Search results for: T cell response
6432 Synthesis, Characterization and Applications of Some Selected Dye-Functionalized P and N-Type Nanoparticles in Dye Sensitized Solar Cells
Authors: Arifa Batool, Ghulam Hussain Bhatti, Syed Mujtaba Shah
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Inorganic n-type (TiO2, CdO) and p-type (NiO, CuO) metal oxide nanoparticles were synthesized by a facile wet chemical method at room temperature. The morphological, compositional, structural and optical properties were investigated by scanning electron microscopy, energy dispersive X-ray spectroscopy, FT-IR, XRD analysis, UV/Visible and fluorescence spectroscopy. All semiconducting nanoparticles were photosensitized with Ru (II) based Z907 dye in ethanol solvent by grafting. Grafting of dye on the surface of nanoparticles was confirmed by UV/Visible and FT-IR spectroscopy. The synthesized photo-active nanohybrid was thoroughly blended with P3HT, a solid electrolyte and I-V measurements under solar stimulated radiations 1000 W/m2 (AM 1.5) were recorded. Maximum incident photon to current conversion efficiency (IPCE) of 0.9% was achieved with dye functionalized Z907-TiO2 hybrid, IPCE of 0.72% was achieved with bulk-heterojunction of TiO2-Z907-CuO and IPCE of 0.68% was attained with nanocomposite of TiO2-CdO. TiO2 based Solar cells have maximum Jscvalue i.e.4.63 mA/cm2. Dye-functionalized TiO2-based photovoltaic devices were found more efficient than the reference device but the morphology of the device was a major check in progress.Keywords: solar cell, bulk heterojunction, nanocomposites, photosensitization, dye sensitized solar cell
Procedia PDF Downloads 2786431 Human Development Outcomes and Macroeconomic Indicators Nexus in Nigeria: An Empirical Investigation
Authors: Risikat Oladoyin S. Dauda, Onyebuchi Iwegbu
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This study investigates the response of human development outcomes to selected macroeconomic indicators in Nigeria. Human development outcomes is measured by human development index while the selected macroeconomic variables are inflation rate, real interest rate, government capital expenditure, real exchange rate, current account balance, and savings. Structural Vector Autoregression (SVAR) technique is employed in examining the response of human development index to the macroeconomic shocks. The result from the forecast error variance decomposition and Impulse-Response analysis reveals that fiscal policy (government capital expenditure) shock is the greatest determinant of human development outcomes. This result reiterates the role which the government plays in improving the welfare of the citizenry. The fiscal policy tool is pivotal in human development which comes in the form of investment in education, health, housing, and infrastructure. Further conclusion drawn from this study is that human development outcome positively and significantly responds to shocks from real interest rate, a monetary policy transmission variable and is felt greatly in the short run period. The policy implication of this study is that if capital budget implementation falls below expectations, human development will be engendered. Hence, efforts should be made to ensure that full implementation and appraisal of government capital expenditure is taken sacrosanct as any shock from such plan, engenders human development outcome.Keywords: human development outcome, macroeconomic outcomes, structural vector autoregression, SVAR
Procedia PDF Downloads 1466430 Comparison of Risk Analysis Methodologies Through the Consequences Identification in Chemical Accidents Associated with Dangerous Flammable Goods Storage
Authors: Daniel Alfonso Reséndiz-García, Luis Antonio García-Villanueva
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As a result of the high industrial activity, which arises from the search to satisfy the needs of products and services for society, several chemical accidents have occurred, causing serious damage to different sectors: human, economic, infrastructure and environmental losses. Historically, with the study of this chemical accidents, it has been determined that the causes are mainly due to human errors (inexperienced personnel, negligence, lack of maintenance and deficient risk analysis). The industries have the aim to increase production and reduce costs. However, it should be kept in mind that the costs involved in risk studies, implementation of barriers and safety systems is much cheaper than paying for the possible damages that could occur in the event of an accident, without forgetting that there are things that cannot be replaced, such as human lives.Therefore, it is of utmost importance to implement risk studies in all industries, which provide information for prevention and planning. The aim of this study is to compare risk methodologies by identifying the consequences of accidents related to the storage of flammable, dangerous goods for decision making and emergency response.The methodologies considered in this study are qualitative and quantitative risk analysis and consequence analysis. The latter, by means of modeling software, which provides radius of affectation and the possible scope and magnitude of damages.By using risk analysis, possible scenarios of occurrence of chemical accidents in the storage of flammable substances are identified. Once the possible risk scenarios have been identified, the characteristics of the substances, their storage and atmospheric conditions are entered into the software.The results provide information that allows the implementation of prevention, detection, control, and combat elements for emergency response, thus having the necessary tools to avoid the occurrence of accidents and, if they do occur, to significantly reduce the magnitude of the damage.This study highlights the importance of risk studies applying tools that best suited to each case study. It also proves the importance of knowing the risk exposure of industrial activities for a better prevention, planning and emergency response.Keywords: chemical accidents, emergency response, flammable substances, risk analysis, modeling
Procedia PDF Downloads 836429 Isolation and Characterization of Anti-melanoma (Skin Cancer) Compounds from Corchorus olitorius .L
Authors: Peramachi Sathiyamoorthy, Jacop Gopas, Avi Golan Goldhirsh
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Corchorus olitorius is a leafy vegetable and an industrial crop. The herb has antioxidant, anti inflammatory, and anti-cancer properties. To assay the pharmaceutical properties, aqueous extracts of leaves and seeds from C. olitorius were tested against drug resistant melanoma cell line. The test showed LC50 of the extract was 0.08µg/ml. Aqueous seed extract exhibited higher melanoma inhibiting activity than leaf extract. Dialysis of seed extract showed that the active compound is less than 12 KDa. The compound with <3 KDa MW separated by microconcentration of seed extract showed 70.5 % inhibition of melanoma cell growth. Among the two fractions obtained by Gel filtration with G10 column, the first fraction at 1:2000 dilutions exhibited 100% inhibition of melanoma growth. The compound with Rf value 0.86 (MA4) isolated by TLC separation showed about 98% cytotoxicity against melanoma at 1: 1000 dilutions. Furthermore, HPLC separation of MA4 compound with Superdex 75 column resulted in 4 compounds. Out of 4, one compound showed melanoma inhibition. The active compound is identified by reagent methods as Strophanthidin. Further toxicological and clinical studies will lead to the development of a potential drug to treat drug resistant melanoma.Keywords: corchorus olitorius, melanoma, drug development, strophanthidin
Procedia PDF Downloads 1266428 Seismic Response of Braced Steel Frames with Shape Memory Alloy and Mega Bracing Systems
Authors: Mohamed Omar
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Steel bracing members are widely used in steel structures to reduce lateral displacement and dissipate energy during earthquake motions. Concentric steel bracing provide an excellent approach for strengthening and stiffening steel buildings. Using these braces the designer can hardly adjust the stiffness together with ductility as needed because of buckling of braces in compression. In this study the use of SMA bracing and steel bracing (Mega) utilized in steel frames are investigated. The effectiveness of these two systems in rehabilitating a mid-rise eight-storey steel frames were examined using time-history nonlinear analysis utilizing Seismo-Struct software. Results show that both systems improve the strength and stiffness of the original structure but due to excellent behavior of SMA in nonlinear phase and under compressive forces this system shows much better performance than the rehabilitation system of Mega bracing.Keywords: finite element analysis, seismic response, shapes memory alloy, steel frame, mega bracing
Procedia PDF Downloads 3186427 Characterization of Porosity and Flow in Solid Oxide Fuel Cell with 3D Focused Ion Beam Serial Slicing
Authors: Daniel Phifer, Anna Prokhodtseva
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DualBeam (FIB-SEM) has long been the technology of choice to sub-sample and characterize materials at site-specific locations which are difficult or impossible to extract by conventional embedding/polishing methods. Whereas Ga based FIB provides excellent resolution and enables precise material removal, the current is usually limited and only allows the extraction of small material biopsies typically ranging from 5-70um wide. Xe Plasma FIB, by contrast, has around 38x more current and can remove more material at the same time to extract significant sized chunks (100-1000um) of materials for further analysis. This increased volume has enabled time-prohibitive investigations like large grain 3D serial sectioning and EBSD and micro-machining for micro-mechanical testing. Investigation of the pore spaces with 3D modeling can determine the relative characteristics of the materials to help design or select properties for best function. Pore spaces can be described with a tortuosity number which is calculated by modules in the 3D analysis software. Xe Plasma FIB technology provides a workflow with sufficient volume to characterize porosity when both large-volume 3D materials characterization and nanometer resolution is required to understand the system.Keywords: dual-beam, FIB-SEM, porosity, SOFC, solid oxide fuel cell
Procedia PDF Downloads 2006426 The Effect of Different Levels of Seed and Extract of Harmal (Peganum harmala L.) on Immune Responses of Broiler Chicks
Authors: M. Toghyani, A. Ghasemi, S. A. Tabeidian
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The present study was carried out to evaluate the effect of different levels of dietary seed and extract of Harmal (Peganum harmala L.) on immunity of broiler chicks. A total of 350 one-day old broiler chicks (Ross 308) were randomly allocated to five dietary treatments with four replicates pen of 14 birds each. Dietary treatments consisted of control, 1 and 2 g/kg Harmal seed in diet, 100 and 200 mg/L Harmal seed extract in water. Broilers received dietary treatments from 1 to 42 d. Two birds from each pen were randomly weighed and sacrificed at 42 d of age, the relative weight of lymphoid organs (bursa of Fabercius and spleen) to live weight were calculated. Antibody titers against Newcastle and influenza viruses and sheep red blood cell were measured at 30 d of age. Results showed that the relative weights of lymphoid organs were not affected by dietary treatments. Furthermore, antibody titer against Newcastle and influenza viruses as well as sheep red blood cell antigen were significantly (P<0.05) enhanced by feeding Harmal seed and extract. In conclusion, the results indicated that dietary inclusion of Harmal seed and extract enhanced immunological responses in broiler chicks.Keywords: broiler chicks, Harmal, immunity, Peganum harmala
Procedia PDF Downloads 5426425 Application of Soft Systems Methodology in Solving Disaster Emergency Logistics Problems
Authors: Alhasan Hakami, Arun Kumar, Sung J. Shim, Yousef Abu Nahleh
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In recent years, many high intensity earthquakes have occurred around the world, such as the 2011 earthquake in Tohoku, Japan. These large-scale disasters caused huge casualties and losses. In addition, inefficient disaster response operations also caused the second wave of casualties and losses, and expanded the damage. Effective disaster management can be used to respond to the chaotic situation, and reduce the damage. However, some inefficient disaster response operations are still used. Therefore, this case study chose the 921 earthquakes for analysing disaster emergency logistics problems and proposed the Soft Systems Methodology (SSM) to solve disaster emergency logistics problems. Moreover, it analyses the effect of human factors on system operation, and suggests a solution to improve the system.Keywords: soft systems methodology, emergency logistics, earthquakes, Japan, system operation
Procedia PDF Downloads 4386424 Experimental Investigation of the Impact of Biosurfactants on Residual-Oil Recovery
Authors: S. V. Ukwungwu, A. J. Abbas, G. G. Nasr
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The increasing high price of natural gas and oil with attendant increase in energy demand on world markets in recent years has stimulated interest in recovering residual oil saturation across the globe. In order to meet the energy security, efforts have been made in developing new technologies of enhancing the recovery of oil and gas, utilizing techniques like CO2 flooding, water injection, hydraulic fracturing, surfactant flooding etc. Surfactant flooding however optimizes production but poses risk to the environment due to their toxic nature. Amongst proven records that have utilized other type of bacterial in producing biosurfactants for enhancing oil recovery, this research uses a technique to combine biosurfactants that will achieve a scale of EOR through lowering interfacial tension/contact angle. In this study, three biosurfactants were produced from three Bacillus species from freeze dried cultures using sucrose 3 % (w/v) as their carbon source. Two of these produced biosurfactants were screened with the TEMCO Pendant Drop Image Analysis for reduction in IFT and contact angle. Interfacial tension was greatly reduced from 56.95 mN.m-1 to 1.41 mN.m-1 when biosurfactants in cell-free culture (Bacillus licheniformis) were used compared to 4. 83mN.m-1 cell-free culture of Bacillus subtilis. As a result, cell-free culture of (Bacillus licheniformis) changes the wettability of the biosurfactant treatment for contact angle measurement to more water-wet as the angle decreased from 130.75o to 65.17o. The influence of microbial treatment on crushed rock samples was also observed by qualitative wettability experiments. Treated samples with biosurfactants remained in the aqueous phase, indicating a water-wet system. These results could prove that biosurfactants can effectively change the chemistry of the wetting conditions against diverse surfaces, providing a desirable condition for efficient oil transport in this way serving as a mechanism for EOR. The environmental friendly effect of biosurfactants applications for industrial purposes play important advantages over chemically synthesized surfactants, with various possible structures, low toxicity, eco-friendly and biodegradability.Keywords: bacillus, biosurfactant, enhanced oil recovery, residual oil, wettability
Procedia PDF Downloads 2766423 Exoskeleton Response During Infant Physiological Knee Kinematics And Dynamics
Authors: Breanna Macumber, Victor A. Huayamave, Emir A. Vela, Wangdo Kim, Tamara T. Chamber, Esteban Centeno
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Spina bifida is a type of neural tube defect that affects the nervous system and can lead to problems such as total leg paralysis. Treatment requires physical therapy and rehabilitation. Robotic exoskeletons have been used for rehabilitation to train muscle movement and assist in injury recovery; however, current models focus on the adult populations and not on the infant population. The proposed framework aims to couple a musculoskeletal infant model with a robotic exoskeleton using vacuum-powered artificial muscles to provide rehabilitation to infants affected by spina bifida. The study that drove the input values for the robotic exoskeleton used motion capture technology to collect data from the spontaneous kicking movement of a 2.4-month-old infant lying supine. OpenSim was used to develop the musculoskeletal model, and Inverse kinematics was used to estimate hip joint angles. A total of 4 kicks (A, B, C, D) were selected, and the selection was based on range, transient response, and stable response. Kicks had at least 5° of range of motion with a smooth transient response and a stable period. The robotic exoskeleton used a Vacuum-Powered Artificial Muscle (VPAM) the structure comprised of cells that were clipped in a collapsed state and unclipped when desired to simulate infant’s age. The artificial muscle works with vacuum pressure. When air is removed, the muscle contracts and when air is added, the muscle relaxes. Bench testing was performed using a 6-month-old infant mannequin. The previously developed exoskeleton worked really well with controlled ranges of motion and frequencies, which are typical of rehabilitation protocols for infants suffering with spina bifida. However, the random kicking motion in this study contained high frequency kicks and was not able to accurately replicate all the investigated kicks. Kick 'A' had a greater error when compared to the other kicks. This study has the potential to advance the infant rehabilitation field.Keywords: musculoskeletal modeling, soft robotics, rehabilitation, pediatrics
Procedia PDF Downloads 716422 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients
Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas
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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib
Procedia PDF Downloads 1926421 The Challenges of Security Sector Governance in West African Democracies-The Ecowas Response Mechanism
Authors: Adamu Buba
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As West Africa gradually recovers from the cost of more than a decade of civil conflicts in Liberia, Sierra Leone and Côte d’Ivoire, ECOWAS has continued to place prominence on peace consolidation and the prevention of conflict in the West African Sub-Region. Of particular interest is the recent political uprising in Mali and in this regard, ECOWAS has been repositioning their existing machineries to manage this dispensation more effectively by improving their early warning and mediation capabilities. This paper firstly seeks among other things to provide a conceptual understanding of what security sector governance is, and also highlight the overview of ECOWAS and to closely examine the benchmark for assessing progress in the promotion of democracy and political governance within the sub-region as well as conflict prevention techniques. The views and analysis expressed in this paper is based on secondary method of data collection alone and do not in any way represent the views of the institutions or their representatives involved in this assignment in one way or the other.Keywords: challenges, security, governance, ecowas, response
Procedia PDF Downloads 2466420 Internet-Based Architecture for Machine-to-Machine Communication of a Public Security Network
Authors: Ogwueleka Francisca Nonyelum, Jiya Muhammad
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Poor communication between the victims of the burglaries, road and fire accidents and the agencies, and lack of quick emergency response by the agencies is solved through Machine-to-Machine (M2M) communication. A distress caller is expected to make a call through a network to the respective agency for emergency response but due to some challenges, this often becomes arduous and futile. This research puts forth an Internet-based architecture for Machine-to-Machine (M2M) communication to enhance information dissemination in National Public Security Communication System (NPSCS) network. M2M enables the flow of data between machines and machines and ultimately machines and people with information flowing from a machine over a network, and then through a gateway to a system where it is reviewed and acted on. The research findings showed that Internet-based architecture for M2M communication is most suitable for deployment of a public security network which will allow machines to use Internet to talk to each other.Keywords: machine-to-machine (M2M), internet-based architecture, network, gateway
Procedia PDF Downloads 4726419 The UbiB Family Member Cqd1 Forms a Membrane Contact Site in Mitochondria
Authors: S. Khosravi, X. Chelius, A. Unger, D. Rieger, J. Frickel, T. Sachsenheimer, C. Luechtenborg, R. Schieweck, B. Bruegger, B. Westermann, T. Klecker, W. Neupert, M. E. Harner
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The use of Saccharomyces cerevisiae as a model organism to study eukaryotic cell functions has been used successfully for decades. Like virtually all eukaryotic cells, they contain mitochondria as essential organelles performing various functions, including participation in lipid metabolism. They are separated from the cytosol by a double membrane system consisting of the mitochondrial inner membrane (MIM) and the mitochondrial outer membrane (MOM). This physical separation of the mitochondria requires an exchange of metabolites, proteins, and lipids. Proteinaceous contact sites are thought to be important for this communication. Recently, it was found that Cqd1, in cooperation with Cqd2, controls the distribution of Coenzyme Q within the cell. In this study, a contact site is described, formed by the MOM protein complex Por1-Om14 and the UbiB protein kinase-like MIM protein Cqd1. The present results suggest the additional involvement of Cqd1 in the homeostasis of phospholipids. Moreover, we show that overexpression of the UbiB family proteins also causes tethering of the mitochondria to the endoplasmatic reticulum. Due to the conservation of the subunits of this contact site to higher eukaryotes, its identification in S. cerevisiae might provide promising avenues for further research in other organisms.Keywords: contact sites, mitochondrial architecture, mitochondrial proteins, yeast mitochondria
Procedia PDF Downloads 986418 Modeling Taxane-Induced Peripheral Neuropathy Ex Vivo Using Patient-Derived Neurons
Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider
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Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel
Procedia PDF Downloads 1166417 Challenge Response-Based Authentication for a Mobile Voting System
Authors: Tohari Ahmad, Hudan Studiawan, Iwang Aryadinata, Royyana M. Ijtihadie, Waskitho Wibisono
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A manual voting system has been implemented worldwide. It has some weaknesses which may decrease the legitimacy of the voting result. An electronic voting system is introduced to minimize this weakness. It has been able to provide a better result, in terms of the total time taken in the voting process and accuracy. Nevertheless, people may be reluctant to go to the polling location because of some reasons, such as distance and time. In order to solve this problem, mobile voting is implemented by utilizing mobile devices. There are many mobile voting architectures available. Overall, authenticity of the users is the common problem of all voting systems. There must be a mechanism which can verify the users’ authenticity such that only verified users can give their vote once; others cannot vote. In this paper, a challenge response-based authentication is proposed by utilizing properties of the users, for example, something they have and know. In terms of speed, the proposed system provides good result, in addition to other capabilities offered by the system.Keywords: authentication, data protection, mobile voting, security
Procedia PDF Downloads 4096416 Compact Microstrip Ultra-Wideband Bandstop Filter With Quasi-Elliptic Function Response
Authors: Hussein Shaman, Faris Almansour
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This paper proposes a modified optimum bandstop filter with ultra-wideband stopband. The filter consists of three shunt open-circuited stubs and two non-redundant unit elements. The proposed bandstop filter is designed with unequal electrical lengths of the open-circuited stubs at the mid-stopband. Therefore, the filter can exhibit a quasi-elliptic function response that improves the selectivity and enhances the rejection bandwidth. The filter is designed to exhibit a fractional bandwidth of about 114% at a mid-stopband frequency of 3.0 GHz. The filter is successfully realized in theory, simulated, fabricated and measured. An excellent agreement is obtained between calculated, simulated and measured. The fabricated filter has a compact size with a low insertion loss in the passbands, high selectivity and good attenuation level inside the desired stopbandKeywords: microstrip filter, bandstop filter, UWB filter, transmission line filter
Procedia PDF Downloads 1406415 Modeling Competition Between Subpopulations with Variable DNA Content in Resource-Limited Microenvironments
Authors: Parag Katira, Frederika Rentzeperis, Zuzanna Nowicka, Giada Fiandaca, Thomas Veith, Jack Farinhas, Noemi Andor
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Resource limitations shape the outcome of competitions between genetically heterogeneous pre-malignant cells. One example of such heterogeneity is in the ploidy (DNA content) of pre-malignant cells. A whole-genome duplication (WGD) transforms a diploid cell into a tetraploid one and has been detected in 28-56% of human cancers. If a tetraploid subclone expands, it consistently does so early in tumor evolution, when cell density is still low, and competition for nutrients is comparatively weak – an observation confirmed for several tumor types. WGD+ cells need more resources to synthesize increasing amounts of DNA, RNA, and proteins. To quantify resource limitations and how they relate to ploidy, we performed a PAN cancer analysis of WGD, PET/CT, and MRI scans. Segmentation of >20 different organs from >900 PET/CT scans were performed with MOOSE. We observed a strong correlation between organ-wide population-average estimates of Oxygen and the average ploidy of cancers growing in the respective organ (Pearson R = 0.66; P= 0.001). In-vitro experiments using near-diploid and near-tetraploid lineages derived from a breast cancer cell line supported the hypothesis that DNA content influences Glucose- and Oxygen-dependent proliferation-, death- and migration rates. To model how subpopulations with variable DNA content compete in the resource-limited environment of the human brain, we developed a stochastic state-space model of the brain (S3MB). The model discretizes the brain into voxels, whereby the state of each voxel is defined by 8+ variables that are updated over time: stiffness, Oxygen, phosphate, glucose, vasculature, dead cells, migrating cells and proliferating cells of various DNA content, and treat conditions such as radiotherapy and chemotherapy. Well-established Fokker-Planck partial differential equations govern the distribution of resources and cells across voxels. We applied S3MB on sequencing and imaging data obtained from a primary GBM patient. We performed whole genome sequencing (WGS) of four surgical specimens collected during the 1ˢᵗ and 2ⁿᵈ surgeries of the GBM and used HATCHET to quantify its clonal composition and how it changes between the two surgeries. HATCHET identified two aneuploid subpopulations of ploidy 1.98 and 2.29, respectively. The low-ploidy clone was dominant at the time of the first surgery and became even more dominant upon recurrence. MRI images were available before and after each surgery and registered to MNI space. The S3MB domain was initiated from 4mm³ voxels of the MNI space. T1 post and T2 flair scan acquired after the 1ˢᵗ surgery informed tumor cell densities per voxel. Magnetic Resonance Elastography scans and PET/CT scans informed stiffness and Glucose access per voxel. We performed a parameter search to recapitulate the GBM’s tumor cell density and ploidy composition before the 2ⁿᵈ surgery. Results suggest that the high-ploidy subpopulation had a higher Glucose-dependent proliferation rate (0.70 vs. 0.49), but a lower Glucose-dependent death rate (0.47 vs. 1.42). These differences resulted in spatial differences in the distribution of the two subpopulations. Our results contribute to a better understanding of how genomics and microenvironments interact to shape cell fate decisions and could help pave the way to therapeutic strategies that mimic prognostically favorable environments.Keywords: tumor evolution, intra-tumor heterogeneity, whole-genome doubling, mathematical modeling
Procedia PDF Downloads 656414 Redefining the Croatian Economic Sentiment Indicator
Authors: Ivana Lolic, Petar Soric, Mirjana Cizmesija
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Based on Business and Consumer Survey (BCS) data, the European Commission (EC) regularly publishes the monthly Economic Sentiment Indicator (ESI) for each EU member state. ESI is conceptualized as a leading indicator, aimed ad tracking the overall economic activity. In calculating ESI, the EC employs arbitrarily chosen weights on 15 BCS response balances. This paper raises the predictive quality of ESI by applying nonlinear programming to find such weights that maximize the correlation coefficient of ESI and year-on-year GDP growth. The obtained results show that the highest weights are assigned to the response balances of industrial sector questions, followed by questions from the retail trade sector. This comes as no surprise since the existing literature shows that the industrial production is a plausible proxy for the overall Croatian economic activity and since Croatian GDP is largely influenced by the aggregate personal consumption.Keywords: business and consumer survey, economic sentiment indicator, leading indicator, nonlinear optimization with constraints
Procedia PDF Downloads 4546413 Fast Robust Switching Control Scheme for PWR-Type Nuclear Power Plants
Authors: Piyush V. Surjagade, Jiamei Deng, Paul Doney, S. R. Shimjith, A. John Arul
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In sophisticated and complex systems such as nuclear power plants, maintaining the system's stability in the presence of uncertainties and disturbances and obtaining a fast dynamic response are the most challenging problems. Thus, to ensure the satisfactory and safe operation of nuclear power plants, this work proposes a new fast, robust optimal switching control strategy for pressurized water reactor-type nuclear power plants. The proposed control strategy guarantees a substantial degree of robustness, fast dynamic response over the entire operational envelope, and optimal performance during the nominal operation of the plant. To improve the robustness, obtain a fast dynamic response, and make the system optimal, a bank of controllers is designed. Various controllers, like a baseline proportional-integral-derivative controller, an optimal linear quadratic Gaussian controller, and a robust adaptive L1 controller, are designed to perform distinct tasks in a specific situation. At any instant of time, the most suitable controller from the bank of controllers is selected using the switching logic unit that designates the controller by monitoring the health of the nuclear power plant or transients. The proposed switching control strategy optimizes the overall performance and increases operational safety and efficiency. Simulation studies have been performed considering various uncertainties and disturbances that demonstrate the applicability and effectiveness of the proposed switching control strategy over some conventional control techniques.Keywords: switching control, robust control, optimal control, nuclear power control
Procedia PDF Downloads 1216412 Measuring Organizational Resiliency for Flood Response in Thailand
Authors: Sudha Arlikatti, Laura Siebeneck, Simon A. Andrew
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The objective of this research is to measure organizational resiliency through five attributes namely, rapidity, redundancy, resourcefulness, and robustness and to provide recommendations for resiliency building in flood risk communities. The research was conducted in Thailand following the severe floods of 2011 triggered by Tropical Storm Nock-ten. The floods lasted over eight months starting in June 2011 affecting 65 of the country’s 76 provinces and over 12 million people. Funding from a US National Science Foundation grant was used to collect ephemeral data in rural (Ayutthaya), suburban (Pathum Thani), and urban (Bangkok) provinces of Thailand. Semi-structured face-to-face interviews were conducted in Thai with 44 contacts from public, private, and non-profit organizations including universities, schools, automobile companies, vendors, tourist agencies, monks from temples, faith based organizations, and government agencies. Multiple triangulations were used to analyze the data by identifying selective themes from the qualitative data, validated with quantitative data and news media reports. This helped to obtain a more comprehensive view of how organizations in different geographic settings varied in their understanding of what enhanced or hindered their resilience and consequently their speed and capacities to respond. The findings suggest that the urban province of Bangkok scored highest in resourcefulness, rapidity of response, robustness, and ability to rebound. This is not surprising considering that it is the country’s capital and the seat of government, economic, military and tourism sectors. However, contrary to expectations all 44 respondents noted that the rural province of Ayutthaya was the fastest to recover amongst the three. Its organizations scored high on redundancy and rapidity of response due to the strength of social networks, a flood disaster sub-culture due to annual flooding, and the help provided by monks from and faith based organizations. Organizations in the suburban community of Pathum Thani scored lowest on rapidity of response and resourcefulness due to limited and ambiguous warnings, lack of prior flood experience and controversies that government flood protection works like sandbagging favored the capital city of Bangkok over them. Such a micro-level examination of organizational resilience in rural, suburban and urban areas in a country through mixed methods studies has its merits in getting a nuanced understanding of the importance of disaster subcultures and religious norms for resilience. This can help refocus attention on the strengths of social networks and social capital, for flood mitigation.Keywords: disaster subculture, flood response, organizational resilience, Thailand floods, religious beliefs and response, social capital and disasters
Procedia PDF Downloads 1526411 In Vivo Investigation of microRNA Expression and Function at the Mammalian Synapse by AGO-APP
Authors: Surbhi Surbhi, Andrea Erni, Gunter Meister, Harold Cremer, Christophe Beclin
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MicroRNAs (miRNAs) are short 20-23 nucleotide long non-coding RNAs; there are 2605 miRNA in humans and 1936 miRNA in mouse in total (miRBase). The nervous system expresses the most abundant miRNA and most diverse. MiRNAs play a role in many steps during neurogenesis, like cell proliferation, differentiation, neural patterning, axon pathfinding, etc. Moreover, in vitro studies suggested a role in the regulation of local translation at the synapse, thus controlling neuronal plasticity. However, due to the specific structure of miRNA molecules, an in-vivo confirmation of the general role of miRNAs in the control of neuronal plasticity is still pending. For example, their small size and their high level of sequence homology make difficult the analysis of their cellular and sub-cellular localization in-vivo by in-situ hybridization. Moreover, it was found that only 40% of the expressed miRNA molecules in a cell are included in RNA-Induced Silencing Complexes (RISC) and, therefore, involved in inhibitory interactions while the rest is silent. Definitively, the development of new tools is needed to have a better understanding of the cellular function of miRNAs, in particular their role in neuronal plasticity. Here we describe a new technique called in-vivo AGO-APP designed to investigate miRNA expression and function in-vivo. This technique is based on the expression of a small peptide derived from the human RISC-complex protein TNRC6B, called T6B, which binds all known Argonaute (Ago) proteins with high affinity allowing the efficient immunoprecipitation of AGO-bound miRNAs. We have generated two transgenic mouse lines conditionally expressing T6B either ubiquitously in the cell or targeted at the synapse. A comparison of the repertoire of miRNAs immuno-precipitated from mature neurons of both mouse lines will provide us with a list of miRNAs showing a specific activity at the synapse. The physiological role of these miRNAs will be subsequently addressed through gain and loss of function experiments.Keywords: RNA-induced silencing complexes, TNRC6B, miRNA, argonaute, synapse, neuronal plasticity, neurogenesis
Procedia PDF Downloads 1236410 Inflammatory Alleviation on Microglia Cells by an Apoptotic Mimicry
Authors: Yi-Feng Kao, Huey-Jine Chai, Chin-I Chang, Yi-Chen Chen, June-Ru Chen
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Microglia is a macrophage that resides in brain, and overactive microglia may result in brain neuron damage or inflammation. In this study, the phospholipids was extracted from squid skin and manufactured into a liposome (SQ liposome) to mimic apoptotic body. We then evaluated anti-inflammatory effects of SQ liposome on mouse microglial cell line (BV-2) by lipopolysaccharide (LPS) induction. First, the major phospholipid constituents in the squid skin extract were including 46.2% of phosphatidylcholine, 18.4% of phosphatidylethanolamine, 7.7% of phosphatidylserine, 3.5% of phosphatidylinositol, 4.9% of Lysophosphatidylcholine and 19.3% of other phospholipids by HPLC-UV analysis. The contents of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the squid skin extract were 11.8 and 28.7%, respectively. The microscopic images showed that microglia cells can engulf apoptotic cells or SQ-liposome. In cell based studies, there was no cytotoxicity to BV-2 as the concentration of SQ-liposome was less than 2.5 mg/mL. The LPS induced pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were significant suppressed (P < 0.05) by pretreated 0.03~2.5mg/ml SQ liposome. Oppositely, the anti-inflammatory cytokines transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10) secretion were enhanced (P < 0.05). The results suggested that SQ-liposome possess anti-inflammatory properties on BV-2 and may be a good strategy for against neuro-inflammatory disease.Keywords: apoptotic mimicry, neuroinflammation, microglia, squid processing by-products
Procedia PDF Downloads 4736409 Effect of Renin Angiotensin Pathway Inhibition on the Efficacy of Anti-programmed Cell Death (PD-1/L-1) Inhibitors in Advanced Non-small Cell Lung Cancer Patients- Comparison of Single Hospital Retrospective Assessment to the Published Literature
Authors: Esther Friedlander, Philip Friedlander
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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC
Procedia PDF Downloads 666408 Performance Comparison of Microcontroller-Based Optimum Controller for Fruit Drying System
Authors: Umar Salisu
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This research presents the development of a hot air tomatoes drying system. To provide a more efficient and continuous temperature control, microcontroller-based optimal controller was developed. The system is based on a power control principle to achieve smooth power variations depending on a feedback temperature signal of the process. An LM35 temperature sensor and LM399 differential comparator were used to measure the temperature. The mathematical model of the system was developed and the optimal controller was designed and simulated and compared with the PID controller transient response. A controlled environment suitable for fruit drying is developed within a closed chamber and is a three step process. First, the infrared light is used internally to preheated the fruit to speedily remove the water content inside the fruit for fast drying. Second, hot air of a specified temperature is blown inside the chamber to maintain the humidity below a specified level and exhaust the humid air of the chamber. Third, the microcontroller disconnects the power to the chamber after the moisture content of the fruits is removed to minimal. Experiments were conducted with 1kg of fresh tomatoes at three different temperatures (40, 50 and 60 °C) at constant relative humidity of 30%RH. The results obtained indicate that the system is significantly reducing the drying time without affecting the quality of the fruits. In the context of temperature control, the results obtained showed that the response of the optimal controller has zero overshoot whereas the PID controller response overshoots to about 30% of the set-point. Another performance metric used is the rising time; the optimal controller rose without any delay while the PID controller delayed for more than 50s. It can be argued that the optimal controller performance is preferable than that of the PID controller since it does not overshoot and it starts in good time.Keywords: drying, microcontroller, optimum controller, PID controller
Procedia PDF Downloads 2906407 Comparative Functional Analysis of Two Major Sterol-Biosynthesis Regulating Transcription Factors, Hob1 and Sre1, in Pathogenic Cryptococcus Species Complex
Authors: Dong-Gi Lee, Suyeon Cha, Yong-Sun Bahn
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Sterol lipid is essential for cell membrane structure in eukaryotic cells. In mammalian cells, sterol regulatory element binding proteins (SREBPs) act as principal regulators of cellular cholesterol which is essential for proper cell membrane fluidity and structure. SREBP and sterol regulation are related to levels of cellular oxygen because it is a major substrate for sterol synthesis. Upon cellular sterol and oxygen levels are depleted, SREBP is translocated to the Golgi where it undergoes proteolytic cleavage of N terminus, then it travels to the nucleus to play a role as transcription factor. In yeast cells, synthesis of ergosterol is also highly oxygen consumptive, and Sre1 is a transcription factor known to play a central role in adaptation to growth under low oxygen condition and sterol homeostasis in Cryptococcus neoformans. In this study, we observed phenotypes in other strains of Cryptococcus species by constructing hob1Δ and sre1Δ mutants to confirm whether the functions of both genes are conserved in most serotypes. As a result, hob1Δ showed no noticeable phenotype under treatment of antifungal drugs and most environmental stresses in R265 (C. gattii) and XL280 (C. neoformans), suggesting that Hob1 is related to sterol regulation only in H99 (serotype A). On the other hand, the function of Sre1 was found to be conserved in most serotypes. Furthermore, mating experiment of hob1Δ or sre1Δ showed dramatic defects in serotype A (H99) and D (XL280). It revealed that Hob1 and Sre1 related to mating ability in Cryptococcus species, especially cell fusion efficiency. In conclusion, HOB1 and SRE1 play crucial role in regulating sterol-homeostasis and differentiation in C. neoformans, moreover, Hob1 is specific gene in Cryptococcus neoformans. It suggests that Hob1 is considered as potent factor-targeted new safety antifungal drug.Keywords: cryptococcus neoformans, Hob1, Sre1, sterol regulatory element binding proteins
Procedia PDF Downloads 2496406 Stress as Risk Factor for Onset of Type-2 Diabetes Mellitus in Visakhapatnam Tribal Community of Andhra Pradesh, India
Authors: Vijaya Nirmala Pangi, K. V. Subhramanyam, C. Vijay Lakshmi
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Background: The prevalence of Type 2 Diabetes Mellitus is increasing drastically at a vigorous rate all over the world population. Aim: The present study aims to determine the prevalence of type-2 diabetes mellitus in Paderu tribal area population of Visakhapatnam district, located in northeastern region of Andhra Pradesh. Methods: A random sampling method was followed in 1025 subjects including controls (n=25) and determined 75-g oral glucose tolerance test to assess the presence of type 2 diabetes mellitus. The effect of anthropometric factors like age, gender, literacy, socio economic status, and environmental risk factors such as body fat response, hypertension and psychophysical stress response were determined in the studied subjects. Results: 78 (7.8%) were diabetic. Type 2 Diabetes Mellitus was found to be comparable between the two genders. Prevalence of diabetes was observed to be high in illiterate, low economic status subjects. Body fat response was comparable between control and diabetic subjects. However hypertension, stress associated enzymes showed significant (p < 0.05) decrease in diabetic subjects compared to controls in both the genders. Conclusion: It appears that there is a rising pattern in the prevalence of diabetes mellitus in tribal area, Paderu, Andhra Pradesh, India compared to previous rural studies.Keywords: anthropometric studies, hypertension, oral glucose tolerance test, stress enzymes, type-2 diabetes mellitus
Procedia PDF Downloads 4596405 Dynamic Response Analyses for Human-Induced Lateral Vibration on Congested Pedestrian Bridges
Authors: M. Yoneda
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In this paper, a lateral walking design force per person is proposed and compared with Imperial College test results. Numerical simulations considering the proposed walking design force which is incorporated into the neural-oscillator model are carried out placing much emphasis on the synchronization (the lock-in phenomenon) for a pedestrian bridge model with the span length of 50 m. Numerical analyses are also conducted for an existing pedestrian suspension bridge. As compared with full scale measurements for this suspension bridge, it is confirmed that the analytical method based on the neural-oscillator model might be one of the useful ways to explain the synchronization (the lock-in phenomenon) of pedestrians being on the bridge.Keywords: pedestrian bridge, human-induced lateral vibration, neural-oscillator, full scale measurement, dynamic response analysis
Procedia PDF Downloads 1956404 The Discovery of Competitive Glca Inhibitors That Inhibits the Human Pathogenic Fungi Aspergillus Fumigatus and Candida Albicans
Authors: Reem Al-Shidhani, Isabelle S. R. Storer, Michael J. Bromley, Lydia Tabernero
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Invasive fungal diseases are an increasing global health concern that contributes to the high mortality rates in immunocompromised patients. The rising of antifungal resistance severely lowers the efficacy of the limited antifungal agents available. New antifungal drugs that target new mechanisms are necessary to tackle the current shortfalls. Amongst post- modifications, phosphorylation is a predominant and an outstanding protein alteration in all eukaryotes. In fungi, protein phosphorylation plays a vital role in many signal transduction pathways, including cell cycle, cell growth, metabolism, transcription, differentiation, proliferation, and virulence. The investigation of Aspergillus fumigatus phosphatases revealed seven genes essential for viability. Inhibiting one of these phosphatases is a new interesting route to develop novel antifungal drugs. In this study, we carried out an early drug discovery process targeting oneessential phosphatase, GlcA. Here, we report the identification of new GlcA inhibitors that show antifungal activity. These important finding open a new avenue to the development of novel antifungals to expand the current narrow arsenal of clinical candidates.Keywords: invasive fungal diseases, phosphatases, GlcA, competitive inhibitors
Procedia PDF Downloads 1056403 Effect of Papaverine on Developmental Neurotoxicity: Neurosphere as in vitro Model
Authors: Mohammed Y. Elsherbeny, Mohamed Salama, Ahmed Lotfy, Hossam Fareed, Nora Mohammed
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Background: Developmental neurotoxicity (DNT) entails the toxic effects imparted by various chemicals on brain during the early childhood when human brains are vulnerable during this period. DNT study in vivo cannot determine the effect of the neurotoxins, as it is not applicable, so using the neurosphere cells of lab animals as an alternative is applicable and time saving. Methods: Cell culture: Rat neural progenitor cells were isolated from rat embryos’ brain. The cortices were aseptically dissected out and the tissues were triturated. The dispersed tissues were allowed to settle. The supernatant was then transferred to a fresh tube and centrifuged. The pellet was placed in Hank’s balanced salt solution and cultured as free-floating neurospheres in proliferation medium. Differentiation was initiated by growth factor withdrawal in differentiation medium and plating onto a poly-d-lysine/ laminin matrix. Chemical Exposure: Neurospheres were treated for 2 weeks with papaverine in proliferation medium. Proliferation analyses: Spheres were cultured. After 0, 4, 5, 11 and 14 days, sphere size was determined by software analyses (CellProfiler, version 2.1; Broad Institute). Diameter of each neurosphere was measured and exported to excel file further to statistical analysis. Viability test: Trypsin-EDTA solution was added to neurospheres to dissociate neurospheres into single cells suspension, then viability evaluated by the Trypan Blue exclusion test. Result: As regards proliferation analysis and percentage of viable cells of papaverin treated groups: There was no significant change in cells proliferation compared to control at 0, 4, 5, 11 and 14 days with concentrations 1, 5 and 10 µM of papaverine, but there is a significant change in cell viability compared to control after 1 week and 2 weeks with the same concentrations of papaverine. Conclusion: Papaverine has toxic effect on viability of neural cell, not on their proliferation, so it may produce focal neural lesions not growth morphological changes.Keywords: developmental neurotoxicity, neurotoxin, papaverine, neuroshperes
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