Search results for: X-ray induced photodynamic therapy
1188 A Structure-Switching Electrochemical Aptasensor for Rapid, Reagentless and Single-Step, Nanomolar Detection of C-Reactive Protein
Authors: William L. Whitehouse, Louisa H. Y. Lo, Andrew B. Kinghorn, Simon C. C. Shiu, Julian. A. Tanner
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C-reactive protein (CRP) is an acute-phase reactant and sensitive indicator for sepsis and other life-threatening pathologies, including systemic inflammatory response syndrome (SIRS). Currently, clinical turn-around times for established CRP detection methods take between 30 minutes to hours or even days from centralized laboratories. Here, we report the development of an electrochemical biosensor using redox probe-tagged DNA aptamers functionalized onto cheap, commercially available screen-printed electrodes. Binding-induced conformational switching of the CRP-targeting aptamer induces a specific and selective signal-ON event, which enables single-step and reagentless detection of CRP in as little as 1 minute. The aptasensor dynamic range spans 5-1000nM (R=0.97) or 5-500nM (R=0.99) in 50% diluted human serum, with a LOD of 3nM, corresponding to 2-orders of magnitude sensitivity under the clinically relevant cut-off for CRP. The sensor is stable for up to one week and can be reused numerous times, as judged from repeated real-time dosing and dose-response assays. By decoupling binding events from the signal induction mechanism, structure-switching electrochemical aptamer-based sensors (SS-EABs) provide considerable advantages over their adsorption-based counterparts. Our work expands on the retinue of such sensors reported in the literature and is the first instance of an SS-EAB for reagentless CRP detection. We hope this study can inspire further investigations into the suitability of SS-EABs for diagnostics, which will aid translational R&D toward fully realized devices aimed at point-of-care applications or for use more broadly by the public.Keywords: structure-switching, C-reactive protein, electrochemical, biosensor, aptasensor.
Procedia PDF Downloads 691187 Investigating the Behaviour of Composite Floors (Steel Beams and Concrete Slabs) under Mans Rhythmical Movement
Authors: M. Ali Lotfollahi Yaghin, M. Reza Bagerzadeh Karimi, Ali Rahmani, V. Sadeghi Balkanlou
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Structural engineers have long been trying to develop solutions using the full potential of its composing materials. Therefore, there is no doubt that the structural solution progress is directly related to an increase in materials science knowledge. These efforts in conjunction with up-to-date modern construction techniques have led to an extensive use of composite floors in large span structures. On the other hand, the competitive trends of the world market have long been forcing structural engineers to develop minimum weight and labour cost solutions. A direct consequence of this new design trend is a considerable increase in problems related to unwanted floor vibrations. For this reason, the structural floors systems become vulnerable to excessive vibrations produced by impacts such as human rhythmic activities. The main objective of this paper is to present an analysis methodology for the evaluation of the composite floors human comfort. This procedure takes into account a more realistic loading model developed to incorporate the dynamic effects induced by human walking. The investigated structural models were based on various composite floors, with main spans varying from 5 to 10 m. based on an extensive parametric study the composite floors dynamic response, in terms of peak accelerations, was obtained and compared to the limiting values proposed by several authors and design standards. This strategy was adopted to provide a more realistic evaluation for this type of structure when subjected to vibration due to human walking.Keywords: vibration, resonance, composite floors, people’s rhythmic movement, dynamic analysis, Abaqus software
Procedia PDF Downloads 3001186 Impact of Totiviridae L-A dsRNA Virus on Saccharomyces Cerevisiae Host: Transcriptomic and Proteomic Approach
Authors: Juliana Lukša, Bazilė Ravoitytė, Elena Servienė, Saulius Serva
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Totiviridae L-A virus is a persistent Saccharomyces cerevisiae dsRNA virus. It encodes the major structural capsid protein Gag and Gag-Pol fusion protein, responsible for virus replication and encapsulation. These features also enable the copying of satellite dsRNAs (called M dsRNAs) encoding a secreted toxin and immunity to it (known as killer toxin). Viral capsid pore presumably functions in nucleotide uptake and viral mRNA release. During cell division, sporogenesis, and cell fusion, the virions remain intracellular and are transferred to daughter cells. By employing high throughput RNA sequencing data analysis, we describe the influence of solely L-A virus on the expression of genes in three different S. cerevisiae hosts. We provide a new perception into Totiviridae L-A virus-related transcriptional regulation, encompassing multiple bioinformatics analyses. Transcriptional responses to L-A infection were similar to those induced upon stress or availability of nutrients. It also delves into the connection between the cell metabolism and L-A virus-conferred demands to the host transcriptome by uncovering host proteins that may be associated with intact virions. To better understand the virus-host interaction, we applied differential proteomic analysis of virus particle-enriched fractions of yeast strains that harboreither complete killer system (L-A-lus and M-2 virus), M-2 depleted orvirus-free. Our analysis resulted in the identification of host proteins, associated with structural proteins of the virus (Gag and Gag-Pol). This research was funded by the European Social Fund under the No.09.3.3-LMT-K-712-19-0157“Development of Competences of Scientists, other Researchers, and Students through Practical Research Activities” measure.Keywords: totiviridae, killer virus, proteomics, transcriptomics
Procedia PDF Downloads 1441185 Fused Deposition Modelling as the Manufacturing Method of Fully Bio-Based Water Purification Filters
Authors: Natalia Fijol, Aji P. Mathew
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We present the processing and characterisation of three-dimensional (3D) monolith filters based on polylactic acid (PLA) reinforced with various nature-derived nanospecies such as hydroxyapatite, modified cellulose fibers and chitin fibers. The nanospecies of choice were dispersed in PLA through Thermally Induced Phase Separation (TIPS) method. The biocomposites were developed via solvent-assisted blending and the obtained pellets were further single-screw extruded into 3D-printing filaments and processed into various geometries using Fused Deposition Modelling (FDM) technique. The printed prototypes included cubic, cylindrical and hour-glass shapes with diverse patterns of printing infill as well as varying pore structure including uniform and multiple level gradual pore structure. The pores and channel structure as well as overall shape of the prototypes were designed in attempt to optimize the flux and maximize the adsorption-active time. FDM is a cost and energy-efficient method, which does not require expensive tools and elaborated post-processing maintenance. Therefore, FDM offers the possibility to produce customized, highly functional water purification filters with tuned porous structures suitable for removal of wide range of common water pollutants. Moreover, as 3D printing becomes more and more available worldwide, it allows producing portable filters at the place and time where they are most needed. The study demonstrates preparation route for the PLA-based, fully biobased composite and their processing via FDM technique into water purification filters, addressing water treatment challenges on an industrial scale.Keywords: fused deposition modelling, water treatment, biomaterials, 3D printing, nanocellulose, nanochitin, polylactic acid
Procedia PDF Downloads 1141184 Methicillin Resistant Staphylococcus aureus Specific Bacteriophage Isolation from Sewage Treatment Plant and in vivo Analysis of Phage Efficiency in Swiss Albino Mice
Authors: Pratibha Goyal, Nupur Mathur, Anuradha Singh
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Antibiotic resistance is the worldwide threat to human health in this century. Excessive use of antibiotic after their discovery in 1940 makes certain bacteria to become resistant against antibiotics. Most common antibiotic-resistant bacteria include Staphylococcus aureus, Salmonella typhi, E.coli, Klebsiella pneumonia, and Streptococcus pneumonia. Among all Staphylococcus resistant strain called Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for several lives threatening infection in human commonly found in the hospital environment. Our study aimed to isolate bacteriophage against MRSA from the hospital sewage treatment plant and to analyze its efficiency In Vivo in Swiss albino mice model. Sewage sample for the isolation of bacteriophages was collected from SDMH hospital sewage treatment plant in Jaipur. Bacteriophages isolated by the use of enrichment technique and after characterization, isolated phages used to determine phage treatment efficiency in mice. Mice model used to check the safety and suitability of phage application in human need which in turn directly support the use of natural bacteriophage rather than synthetic chemical to kill pathogens. Results show the plaque formation in-vitro and recovery of MRSA infected mice during the experiment. Favorable lytic efficiency determination of MRSA and Salmonella presents a natural way to treat lethal infections caused by Multidrug-resistant bacteria by using their natural host-pathogen relationship.Keywords: antibiotic resistance, bacteriophages, methicillin resistance Staphylococcus aureus, pathogens, phage therapy, Salmonella typhi
Procedia PDF Downloads 1391183 Influence of Structural Cracks on Transport Performance of Reinforced Concrete
Authors: V. A. Okenyi, K. Yang, P. A. M. Basheer
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Concrete structures in service are constantly under the influence of load. Microstructural cracks often develop in them and considering those in the marine environment; these microcracks often serve as a means for transportation of harmful fluids into the concrete. This paper studies the influence of flexural tensile stress that structural elements undergo on the transport properties of such concrete in the tensile zone of the structural member. Reinforced concrete beams of 1200mm ⨉ 230mm ⨉ 150mm in dimension in a four-point bending set up were subjected to various levels of the loading required to cause a microcrack width of 100µm. The use of Autoclam permeability tests, sorptivity tests as well as the Permit chloride ion migration tests were employed, and results showed that air permeability, sorptivity and water permeability all increased as the load increased in the concrete tensile zone. For air permeability, an increase in stress levels led to more permeability, and the addition of steel macrofibers had no significant effect until at 75% of stress level where it decreased air permeability. For sorptivity, there was no absorption into concrete when no load was added, but water sorptivity index was high at 75% stress levels and higher in steel fiber reinforced concrete (SFRC). Steel macrofibers produced more water permeability into the concrete at 75% stress level under the 100µm crack width considered while steel macrofibers helped in slightly reducing the migration of chloride into concrete by 8.8% reduction, compared to control samples at 75% stress level. It is clear from this research that load-induced cracking leads to an increase in fluid permeability into concrete and the effect of the addition of steel macrofiber to concrete for durability is not significant under 100µm crack width.Keywords: durability, microcracks, SFRC, stress Level, transport properties
Procedia PDF Downloads 1251182 Anticancer Lantadene Derivatives: Synthesis, Cytotoxic and Docking Studies
Authors: A. Monika, Manu Sharma, Hong Boo Lee, Richa Dhingra, Neelima Dhingra
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Nuclear factor-κappa B serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. Inflammation has been recognized as a hallmark and cause of cancer. Natural products present a privileged source of inspiration for chemical probe and drug design. Herbal remedies were the first medicines used by humans due to the many pharmacologically active secondary metabolites produced by plants. Some of the metabolites like Lantadene (pentacyclic triterpenoids) from the weed Lantana camara has been known to inhibit cell division and showed anti-antitumor potential. The C-3 aromatic esters of lantadenes were synthesized, characterized and evaluated for cytotoxicity and inhibitory potential against Tumor necrosis factor alpha-induced activation of Nuclear factor-κappa B in lung cancer cell line A549. The 3-methoxybenzoyloxy substituted lead analogue inhibited kinase activity of the inhibitor of nuclear factor-kappa B kinase in a single-digit micromolar concentration. At the same time, the lead compound showed promising cytotoxicity against A549 lung cancer cells with IC50 ( half maximal inhibitory concentration) of 0.98l µM. Further, molecular docking of 3-methoxybenzoyloxy substituted analogue against Inhibitor of nuclear factor-kappa B kinase (Protein data bank ID: 3QA8) showed hydrogen bonding interaction involving oxygen atom of 3-methoxybenzoyloxy with the Arginine-31 and Glutamine-110. Encouraging results indicate the Lantadene’s potential to be developed as anticancer agents.Keywords: anticancer, lantadenes, pentacyclic triterpenoids, weed
Procedia PDF Downloads 1551181 Magnetic versus Non-Magnetic Adatoms in Graphene Nanoribbons: Tuning of Spintronic Applications and the Quantum Spin Hall Phase
Authors: Saurabh Basu, Sudin Ganguly
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Conductance in graphene nanoribbons (GNR) in presence of magnetic (for example, Iron) and non-magnetic (for example, Gold) adatoms are explored theoretically within a Kane-Mele model for their possible spintronic applications and topologically non-trivial properties. In our work, we have considered the magnetic adatoms to induce a Rashba spin-orbit coupling (RSOC) and an exchange bias field, while the non-magnetic ones induce an RSOC and an intrinsic spin-orbit (SO) coupling. Even though RSOC is present in both, they, however, represent very different physical situations, where the magnetic adatoms do not preserve the time reversal symmetry, while the non-magnetic case does. This has important implications on the topological properties. For example, the non-magnetic adatoms, for moderately strong values of SO, the GNR denotes a quantum spin Hall insulator as evident from a 2e²/h plateau in the longitudinal conductance and presence of distinct conducting edge states with an insulating bulk. Since the edge states are protected by time reversal symmetry, the magnetic adatoms in GNR yield trivial insulators and do not possess any non-trivial topological property. However, they have greater utility than the non-magnetic adatoms from the point of view of spintronic applications. Owing to the broken spatial symmetry induced by the presence of adatoms of either type, all the x, y and z components of the spin-polarized conductance become non-zero (only the y-component survives in pristine Graphene owing to a mirror symmetry present there) and hence become suitable for spintronic applications. However, the values of the spin polarized conductances are at least two orders of magnitude larger in the case of magnetic adatoms than their non-magnetic counterpart, thereby ensuring more efficient spintronic applications. Further the applications are tunable by altering the adatom densities.Keywords: magnetic and non-magnetic adatoms, quantum spin hall phase, spintronic applications, spin polarized conductance, time reversal symmetry
Procedia PDF Downloads 3001180 Assessment of Land Use Land Cover Change-Induced Climatic Effects
Authors: Mahesh K. Jat, Ankan Jana, Mahender Choudhary
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Rapid population and economic growth resulted in changes in large-scale land use land cover (LULC) changes. Changes in the biophysical properties of the Earth's surface and its impact on climate are of primary concern nowadays. Different approaches, ranging from location-based relationships or modelling earth surface - atmospheric interaction through modelling techniques like surface energy balance (SEB) are used in the recent past to examine the relationship between changes in Earth surface land cover and climatic characteristics like temperature and precipitation. A remote sensing-based model i.e., Surface Energy Balance Algorithm for Land (SEBAL), has been used to estimate the surface heat fluxes over Mahi Bajaj Sagar catchment (India) from 2001 to 2020. Landsat ETM and OLI satellite data are used to model the SEB of the area. Changes in observed precipitation and temperature, obtained from India Meteorological Department (IMD) have been correlated with changes in surface heat fluxes to understand the relative contributions of LULC change in changing these climatic variables. Results indicate a noticeable impact of LULC changes on climatic variables, which are aligned with respective changes in SEB components. Results suggest that precipitation increases at a rate of 20 mm/year. The maximum and minimum temperature decreases and increases at 0.007 ℃ /year and 0.02 ℃ /year, respectively. The average temperature increases at 0.009 ℃ /year. Changes in latent heat flux and sensible heat flux positively correlate with precipitation and temperature, respectively. Variation in surface heat fluxes influences the climate parameters and is an adequate reason for climate change. So, SEB modelling is helpful to understand the LULC change and its impact on climate.Keywords: LULC, sensible heat flux, latent heat flux, SEBAL, landsat, precipitation, temperature
Procedia PDF Downloads 1151179 Phytochemical Screening, Antioxidant and Hepatoprotection Assessment of Extracts of Coriandrum sativm L. on Wistar Rats
Authors: Hiba T. Allah ALtieb Gusm ALsied, Amna Beshir Medani Ahmed, Ikram Mohamed ELtayeb, Saad Mohamed Hussein Ayoub
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This study was carried out to determine the hepatoactivity and the antioxidant activity of Coiradrum sativum L. aerial part and fruit extracts against CCL4 induced acute liver damages in Wistar rats. The aerial parts and fruits part of the plant were extracted 96% ethanol with soxhlet apparatus. Hepatic injury was achieved by subcutaneous injection of 3 ml/kg of CCL4 diluted with olive oil with ratio 1:1. The extracts were mixed together 1:1 ratio and given in different doses 100,200,400 mg/kg/day for 5 days under CCL4 induction at 3rd day. The significance of differences between means by using T-test was compared among the groups. The mixture of the two extracts didn’t show any significant result in protecting liver injury (antagonistic effects), it shows high level of liver enzyme like alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (SGOT) and glutamate pyruvate transaminase (SGPT). Serological studies further confirmed the results. The results obtained were compared with silymarin (70 mg/kg/day) orally, the standard drug for hepatoprotection which show recovery close to normalization almost like that of silymarin; therefore, further studies on this plant with different ratios especially in isolated tissue to spot more light on antagonistic effects of the two extracts. Antioxidant activity of the extracts was determined by the DPPH method. The results obtained show high anti-oxidant activity for fruits extract while slight or moderate antioxidant activity to aerial extracts.Keywords: antioxidant, aerial part, Coriadrum sativum L., fruity, hepatoprotection, Silymarin, phytochemical screening
Procedia PDF Downloads 4881178 Harnessing the Generation of Ferromagnetic and Silver Nanostructures from Tropical Aquatic Microbial Nanofactories
Authors: Patricia Jayshree Jacob, Mas Jaffri Masarudinb, Mohd Zobir Hussein, Raha Abdul Rahim
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Iron based ferromagnetic nanoparticles (IONP) and silver nanostructures (AgNP) have found a wide range of application in antimicrobial therapy, cell targeting, and environmental applications. As such, the design of well-defined monodisperse IONPs and AgNPs have become an essential tool in nanotechnology. Fabrication of these nanostructures using conventional methods is not environmentally conducive and weigh heavily on energy and outlays. Selected microorganisms possess the innate ability to reduce metallic ions in colloidal aqueous solution to generate nanoparticles. Hence, harnessing this potential is a way forward in constructing microbial nano-factories, capable of churning out high yields of well-defined IONP’s and AgNP's with physicochemical characteristics on par with the best synthetically produced nanostructures. In this paper, we report the isolation and characterization of bacterial strains isolated from the tropical marine and freshwater ecosystems of Malaysia that demonstrated facile and rapid generation of ferromagnetic nanoparticles and silver nanostructures when precursors such as FeCl₃.6H₂O and AgNO₃ were added to the cell-free bacterial lysate in colloidal solution. Characterization of these nanoparticles was carried out using FESEM, UV Spectrophotometer, XRD, DLS and FTIR. This aerobic bioprocess was carried out at ambient temperature and humidity and has the potential to be developed for environmental friendly, cost effective large scale production of IONP’s. A preliminary bioprocess study on the harvesting time, incubation temperature and pH was also carried out to determine pertinent abiotic parameters contributing to the optimal production of these nanostructures.Keywords: iron oxide nanoparticles, silver nanoparticles, biosynthesis, aquatic bacteria
Procedia PDF Downloads 2841177 Right Cerebellar Stroke with a Right Vertebral Artery Occlusion Following an Embolization of the Right Glomus Tympanicum Tumor
Authors: Naim Izet Kajtazi
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Context: Although rare, glomus tumor (i.e., nonchromaffin chemodectomas and paragan¬gliomas) is the most common middle ear tumor, with female predominance. Pre-operative embolization is often required to devascularize the hypervascular tumor for better surgical outcomes. Process: A 35-year-old female presented with episodes of frequent dizziness, ear fullness, and right ear tinnitus for 12 months. Head imaging revealed a right glomus tympanicum tumor. She underwent pre-operative endovascular embolization of the glomus tympanicum tumor with surgical, cyanoacrylate-based glue. Immediately after the procedure, she developed drowsiness and severe pain in the right temporal region. Further investigations revealed a right cerebellar stroke in the posterior inferior cerebellar artery territory. She was treated with intravenous heparin, followed by one year of oral anticoagulation. With rehabilitation, she significantly recovered from her post embolization stroke. However, the tumor was resected at another institution. Ten years later, follow-up imaging indicated a gradual increase in the size of the glomus jugulare tumor, compressing the nearby critical vascular structures. She subsequently received radiation therapy to treat the residual tumor. Outcome: Currently, she has no neurological deficit, but her mild dizziness, right ear tinnitus, and hearing impairment persist. Relevance: This case highlights the complex nature of these tumors, which often bring challenges to the patients as well as treatment teams. The multi-disciplinary team approach is necessary to tailor the management plan for individual tumors. Although embolization is a safe procedure, careful attention and thoughtful anatomic knowledge regarding dangerous anastomosis are essential to avoid devastating complications. Complications occur due to encountered vessel anomalies and new anastomoses formed during the gluing and changes in hemodynamics.Keywords: stroke, embolization, MRI brain, cerebral angiogram
Procedia PDF Downloads 691176 Low-Density Lipoproteins Mediated Delivery of Paclitaxel and MRI Imaging Probes for Personalized Medicine Applications
Authors: Sahar Rakhshan, Simonetta Geninatti Crich, Diego Alberti, Rachele Stefania
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The combination of imaging and therapeutic agents in the same smart nanoparticle is a promising option to perform a minimally invasive imaging guided therapy. In this study, Low density lipoproteins (LDL), one of the most attractive biodegradable and biocompatible nanoparticles, were used for the simultaneous delivery of Paclitaxel (PTX), a hydrophobic antitumour drug and an amphiphilic contrast agent, Gd-AAZTA-C17, in B16-F10 melanoma cell line. These cells overexpress LDL receptors, as assessed by Flow cytometry analysis. PTX and Gd-AAZTA-C17 loaded LDLs (LDL-PTX-Gd) have been prepared, characterized and their stability was assessed under 72 h incubation at 37 ◦C and compared to LDL loaded with Gd-AAZTA-C17 (LDL-Gd) and LDL-PTX. The cytotoxic effect of LDL-PTX-Gd was evaluated by MTT assay. The anti-tumour drug loaded into LDLs showed a significantly higher toxicity on B16-F10 cells with respect to the commercially available formulation Paclitaxel Kabi (PTX Kabi) used in clinical applications. It was possible to demonstrate a high uptake of LDL-Gd in B16-F10 cells. As a consequence of the high cell uptake, melanoma cells showed significantly high cytotoxic effect when incubated in the presence of PTX (LDL-PTX-Gd). Furthermore, B16-F10 have been used to perform Magnetic Resonance Imaging. By the analysis of the image signal intensity, it was possible to extrapolate the amount of internalized PTX indirectly by the decrease of relaxation times caused by Gd, proportional to its concentration. Finally, the treatment with PTX loaded LDL on B16-F10 tumour bearing mice resulted in a marked reduction of tumour growth compared to the administration of PTX Kabi alone. In conclusion, LDLs are selectively taken-up by tumour cells and can be successfully exploited for the selective delivery of Paclitaxel and imaging agents.Keywords: low density lipoprotein, melanoma cell lines, MRI, paclitaxel, personalized medicine application, theragnostic System
Procedia PDF Downloads 1231175 Space Weather and Earthquakes: A Case Study of Solar Flare X9.3 Class on September 6, 2017
Authors: Viktor Novikov, Yuri Ruzhin
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The studies completed to-date on a relation of the Earth's seismicity and solar processes provide the fuzzy and contradictory results. For verification of an idea that solar flares can trigger earthquakes, we have analyzed a case of a powerful surge of solar flash activity early in September 2017 during approaching the minimum of 24th solar cycle was accompanied by significant disturbances of space weather. On September 6, 2017, a group of sunspots AR2673 generated a large solar flare of X9.3 class, the strongest flare over the past twelve years. Its explosion produced a coronal mass ejection partially directed towards the Earth. We carried out a statistical analysis of the catalogs of earthquakes USGS and EMSC for determination of the effect of solar flares on global seismic activity. New evidence of earthquake triggering due to the Sun-Earth interaction has been demonstrated by simple comparison of behavior of Earth's seismicity before and after the strong solar flare. The global number of earthquakes with magnitude of 2.5 to 5.5 within 11 days after the solar flare has increased by 30 to 100%. A possibility of electric/electromagnetic triggering of earthquake due to space weather disturbances is supported by results of field and laboratory studies, where the earthquakes (both natural and laboratory) were initiated by injection of electrical current into the Earth crust. For the specific case of artificial electric earthquake triggering the current density at a depth of earthquake, sources are comparable with estimations of a density of telluric currents induced by variation of space weather conditions due to solar flares. Acknowledgment: The work was supported by RFBR grant No. 18-05-00255.Keywords: solar flare, earthquake activity, earthquake triggering, solar-terrestrial relations
Procedia PDF Downloads 1421174 Effect of a GABA/5-HTP Mixture on Behavioral Changes and Biomodulation in an Invertebrate Model
Authors: Kyungae Jo, Eun Young Kim, Byungsoo Shin, Kwang Soon Shin, Hyung Joo Suh
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Gamma-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) are amino acids of digested nutrients or food ingredients and these can possibly be utilized as non-pharmacologic treatment for sleep disorder. We previously investigated the GABA/5-HTP mixture is the principal concept of sleep-promoting and activity-repressing management in nervous system of D. melanogaster. Two experiments in this study were designed to evaluate sleep-promoting effect of GABA/5-HTP mixture, to clarify the possible ratio of sleep-promoting action in the Drosophila invertebrate model system. Behavioral assays were applied to investigate distance traveled, velocity, movement, mobility, turn angle, angular velocity and meander of two amino acids and GABA/5-HTP mixture with caffeine treated flies. In addition, differentially expressed gene (DEG) analyses from next generation sequencing (NGS) were applied to investigate the signaling pathway and functional interaction network of GABA/5-HTP mixture administration. GABA/5-HTP mixture resulted in significant differences between groups related to behavior (p < 0.01) and significantly induced locomotor activity in the awake model (p < 0.05). As a result of the sequencing, the molecular function of various genes has relationship with motor activity and biological regulation. These results showed that GABA/5-HTP mixture administration significantly involved the inhibition of motor behavior. In this regard, we successfully demonstrated that using a GABA/5-HTP mixture modulates locomotor activity to a greater extent than single administration of each amino acid, and that this modulation occurs via the neuronal system, neurotransmitter release cycle and transmission across chemical synapses.Keywords: sleep, γ-aminobutyric acid, 5-hydroxytryptophan, Drosophila melanogaster
Procedia PDF Downloads 3071173 Prevalence of Mycobacterium Tuberculosis Infection and Rifampicin Resistance among Presumptive Tuberculosis Cases Visiting Tuberculosis Clinic of Adare General Hospital, Southern Ethiopia
Authors: Degineh Belachew Andarge, Tariku Lambiyo Anticho, Getamesay Mulatu Jara, Musa Mohammed Ali
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Introduction: Tuberculosis (TB) is a communicable chronic disease causedby Mycobacterium tuberculosis (MTB). About one-third of the world’s population is latently infected with MTB. TB is among the top 10 causes of mortality throughout the globe from a single pathogen. Objective: The aim of this study was to determine the prevalence of tuberculosis,rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosis, and associated factors among presumptive tuberculosis cases attending the tuberculosis clinic of Adare General Hospital located in Hawassa city. Methods: A hospital-based cross-sectional study was conducted among 321 tuberculosis suspected patients from April toJuly 2018. Socio-demographic, environmental, and behavioral data were collected using a structured questionnaire. Sputumspecimens were analyzed using GeneXpert. Data entry was made using Epi info version 7 and analyzed by SPSS version 20. Logistic regression models were used to determine the risk factors. A p-value less than 0.05 was taken as a cut point. Results: In this study, the prevalence of Mycobacterium tuberculosis was 98 (30.5%) with 95% confidence interval (25.5–35.8), and the prevalence of rifampicin-resistant/multidrug-resistantMycobacterium tuberculosis among the 98 Mycobacteriumtuberculosis confirmed cases was 4 (4.1%). The prevalence of rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosisamong the tuberculosis suspected patients was 1.24%. Participants who had a history of treatment with anti-tuberculosisdrugs were more likely to develop rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosis. Conclusions: This study identified relatively high rifampicin-resistant/multidrug-resistant Mycobacterium tuberculosis amongtuberculosis suspected patients in the study area. Early detection of drug-resistant Mycobacterium tuberculosis should be givenenough attention to strengthen the management of tuberculosis cases and improve direct observation therapy short-course and eventually minimize the spread of rifampicin-resistant tuberculosis strain in the community.Keywords: rifampicin resistance, mycobacterium tuberculosis, risk factors, prevalence of TB
Procedia PDF Downloads 1101172 Case Presentation Ectopic Cushing's Syndrome Secondary to Thymic Neuroendocrine Tumors Secreting ACTH
Authors: Hasan Frookh Jamal
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This is a case of a 36-year-old Bahraini gentleman diagnosed to have Cushing's Syndrome with a large anterior mediastinal mass. He was sent abroad to the Speciality hospital in Jordan, where he underwent diagnostic video-assisted thoracoscopy, partial thymectomy and pericardial fat excision. Histopathology of the mass was reported to be an Atypical carcinoid tumor with a low Ki67 proliferation index of 5%, the mitotic activity of 4 MF/10HPF and pathological stage classification(pTNM): pT1aN1. MRI of the pituitary gland showed an ill-defined non-enhancing focus of about 3mm on the Rt side of the pituitary on coronal images, with a similar but smaller one on the left side, which could be due to enhancing pattern rather than a real lesion as reported. The patient underwent Ga68 Dotate PET/CT scan post-operatively, which showed multiple somatostatin receptor-positive lesions seen within the tail, body and head of the pancreas and positive somatostatin receptor lymph nodes located between the pancreatic head and IVC. There was no uptake detected at the anterior mediastinum nor at the site of thymic mass resection. There was no evidence of any positive somatostatin uptake at the soft tissue or lymph nodes. The patient underwent IPSS, which proved that the source is, in fact, an ectopic source of ACTH secretion. Unfortunately, the patient's serum cortisol remained elevated after surgery and failed to be suppressed by 1 mg ODST and by 2 days LLDST with a high ACTH value. The patient was started on Osilodrostat for treatment of hypercortisolism for the time being and his future treatment plan with Lutetium-177 Dotate therapy vs. bilateral adrenalectomy is to be considered in an MDT meeting.Keywords: cushing syndrome, neuroendocrine tumur, carcinoid tumor, Thymoma
Procedia PDF Downloads 811171 Numerical Simulation of Axially Loaded to Failure Large Diameter Bored Pile
Authors: M. Ezzat, Y. Zaghloul, T. Sorour, A. Hefny, M. Eid
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Ultimate capacity of large diameter bored piles is usually determined from pile loading tests as recommended by several international codes and foundation design standards. However, loading of this type of piles till achieving apparent failure is practically seldom. In this paper, numerical analyses are carried out to simulate load test of a large diameter bored pile performed at the location of Alzey highway bridge project (Germany). Test results of pile load settlement relationship till failure as well as results of the base and shaft resistances are available. Apparent failure was indicated in this test by the significant increase of the induced settlement during the last load increment applied on the pile head. Measurements of this pile load test are used to assess the quality of the numerical models investigated. Three different material soil models are implemented in the analyses: Mohr coulomb (MC), Soft soil (SS), and Modified Mohr coulomb (MMC). Very good agreement is obtained between the field measured settlement and the calculated settlement using the MMC model. Results of analysis showed also that the MMC constitutive model is superior to MC, and SS models in predicting the ultimate base and shaft resistances of the large diameter bored pile. After calibrating the numerical model, behavior of large diameter bored piles under axial loads is discussed and the formation of the plastic zone around the pile is explored. Results obtained showed that the plastic zone below the base of the pile at failure extended laterally to about four times the pile diameter and vertically to about three times the pile diameter.Keywords: ultimate capacity, large diameter bored piles, plastic zone, failure, pile load test
Procedia PDF Downloads 1421170 Bone Mineral Density of the Lumbar Spine, Femur in Elite Egyptian Male Swimmers
Authors: Magdy Abouzeid
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Introduction: Physical activity has been shown to have a positive effect on bone mineral density (BMD) and bone mineral content (BMC) among children, adolescents, and adults. Sports characterized by little or moderate weight bearing or impact have a low osteogenic effect. However, the action of such sports on bone turnover remains unclear. Swimming, as a non-weight-bearing sport, has been considered to be insignificant in the maintenance of bone mass. Purpose: To examine this issue we measured (BMD) and(BMC) of the lumbar spine, proximal femur via dual energy x-ray absorptiometry in the group of elite male swimmers, and determine the effect of swimming training on bone health and compared the results with matched controls group in age, body weight and height. Materials and Methods: Twenty-five male swimmers (age 20.7+/-0.8 years) training for 12-15 hours/week; and the controls group consisted of 25 non-active male (age 21.3 +/-1.3 years) were studied BMD and BMC of lumbar spine, femur were assessed via (DXA) absorptiometry. Results: There was significant difference between swimmers and control group in BMD and BMC, BMD of Swimmers was significantly greater than controls at all sites. The lumbar spine (1, 08 +/-0.202 vs., 0717+0.57 gxcm (-2), right proximal femur (1, 02 +/-, 044 vs., 771+/-, 027 gxcm (-2), and left proximal femur (1.374+/-0.212 vs. 1.01 +/-0.141 gxcm (-2). Swimmers were significantly taller, and had greater BMC and BMD compared to the controls group (P<0.001). Conclusions: These results suggest that swimming training may be beneficial in the prevention or therapy of OSTEOPENIA, and may lead to increased (BMD) and (BMC) for male swimmers. Swimming may be an effective non-pharmacological intervention for the adults and adolescent. Further research with younger athletes of another type of aquatics sport is warranted to better identify the periods of BMD development during which Aquatics sport has the greatest impact on bone health.Keywords: bone mineral density, lumbar spine, femur, swimming, DXA absorptiometry
Procedia PDF Downloads 3211169 Effects of Forest Bathing on Cardiovascular and Metabolic Parameters in Middle-Aged Males
Authors: Qing Li, Maiko Kobayashi, Shigeyoshi Kumeda, Hiroko Ochiai, Toshiya Ochiai, Takashi Miura, Takahide Kagawa, Michiko Imai, Toshiaki Otsuka, Tomoyuki Kawada
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In the present study, we investigated the effects of a forest bathing program on cardiovascular and metabolic parameters. Nineteen healthy male subjects (mean age: 51.3 ± 8.8 years) were selected after obtaining informed consent. These subjects took day trips to a forest park named Akasawa Shizen Kyuyourin, Agematsu, Nagano Prefecture (situated in central Japan), and to an urban area of Nagano Prefecture as a control in August 2015. On both trips, they walked 2.6 km for 80 min each in the morning and afternoon on Saturdays. Blood and urine were sampled in the morning before and after each trip. Cardiovascular and metabolic parameters were measured. Blood pressure and pulse rate were measured by an ambulatory automatic blood pressure monitor. The Japanese version of the profile of mood states (POMS) test was conducted before, during and after the trips. Ambient temperature and humidity were monitoring during the trips. The forest bathing program significantly reduced pulse rate, and significantly increased the score for vigor and decreased the scores for depression, fatigue, and confusion in the POMS test. The levels of urinary noradrenaline and dopamine after forest bathing were significantly lower than those after urban area walking, suggesting the relaxing effect of the forest bathing program. The level of adiponectin in serum after the forest bathing program was significantly greater than that after urban area walking. There was no significant difference in blood pressure between forest and urban area trips during the trips.Keywords: ambient temperature, blood pressure, forest bathing, forest therapy, human health, POMS, pulse rate
Procedia PDF Downloads 4361168 Characterization of Tailings From Traditional Panning of Alluvial Gold Ore (A Case Study of Ilesa - Southwestern Nigeria Goldfield Tailings Dumps)
Authors: Olaniyi Awe, Adelana R. Adetunji, Abraham Adeleke
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Field observation revealed a lot of artisanal gold mining activities in Ilesa gold belt of southwestern Nigeria. The possibility of alluvial and lode gold deposits in commercial quantities around this location is very high, as there are many resident artisanal gold miners who have been mining and trading alluvial gold ore for decades and to date in the area. Their major process of solid gold recovery from its ore is by gravity concentration using the convectional panning method. This method is simple to learn and fast to recover gold from its alluvial ore, but its effectiveness is based on rules of thumb and the artisanal miners' experience in handling gold ore panning tool while processing the ore. Research samples from five alluvial gold ore tailings dumps were collected and studied. Samples were subjected to particle size analysis and mineralogical and elemental characterization using X-Ray Diffraction (XRD) and Particle-Induced X-ray Emission (PIXE) methods, respectively. The results showed that the tailings were of major quartz in association with albite, plagioclase, mica, gold, calcite and sulphide minerals. The elemental composition analysis revealed a 15ppm of gold concentration in particle size fraction of -90 microns in one of the tailings dumps investigated. These results are significant. It is recommended that heaps of panning tailings should be further reprocessed using other gold recovery methods such as shaking tables, flotation and controlled cyanidation that can efficiently recover fine gold particles that were previously lost into the gold panning tailings. The tailings site should also be well controlled and monitored so that these heavy minerals do not find their way into surrounding water streams and rivers, thereby causing health hazards.Keywords: gold ore, panning, PIXE, tailings, XRD
Procedia PDF Downloads 881167 Vibration Control of a Horizontally Supported Rotor System by Using a Radial Active Magnetic Bearing
Authors: Vishnu A., Ashesh Saha
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The operation of high-speed rotating machinery in industries is accompanied by rotor vibrations due to many factors. One of the primary instability mechanisms in a rotor system is the centrifugal force induced due to the eccentricity of the center of mass away from the center of rotation. These unwanted vibrations may lead to catastrophic fatigue failure. So, there is a need to control these rotor vibrations. In this work, control of rotor vibrations by using a 4-pole Radial Active Magnetic Bearing (RAMB) as an actuator is analysed. A continuous rotor system model is considered for the analysis. Several important factors, like the gyroscopic effect and rotary inertia of the shaft and disc, are incorporated into this model. The large deflection of the shaft and the restriction to axial motion of the shaft at the bearings result in nonlinearities in the system governing equation. The rotor system is modeled in such a way that the system dynamics can be related to the geometric and material properties of the shaft and disc. The mathematical model of the rotor system is developed by incorporating the control forces generated by the RAMB. A simple PD controller is used for the attenuation of system vibrations. An analytical expression for the amplitude and phase equations is derived using the Method of Multiple Scales (MMS). Analytical results are verified with the numerical results obtained using an ‘ode’ solver in-built into MATLAB Software. The control force is found to be effective in attenuating the system vibrations. The multi-valued solutions leading to the jump phenomenon are also eliminated with a proper choice of control gains. Most interestingly, the shape of the backbone curves can also be altered for certain values of control parameters.Keywords: rotor dynamics, continuous rotor system model, active magnetic bearing, PD controller, method of multiple scales, backbone curve
Procedia PDF Downloads 781166 Tribological Properties of Non-Stick Coatings Used in Bread Baking Process
Authors: Maurice Brogly, Edwige Privas, Rajesh K. Gajendran, Sophie Bistac
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Anti-sticky coatings based on perfluoroalkoxy (PFA) coatings are widely used in food processing industry especially for bread making. Their tribological performance, such as low friction coefficient, low surface energy and high heat resistance, make them an appropriate choice for anti-sticky coating application in moulds for food processing industry. This study is dedicated to evidence the transfer of contaminants from the coating due to wear and thermal ageing of the mould. The risk of contamination is induced by the damage of the coating by bread crust during the demoulding stage. The study focuses on the wear resistance and potential transfer of perfluorinated polymer from the anti-sticky coating. Friction between perfluorinated coating and bread crust is modeled by a tribological pin-on-disc test. The cellular nature of the bread crust is modeled by a polymer foam. FTIR analysis of the polymer foam after friction allow the evaluation of the transfer from the perfluorinated coating to polymer foam. Influence of thermal ageing on the physical, chemical and wear properties of the coating are also investigated. FTIR spectroscopic results show that the increase of PFA transfer onto the foam counterface is associated to the decrease of the friction coefficient. Increasing lubrication by film transfer results in the decrease of the friction coefficient. Moreover increasing the friction test parameters conditions (load, speed and sliding distance) also increase the film transfer onto the counterface. Thermal ageing increases the hydrophobic character of the PFA coating and thus also decreases the friction coefficient.Keywords: fluorobased polymer coatings, FTIR spectroscopy, non-stick food moulds, wear and friction
Procedia PDF Downloads 3291165 Time-Dependent Modulation on Depressive Responses and Circadian Rhythms of Corticosterone in Models of Melatonin Deficit
Authors: Jana Tchekalarova, Milena Atanasova, Katerina Georgieva
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Melatonin deficit can cause a disturbance in emotional status and circadian rhythms of the endocrine system in the body. Both pharmacological and alternative approaches are applied for correction of dysfunctions driven by changes in circadian dynamics of many physiological indicators. In the present study, we tested and compare the beneficial effect of agomelatine (40 mg/kg, i.p. for 3 weeks) and endurance training on depressive behavior in two models of melatonin deficit in rat. The role of disturbed circadian rhythms of plasma melatonin and corticosterone secretion in the mechanism of these treatments was also explored. The continuous exercise program attenuated depressive responses associated with disrupted diurnal rhythm of home-cage motor activity, anhedonia in the sucrose preference test, and despair-like behavior in the forced swimming test were attenuated by agomelatine exposed to chronic constant light (CCL) and long-term exercise in pinealectomized rats. Parallel to the observed positive effect on the emotional status, agomelatine restored CCL-induced impairment of circadian patterns of plasma melatonin but not that of corticosterone. In opposite, exercise training diminished total plasma corticosterone levels and corrected its flattened pattern while it was unable to correct melatonin deficit in pinealectomy. These results suggest that the antidepressant-like effect of pharmacological and alternative approach might be mediated via two different mechanism, correction of the disturbed circadian rhythm of melatonin and corticosterone, respectively. Therefore, these treatment approaches might have a potential therapeutic application in different subpopulations of people characterized by a melatonin deficiency. This work was supported by the National Science Fund of Bulgaria (research grant # № DN 03/10; DN# 12/6).Keywords: agomelatine, exercise training, melatonin deficit, corticosterone
Procedia PDF Downloads 1301164 Neuroprotective Effect of Crocus sativus against Cerebral Ischemia in Rats
Authors: Rehab F. Abdel-Rahman, Sally A. El Awdan, Rehab R. Hegazy, Dina F. Mansour, Hanan A. Ogaly, Marwan Abdelbaset
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Disorders of the cerebral circulation are the leading cause of numerous neurological and psychiatric illnesses. The transient middle cerebral artery occlusion model (MCAO) is considered to be a reliable and reproducible rodent model of cerebral ischemia. The purpose of the current study was to examine the neuroprotective effects of Crocus sativus (saffron) in a rat model of left middle cerebral artery MCAO. Male Wistar rats were anesthetized and subjected to 1 h of MCAO followed by 48 h reperfusion or sham surgery. One group of the ischemia operated animals was kept as left brain ischemia/reperfusion (I/R). Another 2 operated groups received saffron extract (100 or 200 mg/kg, i.p) four times (60 min before the surgery, during the surgery, and on days 1 and 2 after the occlusion). During the experiment, behavioral tests were performed. After 72 h the animals were euthanized and their left brain hemispheres were used in the biochemical, histopathological, and immunohistochemical studies. Saffron administration revealed an improvement in I/R-induced alteration of locomotor balance and coordination ability of rats. Moreover, saffron decreased the brain content of malondialdehyde, nitric oxide, brain natriuretic peptide and vascular endothelial growth factor with significant increase of reduced glutathione. Immunohistochemical evaluation of caspase-3 and Bax protein expression revealed reduction in I/R-enhanced apoptosis in saffron treated rats. In conclusion, saffron treatment decreases ischemic brain injury in association with inhibition of apoptotic and oxidative cell death in a dose dependent manner.Keywords: caspase-3, cerebral ischemia, Crocus sativus, rats, vascular endothelial growth factor
Procedia PDF Downloads 2571163 Elastic Collisions of Electrons with DNA and Water From 10 eV to 100 KeV: Scar Macro Investigation
Authors: Aouina Nabila Yasmina, Zine El Abidine Chaoui
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Recently, understanding the interactions of electrons with the DNA molecule and its components has attracted considerable interest because DNA is the main site damaged by ionizing radiation. The interactions of radiation with DNA induce a variety of molecular damage such as single-strand breaks, double-strand breaks, basic damage, cross-links between proteins and DNA, and others, or the formation of free radicals, which, by chemical reactions with DNA, can also lead to breakage of the strand. One factor that can contribute significantly to these processes is the effect of water hydration on the formation and reaction of radiation induced by these radicals in and / or around DNA. B-DNA requires about 30% by weight of water to maintain its native conformation in the crystalline state. The transformation depends on various factors such as sequence, ion composition, concentration and water activity. Partial dehydration converts it to DNA-A. The present study shows the results of theoretical calculations for positrons and electrons elastic scattering with DNA medium and water over a broad energy range from 10 eV to 100 keV. Indeed, electron elastic cross sections and elastic mean free paths are calculated using a corrected form of the independent atom method, taking into account the geometry of the biomolecule (SCAR macro). Moreover, the elastic scattering of electrons and positrons by atoms of the biomolecule was evaluated by means of relativistic (Dirac) partial wave analysis. Our calculated results are compared with theoretical data available in the literature in the absence of experimental data, in particular for positron. As a central result, our electron elastic cross sections are in good agreement with existing theoretical data in the range of 10 eV to 1 keV.Keywords: elastic cross scrion, elastic mean free path, scar macro method, electron collision
Procedia PDF Downloads 601162 FWGE Production From Wheat Germ Using Co-culture of Saccharomyces cerevisiae and Lactobacillus plantarum
Authors: Valiollah Babaeipour, Mahdi Rahaie
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food supplements are rich in specific nutrients and bioactive compounds that eliminate free radicals and improve cellular metabolism. The major bioactive compounds are found in bran and cereal sprouts. Secondary metabolites of these microorganisms have antioxidant properties that can be used alone or in combination with chemotherapy and radiation therapy to treat cancer. Biologically active compounds such as benzoquinone derivatives extracted from fermented wheat germ extract (FWGE) have several positive effects on the overall state of human health and strengthen the immune system. The present work describes the discontinuous fermentation of raw wheat germ for FWGE production through the simultaneous culture process using the probiotic strains of Saccharomyces cerevisiae, Lactobacillus plantarum, and the possibility of using solid waste. To increase production efficiency, first to select important factors in the optimization of each fermentation process, using a factorial statistical scheme of stirring fraction (120 to 200 rpm), dilution of solids to solvent (1 to 8-12), fermentation time (16 to 24 hours) and strain to wheat germ ratio (20% to 50%) were studied and then simultaneous culture was performed to increase the yields of 2 and 6 dimethoxybenzoquinone (2,6-DMBQ). Since 2 and 6 dimethoxy benzoquinone were fermented as the main biologically active compound in wheat germ extract, UV-Vis analysis was performed to confirm the presence of 2 and 6 dimethoxy benzoquinone in the final product. In addition, 2,6-DMBQ of some products was isolated in a non-polar C-18 column and quantified using high performance liquid chromatography (HPLC). Based on our findings, it can be concluded that the increase of 2 and 6 dimethoxybenzoquinone in the simultaneous culture of Saccharomyces cerevisiae - Lactobacillus plantarum compared to pure culture of Saccharomyces cerevisiae (from 1.89 mg / g) to 28.9% (2.66 mg / g) Increased.Keywords: wheat germ, FWGE, saccharomyces cerevisiae, lactobacillus plantarum, co-culture, 2, 6-DMBQ
Procedia PDF Downloads 1281161 An Industrial Steady State Sequence Disorder Model for Flow Controlled Multi-Input Single-Output Queues in Manufacturing Systems
Authors: Anthony John Walker, Glen Bright
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The challenge faced by manufactures, when producing custom products, is that each product needs exact components. This can cause work-in-process instability due to component matching constraints imposed on assembly cells. Clearing type flow control policies have been used extensively in mediating server access between multiple arrival processes. Although the stability and performance of clearing policies has been well formulated and studied in the literature, the growth in arrival to departure sequence disorder for each arriving job, across a serving resource, is still an area for further analysis. In this paper, a closed form industrial model has been formulated that characterizes arrival-to-departure sequence disorder through stable manufacturing systems under clearing type flow control policy. Specifically addressed are the effects of sequence disorder imposed on a downstream assembly cell in terms of work-in-process instability induced through component matching constraints. Results from a simulated manufacturing system show that steady state average sequence disorder in parallel upstream processing cells can be balanced in order to decrease downstream assembly system instability. Simulation results also show that the closed form model accurately describes the growth and limiting behavior of average sequence disorder between parts arriving and departing from a manufacturing system flow controlled via clearing policy.Keywords: assembly system constraint, custom products, discrete sequence disorder, flow control
Procedia PDF Downloads 1771160 Free Energy Computation of A G-Quadruplex-Ligand Structure: A Classical Molecular Dynamics and Metadynamics Simulation Study
Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria
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The DNA G-quadruplex is a four-stranded DNA structure formed by stacked planes of four base paired guanines (G-quartet). Guanine rich DNA sequences appear in many sites of genomic DNA and can potential form G-quadruplexes, such as those occurring at 3'-terminus of the human telomeric DNA. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to down regulate oncogene expression making G-quadruplex an attractive target for anticancer therapy. Many G-quadruplex ligands have been proposed with a planar core to facilitate the pi–pi stacking and electrostatic interactions with the G-quartets. However, many drug candidates are impossibilitated to discriminate a G-quadruplex from a double helix DNA structure. In this context, it is important to investigate the site topology for the interaction of a G-quadruplex with a ligand. In this work, we determine the free energy surface of a G-quadruplex-ligand to study the binding modes of the G-quadruplex (TG4T) with the daunomycin (DM) drug. The complex TG4T-DM is studied using classical molecular dynamics in combination with metadynamics simulations. The metadynamics simulations permit an enhanced sampling of the conformational space with a modest computational cost and obtain free energy surfaces in terms of the collective variables (CV). The free energy surfaces of TG4T-DM exhibit other local minima, indicating the presence of additional binding modes of daunomycin that are not observed in short MD simulations without the metadynamics approach. The results are compared with similar calculations on a different structure (the mutated mu-G4T-DM where the 5' thymines on TG4T-DM have been deleted). The results should be of help to design new G-quadruplex drugs, and understand the differences in the recognition topology sites of the duplex and quadruplex DNA structures in their interaction with ligands.Keywords: g-quadruplex, cancer, molecular dynamics, metadynamics
Procedia PDF Downloads 4581159 Preparation of Zinc Oxide Nanoparticles and Its Anti-diabetic Effect with Momordica Charantia Plant Extract in Diabetic Mice
Authors: Zahid Hussain, Nayyab Sultan
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This study describes the preparation of zinc oxide nanoparticles and their anti-diabetic effect individually and with the combination of Momordica charantia plant extract. This plant is termed bitter melon, balsam pear, bitter gourd, or karela. Blood glucose levels in mice were monitored in their random state before and after the administration of zinc oxide nanoparticles and plant extract. The powdered form of nanoparticles and the selected plant were used as an oral treatment. Diabetes was induced in mice by using a chemical named as streptozotocin. It is an artificial diabetes-inducing chemical. In the case of zinc oxide nanoparticles (3mg/kg) and Momordica charantia plant extract (500mg/kg); the maximum anti-diabetic effect observed was 70% ± 1.6 and 75% ± 1.3, respectively. In the case of the combination of zinc oxide nanoparticles (3mg/kg) and Momordica charantia plant extract (500mg/kg), the maximum anti-diabetic effect observed was 86% ± 2.0. The results obtained were more effective as compared to standard drugs Amaryl (3mg/kg), having an effectiveness of 52% ± 2.4, and Glucophage (500mg/kg), having an effectiveness of 29% ± 2.1. Results indicate that zinc oxide nanoparticles and plant extract in combination are more helpful in treating diabetes as compared to their individual treatments. It is considered a natural treatment without any side effects rather than using standard drugs, which shows adverse side effects on health, and most probably detoxifies in liver and kidneys. More experimental work and extensive research procedures are still required in order to make them applicable to pharmaceutical industries.Keywords: albino mice, amaryl, anti-diabetic effect, blood glucose level, Camellia sinensis, diabetes mellitus, Momordica charantia plant extract, streptozotocin, zinc oxide nanoparticles
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