Search results for: single cell omics
5104 Single and Combined Effects of Diclofenac and Ibuprofen on Daphnia Magna and Some Phytoplankton Species
Authors: Ramatu I. Sha’aba, Mathias A. Chia, Abdullahi B. Alhassan, Yisa A. Gana, Ibrahim M. Gadzama
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Globally, Diclofenac (DLC) and Ibuprofen (IBU) are the most prescribed drugs due to their antipyretic and analgesic properties. They are, however, highly toxic at elevated doses, with the involvement of an already described oxidative stress pathway. As a result, there is rising concern about the ecological fate of analgesics on non-target organisms such as Daphnia magna and Phytoplankton species. Phytoplankton is a crucial component of the aquatic ecosystem that serves as the primary producer at the base of the food chain. However, the increasing presence and levels of micropollutants such as these analgesics can disrupt their community structure, dynamics, and ecosystem functions. This study presents a comprehensive series of the physiology, antioxidant response, immobilization, and risk assessment of Diclofenac and Ibuprofen’s effects on Daphnia magna and the Phytoplankton community using a laboratory approach. The effect of DLC and IBU at 27.16 µg/L and 20.89 µg/L, respectively, for a single exposure and 22.39 µg/L for combined exposure of DLC and IBU for the experimental setup. The antioxidant response increased with increasing levels of stress. The highest stressor to the organism was 1000 µg/L of DLC and 10,000 µg/L of IBU. Peroxidase and glutathione -S-transferase activity was higher for Diclofenac + Ibuprofen. The study showed 60% and 70% immobilization of the organism at 1000 g L-1 of DLC and IBU. The two drugs and their combinations adversely impacted Phytoplankton biomass with increased exposure time. However, combining the drugs resulted in more significant adverse effects on physiological and pigment content parameters. The risk assessment calculation for the risk quotient and toxic unit of the analgesic reveals from this study was RQ Diclofenac = 8.41, TU Diclofenac = 3.68, and RQ Ibuprofen = 718.05 and TU Ibuprofen = 487.70. Hence, these findings demonstrate that the current exposure concentrations of Diclofenac and Ibuprofen can immobilize D. magna. This study shows the dangers of multiple drugs in the aquatic environment because their combinations could have additive effects on the structure and functions of Phytoplankton and are capable of immobilizing D. magna.Keywords: algae, analgesic drug, daphnia magna, toxicity
Procedia PDF Downloads 795103 Modelling Causal Effects from Complex Longitudinal Data via Point Effects of Treatments
Authors: Xiaoqin Wang, Li Yin
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Background and purpose: In many practices, one estimates causal effects arising from a complex stochastic process, where a sequence of treatments are assigned to influence a certain outcome of interest, and there exist time-dependent covariates between treatments. When covariates are plentiful and/or continuous, statistical modeling is needed to reduce the huge dimensionality of the problem and allow for the estimation of causal effects. Recently, Wang and Yin (Annals of statistics, 2020) derived a new general formula, which expresses these causal effects in terms of the point effects of treatments in single-point causal inference. As a result, it is possible to conduct the modeling via point effects. The purpose of the work is to study the modeling of these causal effects via point effects. Challenges and solutions: The time-dependent covariates often have influences from earlier treatments as well as on subsequent treatments. Consequently, the standard parameters – i.e., the mean of the outcome given all treatments and covariates-- are essentially all different (null paradox). Furthermore, the dimension of the parameters is huge (curse of dimensionality). Therefore, it can be difficult to conduct the modeling in terms of standard parameters. Instead of standard parameters, we have use point effects of treatments to develop likelihood-based parametric approach to the modeling of these causal effects and are able to model the causal effects of a sequence of treatments by modeling a small number of point effects of individual treatment Achievements: We are able to conduct the modeling of the causal effects from a sequence of treatments in the familiar framework of single-point causal inference. The simulation shows that our method achieves not only an unbiased estimate for the causal effect but also the nominal level of type I error and a low level of type II error for the hypothesis testing. We have applied this method to a longitudinal study of COVID-19 mortality among Scandinavian countries and found that the Swedish approach performed far worse than the other countries' approach for COVID-19 mortality and the poor performance was largely due to its early measure during the initial period of the pandemic.Keywords: causal effect, point effect, statistical modelling, sequential causal inference
Procedia PDF Downloads 2055102 What Are the Problems in the Case of Analysis of Selenium by Inductively Coupled Plasma Mass Spectrometry in Food and Food Raw Materials?
Authors: Béla Kovács, Éva Bódi, Farzaneh Garousi, Szilvia Várallyay, Dávid Andrási
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For analysis of elements in different food, feed and food raw material samples generally a flame atomic absorption spectrometer (FAAS), a graphite furnace atomic absorption spectrometer (GF-AAS), an inductively coupled plasma optical emission spectrometer (ICP-OES) and an inductively coupled plasma mass spectrometer (ICP-MS) are applied. All the analytical instruments have different physical and chemical interfering effects analysing food and food raw material samples. The smaller the concentration of an analyte and the larger the concentration of the matrix the larger the interfering effects. Nowadays, it is very important to analyse growingly smaller concentrations of elements. From the above analytical instruments generally the inductively coupled plasma mass spectrometer is capable of analysing the smallest concentration of elements. The applied ICP-MS instrument has Collision Cell Technology (CCT) also. Using CCT mode certain elements have better detection limits with 1-3 magnitudes comparing to a normal ICP-MS analytical method. The CCT mode has better detection limits mainly for analysis of selenium (arsenic, germanium, vanadium, and chromium). To elaborate an analytical method for selenium with an inductively coupled plasma mass spectrometer the most important interfering effects (problems) were evaluated: 1) isobaric elemental, 2) isobaric molecular, and 3) physical interferences. Analysing food and food raw material samples an other (new) interfering effect emerged in ICP-MS, namely the effect of various matrixes having different evaporation and nebulization effectiveness, moreover having different quantity of carbon content of food, feed and food raw material samples. In our research work the effect of different water-soluble compounds furthermore the effect of various quantity of carbon content (as sample matrix) were examined on changes of intensity of selenium. So finally we could find “opportunities” to decrease the error of selenium analysis. To analyse selenium in food, feed and food raw material samples, the most appropriate inductively coupled plasma mass spectrometer is a quadrupole instrument applying a collision cell technique (CCT). The extent of interfering effect of carbon content depends on the type of compounds. The carbon content significantly affects the measured concentration (intensities) of Se, which can be corrected using internal standard (arsenic or tellurium).Keywords: selenium, ICP-MS, food, food raw material
Procedia PDF Downloads 5085101 Spontaneous Tumour Lysis in Acute Myeloid Leukemia
Authors: Rojith K. Balakrishnan
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Spontaneous tumour lysis syndrome is a constellation of electrolyte abnormalities and an acute renal failure which occurs in the setting of rapid cell turnover prior to the administration of cytotoxic chemotherapy. While spontaneous tumour lysis well-described in patients with Burkitt lymphoma, it is thought to occur less commonly in patients with other hematological malignancies. We present a case of forty-year-old female who presented with features of acute renal failure, on further evaluation turned out to be a newly diagnosed acute myeloid leukemia with spontaneous tumour lysis best of our knowledge only three cases of AML with spontaneous tumour lysis has reported world wide.Keywords: AML, tumour lysis, renal failure, myeloid leukemia
Procedia PDF Downloads 2945100 Safety and Efficacy of RM-001, Autologous HBG1/2 Promoter-Modified CD34+Hematopoietic Stem and Progenitor Cells, in Transfusion-Dependent β-Thalassemia
Authors: Rongrong Liu, Li Wang, Hui Xu, Jianpei Fang, Sixi Liu, Xiaolin Yin, Junbin Liang, Gaohui Yan, Yaoyun Li, Yali Zhou, Xinyu Li, Yue Li, Lei Shi, Yongrong Lai, Junjiu Huang, Xinhua Zhang
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Background: Beta-Thalassemia is caused by reduced (β+) or absent (β0) synthesis of the β-globin chains of hemoglobin. Transfusions and oral iron chelation therapy have improved the quality of life for patients with Transfusion-Dependent thalassemia (TDT). Recent advances in genome editing platforms of CRISPR-Cas9 have paved the way for induction of HbF by reactivating expression of γ-chain.Aims: We performed CRISPR-Cas9-mediated genome editing of hematopoietic stem cells to mutate HBG1/HBG2 promoter sequence, thereby representing a naturally occurring HPFH-liked mutation, producing RM-001. Here, we present an initial assessment of safety and efficacy of RM-001 in patients with TDT. Methods: Patients (6–35 y of age) with TDT receiving packed red blood cell (pRBC) transfusions of ≥100 mL/kg/y or ≥10 units/y in the previous 2 y were eligible. CD34+ cells were edited with CRISPR-Cas9 using a guide RNA specific for the binding site of BCL11A on the HBG1/2 promoter. Prior to RM-001 product infusion (day 0), patients received myeloablative conditioning with Busulfan from day-7 to day-4. Patients were monitored for AEs Hb expression.Results: Data cut as of 28 Feb 2024, 16 TDT patients have been treated with RM-001 and followed ≥3 months. 5 of these 16 patients had finished their 24 months follow up. Eleven patients have β0/β0 genotype and five patients have β0/β+ genotype. In addition to β-thalassemia, two patients had α- deletion with the genotype of --/αα. Efficacy:All patients received a single dose intravenous infusion of RM-001 cells. 5 of them had been followed 24 months or longer. All patients achieved transfusion-independent (TI, total Hb continued ≥ 9g/dL) (Figure1). Patients demonstrated sustained and clinically meaningful increases in HbF levels since 4 month post-RM-001 infusion (Figure.2). Total hemoglobin in all patients was stable at 10-12g/dL during the follow-up period. Safety:The adverse events observed after RM-001 infusion were consistent with those that are typical of Busulfan-based myeloablation. The allelic editing analysis at 6-month visit showed that the on-target allelic editing frequency in bone marrow cells was 73.44% (64.65% to 84.6%, n=13).Summary/Conclusion: This interim analysis, in which all the 19 patients age from 7.9 to 25yo met the success criteria for the trial with respect to transfusion independence, showed that autologous HBG1/2 promoter-modified CD34+ HSPCs gene therapy resulted in an adequate amount of HbF as early as 2 months after infusion led to near-normal hemoglobin levels, remained transfusion-free through the reported period without product related SAE. After RM-001 infusion, high levels of HbF proportion and on-target editing in bone marrow cells were maintained. Submitted on behalf of the RM-001 Investigators.Keywords: thalassemian, genetherapy, CRISPR/Cas9, HbF
Procedia PDF Downloads 205099 The Quantitative Optical Modulation of Dopamine Receptor-Mediated Endocytosis Using an Optogenetic System
Authors: Qiaoyue Kuang, Yang Li, Mizuki Endo, Takeaki Ozawa
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G protein-coupled receptors (GPCR) are the largest family of receptor proteins that detect molecules outside the cell and activate cellular responses. Of the GPCRs, dopamine receptors, which recognize extracellular dopamine, are essential to mammals due to their roles in numerous physiological events, including autonomic movement, hormonal regulation, emotions, and the reward system in the brain. To precisely understand the physiological roles of dopamine receptors, it is important to spatiotemporally control the signaling mediated by dopamine receptors, which is strongly dependent on their surface expression. Conventionally, chemical-induced interactions were applied to trigger the endocytosis of cell surface receptors. However, these methods were subjected to diffusion and therefore lacked temporal and special precision. To further understand the receptor-mediated signaling and to control the plasma membrane expression of receptors, an optogenetic tool called E-fragment was developed. The C-terminus of a light-sensitive photosensory protein cyptochrome2 (CRY2) was attached to β-Arrestin, and the E-fragment was generated by fusing the C-terminal peptide of vasopressin receptor (V2R) to CRY2’s binding partner protein CIB. The CRY2-CIB heterodimerization triggered by blue light stimulation brings β-Arrestin to the vicinity of membrane receptors and results in receptor endocytosis. In this study, the E-fragment system was applied to dopamine receptors 1 and 2 (DRD1 and DRD2) to control dopamine signaling. First, confocal fluorescence microscope observation qualitatively confirmed the light-induced endocytosis of E-fragment fused receptors. Second, NanoBiT bioluminescence assay verified quantitatively that the surface amount of E-fragment labeled receptors decreased after light treatment. Finally, GloSensor bioluminescence assay results suggested that the E-fragment-dependent receptor light-induced endocytosis decreased cAMP production in DRD1 signaling and attenuated the inhibition effect of DRD2 on cAMP production. The developed optogenetic tool was able to induce receptor endocytosis by external light, providing opportunities to further understand numerous physiological activities by controlling receptor-mediated signaling spatiotemporally.Keywords: dopamine receptors, endocytosis, G protein-coupled receptors, optogenetics
Procedia PDF Downloads 1025098 Using Hemicellulosic Liquor from Sugarcane Bagasse to Produce Second Generation Lactic Acid
Authors: Regiane A. Oliveira, Carlos E. Vaz Rossell, Rubens Maciel Filho
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Lactic acid, besides a valuable chemical may be considered a platform for other chemicals. In fact, the feasibility of hemicellulosic sugars as feedstock for lactic acid production process, may represent the drop of some of the barriers for the second generation bioproducts, especially bearing in mind the 5-carbon sugars from the pre-treatment of sugarcane bagasse. Bearing this in mind, the purpose of this study was to use the hemicellulosic liquor from sugarcane bagasse as a substrate to produce lactic acid by fermentation. To release of sugars from hemicellulose it was made a pre-treatment with a diluted sulfuric acid in order to obtain a xylose's rich liquor with low concentration of inhibiting compounds for fermentation (≈ 67% of xylose, ≈ 21% of glucose, ≈ 10% of cellobiose and arabinose, and around 1% of inhibiting compounds as furfural, hydroxymethilfurfural and acetic acid). The hemicellulosic sugars associated with 20 g/L of yeast extract were used in a fermentation process with Lactobacillus plantarum to produce lactic acid. The fermentation process pH was controlled with automatic injection of Ca(OH)2 to keep pH at 6.00. The lactic acid concentration remained stable from the time when the glucose was depleted (48 hours of fermentation), with no further production. While lactic acid is produced occurs the concomitant consumption of xylose and glucose. The yield of fermentation was 0.933 g lactic acid /g sugars. Besides, it was not detected the presence of by-products, what allows considering that the microorganism uses a homolactic fermentation to produce its own energy using pentose-phosphate pathway. Through facultative heterofermentative metabolism the bacteria consume pentose, as is the case of L. plantarum, but the energy efficiency for the cell is lower than during the hexose consumption. This implies both in a slower cell growth, as in a reduction in lactic acid productivity compared with the use of hexose. Also, L. plantarum had shown to have a capacity for lactic acid production from hemicellulosic hydrolysate without detoxification, which is very attractive in terms of robustness for an industrial process. Xylose from hydrolyzed bagasse and without detoxification is consumed, although the hydrolyzed bagasse inhibitors (especially aromatic inhibitors) affect productivity and yield of lactic acid. The use of sugars and the lack of need for detoxification of the C5 liquor from sugarcane bagasse hydrolyzed is a crucial factor for the economic viability of second generation processes. Taking this information into account, the production of second generation lactic acid using sugars from hemicellulose appears to be a good alternative to the complete utilization of sugarcane plant, directing molasses and cellulosic carbohydrates to produce 2G-ethanol, and hemicellulosic carbohydrates to produce 2G-lactic acid.Keywords: fermentation, lactic acid, hemicellulosic sugars, sugarcane
Procedia PDF Downloads 3735097 Embryotoxicity of Nano-Iron Oxide (Fe2O3) to Bio-Indicator of Pollution of Land Helix Aspersa
Authors: S. Besnaci, S. Bensoltane, H. Locif, S. Saadi
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To validate an ecotoxicological approach to assessing toxicological effects caused by the oxide powder of nano-iron Fe2O3, we searched in the ecotoxicology laboratory cell bodies bio accumulators and bio-indicators of soil pollution the snail Helix aspersa. In this study, we evaluated the toxicity of nano Fe2O3 during a very sensitive phase of development H.aspersa (embryonic stage). During embryonic development, we observed in treated with various concentrations of nano Fe2O3 (1.25 g/l, 1.5 g/l, and 2 g/l) compared to control, the deformation of the membrane of the egg and accumulation of this molecule at the rear of the egg proven by the photographs, as with the influence on the hatching percentage.Keywords: eggs, embryotoxicity, Fe2O3, Helix aspersa, nanoparticles
Procedia PDF Downloads 3765096 Comparison and Validation of a dsDNA biomimetic Quality Control Reference for NGS based BRCA CNV analysis versus MLPA
Authors: A. Delimitsou, C. Gouedard, E. Konstanta, A. Koletis, S. Patera, E. Manou, K. Spaho, S. Murray
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Background: There remains a lack of International Standard Control Reference materials for Next Generation Sequencing-based approaches or device calibration. We have designed and validated dsDNA biomimetic reference materials for targeted such approaches incorporating proprietary motifs (patent pending) for device/test calibration. They enable internal single-sample calibration, alleviating sample comparisons to pooled historical population-based data assembly or statistical modelling approaches. We have validated such an approach for BRCA Copy Number Variation analytics using iQRS™-CNVSUITE versus Mixed Ligation-dependent Probe Amplification. Methods: Standard BRCA Copy Number Variation analysis was compared between mixed ligation-dependent probe amplification and next generation sequencing using a cohort of 198 breast/ovarian cancer patients. Next generation sequencing based copy number variation analysis of samples spiked with iQRS™ dsDNA biomimetics were analysed using proprietary CNVSUITE software. Mixed ligation-dependent probe amplification analyses were performed on an ABI-3130 Sequencer and analysed with Coffalyser software. Results: Concordance of BRCA – copy number variation events for mixed ligation-dependent probe amplification and CNVSUITE indicated an overall sensitivity of 99.88% and specificity of 100% for iQRS™-CNVSUITE. The negative predictive value of iQRS-CNVSUITE™ for BRCA was 100%, allowing for accurate exclusion of any event. The positive predictive value was 99.88%, with no discrepancy between mixed ligation-dependent probe amplification and iQRS™-CNVSUITE. For device calibration purposes, precision was 100%, spiking of patient DNA demonstrated linearity to 1% (±2.5%) and range from 100 copies. Traditional training was supplemented by predefining the calibrator to sample cut-off (lock-down) for amplicon gain or loss based upon a relative ratio threshold, following training of iQRS™-CNVSUITE using spiked iQRS™ calibrator and control mocks. BRCA copy number variation analysis using iQRS™-CNVSUITE™ was successfully validated and ISO15189 accredited and now enters CE-IVD performance evaluation. Conclusions: The inclusion of a reference control competitor (iQRS™ dsDNA mimetic) to next generation sequencing-based sequencing offers a more robust sample-independent approach for the assessment of copy number variation events compared to mixed ligation-dependent probe amplification. The approach simplifies data analyses, improves independent sample data analyses, and allows for direct comparison to an internal reference control for sample-specific quantification. Our iQRS™ biomimetic reference materials allow for single sample copy number variation analytics and further decentralisation of diagnostics to single patient sample assessment.Keywords: validation, diagnostics, oncology, copy number variation, reference material, calibration
Procedia PDF Downloads 665095 Census and Mapping of Oil Palms Over Satellite Dataset Using Deep Learning Model
Authors: Gholba Niranjan Dilip, Anil Kumar
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Conduct of accurate reliable mapping of oil palm plantations and census of individual palm trees is a huge challenge. This study addresses this challenge and developed an optimized solution implemented deep learning techniques on remote sensing data. The oil palm is a very important tropical crop. To improve its productivity and land management, it is imperative to have accurate census over large areas. Since, manual census is costly and prone to approximations, a methodology for automated census using panchromatic images from Cartosat-2, SkySat and World View-3 satellites is demonstrated. It is selected two different study sites in Indonesia. The customized set of training data and ground-truth data are created for this study from Cartosat-2 images. The pre-trained model of Single Shot MultiBox Detector (SSD) Lite MobileNet V2 Convolutional Neural Network (CNN) from the TensorFlow Object Detection API is subjected to transfer learning on this customized dataset. The SSD model is able to generate the bounding boxes for each oil palm and also do the counting of palms with good accuracy on the panchromatic images. The detection yielded an F-Score of 83.16 % on seven different images. The detections are buffered and dissolved to generate polygons demarcating the boundaries of the oil palm plantations. This provided the area under the plantations and also gave maps of their location, thereby completing the automated census, with a fairly high accuracy (≈100%). The trained CNN was found competent enough to detect oil palm crowns from images obtained from multiple satellite sensors and of varying temporal vintage. It helped to estimate the increase in oil palm plantations from 2014 to 2021 in the study area. The study proved that high-resolution panchromatic satellite image can successfully be used to undertake census of oil palm plantations using CNNs.Keywords: object detection, oil palm tree census, panchromatic images, single shot multibox detector
Procedia PDF Downloads 1605094 Residential Satisfaction and Public Perception of Socialized Housing Projects in Davao City, Philippines
Authors: Micah Amor P. Yares
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Aside from the provision of adequate housing, the Philippine government faces the challenge of ensuring that the housing units provided conform to the Filipino’s ambition to self as manifested by owning a small house on a big lot. The study aimed to explore the levels of satisfaction of end-users and the public perception towards socialized housing in Davao City, Philippines. The residential satisfaction survey includes three types of respondents, which are end-users of single-detached, duplex and rowhouse socialized housing units. Respondents were asked to rate their level of satisfaction and perception to the following housing components: Dwelling Unit; Public Facilities; Social Environment; Neighborhood Facilities; Management Systems; and Acquisition and Financing. The data were subjected to Exploratory Factor Analysis to determine if variables can be grouped together, and Confirmatory Factor Analysis to measure if the model fits the construct. In determining which component affects the level of perception and satisfaction, a Multiple Linear Regression Analysis was employed. Lastly, an Individual Samples T-Test was performed to compare the levels of satisfaction and perception among respondents. Results revealed that residents of socialized housing were highly satisfied with their living conditions despite concerns on management systems, public and neighborhood facilities. Residents' satisfaction is primarily influenced by the Social Environment, Acquisition and Financing, and the Dwelling Unit. However, a significant difference in residential satisfaction level was observed among different types of housing with rowhouse residents recording the lowest satisfaction level compared to single-detached and duplex units. Moreover, the general public perceived Socialized housing as moderately satisfactory having the same determinant as the end-users aside from the Public Facilities. This study recommends revisiting the current Socialized Housing policies by considering the feedback from the end-users based on their lived experience and the public according to their perception.Keywords: public perception, residential satisfaction, rowhouse, socialized housing
Procedia PDF Downloads 2365093 3D Interactions in Under Water Acoustic Simulationseffect of Green Synthesized Metal Nanoparticles on Gene Expression in an In-Vitro Model of Non-alcoholic Steatohepatitis
Authors: Nendouvhada Livhuwani Portia, Nicole Sibuyi, Kwazikwakhe Gabuza, Adewale Fadaka
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Metabolic dysfunction-associated liver disease (MASLD) is a chronic condition characterized by excessive fat accumulation in the liver, distinct from conditions caused by alcohol, viral hepatitis, or medications. MASLD is often linked with metabolic syndrome, including obesity, diabetes, hyperlipidemia, and hypertriglyceridemia. This disease can progress to metabolic dysfunction-associated steatohepatitis (MASH), marked by liver inflammation and scarring, potentially leading to cirrhosis. However, only 43-44% of patients with steatosis develop MASH, and 7-30% of those with MASH progress to cirrhosis. The exact mechanisms underlying MASLD and its progression remain unclear, and there are currently no specific therapeutic strategies for MASLD/MASH. While anti-obesity and anti-diabetic medications can reduce progression, they do not fully treat or reverse the disease. As an alternative, green-synthesized metal nanoparticles (MNPs) are emerging as potential treatments for liver diseases due to their anti-diabetic, anti-inflammatory, and anti-obesity properties with minimal side effects. MNPs like gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have been shown to improve metabolic processes by lowering blood glucose, body fat, and inflammation. The study aimed to explore the effects of green-synthesized MNPs on gene expression in an in vitro model of MASH using C3A/HepG2 liver cells. The MASH model was created by exposing these cells to free fatty acids (FFAs) followed by lipopolysaccharide (LPS) to induce inflammation. Cell viability was assessed with the Water-Soluble Tetrazolium (WST)-1 assay, and lipid accumulation was measured using the Oil Red O (ORO) assay. Additionally, mitochondrial membrane potential was assessed by the tetramethyl rhodamine, methyl ester (TMRE) assay, and inflammation was measured with an Enzyme-Linked Immunosorbent Assay (ELISA). The study synthesized AuNPs from Carpobrotus edulis fruit (CeF) and avocado seed (AvoSE) and AgNPs from Salvia africana-lutea (SAL) using optimized conditions. The MNPs were characterized by UV-Vis spectrophotometry and Dynamic Light Scattering (DLS). The nanoparticles were tested at various concentrations for their impact on the C3A/HepG2-induced MASH model. Among the MNPs tested, AvoSE-AuNPs showed the most promise. They reduced cell proliferation and intracellular lipid content more effectively than CeFE-AuNPs and SAL-AgNPs. Molecular analysis using real-time polymerase chain reaction revealed that AvoSE-AuNPs could potentially reverse MASH effects by reducing the expression of key pro-inflammatory and metabolic genes, including tumor necrosis factor-alpha (TNF-α), Fas cell surface death receptor (FAS), Peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ, and Sterol regulatory element-binding protein (SREBPF)-1. Further research is needed to confirm the molecular mechanisms behind the effects of these MNPs and to identify the specific phytochemicals responsible for their synthesis and bioactivities.Keywords: gold nanoparticles, green nanotechnology, metal nanoparticles, obesity
Procedia PDF Downloads 255092 Development and Experimental Validation of Coupled Flow-Aerosol Microphysics Model for Hot Wire Generator
Authors: K. Ghosh, S. N. Tripathi, Manish Joshi, Y. S. Mayya, Arshad Khan, B. K. Sapra
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We have developed a CFD coupled aerosol microphysics model in the context of aerosol generation from a glowing wire. The governing equations can be solved implicitly for mass, momentum, energy transfer along with aerosol dynamics. The computationally efficient framework can simulate temporal behavior of total number concentration and number size distribution. This formulation uniquely couples standard K-Epsilon scheme with boundary layer model with detailed aerosol dynamics through residence time. This model uses measured temperatures (wire surface and axial/radial surroundings) and wire compositional data apart from other usual inputs for simulations. The model predictions show that bulk fluid motion and local heat distribution can significantly affect the aerosol behavior when the buoyancy effect in momentum transfer is considered. Buoyancy generated turbulence was found to be affecting parameters related to aerosol dynamics and transport as well. The model was validated by comparing simulated predictions with results obtained from six controlled experiments performed with a laboratory-made hot wire nanoparticle generator. Condensation particle counter (CPC) and scanning mobility particle sizer (SMPS) were used for measurement of total number concentration and number size distribution at the outlet of reactor cell during these experiments. Our model-predicted results were found to be in reasonable agreement with observed values. The developed model is fast (fully implicit) and numerically stable. It can be used specifically for applications in the context of the behavior of aerosol particles generated from glowing wire technique and in general for other similar large scale domains. Incorporation of CFD in aerosol microphysics framework provides a realistic platform to study natural convection driven systems/ applications. Aerosol dynamics sub-modules (nucleation, coagulation, wall deposition) have been coupled with Navier Stokes equations modified to include buoyancy coupled K-Epsilon turbulence model. Coupled flow-aerosol dynamics equation was solved numerically and in the implicit scheme. Wire composition and temperature (wire surface and cell domain) were obtained/measured, to be used as input for the model simulations. Model simulations showed a significant effect of fluid properties on the dynamics of aerosol particles. The role of buoyancy was highlighted by observation and interpretation of nucleation zones in the planes above the wire axis. The model was validated against measured temporal evolution, total number concentration and size distribution at the outlet of hot wire generator cell. Experimentally averaged and simulated total number concentrations were found to match closely, barring values at initial times. Steady-state number size distribution matched very well for sub 10 nm particle diameters while reasonable differences were noticed for higher size ranges. Although tuned specifically for the present context (i.e., aerosol generation from hotwire generator), the model can also be used for diverse applications, e.g., emission of particles from hot zones (chimneys, exhaust), fires and atmospheric cloud dynamics.Keywords: nanoparticles, k-epsilon model, buoyancy, CFD, hot wire generator, aerosol dynamics
Procedia PDF Downloads 1435091 Prevalence of Pretreatment Drug HIV-1 Mutations in Moscow, Russia
Authors: Daria Zabolotnaya, Svetlana Degtyareva, Veronika Kanestri, Danila Konnov
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An adequate choice of the initial antiretroviral treatment determines the treatment efficacy. In the clinical guidelines in Russia non-nucleoside reverse transcriptase inhibitors (NNRTIs) are still considered to be an option for first-line treatment while pretreatment drug resistance (PDR) testing is not routinely performed. We conducted a cohort retrospective study in HIV-positive treatment naïve patients of the H-clinic (Moscow, Russia) who performed PDR testing from July 2017 to November 2021. All the information was obtained from the medical records anonymously. We analyzed the mutations in reverse transcriptase and protease genes. RT-sequences were obtained by AmpliSens HIV-Resist-Seq kit. Drug resistance was defined using the HIVdb Program v. 8.9-1. PDR was estimated using the Stanford algorithm. Descriptive statistics were performed in Excel (Microsoft Office, 2019). A total of 261 HIV-1 infected patients were enrolled in the study including 197 (75.5%) male and 64 (24.5%) female. The mean age was 34.6±8.3 years. The median CD4 count – 521 cells/µl (IQR 367-687 cells/µl). Data on risk factors of HIV-infection were scarce. The total quantity of strains containing mutations in the reverse transcriptase gene was 75 (28.7%). From these 5 (1.9%) mutations were associated with PDR to nucleoside reverse transcriptase inhibitors (NRTIs) and 30 (11.5%) – with PDR to NNRTIs. The number of strains with mutations in protease gene was 43 (16.5%), from these only 3 (1.1%) mutations were associated with resistance to protease inhibitors. For NNRTIs the most prevalent PDR mutations were E138A, V106I. Most of the HIV variants exhibited a single PDR mutation, 2 were found in 3 samples. Most of HIV variants with PDR mutation displayed a single drug class resistance mutation. 2/37 (5.4%) strains had both NRTIs and NNRTIs mutations. There were no strains identified with PDR mutations to all three drug classes. Though earlier data demonstrated a lower level of PDR in HIV treatment naïve population in Russia and our cohort can be not fully representative as it is taken from the private clinic, it reflects the trend of increasing PDR especially to NNRTIs. Therefore, we consider either pretreatment testing or giving the priority to other drugs as first-line treatment necessary.Keywords: HIV, resistance, mutations, treatment
Procedia PDF Downloads 945090 Antenna for Energy Harvesting in Wireless Connected Objects
Authors: Nizar Sakli, Chayma Bahar, Chokri Baccouch, Hedi Sakli
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If connected objects multiply, they are becoming a challenge in more than one way. In particular by their consumption and their supply of electricity. A large part of the new generations of connected objects will only be able to develop if it is possible to make them entirely autonomous in terms of energy. Some manufacturers are therefore developing products capable of recovering energy from their environment. Vital solutions in certain contexts, such as the medical industry. Energy recovery from the environment is a reliable solution to solve the problem of powering wireless connected objects. This paper presents and study a optically transparent solar patch antenna in frequency band of 2.4 GHz for connected objects in the future standard 5G for energy harvesting and RF transmission.Keywords: antenna, IoT, solar cell, wireless communications
Procedia PDF Downloads 1685089 Optimization of Radiation Therapy with a Nanotechnology Based Enzymatic Therapy
Authors: R. D. Esposito, V. M. Barberá, P. García Morales, P. Dorado Rodríguez, J. Sanz, M. Fuentes, D. Planes Meseguer, M. Saceda, L. Fernández Fornos, M. P. Ventero
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Results obtained by our group on glioblastoma multiforme (GBM) primary cultures , show a dramatic potentiation of radiation effects when 2 units/ml of D-amino acid oxidase (DAO) enzyme are added, free or immobilized in magnetic nanoparticles, to irradiated samples just after the irradiation. Cell cultures were exposed to radiation doses of 7Gy and 15Gy of 6 MV photons from a clinical linear accelerator. At both doses, we observed a clear enhancing effect of radiation-induced damages due to the addition of DAO.Keywords: D-amino Acid Oxidase (DAO) enzyme, magnetic particles, nanotechnology, radiation therapy enhancement
Procedia PDF Downloads 5235088 Endoscopic Pituitary Surgery: Learning Curve and Nasal Quality of Life
Authors: Martin Dupuy, Solange Grunenwald, Pierre-Louis Colombo, Laurence Mahieu, Pomone Richard, Philippe Bartoli
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Endonasal endoscopic trans-sphenoidal surgery for pituitary tumours has become a mainstay of treatment over the last two decades. Although it is generally accepted that there is no significant difference between endoscopic versus microscopic approach for surgical outcomes (endocrine and ophthalmologic status), nasal morbidity seems to the benefit of endoscopic procedures. Minimally invasive endoscopic surgery needs an operative learning curve to achieve surgeon’s efficiency. This learning curve is now well known for surgical outcomes and complications rate, however, few data are available for nasal morbidity. The aim of our series is to document operative experience and nasal quality of life after (NQOL) endoscopic trans-sphenoidal surgery. The prospective pituitary surgical cohort consisted of 525 consecutives patients referred to our Skull Base Diseases Department. Endoscopic procedures were performed by a single neurosurgeon using an uninostril approach. NQOL was evaluated using the Sino-Nasal Test (SNOT-22), the Anterior Base Nasal Inventory (ASBNI) and the Skull Base Inventory Score (SBIS). Data were collected before surgery during hospital stay and 3 months after the surgery. The seventy first patients were compared to the latest 70 patients. There was no significant difference between comparison score before versus after surgery for SNOT-22, ASBNI and SBIS during the single surgeon’s learning curve. Our series demonstrates that in our institution there is no statistically significant learning curve for NQOL after uninostril endoscopic pituitary surgery. A careful progression through sinonasal structures with very limited mucosal incision is associated with minimal morbidity and preserves nasal function. Conservative and minimal invasive approach could be achieved early during learning curve.Keywords: pituitary surgery, quality of life, minimal invasive surgery, learning curve, pituitary tumours, skull base surgery, endoscopic surgery
Procedia PDF Downloads 1245087 Symptom Burden and Quality of Life in Advanced Lung Cancer Patients
Authors: Ammar Asma, Bouafia Nabiha, Dhahri Meriem, Ben Cheikh Asma, Ezzi Olfa, Chafai Rim, Njah Mansour
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Despite recent advances in treatment of the lung cancer patients, the prognosis remains poor. Information is limited regarding health related quality of life (QOL) status of advanced lung cancer patients. The purposes of this study were: to assess patient reported symptom burden, to measure their QOL, and to identify determinant factors associated with QOL. Materials/Methods: A cross sectional study of 60 patients was carried out from over the period of 03 months from February 1st to 30 April 2016. Patients were recruited in two department of health care: Pneumology department in a university hospital in Sousse and an oncology unit in a University Hospital in Kairouan. Patients with advanced stage (III and IV) of lung cancer who were hospitalized or admitted in the day hospital were recruited by convenience sampling. We used a questionnaire administrated and completed by a trained interviewer. This questionnaire is composed of three parts: demographic, clinical and therapeutic information’s, QOL measurements: based on the SF-36 questionnaire, Symptom’s burden measurement using the Lung Cancer Symptom Scale (LCSS). To assess Correlation between symptoms burden and QOL, we compared the scores of two scales two by two using the Pearson correlation. To identify factors influencing QOL in Lung cancer, a univariate statistical analysis then, a stepwise backward approach, wherein the variables with p< 0.2, were carried out to determine the association between SF-36 scores and different variables. Results: During the study period, 60 patients consented to complete symptom and quality of life questionnaires at a single point time (72% were recruited from day hospital). The majority of patients were male (88%), age ranged from 21 to 79 years with a mean of 60.5 years. Among patients, 48 (80%) were diagnosed as having non-small cell lung carcinoma (NSCLC). Approximately, 60 % (n=36) of patients were in stage IV, 25 % in stage IIIa and 15 % in stage IIIb. For symptom burden, the symptom burden index was 43.07 (Standard Deviation, 21.45). Loss of appetite and fatigue were rated as the most severe symptoms with mean scores (SD): 49.6 (25.7) and 58.2 (15.5). The average overall score of SF36 was 39.3 (SD, 15.4). The physical and emotional limitations had the lowest scores. Univariate analysis showed that factors which influence negatively QOL were: married status (p<0.03), smoking cessation after diagnosis (p<0.024), LCSS total score (p<0.001), LCSS symptom burden index (p<0.001), fatigue (p<0.001), loss of appetite (p<0.001), dyspnea (p<0.001), pain (p<0.002), and metastatic stage (p<0.01). In multivariate analysis, unemployment (p<0.014), smoking cessation after diagnosis (p<0.013), consumption of analgesic (p<0.002) and the indication of an analgesic radiotherapy (p<0.001) are revealed as independent determinants of QOL. The result of the correlation analyses between total LCSS scores and the total and individual domain SF36 scores was significant (p<0.001); the higher total LCSS score is, the poorer QOL is. Conclusion: A built in support of lung cancer patients would better control the symptoms and promote the QOL of these patients.Keywords: quality of life, lung cancer, metastasis, symptoms burden
Procedia PDF Downloads 3815086 Effect of Out-Of-Plane Deformation on Relaxation Method of Stress Concentration in a Plate
Authors: Shingo Murakami, Shinichi Enoki
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In structures, stress concentration is a factor of fatigue fracture. Basically, the stress concentration is a phenomenon that should be avoided. However, it is difficult to avoid the stress concentration. Therefore, relaxation of the stress concentration is important. The stress concentration arises from notches and circular holes. There is a relaxation method that a composite patch covers a notch and a circular hole. This relaxation method is used to repair aerial wings, but it is not systematized. Composites are more expensive than single materials. Accordingly, we propose the relaxation method that a single material patch covers a notch and a circular hole, and aim to systematize this relaxation method. We performed FEA (Finite Element Analysis) about an object by using a three-dimensional FEA model. The object was that a patch adheres to a plate with a circular hole. And, a uniaxial tensile load acts on the patched plate with a circular hole. In the three-dimensional FEA model, it is not easy to model the adhesion layer. Basically, the yield stress of the adhesive is smaller than that of adherents. Accordingly, the adhesion layer gets to plastic deformation earlier than the adherents under the yield stress of adherents. Therefore, we propose the three-dimensional FEA model which is applied a nonlinear elastic region to the adhesion layer. The nonlinear elastic region was calculated by a bilinear approximation. We compared the analysis results with the tensile test results to confirm whether the analysis model has usefulness. As a result, the analysis results agreed with the tensile test results. And, we confirmed that the analysis model has usefulness. As a result that the three-dimensional FEA model was used to the analysis, it was confirmed that an out-of-plane deformation occurred to the patched plate with a circular hole. The out-of-plane deformation causes stress increase of the patched plate with a circular hole. Therefore, we investigate that the out-of-plane deformation affects relaxation of the stress concentration in the plate with a circular hole on this relaxation method. As a result, it was confirmed that the out-of-plane deformation inhibits relaxation of the stress concentration on the plate with a circular hole.Keywords: stress concentration, patch, out-of-plane deformation, Finite Element Analysis
Procedia PDF Downloads 2665085 Prevalence and Associated Risk Factors of Age-Related Macular Degeneration in the Retina Clinic at a Tertiary Center in Makkah Province, Saudi Arabia: A Retrospective Record Review
Authors: Rahaf Mandura, Fatmah Abusharkh, Layan Kurdi, Rahaf Shigdar, Khadijah Alattas
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Introduction: Age-related macular degeneration (AMD) in older individuals are serious health issues that severely impact the quality of life of millions globally. In 2020, the fourth leading cause of blindness worldwide was AMD. The global prevalence of AMD is estimated to be around 8.7%. AMD is a progressive disease involving the macular region of the retina, and it has a complex pathophysiology. RPE cell dysfunction plays a crucial step in the pathway leading to irreversible degeneration of photoreceptors with yellowish lipid-rich, protein-containing drusen deposits accumulating between Bruch's membrane and the RPE. Furthermore, lipofuscinogenesis, drusogenesis, inflammation, and neovascularization are four main processes responsible for the formation of the two types of AMD: the wet (exudative, neovascular) and dry (non-exudative, geographic atrophy) types. We retrospectively evaluated the prevalence of AMD among patients visiting the retina clinic at King Abdulaziz University Hospital (Jeddah, Makkah Province, Saudi Arabia) to identify the commonly associated risk factors of AMD. Methods: The records of 3,067 individuals from 2017 to 2021 were reviewed. Of these, 1,935 satisfied the inclusion criteria and were included in this study. We excluded all patient below 18 years, and those who did not undergo fundus imaging or attend their booked appointments, follow-ups, treatments, and referrals were excluded. Results: The prevalence of AMD among the patients was 4%. The age of patients with AMD was significantly greater than those without AMD (72.4 ± 9.8 years vs. 57.2 ± 15.5 years; p < 0.001). Participants with a family history of AMD tended to have the disease more than those without such a history (85.7% vs. 45%; p = 0.043). Ex- and current smokers were more likely to have AMD than non-smokers (34% and 18.6% vs. 7.2%; p < 0.001). Patients with hypertension and those without type 1 diabetes were at a higher risk of developing AMD than those without hypertension (5.5% vs. 2.8%; p = 0.002) and those with type 1 diabetes (4.2% vs. 0.8%; p = 0.040). In contrast, sex, nationality, type 2 diabetes, and abnormal lipid profile were not significantly associated with AMD. Regarding the clinical characteristics of AMD cases, most cases (70.4%) were of the dry type and affected both eyes (77.2%). The disease duration was ≥5 years in 43.1% of the patients. The most frequent chronic diseases associated with AMD were type 2 diabetes (69.1%), hypertension (61.7%), and dyslipidemia (18.5%). Conclusion: In summary, our single tertiary center study showed that AMD is widely prevalent in Jeddah, Saudi Arabia (4%) and linked to a wide range of risk factors. Some of these are modifiable risk factors that can be adjusted to help reduce AMD occurrence. Furthermore, this study has shown the importance of screening and follow-up of family members of patients with AMD to promote early detection and intervention of AMD. We recommend conducting further research on AMD in Saudi Arabia. Concerning the study design, a community-based cross-sectional study would be more helpful for assessing the disease's prevalence. Finally, recruiting a larger sample size is required for more accurate estimation.Keywords: age related macular degeneration, prevelence, risk factor, dry AMD
Procedia PDF Downloads 425084 The Post-Crisis Expansion of European Central Bank Powers: Understanding the Legitimate Boundaries of the ECB's Supervisory Independence and Accountability
Authors: Jakub Gren
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The recent transfer of banking supervision to the ECB has expanded its influence as of a non-majoritarian and technocratic policy-shaper in EU supervisory policies. To fulfil the main policy objectives of the Single Supervisory Mechanism, the ECB has been tasked with building a single supervisory approach to supervised banks across the euro area and is now exclusively responsible for direct supervision of the largest ‘significant’ euro area banks and the oversight of the remaining ‘less significant’ banks. This enhanced supranational position of the ECB significantly alters the EU institutional order and creates powerful incentives to actively pursue integrationist agenda by the ECB. However, this drastic shift has a little impact upon adapting the ECB’s new supervisory mandate to the requirements of democratic legitimacy. Whereas the ECB’s strong pre-crisis independence and limited accountability could be reconciled with democratic principles through a clearly articulated price stability mandate, independence and limited accountability in the context of a more complex supervisory mandate is problematic. Hence, in order to ensure the democratic legitimacy of the ECB/SSM’s supervisory policies, the ECB’s supervisory mandate requires both a lower scope of independence and higher accountability requirements. To address this situation, organizational separation (“Chinese Wall”) between the ECB monetary and supervisory arms was introduced. This separation includes different reporting lines and the relocation of the ECB’s monetary function to a new building complex while leaving its supervisory function at the Euro-tower (“Two Towers”). This paper argues that these measures are not sufficient to establish proper checks and balances on the ECB’s powers to pursue euro zone’s wide supervisory policies. As a remedy, this contribution suggests that the ECB’s Treaties-embedded independence, as set out by art. 130 TFEU, designed to carry out its monetary function shall not be fully applicable to its supervisory function. Indeed functional and conditional reading of this provision to ECB supervisory function could enhance the legitimacy of future ECB’s supervisory action.Keywords: accountability and transparency, democratic governance, financial management, rule of law
Procedia PDF Downloads 2075083 Engineering of Reagentless Fluorescence Biosensors Based on Single-Chain Antibody Fragments
Authors: Christian Fercher, Jiaul Islam, Simon R. Corrie
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Fluorescence-based immunodiagnostics are an emerging field in biosensor development and exhibit several advantages over traditional detection methods. While various affinity biosensors have been developed to generate a fluorescence signal upon sensing varying concentrations of analytes, reagentless, reversible, and continuous monitoring of complex biological samples remains challenging. Here, we aimed to genetically engineer biosensors based on single-chain antibody fragments (scFv) that are site-specifically labeled with environmentally sensitive fluorescent unnatural amino acids (UAA). A rational design approach resulted in quantifiable analyte-dependent changes in peak fluorescence emission wavelength and enabled antigen detection in vitro. Incorporation of a polarity indicator within the topological neighborhood of the antigen-binding interface generated a titratable wavelength blueshift with nanomolar detection limits. In order to ensure continuous analyte monitoring, scFv candidates with fast binding and dissociation kinetics were selected from a genetic library employing a high-throughput phage display and affinity screening approach. Initial rankings were further refined towards rapid dissociation kinetics using bio-layer interferometry (BLI) and surface plasmon resonance (SPR). The most promising candidates were expressed, purified to homogeneity, and tested for their potential to detect biomarkers in a continuous microfluidic-based assay. Variations of dissociation kinetics within an order of magnitude were achieved without compromising the specificity of the antibody fragments. This approach is generally applicable to numerous antibody/antigen combinations and currently awaits integration in a wide range of assay platforms for one-step protein quantification.Keywords: antibody engineering, biosensor, phage display, unnatural amino acids
Procedia PDF Downloads 1465082 Effects of Intercropping Maize (Zea mays L.) with Jack Beans (Canavalia ensiformis L.) at Different Spacing and Weeding Regimes on Crops Productivity
Authors: Oluseun S. Oyelakin, Olalekan W. Olaniyi
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A field experiment was conducted at Ido town in Ido Local Government Area of Oyo state, Nigeria to determine the effects of intercropping maize (Zea mays L.) with Jack bean (Canavalia ensiformis L.) at different spacing and weeding regimes on crops productivity. The treatments were 2 x 2 x 3 factorial arrangement involving two spatial crop arrangements. Spacing of 75 cm x 50 cm and 90 cm x 42 cm (41.667 cm) with two plants per stand resulted in plant population of approximately 53,000 plants/hectare. Also, Randomized Complete Block Design (RCBD) with two cropping patterns (sole and intercrop), three weeding regimes (weedy check, weeds once, and weed twice) with three replicates was used. Data were analyzed with SAS (Statistical Analysis System) and statistical means separated using Least Significant Difference (LSD) (P ≤ 0.05). Intercropping and crop spacing did not have significant influence on the growth parameters and yield parameters. The maize grain yield of 1.11 t/ha obtained under sole maize was comparable to 1.05 t/ha from maize/jack beans. Weeding regime significantly influenced growth and yields of maize in intercropping with Jack beans. Weeding twice resulted in significantly higher growth than that of the other weeding regimes. Plant height at 6 Weeks After Sowing (WAS) under weeding twice regime (3 and 6 WAS) was 83.9 cm which was significantly different from 67.75 cm and 53.47 cm for weeding once (3 WAS) and no weeding regimes respectively. Moreover, maize grain yield of 1.3 t/ha obtained from plots weeded twice was comparable to that of 1.23 t/ha from single weeding and both were significantly higher than 0.71 t/ha maize grain yield obtained from the no weeding control. The dry matter production of Jack beans reduced at some growth stages due to intercropping of maize with Jack beans though with no significance effect on the other growth parameters of the crop. There was no effect on the growth parameters of Jack beans in maize/jack beans intercrop based on cropping spacing while comparable growth and dry matter production in Jack beans were produced in maize/Jack beans mixture with single weeding.Keywords: crop spacing, intercropping, growth parameter, weeding regime, sole cropping, WAS, week after sowing
Procedia PDF Downloads 1445081 Foslip Loaded and CEA-Affimer Functionalised Silica Nanoparticles for Fluorescent Imaging of Colorectal Cancer Cells
Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne
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Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging
Procedia PDF Downloads 2405080 Curbing Abuses of Legal Power in the Society
Authors: Tajudeen Ojo Ibraheem
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In a world characterized by greed and the lust for power and its attendant trappings, abuse of legal power is nothing new to most of us. Legal abuses of power abound in all fields of human endeavour. Accounts of such abuses dominate the mass media and for the average individual, no single day goes by without his getting to hear about at least one such occurrence. This paper briefly looks at the meaning of legal power, what legal abuse is all about, its causes, and some of its manifestations in the society. Its consequences will also be discussed and some suggestions for reform will be made. In the course of the paper, references will be made to various jurisdictions around the world.Keywords: abuse, legal, power, society
Procedia PDF Downloads 4465079 Evaluation of the Effect of Magnetic Field on Fibroblast Attachment in Contact with PHB/Iron Oxide Nanocomposite
Authors: Shokooh Moghadam, Mohammad Taghi Khorasani, Sajjad Seifi Mofarah, M. Daliri
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Through the recent two decades, the use of magnetic-property materials with the aim of target cell’s separation and eventually cancer treatment has incredibly increased. Numerous factors can alter the efficacy of this method on curing. In this project, the effect of magnetic field on adhesion of PDL and L929 cells on nanocomposite of iron oxide/PHB with different density of iron oxides (1%, 2.5%, 5%) has been studied. The nanocamposite mentioned includes a polymeric film of poly hydroxyl butyrate and γ-Fe2O3 particles with the average size of 25 nanometer dispersed in it and during this process, poly vinyl alcohol with 98% hydrolyzed and 78000 molecular weight was used as an emulsion to achieve uniform distribution. In order to get the homogenous film, the solution of PHB and iron oxide nanoparticles were put in a dry freezer and in liquid nitrogen, which resulted in a uniform porous scaffold and for removing porosities a 100◦C press was used. After the synthesis of a desirable nanocomposite film, many different tests were performed, First, the particles size and their distribution in the film were evaluated by transmission electron microscopy (TEM) and even FTIR analysis and DMTA test were run in order to observe and accredit the chemical connections and mechanical properties of nanocomposites respectively. By comparing the graphs of case and control samples, it was established that adding nano particles caused an increase in crystallization temperature and the more density of γ-Fe2O3 lead to more Tg (glass temperature). Furthermore, its dispersion range and dumping property of samples were raised up. Moreover, the toxicity, morphologic changes and adhesion of fibroblast and cancer cells were evaluated by a variety of tests. All samples were grown in different density and in contact with cells for 24 and 48 hours within the magnetic fields of 2×10^-3 Tesla. After 48 hours, the samples were photographed with an optic and SEM and no sign of toxicity was traced. The number of cancer cells in the case of sample group was fairly more than the control group. However, there are many gaps and unclear aspects to use magnetic field and their effects in cancer and all diseases treatments yet to be discovered, not to neglect that there have been prominent step on this way in these recent years and we hope this project can be at least a minimum movement in this issue.Keywords: nanocomposite, cell attachment, magnetic field, cytotoxicity
Procedia PDF Downloads 2595078 Effect of Dietary Organic Zinc Supplementation on Immunocompetance and Reproductive Performance in Rats
Authors: D. Nagalakshmi, S. Parashuramulu K. Sadasiva Rao, G. Aruna, L. Vikram
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The zinc (Zn) is the second most abundant trace element in mammals and birds, forming structural component of over 300 enzymes, playing an important role in anti-oxidant defense, immune response and reproduction. Organic trace minerals are more readily absorbed from the digestive tract and more biologically available compared with its inorganic salt. Thus, the present study was undertaken on 60 adult female Sprague Dawley rats (275±2.04 g) for experimental duration of 12 weeks to investigate the effect of dietary Zn supplementation from various organic sources on immunity, reproduction, oxidative defense mechanism and blood biochemical profile. The rats were randomly allotted to 30 replicates (2 per replicate) which were in turn randomly allotted to 5 dietary treatments varying in Zn source i.e., one inorganic source (Zn carbonate) and 4 organic sources (Zn-proteinate, Zn-propionate, Zn-amino acid complex and Zn-methionine) so as to supply NRC recommended Zn concentration (12 ppm Zn). Supplementation of organic Zn had no effect on various haematological and serum biochemical constituents compared to inorganic Zn fed rats. The TBARS and protein carbonyls concentration in liver indicative of oxidative stress was comparable between various organic and inorganic groups. The glutathione reductase activity in haemolysate (P<0.05) and reduced glutathione concentration in liver (P<0.01) was higher when fed organic Zn and RBC catalase activity was higher (P<0.01) on Zn methionine compared to other organic sources tested and the inorganic source. The humoral immune response assessed as antibody titres against sheep RBC was higher (P<0.05) when fed organic sources of zinc compared to inorganic source. The cell mediated immune response expressed as delayed type hypersensitivity reaction was higher (P<0.05) in rats fed Zn propionate with no effect of other organic Zn sources. The serum progesterone concentration was higher (P<0.05) in rats fed organic Zn sources compared to inorganic zinc. The data on ovarian folliculogenesis indicated that organic Zn supplementation increased (P<0.05) the number of graafian follicles and corpus luteum with no effect on primary, secondary and tertiary follicle number. The study indicated that rats fed organic sources of Zn had higher antioxidant enzyme activities, immune response and serum progesterone concentration with higher number of mature follicles. Though the effect of feeding various organic sources were comparable, rats fed zinc methionine had higher antioxidant activity and cell mediated immune response was higher in rats on Zn propionate.Keywords: organic zinc, immune, rats, reproductive
Procedia PDF Downloads 2865077 Study on the Central Differencing Scheme with the Staggered Version (STG) for Solving the Hyperbolic Partial Differential Equations
Authors: Narumol Chintaganun
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In this paper we present the second-order central differencing scheme with the staggered version (STG) for solving the advection equation and Burger's equation. This scheme based on staggered evolution of the re-constructed cell averages. This scheme results in the second-order central differencing scheme, an extension along the lines of the first-order central scheme of Lax-Friedrichs (LxF) scheme. All numerical simulations presented in this paper are obtained by finite difference method (FDM) and STG. Numerical results are shown that the STG gives very good results and higher accuracy.Keywords: central differencing scheme, STG, advection equation, burgers equation
Procedia PDF Downloads 5575076 Atherosclerosis Prevalence Within Populations of the Southeastern United States
Authors: Samuel P. Prahlow, Anthony Sciuva, Katherine Bombly, Emily Wilson, Shiv Dhiman, Savita Arya
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A prevalence cohort study of atherosclerotic lesions within cadavers was performed to better understand and characterize the prevalence of atherosclerosis among Georgia residents within body donors in the Philadelphia College of Osteopathic Medicine (PCOM) - Georgia body donor program. We procured specimens from cadavers used for medical students, physical therapy students, and biomedical science students cadaveric anatomical dissection at PCOM - South Georgia and PCOM - Georgia. Tissues were prepared using hematoxylin and eosin (H&E) stainas histological slides by Colquitt Regional Medical Center Laboratory Services. One section from each of the following arteries was taken after cadaveric dissection at the site of most calcification palpated grossly (if present): left anterior descending coronary artery, left internal carotid artery, abdominal aorta, splenic artery, and hepatic artery. All specimens were graded and categorized according to the American Heart Association’s Modified and Conventional Standards for Atherosclerotic Lesions using x4, x10, x40 microscopic magnification. Our study cohort included 22 cadavers, with 16 females and 6 males. The average age was 72.54, and the median age was 72, with a range of 52 to 90 years old. The cause of death determination listing vascular and/or cardiovascular causes was present on 6 of the 22 death certificates. 19 of 22 (86%) cadavers had at least a single artery grading > 5. Of the cadavers with at least a single artery graded at greater than 5, only 5 of 19 (26%) cadavers had a vascular or cardiovascular cause of death reported. Malignancy was listed as a cause of death on 7 (32%) death certificates. The average atherosclerosis grading of the common hepatic, splenic and left internal carotid arteries (2.15, 3.05, and 3.36 respectively) were lower than the left anterior descending artery and the abdominal aorta (5.16 and 5.86 respectively). This prevalence study characterizes atherosclerosis found in five medium and large systemic arteries within cadavers from the state of Georgia.Keywords: pathology, atherosclerosis, histology, cardiovascular
Procedia PDF Downloads 2165075 An Experience Report on Course Teaching in Information Systems
Authors: Carlos Oliveira
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This paper is a criticism of the traditional model of teaching and presents alternative teaching methods, different from the traditional lecture. These methods are accompanied by reports of experience of their application in a class. It was concluded that in the lecture, the student has a low learning rate and that other methods should be used to make the most engaging learning environment for the student, contributing (or facilitating) his learning process. However, the teacher should not use a single method, but rather a range of different methods to ensure the learning experience does not become repetitive and fatiguing for the student.Keywords: educational practices, experience report, IT in education, teaching methods
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