Search results for: small cell

Authors: Yusuf Yasa, Erkan Mese

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This paper investigates the thermal issue of permanent magnet synchronous generator which is frequently used in direct drive gearless small-scale wind turbine applications. Permanent magnet synchronous generator (PMSG) is designed with 2.5 kW continuous and 6 kW peak power. Then considering generator geometry, mechanical design of wind turbine is performed. Thermal analysis and optimization is carried out considering all wind turbine components to reach realistic results. These issue is extremely important in research and development(R&D) process for wind turbine applications.

Keywords: direct drive, gearless wind turbine, permanent magnet synchronous generator (PMSG), small-scale wind turbine, thermal management

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Authors: Khaoula Bensaida, Osama Eljamal

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The electrical energy generation through Microbial Fuel Cells (MFCs) using microorganisms is a renewable and sustainable approach. It creates truly an efficient technology for power production and wastewater treatment. MFC is an electrochemical device which turns wastewater into electricity. The most important part of MFC is microbes. Nano zero-valent Iron NZVI technique was successfully applied in degrading the chemical pollutants and cleaning wastewater. However, the use of NZVI for enhancing the current production is still not confirmed yet. This study aims to confirm the effect of these particles on the current generation by using MFC. A constructed microbial fuel cell, which utilizes domestic wastewater, has been considered for wastewater treatment and bio-electricity generation. The two electrodes were connected to an external resistor (200 ohms). Experiments were conducted in two steps. First, the MFC was constructed without adding NZVI particles (Control) while at a second step, nanoparticles were added with a concentration of 50mg/L. After 20 hours, the measured voltage increased to 5 and 8mV, respectively. To conclude, the use of zero-valent iron in an MFC system can increase electricity generation.

Keywords: bacterial growth, electricity generation, microbial fuel cell MFC, nano zero-valent iron NZVI.

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Authors: Alexander Kelíšek, Denisa Janasová, Veronika Mitašová

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Weak signals using is often associated with early warning. It is possible to find a link between early warning, respectively early problems detection and risk management. The idea of early warning is very important in the context of crisis management because of the risk prevention possibility. Weak signals are likened to risk symptoms. Nowadays, their usefulness as a tool of proactive problems solving is emphasized. Based on it, it is possible to use weak signals not only in strategic planning, project management, or early warning system, but also as a subsidiary element in risk management. The main question is how to effectively integrate weak signals into risk management. The main aim of the paper is to point out the possibilities of weak signals using in small and medium enterprises risk management.

Keywords: early warning system, weak signals, risk management, small and medium enterprises (SMEs)

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Authors: Z. Jannoo, B. W. Yap, N. Auchoybur, M. A. Lazim

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The two common approaches to Structural Equation Modeling (SEM) are the Covariance-Based SEM (CB-SEM) and Partial Least Squares SEM (PLS-SEM). There is much debate on the performance of CB-SEM and PLS-SEM for small sample size and when distributions are non-normal. This study evaluates the performance of CB-SEM and PLS-SEM under normality and non-normality conditions via a simulation. Monte Carlo Simulation in R programming language was employed to generate data based on the theoretical model with one endogenous and four exogenous variables. Each latent variable has three indicators. For normal distributions, CB-SEM estimates were found to be inaccurate for small sample size while PLS-SEM could produce the path estimates. Meanwhile, for a larger sample size, CB-SEM estimates have lower variability compared to PLS-SEM. Under non-normality, CB-SEM path estimates were inaccurate for small sample size. However, CB-SEM estimates are more accurate than those of PLS-SEM for sample size of 50 and above. The PLS-SEM estimates are not accurate unless sample size is very large.

Keywords: CB-SEM, Monte Carlo simulation, normality conditions, non-normality, PLS-SEM

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Authors: Leo Nnamdi Ozurumba-Dwight

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Messenger ribooxynucleic acid (mRNA) molecules are compositional, protein-based. These proteins, encoding mRNA molecules (which collectively connote the transcriptome), when analyzed by RNA sequencing (RNAseq), unveils the nature of gene expression in the RNA. The obtained gene expression provides clues of cellular traits and their dynamics in presentations. These can be studied in relation to function and responses. RNAseq is a practical concept in Genomics as it enables detection and quantitative analysis of mRNA molecules. Single cell and spatial transcriptomics both present varying avenues for expositions in genomic characteristics of single cells and pooled cells in disease conditions such as cancer, auto-immune diseases, hematopoietic based diseases, among others, from investigated biological tissue samples. Single cell transcriptomics helps conduct a direct assessment of each building unit of tissues (the cell) during diagnosis and molecular gene expressional studies. A typical technique to achieve this is through the use of a single-cell RNA sequencer (scRNAseq), which helps in conducting high throughput genomic expressional studies. However, this technique generates expressional gene data for several cells which lack presentations on the cells’ positional coordinates within the tissue. As science is developmental, the use of complimentary pre-established tissue reference maps using molecular and bioinformatics techniques has innovatively sprung-forth and is now used to resolve this set back to produce both levels of data in one shot of scRNAseq analysis. This is an emerging conceptual approach in methodology for integrative and progressively dependable transcriptomics analysis. This can support in-situ fashioned analysis for better understanding of tissue functional organization, unveil new biomarkers for early-stage detection of diseases, biomarkers for therapeutic targets in drug development, and exposit nature of cell-to-cell interactions. Also, these are vital genomic signatures and characterizations of clinical applications. Over the past decades, RNAseq has generated a wide array of information that is igniting bespoke breakthroughs and innovations in Biomedicine. On the other side, spatial transcriptomics is tissue level based and utilized to study biological specimens having heterogeneous features. It exposits the gross identity of investigated mammalian tissues, which can then be used to study cell differentiation, track cell line trajectory patterns and behavior, and regulatory homeostasis in disease states. Also, it requires referenced positional analysis to make up of genomic signatures that will be sassed from the single cells in the tissue sample. Given these two presented approaches to RNA transcriptomics study in varying quantities of cell lines, with avenues for appropriate resolutions, both approaches have made the study of gene expression from mRNA molecules interesting, progressive, developmental, and helping to tackle health challenges head-on.

Keywords: transcriptomics, RNA sequencing, single cell, spatial, gene expression.

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Authors: Guillaume Soubeyran, Fabrice Micoud, Benoit Morin, Jean-Philippe Poirot-Crouvezier, Magali Reytier

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Proton Exchange Membrane Fuel Cell (PEMFC) technology is considered as a solution for the reduction of CO2 emissions. However, this technology still meets several challenges for high-scale industrialization. In this context, the increase of durability remains a critical aspect for competitiveness of this technology. Fortunately, performance degradations in nominal operating conditions is partially reversible, meaning that if specific conditions are applied, a partial recovery of fuel cell performance can be achieved, while irreversible degradations can only be mitigated. Thus, it is worth studying the optimal conditions to rejuvenate these reversible degradations and assessing the long-term impact of such procedures on the performance of the cell. Reversible degradations consist mainly of anode Pt active sites poisoning by carbon monoxide at the anode, heterogeneities in water management during use, and oxidation/deactivation of Pt active sites at the cathode. The latter is identified as a major source of reversible performance loss caused by the presence oxygen, high temperature and high cathode potential that favor platinum oxidation, especially in high efficiency operating points. Hence, we studied here a recovery procedure aiming at reducing the platinum oxides by decreasing cathode potential during operation. Indeed, the application of short air starvation phase leads to a drop of cathode potential. Cell performances are temporarily increased afterwards. Nevertheless, local temperature and current heterogeneities within the cells are favored and shall be minimized. The consumption of fuel during the recovery phase shall also be considered to evaluate the global efficiency. Consequently, the purpose of this work is to find an optimal compromise between the recovery of reversible degradations by air starvation, the increase of global cell efficiency and the mitigation of irreversible degradations effects. Different operating parameters have first been studied such as cell voltage, temperature and humidity in single cell set-up. Considering the global PEMFC system efficiency, tests showed that reducing duration of recovery phase and reducing cell voltage was the key to ensure an efficient recovery. Recovery phase frequency was a major factor as well. A specific method was established to find the optimal frequency depending on the duration and voltage of the recovery phase. Then, long-term degradations have also been studied by applying FC-DLC cycles based on NEDC cycles on a 4-cell short stack by alternating test sequences with and without recovery phases. Depending on recovery phase timing, cell efficiency during the cycle was increased up to 2% thanks to a mean voltage increase of 10 mV during test sequences with recovery phases. However, cyclic voltammetry tests results suggest that the implementation of recovery phases causes an acceleration of the decrease of platinum active areas that could be due to the high potential variations applied to the cathode electrode during operation.

Keywords: durability, PEMFC, recovery procedure, reversible degradation

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Authors: Geovanna dos Santos Romeiro, Polintia Rayza Brito da Silva, Luis Henrique Moura, Izadora Moreira Do Amaral, Marília Vitória Pinto Milhomem

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Introduction: The nose is one of the most likely sites for the appearance of malignancy on the face. This can be associated with its unique position of exposure to environmental damage, lack of photoprotection and because it is an area susceptible to greater sun exposure. It is already known that the most common type of nasal tumor is basal cell carcinoma. Squamous cell carcinoma is less common but considerably more aggressive, with a tendency to grow rapidly and metastasize. Nasal skin cancer can have a good prognosis, regardless of the type of treatment chosen, i.e., surgery, radiotherapy or electrodissection. However, tumors that are not diagnosed and treated quickly can be harmful and have a greater chance of metastasizing. When curative surgery is performed, therapies and reconstructive surgical procedures are usually required. Objective: The objective is to review the literature on nasal skin tumors and their types and specific locations. Forty-four articles published in Pubmed related to the location of skin cancer in the specific nasal areas region were analyzed. Twelve were excluded for being prior to the year 2000, three with inconclusive results, and one with unbiased conclusions. Results and Conclusion: Regarding the prevalence of types of nasal tumors, basal cell carcinoma comprises the majority, occurring predominantly in the ala, tip and root; squamous cell carcinoma, on the other hand, is more common in the lateral borders and columella. Even so, 2 articles report that the prevalence of metastasis has a higher incidence in squamous cell carcinomas. All of this points to the importance of early location, including regions that are often overlooked in the examination if the patient is wearing glasses. This topic needs further investigation for a greater correlation between anatomy and clinical-surgical implications.

Keywords: skin cancer, melanoma, non-melanoma, surgery

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Authors: H. Oudira, A. Saifi

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The therapeutic utility of certain Auger emitters such as iodine-125 depends on their position within the cell nucleus . Or diagnostically, and to maintain as low as possible cell damage, it is preferable to have radionuclide localized outside the cell or at least the core. One solution to this problem is to consider markers capable of conveying anticancer drugs to the tumor site regardless of their location within the human body. The objective of this study is to simulate the impact of a complex such as bleomycin on single and double strand breaks in the DNA molecule. Indeed, this simulation consists of the following transactions: - Construction of BLM -Fe- DNA complex. - Simulation of the electron’s transport from the metastable state excitation of Fe 57 by the Monte Carlo method. - Treatment of chemical reactions in the considered environment by the diffusion equation. For physical, physico-chemical and finally chemical steps, the geometry of the complex is considered as a sphere of 50 nm centered on the binding site , and the mathematical method used is called step by step based on Monte Carlo codes.

Keywords: concentration, yield, radical species, bleomycin, excitation, DNA

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Authors: Pyi Phyo Maung

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In the study, the calculations of the permeability coefficient, values of the volume and porosity of a unit cell of a woven fabric before and after deformation based on the geometrical parameters are presented. Two types of carbon woven fabric structures were investigated: standard type, which integrated the filament, has a cross sectional shape of a cylinder and spread tow type, which has a rectangular cross sectional shape. The space antennas reflector, which distinctive feature is the presence of the surface of double curvature, is considered as the object of the research. Modeling of the kinetics of the process of impregnation of the reflector for the two types of carbon fabric’s unit cell structures was performed using software RAM-RTM. This work also investigated the influence of the grid angle between warp and welt of the unit cell on the duration of impregnation process. The results showed that decreasing the angle between warp and welt of the unit cell, the decreasing of the permeability values were occurred. Based on the results of calculation samples of the reflectors, their quality was determined. The comparisons of the theoretical and experimental results have been carried out. Comparison of the two textile structures (standard and spread tow) showed that the standard textiles with circular cross section were impregnated faster than spread tows, which have a rectangular cross section.

Keywords: vacuum assistant resin infusion, impregnation time, shear angle, reflector and modeling

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Authors: Herman Susilo, Rahmat Budiman

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Bali province is one of the most famous tourist destinations in Indonesia. As a central tourist destination, Bali is very concerned about the use of clean energy. Since Bali is an area that does not have natural resources, so all of its energy sources are imported from java island and other islands. As an example, currently, Pertagas is developing the use of LNG for the needs of the retail industry. Right now, LNG is transported from the LNG plant facility in Bontang (Kalimantan Province) using ISO Tanks which are transported by cargo ships and then transported by trucks to the island of Bali. After that, LNG from ISO Tank is breakbulk into LNG Cylinders for distribution to retail customers. The existing distribution scheme is very long and costly since the source of LNG is come from another island (Kalimantan) and is relatively far away. To solve this problem, we plan to build the mini-LNG plant on Java Island since there are lots of gas sources available. There are some small gas reserves (flared or stranded gas) that are not yet monetized and are less valuable (cheaper) because the volume is very small. After liquifying the gas from the gas field, the LNG is transported by the truck using ISO Tank. After that, LNG from ISO Tank is breakbulk into LNG Cylinders for distribution to retail customers. From this new LNG distribution scheme, there are 4-5 USD/MMBTU saving compared to the existing distribution scheme. It is hoped that with these cost savings, the number of retail LNG sales can increase rapidly.

Keywords: LNG, LNG retail, mini LNG, small scale LNG

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Authors: K. M. Yoo, M. H. Kang

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Conventional commercial wind turbine design software is limited to large wind turbines due to not incorporating with low Reynold’s Number aerodynamic characteristics typically for small wind turbines. To extract maximum annual energy product from an intermediately designed small wind turbine associated with measured wind data, numerous simulation is highly recommended to have a best fitting planform design with proper airfoil configuration. Since depending upon wind distribution with average wind speed, an optimal wind turbine planform design changes accordingly. It is theoretically not difficult, though, it is very inconveniently time-consuming design procedure to finalize conceptual layout of a desired small wind turbine. Thus, to help simulations easier and faster, a GUI software is developed to conveniently iterate and change airfoil types, wind data, and geometric blade data as well. With magnetic generator torque curve, peak power tracking simulation is also available to better match with the magnetic generator. Small wind turbine often lacks starting torque due to blade optimization. Thus this simulation is also embedded along with yaw design. This software provides various blade cross section details at user’s design convenience such as skin thickness control with fiber direction option, spar shape, and their material properties. Since small wind turbine is under international safety regulations with fatigue damage during normal operations and safety load analyses with ultimate excessive loads, load analyses are provided with each category mandated in the safety regulations.

Keywords: GUI software, Low Reynold’s number aerodynamics, peak power tracking, safety regulations, wind turbine performance optimization

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Authors: Tatheer Zahra

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Auxetic materials have counteractive properties due to re-entrant geometry that enables them to possess Negative Poisson’s Ratio (NPR). These materials have better energy absorbing and shock resistance capabilities as compared to conventional positive Poisson’s ratio materials. The re-entrant geometry can be created through 3D printing for convenient application of these materials. This paper investigates the mechanical properties of 3D printed chiral auxetic geometries of various sizes. Small scale samples were printed using an ordinary 3D printer and were tested under compression and tension to ascertain their strength and deformation characteristics. A maximum NPR of -9 was obtained under compression and tension. The re-entrant chiral cell size has been shown to affect the mechanical properties of the re-entrant chiral auxetics.

Keywords: auxetic materials, 3D printing, Negative Poisson’s Ratio, re-entrant chiral auxetics

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Authors: Sara Pereira-Nogueira, Tim Worbs, Marc Permanyer-Bosser, Reinhold Förster

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While the entry mechanism of lymphocytes into the lymph node via the blood are well described, it is still largely unknown how cells enter lymph nodes that arrive via afferent lymphatics. In order to address this, our group has established a micro-injection technique in mice through which cells are delivered directly into the lymphatic vessel immediately afferent to the popliteal lymph node. Injected cells can then be tracked via multi-colour fluorescence or 2-photon microscopy, and their localization can be analysed within the popliteal or downstream lymph nodes by immunohistology. Since naïve B cells express the chemokine receptor CXCR5 we intra-lymphatically co-injected B cells derived from wildtype and Cxcr5-deficient mice. While CXCR5 does not play a role in guiding B cells out of the subcapsular sinus, it affects their positioning within the lymph node parenchyma, since CXCR5-deficient B cells are impaired in migrating into the B cell follicle. The knowledge obtained by studying B-cell migration may prove beneficial in clinical settings regarding tumor metastasis or autoimmune diseases.

Keywords: afferent lymphatics, B cell migration, chemokine, intra-lymphatic injection

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Authors: N. Ikasari, T. Sumransat, U. Eko, R. Kusumastuti

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Small and medium enterprises (SMEs) are regarded as the engine for economic development, notwithstanding their continuous financing conundrum. In the case of developing countries, access to finance is a reflection of the effectiveness of government policy. The widely accepted perspective to assess small businesses’ access to finance is that of economic view. The existing body of literature presents access to finance in three dimensions; they are accessibility, eligibility and affordability. Within this perspective, the role of socio-cultural has not explored. This study is aimed at investigating the existence of any socio-cultural factors within access to finance issue in Asian countries where governance is enriched by countries’ values and beliefs. The significance of this study is the instigation of supplementary dimension to assess access to finance that eventually contributes to the development of micro-finance policy. Indonesia and Thailand are selected as cases in point, where distinction is drawn on the level of cultural diversity and micro-finance policy in respective country. A questionnaire is used to collect information related to the three dimensions of access to finance as well as to explore alternative financing reasoning to elaborate the issue from the demand side. Questionnaires are distributed to 60 small business owners operating in Indonesia and the same number in Thailand. In order to present a complete understanding on the matter at hand, interviews with banks are conducted to capture the perspective as presented by the supply side. Research findings show that small business owners and banks in Indonesia and Thailand are in agreement that access to finance is not deemed as an issue. However, trust issue that exists mutually between financing users and providers leads small business owners in Indonesia to look for alternative financing other than banks. The findings contribute to the refinement of micro-financing policy in Indonesia and Thailand.

Keywords: access to finance, Indonesia, small and medium enterprises, Thailand

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Authors: Abbas Pourreza

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MicroRNAs (miRNAs) are small single-stranded non-coding RNAs. They are almost 18-25 nucleotides long and very conservative through evolution. They are involved in adjusting the expression of numerous genes due to the existence of a complementary region, generally in the 3' untranslated regions (UTR) of target genes, against particular mRNAs in the cell. Also, miRNAs have been proven to be involved in cell development, differentiation, proliferation, and apoptosis. More than 2000 miRNAs have been recognized in human cells, and these miRNAs adjust approximately one-third of all genes in human cells. Dysregulation of miRNA originated from abnormal DNA methylation patterns of the locus, cause to down-regulated or overexpression of miRNAs, and it may affect tumor formation or development of it. Breast cancer (BC) is the most commonly identified cancer, the most prevalent cancer (23%), and the second-leading (14%) mortality in all types of cancer in females. BC can be classified based on the status (+/−) of the hormone receptors, including estrogen receptor (ER), progesterone receptor (PR), and the Receptor tyrosine-protein kinase erbB-2 (ERBB2 or HER2). Currently, there are four main molecular subtypes of BC: luminal A, approximately 50–60 % of BCs; luminal B, 10–20 %; HER2 positive, 15–20 %, and 10–20 % considered Basal (triple-negative breast cancer (TNBC)) subtype. Aberrant expression of miR-145, miR-21, miR-10b, miR-125a, and miR-206 was detected by Stem-loop real-time RT-PCR in BC cases. Breast tumor formation and development may result from down-regulation of a tumor suppressor miRNA such as miR-145, miR-125a, and miR-206 and/or overexpression of an oncogenic miRNA such as miR-21 and miR-10b. MiR-125a, miR-206, miR-145, miR-21, and miR-10b are hugely predicted to be new tumor markers for the diagnosis and prognosis of BC. MiR-21 and miR-125a could play a part in the treatment of HER-2-positive breast cancer cells, while miR-145 and miR-206 could speed up the evolution of cure techniques for TNBC. To conclude, miRNAs will be presented as hopeful molecules to be used in the primary diagnosis, prognosis, and treatment of BC and battle as opposed to its developed drug resistance.

Keywords: breast cancer, HER2 positive, miRNA, TNBC

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Authors: Fatemeh Abbasi, Arne Hofemeier, Timo Betz

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Muscle growth and regeneration critically depend on satellite cells (SCs) which are muscle stem cells located between the basal lamina and myofibres. Upon damage, SCs become activated, enter the cell cycle, and give rise to myoblasts that form new myofibres, while a sub-population self-renew and re-populate the muscle stem cell niche. In aged muscle as well as in certain muscle diseases such as muscular dystrophy, some of the SCs lose their regenerative ability. Although it is demonstrated that the chemical composition of SCs quiescent niche is different from the activated niche, the mechanism initially activated in the SCs remains unknown. While extensive research efforts focused on potential chemical activation, no such factor has been identified to the author’s best knowledge. However, it is substantiated that niche mechanics affects SCs behaviors, such as stemness and engraftment. We hypothesize that mechanical stress in the healthy niche (homeostasis) is different from the regenerative niche and that this difference could serve as an early signal activating SCs upon fiber damage. To investigate this hypothesis, we develop a biomimetic system to reconstitute both, the mechanical and the chemical environment of the SC niche. Cells will be confined between two elastic polyacrylamide (PAA) hydrogels with controlled elastic moduli and functionalized surface chemistry. By controlling the distance between the PAA hydrogel surfaces, we vary the compression forces exerted by the substrates on the cells, while the lateral displacement of the upper hydrogel will create controlled shear forces. To establish such a system, a simplified system is presented. We engineered a sandwich-like configuration of two elastic PAA layer with stiffnesses between 1 and 10 kPa and confined a precursor myoblast cell line (C2C12) in between these layers. Our initial observations in this sandwich model indicate that C2C12 cells show different behaviors under mechanical compression if compared to a control one-layer gel without compression. Interestingly, this behavior is stiffness-dependent. While the shape of C2C12 cells in the sandwich consisting of two stiff (10 kPa) layers was much more elongated, showing almost a neuronal phenotype, the cell shape in a sandwich situation consisting of one stiff and one soft (1 kPa) layer was more spherical. Surprisingly, even in proliferation medium and at very low cell density, the sandwich situation stimulated cell differentiation with increased striation and myofibre formation. Such behavior is commonly found for confluent cells in differentiation medium. These results suggest that mechanical changes in stiffness and applied pressure might be a relevant stimulation for changes in muscle cell behavior.

Keywords: C2C12 cells, compression, force, satellite cells, skeletal muscle

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Authors: Wahid Terro, Miray Terro, Franco Lugnani

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Roughly 90% of mouth cancer is squamous cell carcinoma. Oral region metastases are considered uncommon. The most frequent sources of metastatic tumors to the mouth are primary cancers from the lung and breast with the latter being the most common site for tumors that metastasize to the jawbones. Treatment involves surgery, radiation, chemotherapy, or a combination of these. However, these treatment modalities entail severe aesthetic and functional side effects. This article aims to present an alternative and unprecedented treatment modality for metastatic mandibular bone carcinoma – Cryosurgery. A 37-year-old female patient presented with gradually increasing pain over several weeks whose radiological tests revealed a formation of mass in the left mandibular ramus. A biopsy obtained by bone puncture of the ramus was reported to be metastatic breast squamous cell carcinoma. The patient has been successfully treated without esthetic and functional side effects by using for the first-time worldwide cryosurgery. We conclude that it is value promoting this method for current and future use.

Keywords: carcinoma, mandible, metastasis, breast

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Authors: Rima Harche, Abdelkader Mouheb

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The Algiers refinery as all the other refineries always suffers from the problem of stopping of the tubes of heat exchanger. For that a study experimental of this phenomenon was undertaken in site on the cell of heat exchangers E101 (E101 CBA and E101 EDF) intended for the heating of the crude before its fractionation, which are exposed to the problem of the fouling on the side tubes exchangers. It is of tube-calenders type with head floating. Each cell is made up of three heat exchangers, laid out in series.

Keywords: fouling, fluid temperatue , oil, tubular heat exchanger, fouling resistance, modeling, heat transfer coefficient

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Authors: Leo Nnamdi Ozurumba-Dwight

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Single-cell genomic analytical systems have proved to be a platform to isolate bulk cells into selected single cells for genomic, proteomic, and related metabolomic studies. This is enabling systematic investigations of the level of heterogeneity in a diverse and wide pool of cell populations. Single cell technologies, embracing techniques such as high parameter flow cytometry, single-cell sequencing, and high-resolution images are playing vital roles in these investigations on messenger ribonucleic acid (mRNA) molecules and related gene expressions in tracking the nature and course of disease conditions. This entails targeted molecular investigations on unit cells that help us understand cell behavoiur and expressions, which can be examined for their health implications on the health state of patients. One of the vital good sides of single-cell RNA sequencing (scRNA seq) is its probing capacity to detect deranged or abnormal cell populations present within homogenously perceived pooled cells, which would have evaded cursory screening on the pooled cell populations of biological samples obtained as part of diagnostic procedures. Despite conduction of just single-cell transcriptome analysis, scRNAseq now permits comparison of the transcriptome of the individual cells, which can be evaluated for gene expressional patterns that depict areas of heterogeneity with pharmaceutical drug discovery and clinical treatment applications. It is vital to strictly work through the tools of investigations from wet lab to bioinformatics and computational tooled analyses. In the precise steps for scRNAseq, it is critical to do thorough and effective isolation of viable single cells from the tissues of interest using dependable techniques (such as FACS) before proceeding to lysis, as this enhances the appropriate picking of quality mRNA molecules for subsequent sequencing (such as by the use of Polymerase Chain Reaction machine). Interestingly, scRNAseq can be deployed to analyze various types of biological samples such as embryos, nervous systems, tumour cells, stem cells, lymphocytes, and haematopoietic cells. In haematopoietic cells, it can be used to stratify acute myeloid leukemia patterns in patients, sorting them out into cohorts that enable re-modeling of treatment regimens based on stratified presentations. In immunotherapy, it can furnish specialist clinician-immunologist with tools to re-model treatment for each patient, an attribute of precision medicine. Finally, the good predictive attribute of scRNAseq can help reduce the cost of treatment for patients, thus attracting more patients who would have otherwise been discouraged from seeking quality clinical consultation help due to perceived high cost. This is a positive paradigm shift for patients’ attitudes primed towards seeking treatment.

Keywords: immunotherapy, transcriptome, re-modeling, mRNA, scRNA-seq

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Authors: Karl Kingsley

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Many mechanisms are involved in the control of cellular differentiation and growth, which are often dysregulated in many cancers. Many distinct pathways are involved in these mechanisms of control, including deoxyribonuclease (DNA) methyltransferase and histone deacetylase (HDAC) activation that controls both genetic and epigenetic modifications and micro ribonucleic acid (RNA) expression. Less is known about the expression of DNA methyltransferase (DNMT) and HDAC in oral cancers and the effect on microRNA expression. The primary objective of this study was to evaluate the expression of DNMT and HDAC family members in oral cancer and the concomitant expression of cancer-associated microRNAs. Using commercially available oral cancers, including squamous cell carcinoma (SCC)-4, SCC-9, SCC-15, and SCC-25, RNA was extracted and screened for DNMT, HDAC, and microRNA expression using highly-specific primers and quantitative polymerase chain reaction (qPCR). These data revealed low or absent expression of DNMT-1, which is associated with cellular differentiation but increased expression of DNMT-3a and DNMT-3b in all SCC cell lines compared with normal non-cancerous cell controls. In addition, no expression of HDAC1 and HDAC2 expression was found among the normal, non-cancerous cells but was highly expressed in each of the SCC cell lines examined. Differential expression of oncogenic and cancer-associated microRNAs was also observed among the SCC cell lines, including miR-21, miR-133, miR-149, miR-155, miR-365, and miR-720. These findings also appeared to vary according to observed growth rates among these cells. These data may be the first to demonstrate the expression and association between HDAC and DNMT3 family members among oral cancers. In addition, the differential expression of these epigenetic modifiers may be associated with the expression of specific microRNAs in these cancers, which have not previously been observed to the best of the author's knowledge. In addition, some associations and relationships may exist between the expression of these biomarkers and the rates of growth and proliferation, which may suggest that these expression patterns might represent potentially useful biomarkers to determine tumor aggressiveness and other phenotypic behaviors among oral cancers.

Keywords: oral cancer, DNA methyltransferase, histone deacetylase, microRNA

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Authors: Ya L. V., Benjamin Ong Wei Lin, Wanli Niu, Benjamin Seah Chin Tat

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This article introduces a methodology that improves reliability and cyclability of 2nd-life Li-ion battery system repurposed as an energy storage system (ESS). Most of the 2nd-life retired battery systems in the market have module/pack-level state-of-health (SOH) indicator, which is utilized for guiding appropriate depth-of-discharge (DOD) in the application of ESS. Due to the lack of cell-level SOH indication, the different degrading behaviors among various cells cannot be identified upon reaching retired status; in the end, considering end-of-life (EOL) loss and pack-level DOD, the repurposed ESS has to be oversized by > 1.5 times to complement the application requirement of reliability and cyclability. This proposed battery grading algorithm, using non-invasive methodology, is able to detect outlier cells based on historical voltage data and calculate cell-level historical maximum temperature data using semi-analytic methodology. In this way, the individual battery cell in the 2nd-life battery system can be graded in terms of SOH on basis of the historical voltage fluctuation and estimated historical maximum temperature variation. These grades will have corresponding DOD grades in the application of the repurposed ESS to enhance system reliability and cyclability. In all, this introduced battery grading algorithm is non-invasive, compatible with all kinds of retired Li-ion battery systems which lack of cell-level SOH indication, as well as potentially being embedded into battery management software for preventive maintenance and real-time cyclability optimization.

Keywords: battery grading algorithm, 2nd-life repurposing battery system, semi-analytic methodology, reliability and cyclability

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Authors: David A. Ullisch, Yantree D. Sankar-Thomas, Stefan Wilke, Thomas Selge, Matthias Pump, Thomas Leibold, Kai Schütte, Gilbert Gorr

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Plants have been considered as a source of natural substances for ages. Secondary metabolites from plants are utilized especially in medical applications but are more and more interesting as cosmetical ingredients and in the field of nutraceuticals. However, supply of compounds from natural harvest can be limited by numerous factors i.e. endangered species, low product content, climate impacts and cost intensive extraction. Especially in the pharmaceutical industry the ability to provide sufficient amounts of product and high quality are additional requirements which in some cases are difficult to fulfill by plant harvest. Whereas in many cases the complexity of secondary metabolites precludes chemical synthesis on a reasonable commercial basis, plant cells contain the biosynthetic pathway – a natural chemical factory – for a given compound. A promising approach for the sustainable production of natural products can be plant cell fermentation (PCF®). A thoroughly accomplished development process comprises the identification of a high producing cell line, optimization of growth and production conditions, the development of a robust and reliable production process and its scale-up. In order to address persistent, long lasting production, development of cryopreservation protocols and generation of working cell banks is another important requirement to be considered. So far the most prominent example using a PCF® process is the production of the anticancer compound paclitaxel. To demonstrate the power of plant suspension cultures here we present three case studies: 1) For more than 17 years Phyton produces paclitaxel at industrial scale i.e. up to 75,000 L in scale. With 60 g/kg dw this fully controlled process which is applied according to GMP results in outstanding high yields. 2) Thapsigargin is another anticancer compound which is currently isolated from seeds of Thapsia garganica. Thapsigargin is a powerful cytotoxin – a SERCA inhibitor – and the precursor for the derivative ADT, the key ingredient of the investigational prodrug Mipsagargin (G-202) which is in several clinical trials. Phyton successfully generated plant cell lines capable to express this compound. Here we present data about the screening for high producing cell lines. 3) The third case study covers ingenol-3-mebutate. This compound is found in the milky sap of the intact plants of the Euphorbiacae family at very low concentrations. Ingenol-3-mebutate is used in Picato® which is approved against actinic keratosis. Generation of cell lines expressing significant amounts of ingenol-3-mebutate is another example underlining the strength of plant cell culture. The authors gratefully acknowledge Inspyr Therapeutics for funding.

Keywords: Ingenol-3-mebutate, plant cell culture, sustainability, thapsigargin

Procedia PDF Downloads 232

Authors: Jienny Lee, In-Soo Cho, Sang-Ho Cha

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Adult mesenchymal stem cells (MSCs) have been investigated using preclinical approaches for tissue regeneration. Porcine MSCs (pMSCs) are capable of growing and attaching to plastic with a fibroblast-like morphology and then differentiating into bone, adipose, and cartilage tissues in vitro. This study was conducted to investigate the proliferating abilities, differentiation potentials, and multipotency of miniature pig adipose tissue-derived MSCs (mpAD-MSCs) with or without long-term cryopreservation, considering that cryostorage has the potential for use in clinical applications. After confirming the characteristics of the mpAD-MSCs, we examined the effect of long-term cryopreservation (> 2 years) on expression of cell surface markers (CD34, CD90 and CD105), proliferating abilities (cumulative population doubling level, doubling time, colony-forming unit, and MTT assay) and differentiation potentials into mesodermal cell lineages. As a result, the expression of cell surface markers is similar between thawed and fresh mpAD-MSCs. However, long-term cryopreservation significantly lowered the differentiation potentials (adipogenic, chondrogenic, and osteogenic) of mpAD-MSCs. When compared with fresh mpAD-MSCs, thawed mpAD-MSCs exhibited lower expression of mesodermal cell lineage-related genes such as peroxisome proliferator-activated receptor-g2, lipoprotein lipase, collagen Type II alpha 1, osteonectin, and osteocalcin. Interestingly, long-term cryostoraged mpAD-MSCs exhibited significantly higher cell viability than the fresh mpAD-MSCs. Long-term cryopreservation induced a 30% increase in the cell viability of mpAD-MSCs when compared with the fresh mpAD-MSCs at 5 days after thawing. However, long-term cryopreservation significantly lowered expression of stemness markers such as Oct3/4, Sox2, and Nanog. Furthermore, long-term cryopreservation negatively affected expression of senescence-associated genes such as telomerase reverse transcriptase and heat shock protein 90 of mpAD-MSCs when compared with the fresh mpAD-MSCs. The results from this study might be important for the successful application of MSCs in clinical trials after long-term cryopreservation.

Keywords: mesenchymal stem cells, cryopreservation, stemness, senescence

Procedia PDF Downloads 219

Authors: Bruno Baptista, Andreia S. R. Oliveira, Patricia V. Mendonca, Jorge F. J. Coelho, Fani Sousa

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Drug delivery systems are designed to allow adequate protection and controlled delivery of drugs to specific locations. These systems aim to reduce side effects and control the biodistribution profile of drugs, thus improving therapeutic efficacy. This study involved the synthesis of polymeric nanoparticles, based on amphiphilic diblock copolymers, comprising a biocompatible, poly (oligo (ethylene oxide) methyl ether methacrylate (POEOMA) as hydrophilic segment and a pH-sensitive block, the poly (2-diisopropylamino)ethyl methacrylate) (PDPA). The objective of this work was the development of polymeric pH-responsive nanoparticles to encapsulate and carry small RNAs as a model to further develop non-coding RNAs delivery systems with therapeutic value. The responsiveness of PDPA to pH allows the electrostatic interaction of these copolymers with nucleic acids at acidic pH, as a result of the protonation of the tertiary amine groups of this polymer at pH values below its pKa (around 6.2). Initially, the molecular weight parameters and chemical structure of the block copolymers were determined by size exclusion chromatography (SEC) and nuclear magnetic resonance (1H-NMR) spectroscopy, respectively. Then, the complexation with small RNAs was verified, generating polyplexes with sizes ranging from 300 to 600 nm and with encapsulation efficiencies around 80%, depending on the molecular weight of the polymers, their composition, and concentration used. The effect of pH on the morphology of nanoparticles was evaluated by scanning electron microscopy (SEM) being verified that at higher pH values, particles tend to lose their spherical shape. Since this work aims to develop systems for the delivery of non-coding RNAs, studies on RNA protection (contact with RNase, FBS, and Trypsin) and cell viability were also carried out. It was found that they induce some protection against constituents of the cellular environment and have no cellular toxicity. In summary, this research work contributes to the development of pH-sensitive polymers, capable of protecting and encapsulating RNA, in a relatively simple and efficient manner, to further be applied on drug delivery to specific sites where pH may have a critical role, as it can occur in several cancer environments.

Keywords: drug delivery systems, pH-responsive polymers, POEOMA-b-PDPA, small RNAs

Procedia PDF Downloads 244

Authors: D. H. Park, Y. H. Tak, H. H. Kwon, G. J. Kwon, H. G. Kim

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This study focused on developing forging technology of a large-diameter cam ring gear from the small bar. The analyses of temperature variation and deformation behavior of the material are important to obtain the optimal forging products. The hot compression test was carried out to know formability at high temperature. In order to define the optimum forging conditions including material temperature, strain and forging load, the finite element method was used to simulate the forging process of cam ring gear parts. Test results were in good agreement with the simulations. An existing cam ring gear is presented the chips generated by cutting the rod material and the durability issues, but this would be to develop a large-diameter cam ring gear forging parts for truck in order to solve the durability problem and the material waste.

Keywords: forging technology, cam ring, gear, truck, small bar

Procedia PDF Downloads 276

Authors: Vineeth Siripuram, Abhineet Nigam

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A bioreactor is an engineered system that supports a biologically active environment. Along the years, the advancements in bioreactors have been widely accepted all over the world for varied applications ranging from sewage treatment to tissue cloning. Driven by tissue and organ shortage, tissue engineering has emerged as an alternative to transplantation for the reconstruction of lost or damaged organs. In this study, Computational fluid dynamics (CFD) has been used to model porous medium flow in scaffolds (taken from the literature) with different flow patterns. A detailed analysis of different scaffold geometries and their influence on cell deposition in the perfusion system is been carried out using Computational fluid dynamics (CFD). Considering the fact that, the scaffold should mimic the organs or tissues structures in a three-dimensional manner, certain assumptions were made accordingly. The research on scaffolds has been extensively carried out in different bioreactors. However, there has been less focus on the morphology of the scaffolds and the flow patterns in which the perfusion system is laid upon. The objective of this paper is to employ a computational approach using CFD simulation to determine the optimal morphology and the anisotropic measurements of the various samples of scaffolds. Using predictive computational modelling approach, variables which exert dominant effects on the cell deposition within the scaffold were prioritised and corresponding changes in morphology of scaffold and flow patterns in the perfusion systems are made. A Eulerian approach was carried on in multiple CFD simulations, and it is observed that the morphological and topological changes in the scaffold perfusion system are of great importance in the commercial applications of scaffolds.

Keywords: cell seeding, CFD, flow patterns, modelling, perfusion systems, scaffold

Procedia PDF Downloads 145

Authors: Vongsathorn Ngampuak, Yutachai Chookaew, Wipawee Dejtisakdi

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Dunaliella salina has great potential as a system for generating commercially valuable products, including beta-carotene, pharmaceuticals, and biofuels. Our goal is to improve this potential by enhancing growth rate and other properties of D. salina under optimal growth conditions. We used ethyl methane sulfonate (EMS) to generate random mutants in D. salina KU11, a strain classified in Thailand. In a preliminary experiment, we first treated D. salina cells with 0%, 0.8%, 1.0%, 1.2%, 1.44% and 1.66% EMS to generate a killing curve. After that, we randomly picked 30 candidates from approximately 300 isolated survivor colonies from the 1.44% EMS treatment (which permitted 30% survival) as an initial test of the mutant screen. Among the 30 survivor lines, we found that 2 strains (mutant #17 and #24) had significantly improved growth rates and cell number accumulation at stationary phase approximately up to 1.8 and 1.45 fold, respectively, 2 strains (mutant #6 and #23) had significantly decreased growth rates and cell number accumulation at stationary phase approximately down to 1.4 and 1.35 fold, respectively, while 26 of 30 lines had similar growth rates compared with the wild type control. We also analyzed cell size for each strain and found there was no significant difference comparing all mutants with the wild type. In addition, mutant #24 had shown an increase of biomass accumulation approximately 1.65 fold compared with the wild type strain on day 5 that was entering early stationary phase. From these preliminary results, it could be feasible to identify D. salina mutants with significant improved growth rate, cell accumulation and biomass production compared to the wild type for the further study; this makes it possible to improve this microorganism as a platform for biotechnology application.

Keywords: Dunaliella salina, ethyl methyl sulfonate, growth rate, biomass

Procedia PDF Downloads 227

Authors: Iulianna Taritsa, Kuldeep Neote, Eric Fossel

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Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence – a gap that can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells, which can later present those tumorigenic antigens to T cells. Previous research has shown that oxidative agents administered in the tumor microenvironment can initiate LIICD. We generated a fusion protein between an oxidative agent known as xanthine oxidase (XO) and a mini-antibody specific for EGFR/HER2-sensitive breast tumor cells. The anti-EGFR single domain antibody fragment is uniquely sourced from llama, which is functional without the presence of a light chain. These llama micro-antibodies have been shown to be better able to penetrate tissues and have improved physicochemical stability as compared to traditional monoclonal antibodies. We demonstrate that the fusion protein created is stable and can induce early markers of immunogenic cell death in an in vitro human breast cancer cell line (SkBr3). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of SkBr3 cells dosed with doxorubicin (a known inducer of LIICD) and a negative control dosed with cisplatin (a known inducer of cell death, but not of the immunogenic variety). We looked at each marker at various time points after cancer cells were treated with the XO/antibody fusion protein, doxorubicin, and cisplatin. Upregulated biomarkers after treatment with the fusion protein indicate an immunogenic response. We thus show the potential for this fusion protein to induce an anticancer effect paired with an adaptive immune response against EGFR/HER2+ cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method for patients and serves as the gateway to developing a new treatment approach against breast cancer.

Keywords: apoptosis, breast cancer, immunogenic cell death, lysosome

Procedia PDF Downloads 189

Authors: Lise P. Labéjof, Ivna Mororó, Raquel G. Bastos, Maria Isabel G. Severo, Arno H. de Oliveira

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This work presents an alternative mode of intestine mucosa renewal that may allow to better understand the total loss of villi after irradiation. It was tested a morphological method of 3d reconstruction using micrographs of serial sections of rat duodenum. We used hundreds of sections of each specimen of duodenum placed on glass slides and examined under a light microscope. Those containing the detachment, approximately a dozen, were chosen for observation under a transmission electron microscope (TEM). Each of these sections was glued on a block of epon resin and recut into a hundred of 60 nm-thick sections. Ribbons of these ultrathin sections were distributed on a series of copper grids in the same order of appearance than during the process of microstomia. They were then stained by solutions of uranyl and lead salts and observed under a TEM. The sections were pictured and the electron micrographs showing signs of cells detachment were transferred into two softwares, ImageJ to align the cellular structures and Reconstruct to realize the 3d reconstruction. It has been detected epithelial cells that exhibited all signs of programmed cell death and localized at the villus-crypt junction. Their nucleus was irregular in shape with a condensed chromatin in clumps. Their cytoplasm was darker than that of neighboring cells, containing many swollen mitochondria. In some places of the sections, we could see intercellular spaces enlarged by the presence of shrunk cells which displayed a plasma membrane with an irregular shape in thermowell as if the cell interdigitations would distant from each other. The three-dimensional reconstruction of the crypts has allowed observe gradual loss of intercellular contacts of crypt cells in the longitudinal plan of the duodenal mucosa. In the transverse direction, there was a gradual increase of the intercellular space as if these cells moved away from one another. This observation allows assume that the gradual remoteness of the cells at the villus-crypt junction is the beginning of the mucosa detachment. Thus, the shrinking of cells due to apoptosis is the way that they detach from the mucosa and progressively the villi also. These results are in agreement with our initial hypothesis and thus have demonstrated that the villi become detached from the mucosa at the villus-crypt junction by the programmed cell death process. This type of loss of entire villus helps explain the rapid denudation of the intestinal mucosa in case of irradiation.

Keywords: 3dr, transmission electron microscopy, ionizing radiations, rat small intestine, apoptosis

Procedia PDF Downloads 368

Authors: K. Matušínská, Z. Bednarčík, M. Klepek

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This paper examines international marketing in business practice of Czech exporting small and medium-sized enterprises (SMEs) with regard to the strategic perspectives. Research was focused on Czech exporting SMEs from Moravian-Silesia region and their behaviour on international markets. For purpose of collecting data, a questionnaire was given to 262 SMEs involved in international business. Statistics utilized in this research included frequency, mean, percentage, and chi-square test. Data were analysed by Statistical Package for the Social Sciences software. The research analysis disclosed that there is certain space for improvement in strategic marketing especially in marketing research, perception of cultural and social differences, product adaptation and usage of marketing communication tools.

Keywords: international marketing, marketing mix, marketing research, small and medium-sized enterprises, strategic marketing

Procedia PDF Downloads 309