Search results for: extrapyramidal side effects/disorder
7763 Synthesis of 5'-Azidonucleosides as Building Blocks for the Preparation of Biologically Active Bioconjugates
Authors: Brigitta Bodnár, Lajos Kovács, Zoltán Kupihár
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The cancer cells require higher amount of nucleoside building blocks for their proliferation, therefore they have significantly higher uptake of nucleosides by the different nucleoside transporters. Therefore, the conjugation with nucleosides may significantly increase the efficiency and selectivity of potential active pharmaceutical ingredients. On the other hand, the advantage of using a nucleoside could be either the higher activity on targeted enzymes overrepresented in cancer cells or an enhanced cellular uptake of the bioconjugates in these cells compared to the healthy ones. This fact can be used to make the nucleosides, as targeting moieties covalently bound to anti-cancer drug molecules which can selectively accumulate in cancer cells. However, in order to form the nucleoside-drug conjugates, such nucleoside building blocks are needed, which can selectively be coupled to the drug molecules containing even a high number of diverse functional groups. One of the most selective conjugation techniques is the copper-catalyzed azide-alkyne click reaction that requires the presence of an alkyl group on one of the conjugated molecules and an azide group on the other. In case of nucleosides, the development of azide group is simpler for which the replacement of the 5'-hydroxy group is the most suitable. This transformation generally involves many side reactions and result in very low yields. In addition, during our experiments, the transformation of the 2'-deoxyguanosine to the corresponding 5'-deoxy-5’-azido-2’-deoxyguanosine could not be performed with any of the methods described in the literature. Therefore, we have tried to overcome these difficulties with not only using the traditional process based on the 2 step exchange of tosyl to azide, but also using the Mitsunobu reaction which requires only one step. However, this path proved to be unsuccessful in spite of the optimizing the reaction conditions. Finally, a method has been developed whereby the azide groups were incorporated into the 5’-position resulting in significantly better yields compared to all other previous methods, and we were able to produce all the four nucleoside derivatives.Keywords: 5'-azidonucleosides, bioconjugate, click reaction, proliferation
Procedia PDF Downloads 2467762 Therapeutic Effects of Guar Gum Nanoparticles in Oxazolone-Induced Atopic Dermatitis
Authors: Nandita Ghosh, Shinjini Mitra, Ena Ray Banerjee
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Atopic dermatitis (AD) is a chronic disease of the skin, involving itchy, reddish, and scaly lesions. It mainly affects children and has a high prevalence in developing countries. The AD may occur due to environmental or genetic factors. There is no permanent cure for the AD. Currently, all therapeutic strategies involve methods to simply alleviate the symptoms, and include lotions and corticosteroids, which have adverse effects. Use of phytochemicals and natural products has not yet been exploited fully. The particle used in this study is derived from Cyamopsis tetragonoloba, an edible polysaccharide with a galactomannan component. The mannose component mainly increases its specificity towards cellular uptake by mannose receptors, highly expressed by the macrophage. The aim of this study was to determine the therapeutic effect of guar gum nanoparticles (GN) in vitro and in vivo in the AD. To assess the wound healing capacity of the guar gum nanoparticle (GN), we first treated adherent NIH3T3 cells, with a scratch injury, with GN. GN successfully healed the wound caused by the scratch. In the in vivo experiment, Balb/c mice ear were topically treated with oxazolone (oxa) to induce AD and then were topically treated with GN. The ear thickness was increased significantly till day 28 on the treatment of Oxa. The GN application showed a significant decrease in the thickness as assessed on day 28. The total cell count of skin cells showed fold increase when treated with oxa, was again decreased on topical application of GN on the affected skin. The eosinophil count, as assessed by Giemsa staining was also increased when treated with oxa, GN application led to a significant decrease. The IgE level was assessed in the serum samples which showed that GN helped in restoring the alleviated IgE level. The T helper cells and the macrophage population showed increased percentage when treated with oxa, the GN application. This was examined by flow cytometry. The H&E staining of the ear tissue showed epidermal thickness in the oxa treated mice, GN application showed reduced cellular filtration followed by epidermal thickness. Thus our assays showed that GN was successful in alleviating the disease caused by Oxa when administered topically.Keywords: allergen, inflammation, nanodrug, wound
Procedia PDF Downloads 2437761 Implementation of Environmental Sustainability into Event Management
Authors: Özlem Küçükakça
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The world population is rapidly growing. In the last few decades, environmental protection and climate change have been remarked as a global concern. All events have their own ecological footprint. Therefore, all participants who take part in the events, from event organizer to audience should be responsible for reducing carbon emissions. Currently, there is a literature gap which investigates the relationship between events and environment. Hence, this study is conducted to investigate how to implement environmental sustainability in the event management. Therefore, a wide literature and also the UK festivals database have been investigated. Finally, environmental effects and the solution of reducing impacts at events were discussed.Keywords: ecological footprint, environmental sustainability, events, sustainability
Procedia PDF Downloads 3047760 The Side Effect of the Perforation Shape towards Behaviour Flexural in Castellated Beam
Authors: Harrys Purnama, Wardatul Jannah, Rizkia Nita Hawari
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In the development of the times, there are many materials used to plan a building structure. Steel became one of the most widely used materials in building construction that works as the main structure. Steel Castellated Beam is a type of innovation in the use of steel in building construction. Steel Castellated Beam is a beam that used for long span construction (more than 10 meters). The Castellated Beam is two steel profiles that unified into one to get the appropriate profile height (more than 10 meters). The profile is perforated to minimize the profile's weight, increase the rate, save costs, and have architectural value. The perforations shape in the Castellated Beam can be circular, elliptical, hexagonal, and rectangular. The Castellated beam has a height (h) almost 50% higher than the initial profile thus increasing the axial bending value and the moment of inertia (Iₓ). In this analysis, there are 3 specimens were used with 12.1 meters span of Castellated Beam as the sample with varied perforation, such us round, hexagon, and octagon. Castellated Beam testing system is done with computer-based applications that named Staad Pro V8i. It is to provide a central load in the middle of the steel beam span. It aims to determine the effect of perforation on bending behavior on the steel Castellated Beam by applying some form of perforations on the steel Castellated Beam with test specimen WF 200.100.5.5.8. From the analysis, results found the behavior of steel Castellated Beam when receiving such central load. From the results of the analysis will be obtained the amount of load, shear, strain, and Δ (deflection). The result of analysis by using Staad Pro V8i shows that with the different form of perforations on the profile of Castellated steel, then we get the different tendency of inertia moment. From the analysis, results obtained the moment of the greatest inertia can increase the stiffness of Castellated steel. By increasing the stiffness of the steel Castellated Beam the deflection will be smaller, so it can withstand the moment and a large strength. The results of the analysis show that the most effective and efficient perforations are the steel beam with a hexagon perforation shape.Keywords: Castellated Beam, the moment of inertia, stress, deflection, bending test
Procedia PDF Downloads 1687759 Monetary Policy and Assets Prices in Nigeria: Testing for the Direction of Relationship
Authors: Jameelah Omolara Yaqub
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One of the main reasons for the existence of central bank is that it is believed that central banks have some influence on private sector decisions which will enable the Central Bank to achieve some of its objectives especially that of stable price and economic growth. By the assumption of the New Keynesian theory that prices are fully flexible in the short run, the central bank can temporarily influence real interest rate and, therefore, have an effect on real output in addition to nominal prices. There is, therefore, the need for the Central Bank to monitor, respond to, and influence private sector decisions appropriately. This thus shows that the Central Bank and the private sector will both affect and be affected by each other implying considerable interdependence between the sectors. The interdependence may be simultaneous or not depending on the level of information, readily available and how sensitive prices are to agents’ expectations about the future. The aim of this paper is, therefore, to determine whether the interdependence between asset prices and monetary policy are simultaneous or not and how important is this relationship. Studies on the effects of monetary policy have largely used VAR models to identify the interdependence but most have found small effects of interaction. Some earlier studies have ignored the possibility of simultaneous interdependence while those that have allowed for simultaneous interdependence used data from developed economies only. This study, therefore, extends the literature by using data from a developing economy where information might not be readily available to influence agents’ expectation. In this study, the direction of relationship among variables of interest will be tested by carrying out the Granger causality test. Thereafter, the interaction between asset prices and monetary policy in Nigeria will be tested. Asset prices will be represented by the NSE index as well as real estate prices while monetary policy will be represented by money supply and the MPR respectively. The VAR model will be used to analyse the relationship between the variables in order to take account of potential simultaneity of interdependence. The study will cover the period between 1980 and 2014 due to data availability. It is believed that the outcome of the research will guide monetary policymakers especially the CBN to effectively influence the private sector decisions and thereby achieve its objectives of price stability and economic growth.Keywords: asset prices, granger causality, monetary policy rate, Nigeria
Procedia PDF Downloads 2207758 Effects of Methods of Confinement during Transportation of Market Pigs on Meat Quality
Authors: Pongchan Na-Lampang
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The objective of this study was to compare the results of transport of slaughter pigs to slaughterhouse by 2 methods, i.e. individual confined and group confined on the truck on meat quality. The pigs were transported for 1 h on a distance of 70 km. The stocking densities were 0.35 m2/pig and 0.48 m2 for group and individual crate treatment, respectively. It was found that meat quality of pigs transported by 2 different methods as measured in terms of pH level (at 45 min and 48 hr post mortem), color (brightness, redness and yellowness) and water holding capacity was not significantly different.Keywords: market pig, transportation, meat quality, confinement
Procedia PDF Downloads 3897757 Impact of Fischer-Tropsch Wax on Ethylene Vinyl Acetate/Waste Crumb Rubber Modified Bitumen: An Energy-Sustainability Nexus
Authors: Keith D. Nare, Mohau J. Phiri, James Carson, Chris D. Woolard, Shanganyane P. Hlangothi
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In an energy-intensive world, minimizing energy consumption is paramount to cost saving and reducing the carbon footprint. Improving mixture procedures utilizing warm mix additive Fischer-Tropsch (FT) wax in ethylene vinyl acetate (EVA) and modified bitumen highlights a greener and sustainable approach to modified bitumen. In this study, the impact of FT wax on optimized EVA/waste crumb rubber modified bitumen is assayed with a maximum loading of 2.5%. The rationale of the FT wax loading is to maintain the original maximum loading of EVA in the optimized mixture. The phase change abilities of FT wax enable EVA co-crystallization with the support of the elastomeric backbone of crumb rubber. Less than 1% loading of FT wax worked in the EVA/crumb rubber modified bitumen energy-sustainability nexus. Response surface methodology approach to the mixture design is implemented amongst the different loadings of FT wax, EVA for a consistent amount of crumb rubber and bitumen. Rheological parameters (complex shear modulus, phase angle and rutting parameter) were the factors used as performance indicators of the different optimized mixtures. The low temperature chemistry of the optimized mixtures is analyzed using elementary beam theory and the elastic-viscoelastic correspondence principle. Master curves and black space diagrams are developed and used to predict age-induced cracking of the different long term aged mixtures. Modified binder rheology reveals that the strain response is not linear and that there is substantial re-arrangement of polymer chains as stress is increased, this is based on the age state of the mixture and the FT wax and EVA loadings. Dominance of individual effects is evident over effects of synergy in co-interaction of EVA and FT wax. All-inclusive FT wax and EVA formulations were best optimized in mixture 4 with mixture 7 reflecting increase in ease of workability. Findings show that interaction chemistry of bitumen, crumb rubber EVA, and FT wax is first and second order in all cases involving individual contributions and co-interaction amongst the components of the mixture.Keywords: bitumen, crumb rubber, ethylene vinyl acetate, FT wax
Procedia PDF Downloads 1737756 Optimized Parameters for Simultaneous Detection of Cd²⁺, Pb²⁺ and CO²⁺ Ions in Water Using Square Wave Voltammetry on the Unmodified Glassy Carbon Electrode
Authors: K. Sruthi, Sai Snehitha Yadavalli, Swathi Gosh Acharyya
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Water is the most crucial element for sustaining life on earth. Increasing water pollution directly or indirectly leads to harmful effects on human life. Most of the heavy metal ions are harmful in their cationic form. These heavy metal ions are released by various activities like disposing of batteries, industrial wastes, automobile emissions, and soil contamination. Ions like (Pb, Co, Cd) are carcinogenic and show many harmful effects when consumed more than certain limits proposed by WHO. The simultaneous detection of the heavy metal ions (Pb, Co, Cd), which are highly toxic, is reported in this study. There are many analytical methods for quantifying, but electrochemical techniques are given high priority because of their sensitivity and ability to detect and recognize lower concentrations. Square wave voltammetry was preferred in electrochemical methods due to the absence of background currents which is interference. Square wave voltammetry was performed on GCE for the quantitative detection of ions. Three electrode system consisting of a glassy carbon electrode as the working electrode (3 mm diameter), Ag/Agcl electrode as the reference electrode, and a platinum wire as the counter electrode was chosen for experimentation. The mechanism of detection was done by optimizing the experimental parameters, namely pH, scan rate, and temperature. Under the optimized conditions, square wave voltammetry was performed for simultaneous detection. Scan rates were varied from 5 mV/s to 100 mV/s and found that at 25 mV/s all the three ions were detected simultaneously with proper peaks at particular stripping potential. The variation of pH from 3 to 8 was done where the optimized pH was taken as pH 5 which holds good for three ions. There was a decreasing trend at starting because of hydrogen gas evolution, and after pH 5 again there was a decreasing trend that is because of hydroxide formation on the surface of the working electrode (GCE). The temperature variation from 25˚C to 45˚C was done where the optimum temperature concerning three ions was taken as 35˚C. Deposition and stripping potentials were given as +1.5 V and -1.5 V, and the resting time of 150 seconds was given. Three ions were detected at stripping potentials of Cd²⁺ at -0.84 V, Pb²⁺ at -0.54 V, and Co²⁺ at -0.44 V. The parameters of detection were optimized on a glassy carbon electrode for simultaneous detection of the ions at lower concentrations by square wave voltammetry.Keywords: cadmium, cobalt, lead, glassy carbon electrode, square wave anodic stripping voltammetry
Procedia PDF Downloads 1177755 Toxicological and Histopathological Studies on the Effect of Tartrazine in Male Albino Rats
Authors: F. Alaa Ali, S. A. Sherein Abdelgayed, S. Osama. EL-Tawil, M. Adel Bakeer
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Tartrazine is an organic azo dyes food additive widely used in foods, drugs, and cosmetics. The present study aimed to investigate the toxic effects of tartrazine on kidneys and liver biomarkers in addition to the investigation of oxidative stress and change of histopathological structure of liver and kidneys in 30 male rats. Tartrazine was orally administrated daily at dose 200 mg/ kg bw (1/ 10 LD50) for sixty days. Serum and tissue samples were collected at the end of the experiment to investigate the underlying mechanism of tartrazine through assessment oxidative stress (Glutathione (GSH), Superoxide dismutase (SOD) and malondialdehyde (MDA) and biochemical markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), Total protein and Urea). Liver and kidneys tissue were collected and preserved in 10% formalin for histopathological examination. The obtained values were statistically analyzed by one way analysis of variance (ANOVA) followed by multiple comparison test. Biochemical analysis revealed that tartrazine induced significant increase in serum ALT, AST, total protein, urea level compared to control group. Tartrazine showed significant decrease in liver GSH and SOD where their values when compared to control group. Tartrazine induced increase in liver MDA compared to control group. Histopathology of the liver showed diffuse vacuolar degeneration in hepatic parenchyma, the portal area showed sever changes sever in hepatoportal blood vessels and in the bile ducts. The kidneys showed degenerated tubules at the cortex together with mononuclear leucocytes inflammatory cells infiltration. There is perivascular edema with inflammatory cell infiltration surrounding the congested and hyalinized vascular wall of blood vessel. The present study indicates that the subchronic effects of tartrazine have a toxic effect on the liver and kidneys together with induction of oxidative stress by formation of free radicals. Therefore, people should avoid the hazards of consuming tartrazine.Keywords: albino rats, tartrazine, toxicity, pathology
Procedia PDF Downloads 3577754 Identification of a Lead Compound for Selective Inhibition of Nav1.7 to Treat Chronic Pain
Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov
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Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development
Procedia PDF Downloads 1247753 Representation of Phonemic Changes in Arabic Dialect of Yemen: Speech Disorder and Consonant Substitution
Authors: Sadeq Al Yaari, Muhammad Alkhunayn, Adham Al Yaari, Montaha Al Yaari, Ayman Al Yaari, Aayah Al Yaari, Sajedah Al Yaari, Fatehi Eissa
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Introduction: Like many dialects, the Arabic dialect of Yemen (ADY) exhibited utterance phonemic distinction- vowel deletion, lengthening, and insertion- that were investigated using speakers from different dialectal backgrounds, with particular focus on the difference typically developing and achieving speakers and those suffering linguistic problems make. Phonological variations were found to be inevitable, suggesting further investigation of consonants to see to what extent they are prone to such phonemic changes. This study investigates the patterns of consonant substitution in ADY by examining if there is a clear-cut line between normal and pathological consonants to decide which of these consonants is substituted more. Methods: A total of hundred and twenty nine Yemeni male participants (age= 6-13) were enrolled in this study. Participants were preassigned into two groups (Articulation disorders (AD) group= 42 and typically developing and achieving group (TD) = 70), each of which consists of five sub-groups in decided sociolinguistic classification. In a 45 minute-session, 180 pictures of commonly used verbs (4 pics/m.) were presented to participants who were asked to impulsively describe these verbs before their production was psychoneurolinguistically and statistically analyzed. Results: There was a pattern of consonant substitution in some dialects that participants from both groups have in common: Voiceless consonants (/t/, /ṣ/,/s/, /ḥ, /k/, /ʃ/, /f//, and /k/) in northern and eastern dialects; voiced consonants (/q/, /gh/, /Ʒ/, /g/,/ḍ/, /b/, and /d/) in southern, eastern, western and central dialects; and voiceless and voiced consonants(/t/, /f/, /Ø/, /ṣ/, /s/, /q/, /gh/, /Ʒ/, /g/,/ḍ/, and /b/) in southern dialect. Voiceless consonants (/t/, /ṣ/,/s/, /ḥ, /k/, /ʃ/, /f//, /Ø/and /k/) found to be substituted more by ADY speakers of both AD and TD groups followed by voiced consonants (/q/, /gh/, /Ʒ/, /g/,/ḍ/,/d/ /b/, and /ð/), nasals (/m/, /n/), mute (/h/), semi-vowels (/w/ and /j/) and laterals (/l/ and /r/). Unexpectedly, a short vowel (/æ/) and two long vowels (/u: and /a:/) were found to substitute consonants in ADY both by AD and TD participants. Conclusions: AD and TD participants of ADY substitute consonants in their dialectal speech. Consonant substitution processes cover not only consonants but extend to include monophthongs. The finding that speakers of ADY substitute consonants in multisyllabic words is probably due to the fact that the sociolinguistic factor plays a pivotal role in the problematic substitution of consonants in ADY speakers. Larger longitudinal studies are necessary to further investigate the effect of sociolinguistic background on phonological variations, notably sound change in the speech of Yemeni TD speakers compared to those with linguistic impairments.Keywords: consonant substitution, Arabic dialect of Yemen, phonetics, phonology, syllables, articulation disorders
Procedia PDF Downloads 447752 Analysis in Mexico on Workers Performing Highly Repetitive Movements with Sensory Thermography in the Surface of the Wrist and Elbows
Authors: Sandra K. Enriquez, Claudia Camargo, Jesús E. Olguín, Juan A. López, German Galindo
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Currently companies have increased the number of disorders of cumulative trauma (CTDs), these are increasing significantly due to the Highly Repetitive Movements (HRM) performed in workstations, which causes economic losses to businesses, due to temporary and permanent disabilities of workers. This analysis focuses on the prevention of disorders caused by: repeatability, duration and effort; And focuses on reducing cumulative trauma disorders such as occupational diseases using sensory thermography as a noninvasive method, the above is to evaluate the injuries could have workers to perform repetitive motions. Objectives: The aim is to define rest periods or job rotation before they generate a CTD, this sensory thermography by analyzing changes in temperature patterns on wrists and elbows when the worker is performing HRM over a period of time 2 hours and 30 minutes. Information on non-work variables such as wrist and elbow injuries, weight, gender, age, among others, and work variables such as temperature workspace, repetitiveness and duration also met. Methodology: The analysis to 4 industrial designers, 2 men and 2 women to be specific was conducted in a business in normal health for a period of 12 days, using the following time ranges: the first day for every 90 minutes continuous work were asked to rest 5 minutes, the second day for every 90 minutes of continuous work were asked to rest 10 minutes, the same to work 60 and 30 minutes straight. Each worker was tested with 6 different ranges at least twice. This analysis was performed in a controlled room temperature between 20 and 25 ° C, and a time to stabilize the temperature of the wrists and elbows than 20 minutes at the beginning and end of the analysis. Results: The range time of 90 minutes working continuous and a rest of 5 minutes of activity is where the maximum temperature (Tmax) was registered in the wrists and elbows in the office, we found the Tmax was 35.79 ° C with a difference of 2.79 ° C between the initial and final temperature of the left elbow presented at the individual 4 during the 86 minutes, in of range in 90 minutes continuously working and rested for 5 minutes of your activity. Conclusions: It is possible with this alternative technology is sensory thermography predict ranges of rotation or rest for the prevention of CTD to perform HRM work activities, obtaining with this reduce occupational disease, quotas by health agencies and increasing the quality of life of workers, taking this technology a cost-benefit acceptable in the future.Keywords: sensory thermography, temperature, cumulative trauma disorder (CTD), highly repetitive movement (HRM)
Procedia PDF Downloads 4297751 Polymeric Nanocarriers for Intranasal Delivery of Cannabidiol in Neurodevelopmental Disorders
Authors: Rania Awad, Avi Avital, Alejandro Sosnik
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Neurodevelopmental disorders, including autism spectrum disorder (ASD), affect 5.9% of the global population. Recently, research indicated the potential therapeutic use of cannabidiol (CBD) to treat different neurodevelopmental disorders, including ASD. Intranasal drug delivery (IN) is a non-invasive and painless administration route that enhances drug bioavailability in the brain by bypassing the blood-brain barrier. However, IN has limited bioavailability due to the low nasal mucosa permeability. Various polymeric nanoparticles (NPs) have been investigated for IN delivery with different successes. In this study, we investigate the nanoencapsulation of CBD within self-assembled polymeric NPs for nose-to-brain delivery in ASD to increase the bioavailability of CBD in the brain. The nanoencapsulation of CBD within self-assembled polymeric NPs, namely poly (ethylene oxide)-b-poly (propylene oxide)-b-poly (ethylene oxide) (PEO-PPO-PEO) polymeric micelles, was assessed. The CBD-loaded system was characterized by different methods. The compatibility was assessed in the nasal septum epithelium cell line Rpmi 2650. In vitro, permeability studies were conducted using Rpmi2650 cell monolayers cultured in semipermeable membranes 2650. The accumulation of CBD-loaded NPs labeled with near-infra-red fluorescent dye in the brain was measured after IN and oral administration after 20 and 45 min using IVIS spectrum CT imaging (IVIS-CT). Pharmacokinetic (PK) studies were conducted to assess the CBD concentration in rat plasma and brain tissues at different time points, PK parameters were measured and analyzed. Then, the effect of IN and oral administration of CBD-loaded NPs on a social cooperation test, which is a relevant behavioral test in the ASD model in rats, was investigated. Initially, we produced Pluronic® F127 polymeric micelles loaded with 25% w/w of CBD, with a size of 23 ± 1 nm, with suitable physical properties for IN administration. Then, Pluronic® F127 nanoparticles (F127 NPs) in the medium showed good compatibility and permeability in Rpmi 2650 cells. In the IVIS-CT study, the accumulation of IN administration of CBD-loaded F127 in the rat's brains was higher than the oral. Pharmacokinetic analysis of rat brain tissues revealed that, 20 minutes after administration, the concentration of CBD was higher following a 5 mg/kg nasal administration compared to a 15 mg/kg oral administration of CBD-loaded F127. Followed by IN administration of CBD-loaded F127 improved the social cooperation performance of the ASD model in rats as compared to oral and control groups.Keywords: drug delivery to the brain, Intranasal drug delivery, nanoencapsulation, neurodevelopmental disorders, polymeric nanoparticles.
Procedia PDF Downloads 27750 Health Risk Assessment of Trihalogenmethanes in Drinking Water
Authors: Lenka Jesonkova, Frantisek Bozek
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Trihalogenmethanes (THMs) are disinfection byproducts with non-carcinogenic and genotoxic effects. The contamination of 6 sites close to the water treatment plant has been monitored in second largest city of the Czech Republic. Health risk assessment including both non-carcinogenic and genotoxic risk for long term exposition was realized using the critical concentrations. Concentrations of trihalogenmethanes met national standards in all samples. Risk assessment proved that health risks from trihalogenmethanes are acceptable on each site.Keywords: drinking water, health risk assessment, trihalogenmethanes, water pollution
Procedia PDF Downloads 5207749 The EU Omnipotence Paradox: Inclusive Cultural Policies and Effects of Exclusion
Authors: Emmanuel Pedler, Elena Raevskikh, Maxime Jaffré
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Can the cultural geography of European cities be durably managed by European policies? To answer this question, two hypotheses can be proposed. (1) Either European cultural policies are able to erase cultural inequalities between the territories through the creation of new areas of cultural attractiveness in each beneficiary neighborhood, city or country. Or, (2) each European region historically rooted in a number of endogenous socio-historical, political or demographic factors is not receptive to exogenous political influences. Thus, the cultural attractiveness of a territory is difficult to measure and to impact by top-down policies in the long term. How do these two logics - European and local - interact and contribute to the emergence of a valued, popular sense of a common European cultural identity? Does this constant interaction between historical backgrounds and new political concepts encourage a positive identification with the European project? The European cultural policy programs, such as ECC (European Capital of Culture), seek to develop new forms of civic cohesion through inclusive and participative cultural events. The cultural assets of a city elected ‘ECC’ are mobilized to attract a wide range of new audiences, including populations poorly integrated into local cultural life – and consequently distant from pre-existing cultural offers. In the current context of increasingly heterogeneous individual perceptions of Europe, the ECC program aims to promote cultural forms and institutions that should accelerate both territorial and cross-border European cohesion. The new cultural consumption pattern is conceived to stimulate integration and mobility, but also to create a legitimate and transnational ideal European citizen type. Our comparative research confronts contrasting cases of ‘European Capitals of Culture’ from the south and from the north of Europe, cities recently concerned by the ECC political mechanism and cities that were elected ECC in the past, multi-centered cultural models vs. highly centralized cultural models. We aim to explore the impacts of European policies on the urban cultural geography, but also to understand the current obstacles for its efficient implementation.Keywords: urbanism, cultural policies, cultural institutions, european cultural capitals, heritage industries, exclusion effects
Procedia PDF Downloads 2617748 Dominant Correlation Effects in Atomic Spectra
Authors: Hubert Klar
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High double excitation of two-electron atoms has been investigated using hyperpherical coordinates within a modified adiabatic expansion technique. This modification creates a novel fictitious force leading to a spontaneous exchange symmetry breaking at high double excitation. The Pauli principle must therefore be regarded as approximation valid only at low excitation energy. Threshold electron scattering from high Rydberg states shows an unexpected time reversal symmetry breaking. At threshold for double escape we discover a broad (few eV) Cooper pair.Keywords: correlation, resonances, threshold ionization, Cooper pair
Procedia PDF Downloads 3487747 Monitoring Systemic Risk in the Hedge Fund Sector
Authors: Frank Hespeler, Giuseppe Loiacono
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We propose measures for systemic risk generated through intra-sectorial interdependencies in the hedge fund sector. These measures are based on variations in the average cross-effects of funds showing significant interdependency between their individual returns and the moments of the sector’s return distribution. The proposed measures display a high ability to identify periods of financial distress, are robust to modifications in the underlying econometric model and are consistent with intuitive interpretation of the results.Keywords: hedge funds, systemic risk, vector autoregressive model, risk monitoring
Procedia PDF Downloads 3257746 Effect of Cognitive Rehabilitation in Pediatric Population with Acquired Brain Injury: A Pilot Study
Authors: Carolina Beltran, Carlos De Los Reyes
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Acquired brain injury (ABI) is any physical and functional injury secondary to events that affect the brain tissue. It is one of the biggest causes of disability in the world and it has a high annual incidence in the pediatric population. There are several causes of ABI such as traumatic brain injury, central nervous system infection, stroke, hypoxia, tumors and others. The consequences can be cognitive, behavioral, emotional and functional. The cognitive rehabilitation is necessary to achieve the best outcomes for pediatric people with ABI. Cognitive orientation to daily occupational performance (CO-OP) is an individualized client-centered, performance-based, problem-solving approach that focuses on the strategy used to support the acquisition of three client-chosen goals. It has demonstrated improvements in the pediatric population with other neurological disorder but not in Spanish speakers with ABI. Aim: The main objective of this study was to determine the efficacy of cognitive orientation to daily occupational performances (CO-OP) adapted to Spanish speakers, in the level of independence and behavior in a pediatric population with ABI. Methods: Case studies with measure pre/post-treatment were used in three children with ABI, sustained at least before 6 months assessment, in school, aged 8 to 16 years, age ABI after 6 years old and above average intellectual ability. Twelve sessions of CO-OP adapted to Spanish speakers were used and videotaped. The outcomes were based on cognitive, behavior and functional independence measurements such as Child Behavior Checklist (CBCL), Behavior Rating Inventory of Executive Function (BRIEF), The Vineland Adaptive Behavior Scales (VINELAND, Social Support Scale (MOS-SSS) and others neuropsychological measures. This study was approved by the ethics committee of Universidad del Norte in Colombia. Informed parental written consent was obtained for all participants. Results: children were able to identify three goals and use the global strategy ‘goal-plan-do-check’ during each session. Verbal self-instruction was used by all children. CO-OP showed a clinically significant improvement in goals regarding with independence level and behavior according to parents and teachers. Conclusion: The results indicated that CO-OP and the use of a global strategy such as ‘goal-plan-do-check’ can be used in children with ABI in order to improve their specific goals. This is a preliminary version of a big study carrying in Colombia as part of the experimental design.Keywords: cognitive rehabilitation, acquired brain injury, pediatric population, cognitive orientation to daily occupational performance
Procedia PDF Downloads 1067745 The Climate Change and Soil Degradation in the Czech Republic
Authors: Miroslav Dumbrovsky
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The paper deals with impacts of climate change with the main emphasis on land degradation, agriculture and forestry management in the landscape. Land degradation, due to adverse effect of farmers activities, as a result of inappropriate conventional technologies, was a major issue in the Czech Republic during the 20th century and will remain for solving in the 21st century. The importance of land degradation is very high because of its impact on crop productivity and many other adverse effects. Land degradation through soil degradation is causing losses on crop productivity and quality of the environment, through decreasing quality of soil and water (especially water resources). Negative effects of conventional farming practices are increased water erosion, as well as crusting and compaction of the topsoil and subsoil. Soil erosion caused by water destructs the soil’s structure, reduces crop productivity due to deterioration in soil physical and chemical properties such as infiltration rate, water-holding capacity, loss of nutrients needed for crop production, and loss of soil carbon. Water erosion occurs on fields with row crops (maize, sunflower), especially during the rainfall period from April to October. Recently there is a serious problem of greatly expanded production of biofuels and bioenergy from field crops. The result is accelerated soil degradation. The damages (on and off- site) are greater than the benefits. An effective soil conservation requires an appropriate complex system of measures in the landscape. They are also important to continue to develop new sophisticated methods and technologies for decreasing land degradation. The system of soil conservation solving land degradation depend on the ability and the willingness of land users to apply them. When we talk about land degradation, it is not just a technical issue but also an economic and political issue. From a technical point of view, we have already made many positive steps, but for successful solving the problem of land degradation is necessary to develop suitable economic and political tools to increase the willingness and ability of land users to adopt conservation measures.Keywords: land degradation, soil erosion, soil conservation, climate change
Procedia PDF Downloads 3757744 Neuropsychological Assessment and Rehabilitation Settings for Developmental Dyslexia in Children in Greece: The Use of Music at Intervention Protocols
Authors: Argyris B. Karapetsas, Rozi M. Laskaraki, Aikaterini A. Karapetsa, Maria Bampou, Valentini N. Vamvaka
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The main aim of the current protocol is the contribution of neuropsychology in both assessment and rehabilitation settings for children with dyslexia. Objectives: The purpose of this study was to evaluate the significant role of neuropsychological assessment including both Psychometric and electrophysiological tests as well as to investigate the effectiveness of an Auditory Training program, designed via Music designed for children with Developmental Dyslexia (DD). Materials: In our study, participated 45 third-, and fourth-grade students with DD and a matched control group (n=45). Method: At the first phase of the protocol, children underwent a clinical assessment, including both electrophysiological, i.e. Event Related Potentials (ERPs) esp. P300 waveform, and psychometric tests, being conducted in Laboratory of Neuropsychology, at University of Thessaly, in Volos, Greece. Assessment’s results confirmed statistically significant lower performance for children with DD for all tests, compared to the typical readers of the control group. After evaluation, a subgroup of children with DD participated in a Rehabilitation Program including digitized musical auditory training activities. Results: The electrophysiological recordings after the intervention revealed shorter, almost similar, P300 latency values for children with DD to those of the control group, indicating the beneficial effects of the Intervention, thus enabling children develop reading skills and become successful readers. Discussion: Similar research data confirm the crucial role of neuropsychology in both diagnosis and treatment of common disorders, observed in children. Indeed, as for DD, there is growing evidence that brain activity dysfunction does occur, as it is confirmed by neuropsychological assessment and also musical auditory training may have remedial effects. Conclusions: The outcomes of the current study suggest that due to the neurobiological origin of DD, neuropsychology may give the means in both neuropsychological assessment and rehabilitation, enabling professionals to cope with cerebral dysfunction and recovery more efficiently.Keywords: diagnosis, dyslexia, ERPs, Music, neuropsychology, rehabilitation
Procedia PDF Downloads 1337743 Trends, Attitude, and Knowledge about the Methods of Labour Pain Management among Polish Women
Authors: Kinga Zebrowska, Maria Falis, Katarzyna Kosinska-Kaczynska, Bartosz Godek, Olga Plaza, Katarzyna Kwiatkowska
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Introduction: According to the ministerial decree of 16 August 2018, each woman in Poland during childbirth has the right to the pharmacological and non-pharmacological labour pain management (LPM). Aim: The aim of the study was to assess the knowledge of Polish mothers about pharmacological and non-pharmacological LPM, to investigate which methods they chose and their satisfaction with chosen ones. Material And Methods: A prospective cross-sectional study was performed among women who gave birth between 2015 and 2018. The self-composed questionnaire was distributed via the Internet in October 2018. Results: 13.727 women participated in the study. 75% have learned about LPM from the Internet. 68% of them did not gain any information on LPM from doctors during their prenatal appointments Safety of the newborn (46%), midwife’s advice (40%) and the chance of the immediate pain relief (39%) were the most important issues while choosing LPM. Respondents used a wide range of non-pharmacological methods, such as the assistance of partner during labour (81%), physical activity (58%), immersion in water (37%), relaxation techniques (15%) and others. 11% of mothers did not use any of the LPM methods. 52% of women declared that they wanted to use the pharmacological anaesthesia, while 49% had it performed (28% epidural, 16% inhaled anaesthesia, 5% parenteral opioids). Pharmacological methods were unavailable due to lack of anaesthesiologist in the maternity ward (41%) or inaccessibility of the chosen methods in the hospital (31%) and too advanced labour (43%). 48% of respondents did not decide to use pharmacological methods, because the pain was bearable (29%), anxiety of child’s health (17%), or belief that the pain is natural and it should not be avoided (16%). 83% of respondents believed that epidural analgesia has no influence on the time needed to gain a full cervix dilatation and 81% of them claimed that serious spinal cord injury is a common side effect of epidural. 51% believed that epidural increases the risk of caesarean section. Conclusions: The knowledge about the methods of LPM is not satisfactory. We should focus on well- maintained education guided by doctors, midwives, and media.Keywords: childbirth, labour pain management, maternity experiences, obstetrics
Procedia PDF Downloads 1527742 Lateral Buckling of Nanoparticle Additive Composite Beams
Authors: Gürkan Şakar, Akgün Alsaran, Emrah E. Özbaldan
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In this study, lateral buckling analysis of composite beams with particle additive was carried out experimentally and numerically. The effects of particle type, particle addition ratio on buckling loads of composite beams were determined. The numerical studies were performed with ANSYS package. In the analyses, clamped-free boundary condition was assumed. The load carrying capabilities of composite beams were influenced by different particle types and particle addition ratios.Keywords: lateral buckling, nanoparticle, composite beam, numeric analysis
Procedia PDF Downloads 4757741 Antimicrobial Effects and Phytochemical Analysis of Chrysophyllum Albidum Plant Parts (Leaves, Roots and Seeds) Extracts on Bacterial Isolates from Urinary Catheters
Authors: Ebere Christian Ugochukwu, Okafor Josephine, Oyawoye Tomisin
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The occurrence of multidrug resistance patterns that have been developed by bacteria has made it difficult to properly treat infections using standard clinical medications. Hence, the use of herbs as an alternative source of therapy is considered cheap and easily accessible to locals. This research explored the antimicrobial effects of aqueous and ethanolic extracts obtained from Chrysophyllum albidum (commonly called ‘Agbalumo’ in southwest Nigeria and ‘Udara’ in the eastern and southern parts of Nigeria) plant parts (leaves, roots and seeds) against bacteria isolated from urinary catheter tips. The following isolates were obtained; Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Proteus mirabilis, and Klebsiella aerogenes. The agar well diffusion method was used. The average percentages of antimicrobial resistance of the isolates to gentamycin were 45.5% for P. aeruginosa, 42.1% for E. coli, 46.9% for K. aerogenes, and ˃90% for other isolates. Qualitative phytochemical screening of the plant parts extracts was done using chemical test for the screening and identification of bioactive chemical constituents. The ethanolic extract mixtures (leaf, root and seed) had the greatest effect on all the isolates, with inhibition zones (IZs) ranging from 8-26 mm and MICs ranging from <16-32 mg/ml. The Potencies of the C. albidum extracts based on the IZ and MIC values were greater in the extract mixtures, followed by those in the roots. Phytochemical screening revealed that all the extracts contained phenol except for the seeds while tannins were present in all the extracts except the leaves. The activity of the ethanolic extracts of each part at high and low concentrations was greater than that of the aqueous extracts at the same concentrations (p<0.05). The acute toxicity results showed that the LD50 of the extracts was ˃5000 mg/body weight, indicating no toxicity. The antibacterial activities of the extract mixtures and roots on the isolates confirmed the use of C. albidum in folk medicine for the treatment of CAUTIs, hence indicating its antibacterial potential for use in novel antibiotic production.Keywords: antimicrobials, susceptibility, minimum inhibitory concentration, extracts
Procedia PDF Downloads 297740 Coils and Antennas Fabricated with Sewing Litz Wire for Wireless Power Transfer
Authors: Hikari Ryu, Yuki Fukuda, Kento Oishi, Chiharu Igarashi, Shogo Kiryu
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Recently, wireless power transfer has been developed in various fields. Magnetic coupling is popular for feeding power at a relatively short distance and at a lower frequency. Electro-magnetic wave coupling at a high frequency is used for long-distance power transfer. The wireless power transfer has attracted attention in e-textile fields. Rigid batteries are required for many body-worn electric systems at the present time. The technology enables such batteries to be removed from the systems. Flexible coils have been studied for such applications. Coils with a high Q factor are required in the magnetic-coupling power transfer. Antennas with low return loss are needed for the electro-magnetic coupling. Litz wire is so flexible to fabricate coils and antennas sewn on fabric and has low resistivity. In this study, the electric characteristics of some coils and antennas fabricated with the Litz wire by using two sewing techniques are investigated. As examples, a coil and an antenna are described. Both were fabricated with 330/0.04 mm Litz wire. The coil was a planar coil with a square shape. The outer side was 150 mm, the number of turns was 15, and the pitch interval between each turn was 5 mm. The Litz wire of the coil was overstitched with a sewing machine. The coil was fabricated as a receiver coil for a magnetic coupled wireless power transfer. The Q factor was 200 at a frequency of 800 kHz. A wireless power system was constructed by using the coil. A power oscillator was used in the system. The resonant frequency of the circuit was set to 123 kHz, where the switching loss of power FETs was small. The power efficiencies were 0.44 – 0.99, depending on the distance between the transmitter and receiver coils. As an example of an antenna with a sewing technique, a fractal pattern antenna was stitched on a 500 mm x 500 mm fabric by using a needle punch method. The pattern was the 2nd-oder Vicsec fractal. The return loss of the antenna was -28 dB at a frequency of 144 MHz.Keywords: e-textile, flexible coils and antennas, Litz wire, wireless power transfer
Procedia PDF Downloads 1337739 Interaction of Steel Slag and Zeolite on Ammonium Nitrogen Removal and Its Illumination on a New Carrier Filling Configuration for Constructed Wetlands
Authors: Hongtao Zhu, Dezhi Sun
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Nitrogen and phosphorus are essential nutrients for biomass growth. But excessive nitrogen and phosphorus can contribute to accelerated eutrophication of lakes and rivers. Constructed wetland is an efficient and eco-friendly wastewater treatment technology with low operating cost and low-energy consumption. Because of high affinity with ammonium ion, zeolite, as a common substrate, is applied in constructed wetlands worldwide. Another substrate seen commonly for constructed wetlands is steel slag, which has high contents of Ca, Al, or Fe, and possesses a strong affinity with phosphate. Due to the excellent ammonium removal ability of zeolite and phosphate removal ability of steel slag, they were considered to be combined in the substrate bed of a constructed wetland in order to enhance the simultaneous removal efficiencies of nitrogen and phosphorus. In our early tests, zeolite and steel slag were combined with each other in order to simultaneously achieve a high removal efficiency of ammonium-nitrogen and phosphate-phosphorus. However, compared with the results when only zeolite was used, the removal efficiency of ammonia was sharply decreased when zeolite and steel slag were used together. The main objective of this study was to establish an overview of the interaction of steel slag and zeolite on ammonium nitrogen removal. The CaO dissolution from slag, as well as the effects of influencing parameters (i.e. pH and Ca2+ concentration) on the ammonium adsorption onto zeolite, was systematically studied. Modeling results of Ca2+ and OH- release from slag indicated that pseudo-second order reaction had a better fitness than pseudo-first order reaction. Changing pH value from 7 to 12 would result in a drastic reduction of the ammonium adsorption capacity on zeolite, from the peak at pH7. High Ca2+ concentration in solution could also inhibit the adsorption of ammonium onto zeolite. The mechanism for steel slag inhibiting the ammonium adsorption capacity of zeolite includes: on one hand, OH- released from steel slag can react with ammonium ions to produce molecular form ammonia (NH3∙H2O), which would cause the dissociation of NH4+ from zeolite. On the other hand, Ca2+ could replace the NH4+ ions to adhere onto the surface of zeolite. An innovative substrate filling configuration that zeolite and steel slag are placed sequentially was proposed to eliminate the disadvantageous effects of steel slag. Experimental results showed that the novel filling configuration was superior to the other two contrast filling configurations in terms of ammonium removal.Keywords: ammonium nitrogen, constructed wetlands, steel slag, zeolite
Procedia PDF Downloads 2557738 The Confounding Role of Graft-versus-Host Disease in Animal Models of Cancer Immunotherapy: A Systematic Review
Authors: Hami Ashraf, Mohammad Heydarnejad
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Introduction: The landscape of cancer treatment has been revolutionized by immunotherapy, offering novel therapeutic avenues for diverse cancer types. Animal models play a pivotal role in the development and elucidation of these therapeutic modalities. Nevertheless, the manifestation of Graft-versus-Host Disease (GVHD) in such models poses significant challenges, muddling the interpretation of experimental data within the ambit of cancer immunotherapy. This study is dedicated to scrutinizing the role of GVHD as a confounding factor in animal models used for cancer immunotherapy, alongside proposing viable strategies to mitigate this complication. Method: Employing a systematic review framework, this study undertakes a comprehensive literature survey including academic journals in PubMed, Embase, and Web of Science databases and conference proceedings to collate pertinent research that delves into the impact of GVHD on animal models in cancer immunotherapy. The acquired studies undergo rigorous analysis and synthesis, aiming to assess the influence of GVHD on experimental results while identifying strategies to alleviate its confounding effects. Results: Findings indicate that GVHD incidence significantly skews the reliability and applicability of experimental outcomes, occasionally leading to erroneous interpretations. The literature surveyed also sheds light on various methodologies under exploration to counteract the GVHD dilemma, thereby bolstering the experimental integrity in this domain. Conclusion: GVHD's presence critically affects both the interpretation and validity of experimental findings, underscoring the imperative for strategies to curtail its confounding impacts. Current research endeavors are oriented towards devising solutions to this issue, aiming to augment the dependability and pertinence of experimental results. It is incumbent upon researchers to diligently consider and adjust for GVHD's effects, thereby enhancing the translational potential of animal model findings to clinical applications and propelling progress in the arena of cancer immunotherapy.Keywords: graft-versus-host disease, cancer immunotherapy, animal models, preclinical model
Procedia PDF Downloads 517737 Morphological Studies of the Gills of the Red Swamp Freshwater Crayfish Procambarus clarkii (Crustacea: Decapoda: Cambarids) (Girard 1852) from the River Nile and Its Branches in Egypt
Authors: Mohamed M. A. Abumandour
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The red swamp freshwater crayfish breathe through three types of feather-like trichobranchiate gills; podobranchiae, arthrobranchiae and pleurobranchiae. All gills have the same general structure and appearance; plume-like with single broad setiferous, and single axis. The gill consists of axis with numerous finger-like filaments, having three morphological types; round, pointed and somewhat hooked shaped. The direction of filaments vary according their position; in middle region were nearly perpendicular to gill axis while in the apex were nearly parallel to axis. There were characteristic system of gill spines on; central axis (two types were distinguishable by presence of socket), basal plate, setobranch (long non-branched and short multidenticulate) and on the bilobed epipodal plate. There are four shape of spinated-like distal region of setobranch seta; two pointed processes (longitudinal arrangement and irregular arranged) and two broad processes (transverse triangular and multidenticulate). The bilobed epipodal plate devoid from any filaments and extended from outer side of podobranchiae as triangular basal part then extended between the gills as cord-like middle part then pass under the gill to lies against the thoracic body wall. By SEM, the apical part of bilobed epipodal plate have serrated free border and corrugated surface while the middle part have none serrated free border. There are two methods of gill cleaning mechanism in crayfish; passive and active method. The passive method occurred by; setae of setobranch, branchiostegite, bilobed epipodal plate, setiferous arthrodial lamellae and reversing the respiratory water through a narrow spaced branchial chamber.Keywords: crayfis, gill spines, setobranch, gill setae, cleaning mechanisms
Procedia PDF Downloads 4107736 The Factors of Supply Chain Collaboration
Authors: Ghada Soltane
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The objective of this study was to identify factors impacting supply chain collaboration. a quantitative study was carried out on a sample of 84 Tunisian industrial companies. To verify the research hypotheses and test the direct effect of these factors on supply chain collaboration a multiple regression method was used using SPSS 26 software. The results show that there are four factors direct effects that affect supply chain collaboration in a meaningful and positive way, including: trust, engagement, information sharing and information qualityKeywords: supply chain collaboration, factors of collaboration, principal component analysis, multiple regression
Procedia PDF Downloads 497735 Antiproliferative and Apoptotic Effects of an Enantiomerically Pure β-Dipeptide Derivative through PI3K/Akt-Dependent and -Independent Pathways in Human Hormone-Refractory Prostate Cancer Cells
Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh
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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt
Procedia PDF Downloads 2827734 Health Risk Assessment of Exposing to Benzene in Office Building around a Chemical Industry Based on Numerical Simulation
Authors: Majid Bayatian, Mohammadreza Ashouri
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Releasing hazardous chemicals is one of the major problems for office buildings in the chemical industry and, therefore, environmental risks are inherent to these environments. The adverse health effects of the airborne concentration of benzene have been a matter of significant concern, especially in oil refineries. The chronic and acute adverse health effects caused by benzene exposure have attracted wide attention. Acute exposure to benzene through inhalation could cause headaches, dizziness, drowsiness, and irritation of the skin. Chronic exposures have reported causing aplastic anemia and leukemia at the occupational settings. Association between chronic occupational exposure to benzene and the development of aplastic anemia and leukemia were documented by several epidemiological studies. Numerous research works have investigated benzene emissions and determined benzene concentration at different locations of the refinery plant and stated considerable health risks. The high cost of industrial control measures requires justification through lifetime health risk assessment of exposed workers and the public. In the present study, a Computational Fluid Dynamics (CFD) model has been proposed to assess the exposure risk of office building around a refinery due to its release of benzene. For simulation, GAMBIT, FLUENT, and CFD Post software were used as pre-processor, processor, and post-processor, and the model was validated based on comparison with experimental results of benzene concentration and wind speed. Model validation results showed that the model is highly validated, and this model can be used for health risk assessment. The simulation and risk assessment results showed that benzene could be dispersion to an office building nearby, and the exposure risk has been unacceptable. According to the results of this study, a validated CFD model, could be very useful for decision-makers for control measures and possibly support them for emergency planning of probable accidents. Also, this model can be used to assess exposure to various types of accidents as well as other pollutants such as toluene, xylene, and ethylbenzene in different atmospheric conditions.Keywords: health risk assessment, office building, Benzene, numerical simulation, CFD
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