Search results for: breast cancer cell lines

Authors: Noradin Ghadimi, Nima Amjady, Oveis Abedinia, Roza Poursoleiman

Abstract:

This paper proposed an Improved Honey Bee Mating Optimization (IHBMO) for a planning paradigm for network upgrade. The proposed technique is a new meta-heuristic algorithm which inspired by mating of the honey bee. The paradigm is able to select amongst several choices equi-cost one assuring the optimum in terms of voltage profile, considering various scenarios of DG penetration and load demand. The distributed generation (DG) has created a challenge and an opportunity for developing various novel technologies in power generation. DG prepares a multitude of services to utilities and consumers, containing standby generation, peaks chopping sufficiency, base load generation. The proposed algorithm is applied over the 30 lines, 28 buses power system. The achieved results demonstrate the good efficiency of the DG using the proposed technique in different scenarios.

Keywords: distributed generation, IHBMO, renewable energy units, network upgrade

Procedia PDF Downloads 488

Authors: Chen Wang, Jared Evans, Yan Asmann

Abstract:

With the quick evolvement of next-generation sequencing techniques, whole-exome or exome-panel data have become a cost-effective way for detection of small exonic mutations, but there has been a growing desire to accurately detect copy number variations (CNVs) as well. In order to address this research and clinical needs, we developed a sequencing coverage pattern-based method not only for copy number detections, data integrity checks, CNV calling, and visualization reports. The developed methodologies include complete automation to increase usability, genome content-coverage bias correction, CNV segmentation, data quality reports, and publication quality images. Automatic identification and removal of poor quality outlier samples were made automatically. Multiple experimental batches were routinely detected and further reduced for a clean subset of samples before analysis. Algorithm improvements were also made to improve somatic CNV detection as well as germline CNV detection in trio family. Additionally, a set of utilities was included to facilitate users for producing CNV plots in focused genes of interest. We demonstrate the somatic CNV enhancements by accurately detecting CNVs in whole exome-wide data from the cancer genome atlas cancer samples and a lymphoma case study with paired tumor and normal samples. We also showed our efficient reuses of existing exome sequencing data, for improved germline CNV calling in a family of the trio from the phase-III study of 1000 Genome to detect CNVs with various modes of inheritance. The performance of the developed method is evaluated by comparing CNV calling results with results from other orthogonal copy number platforms. Through our case studies, reuses of exome sequencing data for calling CNVs have several noticeable functionalities, including a better quality control for exome sequencing data, improved joint analysis with single nucleotide variant calls, and novel genomic discovery of under-utilized existing whole exome and custom exome panel data.

Keywords: bioinformatics, computational genetics, copy number variations, data reuse, exome sequencing, next generation sequencing

Procedia PDF Downloads 257

Authors: M. S. Jouini, A. Al-Sumaiti, M. Tembely, K. Rahimov

Abstract:

Characterizing rock properties of carbonate reservoirs is highly challenging because of rock heterogeneities revealed at several length scales. In the last two decades, the Digital Rock Physics (DRP) approach was implemented successfully in sandstone rocks reservoirs in order to understand rock properties behaviour at the pore scale. This approach uses 3D X-ray Microtomography images to characterize pore network and also simulate rock properties from these images. Even though, DRP is able to predict realistic rock properties results in sandstone reservoirs it is still suffering from a lack of clear workflow in carbonate rocks. The main challenge is the integration of properties simulated at different scales in order to obtain the effective rock property of core plugs. In this paper, we propose several approaches to characterize absolute permeability in some carbonate core plugs samples using multi-scale numerical simulation workflow. In this study, we propose a procedure to simulate porosity and absolute permeability of a carbonate rock sample using textures of Micro-Computed Tomography images. First, we discretize X-Ray Micro-CT image into a regular grid. Then, we use a textural parametric model to classify each cell of the grid using supervised classification. The main parameters are first and second order statistics such as mean, variance, range and autocorrelations computed from sub-bands obtained after wavelet decomposition. Furthermore, we fill permeability property in each cell using two strategies based on numerical simulation values obtained locally on subsets. Finally, we simulate numerically the effective permeability using Darcy’s law simulator. Results obtained for studied carbonate sample shows good agreement with the experimental property.

Keywords: multiscale modeling, permeability, texture, micro-tomography images

Procedia PDF Downloads 185

Authors: Parisa Mansour

Abstract:

Understanding how vision works in both health and disease involves understanding the anatomy and physiology of the eye as well as the neural pathways involved in visual perception. The development of imaging techniques for the visual system is essential for understanding the neural foundation of visual function or impairment. MRI provides a way to examine neural circuit structure and function without invasive procedures, allowing for the detection of brain tissue abnormalities in real time. One of the advanced MRI methods is manganese-enhanced MRI (MEMRI), which utilizes active manganese contrast agents to enhance brain tissue signals in T1-weighted imaging, showcasing connectivity and activity levels. The way manganese ions build up in the eye, and visual pathways can be due to their spread throughout the body or by moving locally along axons in a forward direction and entering neurons through calcium channels that are voltage-gated. The paramagnetic manganese contrast is utilized in MRI for various applications in the visual system, such as imaging neurodevelopment and evaluating neurodegeneration, neuroplasticity, neuroprotection, and neuroregeneration. In this assessment, we outline four key areas of scientific research where MEMRI can play a crucial role - understanding brain structure, mapping nerve pathways, monitoring nerve cell function, and distinguishing between different types of glial cell activity. We discuss various studies that have utilized MEMRI to investigate the visual system, including delivery methods, spatiotemporal features, and biophysical analysis. Based on this literature, we have pinpointed key issues in the field related to toxicity, as well as sensitivity and specificity of manganese enhancement. We will also examine the drawbacks and other options to MEMRI that could offer new possibilities for future exploration.

Keywords: glial activity, manganese-enhanced magnetic resonance imaging, neuroarchitecture, neuronal activity, neuronal tract tracing, visual pathway, eye

Procedia PDF Downloads 42

Authors: T. Abdelkrim, K. Ben Seddik, B. Bezza, K. Benamrane, Aeh. Benkhelifa

Abstract:

This paper proposes an implementation of boost converter for a resistive load using photovoltaic energy as a source. The model of photovoltaic cell and operating principle of boost converter are presented. A PIC micro controller is used in the close loop control to generate pulses for controlling the converter circuit. To performance evaluation of boost converter, a variation of output voltage of PV panel is done by shading one and two cells.

Keywords: boost converter, microcontroller, photovoltaic power generation, shading cells

Procedia PDF Downloads 879

Authors: Jose Melena, Rosa Santander, Tanya Gonzalez, Richard Duque, Juan Illanes

Abstract:

Ecuador is one of the countries with the greatest aquatic biodiversity worldwide. In particular, there are at least a dozen native marine species with great aquaculture potential locally. This research concerns one of those species. It has proposed to implement experimental protocols in order to induce spawning and to generate the early larval development of the giant reef clam P. multicostata under controlled conditions. Bioassays were carried out with one adult batch (n= 8) with an average valvar length of 118,4 ± 5,8 mm, which were collected near of the Puerto Santa Rosa (2° 12' 30'' S, 80° 58' 28'' W), Santa Elena Province. During a short acclimation stage, the eight adults of giant reef clam P. multicostata were exposed to thermal stress. Briefly, the experimental protocol for spawning induction was based on the application of 20°C for 1 h and 30°C for 1 h on P. multicostata broodstock at least three consecutive times by one day. After spawning, collected sexual material was released for external fertilization process. After the delivery of gametes, it was achieved 3,25 × 10⁶ viable zygotes. As results, fertilized eggs had 56 µm diameter; while first and second cell divisions were observed to 2,5 h post-fertilization, with individual average length of 68 ± 5 µm and polar body. Latter cell divisions, including gastrula stage, appeared at 9 h post-fertilization, with individual average length of 73 ± 4 µm and trochophore stage at 15 h post-fertilization with individual average length of 75 ± 4 µm. In addition, veliger stage was registered at 20 h post-fertilization with individual average length of 82 ± 6 µm. Umboned larvae appeared at day 8 post-fertilization, with individual average length of 148 ± 6 µm. These pioneering results worldwide can strengthen the local conservation process of the overexploited P. multicostata and to encourage its production for commercial purposes.

Keywords: Ecuador, larval development, Periglypta multicostata, spawning induction

Procedia PDF Downloads 137

Authors: Younus Mohammad, Anita B. Fallah, Ben J. Boyd, Shakila B. Rizwan

Abstract:

N-acylethanolamines (NAEs) are endogenous lipids, which have neuromodulatory properties. NAEs have shown neuroprotective properties in various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and ischemic stroke. However, NAEs are eliminated rapidly in vivo by enzymatic hydrolysis. We propose to encapsulate NAEs in liquid crystalline nanoparticles (cubosomes) to increase their biological half-life and explore their therapeutic potential. Recently, we have reported the co-formulation and nanostructural characterization of cubosomes containing the NAE, oleoylethanolamide and a synthetic cubosome forming lipid phytantriol. Here, we report on the formulation of cubosomes with the NAE, linoleoylethanolamide (LEA) as the core cubosome forming lipid. LEA-cubosomes were formulated in the presence of three different steric stabilisers: two brain targeting ligands, Tween 80 and Pluronic P188 and a control, Pluronic F127. Size, morphology and internal structure of formulations were characterized by dynamic light scattering (DLS), cryogenic transmission electron microscopy (Cryo–TEM) and small angle X–ray scattering (SAXS), respectively. Chemical stability of LEA in formulations was investigated using high-performance liquid chromatography (HPLC). Cytotoxicity of formulations towards human cerebral microvascular endothelial cell line (hCMEC/D3) was also investigated using an MTT (3-[4, 5- dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay. All cubosome formulations had mean particle size of less than 250 nm and were uniformly distributed with polydispersity indices less than 0.2. Cubosomes produced had a bicontinuous cubic internal structure with an Im3m space group but different lattice parameters, indicating the different modes of interaction between the stabilisers and LEA. LEA in formulations was found to be chemically stable. At concentrations of up to 20 µg/mL LEA in the presence of all the stabilisers, greater than 80% cell viability was observed.

Keywords: blood-brain barrier, cubosomes, linoleoyl ethanolamide, N-acylethanolamines (NAEs)

Procedia PDF Downloads 203

Authors: Asegid Belay Kebede, Getachew Biru Worku

Abstract:

The Earth and its inhabitants have faced an existential threat as a result of severe manmade actions. Global warming and climate change have been the most apparent manifestations of this threat throughout the world, with increasingly intense heat waves, temperature rises, flooding, sea-level rise, ice sheet melting, and so on. One of the major contributors to this disaster is the ever-increasing production and consumption of energy, which is still primarily fossil-based and emits billions of tons of hazardous GHG. The transportation industry is recognized as the biggest actor in terms of emissions, accounting for 24% of direct CO2 emissions and being one of the few worldwide sectors where CO2 emissions are still growing. Rail transportation, which includes all from light rail transit to high-speed rail services, is regarded as one of the most efficient modes of transportation, accounting for 9% of total passenger travel and 7% of total freight transit. Nonetheless, there is still room for improvement in the transportation sector, which might be done by incorporating alternative and/or renewable energy sources. As a result of these rapidly changing global energy situations and rapidly dwindling fossil fuel supplies, we were driven to analyze the possibility of renewable energy sources for traction applications. Even a small achievement in energy conservation or harnessing might significantly influence the total railway system and have the potential to transform the railway sector like never before. As a result, the paper begins by assessing the potential for photovoltaic (PV) power generation on train rooftops and existing infrastructure such as railway depots, passenger stations, traction substation rooftops, and accessible land along rail lines. As a result, a method based on a Google Earth system (using Helioscopes software) is developed to assess the PV potential along rail lines and on train station roofs. As an example, the Addis Ababa light rail transit system (AA-LRTS) is utilized. The case study examines the electricity-generating potential and economic performance of photovoltaics installed on AALRTS. As a consequence, the overall capacity of solar systems on all stations, including train rooftops, reaches 72.6 MWh per day, with an annual power output of 10.6 GWh. Throughout a 25-year lifespan, the overall CO2 emission reduction and total profit from PV-AA-LRTS can reach 180,000 tons and 892 million Ethiopian birrs, respectively. The PV-AA-LRTS has a 200% return on investment. All PV stations have a payback time of less than 13 years, and the price of solar-generated power is less than $0.08/kWh, which can compete with the benchmark price of coal-fired electricity. Our findings indicate that PV-AA-LRTS has tremendous potential, with both energy and economic advantages.

Keywords: sustainable development, global warming, energy crisis, photovoltaic energy conversion, techno-economic analysis, transportation system, light rail transit

Procedia PDF Downloads 76

Authors: Rahma Goussi, Walid Derbali, Arafet Manaa, Simone Cantamessa, Graziella Berta, Chedly Abdelly, Roberto Barbato

Abstract:

Salinity is one of the most important abiotic affecting plant growth and productivity worldwide. Photosynthesis, together with cell growth, is among the primary processes to be affected by salinity. Here, we report the effects of salinity stress on the primary processes of photosynthesis in a model halophyte Thellungiella Salsuginea. Plants were cultivated in hydroponic system with different NaCl concentrations (0, 100, 200 and 400 mM) during 2 weeks. The obtained results showed an obvious change in the photosynthetic efficiency of photosystem I (PSI) and phostosytem II (PSII), related to NaCl concentration supplemented to the medium and the stress duration considered. With moderate salinity (100 and 200 mM NaCl), no significant variation was observed in photosynthetic parameters of PSI and PSII and Chl fluorescence whatever the time of stress application. Also, the photosynthesis apparatus Fo, Fm and Fv fluorescence, as well as Fv/Fm were not affected by salt stress. While a significant decrease was observed on quantum yields Y(I), Y(II) and electron transport rate ETR(I), ETR(II) under high salt treatment (400 mM NaCl) with prolonged period (15 days). This reduction is quantitatively compensated by a corresponding increase of energy dissipation Y(NPQ) and a progressive decrease in Fv/Fm under salt treatment. The intensity of the OJIP fluorescence transient decreased with increase in NaCl concentration, with a major effect observed during prolonged period of salt stress. Ultrastructural analysis with Light Microscopy and Transmission Electron Microscopy of T. salsuginea chloroplasts showed some cellular changes, such as the shape of the mesophyll cells and number of chloroplast/cell only under higher NaCl concentration. Salt-stress caused the swelling of thylakoids in T. Salsuginea mesophyll with more accumulation of starch as compared to control plant.

Keywords: fluorescence, halophyte, photosynthesis, salt stress

Procedia PDF Downloads 376

Authors: Marcio Mesquita, Diogo Henrique Morato de Moraes, Henrique Fonseca Elias de Oliveira, Rilner Alves Flores, Mateus Rodrigues Ferreira, Dalva Graciano Ribeiro

Abstract:

This study aimed to analyze the movement of water in irrigated and non-irrigated rice (Oryza sativa L.) leaves, from the xylem to the stomata, through numerical simulations. Through three-dimensional modeling, it was possible to determine how the spacing of parenchyma cells and the permeability of these cells influence the apoplastic flow and the opening of the stomata. The thickness of the cuticle and the number of vascular bundles are greater in plants subjected to water stress, indicating an adaptive response of plants to environments with water deficit. In addition, numerical simulations revealed that the opening of the stomata, the permeability of the parenchyma cells and the cell spacing have significant impacts on the energy loss and the speed of water movement. It was observed that a more open stoma facilitates water flow, decreasing the resistance and energy required for transport, while higher levels of permeability reduce energy loss, indicating that a more permeable tissue allows for more efficient water transport. Furthermore, it was possible to note that stomatal aperture, parenchyma permeability and cell spacing are crucial factors in the efficient water management of plants, especially under water stress conditions. These insights are essential for the development of more effective agricultural management strategies and for the breeding of plant varieties that are more resistant to adverse growing conditions. Computed fluid dynamics has allowed us to overcome the limitations of conventional techniques by providing a means to visualize and understand the complex hydrodynamic processes within the vascular system of plants.

Keywords: numerical modeling, vascular anatomy, vascular hydrodynamics, xylem, Oryza sativa L.

Procedia PDF Downloads 20

Authors: Enoch Kudoahor, Nan Zheng

Abstract:

We describe the use of readily available self-doped TiO2 and visible light, under a mild condition to synthesize a class of monocyclic, bicyclic, and benzocyclobutene amino compounds containing the endoperoxide bridges; their derivatives and further test their effective clinical activities against malaria, cancer, and their resistances. Considering their stable under photooxidation conditions and recyclability, we use a self-doped TiO2 under a visible condition to synthesize these classes of amino endoperoxides. These amino endoperoxides are stable over a period compared to classes of endoperoxides.

Keywords: catalysis, endoperoxides, titanium dioxide, visible light

Procedia PDF Downloads 156

Authors: Nalan Kaya, D. Ozlem Dabak, Gonca Ozan, Elif Erdem, Enver Ozan

Abstract:

One of the common causes of cardiovascular disease (CVD) is smoking. Moreover, tobacco smoke decreases the amount of oxygen that the blood can carry and increases the tendency for blood clots. Ellagic acid is a powerful antioxidant found especially in red fruits. It was shown to block atherosclerotic process suppressing oxidative stress and inflammation. The aim of this study was to examine the protective effects of ellagic acid against oxidative damage on heart tissues of rats induced by tobacco smoke. Twenty-four male adult (8 weeks old) Spraque-Dawley rats were divided randomly into 4 equal groups: group I (Control), group II (Tobacco smoke), group III (Tobacco smoke + corn oil) and group IV (Tobacco smoke + ellagic acid). The rats in group II, III and IV, were exposed to tobacco smoke 1 hour twice a day for 12 weeks. In addition to tobacco smoke exposure, 12 mg/kg ellagic acid (dissolved in corn oil), was applied to the rats in group IV by oral gavage. An equal amount of corn oil used in solving ellagic acid was applied to the rats by oral gavage in group III. At the end of the experimental period, rats were decapitated. Heart tissues and blood samples were taken. Histological and biochemical analyzes were performed. Vascular congestion, hyperemic areas, inflammatory cell infiltration and increased connective tissue in the perivascular area were observed in tobacco smoke and tobacco smoke + corn oil groups. Increased connective tissue in the perivascular area, hemorrhage and inflammatory cell infiltration were decreased in tobacco smoke + EA group. Group-II GSH level was not changed (significantly), CAT, SOD, GPx activities were significantly higher than group-I. Compared to group-II, group-IV GSH, SOD, CAT, GPx activities were increased, and MDA level was decreased significantly. Group-II and Group-III levels were similar. The results indicate that ellagic acid could protect the heart tissue from the tobacco smoke harmful effects.

Keywords: ellagic acid, heart, rat, tobacco smoke

Procedia PDF Downloads 227

Authors: Lígia Pimentel, Miguel Pereira, Manuela Pintado

Abstract:

Wheat germ is a by-product of wheat flour refining. Despite this by-product being a source of proteins, lipids, fibres and complex carbohydrates, and consequently a valuable ingredient to be used in Food Industry, only few applications have been studied. The main goal of this study was to assess the potential prebiotic effect of natural wheat germ. The prebiotic potential was evaluated by in vitro assays with individual microbial strains (Lactobacillus paracasei L26 and Lactobacillus casei L431). A simulated model of the gastrointestinal digestion was also used including the conditions present in the mouth (artificial saliva), oesophagus–stomach (artificial gastric juice), duodenum (artificial intestinal juice) and ileum. The effect of natural wheat germ and wheat germ after digestion on the growth of lactic acid bacteria was studied by growing those microorganisms in de Man, Rogosa and Sharpe (MRS) broth (with 2% wheat germ and 1% wheat germ after digestion) and incubating at 37 ºC for 48 h with stirring. A negative control consisting of MRS broth without glucose was used and the substrate was also compared to a commercial prebiotic fructooligosaccharides (FOS). Samples were taken at 0, 3, 6, 9, 12, 24 and 48 h for bacterial cell counts (CFU/mL) and pH measurement. Results obtained showed that wheat germ has a stimulatory effect on the bacteria tested, presenting similar (or even higher) results to FOS, when comparing to the culture medium without glucose. This was demonstrated by the viable cell counts and also by the decrease on the medium pH. Both L. paracasei L26 and L. casei L431 could use these compounds as a substitute for glucose with an enhancement of growth. In conclusion, we have shown that wheat germ stimulate the growth of probiotic lactic acid bacteria. In order to understand if the composition of gut bacteria is altered and if wheat germ could be used as potential prebiotic, further studies including faecal fermentations should be carried out. Nevertheless, wheat germ seems to have potential to be a valuable compound to be used in Food Industry, mainly in the Bakery Industry.

Keywords: by-products, functional ingredients, prebiotic potential, wheat germ

Procedia PDF Downloads 489

Authors: Kinyas Aydin, Fatih Erguney, Tolga Ceper, Serap Ozay, Ipar N. Uzun, Sebnem Kemaloglu Dogan, Deniz Tunc

Abstract:

In order to meet high growth rates in baby diaper industry worldwide, the high-speed textile backsheet lamination lines have recently been introduced to the market for non-woven/film lamination applications. It is a process where two substrates are bonded to each other via hotmelt adhesive (HMA). Nonwoven (NW) lamination system basically consists of 4 components; polypropylene (PP) nonwoven, polyethylene (PE) film, HMA and applicator system. Each component has a substantial effect on the process efficiency of continuous line and final product properties. However, for a precise subject cover, we will be addressing only the main challenges and possible solutions in this paper. The NW is often produced by spunbond method (SSS or SMS configuration) and has a 10-12 gsm (g/m²) basis weight. The NW rolls can have a width and length up to 2.060 mm and 30.000 linear meters, respectively. The PE film is the 2ⁿᵈ component in TBS lamination, which is usually a 12-14 gsm blown or cast breathable film. HMA is a thermoplastic glue (mostly rubber based) that can be applied in a large range of viscosity ranges. The main HMA application technology in TBS lamination is the slot die application in which HMA is spread on the top of the NW along the whole width at high temperatures in the melt form. Then, the NW is passed over chiller rolls with a certain open time depending on the line speed. HMAs are applied at certain levels in order to provide a proper de-lamination strength in cross and machine directions to the entire structure. Current TBS lamination line speed and width can be as high as 800 m/min and 2100 mm, respectively. They also feature an automated web control tension system for winders and unwinders. In order to run a continuous trouble-free mass production campaign on the fast industrial TBS lines, rheological properties of HMAs and micro-properties of NWs can have adverse effects on the line efficiency and continuity. NW fiber orientation and fineness, as well as spun/melt blown composition fabric micro-level properties, are the significant factors to affect the degree of “HMA bleed through.” As a result of this problem, frequent line stops are observed to clean the glue that is being accumulated on the chiller rolls, which significantly reduces the line efficiency. HMA rheology is also important and to eliminate any bleed through the problem; one should have a good understanding of rheology driven potential complications. So, the applied viscosity/temperature should be optimized in accordance with the line speed, line width, NW characteristics and the required open time for a given HMA formulation. In this study, we will show practical aspects of potential preventative actions to minimize the HMA bleed through the problem, which may stem from both HMA rheological properties and NW spun melt/melt blown fiber characteristics.

Keywords: breathable, hotmelt, nonwoven, textile backsheet lamination, spun/melt blown

Procedia PDF Downloads 363

Authors: Gehan ElAkabawy

Abstract:

Background: Diabetes mellitus causes severe deteriorations of almost all the organs and systems of the body, as well as significant damage to the oral cavity. The oral changes are mainly related to salivary glands dysfunction characterized by hyposalivation and xerostomia, which significantly reduce diabetic patients’ quality of life. Human dental pulp stem cells represent a promising source for cell-based therapies, owing to their easy, minimally invasive surgical access, and high proliferative capacity. It was reported that the trophic support mediated by dental pulp stem cells can rescue the functional and structural alterations of damaged salivary glands. However, potential differentiation and paracrine effects of human dental pulp stem cells in diabetic-induced parotid gland damage have not been previously investigated. Our study aimed to investigate the therapeutic effects of intravenous transplantation of human dental pulp stem cells (hDPSCs) on parotid gland injury in a rat model of streptozotocin (STZ)-induced type 1 diabetes. Methods: Thirty Sprague-Dawley male rats were randomly categorised into three groups: control, diabetic (STZ), and transplanted (STZ+hDPSCs). hDPSCs or vehicle was injected into the tail vein 7 days after STZ injection. The fasting blood glucose levels were monitored weekly. A glucose tolerance test was performed, and the parotid gland weight, salivary flow rate, oxidative stress indices, parotid gland histology, and caspase-3, vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) expression in parotid tissues were assessed 28 days post-transplantation. Results: Transplantation of hDPSCs downregulated blood glucose, improved the salivary flow rate, and reduced oxidative stress. The cells migrated to, survived, and differentiated into acinar, ductal, and myoepithelial cells in the STZ-injured parotid gland. Moreover, they downregulated the expression of caspase-3 and upregulated the expression of VEGF and PCNA, likely exerting pro-angiogenetic and antiapoptotic effects and promoting endogenous regeneration. In addition, the transplanted cells enhanced the parotid nitric oxide (NO) -tetrahydrobiopterin (BH4) pathway. Conclusions: Our results show that hDPSCs can migrate to and survive within the STZ-injured parotid gland, where they prevent its functional and morphological damage by restoring normal glucose levels, differentiating into parotid cell populations, and stimulating paracrine-mediated regeneration. Thus, hDPSCs may have therapeutic potential in the treatment of diabetes-induced parotid gland injury.

Keywords: dental pulp stem cells, diabetes, streptozotocin, parotid gland

Procedia PDF Downloads 198

Authors: Shatakshi Garg

Abstract:

As the world continues to grapple with the COVID-19 pandemic, India, one of the most populous democratic federal developing nation, continues to report the highest active cases and deaths, as well as struggle to let its health infrastructure not succumb to the exponentially growing requirements of hospital beds, ventilators, oxygen to save thousands of lives daily at risk. In this context, the paper outlines the handling of the COVID-19 pandemic since it first hit India in January 2020 – the policy decisions taken by the Union and the State governments from the larger perspective of its federal structure. The Constitution of India adopted in 1950 enshrined the federal relations between the Union and the State governments by way of the constitutional division of revenue-raising and expenditure responsibilities. By way of the 72nd and 73rd Amendments in the Constitution, powers and functions were devolved further to the third tier, namely the local governments, with the intention of further strengthening the federal structure of the country. However, with time, several constitutional amendments have shifted the scales in favour of the union government. The paper briefly traces some of these major amendments as well as some policy decisions which made the federal relations asymmetrical. As a result, data on key fiscal parameters helps establish how the union government gained upper hand at the expense of weak state governments, reducing the local governments to mere constitutional bodies without adequate funds and fiscal autonomy to carry out the assigned functions. This quasi-federal structure of India with the union government amassing the majority of power in terms of ‘funds, functions and functionaries’ exposed the perils of weakening sub-national governments post COVID-19 pandemic. With a complex quasi-federal structure and a heterogeneous population of over 1.3 billion, the announcement of a sudden nationwide lockdown by the union government was followed by a plight of migrants struggling to reach homes safely in the absence of adequate arrangements for travel and safety-net made by the union government. With limited autonomy enjoyed by the states, they were mostly dictated by the union government on most aspects of handling the pandemic, including protocols for lockdown, re-opening post lockdown, and vaccination drive. The paper suggests that certain policy decisions like demonetization, the introduction of GST, etc., taken by the incumbent government since 2014 when they first came to power, have further weakened the states and local governments, which have amounted to catastrophic losses, both economic and human. The role of the executive, legislature and judiciary are explored to establish how all these three arms of the government have worked simultaneously to further weaken and expose the fault-lines of the federal structure of India, which has lent the nation incapacitated to handle this pandemic. The paper then suggests the urgency of re-looking at the federal structure of the country and undertaking measures that strengthen the sub-national governments and restore the federal spirit as was enshrined in the constitution to avoid mammoth human and economic losses from a pandemic of this sort.

Keywords: COVID-19 pandemic, India, federal structure, economic losses

Procedia PDF Downloads 180

Authors: Ramon Hernán, Maria Teresa Corzo

Abstract:

This study examines the impact and contribution of the main journals in the discipline of behavioral finance to determine the state of the art of the discipline and the growth lines and concepts studied to date. This is a unique and novel study given that a review of the discipline has not been carried out through the keywords of the articles that allows visualizing through this component of the research, which are the main topics of discussion and the relationships that arise between the concepts discussed. To carry out this study, 3,876 articles have been taken as a reference, which includes 15,859 keywords from the main journals responsible for the growth of the discipline.; Journal of Behavioral Finance, Review of Behavioral Finance, Journal of Behavioral and Experimental Economics, Journal of Behavioral and Experimental Economics and Review of Behavioral Finance. The results indicate which are the topics most covered in the discipline throughout the period from 2000 to 2020, how these concepts have been dealt with on a recurring basis along with others throughout the aforementioned period and how the different concepts have been grouped based on the keywords established by the authors for the classification of their articles with a network diagram to complete the analysis.

Keywords: behavioral finance, keywords, co-words, top journals, data visualization

Procedia PDF Downloads 193

Authors: Ananya Govindarajan

Abstract:

Tetrahymena thermophila is a single-cell, eukaryotic organism that belongs to the Protozoa Kingdom. Tetrahymena thermophila is often used in signal transduction pathway studies because of its ability to model sensory input and the effects of environmental conditions such as chemicals and temperature. The recently discovered G37 chemorepellent receptor showed increased responsiveness to all chemorepellents. Investigating the mutant G37 Tetrahymena gene in various test solutions, including ferric chloride, ferrous sulfate, hydrogen peroxide, tetrazolium blue, potassium chloride, and dithiothreitol were performed to determine the role of oxidants and reducing agents with the mutant and wild-type cells (CU427) to assess the role of the receptor. Behavioral assays and recordings processed by ImageJ indicated that ferric chloride, hydrogen peroxide, and tetrazolium blue yielded little to no chemorepellent responses from G37 cells (<20% ARs). CU427 cells were over-responsive based on the mean percent of cells (>50% ARs). Reducing agents elicited chemorepellent responses from both G37 and CU427, in addition to potassium chloride. Cell responses were classified as over-responsive (>50% ARs). Dithiothreitol yielded unexpected results as G37 (37.0% ARs) and CU427 (38.1% ARs) had relatively similar responses and were only responsive and not over-responsive to the reducing agent test chemical solution. Ultimately, this indicates that the G37 receptor is more interactive with molecules that are reducing agents or non-oxidant compounds; G37 may be unable to sense and respond to oxidants effectively, further elucidating the pathways of the G37 strain and nature of this receptor. Results also indicate that the CSF most likely contained an oxidant, like ferric chloride. This research can be further applied to neuronal influences and how specific compounds may affect human neurons individually and their excitability as the responses model action potentials and membrane potential.

Keywords: tetrahymena thermophila, signal transduction, chemosensory, oxidant, reducing agent

Procedia PDF Downloads 132

Authors: Shakir Ullah

Abstract:

This article reviews social science understanding to explore the challenges megaprojects face before and after implementation. It also sheds light on the problems directly and indirectly caused by mega development projects in the project implemented areas. By Using a qualitative approach such as thematic analysis, the article uses recent literature such as published articles, government reports, and books to cite examples of different mega projects worldwide. The study report that mega development projects are a necessary element of the modern-day infrastructural development process as they represent the perfect example of urban socioeconomic development. They are introduced and implemented by multinational companies with the support of state authorities to produce the common good. However, they are not devoid of their critical challenges and bring implicit and explicit problems to the targeted localities. The article takes insights from social science research for suggestions on how to reduce the challenges faced by project implementers and problems received by local people due to the fault lines of such projects.

Keywords: development, mega-projects, challenges, problems

Procedia PDF Downloads 104

Authors: Christos E. Lampropoulos, Maria Konsta, Tamta Sirbilatze, Ifigenia Apostolou, Vicky Dradaki, Konstantina Panouria, Irini Dri, Christina Kordali, Vaggelis Lambas, Georgios Mavras

Abstract:

Objectives: Full Mini Nutritional Assessment (MNA) questionnaire is one of the most useful tools in diagnosis of malnutrition in hospitalized patients, which is related to increased morbidity and mortality. The purpose of our study was to assess the nutritional status of elderly, hospitalized patients and examine the hypothesis that MNA may predict mortality and extension of hospitalization. Methods: One hundred fifty patients (78 men, 72 women, mean age 80±8.2) were included in this cross-sectional study. The following data were taken into account in analysis: anthropometric and laboratory data, physical activity (International Physical Activity Questionnaires, IPAQ), smoking status, dietary habits, cause and duration of current admission, medical history (co-morbidities, previous admissions). Primary endpoints were mortality (from admission until 6 months afterwards) and duration of admission. The latter was compared to national guidelines for closed consolidated medical expenses. Logistic regression and linear regression analysis were performed in order to identify independent predictors for mortality and extended hospitalization respectively. Results: According to MNA, nutrition was normal in 54/150 (36%) of patients, 46/150 (30.7%) of them were at risk of malnutrition and the rest 50/150 (33.3%) were malnourished. After performing multivariate logistic regression analysis we found that the odds of death decreased 20% per each unit increase of full MNA score (OR=0.8, 95% CI 0.74-0.89, p < 0.0001). Patients who admitted due to cancer were 23 times more likely to die, compared to those with infection (OR=23, 95% CI 3.8-141.6, p=0.001). Similarly, patients who admitted due to stroke were 7 times more likely to die (OR=7, 95% CI 1.4-34.5, p=0.02), while these with all other causes of admission were less likely (OR=0.2, 95% CI 0.06-0.8, p=0.03), compared to patients with infection. According to multivariate linear regression analysis, each increase of unit of full MNA, decreased the admission duration on average 0.3 days (b:-0.3, 95% CI -0.45 - -0.15, p < 0.0001). Patients admitted due to cancer had on average 6.8 days higher extension of hospitalization, compared to those admitted for infection (b:6.8, 95% CI 3.2-10.3, p < 0.0001). Conclusion: Mortality and extension of hospitalization is significantly increased in elderly, malnourished patients. Full MNA score is a useful diagnostic tool of malnutrition.

Keywords: duration of admission, malnutrition, mini nutritional assessment score, prognostic factors for mortality

Procedia PDF Downloads 313

Authors: Rahim Ada, Mustafa Harmankaya, Sadiye Ayse Celik

Abstract:

The safflower seed contains about 25-40% solvent extract and 20-33% fiber. It is well known that dietary phospholipids lower serum cholesterol levels effectively. The nutrient composition of safflower seed changes depending on region, soil and genotypes. This research was made by using of six natural selected (A22, A29, A30, C12, E1, F4, G8, G12, J27) and three commercial (Remzibey, Dincer, Black Sun1) varieties of safflower genotypes. The research was conducted on field conditions for two years (2009 and 2010) in randomized complete block design with three replications in Konya-Turkey ecological conditions. Oil contents, mineral contents and their correlations were determined in the research. According to the results, oil content was ranged from 22.38% to 34.26%, while the minerals were in between the following values: 1469, 04-2068.07 mg kg^-1 for Ca, 7.24-11.71 mg kg^-1 for B, 13.29-17.41 mg kg^-1 for Cu, 51.00-79.35 mg kg^-1 for Fe, 3988-6638.34 mg kg^-1 for K, 1418.61-2306.06 mg kg^-1 for Mg, 11.37-17.76 mg kg^-1 for Mn, 4172.33-7059.58 mg kg^-1 for P and 32.60-59.00 mg kg^-1 for Zn. Correlation analysis that was made separately for the commercial varieties and wild lines showed that high level of oil content was negatively affected by all the investigated minerals except for K and Zn in the commercial varieties.

Keywords: safflower, oil, quality, mineral content

Procedia PDF Downloads 268

Authors: Amanda Cristina de Oliveira, Elias de Souza Monteiro Filho, Roberta Ceriani

Abstract:

Liquid-liquid extraction in aqueous two-phase systems (ATPSs) constitutes a powerful tool for purifying bio-materials, such as cells, organelles, proteins, among others. In this work, the extraction of the bovine serum albumin (BSA) has been studied in systems formed by polyethylene glycol (PEG) (1500, 4000, and 6000 g.mol⁻¹) + potassium sodium tartrate + water at 303.15°K. Phase diagrams were obtained by turbidimetry and Merchuk’s method (1998). The experimental tie-lines were described using the Othmer-Tobias and Bancroft correlations. ATPSs were correlated with the nonrandom two-liquid (NRTL) model. The results were considered excellent according to global root-mean-square deviations found which were between 0,72 and 1,13%. The concentrations of the proteins in each phase were determined by spectrophotometry at 280 nm, finding partition efficiencies greater than 71%.

Keywords: aqueous two phases systems, bovine serum albumin , liquid-liquid extraction, polyethylene glycol

Procedia PDF Downloads 161

Authors: Anuj Kumar, Kummara M. Rao, Sung S. Han

Abstract:

Bone tissue engineering has emerged as a potentially alternative method for localized bone defects or diseases, congenital deformation, and surgical reconstruction. The designing and the fabrication of the ideal scaffold is a great challenge, in restoring of the damaged bone tissues via cell attachment, proliferation, and differentiation under three-dimensional (3D) biological micro-/nano-environment. In this case, hydrogel system composed of high hydrophilic 3D polymeric-network that is able to mimic some of the functional physical and chemical properties of the extracellular matrix (ECM) and possibly may provide a suitable 3D micro-/nano-environment (i.e., resemblance of native bone tissues). Thus, this proposed hydrogel system is highly permeable and facilitates the transport of the nutrients and metabolites. However, the use of hydrogels in bone tissue engineering is limited because of their low mechanical properties (toughness and stiffness) that continue to posing challenges in designing and fabrication of tough and stiff hydrogels along with improved bioactive properties. For this purpose, in our lab, polyacrylamide-based hybrid hydrogels were synthesized by involving sodium alginate, cellulose nanocrystals and silica-based glass using one-step free-radical polymerization. The results showed good in vitro apatite-forming ability (biomineralization) and improved mechanical properties (under compression in the form of strength and stiffness in both wet and dry conditions), and in vitro osteoblastic (MC3T3-E1 cells) cytocompatibility. For in vitro cytocompatibility assessment, both qualitative (attachment and spreading of cells using FESEM) and quantitative (cell viability and proliferation using MTT assay) analyses were performed. The obtained hybrid hydrogels may potentially be used in bone tissue engineering applications after establishment of in vivo characterization.

Keywords: bone tissue engineering, cellulose nanocrystals, hydrogels, polyacrylamide, sodium alginate

Procedia PDF Downloads 152

Authors: Gülşen Akın Evingür, Önder Pekcan

Abstract:

The fractal analysis is a bridge between the microstructure and macroscopic properties of gels. Fractal structure is usually provided to define the complexity of crosslinked molecules. The complexity in gel systems is described by the fractal dimension (Df). In this study, polyacrylamide- graphene oxide (GO) composite gels were prepared by free radical crosslinking copolymerization. The fractal analysis of polyacrylamide- graphene oxide (GO) composite gels were analyzed in various GO contents during gelation and were investigated by using Fluorescence Technique. The analysis was applied to estimate Df s of the composite gels. Fractal dimension of the polymer composite gels were estimated based on the power law exponent values using scaling models. In addition, here we aimed to present the geometrical distribution of GO during gelation. And we observed that as gelation proceeded GO plates first organized themselves into 3D percolation cluster with Df=2.52, then goes to diffusion limited clusters with Df =1.4 and then lines up to Von Koch curve with random interval with Df=1.14. Here, our goal is to try to interpret the low conductivity and/or broad forbidden gap of GO doped PAAm gels, by the distribution of GO in the final form of the produced gel.

Keywords: composite gels, fluorescence, fractal, scaling

Procedia PDF Downloads 308

Authors: Darawan Augsornwan, Artitaya Sabangbal, Maneewan Srijan, Kanokarn Kongpitee, Lalida Petphai, Palakorn Surakunprapha

Abstract:

Background: Srinagarind Hospital, Ward 3C, has patients with head and neck cancer, congenital urology anomalies such as hypospadis, cleft lip and cleft palate and congenital megacolon who need surgery. Undergoing surgery is a difficult time for patients/ family; they feel fear and anxiety. Nurses work closely with patients and family for 24 hours in the process of patients care, so should have the good nursing ability, innovation and an efficient nursing care system to promote patients self-care ability reducing suffering and preventing complications. From previous nursing outcomes we found patients did not receive appropriate information, could not take care of their wound, not early ambulation after the operation and lost follow-up. Objective: to develop the nursing system for patients who were undergoing an operation. Method: this is a participation action research. The sample population was 11 nurses and 60 patients. This study was divided into 3 phase: Phase 1. Situation review In this phase we review the clinical outcomes, the process of care from documents such as nurses note and interview nurses, patients and family about the process of care by nurses. Phase 2: focus group with 11 nurses, searching guideline for specific care, nursing care system then establish the protocol. This phase we have the protocol for giving information, teaching protocol and teaching record, leaflet for all of top five diseases, make video media to convey information, ambulation package and protocol for patients with head and neck cancer, patients zoning, primary nurse, improved job description for each staff level. Program to record number of patients, kind of medical procedures for showing nurses activity each day. Phase 3 implementation and evaluation. Result: patients/family receive appropriate information about deep breathing exercise, cough, early ambulation after the operation, information during the stay in the hospital. Patients family satisfaction is 95.04 percent, appropriate job description for a practical nurse, nurse aid, and worker. Nurses satisfaction is 95 percent. The complications can be prevented. Conclusion: the nursing system is the dynamic process using evidence to develop nursing care. The appropriate system depends on context and needs to keep an eye on every event.

Keywords: development, nursing system, patients undergoing operation, 3C Ward

Procedia PDF Downloads 265

Authors: Abul B. M. M. K. Islam, Mandar Dave, Roderick V. Jensen, Ashok R. Amin

Abstract:

A systems approach was applied to characterize differentially expressed transcripts, bioinformatics pathways, and proteins and prostaglandins (PGs) from lung fibroblasts procured from wild-type (WT), COX-1-/- and COX-2-/- mice to understand system level control mechanism. Bioinformatics analysis of COX-2 and COX-1 ablated cells induced COX-1 and COX-2 specific signature respectively, which significantly overlapped with an 'IL-1β induced inflammatory signature'. This defined novel cross-talk signals that orchestrated coordinated activation of pathways of sterile inflammation sensed by cellular stress. The overlapping signals showed significant over-representation of shared pathways for interferon y and immune responses, T cell functions, NOD, and toll-like receptor signaling. Gene Ontology Biological Process (GOBP) and pathway enrichment analysis specifically showed an increase in mRNA expression associated with: (a) organ development and homeostasis in COX-1-/- cells and (b) oxidative stress and response, spliceosomes and proteasomes activity, mTOR and p53 signaling in COX-2-/- cells. COX-1 and COX-2 showed signs of functional pathways committed to cell cycle and DNA replication at the genomics level. As compared to WT, metabolomics analysis revealed a significant increase in COX-1 mRNA and synthesis of basal levels of eicosanoids (PGE2, PGD2, TXB2, LTB4, PGF1α, and PGF2α) in COX-2 ablated cells and increase in synthesis of PGE2, and PGF1α in COX-1 null cells. There was a compensation of PGE2 and PGF1α in COX-1-/- and COX-2-/- cells. Collectively, these results support a broader, differential and collaborative regulation of both COX-1 and COX-2 pathways at the metabolic, signaling, and genomics levels in cellular homeostasis and sterile inflammation induced by cellular stress.

Keywords: cyclooxygenases, inflammation, lung fibroblasts, systemic

Procedia PDF Downloads 293

Authors: Amir Lotfi, Seyed Hamid Hosseini

Abstract:

During the recent past, due to the increase of electrical energy demand and governmental resources constraints in creating additional capacity in the generation, transmission, and distribution, privatization, and restructuring in electrical industry have been considered. So, in most of the countries, different parts of electrical industry like generation, transmission, and distribution have been separated in order to create competition. Considering these changes, environmental issues, energy growth, investment of private equity in energy generation units and difficulties of transmission lines expansion, distributed generation (DG) units have been used in power systems. Moreover, reduction in the need for transmission and distribution, the increase of reliability, improvement of power quality, and reduction of power loss have caused DG to be placed in power systems. On the other hand, considering low liquidity need, private investors tend to spend their money for DGs. In this project, the main goal is to offer an algorithm for planning and placing DGs in order to reduce the need for transmission and distribution network.

Keywords: planning, transmission, distributed generation, power security, power systems

Procedia PDF Downloads 481

Authors: Daya Rani

Abstract:

Non-metal-based compounds have emerged as promising electrodes in recent years to replace scarce and expensive transition-metals for energy storage applications. Herein, a simple electro-spinning technique followed by carbonization is used to create tetraphosphorus triselenide(P4Se3)nano-flakes encapsulated in carbon nanofiber (P4Se3@CNF) to obtain a binder-free, metal-free and flexible hybrid electrode with high electrical conductivity and cyclic stability. A remarkable capacitive performance (5.5-folds@P4Se3) of 810Fg-1/[email protected] has been obtained using P4Se3@CNF electrode with an excellent rate capability compared to pristine(P4Se3) which is further supported by theoretical calculations via intercalating graphene within bare P4Se3 flakes inducing partial charge redistribution in hetero-structure. A flexible pouch-type hybrid-supercapacitor followed by coin-cell has been manufactured offering exceptional energy-density without sacrificing power density and ultra-long durability over 35000 and 100000-cycles with capacitance-retention of 99.77% and 100%, respectively. It has been demonstrated that as-fabricated device has practical usefulness towards renewable energy harvesting and storage via integrating commercial solar cell module with supercapattery array that can enlighten the blue LED approximately for 31minutes, rotate the homemade windmill device, power Arduino and glow “INST” against 2minutes of charging. This work demonstrates a facile route towards the development of metal-free electrochemical renewable energy storage/transfer devices offering an inevitable adoption in industrial platforms.

Keywords: metal free, carbon nano-fiber, pouch-type hybrid super-capacitor, nano-flakes

Procedia PDF Downloads 27

Authors: Soumyadeep Bhaduri, Rahul Ghosh, Rahul Shukla, Manaswini Behera

Abstract:

The textile industry consumes a substantial amount of water throughout the processing and production of textile fabrics. The water eventually turns into wastewater, where it acts as an immense damaging nuisance due to its dye content. Wastewater streams contain a percentage ranging from 2.0% to 50.0% of the total weight of dye used, depending on the dye class. The management of dye effluent in textile industries presents a formidable challenge to global sustainability. The current focus is on implementing wastewater treatment technology that enable the recycling of wastewater, reduce energy usage and offset carbon emissions. Microbial fuel cell (MFC) is a device that utilizes microorganisms as a bio-catalyst to effectively treat wastewater while also producing electricity. The MFC harnesses the chemical energy present in wastewater by oxidizing organic compounds in the anodic chamber and reducing an electron acceptor in the cathodic chamber, thereby generating electricity. This research investigates the potential of MFCs to tackle this challenge of azo dye removal with simultaneously generating electricity. Although MFCs are well-established for wastewater treatment, their application in dye decolorization with concurrent electricity generation remains relatively unexplored. This study aims to address this gap by assessing the effectiveness of MFCs as a sustainable solution for treating wastewater containing azo dyes. By harnessing microorganisms as biocatalysts, MFCs offer a promising avenue for environmentally friendly dye effluent management. The performance of MFCs in treating azo dyes and generating electricity was evaluated by optimizing the Chemical Oxygen Demand (COD) and Hydraulic Retention Time (HRT) of influent. COD and HRT values ranged from 1600 mg/L to 2400 mg/L and 5 to 9 days, respectively. Results showed that the maximum open circuit voltage (OCV) reached 648 mV at a COD of 2400 mg/L and HRT of 5 days. Additionally, maximum COD removal of 98% and maximum color removal of 98.91% were achieved at a COD of 1600 mg/L and HRT of 9 days. Furthermore, the study observed a maximum power density of 19.95 W/m3 at a COD of 2400 mg/L and HRT of 5 days. Electrochemical analysis, including linear sweep voltammetry (LSV), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were done to find out the response current and internal resistance of the system. To optimize pH and dye concentration, pH values were varied from 4 to 10, and dye concentrations ranged from 25 mg/L to 175 mg/L. The highest voltage output of 704 mV was recorded at pH 7, while a dye concentration of 100 mg/L yielded the maximum output of 672 mV. This study demonstrates that MFCs offer an efficient and sustainable solution for treating azo dyes in textile industry wastewater, while concurrently generating electricity. These findings suggest the potential of MFCs to contribute to environmental remediation and sustainable development efforts on a global scale.

Keywords: textile wastewater treatment, microbial fuel cell, renewable energy, sustainable wastewater treatment

Procedia PDF Downloads 23

Authors: Tamar Lin, Nufar Buchshtab, Yifat Elharar, Julian Nicenboim, Rotem Edgar, Iddo Weiner, Lior Zelcbuch, Ariel Cohen, Sharon Kredo-Russo, Inbar Gahali-Sass, Naomi Zak, Sailaja Puttagunta, Merav Bassan

Abstract:

Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is characterized by dry skin and flares of eczematous lesions and intense pruritus. Multiple lines of evidence suggest that AD is associated with increased colonization by Staphylococcus aureus, which contributes to disease pathogenesis through the release of virulence factors that affect both keratinocytes and immune cells, leading to disruption of the skin barrier and immune cell dysfunction. The aim of the current study is to develop a bacteriophage-based product that specifically targets S. aureus. Methods: For the discovery of phage, environmental samples were screened on 118 S. aureus strains isolated from skin samples, followed by multiple enrichment steps. Natural phages were isolated, subjected to Next-generation Sequencing (NGS), and analyzed using proprietary bioinformatics tools for undesirable genes (toxins, antibiotic resistance genes, lysogeny potential), taxonomic classification, and purity. Phage host range was determined by an efficiency of plating (EOP) value above 0.1 and the ability of the cocktail to completely lyse liquid bacterial culture under different growth conditions (e.g., temperature, bacterial stage). Results: Sequencing analysis demonstrated that the 118 S. aureus clinical strains were distributed across the phylogenetic tree of all available Refseq S. aureus (~10,750 strains). Screening environmental samples on the S. aureus isolates resulted in the isolation of 50 lytic phages from different genera, including Silviavirus, Kayvirus, Podoviridae, and a novel unidentified phage. NGS sequencing confirmed the absence of toxic elements in the phages’ genomes. The host range of the individual phages, as measured by the efficiency of plating (EOP), ranged between 41% (48/118) to 79% (93/118). Host range studies in liquid culture revealed that a subset of the phages can infect a broad range of S. aureus strains in different metabolic states, including stationary state. Combining the single-phage EOP results of selected phages resulted in a broad host range cocktail which infected 92% (109/118) of the strains. When tested in vitro in a liquid infection assay, clearance was achieved in 87% (103/118) of the strains, with no evidence of phage resistance throughout the study (24 hours). A S. aureus host was identified that can be used for the production of all the phages in the cocktail at high titers suitable for large-scale manufacturing. This host was validated for the absence of contaminating prophages using advanced NGS methods combined with multiple production cycles. The phages are produced under optimized scale-up conditions and are being used for the development of a topical formulation (BX005) that may be administered to subjects with atopic dermatitis. Conclusions: A cocktail of natural phages targeting S. aureus was effective in reducing bacterial burden across multiple assays. Phage products may offer safe and effective steroid-sparing options for atopic dermatitis.

Keywords: atopic dermatitis, bacteriophage cocktail, host range, Staphylococcus aureus

Procedia PDF Downloads 155