitted power. The damping of the oscillations can be carried out with the reconfiguration of the network or the replacement of generators, but such solution is not economically reasonable. The only cost-effective solution to improve the damping of power oscillations is to use power system stabilizers. Power system stabilizer represents a part of synchronous generator control system. It utilizes semiconductor’s excitation system connected to the rotor field excitation winding to increase the damping of the power system. The majority of the synchronous generators are equipped with the conventional power system stabilizers with fixed parameters. The control structure of the conventional power system stabilizers and the tuning procedure are based on the linear control theory. Conventional power system stabilizers are simple to realize, but they show non-sufficient damping improvement in the entire operating conditions. This is the reason that advanced control theories are used for development of better power system stabilizers. In this paper, the adaptive control theory for power system stabilizers design and synthesis is studied. The presented work is focused on the use of model reference adaptive control approach. Control signal, which assures that the controlled plant output will follow the reference model output, is generated by the adaptive algorithm. Adaptive gains are obtained as a combination of the "proportional" term and with the σ-term extended "integral" term. The σ-term is introduced to avoid divergence of the integral gains. The necessary condition for asymptotic tracking is derived by means of hyperstability theory. The benefits of the proposed model reference adaptive power system stabilizer were evaluated as objectively as possible by means of a theoretical analysis, numerical simulations and laboratory realizations. Damping of the synchronous generator oscillations in the entire operating range was investigated. Obtained results show the improved damping in the entire operating area and the increase of the power system stability. The results of the presented work will help by the development of the model reference power system stabilizer which should be able to replace the conventional stabilizers in power systems.

Keywords: power system, stability, oscillations, power system stabilizer, model reference adaptive control

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612 Clinical Applications of Amide Proton Transfer Magnetic Resonance Imaging: Detection of Brain Tumor Proliferative Activity

Authors: Fumihiro Ima, Shinichi Watanabe, Shingo Maeda, Haruna Imai, Hiroki Niimi

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It is important to know growth rate of brain tumors before surgery because it influences treatment planning including not only surgical resection strategy but also adjuvant therapy after surgery. Amide proton transfer (APT) imaging is an emerging molecular magnetic resonance imaging (MRI) technique based on chemical exchange saturation transfer without administration of contrast medium. The underlying assumption in APT imaging of tumors is that there is a close relationship between the proliferative activity of the tumor and mobile protein synthesis. We aimed to evaluate the diagnostic performance of APT imaging of pre-and post-treatment brain tumors. Ten patients with brain tumor underwent conventional and APT-weighted sequences on a 3.0 Tesla MRI before clinical intervention. The maximum and the minimum APT-weighted signals (APTWmax and APTWmin) in each solid tumor region were obtained and compared before and after clinical intervention. All surgical specimens were examined for histopathological diagnosis. Eight of ten patients underwent adjuvant therapy after surgery. Histopathological diagnosis was glioma in 7 patients (WHO grade 2 in 2 patients, WHO grade 3 in 3 patients and WHO grade 4 in 2 patients), meningioma WHO grade1 in 2 patients and primary lymphoma of the brain in 1 patient. High-grade gliomas showed significantly higher APTW-signals than that in low-grade gliomas. APTWmax in one huge parasagittal meningioma infiltrating into the skull bone was higher than that in glioma WHO grade 4. On the other hand, APTWmax in another convexity meningioma was the same as that in glioma WHO grade 3. Diagnosis of primary lymphoma of the brain was possible with APT imaging before pathological confirmation. APTW-signals in residual tumors decreased dramatically within one year after adjuvant therapy in all patients. APT imaging demonstrated excellent diagnostic performance for the planning of surgery and adjuvant therapy of brain tumors.

Keywords: amides, magnetic resonance imaging, brain tumors, cell proliferation

Procedia PDF Downloads 126
611 Methylglyoxal Induced Glycoxidation of Human Low Density Lipoprotein: A Biophysical Perspective and Its Role in Diabetes and Periodontitis

Authors: Minhal Abidi, Moinuddin

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Diabetes mellitus (DM) induced metabolic abnormalities causes oxidative stress which leads to the pathogenesis of complications associated with diabetes like retinopathy, nephropathy periodontitis etc. Combination of glycation and oxidation 'glycoxidation' occurs when oxidative reactions affect the early state of glycation products. Low density lipoprotein (LDL) is prone to glycoxidative attack by sugars and methylglyoxal (MGO) being a strong glycating agent may have severe impact on its structure and consequent role in diabetes. Pro-inflammatory cytokines like IL1β and TNFα produced by the action of gram negative bacteria in periodontits (PD) can in turn lead to insulin resistance. This work discusses modifications to LDL as a result of glycoxidation. The changes in the protein molecule have been characterized by various physicochemical techniques and the immunogenicity of the modified molecules was also evaluated as they presented neo-epitopes. Binding of antibodies present in diabetes patients to the native and glycated LDL has been evaluated. Role of modified epitopes in the generation of antibodies in diabetes and periodontitis has been discussed. The structural perturbations induced in LDL were analyzed by UV–Vis, fluorescence, circular dichroism and FTIR spectroscopy, molecular docking studies, thermal denaturation studies, Thioflavin T assay, isothermal titration calorimetry, comet assay. MALDI-TOF, ketoamine moieties, carbonyl content and HMF content were also quantitated in native and glycated LDL. IL1β and TNFα levels were also measured in the type 2 DM and PD patients. We report increased carbonyl content, ketoamine moieties and HMF content in glycated LDL as compared to native analogue. The results substantiate that in hyperglycemic state MGO modification of LDL causes structural perturbations making the protein antigenic which could obstruct normal physiological functions and might contribute in the development of secondary complications in diabetic patients like periodontitis.

Keywords: advanced glycation end products, diabetes mellitus, glycation, glycoxidation, low density lipoprotein, periodontitis

Procedia PDF Downloads 182
610 Rooibos Extract Antioxidants: In vitro Models to Assess Their Bioavailability

Authors: Ntokozo Dambuza, Maryna Van De Venter, Trevor Koekemoer

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Oxidative stress contributes to the pathogenesis of many diseases and consequently antioxidant therapy has attracted much attention as a potential therapeutic strategy. Regardless of the quantities ingested, antioxidants need to reach the diseased tissues at concentrations sufficient to combat oxidative stress. Bioavailability is thus a defining criterion for the therapeutic efficacy of antioxidants. In addition, therapeutic antioxidants must possess biologically relevant characteristics which can target the specific molecular mechanisms responsible for disease related oxidative stress. While many chemical antioxidant assays are available to quantify antioxidant capacity, they relate poorly to the biological environment and provide no information as to the bioavailability. The present comparative study thus aims to characterise green and fermented rooibos extracts, well recognized for their exceptional antioxidant capacity, in terms of antioxidant bioavailability and efficacy in a disease relevant cellular setting. Chinese green tea antioxidant activity was also evaluated. Chemical antioxidant assays (FRAP, DPPH and ORAC) confirmed the potent antioxidant capacity of both green and fermented rooibos, with green rooibos possessing antioxidant activity superior to that of fermented rooibos and Chinese green tea. Bioavailability was assessed using the PAMPA assay and the results indicate that green and fermented rooibos have a permeation coefficient of 5.7 x 10-6 and 6.9 x 10-6 cm/s, respectively. Chinese green tea permeability coefficient was 8.5 x 10-6 cm/s. These values were comparable to those of rifampicin, which is known to have a high permeability across intestinal epithelium with a permeability coefficient of 5 x 10 -6 cm/s. To assess the antioxidant efficacy in a cellular context, U937 and red blood cells were pre-treated with rooibos and Chinese green tea extracts in the presence of a dye DCFH-DA and then exposed to oxidative stress. Green rooibos exhibited highest activity with an IC50 value of 29 μg/ml and 70 μg/ml, when U937 and red blood cells were exposed oxidative stress, respectively. Fermented rooibos and Chinese green tea had IC50 values of 61 μg/ml and 57 μg/ml for U937, respectively, and 221 μg/ml and 405 μg/ml for red blood cells, respectively. These results indicate that fermented and green rooibos extracts were able to permeate the U937 cells and red blood cell membrane and inhibited oxidation of DCFH-DA to a fluorescent DCF within the cells.

Keywords: rooibos, antioxidants, permeability, bioavailability

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609 Component Test of Martensitic/Ferritic Steels and Nickel-Based Alloys and Their Welded Joints under Creep and Thermo-Mechanical Fatigue Loading

Authors: Daniel Osorio, Andreas Klenk, Stefan Weihe, Andreas Kopp, Frank Rödiger

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Future power plants currently face high design requirements due to worsening climate change and environmental restrictions, which demand high operational flexibility, superior thermal performance, minimal emissions, and higher cyclic capability. The aim of the paper is, therefore, to investigate the creep and thermo-mechanical material behavior of improved materials experimentally and welded joints at component scale under near-to-service operating conditions, which are promising for application in highly efficient and flexible future power plants. These materials promise an increase in flexibility and a reduction in manufacturing costs by providing enhanced creep strength and, therefore, the possibility for wall thickness reduction. At the temperature range between 550°C and 625°C, the investigation focuses on the in-phase thermo-mechanical fatigue behavior of dissimilar welded joints of conventional materials (ferritic and martensitic material T24 and T92) to nickel-based alloys (A617B and HR6W) by means of membrane test panels. The temperature and external load are varied in phase during the test, while the internal pressure remains constant. At the temperature range between 650°C and 750°C, it focuses on the creep behavior under multiaxial stress loading of similar and dissimilar welded joints of high temperature resistant nickel-based alloys (A740H, A617B, and HR6W) by means of a thick-walled-component test. In this case, the temperature, the external axial load, and the internal pressure remain constant during testing. Numerical simulations are used for the estimation of the axial component load in order to induce a meaningful damage evolution without causing a total component failure. Metallographic investigations after testing will provide support for understanding the damage mechanism and the influence of the thermo-mechanical load and multiaxiality on the microstructure change and on the creep and TMF- strength.

Keywords: creep, creep-fatigue, component behaviour, weld joints, high temperature material behaviour, nickel-alloys, high temperature resistant steels

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608 Structural Optimization, Design, and Fabrication of Dissolvable Microneedle Arrays

Authors: Choupani Andisheh, Temucin Elif Sevval, Bediz Bekir

Abstract:

Due to their various advantages compared to many other drug delivery systems such as hypodermic injections and oral medications, microneedle arrays (MNAs) are a promising drug delivery system. To achieve enhanced performance of the MN, it is crucial to develop numerical models, optimization methods, and simulations. Accordingly, in this work, the optimized design of dissolvable MNAs, as well as their manufacturing, is investigated. For this purpose, a mechanical model of a single MN, having the geometry of an obelisk, is developed using commercial finite element software. The model considers the condition in which the MN is under pressure at the tip caused by the reaction force when penetrating the skin. Then, a multi-objective optimization based on non-dominated sorting genetic algorithm II (NSGA-II) is performed to obtain geometrical properties such as needle width, tip (apex) angle, and base fillet radius. The objective of the optimization study is to reach a painless and effortless penetration into the skin along with minimizing its mechanical failures caused by the maximum stress occurring throughout the structure. Based on the obtained optimal design parameters, master (male) molds are then fabricated from PMMA using a mechanical micromachining process. This fabrication method is selected mainly due to the geometry capability, production speed, production cost, and the variety of materials that can be used. Then to remove any chip residues, the master molds are cleaned using ultrasonic cleaning. These fabricated master molds can then be used repeatedly to fabricate Polydimethylsiloxane (PDMS) production (female) molds through a micro-molding approach. Finally, Polyvinylpyrrolidone (PVP) as a dissolvable polymer is cast into the production molds under vacuum to produce the dissolvable MNAs. This fabrication methodology can also be used to fabricate MNAs that include bioactive cargo. To characterize and demonstrate the performance of the fabricated needles, (i) scanning electron microscope images are taken to show the accuracy of the fabricated geometries, and (ii) in-vitro piercing tests are performed on artificial skin. It is shown that optimized MN geometries can be precisely fabricated using the presented fabrication methodology and the fabricated MNAs effectively pierce the skin without failure.

Keywords: microneedle, microneedle array fabrication, micro-manufacturing structural optimization, finite element analysis

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607 Discrimination of Bio-Analytes by Using Two-Dimensional Nano Sensor Array

Authors: P. Behera, K. K. Singh, D. K. Saini, M. De

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Implementation of 2D materials in the detection of bio analytes is highly advantageous in the field of sensing because of its high surface to volume ratio. We have designed our sensor array with different cationic two-dimensional MoS₂, where surface modification was achieved by cationic thiol ligands with different functionality. Green fluorescent protein (GFP) was chosen as signal transducers for its biocompatibility and anionic nature, which can bind to the cationic MoS₂ surface easily, followed by fluorescence quenching. The addition of bio-analyte to the sensor can decomplex the cationic MoS₂ and GFP conjugates, followed by the regeneration of GFP fluorescence. The fluorescence response pattern belongs to various analytes collected and transformed to linear discriminant analysis (LDA) for classification. At first, 15 different proteins having wide range of molecular weight and isoelectric points were successfully discriminated at 50 nM with detection limit of 1 nM. The sensor system was also executed in biofluids such as serum, where 10 different proteins at 2.5 μM were well separated. After successful discrimination of protein analytes, the sensor array was implemented for bacteria sensing. Six different bacteria were successfully classified at OD = 0.05 with a detection limit corresponding to OD = 0.005. The optimized sensor array was able to classify uropathogens from non-uropathogens in urine medium. Further, the technique was applied for discrimination of bacteria possessing resistance to different types and amounts of drugs. We found out the mechanism of sensing through optical and electrodynamic studies, which indicates the interaction between bacteria with the sensor system was mainly due to electrostatic force of interactions, but the separation of native bacteria from their drug resistant variant was due to Van der Waals forces. There are two ways bacteria can be detected, i.e., through bacterial cells and lysates. The bacterial lysates contain intracellular information and also safe to analysis as it does not contain live cells. Lysates of different drug resistant bacteria were patterned effectively from the native strain. From unknown sample analysis, we found that discrimination of bacterial cells is more sensitive than that of lysates. But the analyst can prefer bacterial lysates over live cells for safer analysis.

Keywords: array-based sensing, drug resistant bacteria, linear discriminant analysis, two-dimensional MoS₂

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