Search results for: packed cell volume
2531 Detection of Bcl2 Polymorphism in Patient with Hepatocellular carcinoma
Authors: Mohamed Abdel-Hamid, Olfat Gamil Shaker, Doha El-Sayed Ellakwa, Eman Fathy Abdel-Maksoud
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Introduction: Despite advances in the knowledge of the molecular virology of hepatitis C virus (HCV), the mechanisms of hepatocellular injury in HCV infection are not completely understood. Hepatitis C viral infection (HCV) influences the susceptibility to apoptosis. This could lead to insufficient antiviral immune response and persistent viral infection. Aim of this study: was to examine whether BCL-2 gene polymorphism at codon 43 (+127G/A or Ala43Thr) has an impact on development of hepatocellular carcinoma caused by chronic hepatitis C Egyptian patients. Subjects and Methods: The study included three groups; group 1: composing of 30 patients with hepatocellular carcinoma (HCC), group 2 composing of 30 patients with HCV, group 3 composing of 30 healthy subjects matching the same age and socioeconomic status were taken as a control group. Gene polymorphism of BCL2 (Ala43Thr) were evaluated by PCR-RFLP technique and measured for all patients and controls. Results: The summed 43Thr genotype was more frequent and statistically significant in HCC patients as compared to control group. This genotype of BCL2 gene may inhibit the programmed cell death which leads to disturbance in tissue and cells homeostasis and reduction in immune regulation. This result leads to viral replication and HCV persistence. Moreover, virus produces variety of mechanisms to block genes participated in apoptosis. This mechanism proves that HCV patients who have 43Thr genotype are more susceptible to HCC. Conclusion: The data suggest for the first time that the BCL2 polymorphism is associated with the susceptibility to HCC in Egyptian populations and might be used as molecular markers for evaluating HCC risk. This study clearly demonstrated that Chronic HCV exhibit a deregulation of apoptosis with the disease progression. This provides an insight into the pathogenesis of chronic HCV infection, and may contribute to the therapy.Keywords: BCL2 gene, Hepatitis C Virus, Hepatocellular carcinoma, sensitivity, specificity, apoptosis
Procedia PDF Downloads 5082530 Harmful Algal Blooming Micro-Algae in Kenya’s Coastal Waters
Authors: Nancy Awuor Oduor, Nils Moosdorf
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Harmful Algal Blooms (HABs) are a threat to coastal water quality, marine biodiversity, and human health. The attention on HABs and associated phycotoxins is still very low in tropical coastal developing countries despite the high dependence of local communities on coastal and marine resources for food and livelihoods and the growing evidence of the global increase in HABs frequency, toxicity, and geographical expansion. Lack of HABs monitoring thus creates a high risk of exposure due to uncertainty. This study assessed the spatial and temporal variability and effects of potential HAB-forming species in Kenya’s coastal waters. The preliminary results from 463 sampled collected over a series of 10 coastal surveys conducted over 267 Km of Kenya’s coastline between August 2021 and July 2022 revealed the presence of 87 potential algal blooming species belonging to 47 genera dominated by species capable of producing toxins, causing physical harm and high biomass at 41, 31 and 21 % respectively. The taxonomic composition was also dominated by dinoflagellates at 47%, followed by diatoms, cyanobacteria, and silicoflagellates at 39, 12, and 2%, respectively. About 92 % of the toxin-producing species were established in the creek waters. However, there were no significant variations established in species richness between the dry and wet seasons. Paralytic Shellfish Poisoning (PSP) toxin-producing dinoflagellates Alexandrium spp., Aphanizomenon spp., Gonyaulax spp., Gymnodinium spp., and Brachydinium capitatum, and Amnesic Shellfish Poisoning (ASP) Toxin producing diatoms Amphora spp., Nitzschia spp. and Pseudo-nitzschia spp. Frequented the area in low cell densities ranging between 5 and 1500 cells/L. However, no domoic acid (DA) and saxitoxins (SXTs) were detected during the July surveys. This does not mean that the toxins are absent in the area, and longer studies are recommended.Keywords: harmful algal blooms, phycotoxins, saxitoxin, domoic acid, Kenya
Procedia PDF Downloads 632529 The Impact of Working Environment Condition and Lifestyle Factors in Male Infertility in South of Iran
Authors: Shabnam Etemadi
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Background: Infertility is one of the most important issues in any society due to its psychological, medical and economic consequences that can greatly influence overall health and life. This study aims to assess the relationship between inhalation or exposing workplace pollution and dysfunction of the male reproductive system. Semen samples are male employees in south of Iran who exposed to work environmental pollutants for long hours. Method: Due to descriptive-analytical, the analysis of all interviews of all male patients of Bu Ali Medical Center and Pasteur Laboratory are conducted within 6 months. Random sampling numbered and patients signed informed consent. To analyze the data, Miller's fertility motivation questionnaires and the Miller-Smith lifestyle assessment inventory are used and Working Conditions Survey is developed. For analyzing the collecting data SPSS is used. Findings: Although sperm motility and volume had no statistically significant relationship with any of the lifestyle components, the weak relationship between sperm movement and work environment conditions (P = 0.07) lead to other factors to be investigated. * Among the factors of Working Environment Condition, smoking, work in the open environment and presence of more than 6 hours in the work environment with sperm mobility, smoking, contact with chemicals and radioactive with sperm volume at a level less than 0.05 had a statistically significant relationship. Conclusion: Finding revealed the environment pollution is one of the important factors in male infertility and strengthens this hypothesis. Working Environmental pollutants in the field of metropolitan pollution should be considered as a unifying hypothesis, possibly could interfere with male reproductive function.Keywords: infertility, lifestyle, workplace pollution, male infertility
Procedia PDF Downloads 282528 Evaluation of Total Phenolic Content and Antioxidant Activity in Amaranth Seeds Grown in Latvia
Authors: Alla Mariseva, Ilze Beitane
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Daily intake of products rich in antioxidants that scavenge free radicals in cell membranes is an effective way to combat oxidative stress. Last year there was noticed higher interest towards the identification and utilization of plants rich in antioxidant compounds as they may behave as preventive medicine. Amaranth seeds due to polyphenols, anthocyanins, flavonoids, and tocopherols are characterized by high antioxidant activity. The study aimed to evaluate the total phenolic content and radical scavenging activity of amaranth seeds cultivated in 2020 in two farms in Latvia. One sample of amaranth seeds came from an organic farm, the other – from a conventional farm. The total phenol content of amaranth seed extracts was measured with the Folin-Ciocalte spectrophotometric method. The total phenols were expressed as gallic acid equivalents (GAE) per 100 g dry weight (DW) of the samples. The antioxidant activity of amaranth seed extracts was calculated based on scavenging activities of the stable 2.2-diphenyl-1-picrylhydrazyl (DPPH˙) radical, the radical scavenging capacity (ABTS) was demonstrated as Trolox mM equivalents (TE) per 100 g-1 dry weight. Three parallel measurements were performed on all samples. There were significant differences between organic and conventional amaranth seeds in terms of total phenolic content and antioxidant activity. Organic amaranth seeds showed higher total phenolic content compared to conventional amaranth seeds, 65.4±6.0 mg GAE 100 g⁻¹ DW and 43.4±7.8 mg GAE 100 g⁻¹ DW respectively. Organic amaranth seeds were also characterized by higher DPPH radical scavenging activity (7.9±0.4 mM TE 100 g⁻¹ of dry matter) and ABTS radical scavenging capacity (13.2±1.5 mM TE 100 g⁻¹ of dry matter). The results obtained on total phenolic content and antioxidant activity of amaranth seeds grown in Latvia confirmed that the samples have a high biological value; therefore, it would be necessary to promote their consumption by including them in various food products, including vegan products, increasing their nutritional value.Keywords: ABTS, amaranth seeds, antioxidant activity, DPPH, total phenolic content
Procedia PDF Downloads 2232527 An Integrated CFD and Experimental Analysis on Double-Skin Window
Authors: Sheam-Chyun Lin, Wei-Kai Chen, Hung-Cheng Yen, Yung-Jen Cheng, Yu-Cheng Chen
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Result from the constant dwindle in natural resources, the alternative way to reduce the costs in our daily life would be urgent to be found in the near future. As the ancient technique based on the theory of solar chimney since roman times, the double-skin façade are simply composed of two large glass panels in purpose of daylighting and also natural ventilation in the daytime. Double-skin façade is generally installed on the exterior side of buildings as function as the window, so there’s always a huge amount of passive solar energy the façade would receive to induce the airflow every sunny day. Therefore this article imposes a domestic double-skin window for residential usage and attempts to improve the volume flow rate inside the cavity between the panels by the frame geometry design, the installation of outlet guide plate and the solar energy collection system. Note that the numerical analyses are applied to investigate the characteristics of flow field, and the boundary conditions in the simulation are totally based on the practical experiment of the original prototype. Then we redesign the prototype from the knowledge of the numerical results and fluid dynamic theory, and later the experiments of modified prototype will be conducted to verify the simulation results. The velocities at the inlet of each case are increase by 5%, 45% and 15% from the experimental data, and also the numerical simulation results reported 20% improvement in volume flow rate both for the frame geometry design and installation of outlet guide plate.Keywords: solar energy, double-skin façades, thermal buoyancy, fluid machinery
Procedia PDF Downloads 4992526 Synthesis and Characterization of Heterogeneous Silver Nanoparticles for Protection of Ancient Egyptian Artifacts from Microbial Deterioration
Authors: Mohamed Abd Elfattah Ibraheem Elghrbawy
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Biodeterioration of cultural heritage is a complex process which is caused by the interaction of many physical, chemical and biological agents; the growth of microorganisms can cause staining, cracking, powdering, disfigurement and displacement of monuments material, which leads to the permanent loss of monuments material. Organisms causing biodeterioration on monuments have usually been controlled by chemical products (biocides). In order to overcome the impact of biocides on the environment, human health and monument substrates, alternative tools such as antimicrobial agents from natural products can be used for monuments conservation and protection. The problem is how to formulate antibacterial agents with high efficiency and low toxicity. Various types of biodegradable metal nanoparticles (MNPs) have many applications in plant extract delivery. So, Nano-encapsulation of metal and natural antimicrobial agents using polymers such as chitosan increases their efficacy, specificity and targeting ability. Green synthesis and characterization of metal nanoparticles such as silver with natural products extracted from some plants having antimicrobial properties, using the ecofriendly method one pot synthesis. Encapsulation of the new synthesized mixture using some biopolymers such as chitosan nanoparticles. The dispersions and homogeneity of the antimicrobial heterogeneous metal nanoparticles encapsulated by biopolymers will be characterized and confirmed by Fourier Transform Infrared Spectroscopy (FTIR), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM) and Zeta seizer. The effect of the antimicrobial biopolymer metal nano-formulations on normal human cell lines will be investigated to evaluate the environmental safety of these formulations. The antimicrobial toxic activity of the biopolymeric antimicrobial metal nanoparticles formulations will be will be investigated to evaluate their efficiency towards different pathogenic bacteria and fungi.Keywords: antimicrobial, biodeterioration, chitosan, cultural heritage, silver
Procedia PDF Downloads 812525 Phenotypic Characterization of Dental Pulp Stem Cells Isolated from Irreversible Pulpitis with Dental Pulp Stem Cells from Impacted Teeth
Authors: Soumya S., Manju Nidagodu Jayakumar, Vellore Kannan Gopinath
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Dental pulp inflammation resulting from dental caries often leads to a pathologic condition known as irreversible pulpitis and the currently managed by root canal treatment. Extirpation of the entire pulp tissue is done during this procedure, and the canal space is filled with synthetic materials. Recent studies in the stem cell biology state that some portion of the irreversibly inflamed pulp tissue could be viable with progenitor cells, having the properties similar to that of Mesenchymal stem cells. Hence, we aim to isolate Dental Pulp Stem Cells (DPSCs) from patients diagnosed with severe irreversible pulpitis and characterize the cells for the MSC specific markers. The pulp tissue was collected from the dental clinic and subjected to collagenase/dispase digestion. The isolated cells were expanded in culture, and the phenotypic characterization was done using flow cytometry. MSC specific markers such as CD-90, CD-73, and CD-105 were analysed along with negative markers such as CD-14 and CD-45. The isolated cells expressed positive expression for CD markers with CD90 and CD105 ( > 95%) and CD73 (19%). The cells did not express the negative markers CD-14 and CD-45. The commercially available DPSCs from vital extracted teeth, preferably molar/wisdom teeth with large pulp cavity or incomplete root growth in young patients (aged 15-30 years) showed more than 90% expression for all the CD markers such as CD-90, 73 and 105, whereas negative for CD-14 and CD-45. The DPSCs isolated from inflamed pulp tissue showed a less expression for CD-73 compared to the commercially available DPSCs whereas, as the other two markers were found to show similar percentage of positive expression. This could be attributed to the fact that the pulp population is very heterogeneous and we used the pooled tissue from different patients. Hence the phenotypic characterization and comparison with the commercially available DPSCs proved that the inflamed pulp tissue is a good source of MSC like cells which can be utilized further for regenerative application.Keywords: collagenase/dispase, dental pulp stem cells, flow cytometry, irreversible pulpitis
Procedia PDF Downloads 2522524 Secondary True to Life Polyethylene Terephthalate Nanoplastics: Obtention, Characterization, and Hazard Evaluation
Authors: Aliro Villacorta, Laura Rubio, Mohamed Alaraby, Montserrat López Mesas, Victor Fuentes-Cebrian, Oscar H. Moriones, Ricard Marcos, Alba Hernández.
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Micro and nano plastics (MNPLs) are emergent environmental pollutants requiring urgent information on their potential risks to human health. One of the problems associated with the evaluation of their undesirable effects is the lack of real samples matching those resulting from the environmental degradation of plastic wastes. To such end, we propose an easy method to obtain polyethylene terephthalate nano plastics from water plastic bottles (PET-NPLs) but, in principle, applicable to any other plastic goods sources. An extensive characterization indicates that the proposed process produces uniform samples of PET-NPLs of around 100 nm, as determined by using a multi-angle and dynamic light scattering methodology. An important point to be highlighted is that to avoid the metal contamination resulting from methods using metal blades/burrs for milling, trituration, or sanding, we propose to use diamond burrs to produce metal-free samples. To visualize the toxicological profile of the produced PET-NPLs, we have evaluated their ability to be internalized by cells, their cytotoxicity, and their ability to induce oxidative stress and induce DNA damage. In this preliminary approach, we have detected their cellular uptake, but without the induction of significant biological effects. Thus, no relevant increases in toxicity, reactive oxygen species (ROS) induction, or DNA damage -as detected with the comet assay- have been observed. The use of real samples, as produced in this study, will generate relevant data in the discussion about the potential health risks associated with MNPLs exposures.Keywords: nanoplastics, polyethylene terephthalate, physicochemical characterization, cell uptake, cytotoxicity
Procedia PDF Downloads 982523 Micromechanical Modelling of Ductile Damage with a Cohesive-Volumetric Approach
Authors: Noe Brice Nkoumbou Kaptchouang, Pierre-Guy Vincent, Yann Monerie
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The present work addresses the modelling and the simulation of crack initiation and propagation in ductile materials which failed by void nucleation, growth, and coalescence. One of the current research frameworks on crack propagation is the use of cohesive-volumetric approach where the crack growth is modelled as a decohesion of two surfaces in a continuum material. In this framework, the material behavior is characterized by two constitutive relations, the volumetric constitutive law relating stress and strain, and a traction-separation law across a two-dimensional surface embedded in the three-dimensional continuum. Several cohesive models have been proposed for the simulation of crack growth in brittle materials. On the other hand, the application of cohesive models in modelling crack growth in ductile material is still a relatively open field. One idea developed in the literature is to identify the traction separation for ductile material based on the behavior of a continuously-deforming unit cell failing by void growth and coalescence. Following this method, the present study proposed a semi-analytical cohesive model for ductile material based on a micromechanical approach. The strain localization band prior to ductile failure is modelled as a cohesive band, and the Gurson-Tvergaard-Needleman plasticity model (GTN) is used to model the behavior of the cohesive band and derived a corresponding traction separation law. The numerical implementation of the model is realized using the non-smooth contact method (NSCD) where cohesive models are introduced as mixed boundary conditions between each volumetric finite element. The present approach is applied to the simulation of crack growth in nuclear ferritic steel. The model provides an alternative way to simulate crack propagation using the numerical efficiency of cohesive model with a traction separation law directly derived from porous continuous model.Keywords: ductile failure, cohesive model, GTN model, numerical simulation
Procedia PDF Downloads 1492522 Traumatic Chiasmal Syndrome Following Traumatic Brain Injury
Authors: Jiping Cai, Ningzhi Wangyang, Jun Shao
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Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality that leads to structural and functional damage in several parts of the brain, such as cranial nerves, optic nerve tract or other circuitry involved in vision and occipital lobe, depending on its location and severity. As a result, the function associated with vision processing and perception are significantly affected and cause blurred vision, double vision, decreased peripheral vision and blindness. Here two cases complaining of monocular vision loss (actually temporal hemianopia) due to traumatic chiasmal syndrome after frontal head injury were reported, and were compared the findings with individual case reports published in the literature. Reported cases of traumatic chiasmal syndrome appear to share some common features, such as injury to the frontal bone and fracture of the anterior skull base. The degree of bitemporal hemianopia and visual loss acuity have a variable presentation and was not necessarily related to the severity of the craniocerebral trauma. Chiasmal injury may occur even in the absence bony chip impingement. Isolated bitemporal hemianopia is rare and clinical improvement usually may not occur. Mechanisms of damage to the optic chiasm after trauma include direct tearing, contusion haemorrhage and contusion necrosis, and secondary mechanisms such as cell death, inflammation, edema, neurogenesis impairment and axonal damage associated with TBI. Beside visual field test, MRI evaluation of optic pathways seems to the strong objective evidence to demonstrate the impairment of the integrity of visual systems following TBI. Therefore, traumatic chiasmal syndrome should be considered as a differential diagnosis by both neurosurgeons and ophthalmologists in patients presenting with visual impairment, especially bitemporal hemianopia after head injury causing frontal and anterior skull base fracture.Keywords: bitemporal hemianopia, brain injury, optic chiasma, traumatic chiasmal syndrome.
Procedia PDF Downloads 792521 Development of Strategy for Enhanced Production of Industrial Enzymes by Microscopic Fungi in Submerged Fermentation
Authors: Zhanara Suleimenova, Raushan Blieva, Aigerim Zhakipbekova, Inkar Tapenbayeva, Zhanar Narmuratova
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Green processes are based on innovative technologies that do not negatively affect the environment. Industrial enzymes originated from biological systems can effectively contribute to sustainable development through being isolated from microorganisms which are fermented using primarily renewable resources. Many widespread microorganisms secrete a significant amount of biocatalysts into the environment, which greatly facilitates the task of their isolation and purification. The ability to control the enzyme production through the regulation of their biosynthesis and the selection of nutrient media and cultivation conditions allows not only to increase the yield of enzymes but also to obtain enzymes with certain properties. In this regard, large potentialities are embedded in immobilized cells. Enzyme production technology in a secreted active form enabling industrial application on an economically feasible scale has been developed. This method is based on the immobilization of enzyme producers on a solid career. Immobilizing has a range of advantages: decreasing the price of the final product, absence of foreign substances, controlled process of enzyme-genesis, the ability of various enzymes' simultaneous production, etc. Design of proposed equipment gives the opportunity to increase the activity of immobilized cell culture filtrate comparing to free cells, growing in periodic culture conditions. Such technology allows giving a 10-times raise in culture productivity, to prolong the process of fungi cultivation and periods of active culture liquid generation. Also, it gives the way to improve the quality of filtrates (to make them more clear) and exclude time-consuming processes of recharging fermentative vials, that require manual removing of mycelium.Keywords: industrial enzymes, immobilization, submerged fermentation, microscopic fungi
Procedia PDF Downloads 1412520 Removal of Cr (VI) from Water through Adsorption Process Using GO/PVA as Nanosorbent
Authors: Syed Hadi Hasan, Devendra Kumar Singh, Viyaj Kumar
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Cr (VI) is a known toxic heavy metal and has been considered as a priority pollutant in water. The effluent of various industries including electroplating, anodizing baths, leather tanning, steel industries and chromium based catalyst are the major source of Cr (VI) contamination in the aquatic environment. Cr (VI) show high mobility in the environment and can easily penetrate cell membrane of the living tissues to exert noxious effects. The Cr (VI) contamination in drinking water causes various hazardous health effects to the human health such as cancer, skin and stomach irritation or ulceration, dermatitis, damage to liver, kidney circulation and nerve tissue damage. Herein, an attempt has been done to develop an efficient adsorbent for the removal of Cr (VI) from water. For this purpose nanosorbent composed of polyvinyl alcohol functionalized graphene oxide (GO/PVA) was prepared. Thus, obtained GO/PVA was characterized through FTIR, XRD, SEM, and Raman Spectroscopy. As prepared nanosorbent of GO/PVA was utilized for the removal Cr (VI) in batch mode experiment. The process variables such as contact time, initial Cr (VI) concentration, pH, and temperature were optimized. The maximum 99.8 % removal of Cr (VI) was achieved at initial Cr (VI) concentration 60 mg/L, pH 2, temperature 35 °C and equilibrium was achieved within 50 min. The two widely used isotherm models viz. Langmuir and Freundlich were analyzed using linear correlation coefficient (R2) and it was found that Langmuir model gives best fit with high value of R2 for the data of present adsorption system which indicate the monolayer adsorption of Cr (VI) on the GO/PVA. Kinetic studies were also conducted using pseudo-first order and pseudo-second order models and it was observed that chemosorptive pseudo-second order model described the kinetics of current adsorption system in better way with high value of correlation coefficient. Thermodynamic studies were also conducted and results showed that the adsorption was spontaneous and endothermic in nature.Keywords: adsorption, GO/PVA, isotherm, kinetics, nanosorbent, thermodynamics
Procedia PDF Downloads 3892519 Correlation of Leptin with Clinico-Pathological Features of Breast Cancer
Authors: Saad Al-Shibli, Nasser Amjad, Muna Al Kubaisi, Norra Harun, Shaikh Mizan
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Leptin is a multifunctional hormone produced mainly by adipocyte. Leptin and its receptor have long been found associated with breast cancer. The main aim of this study is to investigate the correlation between Leptin/Leptin receptor and the clinicopathological features of breast cancer. Blood samples for ELISA, tissue samples from tumors and adjacent breast tissue were taken from 51 women with breast cancer with a control group of 40 women with a negative mammogram. Leptin and Leptin receptor in the tissues were estimated by immunohistochemistry (IHC). They were localized at the subcellular level by immunocytochemistry using transmission electron microscopy (TEM). Our results showed significant difference in serum leptin level between control and the patient group, but no difference between pre and post-operative serum leptin levels in the patient group. By IHC, we found that the majority of the breast cancer cells studied, stained positively for leptin and leptin receptors with co-expression of leptin and its receptors. No significant correlation was found between leptin/leptin receptors expression with the race, menopausal status, lymph node metastasis, estrogen receptor expression, progesterone receptor expression, HER2 expression and tumor size. Majority of the patients with distant metastasis were associated with high leptin and leptin receptor expression. TEM views both Leptin and Leptin receptor were found highly concentrated within and around the nucleus of the cancer breast cells, indicating nucleus is their principal seat of actions while the adjacent breast epithelial cells showed that leptin gold particles are scattered all over the cell with much less than that of the cancerous cells. However, presence of high concentration of leptin does not necessarily prove its over-expression, because it could be internalized from outside by leptin receptor in the cells. In contrast, leptin receptor is definitely over-expressed in the ductal breast cancer cells. We conclude that reducing leptin levels, blocking its downstream tissue specific signal transduction, and/or blocking the upstream leptin receptor pathway might help in prevention and therapy of breast cancer.Keywords: breast cancer, expression, leptin, leptin receptors
Procedia PDF Downloads 1402518 Drug-Based Nanoparticles: Comparative Study of the Effect Drug Type on Release Kinetics and Cell Viability
Authors: Chukwudalu C. Nwazojie, Wole W. Soboyejo, John Obayemi, Ali Salifu Azeko, Sandra M. Jusu, Chinyerem M. Onyekanne
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The conventional methods for the diagnosis and treatment of breast cancer include bulk systematic mammography, ultrasound, dynamic contrast-enhanced fast 3D gradient-echo (GRE) magnetic resonance imaging (MRI), surgery, chemotherapy, and radiotherapy. However, nanoparticles and drug-loaded polymer microspheres for disease (cancer) targeting and treatment have enormous potential to enhance the approaches that are used today. The goal is to produce an implantable biomedical device for localized breast cancer drug delivery within Africa and the world. The main advantage of localized delivery is that it reduces the amount of drug that is needed to have a therapeutic effect. Polymer blends of poly (D,L-lactide-co-glycolide) (PLGA) and polycaprolactone (PCL), which are biodegradable, is used as a drug excipient. This work focuses on the development of PLGA-PCL (poly (D,L-lactide-co-glycolide) (PLGA) blended with based injectable drug microspheres and are loaded with anticancer drugs (prodigiosin (PG), and paclitaxel (PTX) control) and also the conjugated forms of the drug functionalized with LHRH (luteinizing hormone-releasing hormone) (PG-LHRH, and PTX- LHRH control), using a single-emulsion solvent evaporation technique. The encapsulation was done in the presence of PLGA-PCL (as a polymer matrix) and poly-(vinyl alcohol) (PVA) (as an emulsifier). Comparative study of the various drugs release kinetics and degradation mechanisms of the PLGA-PCL with an encapsulated drug is achieved, and the implication of this study is for the potential application of prodigiosin PLGA-PCL loaded microparticles for controlled delivery of cancer drug and treatment to prevent the regrowth or locoregional recurrence, following surgical resection of triple-negative breast tumor.Keywords: cancer, polymers, drug kinetics, nanoparticles
Procedia PDF Downloads 1012517 Pricing and Economic Benefits of Commercial Insurance Incorporated into Home-based Hospice Care
Authors: Lie-Fen Lin, Tzu-Hsuan Lin, Ching-Heng Lin
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Hospice care for terminally ill patients provides not only a better quality of life but also cost-saving benefits. However, the utilization of home-based hospice care (HBH care) remains low even for countries covered by National Health Insurance (NHI) programs in Taiwan. In the current commercial insurance policy, only hospital-based hospice benefits were covered. It may have an influence on the insureds chosen to receive end-of-life care in a hospitalized manner. Thus, how to propose a feasible method to advocate HBH care utilization rate of public health policies is an important issue. A total of 130,219 cancer decedents in the year 2011-2013 from the National Health Insurance Research Database (NHIRD) in Taiwan were included in this study. By adding a day volume pays benefits of HBH care as a commercial insurance rider, will provide alternative benefits for the insureds. A multiple-state Markov chain model was incorporated to estimate the transition intensities of patients in different states at the end of their lives (Non-hospice, HBH, hospital-based hospice), and the premiums were estimated. HBH care insurance benefits provide financial support and reduce the burden of care for patients. The rate-making of this product is very sensitive while the utilization rate is rising, especially for high ages. The proposed HBH care insurance is a feasible way to reduce the financial burden, enhance the care quality and family satisfaction of insureds. Meanwhile, insurance companies can participate in advocating a good medical policy to enhance the social image. In addition, the medical costs of NHI can reduce effectively.Keywords: home-based hospice care, commercial insurance, Markov chain model, the day volume pays
Procedia PDF Downloads 2142516 Optimization of Enzymatic Hydrolysis of Cooked Porcine Blood to Obtain Hydrolysates with Potential Biological Activities
Authors: Miguel Pereira, Lígia Pimentel, Manuela Pintado
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Animal blood is a major by-product of slaughterhouses and still represents a cost and environmental problem in some countries. To be eliminated, blood should be stabilised by cooking and afterwards the slaughterhouses must have to pay for its incineration. In order to reduce the elimination costs and valorise the high protein content the aim of this study was the optimization of hydrolysis conditions, in terms of enzyme ratio and time, in order to obtain hydrolysates with biological activity. Two enzymes were tested in this assay: pepsin and proteases from Cynara cardunculus (cardosins). The latter has the advantage to be largely used in the Portuguese Dairy Industry and has a low price. The screening assays were carried out in a range of time between 0 and 10 h and using a ratio of enzyme/reaction volume between 0 and 5%. The assays were performed at the optimal conditions of pH and temperature for each enzyme: 55 °C at pH 5.2 for cardosins and 37 °C at pH 2.0 for pepsin. After reaction, the hydrolysates were evaluated by FPLC (Fast Protein Liquid Chromatography) and tested for their antioxidant activity by ABTS method. FPLC chromatograms showed different profiles when comparing the enzymatic reactions with the control (no enzyme added). The chromatogram exhibited new peaks with lower MW that were not present in control samples, demonstrating the hydrolysis by both enzymes. Regarding to the antioxidant activity, the best results for both enzymes were obtained using a ratio enzyme/reactional volume of 5% during 5 h of hydrolysis. However, the extension of reaction did not affect significantly the antioxidant activity. This has an industrial relevant aspect in what concerns to the process cost. In conclusion, the enzymatic blood hydrolysis can be a better alternative to the current elimination process allowing to the industry the reuse of an ingredient with biological properties and economic value.Keywords: antioxidant activity, blood, by-products, enzymatic hydrolysis
Procedia PDF Downloads 5102515 Ultra Broad Emission from Fe Doped Carbon Quantum Dots
Authors: Asha Bhardwaj, Pushpendu Biswas
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Carbon Dots (CDs) are known to be absorbing in the UV and emitting in the blue to visible region [1-2]. As CDs have high bio compatibility, high emission efficiency, are environment friendly and are nontoxic in nature, they are a material of great importance for various biomedical as well as optoelectronic applications [3-6]. For bioimaging and photothermal therapy in cancer treatment CDs should be highly photostable, show interaction with NIR band [3], show quick excretion from the body and have high Quantum yields. NIR I stands for emission in the 650-950 nm region and NIR II stands for emission in the 1000-1700 nm range [4]. Penetration depth of NIR II is larger than that of NIR-1 or visible light [5]. Also, it shows heating effect which is beneficial for selective ablation of cancer cells while not harming the healthy cells. Therefore, efforts are being made by the scientific community to synthesize CDs which emit in the NIR II region. Here we report CDs emitting in all the three regions (Visible, NIR I and NIR II) of electromagnetic spectra ranging from 300-1150 nm. Wide range emissive CDs and Fe doped CDs are prepared by a one-step hydrothermal method. Fe concentration has been increased in steps to assess the contribution from Fe incorporation in the CD lattice [6]. The CDs emit in three wavelength ranges, from 300-600 nm, 600-800 nm (NIR I) and 900 – 1150 nm (NIR II). Such kind of broad emission behaviour in single system carbon dots is being reported for the first time. Further excitation wavelength (λex) dependent emission characteristics reveal that the emission peak wavelength values are unaffected by the changing excitation wavelength in the visible region. Also, NIR I and NIR II emission is observed only for 300 and 310 nm excitation, hinting towards two photon and three photon emission [4]. Emission from 650- 1150 nm is not observed for λex > 310 nm. Additionally, as expected the absorption spectra also ranges from 250-600 nm, as compared to commonly observed blue or UV absorption in CDs. The exquisite ultra-wide range emitting nontoxic CDs can find application not only as broad band emitters but also in photothermal therapy for cancer cell theranostics.Keywords: Broad Emission, absorption, Carbon dots, NIR Emission
Procedia PDF Downloads 42514 Associations of Gene Polymorphism of IL-17 a (C737T) with Its Level in Patients with Erysipelas Kazakh Population
Authors: Nazira B. Bekenova, Lydia A. Mukovozova, Andrej M. Grjibovski, Alma Z. Tokayeva, Yerbol M. Smail, Nurlan E. Aukenov
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Erysipelas is an infectious disease with socio-economic significance and prone to prolonged recurrent course (30%). Contribution of genetic factors, in particular the gene polymorphism of cytokines, can be essential in disease etiology and pathogenesis. Interleukin – 17 A are produced by T helpers of 17 type and plays a key role in development of local inflammation process. Local inflammatory process is a dominant in the clinic of erysipelas. Established that the skin and mucosas are primary areas of migration (homing) Th17-cell and their cytokines are stimulate the barrier function of the epithelium. We studied associations between gene polymorphism of IL-17A (C737T) rs 8193036 and IL-17A level in patients with erysipelas Kazakh population. Altogether, 90 cases with erysipelas and 90 healthy controls from an ethnic Kazakh population comprised the sample. Cases were identified at Clinical Infectious Diseases Hospital of Semey (Kazakhstan). The IL-17A (rs8193036) polymorphism was analyzed by a real time polymerase chain reaction. Plasma levels of IL-17 A were assessed by immuneenzyme analysis method using ‘Vector-Best’ test-system (Russia). Differences in levels of IL-17 A between CC, TT, CT groups were studied using Kruskal — Wallis test. Pairwise comparisons were performed using Mann-Whitney tests with Bonferroni correction (New significance level was set to 0.025). We found, that in patients with erysipelas with CC genotype the level of IL-17 A was higher (p= 0, 010) compared to the carriers of CT genotype. When compared the level of IL – 17 A between the patients with TT genotype and patients with CC genotype, also between the patients with CT genotype and patients with TT genotype statistically significant differences are not revealed (p = 0.374 and p = 0.043, respectively). Comparisons of IL-17 A plasma levels between the CC and CT genotypes, between the CC and TT genotypes, and between the TT and CT in healthy patients did not reveal significant differences (p = 0, 291). Therefore, we are determined the associations of gene polymorphism of IL-17 A (C737T) with its level in patients erysipelas carriers CC genotype.Keywords: erysipelas, interleukin – 17 A, Kazakh, polymorphism
Procedia PDF Downloads 4362513 Anti-Obesity Activity of Garcinia xanthochymus: Biochemical Characterization and In vivo Studies in High Fat Diet-Rat Model
Authors: Mahesh M. Patil, K. A. Anu-Appaiah
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Overweight and obesity is a serious medical problem, increasing in prevalence, and affecting millions worldwide. Investigators have been trying from decades to articulate the burden of obesity and related risk factors. To answer this problem, we suggest a new therapeutic anti-obesity compounds from Garcinia xanthochymus fruit. However, there is little published scientific information on non-hydroxycitric acid Garcinia species. Our findings include biochemical characterization of the fruit; in vivo toxicity and bio-efficacy study of G. xanthochymus in high fat diet wistar rat model. We observed that Garcinia pericarp is a rich source of organic acids, polyphenols, mono- (40.63%) and poly-unsaturated fatty acids (16.45%; omega-3: 10.02%). Toxicological studies have showed that Garcinia is safe and had no observed adverse effect level up to 400 mg/kg/day. Body weight and food intake was significantly (P<0.05) reduced in oral gavage treated rats (sonicated Garcinia powder) in 13 weeks. Subcutaneous fat was significantly (P<0.05) reduced in Garcinia treated rats. Hepatocytes significantly (p<0.05) overexpressed sterol regulatory element binding protein 2, liver X receptor- α, liver X receptor- β, lipoprotein lipase and monoacylglycerol lipase. Fatty acid binding protein 1 and peroxisome proliferator activated receptor- α were down regulated as assessed by real time qPCR. Currently our research is focused on the adipocyte obesity related gene expressions, effect of Garcinia on 3T3-adipocyte cell lines and high fat diet induced mice model. This in vivo pre-clinical data suggests that G. xanthochymus may have clinical utility for the treatment of obesity. However, further studies are required to establish its potency.Keywords: Garcinia xanthochymus, anti-obesity, high fat diet, real time qPCR
Procedia PDF Downloads 2522512 Probiotic Potential and Antimicrobial Activity of Enterococcus faecium Isolated from Chicken Caecal and Fecal Samples
Authors: Salma H. Abu Hafsa, A. Mendonca, B. Brehm-Stecher, A. A. Hassan, S. A. Ibrahim
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Enterococci are important inhabitants of the animal intestine and are widely used in probiotic products. A probiotic strain is expected to possess several desirable properties in order to exert beneficial effects. Therefore, the objective of this study was to isolate and characterize strains of Enterococcus sp. from chicken cecal and fecal samples to determine potential probiotic properties. Enterococci were isolated from thirty one chicken cecal and fecal samples collected from a local farm. In vitro studies were performed to assess antibacterial activity (using agar well diffusion and cell free supernatant broth technique against Salmonella enterica serotype Enteritidis), susceptibility to antibiotics (amoxycillin, cotrimoxazole, chloramphenicol, cefuroxime, ceftriaxone, ciprofloxacin, and nalidixic acid), survival in acidic conditions, resistance to bile salts, and their survival during simulated gastric juice conditions at pH 2.5. Isolates were identified using biochemical and molecular assays (API 50 CHL, and API ZYM kits followed by 16S rDNA gene sequence analysis). Two strains were identified, of which, Enteroccocus faecium was capable of inhibiting the growth of S. enteritidis and was susceptible to a wide range of antibiotics. In addition, the isolated strain exhibited significant resistance under highly acidic conditions (pH=2.5) for 8 hours and survived well in bile salt at 0.2% for 24 hours and showing ability to survive in the presence of simulated gastric juice at pH 2.5. Based on these results, the E. faecium isolate fulfills some of the criteria to be considered as a probiotic strain and therefore, could be used as a feed additive with good potential for controlling S. enteritidis in chickens. However, in vivo studies are needed to determine the safety of the strain.Keywords: acid tolerance, antimicrobial activity, Enterococcus faecium, probiotic
Procedia PDF Downloads 3972511 Derivation of a Risk-Based Level of Service Index for Surface Street Network Using Reliability Analysis
Authors: Chang-Jen Lan
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Current Level of Service (LOS) index adopted in Highway Capacity Manual (HCM) for signalized intersections on surface streets is based on the intersection average delay. The delay thresholds for defining LOS grades are subjective and is unrelated to critical traffic condition. For example, an intersection delay of 80 sec per vehicle for failing LOS grade F does not necessarily correspond to the intersection capacity. Also, a specific measure of average delay may result from delay minimization, delay equality, or other meaningful optimization criteria. To that end, a reliability version of the intersection critical degree of saturation (v/c) as the LOS index is introduced. Traditionally, the level of saturation at a signalized intersection is defined as the ratio of critical volume sum (per lane) to the average saturation flow (per lane) during all available effective green time within a cycle. The critical sum is the sum of the maximal conflicting movement-pair volumes in northbound-southbound and eastbound/westbound right of ways. In this study, both movement volume and saturation flow are assumed log-normal distributions. Because, when the conditions of central limit theorem obtain, multiplication of the independent, positive random variables tends to result in a log-normal distributed outcome in the limit, the critical degree of saturation is expected to be a log-normal distribution as well. Derivation of the risk index predictive limits is complex due to the maximum and absolute value operators, as well as the ratio of random variables. A fairly accurate functional form for the predictive limit at a user-specified significant level is yielded. The predictive limit is then compared with the designated LOS thresholds for the intersection critical degree of saturation (denoted as XKeywords: reliability analysis, level of service, intersection critical degree of saturation, risk based index
Procedia PDF Downloads 1312510 Reservoir Characterization using Comparative Petrophysical Testing Approach Acquired with Facies Architecture Properties Analysis
Authors: Axel Priambodo, Dwiharso Nugroho
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Studies conducted to map the reservoir properties based on facies architecture in which to determine the distribution of the petrophysical properties and calculate hydrocarbon reserves in study interval. Facies Architecture analysis begins with stratigraphic correlation that indicates the area is divided into different system tracts. The analysis of distribution patterns and compiling core analysis with facies architecture model show that there are three estuarine facies appear. Formation evaluation begins with shale volume calculation using Asquith-Krygowski and Volan Triangle Method. Proceed to the calculation of the total and effective porosity using the Bateman-Konen and Volan Triangle Method. After getting the value of the porosity calculation was continued to determine the effective water saturation and non-effective by including parameters of water resistivity and resistivity clay. The results of the research show that the Facies Architecture on the field in divided into three main facies which are Estuarine Channel, Estuarine Sand Bar, and Tidal Flat. The petrophysics analysis are done by comparing different methods also shows that the Volan Triangle Method does not give a better result of the Volume Shale than the Gamma Ray Method, but on the other hand, the Volan Triangle Methode is better on calculating porosity compared to the Bateman-Konen Method. The effective porosity distributions are affected by the distribution of the facies. Estuarine Sand Bar has a low porosity number and Estuarine Channel has a higher number of the porosity. The effective water saturation is controlled by structure where on the closure zone the water saturation is lower than the area beneath it. It caused by the hydrocarbon accumulation on the closure zone.Keywords: petrophysics, geology, petroleum, reservoir
Procedia PDF Downloads 3302509 Infusion Pump Historical Development, Measurement and Parts of Infusion Pump
Authors: Samuel Asrat
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Infusion pumps have become indispensable tools in modern healthcare, allowing for precise and controlled delivery of fluids, medications, and nutrients to patients. This paper provides an overview of the historical development, measurement, and parts of infusion pumps. The historical development of infusion pumps can be traced back to the early 1960s when the first rudimentary models were introduced. These early pumps were large, cumbersome, and often unreliable. However, advancements in technology and engineering over the years have led to the development of smaller, more accurate, and user-friendly infusion pumps. Measurement of infusion pumps involves assessing various parameters such as flow rate, volume delivered, and infusion duration. Flow rate, typically measured in milliliters per hour (mL/hr), is a critical parameter that determines the rate at which fluids or medications are delivered to the patient. Accurate measurement of flow rate is essential to ensure the proper administration of therapy and prevent adverse effects. Infusion pumps consist of several key parts, including the pump mechanism, fluid reservoir, tubing, and control interface. The pump mechanism is responsible for generating the necessary pressure to push fluids through the tubing and into the patient's bloodstream. The fluid reservoir holds the medication or solution to be infused, while the tubing serves as the conduit through which the fluid travels from the reservoir to the patient. The control interface allows healthcare providers to program and adjust the infusion parameters, such as flow rate and volume. In conclusion, infusion pumps have evolved significantly since their inception, offering healthcare providers unprecedented control and precision in delivering fluids and medications to patients. Understanding the historical development, measurement, and parts of infusion pumps is essential for ensuring their safe and effective use in clinical practice. Procedia PDF Downloads 682508 The Impact of Sedimentary Heterogeneity on Oil Recovery in Basin-plain Turbidite: An Outcrop Analogue Simulation Case Study
Authors: Bayonle Abiola Omoniyi
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In turbidite reservoirs with volumetrically significant thin-bedded turbidites (TBTs), thin-pay intervals may be underestimated during calculation of reserve volume due to poor vertical resolution of conventional well logs. This paper demonstrates the strong control of bed-scale sedimentary heterogeneity on oil recovery using six facies distribution scenarios that were generated from outcrop data from the Eocene Itzurun Formation, Basque Basin (northern Spain). The variable net sand volume in these scenarios serves as a primary source of sedimentary heterogeneity impacting sandstone-mudstone ratio, sand and shale geometry and dimensions, lateral and vertical variations in bed thickness, and attribute indices. The attributes provided input parameters for modeling the scenarios. The models are 20-m (65.6 ft) thick. Simulation of the scenarios reveals that oil production is markedly enhanced where degree of sedimentary heterogeneity and resultant permeability contrast are low, as exemplified by Scenarios 1, 2, and 3. In these scenarios, bed architecture encourages better apparent vertical connectivity across intervals of laterally continuous beds. By contrast, low net-to-gross Scenarios 4, 5, and 6, have rapidly declining oil production rates and higher water cut with more oil effectively trapped in low-permeability layers. These scenarios may possess enough lateral connectivity to enable injected water to sweep oil to production well; such sweep is achieved at a cost of high-water production. It is therefore imperative to consider not only net-to-gross threshold but also facies stack pattern and related attribute indices to better understand how to effectively manage water production for optimum oil recovery from basin-plain reservoirs.Keywords: architecture, connectivity, modeling, turbidites
Procedia PDF Downloads 272507 Fluid Structure Interaction Study between Ahead and Angled Impact of AGM 88 Missile Entering Relatively High Viscous Fluid for K-Omega Turbulence Model
Authors: Abu Afree Andalib, Rafiur Rahman, Md Mezbah Uddin
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The main objective of this work is to anatomize on the various parameters of AGM 88 missile anatomized using FSI module in Ansys. Computational fluid dynamics is used for the study of fluid flow pattern and fluidic phenomenon such as drag, pressure force, energy dissipation and shockwave distribution in water. Using finite element analysis module of Ansys, structural parameters such as stress and stress density, localization point, deflection, force propagation is determined. Separate analysis on structural parameters is done on Abacus. State of the art coupling module is used for FSI analysis. Fine mesh is considered in every case for better result during simulation according to computational machine power. The result of the above-mentioned parameters is analyzed and compared for two phases using graphical representation. The result of Ansys and Abaqus are also showed. Computational Fluid Dynamics and Finite Element analyses and subsequently the Fluid-Structure Interaction (FSI) technique is being considered. Finite volume method and finite element method are being considered for modelling fluid flow and structural parameters analysis. Feasible boundary conditions are also utilized in the research. Significant change in the interaction and interference pattern while the impact was found. Theoretically as well as according to simulation angled condition was found with higher impact.Keywords: FSI (Fluid Surface Interaction), impact, missile, high viscous fluid, CFD (Computational Fluid Dynamics), FEM (Finite Element Analysis), FVM (Finite Volume Method), fluid flow, fluid pattern, structural analysis, AGM-88, Ansys, Abaqus, meshing, k-omega, turbulence model
Procedia PDF Downloads 4682506 KTiPO4F: The Negative Electrode Material for Potassium Batteries
Authors: Vahid Ramezankhani, Keith J. Stevenson, Stanislav. S. Fedotov
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Lithium-ion batteries (LIBs) play a pivotal role in achieving the key objective “zero-carbon emission” as countries agreed to reach a 1.5ᵒC global warming target according to the Paris agreement. Nowadays, due to the tremendous mobile and stationary consumption of small/large-format LIBs, the demand and consequently the price for such energy storage devices have been raised. The aforementioned challenges originate from the shrinkage of the major applied critical materials in these batteries, such as cobalt (Co), nickel (Ni), Lithium (Li), graphite (G), and manganese (Mn). Therefore, it is imperative to consider alternative elements to address issues corresponding to the limitation of resources around the globe. Potassium (K) is considered an effective alternative to Li since K is a more abundant element, has a higher operating potential, a faster diffusion rate, and the lowest stokes radius in comparison to the closest neighbors in the periodic table (Li and Na). Among all reported materials for metal-ion batteries, some of them possess the general formula AMXO4L [A = Li, Na, K; M = Fe, Ti, V; X = P, S, Si; L= O, F, OH] is of potential to be applied both as anode and cathode and enable researchers to investigate them in the full symmetric battery format. KTiPO4F (KTP structural material) has been previously reported by our group as a promising cathode with decent electronic properties. Herein, we report a synthesis, crystal structure characterization, morphology, as well as K-ion storage properties of KTiPO4F. Our investigation reveals that KTiPO4F delivers discharge capacity > 150 mAh/g at 26.6 mA/g (C/5 current rate) in the potential window of 0.001-3 V. Surprisingly, the cycling performance of C-KTiPO4F//K cell is stable for 1000 cycles at 130 mA/g (C current rate), presenting capacity > 130 mAh/g. More interestingly, we achieved to assemble full symmetric batteries where carbon-coated KTiPO4F serves as both negative and positive electrodes, delivering >70 mAh/g in the potential range of 0.001-4.2V.Keywords: anode material, potassium battery, chemical characterization, electrochemical properties
Procedia PDF Downloads 2222505 The Cleavage of DNA by the Anti-Tumor Drug Bleomycin at the Transcription Start Sites of Human Genes Using Genome-Wide Techniques
Authors: Vincent Murray
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The glycopeptide bleomycin is used in the treatment of testicular cancer, Hodgkin's lymphoma, and squamous cell carcinoma. Bleomycin damages and cleaves DNA in human cells, and this is considered to be the main mode of action for bleomycin's anti-tumor activity. In particular, double-strand breaks are thought to be the main mechanism for the cellular toxicity of bleomycin. Using Illumina next-generation DNA sequencing techniques, the genome-wide sequence specificity of bleomycin-induced double-strand breaks was determined in human cells. The degree of bleomycin cleavage was also assessed at the transcription start sites (TSSs) of actively transcribed genes and compared with non-transcribed genes. It was observed that bleomycin preferentially cleaved at the TSSs of actively transcribed human genes. There was a correlation between the degree of this enhanced cleavage at TSSs and the level of transcriptional activity. Bleomycin cleavage is also affected by chromatin structure and at TSSs, the peaks of bleomycin cleavage were approximately 200 bp apart. This indicated that bleomycin was able to detect phased nucleosomes at the TSSs of actively transcribed human genes. The genome-wide cleavage pattern of the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin was also investigated in human cells. As found for bleomycin, these bleomycin analogues also preferentially cleaved at the TSSs of actively transcribed human genes. The cytotoxicity (IC₅₀ values) of these bleomycin analogues was determined. It was found that the degree of enhanced cleavage at TSSs was inversely correlated with the IC₅₀ values of the bleomycin analogues. This suggested that the level of cleavage at the TSSs of actively transcribed human genes was important for the cytotoxicity of bleomycin and analogues. Hence this study provided a deeper understanding of the cellular processes involved in the cancer chemotherapeutic activity of bleomycin.Keywords: anti-tumour activity, bleomycin analogues, chromatin structure, genome-wide study, Illumina DNA sequencing
Procedia PDF Downloads 1212504 Identification of the Key Enzyme of Roseoflavin Biosynthesis
Authors: V. Konjik, J. Schwartz, R. Sandhoff, M. Mack
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The rising number of multi-resistant pathogens demands the development of new antibiotics in order to reduce the lethal risk of infections. Here, we investigate roseoflavin, a vitamin B2 analogue which is produced by Streptomyces davawensis and Streptomyces cinnabarinus. We consider roseoflavin to be a 'Trojan horse' compound. Its chemical structure is very similar to riboflavin but in fact it is a toxin. Furthermore, it is a clever strategy with regard to the delivery of an antibiotic to its site of action but also with regard to the production of this chemical: The producer cell has only to convert a vitamin (which is already present in the cytoplasm) into a vitamin analog. Roseoflavin inhibits the activity of Flavin depending proteins, which makes up to 3.5 % of predicted proteins in organisms sequenced so far. We sequentially knocked out gene clusters and later on single genes in order to find the ones which are involved in the roseoflavin biosynthesis. Consequently, we identified the gene rosB, coding for the protein carrying out the first step of roseoflavin biosynthesis, starting form Flavin mononucleotide. Here we show, that the protein RosB has so far unknown features. It is per se an oxidoreductase, a decarboxylase and an aminotransferase, all rolled into one enzyme. A screen of cofactors revealed needs of oxygen, NAD+, thiamine and glutamic acid to carry out its function. Surprisingly, thiamine is not only needed for the decaboxylation step, but also for the oxidation of 8-demethyl-8-formyl Flavin mononucleotide. We had managed to isolate three different Flavin intermediates with different oxidation states, which gave us a mechanistic insight of RosB functionality. Our work points to a so far new function of thiamine in Streptomyces davawensis. Additionally, RosB could be extremely useful for chemical synthesis. Careful engineering of RosB may allow the site-specific replacement of methyl groups by amino groups in polyaromatic compounds of commercial interest. Finally, the complete clarification of the roseoflavin biosynthesis opens the possibility of engineering cost-effective roseoflavin producing strains.Keywords: antibiotic, flavin analogue, roseoflavin biosynthesis, vitamin B2
Procedia PDF Downloads 2432503 Increase of the Nanofiber Degradation Rate Using PCL-PEO and PCL-PVP as a Shell in the Electrospun Core-Shell Nanofibers Using the Needleless Blades
Authors: Matej Buzgo, Erico Himawan, Ksenija JašIna, Aiva Simaite
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Electrospinning is a versatile and efficient technology for producing nanofibers for biomedical applications. One of the most common polymers used for the preparation of nanofibers for regenerative medicine and drug delivery applications is polycaprolactone (PCL). PCL is a biocompatible and bioabsorbable material that can be used to stimulate the regeneration of various tissues. It is also a common material used for the development of drug delivery systems by blending the polymer with small active molecules. However, for many drug delivery applications, e.g. cancer immunotherapy, PCL biodegradation rate that may exceed 9 months is too long, and faster nanofiber dissolution is needed. In this paper, we investigate the dissolution and small molecule release rates of PCL blends with two hydrophilic polymers: polyethylene oxide (PEO) or polyvinylpyrrolidone (PVP). We show that adding hydrophilic polymer to the PCL reduces the water contact angle, increases the dissolution rate, and strengthens the interactions between the hydrophilic drug and polymer matrix that further sustain its release. Finally using this method, we were also able to increase the nanofiber degradation rate when PCL-PEO and PCL-PVP were used as a shell in the electrospun core-shell nanofibers and spread up the release of active proteins from their core. Electrospinning can be used for the preparation of the core-shell nanofibers, where active ingredients are encapsulated in the core and their release rate is regulated by the shell. However, such fibers are usually prepared by coaxial electrospinning that is an extremely low-throughput technique. An alternative is emulsion electrospinning that could be upscaled using needleless blades. In this work, we investigate the possibility of using emulsion electrospinning for encapsulation and sustained release of the growth factors for the development of the organotypic skin models. The core-shell nanofibers were prepared using the optimized formulation and the release rate of proteins from the fibers was investigated for 2 weeks – typical cell culture conditions.Keywords: electrospinning, polycaprolactone (PCL), polyethylene oxide (PEO), polyvinylpyrrolidone (PVP)
Procedia PDF Downloads 2742502 Phenotypical and Genotypical Diagnosis of Cystic Fibrosis in 26 Cases from East and South Algeria
Authors: Yahia Massinissa, Yahia Mouloud
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Cystic fibrosis (CF), the most common lethal genetic disease in the Europe population, is caused by mutations in the transmembrane conductance regulator gene (CFTR). It affects most organs including an epithelial tissue, base of hydroelectrolytic transepithelial transport, notably that aerial ways, the pancreas, the biliary ways, the intestine, sweat glands and the genital tractus. The gene whose anomalies are responsible of the cystic fibrosis codes for a protein Cl channel named CFTR (cystic fibrosis transmembrane conductance regulator) that exercises multiple functions in the cell, one of the most important in control of sodium and chlorine through epithelia. The deficient function translates itself notably by an abnormal production of viscous secretion that obstructs the execrator channels of this target organ: one observes then a dilatation, an inflammation and an atrophy of these organs. It also translates itself by an increase of the concentration in sodium and in chloride in sweat, to the basis of the sweat test. In order to do a phenotypical and genotypical diagnosis at a part of the Algerian population, our survey has been carried on 16 patients with evocative symptoms of the cystic fibrosis at that the clinical context has been confirmed by a sweat test. However, anomalies of the CFTR gene have been determined by electrophoresis in gel of polyacrylamide of the PCR products (polymerase chain reaction), after enzymatic digestion, then visualized to the ultraviolet (UV) after action of the ethidium bromide. All mutations detected at the time of our survey have already been identified at patients attained by this pathology in other populations of the world. However, the important number of found mutation with regard to the one of the studied patients testifies that the origin of this big clinical variability that characterizes the illness in the consequences of an enormous diversity of molecular defects of the CFTR gene.Keywords: cystic fibrosis, CFTR gene, polymorphism, algerian population, sweat test, genotypical diagnosis
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