Search results for: cell connection
473 Multi-Omics Integrative Analysis Coupled to Control Theory and Computational Simulation of a Genome-Scale Metabolic Model Reveal Controlling Biological Switches in Human Astrocytes under Palmitic Acid-Induced Lipotoxicity
Authors: Janneth Gonzalez, Andrés Pinzon Velasco, Maria Angarita
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Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatorypathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, broad studies with a systemic point of view on the neurodegenerative role of PA and the neuro-protective mechanisms of tibolone are lacking. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also applied a control theory approach to identify those reactions that exert more control in the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a switch in energy source use through inhibition of folate cycle and fatty acid β‐oxidation and upregulation of ketone bodies formation. We found 25 metabolic switches under PA‐mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation of metabolic pathways that may increase neurotoxicity and represent potential treatment targets. Finally, the overall framework of our approach facilitates the understanding of complex metabolic regulation, and it can be used for in silico exploration of the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics
Procedia PDF Downloads 97472 Removal of Total Petroleum Hydrocarbons from Contaminated Soils by Electrochemical Method
Authors: D. M. Cocârță, I. A. Istrate, C. Streche, D. M. Dumitru
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Soil contamination phenomena are a wide world issue that has received the important attention in the last decades. The main pollutants that have affected soils are especially those resulted from the oil extraction, transport and processing. This paper presents results obtained in the framework of a research project focused on the management of contaminated sites with petroleum products/ REMPET. One of the specific objectives of the REMPET project was to assess the electrochemical treatment (improved with polarity change respect to the typical approach) as a treatment option for the remediation of total petroleum hydrocarbons (TPHs) from contaminated soils. Petroleum hydrocarbon compounds attach to soil components and are difficult to remove and degrade. Electrochemical treatment is a physicochemical treatment that has gained acceptance as an alternative method, for the remediation of organic contaminated soils comparing with the traditional methods as bioremediation and chemical oxidation. This type of treatment need short time and have high removal efficiency, being usually applied in heterogeneous soils with low permeability. During the experimental tests, the following parameters were monitored: pH, redox potential, humidity, current intensity, energy consumption. The electrochemical method was applied in an experimental setup with the next dimensions: 450 mm x 150 mm x 150 mm (L x l x h). The setup length was devised in three electrochemical cells that were connected at two power supplies. The power supplies configuration was provided in such manner that each cell has a cathode and an anode without overlapping. The initial value of TPH concentration in soil was of 1420.28 mg/kgdw. The remediation method has been applied for only 21 days, when it was already noticed an average removal efficiency of 31 %, with better results in the anode area respect to the cathode one (33% respect to 27%). The energy consumption registered after the development of the experiment was 10.6 kWh for exterior power supply and 16.1 kWh for the interior one. Taking into account that at national level, the most used methods for soil remediation are bioremediation (which needs too much time to be implemented and depends on many factors) and thermal desorption (which involves high costs in order to be implemented), the study of electrochemical treatment will give an alternative to these two methods (and their limitations).Keywords: electrochemical remediation, pollution, total petroleum hydrocarbons, soil contamination
Procedia PDF Downloads 240471 Community Strengths and Indigenous Resilience as Drivers for Health Reform Change
Authors: Shana Malio-Satele, Lemalu Silao Vaisola Sefo
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Introductory Statement: South Seas Healthcare is Ōtara’s largest Pacific health provider in South Auckland, New Zealand. Our vision is excellent health and well-being for Pacific people and all communities through strong Pacific values. During the DELTA and Omicron outbreak of COVID-19, our Pacific people, indigenous Māori, and the community of South Auckland were disproportionately affected and faced significant hardship with existing inequities magnified. This study highlights the community-based learnings of harnessing community-based strengths such as indigenous resilience, family-informed experiences and stories that provide critical insights that inform health reform changes that will be sustainable and equitable for all indigenous populations. This study is based on critical learnings acquired during COVID-19 that challenge the deficit narrative common in healthcare about indigenous populations. This study shares case studies of marginalised groups and religious groups and the successful application of indigenous cultural strengths, such as collectivism, positive protective factors, and using trusted relationships to create meaningful change in the way healthcare is delivered. The significance of this study highlights the critical conditions needed to adopt a community-informed way of creating integrated healthcare that works and the role that the community can play in being part of the solution. Methodologies: Key methodologies utilised are indigenous and Pacific-informed. To achieve critical learnings from the community, Pacific research methodologies, heavily informed by the Polynesian practice, were applied. Specifically, this includes; Teu Le Va (Understanding the importance of trusted relationships as a way of creating positive health solutions); The Fonofale Methodology (A way of understanding how health incorporates culture, family, the physical, spiritual, mental and other dimensions of health, as well as time, context and environment; The Fonua Methodology – Understanding the overall wellbeing and health of communities, families and individuals and their holistic needs and environmental factors and the Talanoa methodology (Researching through conversation, where understanding the individual and community is through understanding their history and future through stories). Major Findings: Key findings in the study included: 1. The collectivist approach in the community is a strengths-based response specific to populations, which highlights the importance of trusted relationships and cultural values to achieve meaningful outcomes. 2. The development of a “village model” which identified critical components to achieving health reform change; system navigation, a sense of service that was culturally responsive, critical leadership roles, culturally appropriate support, and the ability to influence the system enablers to support an alternative way of working. Concluding Statement: There is a strong connection between community-based strengths being implemented into healthcare strategies and reforms and the sustainable success of indigenous populations and marginalised communities accessing services that are cohesive, equitably resourced, accessible and meaningful for families. This study highlights the successful community-informed approaches and practices used during the COVID-19 response in New Zealand that are now being implemented in the current health reform.Keywords: indigenous voice, community voice, health reform, New Zealand
Procedia PDF Downloads 89470 Comparison of Monte Carlo Simulations and Experimental Results for the Measurement of Complex DNA Damage Induced by Ionizing Radiations of Different Quality
Authors: Ifigeneia V. Mavragani, Zacharenia Nikitaki, George Kalantzis, George Iliakis, Alexandros G. Georgakilas
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Complex DNA damage consisting of a combination of DNA lesions, such as Double Strand Breaks (DSBs) and non-DSB base lesions occurring in a small volume is considered as one of the most important biological endpoints regarding ionizing radiation (IR) exposure. Strong theoretical (Monte Carlo simulations) and experimental evidence suggests an increment of the complexity of DNA damage and therefore repair resistance with increasing linear energy transfer (LET). Experimental detection of complex (clustered) DNA damage is often associated with technical deficiencies limiting its measurement, especially in cellular or tissue systems. Our groups have recently made significant improvements towards the identification of key parameters relating to the efficient detection of complex DSBs and non-DSBs in human cellular systems exposed to IR of varying quality (γ-, X-rays 0.3-1 keV/μm, α-particles 116 keV/μm and 36Ar ions 270 keV/μm). The induction and processing of DSB and non-DSB-oxidative clusters were measured using adaptations of immunofluorescence (γH2AX or 53PB1 foci staining as DSB probes and human repair enzymes OGG1 or APE1 as probes for oxidized purines and abasic sites respectively). In the current study, Relative Biological Effectiveness (RBE) values for DSB and non-DSB induction have been measured in different human normal (FEP18-11-T1) and cancerous cell lines (MCF7, HepG2, A549, MO59K/J). The experimental results are compared to simulation data obtained using a validated microdosimetric fast Monte Carlo DNA Damage Simulation code (MCDS). Moreover, this simulation approach is implemented in two realistic clinical cases, i.e. prostate cancer treatment using X-rays generated by a linear accelerator and a pediatric osteosarcoma case using a 200.6 MeV proton pencil beam. RBE values for complex DNA damage induction are calculated for the tumor areas. These results reveal a disparity between theory and experiment and underline the necessity for implementing highly precise and more efficient experimental and simulation approaches.Keywords: complex DNA damage, DNA damage simulation, protons, radiotherapy
Procedia PDF Downloads 325469 Electromagnetic Energy Harvesting by Using a Rectenna with a Metamaterial Lens
Authors: Ursula D. C. Resende, Fabiano S. Bicalho, Sandro T. M. Gonçalves
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The growing demand for cheap and clean energy sources have been motivated by the study and development of distinct technologies and devices able to provide different amounts of energy. In order to supply energy for small loads, the energy from the electromagnetic spectrum can be harvested. This possibility is particularly interesting because this kind of energy is constantly available in the environment and the number of radiofrequency sources is permanently increasing, due to advances in telecommunications services. A rectenna, which is a combination of an antenna and a rectifier circuit, is an equipment that can efficiently perform the electromagnetic energy harvesting. However, since the amount of electromagnetic energy available in the environment is very small, limited values of power can be harvested by the rectenna. Therefore, several technical strategies have been investigated in order to increase this amount of power. In this work, a metamaterial electromagnetic lens is used to improve the electromagnetic energy harvesting. The rectenna investigated was designed and optimized to charge a Li-Ion battery using the electromagnetic energy from an internet Wi-Fi commercial router model TL-WR841HP operating in 2.45 GHz with maximal output power equal to 18 dBm. The rectenna consists of a high directive antenna, a double voltage rectifier circuit and a metamaterial lens. The printed antenna, constituted of two rectangular radiator elements, was projected and optimized by using the Computer Simulation Software (CST) in order to obtain high directivities and values of S11 parameter below -10 dB in 2.45 GHz. The antenna was printed over a double-sided copper fiberglass substrate, FR4, with characterized relative electric permittivity εr = 4.3 and tangent of losses δ = 0.01. The rectifier circuit, which incorporates a circuit for impedance matching and uses the Schottky diode HSMS-2852, was projected and optimized by using Advanced Design Software (ADS) and built over the same FR4 substrate. The metamaterial cell is composed of two Square Split Ring Resonator (S-SRR) and a thin wire in order to operate with negative values of εr and relative magnetic permeability in 2.45 GHz. In order to evaluate the performance of the purposed rectenna two experimental charging tests were performed, one without and other with the metamaterial lens. The result obtained demonstrate that the electromagnetic lens was able to significantly increase the levels of electric current delivered to the battery, approximately 44%.Keywords: electromagnetic energy harvesting, electromagnetic lens, metamaterial, rectenna
Procedia PDF Downloads 143468 Machine Learning Approach for Automating Electronic Component Error Classification and Detection
Authors: Monica Racha, Siva Chandrasekaran, Alex Stojcevski
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The engineering programs focus on promoting students' personal and professional development by ensuring that students acquire technical and professional competencies during four-year studies. The traditional engineering laboratory provides an opportunity for students to "practice by doing," and laboratory facilities aid them in obtaining insight and understanding of their discipline. Due to rapid technological advancements and the current COVID-19 outbreak, the traditional labs were transforming into virtual learning environments. Aim: To better understand the limitations of the physical laboratory, this research study aims to use a Machine Learning (ML) algorithm that interfaces with the Augmented Reality HoloLens and predicts the image behavior to classify and detect the electronic components. The automated electronic components error classification and detection automatically detect and classify the position of all components on a breadboard by using the ML algorithm. This research will assist first-year undergraduate engineering students in conducting laboratory practices without any supervision. With the help of HoloLens, and ML algorithm, students will reduce component placement error on a breadboard and increase the efficiency of simple laboratory practices virtually. Method: The images of breadboards, resistors, capacitors, transistors, and other electrical components will be collected using HoloLens 2 and stored in a database. The collected image dataset will then be used for training a machine learning model. The raw images will be cleaned, processed, and labeled to facilitate further analysis of components error classification and detection. For instance, when students conduct laboratory experiments, the HoloLens captures images of students placing different components on a breadboard. The images are forwarded to the server for detection in the background. A hybrid Convolutional Neural Networks (CNNs) and Support Vector Machines (SVMs) algorithm will be used to train the dataset for object recognition and classification. The convolution layer extracts image features, which are then classified using Support Vector Machine (SVM). By adequately labeling the training data and classifying, the model will predict, categorize, and assess students in placing components correctly. As a result, the data acquired through HoloLens includes images of students assembling electronic components. It constantly checks to see if students appropriately position components in the breadboard and connect the components to function. When students misplace any components, the HoloLens predicts the error before the user places the components in the incorrect proportion and fosters students to correct their mistakes. This hybrid Convolutional Neural Networks (CNNs) and Support Vector Machines (SVMs) algorithm automating electronic component error classification and detection approach eliminates component connection problems and minimizes the risk of component damage. Conclusion: These augmented reality smart glasses powered by machine learning provide a wide range of benefits to supervisors, professionals, and students. It helps customize the learning experience, which is particularly beneficial in large classes with limited time. It determines the accuracy with which machine learning algorithms can forecast whether students are making the correct decisions and completing their laboratory tasks.Keywords: augmented reality, machine learning, object recognition, virtual laboratories
Procedia PDF Downloads 134467 Effective Doping Engineering of Na₃V₂(PO₄)₂F₃ as a High-Performance Cathode Material for Sodium-Ion Batteries
Authors: Ramon Alberto Paredes Camacho, Li Lu
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Sustainable batteries are possible through the development of cheaper and greener alternatives whose most feasible option is epitomized by Sodium-Ion Batteries (SIB). Na₃V₂(PO₄)₂F₃ (NVPF) an important member of the Na-superionic-conductor (NASICON) materials, has recently been in the spotlight due to its interesting electrochemical properties when used as cathode namely, high specific capacity of 128 mA h g-¹, high energy density of 507 W h Kg-¹, increased working potential at which vanadium redox couples can be activated (with an average value around 3.9 V), and small volume variation of less than 2%. These traits grant NVPF an excellent perspective as a cathode material for the next generation of sodium batteries. Unfortunately, because of its low inherent electrical conductivity and a high energy barrier that impedes the mobilization of all the available Na ions per formula, the overall electrochemical performance suffers substantial degradation, finally obstructing its industrial use. Many approaches have been developed to remediate these issues where nanostructural design, carbon coating, and ion doping are the most effective ones. This investigation is focused on enhancing the electrochemical response of NVPF by doping metal ions in the crystal lattice, substituting vanadium atoms. A facile sol-gel process is employed, with citric acid as the chelator and the carbon source. The optimized conditions circumvent fluorine sublimation, ratifying the material’s purity. One of the reasons behind the large ionic improvement is the attraction of extra Na ions into the crystalline structure due to a charge imbalance produced by the valence of the doped ions (+2), which is lower than the one of vanadium (+3). Superior stability (higher than 90% at a current density of 20C) and capacity retention at an extremely high current density of 50C are demonstrated by our doped NVPF. This material continues to retain high capacity values at low and high temperatures. In addition, full cell NVPF//Hard Carbon shows capacity values and high stability at -20 and 60ºC. Our doping strategy proves to significantly increase the ionic and electronic conductivity of NVPF even at extreme conditions, delivering outstanding electrochemical performance and paving the way for advanced high-potential cathode materials.Keywords: sodium-ion batteries, cathode materials, NASICON, Na3V2(PO4)2F3, Ion doping
Procedia PDF Downloads 57466 Barriers and Enablers to Climate and Health Adaptation Planning in Small Urban Areas in the Great Lakes Region
Authors: Elena Cangelosi, Wayne Beyea
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This research expands the resilience planning literature by exploring the barriers and enablers to climate and health adaptation planning for small urban, coastal Great Lakes communities. With funding from the United States Centers for Disease Control and Prevention (CDC) Climate Ready City and States Initiative, this research took place during a 3-year pilot intervention project which integrates urban planning and public health. The project used the CDC’s Building Resilience Against Climate Effects (BRACE) framework to prevent or reduce the human health impacts from climate change in Marquette County, Michigan. Using a deliberation with the analysis planning process, interviews, focus groups, and community meetings with over 25 stakeholder groups and over 100 participants identified the area’s climate-related health concerns and adaptation interventions to address those concerns. Marquette County, on the shores of Lake Superior, the largest of the Great Lakes, was selected for the project based on their existing adaptive capacity and proactive approach to climate adaptation planning. With Marquette County as the context, this study fills a gap in the adaptation literature, which currently heavily emphasizes large-urban or agriculturally-based rural areas, and largely neglects small urban areas. This research builds on the qualitative case-study, survey, and interview approach established by previous researchers on contextual barriers and enablers for adaptation planning. This research uses a case study approach, including surveys and interviews of public officials, to identify the barriers and enablers for climate and health adaptation planning for small-urban areas within a large, non-agricultural, Great Lakes county. The researchers hypothesize that the barriers and enablers will, in some cases, overlap those found in other contexts, but in many cases, will be unique to a rural setting. The study reveals that funding, staff capacity, and communication across a large, rural geography act as the main barriers, while strong networks and collaboration, interested leaders, and community interest through a strong human-land connection act as the primary enablers. Challenges unique to rural areas are revealed, including weak opportunities for grant funding, large geographical distances, communication challenges with an aging and remote population, and the out-migration of education residents. Enablers that may be unique to rural contexts include strong collaborative relationships across jurisdictions for regional work and strong connections between residents and the land. As the factors that enable and prevent climate change planning are highly contextual, understanding, and appropriately addressing the unique factors at play for small-urban communities is key for effective planning in those areas. By identifying and addressing the barriers and enablers to climate and health adaptation planning for small-urban, coastal areas, this study can help Great Lakes communities appropriately build resilience to the adverse impacts of climate change. In addition, this research expands the breadth of research and understanding of the challenges and opportunities planners confront in the face of climate change.Keywords: climate adaptation and resilience, climate change adaptation, climate change and urban resilience, governance and urban resilience
Procedia PDF Downloads 120465 Two-Component Biocompartible Material for Reconstruction of Articular Hyaline Cartilage
Authors: Alena O. Stepanova, Vera S. Chernonosova, Tatyana S. Godovikova, Konstantin A. Bulatov, Andrey Y. Patrushev, Pavel P. Laktionov
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Trauma and arthrosis, not to mention cartilage destruction in overweight and elders put hyaline cartilage lesion among the most frequent diseases of locomotor system. These problems combined with low regeneration potential of the cartilage make regeneration of articular cartilage a high-priority task of tissue engineering. Many types of matrices, the procedures of their installation and autologous chondrocyte implantation protocols were offered, but certain aspects including adhesion of the implant with surrounding cartilage/bone, prevention of the ossification and fibrosis were not resolved. Simplification and acceleration of the procedures resulting in restoration of normal cartilage are also required. We have demonstrated that human chondroblasts can be successfully cultivated at the surface of electrospun scaffolds and produce extracellular matrix components in contrast to chondroblasts grown in homogeneous hydrogels. To restore cartilage we offer to use stacks of electrospun scaffolds fixed with photopolymerized solution of prepared from gelatin and chondroitin-4-sulfate both modified by glycidyl methacrylate and non-toxic photoinitator Darocur 2959. Scaffolds were prepared from nylon 6, polylactide-co-glicolide and their mixtures with modified gelatin. Illumination of chondroblasts in photopolymerized solution using 365 nm LED light had no effect on cell viability at compressive strength of the gel less than0,12 MPa. Stacks of electrospun scaffolds provide good compressive strength and have the potential for substitution with cartilage when biodegradable scaffolds are used. Vascularization can be prevented by introduction of biostable scaffolds in the layers contacting the subchondral bone. Studies of two-component materials (2-3 sheets of electrospun scaffold) implanted in the knee-joints of rabbits and fixed by photopolymerization demonstrated good crush resistance, biocompatibility and good adhesion of the implant with surrounding cartilage. Histological examination of the implants 3 month after implantation demonstrates absence of any inflammation and signs of replacement of the biodegradable scaffolds with normal cartilage. The possibility of intraoperative population of the implants with autologous cells is being investigated.Keywords: chondroblasts, electrospun scaffolds, hyaline cartilage, photopolymerized gel
Procedia PDF Downloads 283464 Therapeutic Effect of Indane 1,3-Dione Derivatives in the Restoration of Insulin Resistance in Human Liver Cells and in Db/Db Mice Model: Biochemical, Physiological and Molecular Insights of Investigation
Authors: Gulnaz Khan, Meha F. Aftab, Munazza Murtaza, Rizwana S. Waraich
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Advanced glycation end products (AGEs) precursor and its abnormal accumulation cause damage to various tissues and organs. AGEs have pathogenic implication in several diseases including diabetes. Existing AGEs inhibitors are not in clinical use, and there is a need for development of novel inhibitors. The present investigation aimed at identifying the novel AGEs inhibitors and assessing their mechanism of action for treating insulin resistance in mice model of diabetes. Novel derivatives of benzylidene of indan-1,3-dione were synthesized. The compounds were selected to study their action mechanism in improving insulin resistance, in vitro, in human hepatocytes and murine adipocytes and then, in vivo, in mice genetic model of diabetes (db/db). Mice were treated with novel derivatives of benzylidene of indane 1,3-dione. AGEs mediated ROS production was measured by dihydroethidium fluorescence assay. AGEs level in the serum of treated mice was observed by ELISA. Gene expression of receptor for AGEs (RAGE), PPAR-gamma, TNF-alpha and GLUT-4 was evaluated by RT-PCR. Glucose uptake was measured by fluorescent method. Microscopy was used to analyze glycogen synthesis in muscle. Among several derivatives of benzylidene of indan-1,3-dione, IDD-24, demonstrated highest inhibition of AGESs. IDD-24 significantly reduced AGEs formation and expression of receptor for advanced glycation end products (RAGE) in fat, liver of db/db mice. Suppression of AGEs mediated ROS production was also observed in hepatocytes and fat cell, after treatment with IDD-24. Glycogen synthesis was increased in muscle tissue of mice treated with IDD-24. In adipocytes, IDD-24 prevented AGEs induced reduced glucose uptake. Mice treated with IDD-24 exhibited increased glucose tolerance, serum adiponectin levels and decreased insulin resistance. The result of present study suggested that IDD-24 can be a possible treatment target to address glycotoxins induced insulin resistance.Keywords: advance glycation end product, hyperglycemia, indan-1, 3-dione, insulin resistance
Procedia PDF Downloads 158463 SARS-CoV-2: Prediction of Critical Charged Amino Acid Mutations
Authors: Atlal El-Assaad
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Viruses change with time through mutations and result in new variants that may persist or disappear. A Mutation refers to an actual change in the virus genetic sequence, and a variant is a viral genome that may contain one or more mutations. Critical mutations may cause the virus to be more transmissible, with high disease severity, and more vulnerable to diagnostics, therapeutics, and vaccines. Thus, variants carrying such mutations may increase the risk to human health and are considered variants of concern (VOC). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - the contagious in humans, positive-sense single-stranded RNA virus that caused coronavirus disease 2019 (COVID-19) - has been studied thoroughly, and several variants were revealed across the world with their corresponding mutations. SARS-CoV-2 has four structural proteins, known as the S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins, but prior study and vaccines development focused on genetic mutations in the S protein due to its vital role in allowing the virus to attach and fuse with the membrane of a host cell. Specifically, subunit S1 catalyzes attachment, whereas subunit S2 mediates fusion. In this perspective, we studied all charged amino acid mutations of the SARS-CoV-2 viral spike protein S1 when bound to Antibody CC12.1 in a crystal structure and assessed the effect of different mutations. We generated all missense mutants of SARS-CoV-2 protein amino acids (AAs) within the SARS-CoV-2:CC12.1 complex model. To generate the family of mutants in each complex, we mutated every charged amino acid with all other charged amino acids (Lysine (K), Arginine (R), Glutamic Acid (E), and Aspartic Acid (D)) and studied the new binding of the complex after each mutation. We applied Poisson-Boltzmann electrostatic calculations feeding into free energy calculations to determine the effect of each mutation on binding. After analyzing our data, we identified charged amino acids keys for binding. Furthermore, we validated those findings against published experimental genetic data. Our results are the first to propose in silico potential life-threatening mutations of SARS-CoV-2 beyond the present mutations found in the five common variants found worldwide.Keywords: SARS-CoV-2, variant, ionic amino acid, protein-protein interactions, missense mutation, AESOP
Procedia PDF Downloads 113462 Targeted Delivery of Sustained Release Polymeric Nanoparticles for Cancer Therapy
Authors: Jamboor K. Vishwanatha
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Among the potent anti-cancer agents, curcumin has been found to be very efficacious against various cancer cells. Despite multiple medicinal benefits of curcumin, poor water solubility, poor physiochemical properties and low bioavailability continue to pose major challenges in developing a formulation for clinical efficacy. To improve its potential application in the clinical area, we formulated poly lactic-co-glycolic acid (PLGA) nanoparticles. The PLGA nanoparticles were formulated using solid-oil/water emulsion solvent evaporation method and then characterized for percent yield, encapsulation efficiency, surface morphology, particle size, drug distribution within nanoparticles and drug polymer interaction. Our studies showed the successful formation of smooth and spherical curcumin loaded PLGA nanoparticles with a high percent yield of about 92.01±0.13% and an encapsulation efficiency of 90.88±0.14%. The mean particle size of the nanoparticles was found to be 145nm. The in vitro drug release profile showed 55-60% drug release from the nanoparticles over a period of 24 hours with continued sustained release over a period of 8 days. Exposure to curcumin loaded nanoparticles resulted in reduced cell viability of cancer cells compared to normal cells. We used a novel non-covalent insertion of a homo-bifunctional spacer for targeted delivery of curcumin to various cancer cells. Functionalized nanoparticles for antibody/targeting agent conjugation was prepared using a cross-linking ligand, bis(sulfosuccinimidyl) suberate (BS3), which has reactive carboxyl group to conjugate efficiently to the primary amino groups of the targeting agents. In our studies, we demonstrated successful conjugation of antibodies, Annexin A2 or prostate specific membrane antigen (PSMA), to curcumin loaded PLGA nanoparticles for targeting to prostate and breast cancer cells. The percent antibody attachment to PLGA nanoparticles was found to be 92.8%. Efficient intra-cellular uptake of the targeted nanoparticles was observed in the cancer cells. These results have emphasized the potential of our multifunctional curcumin nanoparticles to improve the clinical efficacy of curcumin therapy in patients with cancer.Keywords: polymeric nanoparticles, cancer therapy, sustained release, curcumin
Procedia PDF Downloads 325461 Septin 11, Cytoskeletal Protein Involved in the Regulation of Lipid Metabolism in Adipocytes
Authors: Natalia Moreno-Castellanos, Amaia Rodriguez, Gema Frühbeck
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Introduction: In adipocytes, the cytoskeleton undergoes important expression and distribution in adipocytes rearrangements during adipogenesis and in obesity. Indeed, a role for these proteins in the regulation of adipocyte differentiation and response to insulin has been demonstrated. Recently, septins have been considered as new components of the cytoskeletal network that interact with other cytoskeletal elements (actin and tubulin) profoundly modifying their dynamics. However, these proteins have not been characterized as yet in adipose tissue. In this work, were examined the cellular, molecular and functional features of a member of this family, septin 11 (SEPT11), in adipocytes and evaluated the impact of obesity on the expression of this protein in human adipose tissue. Methods: Adipose gene and protein expression levels of SEPT11 were analysed in human samples. SEPT11 distribution was evaluated by immunocytochemistry, electronic microscopy, and subcellular fractionation techniques. GST-pull down, immunoprecipitation and a Yeast-Two Hybrid (Y2H) screening were used to identify the SEPT11 interactome. Gene silencing was employed to assess the role of SEPT11 in the regulation of insulin signaling and lipid metabolism in adipocytes. Results: SEPT11 is expressed in human adipocytes, and its levels increased in both omental and subcutaneous adipose tissue in obesity, with SEPT11 mRNA content positively correlating with parameters of insulin resistance in subcutaneous fat. In non-stimulated adipocytes, SEPT11 immunoreactivity showed a ring-like distribution at the cell surface and associated to caveolae. Biochemical analyses showed that SEPT11 interacted with the main component of caveolae, caveolin-1 (CAV1) as well as with the fatty acid-binding protein, FABP5. Notably, the three proteins redistributed and co-localized at the surface of lipid droplets upon exposure of adipocytes to oleate. In this line, SEPT11 silencing in 3T3-L1 adipocytes impaired insulin signaling and decreased insulin-induced lipogenesis. Conclusions: Those findings demonstrate that SEPT11 is a novel component of the adipocyte cytoskeleton that plays an important role in the regulation of lipid traffic, metabolism and can thus represent a potential biomarker of insulin resistance in obesity in adipocytes through its interaction with both CAV1 and FABP5.Keywords: caveolae, lipid metabolism, obesity, septins
Procedia PDF Downloads 212460 Expert Supporting System for Diagnosing Lymphoid Neoplasms Using Probabilistic Decision Tree Algorithm and Immunohistochemistry Profile Database
Authors: Yosep Chong, Yejin Kim, Jingyun Choi, Hwanjo Yu, Eun Jung Lee, Chang Suk Kang
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For the past decades, immunohistochemistry (IHC) has been playing an important role in the diagnosis of human neoplasms, by helping pathologists to make a clearer decision on differential diagnosis, subtyping, personalized treatment plan, and finally prognosis prediction. However, the IHC performed in various tumors of daily practice often shows conflicting and very challenging results to interpret. Even comprehensive diagnosis synthesizing clinical, histologic and immunohistochemical findings can be helpless in some twisted cases. Another important issue is that the IHC data is increasing exponentially and more and more information have to be taken into account. For this reason, we reached an idea to develop an expert supporting system to help pathologists to make a better decision in diagnosing human neoplasms with IHC results. We gave probabilistic decision tree algorithm and tested the algorithm with real case data of lymphoid neoplasms, in which the IHC profile is more important to make a proper diagnosis than other human neoplasms. We designed probabilistic decision tree based on Bayesian theorem, program computational process using MATLAB (The MathWorks, Inc., USA) and prepared IHC profile database (about 104 disease category and 88 IHC antibodies) based on WHO classification by reviewing the literature. The initial probability of each neoplasm was set with the epidemiologic data of lymphoid neoplasm in Korea. With the IHC results of 131 patients sequentially selected, top three presumptive diagnoses for each case were made and compared with the original diagnoses. After the review of the data, 124 out of 131 were used for final analysis. As a result, the presumptive diagnoses were concordant with the original diagnoses in 118 cases (93.7%). The major reason of discordant cases was that the similarity of the IHC profile between two or three different neoplasms. The expert supporting system algorithm presented in this study is in its elementary stage and need more optimization using more advanced technology such as deep-learning with data of real cases, especially in differentiating T-cell lymphomas. Although it needs more refinement, it may be used to aid pathological decision making in future. A further application to determine IHC antibodies for a certain subset of differential diagnoses might be possible in near future.Keywords: database, expert supporting system, immunohistochemistry, probabilistic decision tree
Procedia PDF Downloads 224459 Parameters of Main Stage of Discharge between Artificial Charged Aerosol Cloud and Ground in Presence of Model Hydrometeor Arrays
Authors: D. S. Zhuravkova, A. G. Temnikov, O. S. Belova, L. L. Chernensky, T. K. Gerastenok, I. Y. Kalugina, N. Y. Lysov, A.V. Orlov
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Investigation of the discharges from the artificial charged water aerosol clouds in presence of the arrays of the model hydrometeors could help to receive the new data about the peculiarities of the return stroke formation between the thundercloud and the ground when the large volumes of the hail particles participate in the lightning discharge initiation and propagation stimulation. Artificial charged water aerosol clouds of the negative or positive polarity with the potential up to one million volts have been used. Hail has been simulated by the group of the conductive model hydrometeors of the different form. Parameters of the impulse current of the main stage of the discharge between the artificial positively and negatively charged water aerosol clouds and the ground in presence of the model hydrometeors array and of its corresponding electromagnetic radiation have been determined. It was established that the parameters of the array of the model hydrometeors influence on the parameters of the main stage of the discharge between the artificial thundercloud cell and the ground. The maximal values of the main stage current impulse parameters and the electromagnetic radiation registered by the plate antennas have been found for the array of the model hydrometeors of the cylinder revolution form for the negatively charged aerosol cloud and for the array of the hydrometeors of the plate rhombus form for the positively charged aerosol cloud, correspondingly. It was found that parameters of the main stage of the discharge between the artificial charged water aerosol cloud and the ground in presence of the model hydrometeor array of the different considered forms depend on the polarity of the artificial charged aerosol cloud. In average, for all forms of the investigated model hydrometeors arrays, the values of the amplitude and the current rise of the main stage impulse current and the amplitude of the corresponding electromagnetic radiation for the artificial charged aerosol cloud of the positive polarity were in 1.1-1.9 times higher than for the charged aerosol cloud of the negative polarity. Thus, the received results could indicate to the possible more important role of the big volumes of the large hail arrays in the thundercloud on the parameters of the return stroke for the positive lightning.Keywords: main stage of discharge, hydrometeor form, lightning parameters, negative and positive artificial charged aerosol cloud
Procedia PDF Downloads 256458 Mathematical Study of CO₂ Dispersion in Carbonated Water Injection Enhanced Oil Recovery Using Non-Equilibrium 2D Simulator
Authors: Ahmed Abdulrahman, Jalal Foroozesh
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CO₂ based enhanced oil recovery (EOR) techniques have gained massive attention from major oil firms since they resolve the industry's two main concerns of CO₂ contribution to the greenhouse effect and the declined oil production. Carbonated water injection (CWI) is a promising EOR technique that promotes safe and economic CO₂ storage; moreover, it mitigates the pitfalls of CO₂ injection, which include low sweep efficiency, early CO₂ breakthrough, and the risk of CO₂ leakage in fractured formations. One of the main challenges that hinder the wide adoption of this EOR technique is the complexity of accurate modeling of the kinetics of CO₂ mass transfer. The mechanisms of CO₂ mass transfer during CWI include the slow and gradual cross-phase CO₂ diffusion from carbonated water (CW) to the oil phase and the CO₂ dispersion (within phase diffusion and mechanical mixing), which affects the oil physical properties and the spatial spreading of CO₂ inside the reservoir. A 2D non-equilibrium compositional simulator has been developed using a fully implicit finite difference approximation. The material balance term (k) was added to the governing equation to account for the slow cross-phase diffusion of CO₂ from CW to the oil within the gird cell. Also, longitudinal and transverse dispersion coefficients have been added to account for CO₂ spatial distribution inside the oil phase. The CO₂-oil diffusion coefficient was calculated using the Sigmund correlation, while a scale-dependent dispersivity was used to calculate CO₂ mechanical mixing. It was found that the CO₂-oil diffusion mechanism has a minor impact on oil recovery, but it tends to increase the amount of CO₂ stored inside the formation and slightly alters the residual oil properties. On the other hand, the mechanical mixing mechanism has a huge impact on CO₂ spatial spreading (accurate prediction of CO₂ production) and the noticeable change in oil physical properties tends to increase the recovery factor. A sensitivity analysis has been done to investigate the effect of formation heterogeneity (porosity, permeability) and injection rate, it was found that the formation heterogeneity tends to increase CO₂ dispersion coefficients, and a low injection rate should be implemented during CWI.Keywords: CO₂ mass transfer, carbonated water injection, CO₂ dispersion, CO₂ diffusion, cross phase CO₂ diffusion, within phase CO2 diffusion, CO₂ mechanical mixing, non-equilibrium simulation
Procedia PDF Downloads 176457 Anti-lipidemic and Hematinic Potentials of Moringa Oleifera Leaves: A Clinical Trial on Type 2 Diabetic Subjects in a Rural Nigerian Community
Authors: Ifeoma C. Afiaenyi, Elizabeth K. Ngwu, Rufina N. B. Ayogu
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Diabetes has crept into the rural areas of Nigeria, causing devastating effects on its sufferers; most of them could not afford diabetic medications. Moringa oleifera has been used extensively in animal models to demonstrate its antilipidaemic and haematinic qualities; however, there is a scarcity of data on the effect of graded levels of Moringa oleifera leaves on the lipid profile and hematological parameters in human diabetic subjects. The study determined the effect of Moringa oleifera leaves on the lipid profile and hematological parameters of type 2 diabetic subjects in Ukehe, a rural Nigerian community. Twenty-four adult male and female diabetic subjects were purposively selected for the study. These subjects were shared into four groups of six subjects each. The diets used in the study were isocaloric. A control group (diabetics, group 1) was fed diets without Moringa oleifera leaves. Experimental groups 2, 3 and 4 received 20g, 40g and 60g of Moringa oleifera leaves daily, respectively, in addition to the diets. The subjects' lipid profile and hematological parameters were measured prior to the feeding trial and at the end of the feeding trial. The feeding trial lasted for fourteen days. The data obtained were analyzed using the computer program Statistical Product for Service Solution (SPSS) for windows version 21. A Paired-samples t-test was used to compare the means of values collected before and after the feeding trial within the groups and significance was accepted at p < 0.05. There was a non-significant (p > 0.05) decrease in the mean total cholesterol of the subjects in groups 1, 2 and 3 after the feeding trial. There was a non-significant (p > 0.05) decrease in the mean triglyceride levels of the subjects in group 1 after the feeding trial. Groups 1 and 3 subjects had a non-significant (p > 0.05) decrease in their mean low-density lipoprotein (LDL) cholesterol after the feeding trial. Groups 1, 2 and 4 had a significant (p < 0.05) increase in their mean high-density lipoprotein (HDL) cholesterol after the feeding trial. A significant (p < 0.05) decrease in the mean hemoglobin level was observed only in group 4 subjects. Similarly, there was a significant (p < 0.05) decrease in the mean packed cell volume of group 4 subjects. It was only in group 4 that a significant (p < 0.05) decrease in the mean white blood cells of the subjects was also observed. The changes observed in the parameters assessed were not dose-dependent. Therefore, a similar study of longer duration and more samples is imperative to authenticate these results.Keywords: anemia, diabetic subjects, lipid profile, moringa oleifera
Procedia PDF Downloads 199456 Transcriptome Sequencing of the Spleens Reveals Genes Involved in Antiviral Response in Chickens Infected with Castv
Authors: Sajewicz-Krukowska Joanna, Domańska-Blicharz Katarzyna, Tarasiuk Karolina, Marzec-Kotarska Barbara
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Astroviral infections pose a significant problem in the poultry industry, leading to multiple adverse effects such as decreased egg production, breeding disorders, poor weight gain, and even increased mortality. Commonly observed chicken astrovirus (CAstV) was recently reported to be responsible for "white chicks syndrome" associated with increased embryo/chick mortality. The CAstV-mediated pathogenesis in chicken occurs due to complex interactions between the infectious pathogen and the immune system. Many aspects of CAstV-chicken interactions remain unclear, and there is no information available regarding gene expression changes in the chicken's spleen in response to CAstV infection. We aimed to investigate the molecular background triggered by CAstV infection. Ten 21-day-old SPF White Leghorn chickens were divided into two groups of 5 birds each. One group was inoculated with CAstV, and the other was used as the negative control. On 4th dpi, spleen samples were collected and immediately frozen at -70°C for RNA isolation. We analysed transcriptional profiles of the chickens' spleens at the 4th day following infection using RNA-seq to establish differentially expressed genes (DEGs). The RNA-seq findings were verified by quantitative real-time PCR (qRT-PCR). A total of 31959 transcripts were identified in response to CAstV infection. Eventually 45 DEGs (p-value<0.05; Log2Foldchange>1)were recognized in the spleen after CAstV infection (26 upregulated DEGs and 19 downregulated DEGs). qRT-PCR performed on 4 genes (IFIT5, OASL, RASD1, DDX60) confirmed RNAseq results. Top differentially expressed genes belonged to novel putative IFN-induced CAstV restriction factors. Most of the DEGs were associated with RIG-I–like signalling pathway or, more generally, with an innate antiviral response(upregulated: BLEC3, CMPK2, IFIT5, OASL, DDX60, IFI6, and downregulated: SPIK5, SELENOP, HSPA2, TMEM158, RASD1, YWHAB). The study provided a global analysis of host transcriptional changes that occur during CAstV infection in vivo and proved the cell cycle in the spleen and immune signalling in chickens were predominantly affected upon CAstV infection.Keywords: chicken astrovirus, CastV, RNA-seq, transcriptome, spleen
Procedia PDF Downloads 154455 A Web-Based Systems Immunology Toolkit Allowing the Visualization and Comparative Analysis of Publically Available Collective Data to Decipher Immune Regulation in Early Life
Authors: Mahbuba Rahman, Sabri Boughorbel, Scott Presnell, Charlie Quinn, Darawan Rinchai, Damien Chaussabel, Nico Marr
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Collections of large-scale datasets made available in public repositories can be used to identify and fill gaps in biomedical knowledge. But first, these data need to be made readily accessible to researchers for analysis and interpretation. Here a collection of transcriptome datasets was made available to investigate the functional programming of human hematopoietic cells in early life. Thirty two datasets were retrieved from the NCBI Gene Expression Omnibus (GEO) and loaded in a custom, interactive web application called the Gene Expression browser (GXB), designed for visualization and query of integrated large-scale data. Multiple sample groupings and gene rank lists were created based on the study design and variables in each dataset. Web links to customized graphical views can be generated by users and subsequently be used to graphically present data in manuscripts for publication. The GXB tool also enables browsing of a single gene across datasets, which can provide information on the role of a given molecule across biological systems. The dataset collection is available online. As a proof-of-principle, one of the datasets (GSE25087) was re-analyzed to identify genes that are differentially expressed by regulatory T cells in early life. Re-analysis of this dataset and a cross-study comparison using multiple other datasets in the above mentioned collection revealed that PMCH, a gene encoding a precursor of melanin-concentrating hormone (MCH), a cyclic neuropeptide, is highly expressed in a variety of other hematopoietic cell types, including neonatal erythroid cells as well as plasmacytoid dendritic cells upon viral infection. Our findings suggest an as yet unrecognized role of MCH in immune regulation, thereby highlighting the unique potential of the curated dataset collection and systems biology approach to generate new hypotheses which can be tested in future mechanistic studies.Keywords: early-life, GEO datasets, PMCH, interactive query, systems biology
Procedia PDF Downloads 296454 Identification and Characterization of in Vivo, in Vitro and Reactive Metabolites of Zorifertinib Using Liquid Chromatography Lon Trap Mass Spectrometry
Authors: Adnan A. Kadi, Nasser S. Al-Shakliah, Haitham Al-Rabiah
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Zorifertinib is a novel, potent, oral, a small molecule used to treat non-small cell lung cancer (NSCLC). zorifertinib is an Epidermal Growth Factor Receptor (EGFR) inhibitor and has good blood–brain barrier permeability for (NSCLC) patients with EGFR mutations. zorifertinibis currently at phase II/III clinical trials. The current research reports the characterization and identification of in vitro, in vivo and reactive intermediates of zorifertinib. Prediction of susceptible sites of metabolism and reactivity pathways (cyanide and GSH) of zorifertinib were performed by the Xenosite web predictor tool. In-vitro metabolites of zorifertinib were performed by incubation with rat liver microsomes (RLMs) and isolated perfused rat liver hepatocytes. Extraction of zorifertinib and it's in vitro metabolites from the incubation mixtures were done by protein precipitation. In vivo metabolism was done by giving a single oral dose of zorifertinib(10 mg/Kg) to Sprague Dawely rats in metabolic cages by using oral gavage. Urine was gathered and filtered at specific time intervals (0, 6, 12, 18, 24, 48, 72,96and 120 hr) from zorifertinib dosing. A similar volume of ACN was added to each collected urine sample. Both layers (organic and aqueous) were injected into liquid chromatography ion trap mass spectrometry(LC-IT-MS) to detect vivozorifertinib metabolites. N-methyl piperizine ring and quinazoline group of zorifertinib undergoe metabolism forming iminium and electro deficient conjugated system respectively, which are very reactive toward nucleophilic macromolecules. Incubation of zorifertinib with RLMs in the presence of 1.0 mM KCN and 1.0 Mm glutathione were made to check reactive metabolites as it is often responsible for toxicities associated with this drug. For in vitro metabolites there were nine in vitro phase I metabolites, four in vitro phase II metabolites, eleven reactive metabolites(three cyano adducts, five GSH conjugates metabolites, and three methoxy metabolites of zorifertinib were detected by LC-IT-MS. For in vivo metabolites, there were eight in vivo phase I, tenin vivo phase II metabolitesofzorifertinib were detected by LC-IT-MS. In vitro and in vivo phase I metabolic pathways wereN- demthylation, O-demethylation, hydroxylation, reduction, defluorination, and dechlorination. In vivo phase II metabolic reaction was direct conjugation of zorifertinib with glucuronic acid and sulphate.Keywords: in vivo metabolites, in vitro metabolites, cyano adducts, GSH conjugate
Procedia PDF Downloads 198453 Addressing the Gap in Health and Wellbeing Evidence for Urban Real Estate Brownfield Asset Management Social Needs and Impact Analysis Using Systems Mapping Approach
Authors: Kathy Pain, Nalumino Akakandelwa
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The study explores the potential to fill a gap in health and wellbeing evidence for purposeful urban real estate asset management to make investment a powerful force for societal good. Part of a five-year programme investigating the root causes of unhealthy urban development funded by the United Kingdom Prevention Research Partnership (UKPRP), the study pilots the use of a systems mapping approach to identify drivers and barriers to the incorporation of health and wellbeing evidence in urban brownfield asset management decision-making. Urban real estate not only provides space for economic production but also contributes to the quality of life in the local community. Yet market approaches to urban land use have, until recently, insisted that neo-classical technology-driven efficient allocation of economic resources should inform acquisition, operational, and disposal decisions. Buildings in locations with declining economic performance have thus been abandoned, leading to urban decay. Property investors are recognising the inextricable connection between sustainable urban production and quality of life in local communities. The redevelopment and operation of brownfield assets recycle existing buildings, minimising embodied carbon emissions. It also retains established urban spaces with which local communities identify and regenerate places to create a sense of security, economic opportunity, social interaction, and quality of life. Social implications of urban real estate on health and wellbeing and increased adoption of benign sustainability guidance in urban production are driving the need to consider how they affect brownfield real estate asset management decisions. Interviews with real estate upstream decision-makers in the study, find that local social needs and impact analysis is becoming a commercial priority for large-scale urban real estate development projects. Evidence of the social value-added of proposed developments is increasingly considered essential to secure local community support and planning permissions, and to attract sustained inward long-term investment capital flows for urban projects. However, little is known about the contribution of population health and wellbeing to socially sustainable urban projects and the monetary value of the opportunity this presents to improve the urban environment for local communities. We report early findings from collaborations with two leading property companies managing major investments in brownfield urban assets in the UK to consider how the inclusion of health and wellbeing evidence in social valuation can inform perceptions of brownfield development social benefit for asset managers, local communities, public authorities and investors for the benefit of all parties. Using holistic case studies and systems mapping approaches, we explore complex relationships between public health considerations and asset management decisions in urban production. Findings indicate a strong real estate investment industry appetite and potential to include health as a vital component of sustainable real estate social value creation in asset management strategies.Keywords: brownfield urban assets, health and wellbeing, social needs and impact, social valuation, sustainable real estate, systems mapping
Procedia PDF Downloads 69452 Complex Dynamics in a Morphologically Heterogeneous Biological Medium
Authors: Turky Al-Qahtani, Roustem Miftahof
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Introduction: Under common assumptions of excitabi-lity, morphological (cellular) homogeneity, and spatial structural anomalies added as required, it has been shown that biological systems are able to display travelling wave dynamics. Being not self-sustainable, existence depends on the electrophysiological state of transmembrane ion channels and it requires an extrinsic/intrinsic periodic source. However, organs in the body are highly multicellular, heterogeneous, and their functionality is the outcome of electro-mechanical conjugation, rather than excitability only. Thus, peristalsis in the gut relies on spatiotemporal myoelectrical pattern formations between the mechanical, represented by smooth muscle cells (SM), and the control, comprised of a chain of primary sensory and motor neurones, components. Synaptically linked through the afferent and efferent pathways, they form a functional unit (FU) of the gut. Aims: These are: i) to study numerically the complex dynamics, and ii) to investigate the possibility of self-sustained myoelectrical activity in the FU. Methods: The FU recreates the following sequence of physiological events: deformation of mechanoreceptors of located in SM; generation and propagation of electrical waves of depolarisation - spikes - along the axon to the soma of the primary neurone; discharge of the primary neurone and spike propagation towards the motor neurone; burst of the motor neurone and transduction of spikes to SM, subsequently producing forces of contraction. These are governed by a system of nonlinear partial and ordinary differential equations being a modified version of the Hodgkin-Huxley model and SM fibre mechanics. In numerical experiments; the source of excitation is mechanical stretches of SM at a fixed amplitude and variable frequencies. Results: Low frequency (0.5 < v < 2 Hz) stimuli cause the propagation of spikes in the neuronal chain and, finally, the generation of active forces by SM. However, induced contractions are not sufficient to initiate travelling wave dynamics in the control system. At frequencies, 2 < v < 4 Hz, multiple low amplitude and short-lasting contractions are observed in SM after the termination of stretching. For frequencies (0.5 < v < 4 Hz), primary and sensory neurones demonstrate strong connectivity and coherent electrical activity. Significant qualitative and quantitative changes in dynamics of myoelectical patterns with a transition to a self-organised mode are recorded with the high degree of stretches at v = 4.5 Hz. Increased rates of deformation lead to the production of high amplitude signals at the mechanoreceptors with subsequent self-sustained excitation within the neuronal chain. Remarkably, the connection between neurones weakens resulting in incoherent firing. Further increase in a frequency of stimulation (v > 4.5 Hz) has a detrimental effect on the system. The mechanical and control systems become disconnected and exhibit uncoordinated electromechanical activity. Conclusion: To our knowledge, the existence of periodic activity in a multicellular, functionally heterogeneous biological system with mechano-electrical dynamics, such as the FU, has been demonstrated for the first time. These findings support the notion of possible peristalsis in the gut even in the absence of intrinsic sources - pacemaker cells. Results could be implicated in the pathogenesis of intestinal dysrythmia, a medical condition associated with motor dysfunction.Keywords: complex dynamics, functional unit, the gut, dysrythmia
Procedia PDF Downloads 204451 Transcriptomic Analysis for Differential Expression of Genes Involved in Secondary Metabolite Production in Narcissus Bulb and in vitro Callus
Authors: Aleya Ferdausi, Meriel Jones, Anthony Halls
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The Amaryllidaceae genus Narcissus contains secondary metabolites, which are important sources of bioactive compounds such as pharmaceuticals indicating that their biological activity extends from the native plant to humans. Transcriptome analysis (RNA-seq) is an effective platform for the identification and functional characterization of candidate genes as well as to identify genes encoding uncharacterized enzymes. The biotechnological production of secondary metabolites in plant cell or organ cultures has become a tempting alternative to the extraction of whole plant material. The biochemical pathways for the production of secondary metabolites require primary metabolites to undergo a series of modifications catalyzed by enzymes such as cytochrome P450s, methyltransferases, glycosyltransferases, and acyltransferases. Differential gene expression analysis of Narcissus was obtained from two conditions, i.e. field and in vitro callus. Callus was obtained from modified MS (Murashige and Skoog) media supplemented with growth regulators and twin-scale explants from Narcissus cv. Carlton bulb. A total of 2153 differentially expressed transcripts were detected in Narcissus bulb and in vitro callus, and 78.95% of those were annotated. It showed the expression of genes involved in the biosynthesis of alkaloids were present in both conditions i.e. cytochrome P450s, O-methyltransferase (OMTs), NADP/NADPH dehydrogenases or reductases, SAM-synthetases or decarboxylases, 3-ketoacyl-CoA, acyl-CoA, cinnamoyl-CoA, cinnamate 4-hydroxylase, alcohol dehydrogenase, caffeic acid, N-methyltransferase, and NADPH-cytochrome P450s. However, cytochrome P450s and OMTs involved in the later stage of Amaryllidaceae alkaloids biosynthesis were mainly up-regulated in field samples. Whereas, the enzymes involved in initial biosynthetic pathways i.e. fructose biphosphate adolase, aminotransferases, dehydrogenases, hydroxyl methyl glutarate and glutamate synthase leading to the biosynthesis of precursors; tyrosine, phenylalanine and tryptophan for secondary metabolites were up-regulated in callus. The knowledge of probable genes involved in secondary metabolism and their regulation in different tissues will provide insight into the Narcissus plant biology related to alkaloid production.Keywords: narcissus, callus, transcriptomics, secondary metabolites
Procedia PDF Downloads 143450 The Effect of the Spinacia oleracea Extract on the Control of the Green Mold 'Penilillium digitatum' at the Post Harvested Citrus
Authors: Asma Chbani, Douaa Salim, Josephine Al Alam, Pascale De Caro
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Penicillium digitatum, the causal agent of citrus green mold, is responsible for 90% of post-harvest losses. Chemical fungicides remain the most used products for protection against this pathogen but are also responsible for damage to human health and the environment. The aim of this study is to evaluate the ability of Spinacia oleracea extract to serve as biological control agents, an alternative to harmful synthetic fungicides, against orange decay for storing fruit caused by P. digitatum. In this study, we studied the implication of a crude extract of a green plant, Spinacia oleracea, in the protection of oranges against P. digitatum. Thus, in vivo antifungal tests as well as adhesion test were done. For in vivo antifungal test, oranges were pulverized with the prepared crude extracts at different concentrations ranged from 25 g L⁻¹ to 200 g L⁻¹, contaminated by the fungus and then observed during 8 weeks for their macroscopic changes at 24°C. For adhesion test, the adhesion index is defined as the number of Penicillium digitatum spores fixed per orange cell. An index greater than 25 is the indicator of a strong adhesion, whereas for an index less than 10, the adhesion is low. Ten orange cells were examined in triplicate for each extract, and the averages of adherent cells were calculated. Obtained results showed an inhibitory activity of the Penicillium development with the aqueous extract of dry Spinacia oleracea with a concentration of 50 g L⁻¹ considered as the minimal protective concentration. The prepared extracts showed a greater inhibition of the development of P. digitatum up to 10 weeks, even greater than the fungicide control Nystatin. Adhesion test’s results showed that the adhesion of P. digitatum spores to the epidermal cells of oranges in the presence of the crude spinach leaves extract is weak; the mean of the obtained adhesion index was estimated to 2.7. However, a high adhesion was observed with water used a negative control. In conclusion, all these results confirm that the use of this green plant highly rich in chlorophyll having several phytotherapeutic activities, could be employed as a great treatment for protection of oranges against mold and also as an alternative for chemical fungicides.Keywords: Penicillium digitatum, Spinacia oleracea, oranges, biological control, postharvest diseases
Procedia PDF Downloads 172449 Application of the Pattern Method to Form the Stable Neural Structures in the Learning Process as a Way of Solving Modern Problems in Education
Authors: Liudmyla Vesper
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The problems of modern education are large-scale and diverse. The aspirations of parents, teachers, and experts converge - everyone interested in growing up a generation of whole, well-educated persons. Both the family and society are expected in the future generation to be self-sufficient, desirable in the labor market, and capable of lifelong learning. Today's children have a powerful potential that is difficult to realize in the conditions of traditional school approaches. Focusing on STEM education in practice often ends with the simple use of computers and gadgets during class. "Science", "technology", "engineering" and "mathematics" are difficult to combine within school and university curricula, which have not changed much during the last 10 years. Solving the problems of modern education largely depends on teachers - innovators, teachers - practitioners who develop and implement effective educational methods and programs. Teachers who propose innovative pedagogical practices that allow students to master large-scale knowledge and apply it to the practical plane. Effective education considers the creation of stable neural structures during the learning process, which allow to preserve and increase knowledge throughout life. The author proposed a method of integrated lessons – cases based on the maths patterns for forming a holistic perception of the world. This method and program are scientifically substantiated and have more than 15 years of practical application experience in school and student classrooms. The first results of the practical application of the author's methodology and curriculum were announced at the International Conference "Teaching and Learning Strategies to Promote Elementary School Success", 2006, April 22-23, Yerevan, Armenia, IREX-administered 2004-2006 Multiple Component Education Project. This program is based on the concept of interdisciplinary connections and its implementation in the process of continuous learning. This allows students to save and increase knowledge throughout life according to a single pattern. The pattern principle stores information on different subjects according to one scheme (pattern), using long-term memory. This is how neural structures are created. The author also admits that a similar method can be successfully applied to the training of artificial intelligence neural networks. However, this assumption requires further research and verification. The educational method and program proposed by the author meet the modern requirements for education, which involves mastering various areas of knowledge, starting from an early age. This approach makes it possible to involve the child's cognitive potential as much as possible and direct it to the preservation and development of individual talents. According to the methodology, at the early stages of learning students understand the connection between school subjects (so-called "sciences" and "humanities") and in real life, apply the knowledge gained in practice. This approach allows students to realize their natural creative abilities and talents, which makes it easier to navigate professional choices and find their place in life.Keywords: science education, maths education, AI, neuroplasticity, innovative education problem, creativity development, modern education problem
Procedia PDF Downloads 62448 Skin-to-Skin Contact Simulation: Improving Health Outcomes for Medically Fragile Newborns in the Neonatal Intensive Care Unit
Authors: Gabriella Zarlenga, Martha L. Hall
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Introduction: Premature infants are at risk for neurodevelopmental deficits and hospital readmissions, which can increase the financial burden on the health care system and families. Kangaroo care (skin-to-skin contact) is a practice that can improve preterm infant health outcomes. Preterm infants can acquire adequate body temperature, heartbeat, and breathing regulation through lying directly on the mother’s abdomen and in between her breasts. Due to some infant’s condition, kangaroo care is not a feasible intervention. The purpose of this proof-of-concept research project is to create a device which simulates skin-to-skin contact for pre-term infants not eligible for kangaroo care, with the aim of promoting baby’s health outcomes, reducing the incidence of serious neonatal and early childhood illnesses, and/or improving cognitive, social and emotional aspects of development. Methods: The study design is a proof-of-concept based on a three-phase approach; (1) observational study and data analysis of the standard of care for 2 groups of pre-term infants, (2) design and concept development of a novel device for pre-term infants not currently eligible for standard kangaroo care, and (3) prototyping, laboratory testing, and evaluation of the novel device in comparison to current assessment parameters of kangaroo care. A single center study will be conducted in an area hospital offering Level III neonatal intensive care. Eligible participants include newborns born premature (28-30 weeks of age) admitted to the NICU. The study design includes 2 groups: a control group receiving standard kangaroo care and an experimental group not eligible for kangaroo care. Based on behavioral analysis of observational video data collected in the NICU, the device will be created to simulate mother’s body using electrical components in a thermoplastic polymer housing covered in silicone. It will be designed with a microprocessor that controls simulated respiration, heartbeat, and body temperature of the 'simulated caregiver' by using a pneumatic lung, vibration sensors (heartbeat), pressure sensors (weight/position), and resistive film to measure temperature. A slight contour of the simulator surface may be integrated to help position the infant correctly. Control and monitoring of the skin-to-skin contact simulator would be performed locally by an integrated touchscreen. The unit would have built-in Wi-Fi connectivity as well as an optional Bluetooth connection in which the respiration and heart rate could be synced with a parent or caregiver. A camera would be integrated, allowing a video stream of the infant in the simulator to be streamed to a monitoring location. Findings: Expected outcomes are stabilization of respiratory and cardiac rates, thermoregulation of those infants not eligible for skin to skin contact with their mothers, and real time mother Bluetooth to the device to mimic the experience in the womb. Results of this study will benefit clinical practice by creating a new standard of care for premature neonates in the NICU that are deprived of skin to skin contact due to various health restrictions.Keywords: kangaroo care, wearable technology, pre-term infants, medical design
Procedia PDF Downloads 156447 Therapeutic Effects of Toll Like Receptor 9 Ligand CpG-ODN on Radiation Injury
Authors: Jianming Cai
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Exposure to ionizing radiation causes severe damage to human body and an safe and effective radioprotector is urgently required for alleviating radiation damage. In 2008, flagellin, an agonist of TLR5, was found to exert radioprotective effects on radiation injury through activating NF-kB signaling pathway. From then, the radioprotective effects of TLR ligands has shed new lights on radiation protection. CpG-ODN is an unmethylated oligonucleotide which activates TLR9 signaling pathway. In this study, we demonstrated that CpG-ODN has therapeutic effects on radiation injuries induced by γ ray and 12C6+ heavy ion particles. Our data showed that CpG-ODN increased the survival rate of mice after whole body irradiation and increased the number of leukocytes as well as the bone marrow cells. CpG-ODN also alleviated radiation damage on intestinal crypt through regulating apoptosis signaling pathway including bcl2, bax, and caspase 3 etc. By using a radiation-induced pulmonary fibrosis model, we found that CpG-ODN could alleviate structural damage, within 20 week after whole–thorax 15Gy irradiation. In this model, Th1/Th2 imbalance induced by irradiation was also reversed by CpG-ODN. We also found that TGFβ-Smad signaling pathway was regulated by CpG-ODN, which accounts for the therapeutic effects of CpG-ODN in radiation-induced pulmonary injury. On another hand, for high LET radiation protection, we investigated protective effects of CpG-ODN against 12C6+ heavy ion irradiation and found that after CpG-ODN treatment, the apoptosis and cell cycle arrest induced by 12C6+ irradiation was reduced. CpG-ODN also reduced the expression of Bax and caspase 3, while increased the level of bcl2. Then we detected the effect of CpG-ODN on heavy ion induced immune dysfunction. Our data showed that CpG-ODN increased the survival rate of mice and also the leukocytes after 12C6+ irradiation. Besides, the structural damage of immune organ such as thymus and spleen was also alleviated by CpG-ODN treatment. In conclusion, we found that TLR9 ligand, CpG-ODN reduced radiation injuries in response to γ ray and 12C6+ heavy ion irradiation. On one hand, CpG-ODN inhibited the activation of apoptosis induced by radiation through regulating bcl2, bax and caspase 3. On another hand, through activating TLR9, CpG-ODN recruit MyD88-IRAK-TRAF6 complex, activating TAK1, IRF5 and NF-kB pathway, and thus alleviates radiation damage. This study provides novel insights into protection and therapy of radiation damages.Keywords: TLR9, CpG-ODN, radiation injury, high LET radiation
Procedia PDF Downloads 480446 Exploring Penicillin Resistance in Gonococcal Penicillin Binding Protein-2: Molecular Docking and Ligand Interaction Analysis
Authors: Sinethemba Yakobi, Lindiwe Zuma, Ofentse Pooe
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Gonococcal infections present a notable public health issue, and the major approach for treatment involves using β-lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in Neisseria gonorrhoeae. This study examines the influence of flavonoids, namely rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research clarifies the structural effects of particular mutations, such as inserting an aspartate residue at position 345 (Asp-345a) in the PBP2 protein. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely P551S and F504L, significantly impact the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasizing its exceptional binding affinity and potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin's exceptional antioxidant effects and strong affinity for the substrate binding site. The study's wider ramifications pertain to the pressing requirement for antiviral treatments in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in N. gonorrhoeae. Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant N. gonorrhoeae bacteria. The verified simulation outcomes establish a basis for creating potent inhibitors and medicinal therapies to combat infectious illnesses.Keywords: phytochemicals, penicillin-binding protein 2, gonococcal infection, ligand-protein interaction, binding energy, neisseria gonorrhoeae FA19, neisseria gonorrhoeae FA6140, flavonoids
Procedia PDF Downloads 69445 Wind Turbine Scaling for the Investigation of Vortex Shedding and Wake Interactions
Authors: Sarah Fitzpatrick, Hossein Zare-Behtash, Konstantinos Kontis
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Traditionally, the focus of horizontal axis wind turbine (HAWT) blade aerodynamic optimisation studies has been the outer working region of the blade. However, recent works seek to better understand, and thus improve upon, the performance of the inboard blade region to enhance power production, maximise load reduction and better control the wake behaviour. This paper presents the design considerations and characterisation of a wind turbine wind tunnel model devised to further the understanding and fundamental definition of horizontal axis wind turbine root vortex shedding and interactions. Additionally, the application of passive and active flow control mechanisms – vortex generators and plasma actuators – to allow for the manipulation and mitigation of unsteady aerodynamic behaviour at the blade inboard section is investigated. A static, modular blade wind turbine model has been developed for use in the University of Glasgow’s de Havilland closed return, low-speed wind tunnel. The model components - which comprise of a half span blade, hub, nacelle and tower - are scaled using the equivalent full span radius, R, for appropriate Mach and Strouhal numbers, and to achieve a Reynolds number in the range of 1.7x105 to 5.1x105 for operational speeds up to 55m/s. The half blade is constructed to be modular and fully dielectric, allowing for the integration of flow control mechanisms with a focus on plasma actuators. Investigations of root vortex shedding and the subsequent wake characteristics using qualitative – smoke visualisation, tufts and china clay flow – and quantitative methods – including particle image velocimetry (PIV), hot wire anemometry (HWA), and laser Doppler anemometry (LDA) – were conducted over a range of blade pitch angles 0 to 15 degrees, and Reynolds numbers. This allowed for the identification of shed vortical structures from the maximum chord position, the transitional region where the blade aerofoil blends into a cylindrical joint, and the blade nacelle connection. Analysis of the trailing vorticity interactions between the wake core and freestream shows the vortex meander and diffusion is notably affected by the Reynold’s number. It is hypothesized that the shed vorticity from the blade root region directly influences and exacerbates the nacelle wake expansion in the downstream direction. As the design of inboard blade region form is, by necessity, driven by function rather than aerodynamic optimisation, a study is undertaken for the application of flow control mechanisms to manipulate the observed vortex phenomenon. The designed model allows for the effective investigation of shed vorticity and wake interactions with a focus on the accurate geometry of a root region which is representative of small to medium power commercial HAWTs. The studies undertaken allow for an enhanced understanding of the interplay of shed vortices and their subsequent effect in the near and far wake. This highlights areas of interest within the inboard blade area for the potential use of passive and active flow control devices which contrive to produce a more desirable wake quality in this region.Keywords: vortex shedding, wake interactions, wind tunnel model, wind turbine
Procedia PDF Downloads 235444 ANSYS FLUENT Simulation of Natural Convection and Radiation in a Solar Enclosure
Authors: Sireetorn Kuharat, Anwar Beg
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In this study, multi-mode heat transfer characteristics of spacecraft solar collectors are investigated computationally. Two-dimensional steady-state incompressible laminar Newtonian viscous convection-radiative heat transfer in a rectangular solar collector geometry. The ANSYS FLUENT finite volume code (version 17.2) is employed to simulate the thermo-fluid characteristics. Several radiative transfer models are employed which are available in the ANSYS workbench, including the classical Rosseland flux model and the more elegant P1 flux model. Mesh-independence tests are conducted. Validation of the simulations is conducted with a computational Harlow-Welch MAC (Marker and Cell) finite difference method and excellent correlation. The influence of aspect ratio, Prandtl number (Pr), Rayleigh number (Ra) and radiative flux model on temperature, isotherms, velocity, the pressure is evaluated and visualized in color plots. Additionally, the local convective heat flux is computed and solutions are compared with the MAC solver for various buoyancy effects (e.g. Ra = 10,000,000) achieving excellent agreement. The P1 model is shown to better predict the actual influence of solar radiative flux on thermal fluid behavior compared with the limited Rosseland model. With increasing Rayleigh numbers the hot zone emanating from the base of the collector is found to penetrate deeper into the collector and rises symmetrically dividing into two vortex regions with very high buoyancy effect (Ra >100,000). With increasing Prandtl number (three gas cases are examined respectively hydrogen gas mixture, air and ammonia gas) there is also a progressive incursion of the hot zone at the solar collector base higher into the solar collector space and simultaneously a greater asymmetric behavior of the dual isothermal zones. With increasing aspect ratio (wider base relative to the height of the solar collector geometry) there is a greater thermal convection pattern around the whole geometry, higher temperatures and the elimination of the cold upper zone associated with lower aspect ratio.Keywords: thermal convection, radiative heat transfer, solar collector, Rayleigh number
Procedia PDF Downloads 119