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148 A Microwave and Millimeter-Wave Transmit/Receive Switch Subsystem for Communication Systems
Authors: Donghyun Lee, Cam Nguyen
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Multi-band systems offer a great deal of benefit in modern communication and radar systems. In particular, multi-band antenna-array radar systems with their extended frequency diversity provide numerous advantages in detection, identification, locating and tracking a wide range of targets, including enhanced detection coverage, accurate target location, reduced survey time and cost, increased resolution, improved reliability and target information. An accurate calibration is a critical issue in antenna array systems. The amplitude and phase errors in multi-band and multi-polarization antenna array transceivers result in inaccurate target detection, deteriorated resolution and reduced reliability. Furthermore, the digital beam former without the RF domain phase-shifting is less immune to unfiltered interference signals, which can lead to receiver saturation in array systems. Therefore, implementing integrated front-end architecture, which can support calibration function with low insertion and filtering function from the farthest end of an array transceiver is of great interest. We report a dual K/Ka-band T/R/Calibration switch module with quasi-elliptic dual-bandpass filtering function implementing a Q-enhanced metamaterial transmission line. A unique dual-band frequency response is incorporated in the reception and calibration path of the proposed switch module utilizing the composite right/left-handed meta material transmission line coupled with a Colpitts-style negative generation circuit. The fabricated fully integrated T/R/Calibration switch module in 0.18-μm BiCMOS technology exhibits insertion loss of 4.9-12.3 dB and isolation of more than 45 dB in the reception, transmission and calibration mode of operation. In the reception and calibration mode, the dual-band frequency response centered at 24.5 and 35 GHz exhibits out-of-band rejection of more than 30 dB compared to the pass bands below 10.5 GHz and above 59.5 GHz. The rejection between the pass bands reaches more than 50 dB. In all modes of operation, the IP1-dB is between 4 and 11 dBm. Acknowledgement: This paper was made possible by NPRP grant # 6-241-2-102 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors.Keywords: microwaves, millimeter waves, T/R switch, wireless communications, wireless communications
Procedia PDF Downloads 160147 A Dynamic Cardiac Single Photon Emission Computer Tomography Using Conventional Gamma Camera to Estimate Coronary Flow Reserve
Authors: Maria Sciammarella, Uttam M. Shrestha, Youngho Seo, Grant T. Gullberg, Elias H. Botvinick
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Background: Myocardial perfusion imaging (MPI) is typically performed with static imaging protocols and visually assessed for perfusion defects based on the relative intensity distribution. Dynamic cardiac SPECT, on the other hand, is a new imaging technique that is based on time varying information of radiotracer distribution, which permits quantification of myocardial blood flow (MBF). In this abstract, we report a progress and current status of dynamic cardiac SPECT using conventional gamma camera (Infinia Hawkeye 4, GE Healthcare) for estimation of myocardial blood flow and coronary flow reserve. Methods: A group of patients who had high risk of coronary artery disease was enrolled to evaluate our methodology. A low-dose/high-dose rest/pharmacologic-induced-stress protocol was implemented. A standard rest and a standard stress radionuclide dose of ⁹⁹ᵐTc-tetrofosmin (140 keV) was administered. The dynamic SPECT data for each patient were reconstructed using the standard 4-dimensional maximum likelihood expectation maximization (ML-EM) algorithm. Acquired data were used to estimate the myocardial blood flow (MBF). The correspondence between flow values in the main coronary vasculature with myocardial segments defined by the standardized myocardial segmentation and nomenclature were derived. The coronary flow reserve, CFR, was defined as the ratio of stress to rest MBF values. CFR values estimated with SPECT were also validated with dynamic PET. Results: The range of territorial MBF in LAD, RCA, and LCX was 0.44 ml/min/g to 3.81 ml/min/g. The MBF between estimated with PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (p < 0.001). But the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (p = 0.037). The mean stress MBF value was significantly lower for angiographically abnormal than that for the normal (Normal Mean MBF = 2.49 ± 0.61, Abnormal Mean MBF = 1.43 ± 0. 0.62, P < .001). Conclusions: The visually assessed image findings in clinical SPECT are subjective, and may not reflect direct physiologic measures of coronary lesion. The MBF and CFR measured with dynamic SPECT are fully objective and available only with the data generated from the dynamic SPECT method. A quantitative approach such as measuring CFR using dynamic SPECT imaging is a better mode of diagnosing CAD than visual assessment of stress and rest images from static SPECT images Coronary Flow Reserve.Keywords: dynamic SPECT, clinical SPECT/CT, selective coronary angiograph, ⁹⁹ᵐTc-Tetrofosmin
Procedia PDF Downloads 150146 Biopolymers: A Solution for Replacing Polyethylene in Food Packaging
Authors: Sonia Amariei, Ionut Avramia, Florin Ursachi, Ancuta Chetrariu, Ancuta Petraru
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The food industry is one of the major generators of plastic waste derived from conventional synthetic petroleum-based polymers, which are non-biodegradable, used especially for packaging. These packaging materials, after the food is consumed, accumulate serious environmental concerns due to the materials but also to the organic residues that adhere to them. It is the concern of specialists, researchers to eliminate problems related to conventional materials that are not biodegradable or unnecessary plastic and replace them with biodegradable and edible materials, supporting the common effort to protect the environment. Even though environmental and health concerns will cause more consumers to switch to a plant-based diet, most people will continue to add more meat to their diet. The paper presents the possibility of replacing the polyethylene packaging from the surface of the trays for meat preparations with biodegradable packaging obtained from biopolymers. During the storage of meat products may occur deterioration by lipids oxidation and microbial spoilage, as well as the modification of the organoleptic characteristics. For this reason, different compositions of polymer mixtures and film conditions for obtaining must be studied to choose the best packaging material to achieve food safety. The compositions proposed for packaging are obtained from alginate, agar, starch, and glycerol as plasticizers. The tensile strength, elasticity, modulus of elasticity, thickness, density, microscopic images of the samples, roughness, opacity, humidity, water activity, the amount of water transferred as well as the speed of water transfer through these packaging materials were analyzed. A number of 28 samples with various compositions were analyzed, and the results showed that the sample with the highest values for hardness, density, and opacity, as well as the smallest water vapor permeability, of 1.2903E-4 ± 4.79E-6, has the ratio of components as alginate: agar: glycerol (3:1.25:0.75). The water activity of the analyzed films varied between 0.2886 and 0.3428 (aw< 0.6), demonstrating that all the compositions ensure the preservation of the products in the absence of microorganisms. All the determined parameters allow the appreciation of the quality of the packaging films in terms of mechanical resistance, its protection against the influence of light, the transfer of water through the packaging. Acknowledgments: This work was supported by a grant of the Ministry of Research, Innovation, and Digitization, CNCS/CCCDI – UEFISCDI, project number PN-III-P2-2.1-PED-2019-3863, within PNCDI III.Keywords: meat products, alginate, agar, starch, glycerol
Procedia PDF Downloads 167145 Effective Counseling Techniques Working with At-Risk Youth in Residential and Outpatient Settings
Authors: David A. Scott, Michelle G. Scott
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The problem of juvenile crime, school suspensions and oppositional behaviors indicates a need for a wide range of intervention programs for at-risk youth. Juvenile court systems and mental health agencies are examining alternative ways to deal with at-risk youth that will allow the adolescent to live within their home community. The previous trend that treatment away from home is more effective than treatment near one's community has shifted. Research now suggests that treatment be close to home for several reasons, such as increased treatment success, parental involvement, and reduced costs. Treatment options consist of a wide range of interventions, including outpatient, inpatient, and community-based services (therapeutic group homes, foster care and in-home preservation services). The juvenile justice system, families and other mental health agencies continue to seek the most effective treatment for at-risk youth in their communities. This research examines two possible treatment modalities, a multi-systemic outpatient program and a residential program. Research examining effective, evidence- based counseling will be discussed during this presentation. The presenter recently completed a three-year research grant examining effective treatment modalities for at-risk youth participating in a multi-systemic program. The presenter has also been involved in several research activities gathering data on effective techniques used in residential programs. The data and discussion will be broken down into two parts, each discussing one of the treatment modalities mentioned above. Data on the residential programs was collected on both a sample of 740 at- risk youth over a five-year period and also a sample of 63 participants during a one-year period residing in a residential programs. The effectiveness of these residential services was measured in three ways: services are evaluated by primary referral sources; follow-up data is obtained at various intervals after program participation to measure recidivism (what percentage got back into trouble with the Department of Juvenile Justice); and a more sensitive, "Offense Seriousness Score", has been computed and analyzed prior to, during and after treatment in the residential program. Data on the multi-systemic program was gathered over the past three years on 190 participants. Research will discuss pre and post test results, recidivism rates, academic performance, parental involvement, and effective counseling treatment modalities.Keywords: at-risk youth, group homes, therapeutic group homes, recidivism rates
Procedia PDF Downloads 81144 Multicenter Baseline Survey to Outline Antimicrobial Prescribing Practices at Six Public Sectortertiary Care Hospitals in a Low Middle Income Country
Authors: N. Khursheed, M. Fatima, S. Jamal, A. Raza, S. Rattani, Q. Ahsan, A. Rasheed, M. Jawed
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Introduction: Antibiotics are among the commonly prescribed medicines to treat bacterial infections. Their misuse intensifies resistance, and overuse incurs heavy losses to the healthcare system in terms of increased treatment costs and enhanced disease burden. Studies show that 40% of empirically used antibiotics are irrationally utilized. The objective of this study was to evaluate prescribing pattern of antibiotics at six public sector tertiary care hospitals across Pakistan. Methods: A multicenter cross-sectional point prevalence survey (PPS) was conducted in selected wards of six public sector tertiary care hospitals in Pakistan as part of the Clinical Engagement program by Fleming Fund Country Grant Pakistan in collaboration with Indus Hospital & Health Network (IHHN) from February to March 2021, these included Jinnah Postgraduate Medical Center and Dr. Ruth K. M. Pfau Civil Hospital from Karachi, Sheikh Zayed Hospital Lahore, Nishtar Medical University Hospital Multan, Medical Teaching Institute Hayatabad Medical Complex Peshawar, and Provincial Headquarters Hospital Gilgit. WHO PPS methodology was used for data collection (Hospital, ward, and patient level data was collected). Data was entered into the open-source Kobo Collect application and was analyzed using SPSS (version 22.0). Findings: Medical records of 837 in-patients were surveyed, of which the prevalence of antibiotics use was 78.5%. The most commonly prescribed antimicrobial was Ceftriaxone (21.7%) which is categorized in the Watch group of WHO AWaRe Classification, followed by Metronidazole (17.3%), Cefoperazone/Sulbactam (8.4%), Co-Amoxiclav (6.3%) and Piperacillin/Tazobactam (5.9%). The antibiotics were prescribed largely for surgical prophylaxis (36.7%), followed by community-acquired infections (24.7%). One antibiotic was prescribed to 46.7%, two to 39.9%, and three or more to 12.5 %. Two of six (30%) hospitals had functional drug and therapeutic committees, three (50%) had infection prevention and control committees, and one facility had an antibiotic formulary. Conclusion: Findings demonstrate high consumption of broad-spectrum antimicrobials and emphasizes the importance of expanding the antimicrobial stewardship program. Mentoring clinical teams will help to rationalize antimicrobial use.Keywords: antimicrobial resistance, antimicrobial stewardship, point prevalence survey, antibiotics
Procedia PDF Downloads 104143 Comparision of Neutrophil Response to Curvularia, Bipolaris and Aspergillus Species
Authors: Eszter J. Tóth, Alexandra Hoffmann, Csaba Vágvölgyi, Tamás Papp
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Members of the genera Curvularia and Bipolaris are closely related melanin producing filamentous fungi; both of them have the teleomorph states in genus Cochliobolus. While Bipolaris species infect only plants and may cause serious agriculture damages, some Curvularia species was recovered from opportunistic human infections. The human pathogenic species typically cause phaeohyphomycoses, i.e. mould infections caused by melanised fungi, which can manifest as invasive mycoses with frequent involvement of the central nervous system in immunocompromised patients or as local infections (e.g. keratitis, sinusitis, and cutaneous lesions) in immunocompetent people. Although their plant-fungal interactions have been intensively studied, there is only little information available about the human pathogenic feature of these fungi. The aim of this study was to investigate the neutrophil granulocytes’ response to hyphal forms of Curvularia and Bipolaris in comparison with the response to Aspergillus. In the present study Curvularia lunata SZMC 23759 and Aspergillus fumigatus SZMC 23245 both isolated from human eye infection, and Bipolaris zeicola BRIP 19582b isolated from plant leaf were examined. Neutrophils were isolated from heparinised venous blood of healthy donors with dextran sedimentation followed by centrifugation over Ficoll and hypotonic lysis of erythrocytes. Viability and purity of the cells were checked with trypan blue and Wright staining, respectively. Infection of neutrophils was carried out with germinated conidia in a ratio of 5:1. Production of hydrogen peroxide, superoxide anion, and nitrogen monoxide was measured both intracellularly and extracellularly in response to the germinated spores with or without the supernatant and after serum treatment. ROS and NOS production of neutrophils in interaction with the three fungi were compared. It is already known that Aspergillus species induce ROS production of neutrophils only after serum treatment. Although, in case of C. lunata, serum opsonisation also induced an intensive production of reactive species, lower level of production was measured in the lack of serum as well. After interaction with the plant pathogenic B. zeicola, amount of reactive species found to be similar with and without serum treatment. The presence of germination supernatant decreased the reactive species production in case of each fungus. Interaction with Curvularia, Bipolaris and Aspergillus species induced different response of neutrophils. It seems that recognition of C. lunata and B. zeicola is independent of serum opsonisation, albeit it increases the level of the produced reactive species in response for C. lunata. The study was supported by the grant LP2016-8/2016.Keywords: Curvularia, neutrophils, NOS, ROS, serum opsonisation
Procedia PDF Downloads 197142 Hydration of Three-Piece K Peptide Fragments Studied by Means of Fourier Transform Infrared Spectroscopy
Authors: Marcin Stasiulewicz, Sebastian Filipkowski, Aneta Panuszko
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Background: The hallmark of neurodegenerative diseases, including Alzheimer's and Parkinson's diseases, is an aggregation of the abnormal forms of peptides and proteins. Water is essential to functioning biomolecules, and it is one of the key factors influencing protein folding and misfolding. However, the hydration studies of proteins are complicated due to the complexity of protein systems. The use of model compounds can facilitate the interpretation of results involving larger systems. Objectives: The goal of the research was to characterize the properties of the hydration water surrounding the two three-residue K peptide fragments INS (Isoleucine - Asparagine - Serine) and NSR (Asparagine - Serine - Arginine). Methods: Fourier-transform infrared spectra of aqueous solutions of the tripeptides were recorded on Nicolet 8700 spectrometer (Thermo Electron Co.) Measurements were carried out at 25°C for varying molality of solute. To remove oscillation couplings from water spectra and, consequently, obtain narrow O-D semi-heavy water bands (HDO), the isotopic dilution method of HDO in H₂O was used. The difference spectra method allowed us to isolate the tripeptide-affected HDO spectrum. Results: The structural and energetic properties of water affected by the tripeptides were compared to the properties of pure water. The shift of the values of the gravity center of bands (related to the mean energy of water hydrogen bonds) towards lower values with respect to the ones corresponding to pure water suggests that the energy of hydrogen bonds between water molecules surrounding tripeptides is higher than in pure water. A comparison of the values of the mean oxygen-oxygen distances in water affected by tripeptides and pure water indicates that water-water hydrogen bonds are shorter in the presence of these tripeptides. The analysis of differences in oxygen-oxygen distance distributions between the tripeptide-affected water and pure water indicates that around the tripeptides, the contribution of water molecules with the mean energy of hydrogen bonds decreases, and simultaneously the contribution of strong hydrogen bonds increases. Conclusions: It was found that hydrogen bonds between water molecules in the hydration sphere of tripeptides are shorter and stronger than in pure water. It means that in the presence of the tested tripeptides, the structure of water is strengthened compared to pure water. Moreover, it has been shown that in the vicinity of the Asparagine - Serine - Arginine, water forms stronger and shorter hydrogen bonds. Acknowledgments: This work was funded by the National Science Centre, Poland (grant 2017/26/D/NZ1/00497).Keywords: amyloids, K-peptide, hydration, FTIR spectroscopy
Procedia PDF Downloads 178141 Generalized Synchronization in Systems with a Complex Topology of Attractor
Authors: Olga I. Moskalenko, Vladislav A. Khanadeev, Anastasya D. Koloskova, Alexey A. Koronovskii, Anatoly A. Pivovarov
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Generalized synchronization is one of the most intricate phenomena in nonlinear science. It can be observed both in systems with a unidirectional and mutual type of coupling including the complex networks. Such a phenomenon has a number of practical applications, for example, for the secure information transmission through the communication channel with a high level of noise. Known methods for the secure information transmission needs in the increase of the privacy of data transmission that arises a question about the observation of such phenomenon in systems with a complex topology of chaotic attractor possessing two or more positive Lyapunov exponents. The present report is devoted to the study of such phenomenon in two unidirectionally and mutually coupled dynamical systems being in chaotic (with one positive Lyapunov exponent) and hyperchaotic (with two or more positive Lyapunov exponents) regimes, respectively. As the systems under study, we have used two mutually coupled modified Lorenz oscillators and two unidirectionally coupled time-delayed generators. We have shown that in both cases the generalized synchronization regime can be detected by means of the calculation of Lyapunov exponents and phase tube approach whereas due to the complex topology of attractor the nearest neighbor method is misleading. Moreover, the auxiliary system approaches being the standard method for the synchronous regime observation, for the mutual type of coupling results in incorrect results. To calculate the Lyapunov exponents in time-delayed systems we have proposed an approach based on the modification of Gram-Schmidt orthogonalization procedure in the context of the time-delayed system. We have studied in detail the mechanisms resulting in the generalized synchronization regime onset paying a great attention to the field where one positive Lyapunov exponent has already been become negative whereas the second one is a positive yet. We have found the intermittency here and studied its characteristics. To detect the laminar phase lengths the method based on a calculation of local Lyapunov exponents has been proposed. The efficiency of the method has been verified using the example of two unidirectionally coupled Rössler systems being in the band chaos regime. We have revealed the main characteristics of intermittency, i.e. the distribution of the laminar phase lengths and dependence of the mean length of the laminar phases on the criticality parameter, for all systems studied in the report. This work has been supported by the Russian President's Council grant for the state support of young Russian scientists (project MK-531.2018.2).Keywords: complex topology of attractor, generalized synchronization, hyperchaos, Lyapunov exponents
Procedia PDF Downloads 275140 Gas-Phase Nondestructive and Environmentally Friendly Covalent Functionalization of Graphene Oxide Paper with Amines
Authors: Natalia Alzate-Carvajal, Diego A. Acevedo-Guzman, Victor Meza-Laguna, Mario H. Farias, Luis A. Perez-Rey, Edgar Abarca-Morales, Victor A. Garcia-Ramirez, Vladimir A. Basiuk, Elena V. Basiuk
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Direct covalent functionalization of prefabricated free-standing graphene oxide paper (GOP) is considered as the only approach suitable for systematic tuning of thermal, mechanical and electronic characteristics of this important class of carbon nanomaterials. At the same time, the traditional liquid-phase functionalization protocols can compromise physical integrity of the paper-like material up to its total disintegration. To avoid such undesirable effects, we explored the possibility of employing an alternative, solvent-free strategy for facile and nondestructive functionalization of GOP with two representative aliphatic amines, 1-octadecylamine (ODA) and 1,12-diaminododecane (DAD), as well as with two aromatic amines, 1-aminopyrene (AP) and 1,5-diaminonaphthalene (DAN). The functionalization was performed under moderate heating at 150-180 °C in vacuum. Under such conditions, it proceeds through both amidation and epoxy ring opening reactions. Comparative characterization of pristine and amine-functionalized GOP mats was carried out by using Fourier-transform infrared, Raman, and X-ray photoelectron spectroscopy (XPS), thermogravimetric (TGA) and differential thermal analysis, scanning electron and atomic force microscopy (SEM and AFM, respectively). Besides that, we compared the stability in water, wettability, electrical conductivity and elastic (Young's) modulus of GOP mats before and after amine functionalization. The highest content of organic species was obtained in the case of GOP-ODA, followed by GOP-DAD, GOP-AP and GOP-DAN samples. The covalent functionalization increased mechanical and thermal stability of GOP, as well as its electrical conductivity. The magnitude of each effect depends on the particular chemical structure of amine employed, which allows for tuning a given GOP property. Morphological characterization by using SEM showed that, compared to pristine graphene oxide paper, amine-modified GOP mats become relatively ordered layered assemblies, in which individual GO sheets are organized in a near-parallel pattern. Financial support from the National Autonomous University of Mexico (grants DGAPA-IN101118 and IN200516) and from the National Council of Science and Technology of Mexico (CONACYT, grant 250655) is greatly appreciated. The authors also thank David A. Domínguez (CNyN of UNAM) for XPS measurements and Dr. Edgar Alvarez-Zauco (Faculty of Science of UNAM) for the opportunity to use TGA equipment.Keywords: amines, covalent functionalization, gas-phase, graphene oxide paper
Procedia PDF Downloads 181139 Study of the Removal Efficiency of Azo-Dyes Using Xanthan as Sequestering Agent
Authors: Cedillo Ortiz Cesar Isaac, Marañón-Ruiz Virginia-Francisca, Lozano-Alvarez Juan Antonio, Jáuregui-Rincón Juan, Roger Chiu Zarate
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Introduction: The contamination of water with the azo-dye is a problem worldwide as although wastewater contaminate is treated in a municipal sewage system, still contain a considerable amount of dyes. In the present, there are different processes denominated tertiary method in which it is possible to lower the concentration of the dye. One of these methods is by adsorption onto various materials which can be organic or inorganic materials. The xanthan is a biomaterial as removal agents to decrease the dye content in aqueous solution. The Zimm-Bragg model described the experimental isotherms obtained when this biopolymer was used in the removal of textile dyes. Nevertheless, it was not established if a possible correlation between dye structure and removal efficiency exists. In this sense, the principal objective of this report is to propose a qualitative relationship between the structure of three azo-dyes (Congo Red (CR), Methyl Red (MR) and Methyl Orange (MO)) and their removal efficiency from aqueous environment when xanthan are used as dye sequestering agents. Methods: The dyes were subjected to different pH and ionic strength values to obtain the conditions of maximum dye removal. Afterward, these conditions were used to perform the adsorption isotherm as was reported in the previous study in our group. The Zimm-Bragg model was used to describe the experimental data and the parameters of nucleation (Ku) and cooperativity (U) were obtained by optimization using the R statistical software. The spectra from UV-Visible (aqueous solution), Infrared absorption and Raman spectroscopies (dry samples) were obtained from the biopolymer-dye complex. Results: The removal percent with xanthan in each dye are as follows: with CR had 99.98 % when the pH is 12 and ionic strength is 10.12, with MR had 84.79 % when the pH is 9.5 and ionic strength is 43 and finally the MO had 30 % in pH 4 and 72. It can be seen that when xanthan is used to remove the dyes, exists a lower dependence between structure and removal efficiency. This may be due to the different tendency to form aggregates of each dye. This aggregation capacity and the charge of each dye resulting from the pH and ionic strength values of aqueous solutions are key factors in the dye removal. The experimental isotherm of MR was only that adequately described by Zimm-Bragg model. Because with the CR had the 100 % of remove thus is very difficult obtain de experimental isotherm and finally MO had results fluctuating and therefore was impossible get the accurate data. Conclusions: The study of the removal of three dyes with xanthan as dye sequestering agents suggests that aggregation capacity of dyes and the charge resulting from structural characteristics such as molecular weight and functional groups have a relationship with the removal efficiency. Acknowledgements: We are gratefully acknowledged support for this project by Consejo Nacional de Ciencia y Tecnología, México (CONACyT, Grant No. 632694.)Keywords: adsorption, azo dyes, xanthan gum, Zimm Bragg theory
Procedia PDF Downloads 280138 The Effects of Myelin Basic Protein Charge Isomers on the Methyl Cycle Metabolites in Glial Cells
Authors: Elene Zhuravliova, Tamar Barbakadze, Irina Kalandadze, Elnari Zaalishvili, Lali Shanshiashvili, David Mikeladze
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Background: Multiple sclerosis (MS) is an inflammatory, neurodegenerative disease, which is accompanied by demyelination and autoimmune response to myelin proteins. Among post-translational modifications, which mediate the modulation of inflammatory pathways during MS, methylation is the main one. The methylation of DNA, also amino acids lysine and arginine, occurs in the cell. It was found that decreased trans-methylation is associated with neuroinflammatory diseases. Therefore, abnormal regulation of the methyl cycle could induce demyelination through the action on PAD (peptidyl-arginine-deiminase) gene promoter. PAD takes part in protein citrullination and targets myelin basic protein (MBP), which is affected during demyelination. To determine whether MBP charge isomers are changing the methyl cycle, we have estimated the concentrations of methyl cycle metabolites in MBP-activated primary astrocytes and oligodendrocytes. For this purpose, the action of the citrullinated MBP- C8 and the most cationic MBP-C1 isomers on the primary cells were investigated. Methods: Primary oligodendrocyte and astrocyte cell cultures were prepared from whole brains of 2-day-old Wistar rats. The methyl cycle metabolites, including homocysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH), were estimated by HPLC analysis using fluorescence detection and prior derivatization. Results: We found that the action of MBP-C8 and MBP-C1 induces a decrease in the concentration of both methyl cycle metabolites, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), in astrocytes compared to the control cells. As for oligodendrocytes, the concentration of SAM was increased by the addition of MBP-C1, while MBP-C8 has no significant effect. As for SAH, its concentration was increased compared to the control cells by the action of both MBP-C1 and MBP-C8. A significant increase in homocysteine concentration was observed by the action of the MBP-C8 isomer in both oligodendrocytes and astrocytes. Conclusion: These data suggest that MBP charge isomers change the concentration of methyl cycle metabolites. MBP-C8 citrullinated isomer causes elevation of homocysteine in astrocytes and oligodendrocytes, which may be the reason for decreased astrocyte proliferation and increased oligodendrocyte cell death which takes place in neurodegenerative processes. Elevated homocysteine levels and subsequent abnormal regulation of methyl cycles in oligodendrocytes possibly change the methylation of DNA that activates PAD gene promoter and induces the synthesis of PAD, which in turn provokes the process of citrullination, which is the accompanying process of demyelination. Acknowledgment: This research was supported by the SRNSF Georgia RF17_534 grant.Keywords: myelin basic protein, astrocytes, methyl cycle metabolites, homocysteine, oligodendrocytes
Procedia PDF Downloads 156137 Spectroscopic (Ir, Raman, Uv-Vis) and Biological Study of Copper and Zinc Complexes and Sodium Salt with Cichoric Acid
Authors: Renata Swislocka, Grzegorz Swiderski, Agata Jablonska-Trypuc, Wlodzimierz Lewandowski
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Forming a complex of a phenolic compound with a metal not only alters the physicochemical properties of the ligand (including increase in stability or changes in lipophilicity), but also its biological activity, including antioxidant, antimicrobial and many others. As part of our previous projects, we examined the physicochemical and antimicrobial properties of phenolic acids and their complexes with metals naturally occurring in foods. Previously we studied the complexes of manganese(II), copper(II), cadmium(II) and alkali metals with ferulic, caffeic and p-coumaric acids. In the framework of this study, the physicochemical and biological properties of cicoric acid, its sodium salt, and complexes with copper and zinc were investigated. Cichoric acid is a derivative of both caffeic acid and tartaric acid. It has first been isolated from Cichorium intybus (chicory) but also it occurs in significant amounts in Echinacea, particularly E. purpurea, dandelion leaves, basil, lemon balm and in aquatic plants, including algae and sea grasses. For the study of spectroscopic and biological properties of cicoric acid, its sodium salt, and complexes with zinc and copper a variety of methods were used. Studies of antioxidant properties were carried out in relation to selected stable radicals (method of reduction of DPPH and reduction of FRAP). As a result, the structure and spectroscopic properties of cicoric acid and its complexes with selected metals in the solid state and in the solutions were defined. The IR and Raman spectra of cicoric acid displayed a number of bands that were derived from vibrations of caffeic and tartaric acids moieties. At 1746 and 1716 cm-1 the bands assigned to the vibrations of the carbonyl group of tartaric acid occurred. In the spectra of metal complexes with cichoric these bands disappeared what indicated that metal ion was coordinated by the carboxylic groups of tartaric acid. In the spectra of the sodium salt, a characteristic wide-band vibrations of carboxylate anion occurred. In the spectra of cicoric acid and its salt and complexes, a number of bands derived from the vibrations of the aromatic ring (caffeic acid) were assigned. Upon metal-ligand attachment, the changes in the values of the wavenumbers of these bands occurred. The impact of metals on the antioxidant properties of cicoric acid was also examined. Cichoric acid has a high antioxidant potential. Complexation by metals (zinc, copper) did not significantly affect its antioxidant capacity. The work was supported by the National Science Centre, Poland (grant no. 2015/17/B/NZ9/03581).Keywords: chicoric acid, metal complexes, natural antioxidant, phenolic acids
Procedia PDF Downloads 337136 Weed Out the Bad Seeds: The Impact of Strategic Portfolio Management on Patent Quality
Authors: A. Lefebre, M. Willekens, K. Debackere
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Since the 1990s, patent applications have been booming, especially in the field of telecommunications. However, this increase in patent filings has been associated with an (alleged) decrease in patent quality. The plethora of low-quality patents devalues the high-quality ones, thus weakening the incentives for inventors to patent inventions. Despite the rich literature on strategic patenting, previous research has neglected to emphasize the importance of patent portfolio management and its impact on patent quality. In this paper, we compare related patent portfolios vs. nonrelated patents and investigate whether the patent quality and innovativeness differ between the two types. In the analyses, patent quality is proxied by five individual proxies (number of inventors, claims, renewal years, designated states, and grant lag), and these proxies are then aggregated into a quality index. Innovativeness is proxied by two measures: the originality and radicalness index. Results suggest that related patent portfolios have, on average, a lower patent quality compared to nonrelated patents, thus suggesting that firms use them for strategic purposes rather than for the extended protection they could offer. Even upon testing the individual proxies as a dependent variable, we find evidence that related patent portfolios are of lower quality compared to nonrelated patents, although not all results show significant coefficients. Furthermore, these proxies provide evidence of the importance of adding fixed effects to the model. Since prior research has found that these proxies are inherently flawed and never fully capture the concept of patent quality, we have chosen to run the analyses with individual proxies as supplementary analyses; however, we stick with the comprehensive index as our main model. This ensures that the results are not dependent upon one certain proxy but allows for multiple views of the concept. The presence of divisional applications might be linked to the level of innovativeness of the underlying invention. It could be the case that the parent application is so important that firms are going through the administrative burden of filing for divisional applications to ensure the protection of the invention and the preemption of competition. However, it could also be the case that the preempting is a result of divisional applications being used strategically as a backup plan and prolonging strategy, thus negatively impacting the innovation in the portfolio. Upon testing the level of novelty and innovation in the related patent portfolios by means of the originality and radicalness index, we find evidence for a significant negative association with related patent portfolios. The minimum innovation that has been brought on by the patents in the related patent portfolio is lower compared to the minimum innovation that can be found in nonrelated portfolios, providing evidence for the second argument.Keywords: patent portfolio management, patent quality, related patent portfolios, strategic patenting
Procedia PDF Downloads 94135 Correlation Between Cytokine Levels and Lung Injury in the Syrian Hamster (Mesocricetus Auratus) Covid-19 Model
Authors: Gleb Fomin, Kairat Tabynov, Nurkeldy Turebekov, Dinara Turegeldiyeva, Rinat Islamov
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The level of major cytokines in the blood of patients with COVID-19 varies greatly depending on age, gender, duration and severity of infection, and comorbidity. There are two clinically significant cytokines, IL-6 and TNF-α, which increase in levels in patients with severe COVID-19. However, in a model of COVID-19 in hamsters, TNF-α levels are unchanged or reduced, while the expression of other cytokines reflects the profile of cytokines found in patients’ plasma. The aim of our study was to evaluate the relationship between the level of cytokines in the blood, lungs, and lung damage in the model of the Syrian hamster (Mesocricetus auratus) infected with the SARS-CoV-2 strain. The study used outbred female and male Syrian hamsters (n=36, 4 groups) weighing 80-110 g and 5 months old (protocol IACUC, #4, 09/22/2020). Animals were infected intranasally with the hCoV-19/Kazakhstan/KazNAU-NSCEDI-481/2020 strain and euthanized at 3 d.p.i. The level of cytokines IL-6, TNF-α, IFN-α, and IFN-γ was determined by ELISA MyBioSourse (USA) for hamsters. Lung samples were subjected to histological processing. The presence of pathological changes in histological preparations was assessed on a 3-point scale. The work was carried out in the ABSL-3 laboratory. The data were analyzed in GraphPad Prism 6.00 (GraphPad Software, La Jolla, California, USA). The work was supported by the MES RK grant (AP09259865). In the blood, the level of TNF-α increased in males (p=0.0012) and IFN-γ in males and females (p=0.0001). On the contrary, IFN-α production decreased (p=0.0006). Only TNF-α level increased in lung tissues (p=0.0011). Correlation analysis showed a negative relationship between the level of IL-6 in the blood and lung damage in males (r -0.71, p=0.0001) and females (r-0.57, p=0.025). On the contrary, in males, the level of IL-6 in the lungs and score is positively correlated (r 0.80, p=0.01). The level of IFN-γ in the blood (r -0.64, p=0.035) and lungs (r-0.72, p=0.017) in males has a negative correlation with lung damage. No links were found for TNF-α and IFN-α. The study showed a positive association between lung injury and tissue levels of IL-6 in male hamsters. It is known that in humans, high concentrations of IL-6 in the lungs are associated with suppression of cellular immunity and, as a result, with an increase in the severity of COVID-19. TNF-α and IFN-γ play a key role in the pathogenesis of COVID-19 in hamsters. However, the mechanisms of their activity require more detailed study. IFN-α plays a lesser role in direct lung injury in a Syrian hamster model. We have shown the significance of tissue IL-6 and IFN-γ as predictors of the severity of lung damage in COVID-19 in the Syrian hamster model. Changes in the level of cytokines in the blood may not always reflect pathological processes in the lungs with COVID-19.Keywords: syrian hamster, COVID-19, cytokines, biological model
Procedia PDF Downloads 92134 Reintegrating Forensic Mental Health Service Users into Communities in the Western Cape, South Africa
Authors: Zolani Metu
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The death of more than 140 psychiatric patients who were unethically deinstitutionalized from the Life Esidimeni hospital Johannesburg, in 2016, shined a light on South Africa’s failing public mental healthcare system. Compounded by insufficient research evidence on African deinstitutionalization, this necessitates inquiries into deinstitutionalized mental healthcare, reintegration and community-based mental healthcare within the South African context. This study employed a quantitative research approach which utilized a cross-sectional research design, to investigate experiences with the reintegration of institutionalized forensic mental health service users into communities in the Western Cape, South Africa. A convenience sample of 100 mental health care workers from different occupational and organizational backgrounds in the Western Cape was purposively selected using the Western Cape Health Directorate as a sampling frame. A self-administered questionnaire (SAQ) was used as the data collection instrument. The results of the study indicate that criminogenic factors such as substance use, history of violent behaviour, criminal history and disruptive social behaviour complicate the reintegration of forensic mental health service users into communities. The current extent of reintegration of forensic mental health service users was found to be 'poor' (46%; n= 46); and financial difficulties, criminogenic factors and limited Community-Based Care (CBC) facilities were identified as key barriers to the reintegration process. 56% of all job applications for forensic mental health service users were unsuccessful, and 53% of all applications for their admission into CBC facilities were declined. Although social support (informal) was found to be essential for successful reintegration, institutional support (formal) through assertive community treatment (35%; n= 35) and CBC facilities (21%) and the disability grant (DG=50%) was found to be more important for family coping and reintegration. Moreover, 72% of respondents had positive perceptions about the process of reintegration; no statistically significant relationship was found between years of experience and perceptions about reintegration (P-value = 0.062); and perceptions were not found to be a barrier to reintegration. No statistically significant relationship was found between years of working experience and understanding the legislative framework of deinstitutionalization (P-Value =.0.061). However, using a Chi-square test, a significant relationship (P-value = 0.021) was found between sex and understanding the legal framework involved in the process of reintegration. The study recommends a post-2020 deinstitutionalization agenda that factors-in criminogenic realities associated with forensic mental health service users, and affirms the strengthening of PHC and community based care systems as precedents of successful deinstitutionalization and reintegration of mental health service users.Keywords: forensic mental health, deinstitutionalization, reintegration, mental health service users
Procedia PDF Downloads 165133 The Growth Role of Natural Gas Consumption for Developing Countries
Authors: Tae Young Jin, Jin Soo Kim
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Carbon emissions have emerged as global concerns. Intergovernmental Panel of Climate Change (IPCC) have published reports about Green House Gases (GHGs) emissions regularly. United Nations Framework Convention on Climate Change (UNFCCC) have held a conference yearly since 1995. Especially, COP21 held at December 2015 made the Paris agreement which have strong binding force differently from former COP. The Paris agreement was ratified as of 4 November 2016, they finally have legal binding. Participating countries set up their own Intended Nationally Determined Contributions (INDC), and will try to achieve this. Thus, carbon emissions must be reduced. The energy sector is one of most responsible for carbon emissions and fossil fuels particularly are. Thus, this paper attempted to examine the relationship between natural gas consumption and economic growth. To achieve this, we adopted the Cobb-Douglas production function that consists of natural gas consumption, economic growth, capital, and labor using dependent panel analysis. Data were preprocessed with Principal Component Analysis (PCA) to remove cross-sectional dependency which can disturb the panel results. After confirming the existence of time-trended component of each variable, we moved to cointegration test considering cross-sectional dependency and structural breaks to describe more realistic behavior of volatile international indicators. The cointegration test result indicates that there is long-run equilibrium relationship between selected variables. Long-run cointegrating vector and Granger causality test results show that while natural gas consumption can contribute economic growth in the short-run, adversely affect in the long-run. From these results, we made following policy implications. Since natural gas has positive economic effect in only short-run, the policy makers in developing countries must consider the gradual switching of major energy source, from natural gas to sustainable energy source. Second, the technology transfer and financing business suggested by COP must be accelerated. Acknowledgement—This work was supported by the Energy Efficiency & Resources Core Technology Program of the Korea Institute of Energy Technology Evaluation and Planning (KETEP) granted financial resource from the Ministry of Trade, Industry & Energy, Republic of Korea (No. 20152510101880) and by the National Research Foundation of Korea Grant funded by the Korean Government (NRF-205S1A3A2046684).Keywords: developing countries, economic growth, natural gas consumption, panel data analysis
Procedia PDF Downloads 234132 Effect of Hypoxia on AOX2 Expression in Chlamydomonas reinhardtii
Authors: Maria Ostroukhova, Zhanneta Zalutskaya, Elena Ermilova
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The alternative oxidase (AOX) mediates cyanide-resistant respiration, which bypasses proton-pumping complexes III and IV of the cytochrome pathway to directly transfer electrons from reduced ubiquinone to molecular oxygen. In Chlamydomonas reinhardtii, AOX is a monomeric protein that is encoded by two genes of discrete subfamilies, AOX1 and AOX2. Although AOX has been proposed to play essential roles in stress tolerance of organisms, the role of subfamily AOX2 is largely unknown. In C. reinhardtii, AOX2 was initially identified as one of constitutively low expressed genes. Like other photosynthetic organisms C. reinhardtii cells frequently experience periods of hypoxia. To examine AOX2 transcriptional regulation and role of AOX2 in hypoxia adaptation, real-time PCR analysis and artificial microRNA method were employed. Two experimental approaches have been used to induce the anoxic conditions: dark-anaerobic and light-anaerobic conditions. C. reinhardtii cells exposed to the oxygen deprivation have shown increased AOX2 mRNA levels. By contrast, AOX1 was not an anoxia-responsive gene. In C. reinhardtii, a subset of genes is regulated by transcription factor CRR1 in anaerobic conditions. Notable, the AOX2 promoter region contains the potential motif for CRR1 binding. Therefore, the role of CRR1 in the control of AOX2 transcription was tested. The CRR1-underexpressing strains, that were generated and characterized in this work, exhibited low levels of AOX2 transcripts under anoxic conditions. However, the transformants still slightly induced AOX2 gene expression in the darkness. These confirmed our suggestions that darkness is a regulatory stimulus for AOX genes in C. reinhardtii. Thus, other factors must contribute to AOX2 promoter activity under dark-anoxic conditions. Moreover, knock-down of CRR1 caused a complete reduction of AOX2 expression under light-anoxic conditions. These results indicate that (1) CRR1 is required for AOX2 expression during hypoxia, and (2) AOX2 gene is regulated by CRR1 together with yet-unknown regulatory factor(s). In addition, the AOX2-underexpressing strains were generated. The analysis of amiRNA-AOX2 strains suggested a role of this alternative oxidase in hypoxia adaptation of the alga. In conclusion, the results reported here show that C. reinhardtii AOX2 gene is stress inducible. CRR1 transcriptional factor is involved in the regulation of the AOX2 gene expression in the absence of oxygen. Moreover, AOX2 but not AOX1 functions under oxygen deprivation. This work was supported by Russian Science Foundation (research grant № 16-14-10004).Keywords: alternative oxidase 2, artificial microRNA approach, chlamydomonas reinhardtii, hypoxia
Procedia PDF Downloads 241131 Investigation of the Carbon Dots Optical Properties Using Laser Scanning Confocal Microscopy and TimE-resolved Fluorescence Microscopy
Authors: M. S. Stepanova, V. V. Zakharov, P. D. Khavlyuk, I. D. Skurlov, A. Y. Dubovik, A. L. Rogach
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Carbon dots are small carbon-based spherical nanoparticles, which are typically less than 10 nm in size that can be modified with surface passivation and heteroatoms doping. The light-absorbing ability of carbon dots has attracted a significant amount of attention in photoluminescence for bioimaging and fluorescence sensing applications owing to their advantages, such as tunable fluorescence emission, photo- and thermostability and low toxicity. In this study, carbon dots were synthesized by the solvothermal method from citric acid and ethylenediamine dissolved in water. The solution was heated for 5 hours at 200°C and then cooled down to room temperature. The carbon dots films were obtained by evaporation from a high-concentration aqueous solution. The increase of both luminescence intensity and light transmission was obtained as a result of a 405 nm laser exposure to a part of the carbon dots film, which was detected using a confocal laser scanning microscope (LSM 710, Zeiss). Blueshift up to 35 nm of the luminescence spectrum is observed as luminescence intensity, which is increased more than twofold. The exact value of the shift depends on the time of the laser exposure. This shift can be caused by the modification of surface groups at the carbon dots, which are responsible for long-wavelength luminescence. In addition, a shift of the absorption peak by 10 nm and a decrease in the optical density at the wavelength of 350 nm is detected, which is responsible for the absorption of surface groups. The obtained sample was also studied with time-resolved confocal fluorescence microscope (MicroTime 100, PicoQuant), which made it possible to receive a time-resolved photoluminescence image and construct emission decays of the laser-exposed and non-exposed areas. 5 MHz pulse rate impulse laser has been used as a photoluminescence excitation source. Photoluminescence decay was approximated by two exhibitors. The laser-exposed area has the amplitude of the first-lifetime component (A1) twice as much as before, with increasing τ1. At the same time, the second-lifetime component (A2) decreases. These changes evidence a modification of the surface groups of carbon dots. The detected effect can be used to create thermostable fluorescent marks, the physical size of which is bounded by the diffraction limit of the optics (~ 200-300 nm) used for exposure and to improve the optical properties of carbon dots or in the field of optical encryption. Acknowledgements: This work was supported by the Ministry of Science and Higher Education of Russian Federation, goszadanie no. 2019-1080 and financially supported by Government of Russian Federation, Grant 08-08.Keywords: carbon dots, photoactivation, optical properties, photoluminescence and absorption spectra
Procedia PDF Downloads 165130 Advancing Trustworthy Human-robot Collaboration: Challenges and Opportunities in Diverse European Industrial Settings
Authors: Margarida Porfírio Tomás, Paula Pereira, José Manuel Palma Oliveira
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The decline in employment rates across sectors like industry and construction is exacerbated by an aging workforce. This has far-reaching implications for the economy, including skills gaps, labour shortages, productivity challenges due to physical limitations, and workplace safety concerns. To sustain the workforce and pension systems, technology plays a pivotal role. Robots provide valuable support to human workers, and effective human-robot interaction is essential. FORTIS, a Horizon project, aims to address these challenges by creating a comprehensive Human-Robot Interaction (HRI) solution. This solution focuses on multi-modal communication and multi-aspect interaction, with a primary goal of maintaining a human-centric approach. By meeting the needs of both human workers and robots, FORTIS aims to facilitate efficient and safe collaboration. The project encompasses three key activities: 1) A Human-Centric Approach involving data collection, annotation, understanding human behavioural cognition, and contextual human-robot information exchange. 2) A Robotic-Centric Focus addressing the unique requirements of robots during the perception and evaluation of human behaviour. 3) Ensuring Human-Robot Trustworthiness through measures such as human-robot digital twins, safety protocols, and resource allocation. Factor Social, a project partner, will analyse psycho-physiological signals that influence human factors, particularly in hazardous working conditions. The analysis will be conducted using a combination of case studies, structured interviews, questionnaires, and a comprehensive literature review. However, the adoption of novel technologies, particularly those involving human-robot interaction, often faces hurdles related to acceptance. To address this challenge, FORTIS will draw upon insights from Social Sciences and Humanities (SSH), including risk perception and technology acceptance models. Throughout its lifecycle, FORTIS will uphold a human-centric approach, leveraging SSH methodologies to inform the design and development of solutions. This project received funding from European Union’s Horizon 2020/Horizon Europe research and innovation program under grant agreement No 101135707 (FORTIS).Keywords: skills gaps, productivity challenges, workplace safety, human-robot interaction, human-centric approach, social sciences and humanities, risk perception
Procedia PDF Downloads 52129 Production of Ferroboron by SHS-Metallurgy from Iron-Containing Rolled Production Wastes for Alloying of Cast Iron
Authors: G. Zakharov, Z. Aslamazashvili, M. Chikhradze, D. Kvaskhvadze, N. Khidasheli, S. Gvazava
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Traditional technologies for processing iron-containing industrial waste, including steel-rolling production, are associated with significant energy costs, the long duration of processes, and the need to use complex and expensive equipment. Waste generated during the industrial process negatively affects the environment, but at the same time, it is a valuable raw material and can be used to produce new marketable products. The study of the effectiveness of self-propagating high-temperature synthesis (SHS) methods, which are characterized by the simplicity of the necessary equipment, the purity of the final product, and the high processing speed, is under the wide scientific and practical interest to solve the set problem. The work presents technological aspects of the production of Ferro boron by the method of SHS - metallurgy from iron-containing wastes of rolled production for alloying of cast iron and results of the effect of alloying element on the degree of boron assimilation with liquid cast iron. Features of Fe-B system combustion have been investigated, and the main parameters to control the phase composition of synthesis products have been experimentally established. Effect of overloads on patterns of cast ligatures formation and mechanisms structure formation of SHS products was studied. It has been shown that an increase in the content of hematite Fe₂O₃ in iron-containing waste leads to an increase in the content of phase FeB and, accordingly, the amount of boron in the ligature. Boron content in ligature is within 3-14%, and the phase composition of obtained ligatures consists of Fe₂B and FeB phases. Depending on the initial composition of the wastes, the yield of the end product reaches 91 - 94%, and the extraction of boron is 70 - 88%. Combustion processes of high exothermic mixtures allow to obtain a wide range of boron-containing ligatures from industrial wastes. In view of the relatively low melting point of the obtained SHS-ligature, the positive dynamics of boron absorption by liquid iron is established. According to the obtained data, the degree of absorption of the ligature by alloying gray cast iron at 1450°C is 80-85%. When combined with the treatment of liquid cast iron with magnesium, followed by alloying with the developed ligature, boron losses are reduced by 5-7%. At that, uniform distribution of boron micro-additives in the volume of treated liquid metal is provided. Acknowledgment: This work was supported by Shota Rustaveli Georgian National Science Foundation of Georgia (SRGNSFG) under the GENIE project (grant number № CARYS-19-802).Keywords: self-propagating high-temperature synthesis, cast iron, industrial waste, ductile iron, structure formation
Procedia PDF Downloads 123128 An Analysis of Possible Implications of Patent Term Extension in Pharmaceutical Sector on Indian Consumers
Authors: Anandkumar Rshindhe
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Patents are considered as good monopoly in India. It is a mechanism by which the inventor is encouraged to do invention and also to make available to the society at large with a new useful technology. Patent system does not provide any protection to the invention itself but to the claims (rights) which the patentee has identified in relation to his invention. Thus the patentee is granted monopoly to the extent of his recognition of his own rights in the form of utilities and all other utilities of invention are for the public. Thus we find both benefit to the inventor and the public at large that is the ultimate consumer. But developing any such technology is not free of cost. Inventors do a lot of investment in the coming out with a new technologies. One such example if of Pharmaceutical industries. These pharmaceutical Industries do lot of research and invest lot of money, time and labour in coming out with these invention. Once invention is done or process identified, in order to protect it, inventors approach Patent system to protect their rights in the form of claim over invention. The patent system takes its own time in giving recognition to the invention as patent. Even after the grant of patent the pharmaceutical companies need to comply with many other legal formalities to launch it as a drug (medicine) in market. Thus major portion in patent term is unproductive to patentee and whatever limited period the patentee gets would be not sufficient to recover the cost involved in invention and as a result price of patented product is raised very much, just to recover the cost of invent. This is ultimately a burden on consumer who is paying more only because the legislature has failed to provide for the delay and loss caused to patentee. This problem can be effectively remedied if Patent Term extension is done. Due to patent term extension, the inventor gets some more time in recovering the cost of invention. Thus the end product is much more cheaper compared to non patent term extension.The basic question here arises is that when the patent period granted to a patentee is only 20 years and out of which a major portion is spent in complying with necessary legal formalities before making the medicine available in market, does the company with the limited period of monopoly recover its investment made for doing research. Further the Indian patent Act has certain provisions making it mandatory on the part of patentee to make its patented invention at reasonable affordable price in India. In the light of above questions whether extending the term of patent would be a proper solution and a necessary requirement to protect the interest of patentee as well as the ultimate consumer. The basic objective of this paper would be to check the implications of Extending the Patent term on Indian Consumers. Whether it provides the benefits to the patentee, consumer or a hardship to the Generic industry and consumer.Keywords: patent term extention, consumer interest, generic drug industry, pharmaceutical industries
Procedia PDF Downloads 451127 Autophagy in the Midgut Epithelium of Spodoptera exigua Hübner (Lepidoptera: Noctuidae) Larvae Exposed to Various Cadmium Concentration - 6-Generational Exposure
Authors: Magdalena Maria Rost-Roszkowska, Alina Chachulska-Żymełka, Monika Tarnawska, Maria Augustyniak, Alina Kafel, Agnieszka Babczyńska
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Autophagy is a form of cell remodeling in which an internalization of organelles into vacuoles that are called autophagosomes occur. Autophagosomes are the targets of lysosomes, thus causing digestion of cytoplasmic components. Eventually, it can lead to the death of the entire cell. However, in response to several stress factors, e.g., starvation, heavy metals (e.g., cadmium) autophagy can also act as a pro-survival factor, protecting the cell against its death. The main aim of our studies was to check if the process of autophagy, which could appear in the midgut epithelium after Cd treatment, can be fixed during the following generations of insects. As a model animal, we chose the beet armyworm Spodoptera exigua Hübner (Lepidoptera: Noctuidae), a well-known polyphagous pest of many vegetable crops. We analyzed specimens at final larval stage (5th larval stage), due to its hyperfagy, resulting in great amount of cadmium assimilate. The culture consisted of two strains: a control strain (K) fed a standard diet, and a cadmium strain (Cd), fed on standard diet supplemented with cadmium (44 mg Cd per kg of dry weight of food) for 146 generations, both strains. In addition, the control insects were transferred to the Cd supplemented diet (5 mg Cd per kg of dry weight of food, 10 mg Cd per kg of dry weight of food, 20 mg Cd per kg of dry weight of food, 44 mg Cd per kg of dry weight of food). Therefore, we obtained Cd1, Cd2, Cd3 and KCd experimental groups. Autophagy has been examined using transmission electron microscope. During this process, degenerated organelles were surrounded by a membranous phagophore and enclosed in an autophagosome. Eventually, after the autophagosome fused with a lysosome, an autolysosome was formed and the process of the digestion of organelles began. During the 1st year of the experiment, we analyzed specimens of 6 generations in all the lines. The intensity of autophagy depends significantly on the generation, tissue and cadmium concentration in the insect rearing medium. In the Ist, IInd, IIIrd, IVth, Vth and VIth generation the intensity of autophagy in the midguts from cadmium-exposed strains decreased gradually according to the following order of strains: Cd1, Cd2, Cd3 and KCd. The higher amount of cells with autophagy was observed in Cd1 and Cd2. However, it was still higher than the percentage of cells with autophagy in the same tissues of the insects from the control and multigenerational cadmium strain. This may indicate that during 6-generational exposure to various Cd concentration, a preserved tolerance to cadmium was not maintained. The study has been financed by the National Science Centre Poland, grant no 2016/21/B/NZ8/00831.Keywords: autophagy, cell death, digestive system, ultrastructure
Procedia PDF Downloads 233126 Exposure to Radon on Air in Tourist Caves in Bulgaria
Authors: Bistra Kunovska, Kremena Ivanova, Jana Djounova, Desislava Djunakova, Zdenka Stojanovska
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The carcinogenic effects of radon as a radioactive noble gas have been studied and show a strong correlation between radon exposure and lung cancer occurrence, even in the case of low radon levels. The major part of the natural radiation dose in humans is received by inhaling radon and its progenies, which originates from the decay chain of U-238. Indoor radon poses a substantial threat to human health when build-up occurs in confined spaces such as homes, mines and caves and the risk increases with the duration of radon exposure and is proportional to both the radon concentration and the time of exposure. Tourist caves are a case of special environmental conditions that may be affected by high radon concentration. Tourist caves are a recognized danger in terms of radon exposure to cave workers (guides, employees working in shops built above the cave entrances, etc.), but due to the sensitive nature of the cave environment, high concentrations cannot be easily removed. Forced ventilation of the air in the caves is considered unthinkable due to the possible harmful effects on the microclimate, flora and fauna. The risks to human health posed by exposure to elevated radon levels in caves are not well documented. Various studies around the world often detail very high concentrations of radon in caves and exposure of employees but without a follow-up assessment of the overall impact on human health. This study was developed in the implementation of a national project to assess the potential health effects caused by exposure to elevated levels of radon in buildings with public access under the National Science Fund of Bulgaria, in the framework of grant No КП-06-Н23/1/07.12.2018. The purpose of the work is to assess the radon level in Bulgarian caves and the exposure of the visitors and workers. The number of caves (sampling size) was calculated for simple random selection from total available caves 65 (sampling population) are 13 caves with confidence level 95 % and confidence interval (margin of error) approximately 25 %. A measurement of the radon concentration in air at specific locations in caves was done by using CR-39 type nuclear track-etch detectors that were placed by the participants in the research team. Despite the fact that all of the caves were formed in karst rocks, the radon levels were rather different from each other (97–7575 Bq/m3). An assessment of the influence of the orientation of the caves in the earth's surface (horizontal, inclined, vertical) on the radon concentration was performed. Evaluation of health hazards and radon risk exposure causing by inhaling the radon and its daughter products in each surveyed caves was done. Reducing the time spent in the cave has been recommended in order to decrease the exposure of workers.Keywords: tourist caves, radon concentration, exposure, Bulgaria
Procedia PDF Downloads 189125 Providing Health Promotion Information by Digital Animation to International Visitors in Japan: A Factorial Design View of Nurses
Authors: Mariko Nishikawa, Masaaki Yamanaka, Ayami Kondo
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Background: International visitors to Japan are at a risk of travel-related illnesses or injury that could result in hospitalization in a country where the language and customs are unique. Over twelve million international visitors came to Japan in 2015, and more are expected leading up to the Tokyo Olympics. One aspect of this is the potentially greater demand on healthcare services by foreign visitors. Nurses who take care of them have anxieties and concerns of their knowledge of the Japanese health system. Objectives: An effective distribution of travel-health information is vital for facilitating care for international visitors. Our research investigates whether a four-minute digital animation (Mari Info Japan), designed and developed by the authors and applied to a survey of 513 nurses who take care of foreigners daily, could clarify travel health procedures, reduce anxieties, while making it enjoyable to learn. Methodology: Respondents to a survey were divided into two groups. The intervention group watched Mari Info Japan. The control group read a standard guidebook. The participants were requested to fill a two-page questionnaire called Mari Meter-X, STAI-Y in English and mark a face scale, before and after the interventions. The questions dealt with knowledge of health promotion, the Japanese healthcare system, cultural concerns, anxieties, and attitudes in Japan. Data were collected from an intervention group (n=83) and control group (n=83) of nurses in a hospital, Japan for foreigners from February to March, 2016. We analyzed the data using Text Mining Studio for open-ended questions and JMP for statistical significance. Results: We found that the intervention group displayed more confidence and less anxiety to take care of foreign patients compared to the control group. The intervention group indicated a greater comfort after watching the animation. However, both groups were most likely to be concerned about language, the cost of medical expenses, informed consent, and choice of hospital. Conclusions: From the viewpoint of nurses, the provision of travel-health information by digital animation to international visitors to Japan was more effective than traditional methods as it helped them be better prepared to treat travel-related diseases and injury among international visitors. This study was registered number UMIN000020867. Funding: Grant–in-Aid for Challenging Exploratory Research 2010-2012 & 2014-16, Japanese Government.Keywords: digital animation, health promotion, international visitor, Japan, nurse
Procedia PDF Downloads 307124 Measuring the Impact of Implementing an Effective Practice Skills Training Model in Youth Detention
Authors: Phillipa Evans, Christopher Trotter
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Aims: This study aims to examine the effectiveness of a practice skills framework implemented in three youth detention centres in Juvenile Justice in New South Wales (NSW), Australia. The study is supported by a grant from and Australian Research Council and NSW Juvenile Justice. Recent years have seen a number of incidents in youth detention centres in Australia and other places. These have led to inquiries and reviews with some suggesting that detention centres often do not even meet basic human rights and do little in terms of providing opportunities for rehabilitation of residents. While there is an increasing body of research suggesting that community based supervision can be effective in reducing recidivism if appropriate skills are used by supervisors, there has been less work considering worker skills in youth detention settings. The research that has been done, however, suggest that teaching interpersonal skills to youth officers may be effective in enhancing the rehabilitation culture of centres. Positive outcomes have been seen in a UK detention centre for example, from teaching staff to do five-minute problem-solving interventions. The aim of this project is to examine the effectiveness of training and coaching youth detention staff in three NSW detention centres in interpersonal practice skills. Effectiveness is defined in terms of reductions in the frequency of critical incidents and improvements in the well-being of staff and young people. The research is important as the results may lead to the development of more humane and rehabilitative experiences for young people. Method: The study involves training staff in core effective practice skills and supporting staff in the use of those skills through supervision and de-briefing. The core effective practice skills include role clarification, pro-social modelling, brief problem solving, and relationship skills. The training also addresses some of the background to criminal behaviour including trauma. Data regarding critical incidents and well-being before and after the program implementation are being collected. This involves interviews with staff and young people, the completion of well-being scales, and examination of departmental records regarding critical incidents. In addition to the before and after comparison a matched control group which is not offered the intervention is also being used. The study includes more than 400 young people and 100 youth officers across 6 centres including the control sites. Data collection includes interviews with workers and young people, critical incident data such as assaults, use of lock ups and confinement and school attendance. Data collection also includes analysing video-tapes of centre activities for changes in the use of staff skills. Results: The project is currently underway with ongoing training and supervision. Early results will be available for the conference.Keywords: custody, practice skills, training, youth workers
Procedia PDF Downloads 103123 Psychometric Validation of Czech Version of Spiritual Needs Assessment for Patients: The First Part of Research
Authors: Lucie Mrackova, Helena Kisvetrova
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Spirituality is an integral part of human life. In a secular environment, spiritual needs are often overlooked, especially in acute nursing care. Spiritual needs assessment for patients (SNAP), which also exists in the Czech version (SNAP-CZ), can be used for objective evaluation. The aim of this study was to measure the psychometric properties of SNAP-CZ and to find correlations between SNAP-CZ and sociodemographic and clinical variables. A cross-sectional study with tools assessing spiritual needs (SNAP-CZ), anxiety (Beck Anxiety Inventory; BAI), depression (Beck Depression Inventory; BDI), pain (Visual Analogue Scale; VAS), self-sufficiency (Barthel Index; BI); cognitive function (Montreal Cognitive Test; MoCa) and selected socio-demographic data was performed. The psychometric properties of SNAP-CZ were tested using factor analysis, reliability and validity tests, and correlations between the questionnaire and sociodemographic data and clinical variables. Internal consistency was established with Cronbach’s alfa for the overall score, respective domains, and individual items. Reliability was assessed by test-retest by Interclass correlation coefficient (ICC). Data for correlation analysis were processed according to Pearson's correlation coefficient. The study included 172 trauma patients (the mean age = 40.6 ± 12.1 years) who experienced polytrauma or severe monotrauma. There were a total of 106 (61.6%) male subjects, 140 (81.4%) respondents identified themselves as non-believers. The full-scale Cronbach's alpha was 0.907. The test-retest showed the reliability of the individual domains in the range of 0.924 to 0.960 ICC. Factor analysis resulted in a three-factor solution (psychosocial needs (alfa = 0.788), spiritual needs (alfa = 0.886) and religious needs (alfa = 0.841)). Correlation analysis using Pearson's correlation coefficient showed that the domain of psychosocial needs significantly correlated only with gender (r = 0.178, p = 0.020). Males had a statistically significant lower average value in this domain (mean = 12.5) compared to females (mean = 13.8). The domain of spiritual needs significantly correlated with gender (r = 0.199, p = 0.009), social status (r = 0.156, p = 0.043), faith (r = -0.250, p = 0.001), anxiety (r = 0.194, p = 0.011) and depression (r = 0.155, p = 0.044). The domain of religious needs significantly correlated with age (r = 0,208, p = 0,007), education (r = -0,161, p = 0,035), faith (r = -0,575, p < 0,0001) and depression (r = 0,179, p = 0,019). Overall, the whole SNAP scale significantly correlated with gender (r = 0.219, p = 0.004), social status (r = 0.175, p = 0.023), faith (r = -0.334, p <0.0001), anxiety (r = 0.177, p = 0.022) and depression (r = 0.173, p = 0.025). The results of this study corroborate the reliability of the SNAP-CZ and support its future use in the nursing care of trauma patients in a secular society. Acknowledgment: The study was supported by grant nr. IGA_FZV_2020_003.Keywords: acute nursing care, assessment of spiritual needs, patient, psychometric validation, spirituality
Procedia PDF Downloads 104122 Drug Delivery Cationic Nano-Containers Based on Pseudo-Proteins
Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava
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The elaboration of effective drug delivery vehicles is still topical nowadays since targeted drug delivery is one of the most important challenges of the modern nanomedicine. The last decade has witnessed enormous research focused on synthetic cationic polymers (CPs) due to their flexible properties, in particular as non-viral gene delivery systems, facile synthesis, robustness, not oncogenic and proven gene delivery efficiency. However, the toxicity is still an obstacle to the application in pharmacotherapy. For overcoming the problem, creation of new cationic compounds including the polymeric nano-size particles – nano-containers (NCs) loading with different pharmaceuticals and biologicals is still relevant. In this regard, a variety of NCs-based drug delivery systems have been developed. We have found that amino acid-based biodegradable polymers called as pseudo-proteins (PPs), which can be cleared from the body after the fulfillment of their function are highly suitable for designing pharmaceutical NCs. Among them, one of the most promising are NCs made of biodegradable Cationic PPs (CPPs). For preparing new cationic NCs (CNCs), we used CPPs composed of positively charged amino acid L-arginine (R). The CNCs were fabricated by two approaches using: (1) R-based homo-CPPs; (2) Blends of R-based CPPs with regular (neutral) PPs. According to the first approach NCs we prepared from CPPs 8R3 (composed of R, sebacic acid and 1,3-propanediol) and 8R6 (composed of R, sebacic acid and 1,6-hexanediol). The NCs prepared from these CPPs were 72-101 nm in size with zeta potential within +30 ÷ +35 mV at a concentration 6 mg/mL. According to the second approach, CPPs 8R6 was blended in organic phase with neutral PPs 8L6 (composed of leucine, sebacic acid and 1,6-hexanediol). The NCs prepared from the blends were 130-140 nm in size with zeta potential within +20 ÷ +28 mV depending on 8R6/8L6 ratio. The stability studies of fabricated NCs showed that no substantial change of the particle size and distribution and no big particles’ formation is observed after three months storage. In vitro biocompatibility study of the obtained NPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed both type cathionic NCs are biocompatible. The obtained data allow concluding that the obtained CNCs are promising for the application as biodegradable drug delivery vehicles. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 'New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications'.Keywords: biodegradable polymers, cationic pseudo-proteins, nano-containers, drug delivery vehicles
Procedia PDF Downloads 155121 Thermal Method Production of the Hydroxyapatite from Bone By-Products from Meat Industry
Authors: Agnieszka Sobczak-Kupiec, Dagmara Malina, Klaudia Pluta, Wioletta Florkiewicz, Bozena Tyliszczak
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Introduction: Request for compound of phosphorus grows continuously, thus, it is searched for alternative sources of this element. One of these sources could be by-products from meat industry which contain prominent quantity of phosphorus compounds. Hydroxyapatite, which is natural component of animal and human bones, is leading material applied in bone surgery and also in stomatology. This is material, which is biocompatible, bioactive and osteoinductive. Methodology: Hydroxyapatite preparation: As a raw material was applied deproteinized and defatted bone pulp called bone sludge, which was formed as waste in deproteinization process of bones, in which a protein hydrolysate was the main product. Hydroxyapatite was received in calcining process in chamber kiln with electric heating in air atmosphere in two stages. In the first stage, material was calcining in temperature 600°C within 3 hours. In the next stage unified material was calcining in three different temperatures (750°C, 850°C and 950°C) keeping material in maximum temperature within 3.0 hours. Bone sludge: Bone sludge was formed as waste in deproteinization process of bones, in which a protein hydrolysate was the main product. Pork bones coming from the partition of meat were used as a raw material for the production of the protein hydrolysate. After disintegration, a mixture of bone pulp and water with a small amount of lactic acid was boiled at temperature 130-135°C and under pressure4 bar. After 3-3.5 hours boiled-out bones were separated on a sieve, and the solution of protein-fat hydrolysate got into a decanter, where bone sludge was separated from it. Results of the study: The phase composition was analyzed by roentgenographic method. Hydroxyapatite was the only crystalline phase observed in all the calcining products. XRD investigation was shown that crystallization degree of hydroxyapatite was increased with calcining temperature. Conclusion: The researches were shown that phosphorus content is around 12%, whereas, calcium content amounts to 28% on average. The conducted researches on bone-waste calcining at the temperatures of 750-950°C confirmed that thermal utilization of deproteinized bone-waste was possible. X-ray investigations were confirmed that hydroxyapatite is the main component of calcining products, and also XRD investigation was shown that crystallization degree of hydroxyapatite was increased with calcining temperature. Contents of calcium and phosphorus were distinctly increased with calcining temperature, whereas contents of phosphorus soluble in acids were decreased. It could be connected with higher crystallization degree of material received in higher temperatures and its stable structure. Acknowledgements: “The authors would like to thank the The National Centre for Research and Development (Grant no: LIDER//037/481/L-5/13/NCBR/2014) for providing financial support to this project”.Keywords: bone by-products, bone sludge, calcination, hydroxyapatite
Procedia PDF Downloads 286120 Detection of Alzheimer's Protein on Nano Designed Polymer Surfaces in Water and Artificial Saliva
Authors: Sevde Altuntas, Fatih Buyukserin
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Alzheimer’s disease is responsible for irreversible neural damage of brain parts. One of the disease markers is Amyloid-β 1-42 protein that accumulates in the brain in the form plaques. The basic problem for detection of the protein is the low amount of protein that cannot be detected properly in body liquids such as blood, saliva or urine. To solve this problem, tests like ELISA or PCR are proposed which are expensive, require specialized personnel and can contain complex protocols. Therefore, Surface-enhanced Raman Spectroscopy (SERS) a good candidate for detection of Amyloid-β 1-42 protein. Because the spectroscopic technique can potentially allow even single molecule detection from liquid and solid surfaces. Besides SERS signal can be improved by using nanopattern surface and also is specific to molecules. In this context, our study proposes to fabricate diagnostic test models that utilize Au-coated nanopatterned polycarbonate (PC) surfaces modified with Thioflavin - T to detect low concentrations of Amyloid-β 1-42 protein in water and artificial saliva medium by the enhancement of protein SERS signal. The nanopatterned PC surface that was used to enhance SERS signal was fabricated by using Anodic Alumina Membranes (AAM) as a template. It is possible to produce AAMs with different column structures and varying thicknesses depending on voltage and anodization time. After fabrication process, the pore diameter of AAMs can be arranged with dilute acid solution treatment. In this study, two different columns structures were prepared. After a surface modification to decrease their surface energy, AAMs were treated with PC solution. Following the solvent evaporation, nanopatterned PC films with tunable pillared structures were peeled off from the membrane surface. The PC film was then modified with Au and Thioflavin-T for the detection of Amyloid-β 1-42 protein. The protein detection studies were conducted first in water via this biosensor platform. Same measurements were conducted in artificial saliva to detect the presence of Amyloid Amyloid-β 1-42 protein. SEM, SERS and contact angle measurements were carried out for the characterization of different surfaces and further demonstration of the protein attachment. SERS enhancement factor calculations were also completed via experimental results. As a result, our research group fabricated diagnostic test models that utilize Au-coated nanopatterned polycarbonate (PC) surfaces modified with Thioflavin-T to detect low concentrations of Alzheimer’s Amiloid – β protein in water and artificial saliva medium. This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) Grant No: 214Z167.Keywords: alzheimer, anodic aluminum oxide, nanotopography, surface enhanced Raman spectroscopy
Procedia PDF Downloads 291119 Association between TNF-α and Its Receptor TNFRSF1B Polymorphism with Pulmonary Tuberculosis in Tomsk, Russia Federation
Authors: K. A. Gladkova, N. P. Babushkina, E. Y. Bragina
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Purpose: Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the major public health problems worldwide. It is clear that the immune response to M. tuberculosis infection is a relationship between inflammatory and anti-inflammatory responses in which Tumour Necrosis Factor-α (TNF-α) plays key roles as a pro-inflammatory cytokine. TNF-α involved in various cell immune responses via binding to its two types of membrane-bound receptors, TNFRSF1A and TNFRSF1B. Importantly, some variants of the TNFRSF1B gene have been considered as possible markers of host susceptibility to TB. However, the possible impact of such TNF-α and its receptor genes polymorphism on TB cases in Tomsk is missing. Thus, the purpose of our study was to investigate polymorphism of TNF-α (rs1800629) and its receptor TNFRSF1B (rs652625 and rs525891) genes in population of Tomsk and to evaluate their possible association with the development of pulmonary TB. Materials and Methods: The population distribution features of genes polymorphisms were investigated and made case-control study based on group of people from Tomsk. Human blood was collected during routine patients examination at Tomsk Regional TB Dispensary. Altogether, 234 TB-positive patients (80 women, 154 men, average age is 28 years old) and 205 health-controls (153 women, 52 men, average age is 47 years old) were investigated. DNA was extracted from blood plasma by phenol-chloroform method. Genotyping was carried out by a single-nucleotide-specific real-time PCR assay. Results: First, interpopulational comparison was carried out between healthy individuals from Tomsk and available data from the 1000 Genomes project. It was found that polymorphism rs1800629 region demonstrated that Tomsk population was significantly different from Japanese (P = 0.0007), but it was similar with the following Europeans subpopulations: Italians (P = 0.052), Finns (P = 0.124) and British (P = 0.910). Polymorphism rs525891 clear demonstrated that group from Tomsk was significantly different from population of South Africa (P = 0.019). However, rs652625 demonstrated significant differences from Asian population: Chinese (P = 0.03) and Japanese (P = 0.004). Next, we have compared healthy individuals versus patients with TB. It was detected that no association between rs1800629, rs652625 polymorphisms, and positive TB cases. Importantly, AT genotype of polymorphism rs525891 was significantly associated with resistance to TB (odds ratio (OR) = 0.61; 95% confidence interval (CI): 0.41-0.9; P < 0.05). Conclusion: To the best of our knowledge, the polymorphism of TNFRSF1B (rs525891) was associated with TB, while genotype AT is protective [OR = 0.61] in Tomsk population. In contrast, no significant correlation was detected between polymorphism TNF-α (rs1800629) and TNFRSF1B (rs652625) genes and alveolar TB cases among population of Tomsk. In conclusion, our data expands the molecular particularities associated with TB. The study was supported by the grant of the Russia for Basic Research #15-04-05852.Keywords: polymorphism, tuberculosis, TNF-α, TNFRSF1B gene
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