Search results for: extremely drug- resistant
907 Surface Modified Quantum Dots for Nanophotonics, Stereolithography and Hybrid Systems for Biomedical Studies
Authors: Redouane Krini, Lutz Nuhn, Hicham El Mard Cheol Woo Ha, Yoondeok Han, Kwang-Sup Lee, Dong-Yol Yang, Jinsoo Joo, Rudolf Zentel
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To use Quantum Dots (QDs) in the two photon initiated polymerization technique (TPIP) for 3D patternings, QDs were modified on the surface with photosensitive end groups which are able to undergo a photopolymerization. We were able to fabricate fluorescent 3D lattice structures using photopatternable QDs by TPIP for photonic devices such as photonic crystals and metamaterials. The QDs in different diameter have different emission colors and through mixing of RGB QDs white light fluorescent from the polymeric structures has been created. Metamaterials are capable for unique interaction with the electrical and magnetic components of the electromagnetic radiation and for manipulating light it is crucial to have a negative refractive index. In combination with QDs via TPIP technique polymeric structures can be designed with properties which cannot be found in nature. This makes these artificial materials gaining a huge importance for real-life applications in photonic and optoelectronic. Understanding of interactions between nanoparticles and biological systems is of a huge interest in the biomedical research field. We developed a synthetic strategy of polymer functionalized nanoparticles for biomedical studies to obtain hybrid systems of QDs and copolymers with a strong binding network in an inner shell and which can be modified in the end through their poly(ethylene glycol) functionalized outer shell. These hybrid systems can be used as models for investigation of cell penetration and drug delivery by using measurements combination between CryoTEM and fluorescence studies.Keywords: biomedical study models, lithography, photo induced polymerization, quantum dots
Procedia PDF Downloads 526906 The Test of Memory Malingering and Offence Severity
Authors: Kenji Gwee
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In Singapore, the death penalty remains in active use for murder and drug trafficking of controlled drugs such as heroin. As such, the psychological assessment of defendants can often be of high stakes. The Test of Memory Malingering (TOMM) is employed by government psychologists to determine the degree of effort invested by defendants, which in turn inform on the veracity of overall psychological findings that can invariably determine the life and death of defendants. The purpose of this study was to find out if defendants facing the death penalty were more likely to invest less effort during psychological assessment (to fake bad in hopes of escaping the death sentence) compared to defendants facing lesser penalties. An archival search of all forensic cases assessed in 2012-2013 by Singapore’s designated forensic psychiatric facility yielded 186 defendants’ TOMM scores. Offence severity, coded into 6 rank-ordered categories, was analyzed in a one-way ANOVA with TOMM score as the dependent variable. There was a statistically significant difference (F(5,87) = 2.473, p = 0.038). A Tukey post-hoc test with Bonferroni correction revealed that defendants facing lower charges (Theft, shoplifting, criminal breach of trust) invested less test-taking effort (TOMM = 37.4±12.3, p = 0.033) compared to those facing the death penalty (TOMM = 46.2±8.1). The surprising finding that those facing death penalties actually invested more test taking effort than those facing relatively minor charges could be due to higher levels of cooperation when faced with death. Alternatively, other legal avenues to escape the death sentence may have been preferred over the mitigatory chance of a psychiatric defence.Keywords: capital sentencing, offence severity, Singapore, Test of Memory Malingering
Procedia PDF Downloads 434905 Effective Doping Engineering of Na₃V₂(PO₄)₂F₃ as a High-Performance Cathode Material for Sodium-Ion Batteries
Authors: Ramon Alberto Paredes Camacho, Li Lu
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Sustainable batteries are possible through the development of cheaper and greener alternatives whose most feasible option is epitomized by Sodium-Ion Batteries (SIB). Na₃V₂(PO₄)₂F₃ (NVPF) an important member of the Na-superionic-conductor (NASICON) materials, has recently been in the spotlight due to its interesting electrochemical properties when used as cathode namely, high specific capacity of 128 mA h g-¹, high energy density of 507 W h Kg-¹, increased working potential at which vanadium redox couples can be activated (with an average value around 3.9 V), and small volume variation of less than 2%. These traits grant NVPF an excellent perspective as a cathode material for the next generation of sodium batteries. Unfortunately, because of its low inherent electrical conductivity and a high energy barrier that impedes the mobilization of all the available Na ions per formula, the overall electrochemical performance suffers substantial degradation, finally obstructing its industrial use. Many approaches have been developed to remediate these issues where nanostructural design, carbon coating, and ion doping are the most effective ones. This investigation is focused on enhancing the electrochemical response of NVPF by doping metal ions in the crystal lattice, substituting vanadium atoms. A facile sol-gel process is employed, with citric acid as the chelator and the carbon source. The optimized conditions circumvent fluorine sublimation, ratifying the material’s purity. One of the reasons behind the large ionic improvement is the attraction of extra Na ions into the crystalline structure due to a charge imbalance produced by the valence of the doped ions (+2), which is lower than the one of vanadium (+3). Superior stability (higher than 90% at a current density of 20C) and capacity retention at an extremely high current density of 50C are demonstrated by our doped NVPF. This material continues to retain high capacity values at low and high temperatures. In addition, full cell NVPF//Hard Carbon shows capacity values and high stability at -20 and 60ºC. Our doping strategy proves to significantly increase the ionic and electronic conductivity of NVPF even at extreme conditions, delivering outstanding electrochemical performance and paving the way for advanced high-potential cathode materials.Keywords: sodium-ion batteries, cathode materials, NASICON, Na3V2(PO4)2F3, Ion doping
Procedia PDF Downloads 57904 hsa-miR-1204 and hsa-miR-639 Prominent Role in Tamoxifen's Molecular Mechanisms on the EMT Phenomenon in Breast Cancer Patients
Authors: Mahsa Taghavi
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In the treatment of breast cancer, tamoxifen is a regularly prescribed medication. The effect of tamoxifen on breast cancer patients' EMT pathways was studied. In this study to see if it had any effect on the cancer cells' resistance to tamoxifen and to look for specific miRNAs associated with EMT. In this work, we used continuous and integrated bioinformatics analysis to choose the optimal GEO datasets. Once we had sorted the gene expression profile, we looked at the mechanism of signaling, the ontology of genes, and the protein interaction of each gene. In the end, we used the GEPIA database to confirm the candidate genes. after that, I investigated critical miRNAs related to candidate genes. There were two gene expression profiles that were categorized into two distinct groups. Using the expression profile of genes that were lowered in the EMT pathway, the first group was examined. The second group represented the polar opposite of the first. A total of 253 genes from the first group and 302 genes from the second group were found to be common. Several genes in the first category were linked to cell death, focal adhesion, and cellular aging. Two genes in the second group were linked to cell death, focal adhesion, and cellular aging. distinct cell cycle stages were observed. Finally, proteins such as MYLK, SOCS3, and STAT5B from the first group and BIRC5, PLK1, and RAPGAP1 from the second group were selected as potential candidates linked to tamoxifen's influence on the EMT pathway. hsa-miR-1204 and hsa-miR-639 have a very close relationship with the candidates genes according to the node degrees and betweenness index. With this, the action of tamoxifen on the EMT pathway was better understood. It's important to learn more about how tamoxifen's target genes and proteins work so that we can better understand the drug.Keywords: tamoxifen, breast cancer, bioinformatics analysis, EMT, miRNAs
Procedia PDF Downloads 129903 Real-Time Generative Architecture for Mesh and Texture
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In the evolving landscape of physics-based machine learning (PBML), particularly within fluid dynamics and its applications in electromechanical engineering, robot vision, and robot learning, achieving precision and alignment with researchers' specific needs presents a formidable challenge. In response, this work proposes a methodology that integrates neural transformation with a modified smoothed particle hydrodynamics model for generating transformed 3D fluid simulations. This approach is useful for nanoscale science, where the unique and complex behaviors of viscoelastic medium demand accurate neurally-transformed simulations for materials understanding and manipulation. In electromechanical engineering, the method enhances the design and functionality of fluid-operated systems, particularly microfluidic devices, contributing to advancements in nanomaterial design, drug delivery systems, and more. The proposed approach also aligns with the principles of PBML, offering advantages such as multi-fluid stylization and consistent particle attribute transfer. This capability is valuable in various fields where the interaction of multiple fluid components is significant. Moreover, the application of neurally-transformed hydrodynamical models extends to manufacturing processes, such as the production of microelectromechanical systems, enhancing efficiency and cost-effectiveness. The system's ability to perform neural transfer on 3D fluid scenes using a deep learning algorithm alongside physical models further adds a layer of flexibility, allowing researchers to tailor simulations to specific needs across scientific and engineering disciplines.Keywords: physics-based machine learning, robot vision, robot learning, hydrodynamics
Procedia PDF Downloads 66902 Preventing Neurodegenerative Diseases by Stabilization of Superoxide Dismutase by Natural Polyphenolic Compounds
Authors: Danish Idrees, Vijay Kumar, Samudrala Gourinath
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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by misfolding and aggregation of Cu, Zn superoxide dismutase (SOD1). The use of small molecules has been shown to stabilize the SOD1 dimer and preventing its dissociation and aggregation. In this study, we employed molecular docking, molecular dynamics simulation and surface plasmon resonance (SPR) to study the interactions between SOD1 and natural polyphenolic compounds. In order to explore the noncovalent interaction between SOD1 and natural polyphenolic compounds, molecular docking and molecular dynamic (MD) simulations were employed to gain insights into the binding modes and free energies of SOD1-polyphenolic compounds. MM/PBSA methods were used to calculate free energies from obtained MD trajectories. The compounds, Hesperidin, Ergosterol, and Rutin showed the excellent binding affinity in micromolar range with SOD1. Ergosterol and Hesperidin have the strongest binding affinity to SOD1 and was subjected to further characterization. Biophysical experiments using Circular Dichroism and Thioflavin T fluorescence spectroscopy results show that the binding of these two compounds can stabilize SOD1 dimer and inhibit the aggregation of SOD1. Molecular simulation results also suggest that these compounds reduce the dissociation of SOD1 dimers through direct interaction with the dimer interface. This study will be helpful to develop other drug-like molecules which may have the effect to reduce the aggregation of SOD1.Keywords: amyotrophic lateral sclerosis, molecular dynamics simulation, surface plasmon resonance, superoxide dismutase
Procedia PDF Downloads 139901 PRENACEL: Development and Evaluation of an M-Health Strategy to Improve Prenatal Care in Brazil
Authors: E. M. Vieira, C. S. Vieira, L. P. Bonifácio, L. M. de Oliveira Ciabati, A. C. A. Franzon, F. S. Zaratini, J. A. C. Sanchez, M. S. Andrade, J. P. Dias de Souza
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The quality of prenatal care is key to reduce maternal morbidity and mortality. Communication between the health service and users can stimulate prevention and care. M-health has been an important and low cost strategy to health education. The PRENACEL programme (prenatal in the cell phone) was developed. It consists of a programme of information via SMS from the 20th week of pregnancy up to 12th week after delivery. Messages were about prenatal care, birth, contraception and breastfeeding. Communication of the pregnant woman asking questions about their health was possible. The objective of this study was to evaluate the implementation of PRENACEL as a useful complement to the standard prenatal care. Twenty health clinics were selected and randomized by cluster, 10 as the intervention group and 10 as the control group. In the intervention group, women and their partner were invited to participate. The control group received the standard prenatal care. All women were interviewed in the immediate post-partum and in the 12th and 24th week post-partum. Most women were married, had more than 8 years of schooling and visit the clinic more than 6 times during prenatal care. The intervention group presented lowest percentage of higher economic participants (5.6%), less single mothers and no drug user. It also presented more prenatal care visits than the control group and it was less likely to present Severe Acute Maternal Mortality when compared to control group as well as higher percentage of partners (75.4%) was present at the birth compared to control group. Although the study is still being carried out, preliminary data are showing positive results of the compliance of women to prenatal care.Keywords: cellphone, health technology, prenatal care, prevention
Procedia PDF Downloads 389900 Biodegradable and Bioactive Scaffold for Bone Tissue Engineering
Authors: A. M. Malagon Escandon, J. A. Arenas Alatorre, C. P. Chaires Rosas, N. A. Vazquez Torres, B. Hernandez Tellez, G. Pinon Zarate, M. Herrera Enriquez, A. E. Castell Rodriguez
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The current approach to the treatment of bone defects involves the use of scaffolds that provide a biological and mechanically stable niche to favor tissue repair. Despite the significant progress in the field of bone tissue engineering, several main problems associated are attributed to giving a low biodegradation degree, does not promote osseointegration and regeneration, if the bone is not healing as well as expected or fails to heal, will not be given a proper ossification or new bone formation. The actual approaches of bone tissue regeneration are directed to the use of decellularized native extracellular matrices, which are able of retain their own architecture, mechanic properties, biodegradability and promote new bone formation because they are capable of conserving proteins and other factors that are founded in physiological concentrations. Therefore, we propose an extracellular matrix-based bioscaffolds derived from bovine cancellous bone, which is processed by decellularization, demineralization, and hydrolysis of the collagen protein, these protocols have been successfully carried out in other organs and tissues; the effectiveness of its biosafety has also been previously evaluated in vivo and Food and Drug Administration (FDA) approved. In the specific case of bone, a more complex treatment is needed in comparison with other organs and tissues because is necessary demineralization and collagen denaturalization. The present work was made in order to obtain a temporal scaffold that succeed in degradation in an inversely proportional way to the synthesis of extracellular matrix and the maturation of the bone by the cells of the host.Keywords: bioactive, biodegradable, bone, extracellular matrix-based bioscaffolds, stem cells, tissue engineering
Procedia PDF Downloads 158899 Criminal Psychology: The Relationship Between Posttraumatic Stress Disorder and Criminal Justice Involvement in Vietnam War Veterans
Authors: Danielle Page
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Foregoing studies, statistics, and medical evaluations have established a relationship between Posttraumatic stress disorder (PTSD) and criminal justice involvement in Vietnam veterans. War is highly trauma inducing and can leave combat veterans with mental disorders ranging from psychopathic thoughts to suicidal ideation. The majority of those suffering are unaware that they have PTSD, and as a coping mechanism, they often turn to self isolation. Beyond isolation, many veterans with symptomatic PTSD turn to aggression and substance abuse to cope with their internal agony. The most common crimes committed by veterans with PTSD fall into the assault and drug/alcohol abuse categories. Thus, a relationship is established between veteran populations and the criminal justice system. This research aims to define the relationship between PTSD and criminal justice involvement in veterans, explore the mediating factors in this relationship, and analyze numerous court cases in this subject area. Further, it will examine the ways in which crime rates can be reduced for veterans with symptoms of PTSD. This ranges from the improvement of healthcare systems to the implementation of special courts to handle veteran cases. The contribution of this work to the field of forensic psychology will be significant, as it will analyze preexisting case studies and experimental data in an effort to improve the ways in which veteran cases are handled in the criminal justice system. Military personnel involved in the criminal justice system are a vulnerable population in need of healthcare and legislative attention, and this work will bring us one step closer to providing them with just that.Keywords: forensic psychology, psychotraumatology, PTSD, veterans
Procedia PDF Downloads 91898 Effectiveness of Centromedullary Fixation by Metaizeau Technique in Challenging Pediatric Fractures
Authors: Mohammad Arshad Ikram
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We report three cases of challenging fractures in children treated by intramedullary fixation using the Metaizeau method and achieved anatomical reduction with excellent clinical results. Jean-Paul Metaizeau described the centromedullary fixation for the radial neck in 1980 using K-wires Radial neck fractures are uncommon in children. Treatment of severely displaced fractures is always challenging. Closed reduction techniques are more popular as compared to open reduction due to the low risk of complications. Metaizeau technique of closed reduction with centromedullary pinning is a commonly preferred method of treatment. We present two cases with a severely displaced radial neck fracture, treated by this method and achieved sound union; anatomical position of the radial head and full function were observed two months after surgery. Proximal humerus fractures are another uncommon injury in children accounting for less than 5% of all pediatric fractures. Most of these injuries occur through the growth plate because of its relative weakness. Salter-Harris type I is commonly seen in the younger age group, whereas type II & III occurs in older children and adolescents. In contrast to adults, traumatic glenohumeral dislocation is an infrequently observed condition among children. A combination of proximal humerus fracture and glenohumeral dislocation is extremely rare and occurs in less than 2% of the pediatric population. The management of this injury is always challenging. Treatment ranged from closed reduction with and without internal fixation and open reduction with internal fixation. The children who had closed reduction with centromedullary fixation by the Metaizeau method showed excellent results with the return of full movements at the shoulder in a short time without any complication. We present the case of a child with anterior dislocation of the shoulder associated with a complete displaced proximal humerus metaphyseal fracture. The fracture was managed by closed reduction and then fixation by two centromedullary K-wires using the Metaizeau method, achieving the anatomical reduction of the fracture and dislocation. This method of treatment enables us to achieve excellent radiological and clinical results in a short time.Keywords: glenohumeral, Metaizeau method, pediatric fractures, radial neck
Procedia PDF Downloads 105897 Evaluation of Synthesis and Structure Elucidation of Some Benzimidazoles as Antimicrobial Agents
Authors: Ozlem Temiz Arpaci, Meryem Tasci, Hakan Goker
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Benzimidazole, a structural isostere of indol and purine nuclei that can interact with biopolymers, can be identified as master key. So that benzimidazole compounds are important fragments in medicinal chemistry because of their wide range of biological activities including antimicrobial activity. We planned to synthesize some benzimidazole compounds for developing new antimicrobial drug candidates. In this study, we put some heterocyclic rings on second position and an amidine group on the fifth position of benzimidazole ring and synthesized them using a multiple step procedure. For the synthesis of the compounds, as the first step, 4-chloro-3-nitrobenzonitrile was reacted with cyclohexylamine in dimethyl formamide. Imidate esters (compound 2) were then prepared with absolute ethanol saturated with dry HCl gas. These imidate esters which were not too stable were converted to compound 3 by passing ammonia gas through ethanol. At the Pd / C catalyst, the nitro group is reduced to the amine group (compound 4). Finally, various aldehyde derivatives were reacted with sodium metabisulfite addition products to give compound 5-20. Melting points were determined on a Buchi B-540 melting point apparatus in open capillary tubes and are uncorrected. Elemental analyses were done a Leco CHNS 932 elemental analyzer. 1H-NMR and 13C-NMR spectra were recorded on a Varian Mercury 400 MHz spectrometer using DMSO-d6. Mass spectra were acquired on a Waters Micromass ZQ using the ESI(+) method. The structures of them were supported by spectral data. The 1H-NMR, 13C NMR and mass spectra and elemental analysis results agree with those of the proposed structures. Antimicrobial activity studies of the synthesized compounds are under the investigation.Keywords: benzimidazoles, synthesis, structure elucidation, antimicrobial
Procedia PDF Downloads 155896 FDX1, a Cuproptosis-Related Gene, Identified as a Potential Target for Human Ovarian Aging
Authors: Li-Te Lin, Chia-Jung Li, Kuan-Hao Tsui
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Cuproptosis, a newly identified cell death mechanism, has attracted attention for its association with various diseases. However, the genetic interplay between cuproptosis and ovarian aging remains largely unexplored. This study aims to address this gap by analyzing datasets related to ovarian aging and cuproptosis. Spatial transcriptome analyses were conducted in the ovaries of both young and aged female mice to elucidate the role of FDX1. Comprehensive bioinformatics analyses, facilitated by R software, identified FDX1 as a potential cuproptosis-related gene with implications for ovarian aging. Clinical infertility biopsies were examined to validate these findings, showing consistent results in elderly infertile patients. Furthermore, pharmacogenomic analyses of ovarian cell lines explored the intricate association between FDX1 expression levels and sensitivity to specific small molecule drugs. Spatial transcriptome analyses revealed a significant reduction in FDX1 expression in aging ovaries, supported by consistent findings in biopsies from elderly infertile patients. Pharmacogenomic investigations indicated that modulating FDX1 could influence drug responses in ovarian-related therapies. This study pioneers the identification of FDX1 as a cuproptosis-related gene linked to ovarian aging. These findings not only contribute to understanding the mechanisms of ovarian aging but also position FDX1 as a potential diagnostic biomarker and therapeutic target. Further research may establish FDX1's pivotal role in advancing precision medicine and therapies for ovarian-related conditions.Keywords: cuproptosis, FDX1, ovarian aging, biomarker
Procedia PDF Downloads 39895 Electrochemical Detection of the Chemotherapy Agent Methotrexate in vitro from Physiological Fluids Using Functionalized Carbon Nanotube past Electrodes
Authors: Shekher Kummari, V. Sunil Kumar, K. Vengatajalabathy Gobi
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A simple, cost-effective, reusable and reagent-free electrochemical biosensor is developed with functionalized multiwall carbon nanotube paste electrode (f-CNTPE) for the sensitive and selective determination of the important chemotherapeutic drug methotrexate (MTX), which is widely used for the treatment of various cancer and autoimmune diseases. The electrochemical response of the fabricated electrode towards the detection of MTX is examined by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square wave voltammetry (SWV). CV studies have shown that f-CNTPE electrode system exhibited an excellent electrocatalytic activity towards the oxidation of MTX in phosphate buffer (0.2 M) compared with a conventional carbon paste electrode (CPE). The oxidation peak current is enhanced by nearly two times in magnitude. Applying the DPV method under optimized conditions, a linear calibration plot is achieved over a wide range of concentration from 4.0×10⁻⁷ M to 5.5×10⁻⁶ M with the detection limit 1.6×10⁻⁷ M. further, by applying the SWV method a parabolic calibration plot was achieved starting from a very low concentration of 1.0×10⁻⁸ M, and the sensor could detect as low as 2.9×10⁻⁹ M MTX in 10 s and 10 nM were detected in steady state current-time analysis. The f-CNTPE shows very good selectivity towards the specific recognition of MTX in the presence of important biological interference. The electrochemical biosensor detects MTX in-vitro directly from pharmaceutical sample, undiluted urine and human blood serum samples at a concentration range 5.0×10⁻⁷ M with good recovery limits.Keywords: amperometry, electrochemical detection, human blood serum, methotrexate, MWCNT, SWV
Procedia PDF Downloads 309894 Bimetallic Cu/Au Nanostructures and Bio-Application
Authors: Si Yin Tee
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Bimetallic nanostructures have received tremendous interests as a new class of nanomaterials which may have better technological usefulness with distinct properties from those of individual atoms and molecules or bulk matter. They excelled over the monometallic counterparts because of their improved electronic, optical and catalytic performances. The properties and the applicability of these bimetallic nanostructures not only depend on their size and shape, but also on the composition and their fine structure. These bimetallic nanostructures are potential candidates for bio-applications such as biosensing, bioimaging, biodiagnostics, drug delivery, targeted therapeutics, and tissue engineering. Herein, gold-incorporated copper (Cu/Au) nanostructures were synthesized through the controlled disproportionation of Cu⁺-oleylamine complex at 220 ºC to form copper nanowires and the subsequent reaction with Au³⁺ at different temperatures of 140, 220 and 300 ºC. This is to achieve their synergistic effect through the combined use of the merits of low-cost transition and high-stability noble metals. Of these Cu/Au nanostructures, Cu/Au nanotubes display the best performance towards electrochemical non-enzymatic glucose sensing, originating from the high conductivity of gold and the high aspect ratio copper nanotubes with high surface area so as to optimise the electroactive sites and facilitate mass transport. In addition to high sensitivity and fast response, the Cu/Au nanotubes possess high selectivity against interferences from other potential interfering species and excellent reproducibility with long-term stability. By introducing gold into copper nanostructures at a low level of 3, 1 and 0.1 mol% relative to initial copper precursor, a significant electrocatalytic enhancement of the resulting bimetallic Cu/Au nanostructures starts to occur at 1 mol%. Overall, the present fabrication of stable Cu/Au nanostructures offers a promising low-cost platform for sensitive, selective, reproducible and reusable electrochemical sensing of glucose.Keywords: bimetallic, electrochemical sensing, glucose oxidation, gold-incorporated copper nanostructures
Procedia PDF Downloads 521893 Palladium/Platinum Complexes of Tridentate 4-Acylpyrazolone Thiosemicarbazone with Antioxidant Properties
Authors: Omoruyi G. Idemudia, Alexander P. Sadimenko
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The need for the development of new sustainable bioactive compounds with unique properties that can become potential replacement for commonly used medicinal drugs has continued to gain tremendous research concerns because of the problems of disease resistant to these medicinal drugs and their toxicity effects. NOS-donor heterocycles are particularly of interest as they have showed good pharmacological activities in the midst of their interesting chelating properties towards metal ions, an important characteristic for transition metal based drugs design. These new compounds have also gained application as dye sensitizers in solar cell panels for the generation of renewable solar energy, as greener water purification polymer for supply and management of clean water and as catalysts which are used to reduce the amount of pollutants from industrial reaction processes amongst others, because of their versatile properties. Di-ketone acylpyrazolones and their azomethine schiff bases have been employed as pharmaceuticals as well as analytical reagents, and their application as transition metal complexes have being well established. In this research work, a new 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one-thiosemicarbazone was synthesized from the reaction of 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one and thiosemicarbazide in methanol. The pure isolate of the thiosemicarbazone was further reacted with aqueous solutions of palladium and platinum salts to obtain their metal complexes, in an effort towards the discovery of transition metal based synthetic drugs. These compounds were characterized by means of analytical, spectroscopic, thermogravimetric analysis TGA, as well as x-ray crystallography. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one thiosemicarbazone crystallizes in a triclinic crystal system with a P-1 (No. 2) space group according to x-ray crystallography. The tridentate NOS ligand formed a tetrahedral geometry on coordinating with metal ions. Reported compounds showed varying antioxidant free radical scavenging activities against 2, 2-diphenyl-1-picrylhydrazyl DPPH radical at 100, 200, 300, 400 and 500 µg/ml concentrations. The platinum complex have shown a very good antioxidant property against DPPH with an IC50 of 76.03 µg/ml compared with standard ascorbic acid (IC50 of 74.66 µg/ml) and as such have been identified as a potential anticancer candidate.Keywords: acylpyrazolone, free radical scavenging activities, tridentate ligand, x-ray crystallography
Procedia PDF Downloads 185892 Development of Electrospun Membranes with Defined Polyethylene Collagen and Oxide Architectures Reinforced with Medium and High Intensity Statins
Authors: S. Jaramillo, Y. Montoya, W. Agudelo, J. Bustamante
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Cardiovascular diseases (CVD) are related to affectations of the heart and blood vessels, within these are pathologies such as coronary or peripheral heart disease, caused by the narrowing of the vessel wall (atherosclerosis), which is related to the accumulation of Low-Density Lipoproteins (LDL) in the arterial walls that leads to a progressive reduction of the lumen of the vessel and alterations in blood perfusion. Currently, the main therapeutic strategy for this type of alteration is drug treatment with statins, which inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), responsible for modulating the rate of cholesterol production and other isoprenoids in the mevalonate pathway. This enzyme induces the expression of LDL receptors in the liver, increasing their number on the surface of liver cells, reducing the plasma concentration of cholesterol. On the other hand, when the blood vessel presents stenosis, a surgical procedure with vascular implants is indicated, which are used to restore circulation in the arterial or venous bed. Among the materials used for the development of vascular implants are Dacron® and Teflon®, which perform the function of re-waterproofing the circulatory circuit, but due to their low biocompatibility, they do not have the ability to promote remodeling and tissue regeneration processes. Based on this, the present research proposes the development of a hydrolyzed collagen and polyethylene oxide electrospun membrane reinforced with medium and high-intensity statins, so that in future research it can favor tissue remodeling processes from its microarchitecture.Keywords: atherosclerosis, medium and high-intensity statins, microarchitecture, electrospun membrane
Procedia PDF Downloads 137891 Using Daily Light Integral Concept to Construct the Ecological Plant Design Strategy of Urban Landscape
Authors: Chuang-Hung Lin, Cheng-Yuan Hsu, Jia-Yan Lin
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It is an indispensible strategy to adopt greenery approach on architectural bases so as to improve ecological habitats, decrease heat-island effect, purify air quality, and relieve surface runoff as well as noise pollution, all of which are done in an attempt to achieve sustainable environment. How we can do with plant design to attain the best visual quality and ideal carbon dioxide fixation depends on whether or not we can appropriately make use of greenery according to the nature of architectural bases. To achieve the goal, it is a need that architects and landscape architects should be provided with sufficient local references. Current greenery studies focus mainly on the heat-island effect of urban with large scale. Most of the architects still rely on people with years of expertise regarding the adoption and disposition of plantation in connection with microclimate scale. Therefore, environmental design, which integrates science and aesthetics, requires fundamental research on landscape environment technology divided from building environment technology. By doing so, we can create mutual benefits between green building and the environment. This issue is extremely important for the greening design of the bases of green buildings in cities and various open spaces. The purpose of this study is to establish plant selection and allocation strategies under different building sunshade levels. Initially, with the shading of sunshine on the greening bases as the starting point, the effects of the shades produced by different building types on the greening strategies were analyzed. Then, by measuring the PAR( photosynthetic active radiation), the relative DLI( daily light integral) was calculated, while the DLI Map was established in order to evaluate the effects of the building shading on the established environmental greening, thereby serving as a reference for plant selection and allocation. The discussion results were to be applied in the evaluation of environment greening of greening buildings and establish the “right plant, right place” design strategy of multi-level ecological greening for application in urban design and landscape design development, as well as the greening criteria to feedback to the eco-city greening buildings.Keywords: daily light integral, plant design, urban open space
Procedia PDF Downloads 511890 Rare DCDC2 Mutation Causing Renal-Hepatic Ciliopathy
Authors: Atitallah Sofien, Bouyahia Olfa, Attar Souleima, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir
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Introduction: Ciliopathies are a spectrum of diseases that have in common a defect in the synthesis of ciliary proteins. It is a rare cause of neonatal cholestasis. Clinical presentation varies extremely, and the main affected organs are the kidneys, liver, and pancreas. Methodology: This is a descriptive case report of a newborn who was admitted for exploration of neonatal cholestasis in the Paediatric Department C at the Children’s Hospital of Tunis, where the investigations concluded with a rare genetic mutation. Results: This is the case of a newborn male with no family history of hepatic and renal diseases, born to consanguineous parents, and from a well-monitored uneventful pregnancy. He developed jaundice on the second day of life, for which he received conventional phototherapy in the neonatal intensive care unit. He was admitted at 15 days for mild bronchiolitis. On clinical examination, intense jaundice was noted with normal stool and urine colour. Initial blood work showed an elevation in conjugated bilirubin and a high gamma-glutamyl transferase level. Transaminases and prothrombin time were normal. Abdominal sonography revealed hepatomegaly, splenomegaly, and undifferentiated renal cortex with bilateral medullar micro-cysts. Kidney function tests were normal. The infant received ursodeoxycholic acid and vitamin therapy. Genetic testing showed a homozygous mutation in the DCDC2 gene that hadn’t been documented before confirming the diagnosis of renal-hepatic ciliopathy. The patient has regular follow-ups, and his conjugated bilirubin and gamma-glutamyl transferase levels have been decreasing. Conclusion: Genetic testing has revolutionized the approach to etiological diagnosis in pediatric cholestasis. It enables personalised treatment strategies to better enhance the quality of life of patients and prevent potential complications following adequate long-term monitoring.Keywords: cholestasis, newborn, ciliopathy, DCDC2, genetic
Procedia PDF Downloads 63889 Using Rainfall Simulators to Design and Assess the Post-Mining Erosional Stability
Authors: Ashraf M. Khalifa, Hwat Bing So, Greg Maddocks
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Changes to the mining environmental approvals process in Queensland have been rolled out under the MERFP Act (2018). This includes requirements for a Progressive Rehabilitation and Closure Plan (PRC Plan). Key considerations of the landform design report within the PRC Plan must include: (i) identification of materials available for landform rehabilitation, including their ability to achieve the required landform design outcomes, (ii) erosion assessments to determine landform heights, gradients, profiles, and material placement, (iii) slope profile design considering the interactions between soil erodibility, rainfall erosivity, landform height, gradient, and vegetation cover to identify acceptable erosion rates over a long-term average, (iv) an analysis of future stability based on the factors described above e.g., erosion and /or landform evolution modelling. ACARP funded an extensive and thorough erosion assessment program using rainfall simulators from 1998 to 2010. The ACARP program included laboratory assessment of 35 soil and spoil samples from 16 coal mines and samples from a gold mine in Queensland using 3 x 0.8 m laboratory rainfall simulator. The reliability of the laboratory rainfall simulator was verified through field measurements using larger flumes 20 x 5 meters and catchment scale measurements at three sites (3 different catchments, average area of 2.5 ha each). Soil cover systems are a primary component of a constructed mine landform. The primary functions of a soil cover system are to sustain vegetation and limit the infiltration of water and oxygen into underlying reactive mine waste. If the external surface of the landform erodes, the functions of the cover system cannot be maintained, and the cover system will most likely fail. Assessing a constructed landform’s potential ‘long-term’ erosion stability requires defensible erosion rate thresholds below which rehabilitation landform designs are considered acceptably erosion-resistant or ‘stable’. The process used to quantify erosion rates using rainfall simulators (flumes) to measure rill and inter-rill erosion on bulk samples under laboratory conditions or on in-situ material under field conditions will be explained.Keywords: open-cut, mining, erosion, rainfall simulator
Procedia PDF Downloads 101888 Nanoceutical Intervention (Nanodrug) of Neonatal Hyperbilirubinemias Compared to Conventional Phototherapy
Authors: Samir Kumar Pal
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Background: Targeted rapid degradation of bilirubin has the potential to thwart incipient bilirubin encephalopathy. Uncontrolled hyperbilirubinemia is a potential problem in developing countries, including India, because of the lack of reliable healthcare institutes for conventional phototherapy. In India, most of the rural subjects duel in the exchange limit during transport, leading to a risk of kernicterus when they arrive at the treatment centre. Thus, an alternative pharmaceutical agent is needed for the hours. Objective: Exploration of a distinct therapeutic strategy for the control of neonatal hyperbilirubinemia compared to conventional phototherapy in a clinical setting. Method: We synthesized, characterized and investigated a spinel-structured Manganese citrate nanocomplex (C-Mn₃O₄ NC, the nanodrug) along with conventional phototherapy in neonatal subjects. We have also observed BIND scores in order to assess neurological dysfunctions. Results: Our observational study clearly reveals that the rate of declination of bilirubin in neonatal subjects with nanodrug oral administration and phototherapy is faster compared to that in the case of phototherapy only. The associated neural dysfunctions were also found to be significantly lower in the case of combined therapy. Conclusion: This study demonstrates that combined therapy works better than conventional phototherapy only for the control of hyperbilirubinemia. We have observed that a significant portion of neonatal subjects requiring blood exchange has been prevented with the combined therapeutic strategy. Further compilation of a drug-safety-dossier is warranted to translate this novel therapeutic chemo preventive approach to clinical settings.Keywords: nanodrug, nanoparticle, Neonatal hyperbilirubinemia, alternative to phototherapy, redox modulation, redox medicine
Procedia PDF Downloads 59887 Role of Inflammatory Markers in Arthritic Rats Treated with Ethanolic Bark Extract of Albizia procera
Authors: M. Sangeetha, D. Chamundeeswari, C. Saravanababu, C. Rose, V. Gopal
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Rheumatoid arthritis (RA) is a chronic, progressive, systemic inflammatory disorder affecting the synovial joints and typically producing symmetrical arthritis that leads to joint destruction, which is responsible for the deformity and disability. Despite improvements in the treatment of RA over the past decade, there still is a need for new therapeutic agents that are efficacious, less expensive, and free of severe adverse reactions. The present study aimed to investigate role of inflammatory markers in arthritic rats treated with ethanolic bark extract of Albizia procera. The protective effect of ethanolic bark extract of Albizia procera against complete Freund’s adjuvant (CFA) induced arthritis in rats. Arthritis was induced by an intradermal injection of 0.1 ml FCA in the foot pad of left hind limb of rats. ETBE (100 and 200 mg/kg b.wt./p.o) and the reference drug diclofenac (25 mg/kg b.wt./p.o) were administered to arthritic rats. Paw volume was measured for all the animals before inducing arthritis and thereafter once in seven days by using plethysmometer for 42 days. Gene expression of inflammatory markers such as IL-1β and IL-10 were investigated in paw tissues. Up regulation of IL-1β and Down regulation IL-10 were observed in CFA injected rats when compared to normal rats. ETBE attenuated these alterations dose dependently when compared to the vehicle treated rats. These results provide insights into the mechanism of anti-arthritic activity, and unravel potential therapeutic use of Albizia procera in arthritis.
Keywords: CFA-Complete Freund’s adjuvant, ETBE – ethanolic bark extract, IL- interleukins, RA-rheumatoid arthritis
Procedia PDF Downloads 285886 Engineering Analysis for Fire Safety Using Computational Fluid Dynamic (CFD)
Authors: Munirajulu M, Srikanth Modem
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A large cricket stadium with the capacity to accommodate several thousands of spectators has the seating arena consisting of a two-tier arrangement with an upper and a lower bowl and an intermediate concourse podium level for pedestrian movement to access the bowls. The uniqueness of the stadium is that spectators can have an unobstructed view from all around the podium towards the field of play. Upper and lower bowls are connected by stairs. The stairs landing is a precast slab supported by cantilevered steel beams. These steel beams are fixed to precast columns supporting the stadium structure. The stair slabs are precast concrete supported on a landing slab and cantilevered steel beams. During an event of a fire at podium level between two staircases, fire resistance of steel beams is very critical to life safety. If the steel beam loses its strength due to lack of fire resistance, it will be weak in supporting stair slabs and may lead to a hazard in evacuating occupants from the upper bowl to the lower bowl. In this study, to ascertain fire rating and life safety, a performance-based design using CFD analysis is used to evaluate the steel beams' fire resistance. A fire size of 3.5 MW (convective heat output of fire) with a wind speed of 2.57 m/s is considered for fire and smoke simulation. CFD results show that the smoke temperature near the staircase/ around the staircase does not exceed 1500 C for the fire duration considered. The surface temperature of cantilevered steel beams is found to be less than or equal to 1500 C. Since this temperature is much less than the critical failure temperature of steel (5200 C), it is concluded that the design of structural steel supports on the staircase is adequate and does not need additional fire protection such as fire-resistant coating. CFD analysis provided an engineering basis for the performance-based design of steel structural elements and an opportunity to optimize fire protection requirements. Thus, performance-based design using CFD modeling and simulation of fire and smoke is an innovative way to evaluate fire rating requirements, ascertain life safety and optimize the design with regard to fire protection on structural steel elements.Keywords: fire resistance, life safety, performance-based design, CFD analysis
Procedia PDF Downloads 192885 Network Pharmacological Evaluation of Holy Basil Bioactive Phytochemicals for Identifying Novel Potential Inhibitors Against Neurodegenerative Disorder
Authors: Bhuvanesh Baniya
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Alzheimer disease is illnesses that are responsible for neuronal cell death and resulting in lifelong cognitive problems. Due to their unclear mechanism, there are no effective drugs available for the treatment. For a long time, herbal drugs have been used as a role model in the field of the drug discovery process. Holy basil in the Indian medicinal system (Ayurveda) is used for several neuronal disorders like insomnia and memory loss for decades. This study aims to identify active components of holy basil as potential inhibitors for the treatment of Alzheimer disease. To fulfill this objective, the Network pharmacology approach, gene ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics simulation (MDS) studies were performed. A total of 7 active components in holy basil, 12 predicted neurodegenerative targets of holy basil, and 8063 Alzheimer-related targets were identified from different databases. The network analysis showed that the top ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B were found as significant target related to Alzheimer disease. On the basis of gene ontology and topology analysis results, APP was found as a significant target related to Alzheimer’s disease pathways. Further, the molecular docking results to found that various compounds showed the best binding affinities. Further, MDS top results suggested could be used as potential inhibitors against APP protein and could be useful for the treatment of Alzheimer’s disease.Keywords: holy basil, network pharmacology, neurodegeneration, active phytochemicals, molecular docking and simulation
Procedia PDF Downloads 101884 Cytotoxicity and Androgenic Potential of Antifungal Drug Substances on MDA-KB2 Cells
Authors: Benchouala Amira, Bojic Clement, Poupin Pascal, Cossu Leguille-carole
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The objective of this study is to evaluate in vitro the cytotoxic and androgenic potential of several antifungal molecules (amphotericin B, econazole, ketoconazole and miconazole) on MDA-Kb2 cell lines. This biological model is an effective tool for the detection of endocrine disruptors because it responds well to the main agonist of the androgen receptor (testosterone) and also to an antagonist: flutamide. The cytotoxicity of each chemical compound tested was measured using an MTT assay (tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) which measures the activity of the reductase function of mitochondrial succinate dehydrogenase enzymes of cultured cells. This complementary cytotoxicity test is essential to ensure that the effects of reduction in luminescence intensity observed during androgenic tests are only attributable to the anti-androgenic action of the compounds tested and not to their possible cytotoxic properties. Tests of the androgenic activity of antifungals show that these compounds do not have the capacity to induce transcription of the luciferase gene. These compounds do not exert an androgenic effect on MDA-Kb2 cells in culture for the environmental concentrations tested. The addition of flutamide for the same tested concentrations of antifungal molecules reduces the luminescence induced by amphotericin B, econazole and miconazole, which is explained by a strong interaction of these molecules with flutamide which may have a greater toxic effect than when tested alone. The cytotoxicity test shows that econazole and ketoconazole can cause cell death at certain concentrations tested. This cell mortality is perhaps induced by a direct or indirect action on deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or proteins necessary for cell division.Keywords: cytotoxicity, androgenic potential, antifungals, MDA-Kb2
Procedia PDF Downloads 48883 The Impact of the Method of Extraction on 'Chemchali' Olive Oil Composition in Terms of Oxidation Index, and Chemical Quality
Authors: Om Kalthoum Sallem, Saidakilani, Kamiliya Ounaissa, Abdelmajid Abid
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Introduction and purposes: Olive oil is the main oil used in the Mediterranean diet. Virgin olive oil is valued for its organoleptic and nutritional characteristics and is resistant to oxidation due to its high monounsaturated fatty acid content (MUFAs), and low polyunsaturates (PUFAs) and the presence of natural antioxidants such as phenols, tocopherols and carotenoids. The fatty acid composition, especially the MUFA content, and the natural antioxidants provide advantages for health. The aim of the present study was to examine the impact of method of extraction on the chemical profiles of ‘Chemchali’ olive oil variety, which is cultivated in the city of Gafsa, and to compare it with chetoui and chemchali varieties. Methods: Our study is a qualitative prospective study that deals with ‘Chemchali’ olive oil variety. Analyses were conducted during three months (from December to February) in different oil mills in the city of Gafsa. We have compared ‘Chemchali’ olive oil obtained by continuous method to this obtained by superpress method. Then we have analyzed quality index parameters, including free fatty acid content (FFA), acidity, and UV spectrophotometric characteristics and other physico-chemical data [oxidative stability, ß-carotene, and chlorophyll pigment composition]. Results: Olive oil resulting from super press method compared with continuous method is less acid(0,6120 vs. 0,9760), less oxydazible(K232:2,478 vs. 2,592)(k270:0,216 vs. 0,228), more rich in oleic acid(61,61% vs. 66.99%), less rich in linoleic acid(13,38% vs. 13,98 %), more rich in total chlorophylls pigments (6,22 ppm vs. 3,18 ppm ) and ß-carotene (3,128 mg/kg vs. 1,73 mg/kg). ‘Chemchali’ olive oil showed more equilibrated total content in fatty acids compared with the varieties ’Chemleli’ and ‘Chetoui’. Gafsa’s variety ’Chemlali’ have significantly less saturated and polyunsaturated fatty acids. Whereas it has a higher content in monounsaturated fatty acid C18:2, compared with the two other varieties. Conclusion: The use of super press method had benefic effects on general chemical characteristics of ‘Chemchali’ olive oil, maintaining the highest quality according to the ecocert legal standards. In light of the results obtained in this study, a more detailed study is required to establish whether the differences in the chemical properties of oils are mainly due to agronomic and climate variables or, to the processing employed in oil mills.Keywords: olive oil, extraction method, fatty acids, chemchali olive oil
Procedia PDF Downloads 383882 Electrical Tortuosity across Electrokinetically Remediated Soils
Authors: Waddah S. Abdullah, Khaled F. Al-Omari
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Electrokinetic remediation is one of the most influential and effective methods to decontaminate contaminated soils. Electroosmosis and electromigration are the processes of electrochemical extraction of contaminants from soils. The driving force that causes removing contaminants from soils (electroosmosis process or electromigration process) is voltage gradient. Therefore, the electric field distribution throughout the soil domain is extremely important to investigate and to determine the factors that help to establish a uniform electric field distribution in order to make the clean-up process work properly and efficiently. In this study, small-sized passive electrodes (made of graphite) were placed at predetermined locations within the soil specimen, and the voltage drop between these passive electrodes was measured in order to observe the electrical distribution throughout the tested soil specimens. The electrokinetic test was conducted on two types of soils; a sandy soil and a clayey soil. The electrical distribution throughout the soil domain was conducted with different tests properties; and the electrical field distribution was observed in three-dimensional pattern in order to establish the electrical distribution within the soil domain. The effects of density, applied voltages, and degree of saturation on the electrical distribution within the remediated soil were investigated. The distribution of the moisture content, concentration of the sodium ions, and the concentration of the calcium ions were determined and established in three-dimensional scheme. The study has shown that the electrical conductivity within soil domain depends on the moisture content and concentration of electrolytes present in the pore fluid. The distribution of the electrical field in the saturated soil was found not be affected by its density. The study has also shown that high voltage gradient leads to non-uniform electric field distribution within the electroremediated soil. Very importantly, it was found that even when the electric field distribution is uniform globally (i.e. between the passive electrodes), local non-uniformity could be established within the remediated soil mass. Cracks or air gaps formed due to temperature rise (because of electric flow in low conductivity regions) promotes electrical tortuosity. Thus, fracturing or cracking formed in the remediated soil mass causes disconnection of electric current and hence, no removal of contaminant occur within these areas.Keywords: contaminant removal, electrical tortuousity, electromigration, electroosmosis, voltage distribution
Procedia PDF Downloads 421881 Screening Maize for Compatibility with F. Oxysporum to Enhance Striga asiatica (L.) Kuntze Resistance
Authors: Admire Isaac Tichafa Shayanowako, Mark Laing, Hussein Shimelis
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Striga asiatica is among the leading abiotic constraints to maize production under small-holder farming communities in southern African. However, confirmed sources of resistance to the parasitic weed are still limited. Conventional breeding programmes have been progressing slowly due to the complex nature of the inheritance of Striga resistance, hence there is a need for more innovative approaches. This study aimed to achieve partial resistance as well as to breed for compatibility with Fusarium oxysporum fsp strigae, a soil fungus that is highly specific in its pathogenicity. The agar gel and paper roll assays in conjunction with a glass house pot trial were done to select genotypes based on their potential to stimulate germination of Striga and to test the efficacy of Fusarium oxysporum as a biocontrol agent. Results from agar gel assays showed a moderate to high potential in the release of Strigalactones among the 33 OPVs. Maximum Striga germination distances from the host root of 1.38 cm and up to 46% germination were observed in most of the populations. Considerable resistance was observed in a landrace ‘8lines’ which had the least Striga germination percentage (19%) with a maximum distance of 0.93 cm compared to the resistant check Z-DPLO-DTC1 that had 23% germination at a distance of 1.4cm. The number of fusarium colony forming units significantly deferred (P < 0.05) amongst the genotypes growing between germination papers. The number of crown roots, length of primary root and fresh weight of shoot and roots were highly correlated with concentration of fusarium macrospore counts. Pot trials showed significant differences between the fusarium coated and the uncoated treatments in terms of plant height, leaf counts, anthesis-silks intervals, Striga counts, Striga damage rating and Striga vigour. Striga emergence counts and Striga flowers were low in fusarium treated pots. Plants in fusarium treated pots had non-significant differences in height with the control treatment. This suggests that foxy 2 reduces the impact of Striga damage severity. Variability within fusarium treated genotypes with respect to traits under evaluation indicates the varying degree of compatibility with the biocontrol.Keywords: maize, Striga asiaitca, resistance, compatibility, F. oxysporum
Procedia PDF Downloads 250880 Design, Synthesis and Evaluation of 4-(Phenylsulfonamido)Benzamide Derivatives as Selective Butyrylcholinesterase Inhibitors
Authors: Sushil Kumar Singh, Ashok Kumar, Ankit Ganeshpurkar, Ravi Singh, Devendra Kumar
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In spectrum of neurodegenerative diseases, Alzheimer’s disease (AD) is characterized by the presence of amyloid β plaques and neurofibrillary tangles in the brain. It results in cognitive and memory impairment due to loss of cholinergic neurons, which is considered to be one of the contributing factors. Donepezil, an acetylcholinesterase (AChE) inhibitor which also inhibits butyrylcholinesterase (BuChE) and improves the memory and brain’s cognitive functions, is the most successful and prescribed drug to treat the symptoms of AD. The present work is based on designing of the selective BuChE inhibitors using computational techniques. In this work, machine learning models were trained using classification algorithms followed by screening of diverse chemical library of compounds. The various molecular modelling and simulation techniques were used to obtain the virtual hits. The amide derivatives of 4-(phenylsulfonamido) benzoic acid were synthesized and characterized using 1H & 13C NMR, FTIR and mass spectrometry. The enzyme inhibition assays were performed on equine plasma BuChE and electric eel’s AChE by method developed by Ellman et al. Compounds 31, 34, 37, 42, 49, 52 and 54 were found to be active against equine BuChE. N-(2-chlorophenyl)-4-(phenylsulfonamido)benzamide and N-(2-bromophenyl)-4-(phenylsulfonamido)benzamide (compounds 34 and 37) displayed IC50 of 61.32 ± 7.21 and 42.64 ± 2.17 nM against equine plasma BuChE. Ortho-substituted derivatives were more active against BuChE. Further, the ortho-halogen and ortho-alkyl substituted derivatives were found to be most active among all with minimal AChE inhibition. The compounds were selective toward BuChE.Keywords: Alzheimer disease, butyrylcholinesterase, machine learning, sulfonamides
Procedia PDF Downloads 139879 Colorimetric Measurement of Dipeptidyl Peptidase IV (DPP IV) Activity via Peptide Capped Gold Nanoparticles
Authors: H. Aldewachi, M. Hines, M. McCulloch, N. Woodroofe, P. Gardiner
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DPP-IV is an enzyme whose expression is affected in a variety of diseases, therefore, has been identified as possible diagnostic or prognostic marker for various tumours, immunological, inflammatory, neuroendocrine, and viral diseases. Recently, DPP-IV enzyme has been identified as a novel target for type II diabetes treatment where the enzyme is involved. There is, therefore, a need to develop sensitive and specific methods that can be easily deployed for the screening of the enzyme either as a tool for drug screening or disease marker in biological samples. A variety of assays have been introduced for the determination of DPP-IV enzyme activity using chromogenic and fluorogenic substrates, nevertheless these assays either lack the required sensitivity especially in inhibited enzyme samples or displays low water solubility implying difficulty for use in vivo samples in addition to labour and time-consuming sample preparation. In this study, novel strategies based on exploiting the high extinction coefficient of gold nanoparticles (GNPs) are investigated in order to develop fast, specific and reliable enzymatic assay by investigating synthetic peptide sequences containing a DPP IV cleavage site and coupling them to GNPs. The DPP IV could be detected by colorimetric response of peptide capped GNPs (P-GNPS) that could be monitored by a UV-visible spectrophotometer or even naked eyes, and the detection limit could reach 0.01 unit/ml. The P-GNPs, when subjected to DPP IV, showed excellent selectivity compared to other proteins (thrombin and human serum albumin) , which led to prominent colour change. This provided a simple and effective colorimetric sensor for on-site and real-time detection of DPP IV.Keywords: gold nanoparticles, synthetic peptides, colorimetric detection, DPP-IV enzyme
Procedia PDF Downloads 303878 Diagnostic Value of CT Scan in Acute Appendicitis
Authors: Maria Medeiros, Suren Surenthiran, Abitha Muralithar, Soushma Seeburuth, Mohammed Mohammed
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Introduction: Appendicitis is the most common surgical emergency globally and can have devastating consequences. Diagnostic imaging in acute appendicitis has become increasingly common in aiding the diagnosis of acute appendicitis. Computerized tomography (CT) and ultrasound (US) are the most commonly used imaging modalities for diagnosing acute appendicitis. Pre-operative imaging has contributed to a reduction of negative appendicectomy rates from between 10-29% to 5%. Literature report CT scan has a diagnostic sensitivity of 94% in acute appendicitis. This clinical audit was conducted to establish if the CT scan's diagnostic yield for acute appendicitis matches the literature. CT scan has a high sensitivity and specificity for diagnosing acute appendicitis and its use can result in a lower negative appendicectomy rate. The aim of this study is to compare the pre-operative imaging findings from CT scans to the histopathology results post-operatively and establish the accuracy of CT scans in aiding the diagnosis of acute appendicitis. Methods: This was a retrospective study focusing on adult presentations to the general surgery department in a district general hospital in central London with an impression of acute appendicitis. We analyzed all patients from July 2022 to December 2022 who underwent a CT scan preceding appendicectomy. Pre-operative CT findings and post-operative histopathology findings were compared to establish the efficacy of CT scans in diagnosing acute appendicitis. Our results were also cross-referenced with pre-existing literature. Data was collected and anonymized using CERNER and analyzed in Microsoft Excel. Exclusion criteria: Children, age <16. Results: 65 patients had CT scans in which the report stated acute appendicitis. Of those 65 patients, 62 patients underwent diagnostic laparoscopies. 100% of patients who underwent an appendicectomy with a pre-operative CT scan showing acute appendicitis had acute appendicitis in histopathology analysis. 3 of the 65 patients who had a CT scan showing appendicitis received conservative treatment. Conclusion: CT scans positive for acute appendicitis had 100% sensitivity and a positive predictive value, which matches published research studies (sensitivity of 94%). The use of CT scans in the diagnostic work-up for acute appendicitis can be extremely helpful in a) confirming the diagnosis and b) reducing the rates of negative appendicectomies and consequently reducing unnecessary operative-associated risks for patients, reducing costs and reducing pressure on emergency theatre lists.Keywords: acute apendicitis, CT scan, general surgery, imaging
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