Search results for: CD4 cell count stages
113 Right Atrial Tissue Morphology in Acquired Heart Diseases
Authors: Edite Kulmane, Mara Pilmane, Romans Lacis
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Introduction: Acquired heart diseases remain one of the leading health care problems in the world. Changes in myocardium of the diseased hearts are complex and pathogenesis is still not fully clear. The aim of this study was to identify appearance and distribution of apoptosis, homeostasis regulating factors, and innervation and ischemia markers in right atrial tissue in different acquired heart diseases. Methods: During elective open heart surgery were taken right atrial tissue fragments from 12 patients. All patients were operated because of acquired heart diseases- aortic valve stenosis (5 patients), coronary heart disease (5 patients), coronary heart disease and secondary mitral insufficiency (1 patient) and mitral disease (1 patient). The mean age was (mean±SD) 70,2±7,0 years (range 58-83 years). The tissues were stained with haematoxylin and eosin methods for routine light-microscopical examination and for immunohistochemical detection of protein gene peptide 9.5 (PGP 9.5), human atrial natriuretic peptide (hANUP), vascular endothelial growth factor (VEGF), chromogranin A and endothelin. Apoptosis was detected by TUNEL method. Results: All specimens showed degeneration of cardiomyocytes with lysis of myofibrils, diffuse vacuolization especially in perinuclear region, different size of cells and their nuclei. The severe invasion of connective tissue was observed in main part of all fragments. The apoptotic index ranged from 24 to 91%. One specimen showed region of newly performed microvessels with cube shaped endotheliocytes that were positive for PGP 9.5, endothelin, chromogranin A and VEGF. From all fragments, taken from patients with coronary heart disease, there were observed numerous PGP 9.5-containing nerve fibres, except in patient with secondary mitral insufficiency, who showed just few PGP 9.5 positive nerves. In majority of specimens there were regions observed with cube shaped mixed -VEGF immunoreactive endocardial and epicardial cells. Only VEGF positive endothelial cells were observed just in few specimens. There was no significant difference of hANUP secreting cells among all specimens. All patients operated due to the coronary heart disease moderate to numerous number of chromogranin A positive cells were seen while in patients with aortic valve stenosis tissue demonstrated just few factor positive cells. Conclusions: Complex detection of different factors may indicate selectively disordered morphopathogenetical event of heart disease: decrease of PGP 9.5 nerves suggests the decreased innervation of organ; increased apoptosis indicates the cell death without ingrowth of connective tissue; persistent presence of hANUP proves the unchanged homeostasis of cardiomyocytes probably supported by expression of chromogranins. Finally, decrease of VEGF detects the regions of affected blood vessels in heart affected by acquired heart disease.Keywords: heart, apoptosis, protein-gene peptide 9.5, atrial natriuretic peptide, vascular endothelial growth factor, chromogranin A, endothelin
Procedia PDF Downloads 293112 In vitro Evaluation of Immunogenic Properties of Oral Application of Rabies Virus Surface Glycoprotein Antigen Conjugated to Beta-Glucan Nanoparticles in a Mouse Model
Authors: Narges Bahmanyar, Masoud Ghorbani
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Rabies is caused by several species of the genus Lyssavirus in the Rhabdoviridae family. The disease is deadly encephalitis transmitted from warm-blooded animals to humans, and domestic and wild carnivores play the most crucial role in its transmission. The prevalence of rabies in poor areas of developing salinities is constantly posed as a global threat to public health. According to the World Health Organization, approximately 60,000 people die yearly from rabies. Of these, 60% of deaths are related to the Middle East. Although rabies encephalitis is incurable to date, awareness of the disease and the use of vaccines is the best way to combat the disease. Although effective vaccines are available, there is a high cost involved in vaccine production and management to combat rabies. Increasing the prevalence and discovery of new strains of rabies virus requires the need for safe, effective, and as inexpensive vaccines as possible. One of the approaches considered to achieve the quality and quantity expressed through the manufacture of recombinant types of rabies vaccine. Currently, livestock rabies vaccines are used only in inactivated or live attenuated vaccines, the process of inactivation of which pays attention to considerations. The rabies virus contains a negatively polarized single-stranded RNA genome that encodes the five major structural genes (N, P, M, G, L) from '3 to '5 . Rabies virus glycoprotein G, the major antigen, can produce the virus-neutralizing antibody. N-antigen is another candidate for developing recombinant vaccines. However, because it is within the RNP complex of the virus, the possibility of genetic diversity based on different geographical locations is very high. Glycoprotein G is structurally and antigenically more protected than other genes. Protection at the level of its nucleotide sequence is about 90% and at the amino acid level is 96%. Recombinant vaccines, consisting of a pathogenic subunit, contain fragments of the protein or polysaccharide of the pathogen that have been carefully studied to determine which of these molecules elicits a stronger and more effective immune response. These vaccines minimize the risk of side effects by limiting the immune system's access to the pathogen. Such vaccines are relatively inexpensive, easy to produce, and more stable than vaccines containing viruses or whole bacteria. The problem with these vaccines is that the pathogenic subunits may elicit a weak immune response in the body or may be destroyed before they reach the immune cells, which requires nanoparticles to overcome. Suitable for use as an adjuvant. Among these, biodegradable nanoparticles with functional levels are good candidates as adjuvants for the vaccine. In this study, we intend to use beta-glucan nanoparticles as adjuvants. The surface glycoprotein of the rabies virus (G) is responsible for identifying and binding the virus to the target cell. This glycoprotein is the major protein in the structure of the virus and induces an antibody response in the host. In this study, we intend to use rabies virus surface glycoprotein conjugated with beta-glucan nanoparticles to produce vaccines.Keywords: rabies, vaccines, beta glucan, nanoprticles, adjuvant, recombinant protein
Procedia PDF Downloads 15111 Machine Learning Based Digitalization of Validated Traditional Cognitive Tests and Their Integration to Multi-User Digital Support System for Alzheimer’s Patients
Authors: Ramazan Bakir, Gizem Kayar
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It is known that Alzheimer and Dementia are the two most common types of Neurodegenerative diseases and their visibility is getting accelerated for the last couple of years. As the population sees older ages all over the world, researchers expect to see the rate of this acceleration much higher. However, unfortunately, there is no known pharmacological cure for both, although some help to reduce the rate of cognitive decline speed. This is why we encounter with non-pharmacological treatment and tracking methods more for the last five years. Many researchers, including well-known associations and hospitals, lean towards using non-pharmacological methods to support cognitive function and improve the patient’s life quality. As the dementia symptoms related to mind, learning, memory, speaking, problem-solving, social abilities and daily activities gradually worsen over the years, many researchers know that cognitive support should start from the very beginning of the symptoms in order to slow down the decline. At this point, life of a patient and caregiver can be improved with some daily activities and applications. These activities include but not limited to basic word puzzles, daily cleaning activities, taking notes. Later, these activities and their results should be observed carefully and it is only possible during patient/caregiver and M.D. in-person meetings in hospitals. These meetings can be quite time-consuming, exhausting and financially ineffective for hospitals, medical doctors, caregivers and especially for patients. On the other hand, digital support systems are showing positive results for all stakeholders of healthcare systems. This can be observed in countries that started Telemedicine systems. The biggest potential of our system is setting the inter-user communication up in the best possible way. In our project, we propose Machine Learning based digitalization of validated traditional cognitive tests (e.g. MOCA, Afazi, left-right hemisphere), their analyses for high-quality follow-up and communication systems for all stakeholders. R. Bakir and G. Kayar are with Gefeasoft, Inc, R&D – Software Development and Health Technologies company. Emails: ramazan, gizem @ gefeasoft.com This platform has a high potential not only for patient tracking but also for making all stakeholders feel safe through all stages. As the registered hospitals assign corresponding medical doctors to the system, these MDs are able to register their own patients and assign special tasks for each patient. With our integrated machine learning support, MDs are able to track the failure and success rates of each patient and also see general averages among similarly progressed patients. In addition, our platform also supports multi-player technology which helps patients play with their caregivers so that they feel much safer at any point they are uncomfortable. By also gamifying the daily household activities, the patients will be able to repeat their social tasks and we will provide non-pharmacological reminiscence therapy (RT – life review therapy). All collected data will be mined by our data scientists and analyzed meaningfully. In addition, we will also add gamification modules for caregivers based on Naomi Feil’s Validation Therapy. Both are behaving positively to the patient and keeping yourself mentally healthy is important for caregivers. We aim to provide a therapy system based on gamification for them, too. When this project accomplishes all the above-written tasks, patients will have the chance to do many tasks at home remotely and MDs will be able to follow them up very effectively. We propose a complete platform and the whole project is both time and cost-effective for supporting all stakeholders.Keywords: alzheimer’s, dementia, cognitive functionality, cognitive tests, serious games, machine learning, artificial intelligence, digitalization, non-pharmacological, data analysis, telemedicine, e-health, health-tech, gamification
Procedia PDF Downloads 136110 Estimation of State of Charge, State of Health and Power Status for the Li-Ion Battery On-Board Vehicle
Authors: S. Sabatino, V. Calderaro, V. Galdi, G. Graber, L. Ippolito
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Climate change is a rapidly growing global threat caused mainly by increased emissions of carbon dioxide (CO₂) into the atmosphere. These emissions come from multiple sources, including industry, power generation, and the transport sector. The need to tackle climate change and reduce CO₂ emissions is indisputable. A crucial solution to achieving decarbonization in the transport sector is the adoption of electric vehicles (EVs). These vehicles use lithium (Li-Ion) batteries as an energy source, making them extremely efficient and with low direct emissions. However, Li-Ion batteries are not without problems, including the risk of overheating and performance degradation. To ensure its safety and longevity, it is essential to use a battery management system (BMS). The BMS constantly monitors battery status, adjusts temperature and cell balance, ensuring optimal performance and preventing dangerous situations. From the monitoring carried out, it is also able to optimally manage the battery to increase its life. Among the parameters monitored by the BMS, the main ones are State of Charge (SoC), State of Health (SoH), and State of Power (SoP). The evaluation of these parameters can be carried out in two ways: offline, using benchtop batteries tested in the laboratory, or online, using batteries installed in moving vehicles. Online estimation is the preferred approach, as it relies on capturing real-time data from batteries while operating in real-life situations, such as in everyday EV use. Actual battery usage conditions are highly variable. Moving vehicles are exposed to a wide range of factors, including temperature variations, different driving styles, and complex charge/discharge cycles. This variability is difficult to replicate in a controlled laboratory environment and can greatly affect performance and battery life. Online estimation captures this variety of conditions, providing a more accurate assessment of battery behavior in real-world situations. In this article, a hybrid approach based on a neural network and a statistical method for real-time estimation of SoC, SoH, and SoP parameters of interest is proposed. These parameters are estimated from the analysis of a one-day driving profile of an electric vehicle, assumed to be divided into the following four phases: (i) Partial discharge (SoC 100% - SoC 50%), (ii) Partial discharge (SoC 50% - SoC 80%), (iii) Deep Discharge (SoC 80% - SoC 30%) (iv) Full charge (SoC 30% - SoC 100%). The neural network predicts the values of ohmic resistance and incremental capacity, while the statistical method is used to estimate the parameters of interest. This reduces the complexity of the model and improves its prediction accuracy. The effectiveness of the proposed model is evaluated by analyzing its performance in terms of square mean error (RMSE) and percentage error (MAPE) and comparing it with the reference method found in the literature.Keywords: electric vehicle, Li-Ion battery, BMS, state-of-charge, state-of-health, state-of-power, artificial neural networks
Procedia PDF Downloads 67109 Enhancing the Structural and Electrochemical Performance of Li-Rich Layered Metal Oxides Cathodes for Li-Ion Battery by Coating with the Active Material
Authors: Cyril O. Ehi-Eromosele, Ajayi Kayode
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The Li-rich layered metal oxides (LLO) are the most promising candidates for promising electrodes of high energy Li-ion battery (LIB). In literature, these electrode system has either been designed as a hetero-structure of the primary components (composite) or as a core-shell structure with improved electrochemistry reported for both configurations when compared with its primary components. With the on-going efforts to improve on the electrochemical performance of the LIB, it is important to investigate comparatively the structural and electrochemical characteristics of the core-shell like and ‘composite’ forms of these materials with the same compositions and synthesis conditions which could influence future engineering of these materials. Therefore, this study concerns the structural and electrochemical properties of the ‘composite’ and core-shell like LLO cathode materials with the same nominal composition of 0.5Li₂MnO₃-0.5LiNi₀.₅Mn₀.₃Co₀.₂O₂ (LiNi₀.₅Mn₀.₃Co₀.₂O₂ as core and Li₂MnO₃ as the shell). The results show that the core-shell sample (–CS) gave better electrochemical performance than the ‘composite’ sample (–C). Both samples gave the same initial charge capacity of ~300 mAh/g when cycled at 10 mA/g and comparable charge capacity (246 mAh/g for the –CS sample and 240 mAh/g for the –C sample) when cycled at 200 mA/g. However, the –CS sample gave a higher initial discharge capacity at both current densities. The discharge capacity of the –CS sample was 232 mAh/g and 164 mAh/g while the –C sample is 208 mAh/g and 143 mAh/g at the current densities of 10 mA/g and 200 mA/g, respectively. Electrochemical impedance spectroscopy (EIS) results show that the –CS sample generally exhibited a smaller resistance than the –C sample both for the uncycled and after 50th cycle. Detailed structural analysis is on-going, but preliminary results show that the –CS sample had bigger unit cell volume and a higher degree of cation mixing. The thermal stability of the –CS sample was higher than the –C sample. XPS investigation also showed that the pristine –C sample gave a more reactive surface (showing formation of carbonate species to a greater degree) which could result in the greater resistance seen in the EIS result. To reinforce the results obtained for the 0.5Li₂MnO₃-0.5LiNi₀.₅Mn₀.₃Co₀.₃O₂ composition, the same investigations were extended to another ‘composite’ and core-shell like LLO cathode materials also with the same nominal composition of 0.5Li₂MnO₃-0.5LiNi₀.₃Mn₀.₃Co₀.₃O₂. In this case, the aim was to determine the electrochemical performance of the material using a low Ni content (LiNi₀.₃Mn₀.₃Co₀.₃O₂) as the core to clarify the contributions of the core-shell configuration to the electrochemical performance of these materials. Ni-rich layered oxides show active catalytic surface leading to electrolyte oxidation resulting in poor thermal stability and cycle life. Here, the core-shell sample also gave better electrochemical performance than the ‘composite’ sample with 0.5Li₂MnO₃-0.5LiNi₀.₃Mn₀.₃Co₀.₃O₂ composition. Furthermore, superior electrochemical performance was also recorded for the core-shell like spinel modified LLO (0.5Li₂MnO₃-0.45LiNi₀.₅Mn₀.₃Co₀.₂O₂-0.05LiNi₀.₅Mn₁.₅O₄) when compared to the composite system. These results show that the core-shell configuration can generally be used to improve the structural and electrochemical properties of the LLO and spinel modified LLO materials.Keywords: lithium-ion battery, lithium rich oxide cathode, core-shell structure, composite structure
Procedia PDF Downloads 121108 Antimicrobial Properties of SEBS Compounds with Zinc Oxide and Zinc Ions
Authors: Douglas N. Simões, Michele Pittol, Vanda F. Ribeiro, Daiane Tomacheski, Ruth M. C. Santana
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The increasing demand of thermoplastic elastomers is related to the wide range of applications, such as automotive, footwear, wire and cable industries, adhesives and medical devices, cell phones, sporting goods, toys and others. These materials are susceptible to microbial attack. Moisture and organic matter present in some areas (such as shower area and sink), provide favorable conditions for microbial proliferation, which contributes to the spread of diseases and reduces the product life cycle. Compounds based on SEBS copolymers, poly(styrene-b-(ethylene-co-butylene)-b-styrene, are a class of thermoplastic elastomers (TPE), fully recyclable and largely used in domestic appliances like bath mats and tooth brushes (soft touch). Zinc oxide and zinc ions loaded in personal and home care products have become common in the last years due to its biocidal effect. In that sense, the aim of this study was to evaluate the effect of zinc as antimicrobial agent in compounds based on SEBS/polypropylene/oil/ calcite for use as refrigerator seals (gaskets), bath mats and sink squeegee. Two zinc oxides from different suppliers (ZnO-Pe and ZnO-WR) and one masterbatch of zinc ions (M-Zn-ion) were used in proportions of 0%, 1%, 3% and 5%. The compounds were prepared using a co-rotating double screw extruder (L/D ratio of 40/1 and 16 mm screw diameter). The extrusion parameters were kept constant for all materials. Tests specimens were prepared using the injection molding machine. A compound with no antimicrobial additive (standard) was also tested. Compounds were characterized by physical (density), mechanical (hardness and tensile properties) and rheological properties (melt flow rate - MFR). The Japan Industrial Standard (JIS) Z 2801:2010 was applied to evaluate antibacterial properties against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). The Brazilian Association of Technical Standards (ABNT) NBR 15275:2014 were used to evaluate antifungal properties against Aspergillus niger (A. niger), Aureobasidium pullulans (A. pullulans), Candida albicans (C. albicans), and Penicillium chrysogenum (P. chrysogenum). The microbiological assay showed a reduction over 42% in E. coli and over 49% in S. aureus population. The tests with fungi showed inconclusive results because the sample without zinc also demonstrated an inhibition of fungal development when tested against A. pullulans, C. albicans and P. chrysogenum. In addition, the zinc loaded samples showed worse results than the standard sample when tested against A. niger. The zinc addition did not show significant variation in mechanical properties. However, the density values increased with the rise in ZnO additives concentration, and had a little decrease in M-Zn-ion samples. Also, there were differences in the MFR results in all compounds compared to the standard.Keywords: antimicrobial, home device, SEBS, zinc
Procedia PDF Downloads 322107 Alternative Energy and Carbon Source for Biosurfactant Production
Authors: Akram Abi, Mohammad Hossein Sarrafzadeh
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Because of their several advantages over chemical surfactants, biosurfactants have given rise to a growing interest in the past decades. Advantages such as lower toxicity, higher biodegradability, higher selectivity and applicable at extreme temperature and pH which enables them to be used in a variety of applications such as: enhanced oil recovery, environmental and pharmaceutical applications, etc. Bacillus subtilis produces a cyclic lipopeptide, called surfactin, which is one of the most powerful biosurfactants with ability to decrease surface tension of water from 72 mN/m to 27 mN/m. In addition to its biosurfactant character, surfactin exhibits interesting biological activities such as: inhibition of fibrin clot formation, lyses of erythrocytes and several bacterial spheroplasts, antiviral, anti-tumoral and antibacterial properties. Surfactin is an antibiotic substance and has been shown recently to possess anti-HIV activity. However, application of biosurfactants is limited by their high production cost. The cost can be reduced by optimizing biosurfactant production using cheap feed stock. Utilization of inexpensive substrates and unconventional carbon sources like urban or agro-industrial wastes is a promising strategy to decrease the production cost of biosurfactants. With suitable engineering optimization and microbiological modifications, these wastes can be used as substrates for large-scale production of biosurfactants. As an effort to fulfill this purpose, in this work we have tried to utilize olive oil as second carbon source and also yeast extract as second nitrogen source to investigate the effect on both biomass and biosurfactant production improvement in Bacillus subtilis cultures. Since the turbidity of the culture was affected by presence of the oil, optical density was compromised and no longer could be used as an index of growth and biomass concentration. Therefore, cell Dry Weight measurements with applying necessary tactics for removing oil drops to prevent interference with biomass weight were carried out to monitor biomass concentration during the growth of the bacterium. The surface tension and critical micelle dilutions (CMD-1, CMD-2) were considered as an indirect measurement of biosurfactant production. Distinctive and promising results were obtained in the cultures containing olive oil compared to cultures without it: more than two fold increase in biomass production (from 2 g/l to 5 g/l) and considerable reduction in surface tension, down to 40 mN/m at surprisingly early hours of culture time (only 5hr after inoculation). This early onset of biosurfactant production in this culture is specially interesting when compared to the conventional cultures at which this reduction in surface tension is not obtained until 30 hour of culture time. Reducing the production time is a very prominent result to be considered for large scale process development. Furthermore, these results can be used to develop strategies for utilization of agro-industrial wastes (such as olive oil mill residue, molasses, etc.) as cheap and easily accessible feed stocks to decrease the high costs of biosurfactant production.Keywords: agro-industrial waste, bacillus subtilis, biosurfactant, fermentation, second carbon and nitrogen source, surfactin
Procedia PDF Downloads 301106 Antimicrobial Activities of Lactic Acid Bacteria from Fermented Foods and Probiotic Products
Authors: Alec Chabwinja, Cannan Tawonezvi, Jerneja Vidmar, Constance Chingwaru, Walter Chingwaru
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Objective: To evaluate the potential of commercial fermented / probiotic products available in Zimbabwe or internationally, and strains of Lactobacillus plantarum (L. plantarum) as prophylaxis and therapy against diarrhoeal and sexually transmitted infections. Methods: The antimicrobial potential of cultures of lactobacilli enriched from 4 Zimbabwean commercial food/beverage products, namely Dairibord Lacto sour milk (DLSM), Probrand sour milk (PSM), Kefalos Vuka cheese (KVC) and Chibuku opaque beer (COB); three probiotic products obtainable in Europe and internationally; and four strains of L. plantarum obtained from Balkan traditional cheeses and Zimbabwean foods against clinical strains of Escherichia coli (E. coli) and non-clinical strains of Candida albicans and Rhodotorula spp. was assayed using the well diffusion method. Three commercial Agar diffusion assay and a competitive exclusion assay were carried out on Mueller-Hinton agar. Results: Crude cultures of putative lactobacillus strains obtained from Zimbabwean dairy products (Probrand sour milk, Kefalos Vuka vuka cheese and Chibuku opaque beer) exhibited significantly greater antimicrobial activities against clinical strains of E. coli than strains of L. plantarum isolated from Balkan cheeses (CLP1, CLP2 or CLP3) or crude microbial cultures from commercial paediatric probiotic products (BG, PJ and PL) of a culture of Lactobacillus rhamnosus LGG (p < 0.05). Furthermore, the following has high antifungal activities against the two yeasts: supernatant-free microbial pellet (SFMP) from an extract of M. azedarach leaves (27mm ± 2.5) > cell-free culture supernatants (CFCS) from Maaz Dairy sour milk and Mnandi sour milk (approximately 26mm ± 1.8) > CFCS and SFMP from Amansi hodzeko (25mm ± 1.5) > CFCS from Parinari curatellifolia fruit (24mm ± 1.5), SFMP from P. curatellifolia fruit (24mm ± 1.4) and SFMP from mahewu (20mm ± 1.5). These cultures also showed high tolerance to acidic conditions (~pH4). Conclusions: The putative lactobacilli from four commercial Zimbabwean dairy products (Probrand sour milk, Kefalos Vuka vuka cheese and Chibuku opaque beer), and three strains of L. plantarum from Balkan cheeses (CLP1, CLP2 or CLP3) exhibited high antibacterial activities, while Maaz Dairy sour-, Mnandi sour- and Amansi hodzeko milk products had high antifungal activities. Our selection of Zimbabwean probiotic products has potential for further development into probiotic products for use in the control diarrhea caused by pathogenic strains of E. coli or yeast infections. Studies to characterise the probiotic potential of the live cultures in the products are underway.Keywords: lactic acid bacteria, Staphylococcus aureus, Streptococcus spp, yeast, inhibition, acid tolerance
Procedia PDF Downloads 409105 Surface Acoustic Waves Nebulisation of Liposomes Manufactured in situ for Pulmonary Drug Delivery
Authors: X. King, E. Nazarzadeh, J. Reboud, J. Cooper
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Pulmonary diseases, such as asthma, are generally treated by the inhalation of aerosols that has the advantage of reducing the off-target (e.g., toxicity) effects associated with systemic delivery in blood. Effective respiratory drug delivery requires a droplet size distribution between 1 and 5 µm. Inhalation of aerosols with wide droplet size distribution, out of this range, results in deposition of drug in not-targeted area of the respiratory tract, introducing undesired side effects on the patient. In order to solely deliver the drug in the lower branches of the lungs and release it in a targeted manner, a control mechanism to produce the aerosolized droplets is required. To regulate the drug release and to facilitate the uptake from cells, drugs are often encapsulated into protective liposomes. However, a multistep process is required for their formation, often performed at the formulation step, therefore limiting the range of available drugs or their shelf life. Using surface acoustic waves (SAWs), a pulmonary drug delivery platform was produced, which enabled the formation of defined size aerosols and the formation of liposomes in situ. SAWs are mechanical waves, propagating along the surface of a piezoelectric substrate. They were generated using an interdigital transducer on lithium niobate with an excitation frequency of 9.6 MHz at a power of 1W. Disposable silicon superstrates were etched using photolithography and dry etch processes to create an array of cylindrical through-holes with different diameters and pitches. Superstrates were coupled with the SAW substrate through water-based gel. As the SAW propagates on the superstrate, it enables nebulisation of a lipid solution deposited onto it. The cylindrical cavities restricted the formation of large drops in the aerosol, while at the same time unilamellar liposomes were created. SAW formed liposomes showed a higher monodispersity compared to the control sample, as well as displayed, a faster production rate. To test the aerosol’s size, dynamic light scattering and laser diffraction methods were used, both showing the size control of the aerosolised particles. The use of silicon superstate with cavity size of 100-200 µm, produced an aerosol with a mean droplet size within the optimum range for pulmonary drug delivery, containing the liposomes in which the medicine could be loaded. Additionally, analysis of liposomes with Cryo-TEM showed formation of vesicles with narrow size distribution between 80-100 nm and optimal morphology in order to be used for drug delivery. Encapsulation of nucleic acids in liposomes through the developed SAW platform was also investigated. In vitro delivery of siRNA and DNA Luciferase were achieved using A549 cell line, lung carcinoma from human. In conclusion, SAW pulmonary drug delivery platform was engineered, in order to combine multiple time consuming steps (formation of liposomes, drug loading, nebulisation) into a unique platform with the aim of specifically delivering the medicament in a targeted area, reducing the drug’s side effects.Keywords: acoustics, drug delivery, liposomes, surface acoustic waves
Procedia PDF Downloads 122104 Targeting Apoptosis by Novel Adamantane Analogs as an Emerging Therapy for the Treatment of Hepatocellular Carcinoma Through EGFR, Bcl-2/BAX Cascade
Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam
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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.Keywords: adamantane, EGFR, HCC, apoptosis
Procedia PDF Downloads 144103 Interdigitated Flexible Li-Ion Battery by Aerosol Jet Printing
Authors: Yohann R. J. Thomas, Sébastien Solan
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Conventional battery technology includes the assembly of electrode/separator/electrode by standard techniques such as stacking or winding, depending on the format size. In that type of batteries, coating or pasting techniques are only used for the electrode process. The processes are suited for large scale production of batteries and perfectly adapted to plenty of application requirements. Nevertheless, as the demand for both easier and cost-efficient production modes, flexible, custom-shaped and efficient small sized batteries is rising. Thin-film, printable batteries are one of the key areas for printed electronics. In the frame of European BASMATI project, we are investigating the feasibility of a new design of lithium-ion battery: interdigitated planar core design. Polymer substrate is used to produce bendable and flexible rechargeable accumulators. Direct fully printed batteries lead to interconnect the accumulator with other electronic functions for example organic solar cells (harvesting function), printed sensors (autonomous sensors) or RFID (communication function) on a common substrate to produce fully integrated, thin and flexible new devices. To fulfill those specifications, a high resolution printing process have been selected: Aerosol jet printing. In order to fit with this process parameters, we worked on nanomaterials formulation for current collectors and electrodes. In addition, an advanced printed polymer-electrolyte is developed to be implemented directly in the printing process in order to avoid the liquid electrolyte filling step and to improve safety and flexibility. Results: Three different current collectors has been studied and printed successfully. An ink of commercial copper nanoparticles has been formulated and printed, then a flash sintering was applied to the interdigitated design. A gold ink was also printed, the resulting material was partially self-sintered and did not require any high temperature post treatment. Finally, carbon nanotubes were also printed with a high resolution and well defined patterns. Different electrode materials were formulated and printed according to the interdigitated design. For cathodes, NMC and LFP were efficaciously printed. For anodes, LTO and graphite have shown to be good candidates for the fully printed battery. The electrochemical performances of those materials have been evaluated in a standard coin cell with lithium-metal counter electrode and the results are similar with those of a traditional ink formulation and process. A jellified plastic crystal solid state electrolyte has been developed and showed comparable performances to classical liquid carbonate electrolytes with two different materials. In our future developments, focus will be put on several tasks. In a first place, we will synthesize and formulate new specific nano-materials based on metal-oxyde. Then a fully printed device will be produced and its electrochemical performance will be evaluated.Keywords: high resolution digital printing, lithium-ion battery, nanomaterials, solid-state electrolytes
Procedia PDF Downloads 248102 Integrative Omics-Portrayal Disentangles Molecular Heterogeneity and Progression Mechanisms of Cancer
Authors: Binder Hans
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Cancer is no longer seen as solely a genetic disease where genetic defects such as mutations and copy number variations affect gene regulation and eventually lead to aberrant cell functioning which can be monitored by transcriptome analysis. It has become obvious that epigenetic alterations represent a further important layer of (de-)regulation of gene activity. For example, aberrant DNA methylation is a hallmark of many cancer types, and methylation patterns were successfully used to subtype cancer heterogeneity. Hence, unraveling the interplay between different omics levels such as genome, transcriptome and epigenome is inevitable for a mechanistic understanding of molecular deregulation causing complex diseases such as cancer. This objective requires powerful downstream integrative bioinformatics methods as an essential prerequisite to discover the whole genome mutational, transcriptome and epigenome landscapes of cancer specimen and to discover cancer genesis, progression and heterogeneity. Basic challenges and tasks arise ‘beyond sequencing’ because of the big size of the data, their complexity, the need to search for hidden structures in the data, for knowledge mining to discover biological function and also systems biology conceptual models to deduce developmental interrelations between different cancer states. These tasks are tightly related to cancer biology as an (epi-)genetic disease giving rise to aberrant genomic regulation under micro-environmental control and clonal evolution which leads to heterogeneous cellular states. Machine learning algorithms such as self organizing maps (SOM) represent one interesting option to tackle these bioinformatics tasks. The SOMmethod enables recognizing complex patterns in large-scale data generated by highthroughput omics technologies. It portrays molecular phenotypes by generating individualized, easy to interpret images of the data landscape in combination with comprehensive analysis options. Our image-based, reductionist machine learning methods provide one interesting perspective how to deal with massive data in the discovery of complex diseases, gliomas, melanomas and colon cancer on molecular level. As an important new challenge, we address the combined portrayal of different omics data such as genome-wide genomic, transcriptomic and methylomic ones. The integrative-omics portrayal approach is based on the joint training of the data and it provides separate personalized data portraits for each patient and data type which can be analyzed by visual inspection as one option. The new method enables an integrative genome-wide view on the omics data types and the underlying regulatory modes. It is applied to high and low-grade gliomas and to melanomas where it disentangles transversal and longitudinal molecular heterogeneity in terms of distinct molecular subtypes and progression paths with prognostic impact.Keywords: integrative bioinformatics, machine learning, molecular mechanisms of cancer, gliomas and melanomas
Procedia PDF Downloads 148101 The Development of the Geological Structure of the Bengkulu Fore Arc Basin, Western Edge of Sundaland, Sumatra, and Its Relationship to Hydrocarbon Trapping Mechanism
Authors: Lauti Dwita Santy, Hermes Panggabean, Syahrir Andi Mangga
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The Bengkulu Basin is part of the Sunda Arc system, which is a classic convergent type margin that occur around the southern rim of the Eurasian continental (Sundaland) plate. The basin is located between deep sea trench (Mentawai Outer Arc high) and the volvanic/ magmatic Arc of the Barisan Mountains Range. To the northwest it is bounded by Padang High, to the northest by Barisan Mountains (Sumatra Fault Zone) to the southwest by Mentawai Fault Zone and to the southeast by Semangko High/ Sunda Strait. The stratigraphic succession and tectonic development can be broadly divided into four stage/ periods, i.e Late Jurassic- Early Cretaceous, Late Eocene-Early Oligocene, Late Oligocene-Early Miocene, Middle Miocene-Late Miocene and Pliocene-Plistocene, which are mainly controlled by the development of subduction activities. The Pre Tertiary Basement consist of sedimentary and shallow water limestone, calcareous mudstone, cherts and tholeiitic volcanic rocks, with Late Jurassic to Early Cretaceous in age. The sedimentation in this basin is depend on the relief of the Pre Tertiary Basement (Woyla Terrane) and occured into two stages, i.e. transgressive stage during the Latest Oligocene-Early Middle Miocene Seblat Formation, and the regressive stage during the Latest Middle Miocene-Pleistocene (Lemau, Simpangaur and Bintunan Formations). The Pre-Tertiary Faults were more intensive than the overlying cover, The Tertiary Rocks. There are two main fault trends can be distinguished, Northwest–Southwest Faults and Northeast-Southwest Faults. The NW-SE fault (Ketaun) are commonly laterally persistent, are interpreted to the part of Sumatran Fault Systems. They commonly form the boundaries to the Pre Tertiary basement highs and therefore are one of the faults elements controlling the geometry and development of the Tertiary sedimentary basins.The Northeast-Southwest faults was formed a conjugate set to the Northwest–Southeast Faults. In the earliest Tertiary and reactivated during the Plio-Pleistocene in a compressive mode with subsequent dextral displacement. The Block Faulting accross these two sets of faults related to approximate North–South compression in Paleogene time and produced a series of elongate basins separated by basement highs in the backarc and forearc region. The Bengkulu basin is interpreted having evolved from pull apart feature in the area southwest of the main Sumatra Fault System related to NW-SE trending in dextral shear.Based on Pyrolysis Yield (PY) vs Total Organic Carbon (TOC) diagram show that Seblat and Lemau Formation belongs to oil and Gas Prone with the quality of the source rocks includes into excellent and good (Lemau Formation), Fair and Poor (Seblat Formation). The fine-grained carbonaceous sediment of the Seblat dan Lemau Formations as source rocks, the coarse grained and carbonate sediments of the Seblat and Lemau Formations as reservoir rocks, claystone bed in Seblat and Lemau Formation as caprock. The source rocks maturation are late immature to early mature, with kerogen type II and III (Seblat Formation), and late immature to post mature with kerogen type I and III (Lemau Formation). The burial history show to 2500 m in depthh with paleo temperature reached 80oC. Trapping mechanism occur during Oligo–Miocene and Middle Miocene, mainly in block faulting system.Keywords: fore arc, bengkulu, sumatra, sundaland, hydrocarbon, trapping mechanism
Procedia PDF Downloads 557100 Conceptual Methods of Mitigating Matured Urban Tree Roots Surviving in Conflicts Growth within Built Environment: A Review
Authors: Mohd Suhaizan Shamsuddin
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Urbanization exacerbates the environment quality and pressures of matured urban trees' growth and development in changing environment. The growth of struggled matured urban tree-roots by spreading within the existences of infrastructures, resulting in large damage to the structured and declined growth. Many physiological growths declined or damages by the present and installations of infrastructures within and nearby root zone. Afford to remain both matured urban tree and infrastructures as a service provider causes damage and death, respectively. Inasmuch, spending more expenditure on fixing both or removing matured urban trees as risky to the future environment as the mitigation methods to reduce the problems are unconcerned. This paper aims to explain mitigation method practices of reducing the encountered problems of matured urban tree-roots settling and infrastructures while modified urban soil to sustain at an optimum level. Three categories capturing encountered conflicts growth of matured urban tree-roots growth within and nearby infrastructures by mitigating the problems of limited soil spaces, poor soil structures and soil space barrier installations and maintenance. The limited soil space encountered many conflicts and identified six methods that mitigate the survival tree-roots, such as soil volume/mounding, soil replacement/amendment for the radial trench, soil spacing-root bridge, root tunneling, walkway/pavement rising/diverted, and suspended pavement. The limited soil spaces are mitigation affords of inadequate soil-roots and spreading root settling and modification of construction soil media since the barrier existed and installed in root trails or zones. This is the reason for enabling tree-roots spreading and finds adequate sources (nutrients, water uptake and oxygen), spaces and functioning to stability stand of root anchorage since the matured tree grows larger. The poor soil structures were identified as three methods to mitigate soil materials' problems, and fewer soil voids comprise skeletal soil, structural soil, and soil cell. Mitigation of poor soil structure is altering the existing and introducing new structures by modifying the quantities and materials ratio allowing more voids beneath for roots spreading by considering the above structure of foot and vehicle traffics functioning or load-bearing. The soil space barrier installations and maintenance recognized to sustain both infrastructures and tree-roots grown in limited spaces and its benefits, the root barrier installations and root pruning are recommended. In conclusion, these recommended methods attempt to mitigate the present problems encountered at a particular place and problems among tree-roots and infrastructures exist. The combined method is the best way to alleviates the conflicts since the recognized conflicts are between tree-roots and man-made while the urban soil is modified. These presenting methods are most considered to sustain the matured urban trees' lifespan growth in the urban environment.Keywords: urban tree-roots, limited soil spaces, poor soil structures, soil space barrier and maintenance
Procedia PDF Downloads 19699 Biocompatible Hydrogel Materials Containing Cytostatics for Cancer Treatment
Authors: S. Kudlacik-Kramarczyk, M. Kedzierska, B. Tyliszczak
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Recently, the continuous development of medicine and related sciences has been observed. Particular emphasis is directed on the development of biomaterials, i.e., non-toxic, biocompatible and biodegradable materials that may improve the effectiveness of treatment as well as the comfort of patients. This is particularly important in the case of cancer treatment. Currently, there are many methods of cancer treatment based primarily on chemotherapy and the surgical removal of the tumor, but it is worth noting that these therapies also cause many side effects. Among women, the most common cancer is breast cancer. It may be completely cured, but the consequence of treatment is partial or complete breast mastectomy and radiation therapy, which results in severe skin burns. The skin of the patient after radiation therapy is very burned, and therefore requires intensive care and high frequency of dressing changes. The traditional dressing adheres to the burn wounds and does not absorb adequate amount of exudate from injuries and the patient is forced to change the dressing every 2 hours. Therefore, the main purpose was to develop an innovative combination of dressing material with drug carriers that may be used in anti-cancer therapy. The innovation of this solution is the combination of these two products into one system, i.e., a transdermal system with the possibility of a controlled release of the drug- cytostatic. Besides, the possibility of modifying the hydrogel matrix with aloe vera juice provides this material with new features favorable from the point of view of healing processes of burn wounds resulting from the radiation therapy. In this study, hydrogel materials containing protein spheres with the active substance have been obtained as a result of photopolymerization process. The reaction mixture consisting of the protein (albumin) spheres incorporated with cytostatic, chitosan, adequate crosslinking agent and photoinitiator has been subjected to the UV radiation for 2 minutes. Prepared materials have been subjected to the numerous studies including the analysis of cytotoxicity using murine fibroblasts L929. Analysis was conducted based on the mitochondrial activity test (MTT reduction assay) which involves the determining the number of cells characterized by proper metabolism. Hydrogel materials obtained using different amount of crosslinking agents have been subjected to the cytotoxicity analysis. According to the standards, tested material is defined as cytotoxic when the viability of cells after 24 h incubation with this material is lower than 70%. In the research, hydrogel polymer materials containing protein spheres incorporated with the active substance, i.e. a cytostatic, have been developed. Such a dressing may support the treatment of cancer due to the content of the anti-cancer drug - cytostatic, and may also provide a soothing effect on the healing of the burn wounds resulted from the radiation therapy due to the content of aloe vera juice in the hydrogel matrix. Based on the conducted cytotoxicity studies, it may be concluded that the obtained materials do not adversely affect the tested cell lines, therefore they can be subjected to more advanced analyzes.Keywords: hydrogel polymers, cytostatics, drug carriers, cytotoxicity
Procedia PDF Downloads 13198 Coastal Foodscapes as Nature-Based Coastal Regeneration Systems
Authors: Gulce Kanturer Yasar, Hayriye Esbah Tuncay
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Cultivated food production systems have coexisted harmoniously with nature for thousands of years through ancient techniques. Based on this experience, experimentation, and discovery, these culturally embedded methods have evolved to sustain food production, restore ecosystems, and harmoniously adapt to nature. In this era, as we seek solutions to food security challenges, enhancing and repairing our food production systems is crucial, making them more resilient to future disasters without harming the ecosystem. Instead of unsustainable conventional systems with ongoing destructive effects, we must investigate innovative and restorative production systems that integrate ancient wisdom and technology. Whether we consider agricultural fields, pastures, forests, coastal wetland ecosystems, or lagoons, it is crucial to harness the potential of these natural resources in addressing future global challenges, fostering both socio-economic resilience and ecological sustainability through strategic organization for food production. When thoughtfully designed and managed, marine-based food production has the potential to function as a living infrastructure system that addresses social and environmental challenges despite its known adverse impacts on the environment and local economies. These areas are also stages of daily life, vibrant hubs where local culture is produced and shared, contributing to the distinctive rural character of coastal settlements and exhibiting numerous spatial expressions of public nature. When we consider the history of humanity, indigenous communities have engaged in these sustainable production practices that provide goods for food, trade, culture, and the environment for many ages. Ecosystem restoration and socio-economic resilience can be achieved by combining production techniques based on ecological knowledge developed by indigenous societies with modern technologies. Coastal lagoons are highly productive coastal features that provide various natural services and societal values. They are especially vulnerable to severe physical, ecological, and social impacts of changing, challenging global conditions because of their placement within the coastal landscape. Coastal lagoons are crucial in sustaining fisheries productivity, providing storm protection, supporting tourism, and offering other natural services that hold significant value for society. Although there is considerable literature on the physical and ecological dimensions of lagoons, much less literature focuses on their economic and social values. This study will discuss the possibilities of coastal lagoons to achieve both ecologically sustainable and socio-economically resilient while maintaining their productivity by combining local techniques and modern technologies. The case study will present Turkey’s traditional aquaculture method, "Dalyans," predominantly operated by small-scale farmers in coastal lagoons. Due to human, ecological, and economic factors, dalyans are losing their landscape characteristics and efficiency. These 1000-year-old ancient techniques, rooted in centuries of traditional and agroecological knowledge, are under threat of tourism, urbanization, and unsustainable agricultural practices. Thus, Dalyans have diminished from 29 to approximately 4-5 active Dalyans. To deal with the adverse socio-economic and ecological consequences on Turkey's coastal areas, conserving Dalyans by protecting their indigenous practices while incorporating contemporary methods is essential. This study seeks to generate scenarios that envision the potential ways protection and development can manifest within case study areas.Keywords: coastal foodscape, lagoon aquaculture, regenerative food systems, watershed food networks
Procedia PDF Downloads 7297 Is Brain Death Reversal Possible in Near Future: Intrathecal Sodium Nitroprusside (SNP) Superfusion in Brain Death Patients=The 10,000 Fold Effect
Authors: Vinod Kumar Tewari, Mazhar Husain, Hari Kishan Das Gupta
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Background: Primary or secondary brain death is also accompanied with vasospasm of the perforators other than tissue disruption & further exaggerates the anoxic damage, in the form of neuropraxia. In normal conditions the excitatory impulse propagates as anterograde neurotransmission (ANT) and at the level of synapse, glutamate activates NMDA receptors on postsynaptic membrane. Nitric oxide (NO) is produced by Nitric oxide Synthetase (NOS) in postsynaptic dendride or cell body and travels backwards across a chemical synapse to bind to the axon terminal of a presynaptic neuron for regulation of ANT this process is called as the retrograde neurotransmission (RNT). Thus the primary function of NO is RNT and the purpose of RNT is regulation of chemical neurotransmission at synapse. For this reason, RNT allows neural circuits to create feedback loops. The haem is the ligand binding site of NO receptor (sGC) at presynaptic membrane. The affinity of haem exhibits > 10,000-fold excess for NO than Oxygen (THE 10,000 FOLD EFFECT). In pathological conditions ANT, normal synaptic activity including RNT is absent. NO donors like sodium nitroprusside (SNP) releases NO by activating NOS at the level of postsynaptic area. NO now travels backwards across a chemical synapse to bind to the haem of NO receptor at axon terminal of a presynaptic neuron as in normal condition. NO now acts as impulse generator (at presynaptic membrane) thus bypasses the normal ANT. Also the arteriolar perforators are having Nitric Oxide Synthetase (NOS) at the adventitial side (outer border) on which sodium nitroprusside (SNP) acts; causing release of Nitric Oxide (NO) which vasodilates the perforators causing gush of blood in brain’s tissue and reversal of brain death. Objective: In brain death cases we only think for various transplantations but this study being a pilot study reverses some criteria of brain death by vasodilating the arteriolar perforators. To study the effect of intrathecal sodium nitroprusside (IT SNP) in cases of brain death in which: 1. Retrograde transmission = assessed by the hyperacute timings of reversal 2. The arteriolar perforator vasodilatation caused by NO and the maintenance of reversal of brain death reversal. Methods: 35 year old male, who became brain death after head injury and has not shown any signs of improvement after every maneuver for 6 hours, a single superfusion done by SNP via transoptic canal route for quadrigeminal cistern and cisternal puncture for IV ventricular with SNP done. Results: He showed spontaneous respiration (7 bouts) with TCD studies showing start of pulsations of various branches of common carotid arteries. Conclusions: In future we can give this SNP via transoptic canal route and in IV ventricle before declaring the body to be utilized for transplantations or dead or in broader way we can say that in near future it is possible to revert back from brain death or we have to modify our criterion.Keywords: brain death, intrathecal sodium nitroprusside, TCD studies, perforators, vasodilatations, retrograde transmission, 10, 000 fold effect
Procedia PDF Downloads 40096 Hexahydropyrimidine-2,4-Diones: Synthesis and Cytotoxic Activity
Authors: M. Koksal, T. Ozyazici, E. Gurdal, M. Yarım, E. Demirpolat, M. B. Y. Aycan
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The discovery of new drugs in cancer chemotherapy is still a major topic because of severe side effects, selectivity problems and resistance development potential of existing drugs. In recent years, combined anticancer therapies or multi-acting drugs are clinically preferred over traditional cytotoxic treatment, with the aim of avoiding resistance and toxic side effects. Arrangement of multi-acting targets can be carried out either by combination of several drugs with different mechanisms or by usage of a single chemical compound capable of regulating several targets of a disease with multiple factors. In literature, several pyrimidine and piperazine derivatives have been involved in the structure of many compounds which have been used as chemotherapeutic agents along with wide clinical applications. The aim of this study is to combine pyrimidine and piperazine core structures to research and develop novel piperazinylpyrimidine derivatives with selective cytotoxicity over cancer cells. In this study, a group of novel 6-fluorophenyl-3-[2-(substitutedpiperazinyl)ethyl] hexahydropyrimidine-2,4-dione derivatives designed to observe the desired anticancer activity due to pyrimidine and piperazine based scaffolds. Target compounds were obtained by the reaction of appropriate piperazine derivatives and 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione. The synthetic pathway of 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-dione was started with Rodionov reaction using aldehyde, malonic acid and ammonium acetate in ethanol. Isolated β-fluorophenyl-β-amino acids were treated with 2-chloroethylisocyanate in the presence of an aqueous sodium hydroxide solution at room temperature to yield the sodium salts of the corresponding ureido acids. By addition of a mineral acid, ureido acids were precipitated. Later, these ureido acids were refluxed in thionyl chloride to give the 6-(2/4-fluorophenyl)-3-(2-chloroethyl)hexahydropyrimidine-2,4-di-one which were furthermore treated with secondary amines. Structures of purified compounds were characterized with IR, 1H-NMR, 13C-NMR, mass spectroscopies and elemental analysis. All of the compounds gave satisfactory analytical and spectroscopic data, which were in full accordance with their depicted structures. In IR spectra of the compounds, N-H group was seen at 3230-3213 cm⁻¹. C-H was seen at 3100-2820 cm⁻¹ and C=O vibrational peaks were observed approximately at 1725 and 1665 cm⁻¹ in accordance with literature. In the NMR spectra of target compounds, the methylene protons of piperazine give two separate multiplet peaks around 3.5 and 4.5 ppm representing the successful N-alkylation of the structure. The cytotoxic activity of the synthesized compounds was investigated on human bronchial epithelial (BEAS 2B), lung (A549), colon adenocarcinoma (COLO205) and breast (MCF7) cell lines, by means of sulphorhodamine B (SRB) assays in triplicate. IC₅₀ values of the screened derivatives were found in range of 11.8-78 µM. This project was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 215S157).Keywords: cytotoxicity, hexahydropyrimidine, piperazine, sulphorhodamine B assay
Procedia PDF Downloads 15095 Geomechanics Properties of Tuzluca (Eastern. Turkey) Bedded Rock Salt and Geotechnical Safety
Authors: Mehmet Salih Bayraktutan
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Geomechanical properties of Rock Salt Deposits in Tuzluca Salt Mine Area (Eastern Turkey) are studied for modeling the operation- excavation strategy. The purpose of this research focused on calculating the critical value of span height- which will meet the safety requirements. The Mine Site Tuzluca Hills consist of alternating parallel bedding of Salt ( NaCl ) and Gypsum ( CaS04 + 2 H20) rocks. Rock Salt beds are more resistant than narrow Gypsum interlayers. Rock Salt beds formed almost 97 percent of the total height of the Hill. Therefore, the geotechnical safety of Galleries depends on the mechanical criteria of Rock Salt Cores. General deposition of Tuzluca Basin was finally completed by Tuzluca Evaporites, as for the uppermost stratigraphic unit. They are currently running mining operations performed by classic mechanical excavation, room and pillar method. Rooms and Pillars are currently experiencing an initial stage of fracturing in places. Geotechnical safety of the whole mining area evaluated by Rock Mass Rating (RMR), Rock Quality Designation (RQD) spacing of joints, and the interaction of groundwater and fracture system. In general, bedded rock salt Show large lateral deformation capacity (while deformation modulus stays in relative small values, here E= 9.86 GPa). In such litho-stratigraphic environments, creep is a critical mechanism in failure. Rock Salt creep rate in steady-state is greater than interbedding layers. Under long-lasted compressive stresses, creep may cause shear displacements, partly using bedding planes. Eventually, steady-state creep in time returns to accelerated stages. Uniaxial compression creep tests on specimens were performed to have an idea of rock salt strength. To give an idea, on Rock Salt cores, average axial strength and strain are found as 18 - 24 MPa and 0.43-0.45 %, respectively. Uniaxial Compressive strength of 26- 32 MPa, from bedded rock salt cores. Elastic modulus is comparatively low, but lateral deformation of the rock salt is high under the uniaxial compression stress state. Poisson ratio = 0.44, break load = 156 kN, cohesion c= 12.8 kg/cm2, specific gravity SG=2.17 gr/cm3. Fracture System; spacing of fractures, joints, faults, offsets are evaluated under acting geodynamic mechanism. Two sand beds, each 4-6 m thick, exist near to upper level and at the top of the evaporating sequence. They act as aquifers and keep infiltrated water on top for a long duration, which may result in the failure of roofs or pillars. Two major active seismic ( N30W and N70E ) striking Fault Planes and parallel fracture strands have seismically triggered moderate risk of structural deformation of rock salt bedding sequence. Earthquakes and Floods are two prevailing sources of geohazards in this region—the seismotectonic activity of the Mine Site based on the crossing framework of Kagizman Faults and Igdir Faults. Dominant Hazard Risk sources include; a) Weak mechanical properties of rock salt, gypsum, anhydrite beds-creep. b) Physical discontinuities cutting across the thick parallel layers of Evaporite Mass, c) Intercalated beds of weak cemented or loose sand, clayey sandy sediments. On the other hand, absorbing the effects of salt-gyps parallel bedded deposits on seismic wave amplitudes has a reducing effect on the Rock Mass.Keywords: bedded rock salt, creep, failure mechanism, geotechnical safety
Procedia PDF Downloads 18894 Effect of Toxic Metals Exposure on Rat Behavior and Brain Morphology: Arsenic, Manganese
Authors: Tamar Bikashvili, Tamar Lordkipanidze, Ilia Lazrishvili
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Heavy metals remain one of serious environmental problems due to their toxic effects. The effect of arsenic and manganese compounds on rat behavior and neuromorphology was studied. Wistar rats were assigned to four groups: rats in control group were given regular water, while rats in other groups drank water with final manganese concentration of 10 mg/L (group A), 20 mg/L (group B) and final arsenic concentration 68 mg/L (group C), respectively, for a month. To study exploratory and anxiety behavior and also to evaluate aggressive performance in “home cage” rats were tested in “Open Field” and to estimate learning and memory status multi-branched maze was used. Statistically significant increase of motor and oriental-searching activity in experimental groups was revealed by an open field test, which was expressed in increase of number of lines crossed, rearing and hole reflexes. Obtained results indicated the suppression of fear in rats exposed to manganese. Specifically, this was estimated by the frequency of getting to the central part of the open field. Experiments revealed that 30-day exposure to 10 mg/ml manganese did not stimulate aggressive behavior in rats, while exposure to the higher dose (20 mg/ml), 37% of initially non-aggressive animals manifested aggressive behavior. Furthermore, 25% of rats were extremely aggressive. Obtained data support the hypothesis that excess manganese in the body is one of the immediate causes of enhancement of interspecific predatory aggressive and violent behavior in rats. It was also discovered that manganese intoxication produces non-reversible severe learning disability and insignificant, reversible memory disturbances. Studies of rodents exposed to arsenic also revealed changes in the learning process. As it is known, the distribution of metal ions differs in various brain regions. The principle manganese accumulation was observed in the hippocampus and in the neocortex, while arsenic was predominantly accumulated in nucleus accumbens, striatum, and cortex. These brain regions play an important role in the regulation of emotional state and motor activity. Histopathological analyzes of brain sections illustrated two morphologically distinct altered phenotypes of neurons: (1) shrunk cells with indications of apoptosis - nucleus and cytoplasm were very difficult to be distinguished, the integrity of neuronal cytoplasm was not disturbed; and (2) swollen cells - with indications of necrosis. Pyknotic nucleus, plasma membrane disruption and cytoplasmic vacuoles were observed in swollen neurons and they were surrounded by activated gliocytes. It’s worth to mention that in the cortex the majority of damaged neurons were apoptotic while in subcortical nuclei –neurons were mainly necrotic. Ultrastructural analyses demonstrated that all cell types in the cortex and the nucleus caudatus represent destructed mitochondria, widened neurons’ vacuolar system profiles, increased number of lysosomes and degeneration of axonal endings.Keywords: arsenic, manganese, behavior, learning, neuron
Procedia PDF Downloads 35893 Hybrid Renewable Energy Systems for Electricity and Hydrogen Production in an Urban Environment
Authors: Same Noel Ngando, Yakub Abdulfatai Olatunji
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Renewable energy micro-grids, such as those powered by solar or wind energy, are often intermittent in nature. This means that the amount of energy generated by these systems can vary depending on weather conditions or other factors, which can make it difficult to ensure a steady supply of power. To address this issue, energy storage systems have been developed to increase the reliability of renewable energy micro-grids. Battery systems have been the dominant energy storage technology for renewable energy micro-grids. Batteries can store large amounts of energy in a relatively small and compact package, making them easy to install and maintain in a micro-grid setting. Additionally, batteries can be quickly charged and discharged, allowing them to respond quickly to changes in energy demand. However, the process involved in recycling batteries is quite costly and difficult. An alternative energy storage system that is gaining popularity is hydrogen storage. Hydrogen is a versatile energy carrier that can be produced from renewable energy sources such as solar or wind. It can be stored in large quantities at low cost, making it suitable for long-distance mass storage. Unlike batteries, hydrogen does not degrade over time, so it can be stored for extended periods without the need for frequent maintenance or replacement, allowing it to be used as a backup power source when the micro-grid is not generating enough energy to meet demand. When hydrogen is needed, it can be converted back into electricity through a fuel cell. Energy consumption data is got from a particular residential area in Daegu, South Korea, and the data is processed and analyzed. From the analysis, the total energy demand is calculated, and different hybrid energy system configurations are designed using HOMER Pro (Hybrid Optimization for Multiple Energy Resources) and MATLAB software. A techno-economic and environmental comparison and life cycle assessment (LCA) of the different configurations using battery and hydrogen as storage systems are carried out. The various scenarios included PV-hydrogen-grid system, PV-hydrogen-grid-wind, PV-hydrogen-grid-biomass, PV-hydrogen-wind, PV-hydrogen-biomass, biomass-hydrogen, wind-hydrogen, PV-battery-grid-wind, PV- battery -grid-biomass, PV- battery -wind, PV- battery -biomass, and biomass- battery. From the analysis, the least cost system for the location was the PV-hydrogen-grid system, with a net present cost of about USD 9,529,161. Even though all scenarios were environmentally friendly, taking into account the recycling cost and pollution involved in battery systems, all systems with hydrogen as a storage system produced better results. In conclusion, hydrogen is becoming a very prominent energy storage solution for renewable energy micro-grids. It is easier to store compared with electric power, so it is suitable for long-distance mass storage. Hydrogen storage systems have several advantages over battery systems, including flexibility, long-term stability, and low environmental impact. The cost of hydrogen storage is still relatively high, but it is expected to decrease as more hydrogen production, and storage infrastructure is built. With the growing focus on renewable energy and the need to reduce greenhouse gas emissions, hydrogen is expected to play an increasingly important role in the energy storage landscape.Keywords: renewable energy systems, microgrid, hydrogen production, energy storage systems
Procedia PDF Downloads 9292 Biosurfactants Produced by Antarctic Bacteria with Hydrocarbon Cleaning Activity
Authors: Claudio Lamilla, Misael Riquelme, Victoria Saez, Fernanda Sepulveda, Monica Pavez, Leticia Barrientos
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Biosurfactants are compounds synthesized by microorganisms that show various chemical structures, including glycolipids, lipopeptides, polysaccharide-protein complex, phospholipids, and fatty acids. These molecules have attracted attention in recent years due to the amphipathic nature of these compounds, which allows their application in various activities related to emulsification, foaming, detergency, wetting, dispersion and solubilization of hydrophobic compounds. Microorganisms that produce biosurfactants are ubiquitous, not only present in water, soil, and sediments but in extreme conditions of pH, salinity or temperature such as those present in Antarctic ecosystems. Due to this, it is of interest to study biosurfactants producing bacterial strains isolated from Antarctic environments, with the potential to be used in various biotechnological processes. The objective of this research was to characterize biosurfactants produced by bacterial strains isolated from Antarctic environments, with potential use in biotechnological processes for the cleaning of sites contaminated with hydrocarbons. The samples were collected from soils and sediments in the South Shetland Islands and the Antarctic Peninsula, during the Antarctic Research Expedition INACH 2016, from both pristine and human occupied areas (influenced). The bacteria isolation was performed from solid R2A, M1 and LB media. The selection of strains producing biosurfactants was done by hemolysis test on blood agar plates (5%) and blue agar (CTAB). From 280 isolates, it was determined that 10 bacterial strains produced biosurfactants after stimulation with different carbon sources. 16S rDNA taxonomic markers, using the universal primers 27F-1492R, were used to identify these bacterias. Biosurfactants production was carried out in 250 ml flasks using Bushnell Hass liquid culture medium enriched with different carbon sources (olive oil, glucose, glycerol, and hexadecane) during seven days under constant stirring at 20°C. Each cell-free supernatant was characterized by physicochemical parameters including drop collapse, emulsification and oil displacement, as well as stability at different temperatures, salinity, and pH. In addition, the surface tension of each supernatant was quantified using a tensiometer. The strains with the highest activity were selected, and the production of biosurfactants was stimulated in six liters of culture medium. Biosurfactants were extracted from the supernatants with chloroform methanol (2:1). These biosurfactants were tested against crude oil and motor oil, to evaluate their displacement activity (detergency). The characterization by physicochemical properties of 10 supernatants showed that 80% of them produced the drop collapse, 60% had stability at different temperatures, and 90% had detergency activity in motor and olive oil. The biosurfactants obtained from two bacterial strains showed a high activity of dispersion of crude oil and motor oil with halos superior to 10 cm. We can conclude that bacteria isolated from Antarctic soils and sediments provide biological material of high quality for the production of biosurfactants, with potential applications in the biotechnological industry, especially in hydrocarbons -contaminated areas such as petroleum.Keywords: antarctic, bacteria, biosurfactants, hydrocarbons
Procedia PDF Downloads 27891 Influence of the Use of Fruits Byproducts on the Lipid Profile of Hermetia illucens, Tenebrio molitor and Zophoba morio Larvae
Authors: Rebeca P Ramos-Bueno, Maria Jose Gonzalez-Fernandez, Rosa M. Moreno-Zamora, Antonia Barros Heras, Yolanda Serrano Alonso, Carolina Sanchez Barranco
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Insects are a new source of fatty acids (FA), so they are considered a sustainable and environmentally friendly alternative for both animal feed and the human diet, and furthermore, their harvesting/rearing require a low-tech and low capital investment. For that reason, lipids obtained by insect breeding open interesting possibilities with alimentary and industrial purposes, i.e., the production of biodiesel. Particularly, certain insect species, especially during the larval stage, contain high proportions of fat which is highly dependent on their feed and stage of development. Among them, Hermetia illucens larvae can be bred on food wastes to produce fat- and protein-rich raw materials for food by-product management. So, insects can act as excellent bioconverters of organic waste to nutrient-rich materials. In this regard, the aim of the study was to evaluate the effects of fruit byproducts on the FA compositions of Tenebrio molitor, Zophoba morio, and H. illucens larvae. Firstly, oil was extracted with the green solvent ethyl acetate, and FA methyl ester was obtained and analyzed by GC to show the FA profile. In addition, the triacylglycerol (TAG) profile was obtained by HPLC. Dehydrated watermelon, tomato, and papaya by-products, as well as wheat-based control feed, were assayed. High FA content was reached by Z. morio larvae fed with all fruits; however, no differences were shown in lipid profile with any change. It is worth highlighting that both Z. morio and H. illucens could be selected as the best candidates for biodiesel production due to their high content of saturated FA. On the other hand, T. molitor larvae showed a higher content of monounsaturated FA than control larvae, whereas the n-6 polyunsaturated FA content decreased in larvae fed with fruits. This result indicates that the improvement of the FA profile of Tenebrio can depend on both the type of feeding and the intended use. The lipid profile of H. illucens larvae fed with papaya and tomato showed a slight increase in the content of α-linoleic acid (ALA, 18:3n3). This FA is the precursor of docosahexaenoic acid (DHA, 22:6n3), which plays an important role as a component of structural lipids in cell membranes as well as in the synthesis of eicosanoids, protecting and resolving. Also, it was evaluated the TAG profile of Z. morio larvae due to their highest oil content. The results showed a high oleic acid (OA, 18:1n9) content, which displays modulatory effects in a wide range of physiological functions, having anti-inflammatory and anti-atherogenic properties. In conclusion, this study clearly shows that Z. morio and H. illucens larvae constitute an alternative source of OA- and ALA-rich oils, respectively, which can be devoted for food use, as well as for using in the food and pharmaceutical industries, with agronomic implications. Finally, although the profile of Z. morio was not improved with fruit feeding, this kind of feeding could be used due to its low environmental impact.Keywords: fatty acids, fruit byproducts, Hermetia illucens, Zophoba morio, Tenebrio molitor, insect rearing
Procedia PDF Downloads 14690 Oblique Radiative Solar Nano-Polymer Gel Coating Heat Transfer and Slip Flow: Manufacturing Simulation
Authors: Anwar Beg, Sireetorn Kuharat, Rashid Mehmood, Rabil Tabassum, Meisam Babaie
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Nano-polymeric solar paints and sol-gels have emerged as a major new development in solar cell/collector coatings offering significant improvements in durability, anti-corrosion and thermal efficiency. They also exhibit substantial viscosity variation with temperature which can be exploited in solar collector designs. Modern manufacturing processes for such nano-rheological materials frequently employ stagnation flow dynamics under high temperature which invokes radiative heat transfer. Motivated by elaborating in further detail the nanoscale heat, mass and momentum characteristics of such sol gels, the present article presents a mathematical and computational study of the steady, two-dimensional, non-aligned thermo-fluid boundary layer transport of copper metal-doped water-based nano-polymeric sol gels under radiative heat flux. To simulate real nano-polymer boundary interface dynamics, thermal slip is analysed at the wall. A temperature-dependent viscosity is also considered. The Tiwari-Das nanofluid model is deployed which features a volume fraction for the nanoparticle concentration. This approach also features a Maxwell-Garnet model for the nanofluid thermal conductivity. The conservation equations for mass, normal and tangential momentum and energy (heat) are normalized via appropriate transformations to generate a multi-degree, ordinary differential, non-linear, coupled boundary value problem. Numerical solutions are obtained via the stable, efficient Runge-Kutta-Fehlberg scheme with shooting quadrature in MATLAB symbolic software. Validation of solutions is achieved with a Variational Iterative Method (VIM) utilizing Langrangian multipliers. The impact of key emerging dimensionless parameters i.e. obliqueness parameter, radiation-conduction Rosseland number (Rd), thermal slip parameter (α), viscosity parameter (m), nanoparticles volume fraction (ϕ) on non-dimensional normal and tangential velocity components, temperature, wall shear stress, local heat flux and streamline distributions is visualized graphically. Shear stress and temperature are boosted with increasing radiative effect whereas local heat flux is reduced. Increasing wall thermal slip parameter depletes temperatures. With greater volume fraction of copper nanoparticles temperature and thermal boundary layer thickness is elevated. Streamlines are found to be skewed markedly towards the left with positive obliqueness parameter.Keywords: non-orthogonal stagnation-point heat transfer, solar nano-polymer coating, MATLAB numerical quadrature, Variational Iterative Method (VIM)
Procedia PDF Downloads 13389 Colocalization Analysis to Understand Yttrium Uptake in Saxifraga paniculata Using Complementary Imaging Technics
Authors: Till Fehlauer, Blanche Collin, Bernard Angeletti, Andrea Somogyi, Claire Lallemand, Perrine Chaurand, Cédric Dentant, Clement Levard, Jerome Rose
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Over the last decades, yttrium (Y) has gained importance in high-tech applications. It is an essential part of alloys and compounds used for lasers, displays, or cell phones, for example. Due to its chemical similarities with the lanthanides, Y is often considered a rare earth element (REE). Despite their increased usage, the environmental behavior of REEs remains poorly understood. Especially regarding their interactions with plants, many uncertainties exist. On the one hand, Y is known to have a negative effect on root development and germination, but on the other hand, it appears to promote plant growth at low concentrations. In order to understand these phenomena, a precise knowledge is necessary about how Y is absorbed by the plant and how it is handled once inside the organism. Contradictory studies exist, stating that due to a similar ionic radius, Y and the other REEs might be absorbed through Ca²⁺-channels, while others suspect that Y has a shared pathway with Al³⁺. In this study, laser ablation coupled ICP-MS, and synchrotron-based micro-X-ray fluorescence (µXRF, beamline Nanoscopium, SOLEIL, France) have been used in order to localize Y within the plant tissue and identify associated elements. The plant used in this study is Saxifraga paniculata, a rugged alpine plant that has shown an affinity for Y in previous studies (in prep.). Furthermore, Saxifraga paniculata performs guttation, which means that it possesses phloem sap secreting openings on the leaf surface that serve to regulate root pressure. These so-called hydathodes could provide special insights in elemental transport in plants. The plants have been grown on Y doped soil (500mg/kg DW) for four months. The results showed that Y was mainly concentrated in the roots of Saxifraga paniculata (260 ± 85mg/kg), and only a small amount was translocated to the leaves (10 ± 7.8mg/kg). µXRF analysis indicated that within the root transects, the majority of Y remained in the epidermis and hardly penetrated the stele. Laser ablation coupled ICP-MS confirmed this finding and showed a positive correlation in the roots between Y, Fe, Al, and to a lesser extent Ca. In the stem transect, Y was mainly detected in a hotspot of approximately 40µm in diameter situated in the endodermis area. Within the stem and especially in the hotspot, Y was highly colocalized with Al and Fe. Similar-sized Y hotspots have been detected in/on the leaves. All of them were strongly colocalized with Al and Fe, except for those situated within the hydathodes, which showed no colocalization with any of the measured elements. Accordingly, a relation between Y and Ca during root uptake remains possible, whereas a correlation to Fe and Al appears to be dominant in the aerial parts, suggesting common storage compartments, the formation of complexes, or a shared pathway during translocation.Keywords: laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), Phytoaccumulation, Rare earth elements, Saxifraga paniculata, Synchrotron-based micro-X-ray fluorescence, Yttrium
Procedia PDF Downloads 14888 Mathematical Modeling of Avascular Tumor Growth and Invasion
Authors: Meitham Amereh, Mohsen Akbari, Ben Nadler
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Cancer has been recognized as one of the most challenging problems in biology and medicine. Aggressive tumors are a lethal type of cancers characterized by high genomic instability, rapid progression, invasiveness, and therapeutic resistance. Their behavior involves complicated molecular biology and consequential dynamics. Although tremendous effort has been devoted to developing therapeutic approaches, there is still a huge need for new insights into the dark aspects of tumors. As one of the key requirements in better understanding the complex behavior of tumors, mathematical modeling and continuum physics, in particular, play a pivotal role. Mathematical modeling can provide a quantitative prediction on biological processes and help interpret complicated physiological interactions in tumors microenvironment. The pathophysiology of aggressive tumors is strongly affected by the extracellular cues such as stresses produced by mechanical forces between the tumor and the host tissue. During the tumor progression, the growing mass displaces the surrounding extracellular matrix (ECM), and due to the level of tissue stiffness, stress accumulates inside the tumor. The produced stress can influence the tumor by breaking adherent junctions. During this process, the tumor stops the rapid proliferation and begins to remodel its shape to preserve the homeostatic equilibrium state. To reach this, the tumor, in turn, upregulates epithelial to mesenchymal transit-inducing transcription factors (EMT-TFs). These EMT-TFs are involved in various signaling cascades, which are often associated with tumor invasiveness and malignancy. In this work, we modeled the tumor as a growing hyperplastic mass and investigated the effects of mechanical stress from surrounding ECM on tumor invasion. The invasion is modeled as volume-preserving inelastic evolution. In this framework, principal balance laws are considered for tumor mass, linear momentum, and diffusion of nutrients. Also, mechanical interactions between the tumor and ECM is modeled using Ciarlet constitutive strain energy function, and dissipation inequality is utilized to model the volumetric growth rate. System parameters, such as rate of nutrient uptake and cell proliferation, are obtained experimentally. To validate the model, human Glioblastoma multiforme (hGBM) tumor spheroids were incorporated inside Matrigel/Alginate composite hydrogel and was injected into a microfluidic chip to mimic the tumor’s natural microenvironment. The invasion structure was analyzed by imaging the spheroid over time. Also, the expression of transcriptional factors involved in invasion was measured by immune-staining the tumor. The volumetric growth, stress distribution, and inelastic evolution of tumors were predicted by the model. Results showed that the level of invasion is in direct correlation with the level of predicted stress within the tumor. Moreover, the invasion length measured by fluorescent imaging was shown to be related to the inelastic evolution of tumors obtained by the model.Keywords: cancer, invasion, mathematical modeling, microfluidic chip, tumor spheroids
Procedia PDF Downloads 11087 Altered Proteostasis Contributes to Skeletal Muscle Atrophy during Chronic Hypobaric Hypoxia: An Insight into Signaling Mechanisms
Authors: Akanksha Agrawal, Richa Rathor, Geetha Suryakumar
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Muscle represents about ¾ of the body mass, and a healthy muscular system is required for human performance. A healthy muscular system is dynamically balanced via the catabolic and anabolic process. High altitude associated hypoxia altered this redox balance via producing reactive oxygen and nitrogen species that ultimately modulates protein structure and function, hence, disrupts proteostasis or protein homeostasis. The mechanism by which proteostasis is clinched includes regulated protein translation, protein folding, and protein degradation machinery. Perturbation in any of these mechanisms could increase proteome imbalance in the cellular processes. Altered proteostasis in skeletal muscle is likely to be responsible for contributing muscular atrophy in response to hypoxia. Therefore, we planned to elucidate the mechanism involving altered proteostasis leading to skeletal muscle atrophy under chronic hypobaric hypoxia. Material and Methods-Male Sprague Dawley rats weighing about 200-220 were divided into five groups - Control (Normoxic animals), 1d, 3d, 7d and 14d hypobaric hypoxia exposed animals. The animals were exposed to simulated hypoxia equivalent to 282 torr pressure (equivalent to an altitude of 7620m, 8% oxygen) at 25°C. On completion of chronic hypobaric hypoxia (CHH) exposure, rats were sacrificed, muscle was excised and biochemical, histopathological and protein synthesis signaling were studied. Results-A number of changes were observed with the CHH exposure time period. ROS was increased significantly on 07 and 14 days which were attributed to protein oxidation via damaging muscle protein structure by oxidation of amino acids moiety. The oxidative damage to the protein further enhanced the various protein degradation pathways. Calcium activated cysteine proteases and other intracellular proteases participate in protein turnover in muscles. Therefore, we analysed calpain and 20S proteosome activity which were noticeably increased at CHH exposure as compared to control group representing enhanced muscle protein catabolism. Since inflammatory markers (myokines) affect protein synthesis and triggers degradation machinery. So, we determined inflammatory pathway regulated under hypoxic environment. Other striking finding of the study was upregulation of Akt/PKB translational machinery that was increased on CHH exposure. Akt, p-Akt, p70 S6kinase, and GSK- 3β expression were upregulated till 7d of CHH exposure. Apoptosis related markers, caspase-3, caspase-9 and annexin V was also increased on CHH exposure. Conclusion: The present study provides evidence of disrupted proteostasis under chronic hypobaric hypoxia. A profound loss of muscle mass is accompanied by the muscle damage leading to apoptosis and cell death under CHH. These cellular stress response pathways may play a pivotal role in hypobaric hypoxia induced skeletal muscle atrophy. Further research in these signaling pathways will lead to development of therapeutic interventions for amelioration of hypoxia induced muscle atrophy.Keywords: Akt/PKB translational machinery, chronic hypobaric hypoxia, muscle atrophy, protein degradation
Procedia PDF Downloads 26886 Vascular Targeted Photodynamic Therapy Monitored by Real-Time Laser Speckle Imaging
Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz
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Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging
Procedia PDF Downloads 22285 Effectiveness of Peer Reproductive Health Education Program in Improving Knowledge, Attitude, and Use Health Service of High School Adolescent Girls in Eritrea in 2014
Authors: Ghidey Ghebreyohanes, Eltahir Awad Gasim Khalil, Zemenfes Tsighe, Faiza Ali
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Background: reproductive health (RH) is a state of physical, mental and social well-being in all matters relating to the reproductive system at all stages of life. In East Africa including Eritrea, adolescents comprise more than a quarter of the population. The region holds the highest rates of sexually transmitted diseases, HIV, unwanted pregnancy and unsafe abortion with its complications. Young girls carry the highest burden of reproductive health problems due to their risk taking behavior, lack of knowledge, peer pressure, physiologic immaturity and low socioeconomic status. Design: this was a Community-based, randomized, case-controlled and pre-test-post-test intervention study. Setting: Zoba Debub was randomly selected out of the six zobas in Eritrea. The four high schools out of the 26 in Zoba Debub were randomly selected as study target schools. Over three quarter of the people live on farming. The target population was female students attending grade nine with majority of these girls live in the distant villages and walk to school. The study participants were randomly selected (n=165) from each school. Furthermore, the 1 intervention and 3 controls for the study arms were assigned randomly. Objectives: this study aimed to assess the effectiveness of peer reproductive health education in improving knowledge, attitude, and health service use of high school adolescent girls in Eritrea Methods: the protocol was reviewed and approved by the Scientific and Ethics Committees of Faculty of Nursing Sciences, University of Khartoum. Data was collected using pre-designed and pretested questionnaire emphasizing on reproductive health knowledge, attitude and practice. Sample size was calculated using proportion formula (α 0.01; power of 95%). Measures used were scores and proportions. Descriptive and inferential statistics, t-test and chi square at (α .01), 99% confidence interval were used to compare changes of pre and post-intervention scores using SPSS soft ware. Seventeen students were selected for peer educators by the school principals and other teachers based on inclusion criteria that include: good academic performance and acceptable behavior. One peer educator educated one group composed of 8-10 students for two months. One faculty member was selected to supervise peer educators. The principal investigator conducted the training of trainers and provided supervision and discussion to peer educators every two weeks until the end of intervention. Results: following informed consent, 627 students [164 in intervention and 463 in the control group] with a ratio of 1 to 3, were enrolled in the study. The mean age for the total study population was 15.4±1.0 years. The intervention group mean age was 15.3±1.0 year; while the control group had a mean age of 15.4±1.0. The mean ages for the study arms were similar (p= 0.4). The majority (96 %) of the study participants are from Tigrigna ethnic group. Reproductive knowledge scores which was calculated out of a total 61 grade points: intervention group (pretest 6.7 %, post-test 33.6 %; p= 0.0001); control group (pretest 7.3 %, posttest 7.3 %, p= 0.92). Proportion difference in attitude calculated out of 100%: intervention group (pretest 42.3 % post test 54.7% p= 0.001); controls group (pretest 45%, post test 44.8 p= 0.7). Proportion difference in Practice calculated out of 100 %: intervention group (pretest 15.4%, post test 80.4 % p= 0.0001); control group (pretest 16.8%, posttest 16.9 % p= 0.8). Mothers were quoted as major (> 90 %) source of reproductive health information. All focus group discussants and most of survey participants agreed on the urgent need of reproductive health information and services for adolescent girls. Conclusion: reproductive health knowledge and use of facilities is poor among adolescent girls in sub-urban Eretria. School-based peer reproductive health education is effective and is the best strategy to improve reproductive health knowledge and attitudes.Keywords: reproductive health, adolescent girls, eretria, health education
Procedia PDF Downloads 36284 Case Study on Innovative Aquatic-Based Bioeconomy for Chlorella sorokiniana
Authors: Iryna Atamaniuk, Hannah Boysen, Nils Wieczorek, Natalia Politaeva, Iuliia Bazarnova, Kerstin Kuchta
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Over the last decade due to climate change and a strategy of natural resources preservation, the interest for the aquatic biomass has dramatically increased. Along with mitigation of the environmental pressure and connection of waste streams (including CO2 and heat emissions), microalgae bioeconomy can supply food, feed, as well as the pharmaceutical and power industry with number of value-added products. Furthermore, in comparison to conventional biomass, microalgae can be cultivated in wide range of conditions without compromising food and feed production, thus addressing issues associated with negative social and the environmental impacts. This paper presents the state-of-the art technology for microalgae bioeconomy from cultivation process to production of valuable components and by-streams. Microalgae Chlorella sorokiniana were cultivated in the pilot-scale innovation concept in Hamburg (Germany) using different systems such as race way pond (5000 L) and flat panel reactors (8 x 180 L). In order to achieve the optimum growth conditions along with suitable cellular composition for the further extraction of the value-added components, process parameters such as light intensity, temperature and pH are continuously being monitored. On the other hand, metabolic needs in nutrients were provided by addition of micro- and macro-nutrients into a medium to ensure autotrophic growth conditions of microalgae. The cultivation was further followed by downstream process and extraction of lipids, proteins and saccharides. Lipids extraction is conducted in repeated-batch semi-automatic mode using hot extraction method according to Randall. As solvents hexane and ethanol are used at different ratio of 9:1 and 1:9, respectively. Depending on cell disruption method along with solvents ratio, the total lipids content showed significant variations between 8.1% and 13.9 %. The highest percentage of extracted biomass was reached with a sample pretreated with microwave digestion using 90% of hexane and 10% of ethanol as solvents. Proteins content in microalgae was determined by two different methods, namely: Total Kejadahl Nitrogen (TKN), which further was converted to protein content, as well as Bradford method using Brilliant Blue G-250 dye. Obtained results, showed a good correlation between both methods with protein content being in the range of 39.8–47.1%. Characterization of neutral and acid saccharides from microalgae was conducted by phenol-sulfuric acid method at two wavelengths of 480 nm and 490 nm. The average concentration of neutral and acid saccharides under the optimal cultivation conditions was 19.5% and 26.1%, respectively. Subsequently, biomass residues are used as substrate for anaerobic digestion on the laboratory-scale. The methane concentration, which was measured on the daily bases, showed some variations for different samples after extraction steps but was in the range between 48% and 55%. CO2 which is formed during the fermentation process and after the combustion in the Combined Heat and Power unit can potentially be used within the cultivation process as a carbon source for the photoautotrophic synthesis of biomass.Keywords: bioeconomy, lipids, microalgae, proteins, saccharides
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