Search results for: Titanium Scaffold
137 Reliability-Centered Maintenance Application for the Development of Maintenance Strategy for a Cement Plant
Authors: Nabil Hameed Al-Farsi
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This study’s main goal is to develop a model and a maintenance strategy for a cement factory called Arabian Cement Company, Rabigh Plant. The proposed work here depends on Reliability centric maintenance approach to develop a strategy and maintenance schedule that ensures increasing the reliability of the production system components, thus ensuring continuous productivity. The cost-effective maintenance of the plant’s dependability performance is the key goal of durability-based maintenance is. The cement plant consists of 7 important steps, so, developing a maintenance plan based on Reliability centric maintenance (RCM) method is made up of 10 steps accordingly starting from selecting units and data until performing and updating the model. The processing unit chosen for the analysis of this case is the calcinatory unit regarding model’s validation and the Travancore Titanium Products Ltd (TTP) using the claimed data history acquired from the maintenance department maintenance from the mentioned company. After applying the proposed model, the results of the maintenance simulation justified the plant's existing scheduled maintenance policy being reconsidered. Results represent the need for preventive maintenance for all Class A criticality equipment instead of the planned maintenance and the breakdown one for all other equipment depends on its criticality and an FMEA report. Consequently, the additional cost of preventive maintenance would be offset by the cost savings from breakdown maintenance for the remaining equipment.Keywords: engineering, reliability, strategy, maintenance, failure modes, effects and criticality analysis (FMEA)
Procedia PDF Downloads 171136 Role of Vitamin D in Osseointegration of Dental Implant
Authors: Pouya Khaleghi
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Dental implants are a successful treatment modality for restoring both function and aesthetics. Dental implant treatment has predictive results in the replacement of the lost teeth and has a high success rate even in the long term. The most important factor which is responsible for the positive course of implant treatment is the process of osseointegration between the implant structure and the host’s bone tissue. During recent years, many studies have focused on surgical and prosthetic factors, as well as the implant-related factors. However, implant failure still occurs despite the improvements that have led to the increased survival rate of dental implants, which suggests the possible role of some host-related risk factors. Vitamin D is a fat-soluble vitamin regulating calcium and phosphorus metabolism in tissues. The role of vitamin D in bone healing has been under investigation for several years. Vitamin D deficiency has also been associated with impaired and delayed callus formation and fractures healing; however, the role of vitamin D has not been clarified. Therefore, it is extremely important to study the phenomenon of a connection formed between bone tissue and the surface of a titanium implant and find correlations between the 25- hydroxycholecalciferol concentration in blood serum and the course of osseointegration. Because the processes of bone remodeling are very dynamic in the period of actual osseointegration, it is necessary to obtain the correct concentration of vitamin D3 metabolites in blood serum. In conclusion, the correct level of 25-hydroxycholecalciferol on the day of surgery and vitamin D deficiency treatment have a significant influence on the increase in the bone level at the implant site during the process of osseointegration assessed radiologically.Keywords: implant, osseointegration, vitamin d, dental
Procedia PDF Downloads 171135 Design of Nanoreinforced Polyacrylamide-Based Hybrid Hydrogels for Bone Tissue Engineering
Authors: Anuj Kumar, Kummara M. Rao, Sung S. Han
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Bone tissue engineering has emerged as a potentially alternative method for localized bone defects or diseases, congenital deformation, and surgical reconstruction. The designing and the fabrication of the ideal scaffold is a great challenge, in restoring of the damaged bone tissues via cell attachment, proliferation, and differentiation under three-dimensional (3D) biological micro-/nano-environment. In this case, hydrogel system composed of high hydrophilic 3D polymeric-network that is able to mimic some of the functional physical and chemical properties of the extracellular matrix (ECM) and possibly may provide a suitable 3D micro-/nano-environment (i.e., resemblance of native bone tissues). Thus, this proposed hydrogel system is highly permeable and facilitates the transport of the nutrients and metabolites. However, the use of hydrogels in bone tissue engineering is limited because of their low mechanical properties (toughness and stiffness) that continue to posing challenges in designing and fabrication of tough and stiff hydrogels along with improved bioactive properties. For this purpose, in our lab, polyacrylamide-based hybrid hydrogels were synthesized by involving sodium alginate, cellulose nanocrystals and silica-based glass using one-step free-radical polymerization. The results showed good in vitro apatite-forming ability (biomineralization) and improved mechanical properties (under compression in the form of strength and stiffness in both wet and dry conditions), and in vitro osteoblastic (MC3T3-E1 cells) cytocompatibility. For in vitro cytocompatibility assessment, both qualitative (attachment and spreading of cells using FESEM) and quantitative (cell viability and proliferation using MTT assay) analyses were performed. The obtained hybrid hydrogels may potentially be used in bone tissue engineering applications after establishment of in vivo characterization.Keywords: bone tissue engineering, cellulose nanocrystals, hydrogels, polyacrylamide, sodium alginate
Procedia PDF Downloads 151134 Heat Transfer Enhancement of Structural Concretes Made of Macro-Encapsulated Phase Change Materials
Authors: Ehsan Mohseni, Waiching Tang, Shanyong Wang
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Low thermal conductivity of phase change materials (PCMs) affects the thermal performance and energy storage efficiency of latent heat thermal energy storage systems. In the current research, a structural lightweight concrete with function of indoor temperature control was developed using thermal energy storage aggregates (TESA) and nano-titanium (NT). The macro-encapsulated technique was served to incorporate the PCM into the lightweight aggregate through vacuum impregnation. The compressive strength was measured, and the thermal performance of concrete panel was evaluated by using a self-designed environmental chamber. The impact of NT on microstructure was also assessed via scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) tests. The test results indicated that NT was able to increase the compressive strength by filling the micro pores and making the microstructure denser and more homogeneous. In addition, the environmental chamber experiment showed that introduction of NT into TESA improved the heat transfer of composites noticeably. The changes were illustrated by the reduction in peak temperatures in the centre, outside and inside surfaces of concrete panels by the inclusion of NT. It can be concluded that NT particles had the capability to decrease the energy consumption and obtain higher energy storage efficiency by the reduction of indoor temperature.Keywords: heat transfer, macro-encapsulation, microstructure properties, nanoparticles, phase change material
Procedia PDF Downloads 105133 Synthesis and Tribological Properties of the Al-Cr-N/MoS₂ Self-Lubricating Coatings by Hybrid Magnetron Sputtering
Authors: Tie-Gang Wang, De-Qiang Meng, Yan-Mei Liu
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Ternary AlCrN coatings were widely used to prolong cutting tool life because of their high hardness and excellent abrasion resistance. However, the friction between the workpiece and cutter surface was increased remarkably during machining difficult-to-cut materials (such as superalloy, titanium, etc.). As a result, a lot of cutting heat was generated and cutting tool life was shortened. In this work, an appropriate amount of solid lubricant MoS₂ was added into the AlCrN coating to reduce the friction between the tool and the workpiece. A series of Al-Cr-N/MoS₂ self-lubricating coatings with different MoS₂ contents were prepared by high power impulse magnetron sputtering (HiPIMS) and pulsed direct current magnetron sputtering (Pulsed DC) compound system. The MoS₂ content in the coatings was changed by adjusting the sputtering power of the MoS₂ target. The composition, structure and mechanical properties of the Al-Cr-N/MoS2 coatings were systematically evaluated by energy dispersive spectrometer, scanning electron microscopy, X-ray photoelectron spectroscopy, X-ray diffractometer, nano-indenter tester, scratch tester, and ball-on-disk tribometer. The results indicated the lubricant content played an important role in the coating properties. As the sputtering power of the MoS₂ target was 0.1 kW, the coating possessed the highest hardness 14.1GPa, the highest critical load 44.8 N, and the lowest wear rate 4.4×10−3μm2/N.Keywords: self-lubricating coating, Al-Cr-N/MoS₂ coating, wear rate, friction coefficient
Procedia PDF Downloads 132132 Horizontal Bone Augmentation Using Two Membranes at Dehisced Implant Sites: A Randomized Clinical Study
Authors: Monika Bansal
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Background: Placement of dental implant in narrow alveolar ridge is challenging to be treated. GBR procedure is currently most widely used to augment the deficient alveolar ridges and to treat the fenestration and dehiscence around dental implants. Thus, the objectives of the present study were to evaluate as well as compare the clinical performance of collagen membrane and titanium mesh for horizontal bone augmentation at dehisced implant sites. Methods and material: Total 12 single edentulous implant sites with buccal bone deficiency in 8 subjects were equally divided and treated simultaneously with either of the two membranes and DBBM(Bio-Oss) bone graft. Primary outcome measurements in terms of defect height and defect width were made using a calibrated plastic periodontal probe. Re-entry surgery was performed to remeasure the augmented site and to remove Ti-mesh at 6th month. Independent paired t-tests for the inter-group comparison and student-paired t-tests for the intra-group comparison were performed. The differences were considered to be significant at p ≤ 0.05. Results: Mean defect fill with respect to height and width was 3.50 ± 0.54 mm (87%) and 2.33 ± 0.51 mm (82%) for collagen membrane and 3.83 ± 0.75 mm (92%) and 2.50 ± 0.54 mm (88%) for Ti-mesh group respectively. Conclusions: Within the limitation of the study, it was concluded that mean defect height and width after 6 months were statistically significant within the group without significant difference between them, although defect resolution was better in Ti-mesh.Keywords: collagen membrane, dehiscence, dental implant, horizontal bone, augmentation, ti-mesh
Procedia PDF Downloads 111131 Systematic Identification and Quantification of Substrate Specificity Determinants in Human Protein Kinases
Authors: Manuel A. Alonso-Tarajano, Roberto Mosca, Patrick Aloy
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Protein kinases participate in a myriad of cellular processes of major biomedical interest. The in vivo substrate specificity of these enzymes is a process determined by several factors, and despite several years of research on the topic, is still far from being totally understood. In the present work, we have quantified the contributions to the kinase substrate specificity of i) the phosphorylation sites and their surrounding residues in the sequence and of ii) the association of kinases to adaptor or scaffold proteins. We have used position-specific scoring matrices (PSSMs), to represent the stretches of sequences phosphorylated by 93 families of kinases. We have found negative correlations between the number of sequences from which a PSSM is generated and the statistical significance and the performance of that PSSM. Using a subset of 22 statistically significant PSSMs, we have identified specificity determinant residues (SDRs) for 86% of the corresponding kinase families. Our results suggest that different SDRs can function as positive or negative elements of substrate recognition by the different families of kinases. Additionally, we have found that human proteins with known function as adaptors or scaffolds (kAS) tend to interact with a significantly large fraction of the substrates of the kinases to which they associate. Based on this characteristic we have identified a set of 279 potential adaptors/scaffolds (pAS) for human kinases, which is enriched in Pfam domains and functional terms tightly related to the proposed function. Moreover, our results show that for 74.6% of the kinase– pAS association found, the pAS colocalize with the substrates of the kinases they are associated to. Finally, we have found evidence suggesting that the association of kinases to adaptors and scaffolds, may contribute significantly to diminish the in vivo substrate crossed- specificity of protein kinases. In general, our results indicate the relevance of several SDRs for both the positive and negative selection of phosphorylation sites by kinase families and also suggest that the association of kinases to pAS proteins may be an important factor for the localization of the enzymes with their set of substrates.Keywords: kinase, phosphorylation, substrate specificity, adaptors, scaffolds, cellular colocalization
Procedia PDF Downloads 343130 Antibacterial and Cytotoxicity Activity of Cinchona Alkaloids
Authors: Alma Ramić, Mirjana Skočibušić, Renata Odžak, Tomica Hrenar, Ines Primožič
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In an attempt to identify a new class of antimicrobial agents, the antimicrobial potential of Cinchona alkaloid derivatives was evaluated. The bark of the Cinchona trees is the source of a variety of alkaloids, among which the best known are quinine, quinidine, cinchonine and cinchonidine. They are very useful as organocatalysts in stereoselective synthesis. On the other hand, quinine is traditionally used in the treatment of malaria. Furthermore, Cinchona alkaloids possess various analgesic, anti-inflammatory and anti–arrhythmic properties as well. In this work we present the synthesis of twenty quaternary derivatives of pseudo−enantiomeric Cinchona alkaloid derivatives to evaluate their antibacterial activity. Quaternization of quinuclidine moiety was carried out with groups diverse in their size. The structures of compounds were systematically modified to obtain drug-like properties with proper physical and chemical properties and avoiding toxophore. All compounds were prepared in good yields and were characterized by standard analytical spectroscopy methods (1D and 2D NMR, IR, MS). The antibacterial activities of all compounds were evaluated against series of recent clinical isolates of antibiotic susceptible Gram-positive and resistant Gram-negative pathogens by determining their zone of inhibition and minimum inhibitory concentrations. All compounds showed good to strong broad-spectrum activity, equivalent or better in comparison with standard antibiotics used. Furthermore, seven compounds exhibited significant antibacterial efficiency against Gram-negative isolates. To visualize the results, principal component analysis was used as an additional classification tool. Cytotoxicity of compounds with different cell lines in human cell culture was determined. Based on these results, substituted quaternary Cinchona scaffold can be considered as promising new class of antimicrobials and further investigations should be performed. Supported by Croatian Science Foundation, Project No 3775 ADESIRE.Keywords: antibacterial efficiency, cinchona alkaloids, cytotoxicity, pseudo‐enantiomers
Procedia PDF Downloads 153129 An Investigation of Surface Texturing by Ultrasonic Impingement of Micro-Particles
Authors: Nagalingam Arun Prasanth, Ahmed Syed Adnan, S. H. Yeo
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Surface topography plays a significant role in the functional performance of engineered parts. It is important to have a control on the surface geometry and understanding on the surface details to get the desired performance. Hence, in the current research contribution, a non-contact micro-texturing technique has been explored and developed. The technique involves ultrasonic excitation of a tool as a prime source of surface texturing for aluminum alloy workpieces. The specimen surface is polished first and is then immersed in a liquid bath containing 10% weight concentration of Ti6Al4V grade 5 spherical powders. A submerged slurry jet is used to recirculate the spherical powders under the ultrasonic horn which is excited at an ultrasonic frequency and amplitude of 40 kHz and 70 µm respectively. The distance between the horn and workpiece surface was remained fixed at 200 µm using a precision control stage. Texturing effects were investigated for different process timings of 1, 3 and 5 s. Thereafter, the specimens were cleaned in an ultrasonic bath for 5 mins to remove loose debris on the surface. The developed surfaces are characterized by optical and contact surface profiler. The optical microscopic images show a texture of circular spots on the workpiece surface indented by titanium spherical balls. Waviness patterns obtained from contact surface profiler supports the texturing effect produced from the proposed technique. Furthermore, water droplet tests were performed to show the efficacy of the proposed technique to develop hydrophilic surfaces and to quantify the texturing effect produced.Keywords: surface texturing, surface modification, topography, ultrasonic
Procedia PDF Downloads 221128 On the Development of Medical Additive Manufacturing in Egypt
Authors: Khalid Abdelghany
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Additive Manufacturing (AM) is the manufacturing technology that is used to fabricate fast products direct from CAD models in very short time and with minimum operation steps. Jointly with the advancement in medical computer modeling, AM proved to be a very efficient tool to help physicians, orthopedic surgeons and dentists design and fabricate patient-tailored surgical guides, templates and customized implants from the patient’s CT / MRI images. AM jointly with computer-assisted designing/computer-assisted manufacturing (CAD/CAM) technology have enabled medical practitioners to tailor physical models in a patient-and purpose-specific fashion and helped to design and manufacture of templates, appliances and devices with a high range of accuracy using biocompatible materials. In developing countries, there are some technical and financial limitations of implementing such advanced tools as an essential portion of medical applications. CMRDI institute in Egypt has been working in the field of Medical Additive Manufacturing since 2003 and has assisted in the recovery of hundreds of poor patients using these advanced tools. This paper focuses on the surgical and dental use of 3D printing technology in Egypt as a developing country. The presented case studies have been designed and processed using the software tools and additive manufacturing machines in CMRDI through cooperative engineering and medical works. Results showed that the implementation of the additive manufacturing tools in developed countries is successful and could be economical comparing to long treatment plans.Keywords: additive manufacturing, dental and orthopeadic stents, patient specific surgical tools, titanium implants
Procedia PDF Downloads 315127 Photocatalysis with Fe/Ti-Pillared Clays for the Oxofunctionalization of Alkylaromatics by O2
Authors: Houria Rezala, Jose Luis Valverde, Amaya Romero, Alessandra Molinari, Andrea Maldotti
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A pillared montmorillonite containing iron doped titania (Fe/Ti-PILC) has been prepared from a natural clay. This material has been characterized by X-ray diffraction, nitrogen adsorption, temperature programmed desorption of ammonia, inductively coupled plasma atomic emission spectroscopy, atomic absorption, and diffuse reflectance UV-VIS spectroscopy. The layer structure of Fe/Ti-PILC resulted to be ordered with an insertion of pillars, which caused a slight increase in the basal spacing of the clay. Its specific surface area was about three times larger than that of the parent Na-montmorillonite due principally to the creation of a remarkable microporous network. The doped material was a robust photocatalyst able to oxidize liquid alkyl aromatics to the corresponding carbonylic derivatives, using O2 as the oxidizing species, at mild pressure and temperature conditions. Accumulation of valuable carbonylic derivatives was possible since their over-oxidation to carbon dioxide was negligible. Fe/Ti-PILC was able to discriminate between toluene and cyclohexane in favor of the aromatic compound with an efficiency that is about three times higher than that of titanium pillared clays (Ti-PILC). It is likely that the addition of iron favored the formation of new acid sites able to interact with the aromatic substrate. Iron doping caused a significant TiO2 visible light-induced activity (wavelength > 400 nm) with only minor negative effects on its performance under UV-light irradiation (wavelength > 290 nm).Keywords: alkyl aromatics oxidation, heterogeneous photocatalysis, iron doping, pillared clays
Procedia PDF Downloads 450126 Isolation and Characterization of the First Known Inhibitor Cystine Knot Peptide in Sea Anemone: Inhibitory Activity on Acid-Sensing Ion Channels
Authors: Armando A. Rodríguez, Emilio Salceda, Anoland Garateix, André J. Zaharenko, Steve Peigneur, Omar López, Tirso Pons, Michael Richardson, Maylín Díaz, Yasnay Hernández, Ludger Ständker, Jan Tytgat, Enrique Soto
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Acid-sensing ion channels are cation (Na+) channels activated by a pH drop. These proteins belong to the ENaC/degenerin superfamily of sodium channels. ASICs are involved in sensory perception, synaptic plasticity, learning, memory formation, cell migration and proliferation, nociception, and neurodegenerative disorders, among other processes; therefore those molecules that specifically target these channels are of growing pharmacological and biomedical interest. Sea anemones produce a large variety of ion channels peptide toxins; however, those acting on ligand-gated ion channels, such as Glu-gated, Ach-gated ion channels, and acid-sensing ion channels (ASICs), remain barely explored. The peptide PhcrTx1 is the first compound characterized from the sea anemone Phymanthus crucifer, and it constitutes a novel ASIC inhibitor. This peptide was purified by chromatographic techniques and pharmacologically characterized on acid-sensing ion channels of mammalian neurons using patch-clamp techniques. PhcrTx1 inhibited ASIC currents with an IC50 of 100 nM. Edman degradation yielded a sequence of 32 amino acids residues, with a molecular mass of 3477 Da by MALDI-TOF. No similarity to known sea anemone peptides was found in protein databases. The computational analysis of Cys-pattern and secondary structure arrangement suggested that this is a structurally ICK (Inhibitor Cystine Knot)-type peptide, a scaffold that had not been found in sea anemones but in other venomous organisms. These results show that PhcrTx1 represents the first member of a new structural group of sea anemones toxins acting on ASICs. Also, this peptide constitutes a novel template for the development of drugs against pathologies related to ASICs function.Keywords: animal toxin, inhibitor cystine knot, ion channel, sea anemone
Procedia PDF Downloads 308125 Environmental Effects on Coconut Coir Fiber Epoxy Composites Having TiO₂ as Filler
Authors: Srikanth Korla, Mahesh Sharnangat
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Composite materials are being widely used in Aerospace, Naval, Defence and other branches of engineering applications. Studies on natural fibers is another emerging research area as they are available in abundance, and also due to their eco-friendly in nature. India being one of the major producer of coir, there is always a scope to study the possibilities of exploring coir as reinforment, and with different combinations of other elements of the composite. In present investigation effort is made to utilize properties possessed by natural fiber and make them enable with polymer/epoxy resin. In natural fiber coconut coir is used as reinforcement fiber in epoxy resin with varying weight percentages of fiber and filler material. Titanium dioxide powder (TiO2) is used as filler material with varying weight percentage including 0%, 2% and 4% are considered for experimentation. Environmental effects on the performance of the composite plate are also studied and presented in this project work; Moisture absorption test for composite specimens is conducted using different solvents including Kerosene, Mineral Water and Saline Water, and its absorption capacity is evaluated. Analysis is carried out in different combinations of Coir as fiber and TiO2 as filler material, and the best suitable composite material considering the strength and environmental effects is identified in this work. Therefore, the significant combination of the composite material is with following composition: 2% TiO2 powder 15% of coir fibre and 83% epoxy, under unique mechanical and environmental conditions considered in the work.Keywords: composite materials, moisture test, filler material, natural fibre composites
Procedia PDF Downloads 205124 Solar Photocatalytic Hydrogen Production from Glycerol Reforming Using Ternary Cu/TiO2/Graphene
Authors: Tumelo W. P. Seadira, Thabang Ntho, Cornelius M. Masuku, Michael S. Scurrell
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A ternary Cu/TiO2/rGO photocatalysts was prepared using solvothermal method. Firstly, pure anatase TiO2 hollow spheres were prepared with titanium butoxide, ethanol, ammonium sulphate, and urea via hydrothermal method; and Cu nanoparticles were subsequently loaded on the surface of the hollow spheres by wet impregnation. During the solvothermal process, the deposition and well dispersion of Cu-TiO2 hollow spheres composites onto the graphene oxide surface, as well as the reduction of graphene oxide to graphene were achieved. The morphological and structural properties of the prepared samples were characterized by Brunauer-Emmett-Tellet (BET), X-ray Diffraction (XRD), Scanning Electron Microscope (SEM), Transmission Electron Microscopy (TEM), and UV-vis DRS, and photoelectrochemical. The activities of the prepared catalysts were tested for hydrogen production via simultaneous photocatalytic water-splitting and glycerol reforming under visible light irradiation. The excellent photocatalytic activity of the Cu-TiO2-hollow-spheres/rGO catalyst was attributed the rGO which acts as both storage and transferor of electrons generated at the Cu and TiO2 heterojunction, thus increasing the electron-hole pairs separation. This paper reports the preparation of photocatalyst which is highly active by coupling reduced graphene oxide with nano-structured TiO2 with high surface area that can efficiently harvest the visible light for effective water-splitting and glycerol photocatalytic reforming in order to achieve efficient hydrogen evolution.Keywords: glycerol reforming, hydrogen evolution, graphene oxide, Cu/TiO2-hollow-spheres/rGO
Procedia PDF Downloads 156123 Stem Cell Fate Decision Depending on TiO2 Nanotubular Geometry
Authors: Jung Park, Anca Mazare, Klaus Von Der Mark, Patrik Schmuki
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In clinical application of TiO2 implants on tooth and hip replacement, migration, adhesion and differentiation of neighboring mesenchymal stem cells onto implant surfaces are critical steps for successful bone regeneration. In a recent decade, accumulated attention has been paid on nanoscale electrochemical surface modifications on TiO2 layer for improving bone-TiO2 surface integration. We generated, on titanium surfaces, self-assembled layers of vertically oriented TiO2 nanotubes with defined diameters between 15 and 100 nm and here we show that mesenchymal stem cells finely sense TiO2 nanotubular geometry and quickly decide their cell fate either to differentiation into osteoblasts or to programmed cell death (apoptosis) on TiO2 nanotube layers. These cell fate decisions are critically dependent on nanotube size differences (15-100nm in diameters) of TiO2 nanotubes sensing by integrin clustering. We further demonstrate that nanoscale topography-sensing is feasible not only in mesenchymal stem cells but rather seems as generalized nanoscale microenvironment-cell interaction mechanism in several cell types composing bone tissue network including osteoblasts, osteoclast, endothelial cells and hematopoietic stem cells. Additionally we discuss the synergistic effect of simultaneous stimulation by nanotube-bound growth factor and nanoscale topographic cues on enhanced bone regeneration.Keywords: TiO2 nanotube, stem cell fate decision, nano-scale microenvironment, bone regeneration
Procedia PDF Downloads 431122 Wear Performance of SLM Fabricated 1.2709 Steel Nanocomposite Reinforced by TiC-WC for Mould and Tooling Applications
Authors: Daniel Ferreira, José M. Marques Oliveira, Filipe Oliveira
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Wear phenomena is critical in injection moulding processes, causing failure of the components, and making the parts more expensive with an additional wasting time. When very abrasive materials are being injected inside the steel mould’s cavities, such as polymers reinforced with abrasive fibres, the consequences of the wear are more evident. Maraging steel (1.2709) is commonly employed in moulding components to resist in very aggressive injection conditions. In this work, the wear performance of the SLM produced 1.2709 maraging steel reinforced by ultrafine titanium and tungsten carbide (TiC-WC), was investigated using a pin-on-disk testing apparatus. A polypropylene reinforced with 40 wt.% fibreglass (PP40) disk, was used as the counterpart material. The wear tests were performed at 40 N constant load and 0.4 ms-1 sliding speed at room temperature and humidity conditions. The experimental results demonstrated that the wear rate in the 18Ni300-TiC-WC composite is lower than the unreinforced 18Ni300 matrix. The morphology and chemical composition of the worn surfaces was observed by 3D optical profilometry and scanning electron microscopy (SEM), respectively. The resulting debris, caused by friction, were also analysed by SEM and energy dispersive X-ray spectroscopy (EDS). Their morphology showed distinct shapes and sizes, which indicated that the wear mechanisms, may be different in maraging steel produced by casting and SLM. The coefficient of friction (COF) was recorded during the tests, which helped to elucidate the wear mechanisms involved.Keywords: selective laser melting, nanocomposites, injection moulding, polypropylene with fibreglass
Procedia PDF Downloads 154121 A Photoemission Study of Dye Molecules Deposited by Electrospray on rutile TiO2 (110)
Authors: Nouf Alharbi, James O'shea
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For decades, renewable energy sources have received considerable global interest due to the increase in fossil fuel consumption. The abundant energy produced by sunlight makes dye-sensitised solar cells (DSSCs) a promising alternative compared to conventional silicon and thin film solar cells due to their transparency and tunable colours, which make them suitable for applications such as windows and glass facades. The transfer of an excited electron onto the surface is an important procedure in the DSSC system, so different groups of dye molecules were studied on the rutile TiO2 (110) surface. Currently, the study of organic dyes has become an interest of researchers due to ruthenium being a rare and expensive metal, and metal-free organic dyes have many features, such as high molar extinction coefficients, low manufacturing costs, and ease of structural modification and synthesis. There are, of course, some groups that have developed organic dyes and exhibited lower light-harvesting efficiency ranging between 4% and 8%. Since most dye molecules are complicated or fragile to be deposited by thermal evaporation or sublimation in the ultra-high vacuum (UHV), all dyes (i.e, D5, SC4, and R6) in this study were deposited in situ using the electrospray deposition technique combined with X-ray photoelectron spectroscopy (XPS) as an alternative method to obtain high-quality monolayers of titanium dioxide. These organic molecules adsorbed onto rutile TiO2 (110) are explored by XPS, which can be used to obtain element-specific information on the chemical structure and study bonding and interaction sites on the surface.Keywords: dyes, deposition, electrospray, molecules, organic, rutile, sensitised, XPS
Procedia PDF Downloads 74120 Alpha-To-Omega Phase Transition in Bulk Nanostructured Ti and (α+β) Ti Alloys
Authors: Askar Kilmametov, Julia Ivanisenko, Boris Straumal, Horst Hahn
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The high-pressure α- to ω-phase transition was discovered in elemental Ti and Zr fifty years ago using static high pressure and then observed to appear between 2 and 12 GPa at room temperature, depending on the experimental technique, the pressure environment, and the sample purity. The fact that ω-phase is retained in a metastable state in ambient condition after the removal of the pressure has been used to check the changes in magnetic and superconductive behavior, electron band structure and mechanical properties. However, the fundamental knowledge on a combination of both mechanical treatment and high applied pressure treatments for ω-phase formation in Ti alloys is currently lacking and has to be studied in relation to improved mechanical properties of bulk nanostructured states. In the present study, nanostructured (α+β) Ti alloys containing β-stabilizing elements such as Co, Fe, Cr, Nb were performed by severe plastic deformation, namely high pressure torsion (HPT) technique. HPT-induced α- to ω-phase transformation was revealed in dependence on applied pressure and shear strains by means of X-ray diffraction, transmission electron microscopy, and differential scanning calorimetry. The transformation kinetics was compared with the kinetics of pressure-induced transition. Orientation relationship between α-, β- and ω-phases was taken into consideration and analyzed according to theoretical calculation proposed earlier. The influence of initial state before HPT appeared to be considerable for subsequent α- to ω-phase transition. Thermal stability of the HPT-induced ω-phase was discussed as well in the frame of mechanical behavior of Ti and Ti-based alloys produced by shear deformation under high applied pressure.Keywords: bulk nanostructured materials, high pressure phase transitions, severe plastic deformation, titanium alloys
Procedia PDF Downloads 419119 The Impact of Surface Roughness and PTFE/TiF3/FeF3 Additives in Plain ZDDP Oil on the Friction and Wear Behavior Using Thermal and Tribological Analysis under Extreme Pressure Condition
Authors: Gabi N. Nehme, Saeed Ghalambor
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The use of titanium fluoride and iron fluoride (TiF3/FeF3) catalysts in combination with polutetrafluoroethylene (PTFE) in plain zinc dialkyldithiophosphate (ZDDP) oil is important for the study of engine tribocomponents and is increasingly a strategy to improve the formation of tribofilm and to provide low friction and excellent wear protection in reduced phosphorus plain ZDDP oil. The influence of surface roughness and the concentration of TiF3/FeF3/PTFE were investigated using bearing steel samples dipped in lubricant solution @100°C for two different heating time durations. This paper addresses the effects of water drop contact angle using different surface finishes after treating them with different lubricant combination. The calculated water drop contact angles were analyzed using Design of Experiment software (DOE) and it was determined that a 0.05 μm Ra surface roughness would provide an excellent TiF3/FeF3/PTFE coating for antiwear resistance as reflected in the scanning electron microscopy (SEM) images and the tribological testing under extreme pressure conditions. Both friction and wear performance depend greatly on the PTFE/and catalysts in plain ZDDP oil with 0.05% phosphorous and on the surface finish of bearing steel. The friction and wear reducing effects, which was observed in the tribological tests, indicated a better micro lubrication effect of the 0.05 μm Ra surface roughness treated at 100°C for 24 hours when compared to the 0.1 μm Ra surface roughness with the same treatment.Keywords: scanning electron microscopy, ZDDP, catalysts, PTFE, friction, wear
Procedia PDF Downloads 350118 Azadrachea indica Leaves Extract Assisted Green Synthesis of Ag-TiO₂ for Degradation of Dyes in Aqueous Medium
Authors: Muhammad Saeed, Sheeba Khalid
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Aqueous pollution due to the textile industry is an important issue. Photocatalysis using metal oxides as catalysts is one of the methods used for eradication of dyes from textile industrial effluents. In this study, the synthesis, characterization, and evaluation of photocatalytic activity of Ag-TiO₂ are reported. TiO₂ catalysts with 2, 4, 6 and 8% loading of Ag were prepared by green methods using Azadrachea indica leaves' extract as reducing agent and titanium dioxide and silver nitrate as precursor materials. The 4% Ag-TiO₂ exhibited the best catalytic activity for degradation of dyes. Prepared catalyst was characterized by advanced techniques. Catalytic degradation of methylene blue and rhodamine B were carried out in Pyrex glass batch reactor. Deposition of Ag greatly enhanced the catalytic efficiency of TiO₂ towards degradation of dyes. Irradiation of catalyst excites electrons from conduction band of catalyst to valence band yielding an electron-hole pair. These photoexcited electrons and positive hole undergo secondary reaction and produce OH radicals. These active radicals take part in the degradation of dyes. More than 90% of dyes were degraded in 120 minutes. It was found that there was no loss catalytic efficiency of prepared Ag-TiO₂ after recycling it for two times. Photocatalytic degradation of methylene blue and rhodamine B followed Eley-Rideal mechanism which states that dye reacts in fluid phase with adsorbed oxygen. 27 kJ/mol and 20 kJ/mol were found as activation energy for photodegradation of methylene blue and rhodamine B dye respectively.Keywords: TiO₂, Ag-TiO₂, methylene blue, Rhodamine B., photo degradation
Procedia PDF Downloads 165117 Effect of Solvents in the Extraction and Stability of Anthocyanin from the Petals of Caesalpinia pulcherrima for Natural Dye-Sensitized Solar Cell
Authors: N. Prabavathy, R. Balasundaraprabhu, S. Shalini, Dhayalan Velauthapillai, S. Prasanna, N. Muthukumarasamy
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Dye sensitized solar cell (DSSC) has become a significant research area due to their fundamental and scientific importance in the area of energy conversion. Synthetic dyes as sensitizer in DSSC are efficient and durable but they are costlier, toxic and have the tendency to degrade. Natural sensitizers contain plant pigments such as anthocyanin, carotenoid, flavonoid, and chlorophyll which promote light absorption as well as injection of charges to the conduction band of TiO2 through the sensitizer. But, the efficiency of natural dyes is not up to the mark mainly due to instability of the pigment such as anthocyanin. The stability issues in vitro are mainly due to the effect of solvents on extraction of anthocyanins and their respective pH. Taking this factor into consideration, in the present work, the anthocyanins were extracted from the flower Caesalpinia pulcherrima (C. pulcherrimma) with various solvents and their respective stability and pH values are discussed. The usage of citric acid as solvent to extract anthocyanin has shown good stability than other solvents. It also helps in enhancing the sensitization properties of anthocyanins with Titanium dioxide (TiO2) nanorods. The IPCE spectra show higher photovoltaic performance for dye sensitized TiO2nanorods using citric acid as solvent. The natural DSSC using citric acid as solvent shows a higher efficiency compared to other solvents. Hence citric acid performs to be a safe solvent for natural DSSC in boosting the photovoltaic performance and maintaining the stability of anthocyanins.Keywords: Caesalpinia pulcherrima, citric acid, dye sensitized solar cells, TiO₂ nanorods
Procedia PDF Downloads 290116 Effect of Sintering Time and Porosity on Microstructure, Mechanical and Corrosion Properties of Ti6Al15Mo Alloy for Implant Applications
Authors: Jyotsna Gupta, S. Ghosh, S. Aravindan
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The requirement of artificial prostheses (such as hip and knee joints) has increased with time. Many researchers are working to develop new implants with improved properties such as excellent biocompatibility with no tissue reactions, corrosion resistance in body fluid, high yield strength and low elastic modulus. Further, the morphological properties of the artificial implants should also match with that of the human bone so that cell adhesion, proliferation and transportation of the minerals and nutrition through body fluid can be obtained. Present study attempts to make porous Ti6Al15Mo alloys through powder metallurgy route using space holder technique. The alloy consists of 6wt% of Al which was taken as α phase stabilizer and 15wt% Mo was taken as β phase stabilizer with theoretical density 4.708. Ammonium hydrogen carbonate is used as a space holder in order to generate the porosity. The porosity of these fabricated porous alloys was controlled by adding the 0, 50, 70 vol.% of the space holder content. Three phases were found in the microstructure: α, α_2 and β phase of titanium. Kirkendall pores are observed to be decreased with increase of holding time during sintering and parallelly compressive strength and elastic modulus value increased slightly. Compressive strength and elastic modulus of porous Ti-6Al-15Mo alloy (1.17 g/cm3 density) is found to be suitable for cancellous bone. Released ions from Ti-6Al-15Mo alloy are far below from the permissible limits in human body.Keywords: bone implant, powder metallurgy, sintering time, Ti-6Al-15Mo
Procedia PDF Downloads 144115 In Vitro and in Vivo Evaluation of Nano Collagen Molecules to Enhance Mesenchymal Stem Cells Differentiate into Insulin Producing Cells
Authors: Chin-Tsu Ma, Yi-Jhen Wu, Hsia Ying Cheng, Han Hsiang Huang, Shyh Ming Kuo
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The use of specific molecules including nutrients and pharmacological agents has been tried in modulation of stem cells differentiation (MSCs) to insulin producing cells. The aim of this study is to investigate the ability of nano collagen molecules (nutrient or scaffold) to enhance the MSCs differentiation into insulin-producing cells in combination with nicotinamide and exendin-4 (pharmacological agents) in vitro and in vivo. The results demonstrated that the cells exhibit morphologically islet-like clusters after treatment with nano collagen molecules, nicotinamide and exendin-4. MSCs extra treated with nano collagen molecules showed significant increases in Nkx6.1 and insulin mRNA expression at 14-d and 21-d culture compared with those merely treated with nicotinamide and exendin-4. Early 7-day elevation in PDX-1 mRNA expression was observed. Furthermore, the MSCs exposed to nano collagen molecules produced the highest secretion of insulin (p < 0.05). Type-2 diabetes induced by high-fat diet and low dose of streptozotocin in rat model was built in this study. This rat exhibited higher food intake, water intake, lower glucose tolerance, lower-insulin tolerance, and higher HbA1C (significant increases, p < 0.01) as compared with the normal rat that demonstrated the model of type-2 diabetes was successfully built. Biopsy examinations also showed that obvious destruction of islet. After injection of differentiated MSCs into the destructed pancreas of diabetes rat, more regenerated islet were observed at the rats that treated with nano collagen molecules and exhibited much lower HbA1C as compared with the normal rat and diabetes rat after 4 weeks (significant deceases, p < 0.001). These results indicate that the culturing MSCs with nano collagen molecules, nicotinamide, and exendin-4 are beneficial for MSCs differentiation into islet-like cells. These nano collagen molecules may lead to alternations or up-regulation of gene expression and influence the differentiated outcomes induced by nicotinamide and exendin-4.Keywords: nano collagen molecules, nicotinamide, MSCs, diabetes
Procedia PDF Downloads 410114 The Effect of Different Metal Nanoparticles on Growth and Survival of Pseudomonas syringae Bacteria
Authors: Omar Alhamd, Peter A. Thomas, Trevor J. Greenhough, Annette K. Shrive
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The Pseudomonas syringae species complex includes many plant pathogenic strains with highly specific interactions with varied host species and cultivars. The rapid spread of these bacteria over the last ten years has become a cause for concern. Nanoparticles have previously shown promise in microbiological action. We have therefore investigated in vitro and in vivo the effects of different types and sizes of nanoparticles in order to provide quantitative information about their effect on the bacteria. The effects of several different nanoparticles against several bacteria strains were investigated. The effect of NP on bacterial growth was studied by measuring the optical density, biochemical and nutritional tests, and transmission electron microscopy (TEM) to determine the shape and size of NP. Our results indicate that their effects varied, with either a negative or a positive impact on both bacterial and plant growth. Additionally, the methods of exposure to nanoparticles have a crucial role in accumulation, translocation, growth response and bacterial growth. The results of our studies on the behaviour and effects of nanoparticles in model plants showed. Cerium oxide (CeO₂) and silver (Ag) NP showed significant antibacterial activity against several pathogenic bacteria. It was found that titanium nanoparticles (TiO₂) can have either a negative or a positive impact, according to concentration and size. It is also thought that environmental conditions can have a major influence on bacterial growth. Studies were therefore also carried out under some environmental stress conditions to test bacterial survival and to assess bacterial virulence. All results will be presented including information about the effects of different nanoparticles on Pseudomonas syringae bacteria.Keywords: plant microbiome, nanoparticles, 16S rRNA gene sequencing, bacterial survival
Procedia PDF Downloads 203113 Hydrogel Hybridizing Temperature-Cured Dissolvable Gelatin Microspheres as Non-Anchorage Dependent Cell Carriers for Tissue Engineering Applications
Authors: Dong-An Wang
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All kinds of microspheres have been extensively employed as carriers for drug, gene and therapeutic cell delivery. Most therapeutic cell delivery microspheres rely on a two-step methodology: fabrication of microspheres and subsequent seeding of cells onto them. In this study, we have developed a novel one-step cell encapsulation technique using a convenient and instant water-in-oil single emulsion approach to form cell-encapsulated gelatin microspheres. This technology is adopted for hyaline cartilage tissue engineering, in which autologous chondrocytes are used as therapeutic cells. Cell viability was maintained throughout and after the microsphere formation (75-100 µm diameters) process that avoids involvement of any covalent bonding reactions or exposure to any further chemicals. Further encapsulation of cell-laden microspheres in alginate gels were performed under 4°C via a prompt process. Upon the formation of alginate constructs, they were immediately relocated into CO2 incubator where the temperature was maintained at 37°C; under this temperature, the cell-laden gelatin microspheres dissolved within hours to yield similarly sized cavities and the chondrocytes were therefore suspended within the cavities inside the alginate gel bulk. Hence, the gelatin cell-laden microspheres served two roles: as cell delivery vehicles which can be removable through temperature curing, and as porogens within an alginate hydrogel construct to provide living space for cell growth and tissue development as well as better permeability for mutual diffusions. These cell-laden microspheres, namely “temperature-cured dissolvable gelatin microsphere based cell carriers” (tDGMCs), were further encapsulated in a chondrocyte-laden alginate scaffold system and analyzed by WST-1, gene expression analyses, biochemical assays, histology and immunochemistry stains. The positive results consistently demonstrated the promise of tDGMC technology in delivering these non-anchorage dependent cells (chondrocytes). It can be further conveniently translated into delivery of other non-anchorage dependent cell species, including stem cells, progenitors or iPS cells, for regeneration of tissues in internal organs, such as engineered hepatogenesis or pancreatic regeneration.Keywords: biomaterials, tissue engineering, microsphere, hydrogel, porogen, anchorage dependence
Procedia PDF Downloads 396112 An Inorganic Nanofiber/Polymeric Microfiber Network Membrane for High-Performance Oil/Water Separation
Authors: Zhaoyang Liu
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It has been highly desired to develop a high-performance membrane for separating oil/water emulsions with the combined features of high water flux, high oil separation efficiency, and high mechanical stability. Here, we demonstrated a design for high-performance membranes constructed with ultra-long titanate nanofibers (over 30 µm in length)/cellulose microfibers. An integrated network membrane was achieved with these ultra-long nano/microfibers, contrast to the non-integrated membrane constructed with carbon nanotubes (5 µm in length)/cellulose microfibers. The morphological properties of the prepared membranes were characterized by A FEI Quanta 400 (Hillsboro, OR, United States) environmental scanning electron microscope (ESEM). The hydrophilicity, underwater oleophobicity and oil adhesion property of the membranes were examined using an advanced goniometer (Rame-hart model 500, Succasunna, NJ, USA). More specifically, the hydrophilicity of membranes was investigated by analyzing the spreading process of water into membranes. A filtration device (Nalgene 300-4050, Rochester, NY, USA) with an effective membrane area of 11.3 cm² was used for evaluating the separation properties of the fabricated membranes. The prepared oil-in-water emulsions were poured into the filtration device. The separation process was driven under vacuum with a constant pressure of 5 kPa. The filtrate was collected, and the oil content in water was detected by a Shimadzu total organic carbon (TOC) analyzer (Nakagyo-ku, Kyoto, Japan) to examine the separation efficiency. Water flux (J) of the membrane was calculated by measuring the time needed to collect some volume of permeate. This network membrane demonstrated good mechanical flexibility and robustness, which are critical for practical applications. This network membrane also showed high separation efficiency (99.9%) for oil/water emulsions with oil droplet size down to 3 µm, and meanwhile, has high water permeation flux (6.8 × 10³ L m⁻² h⁻¹ bar⁻¹) at low operation pressure. The high water flux is attributed to the interconnected scaffold-like structure throughout the whole membrane, while the high oil separation efficiency is attributed to the nanofiber-made nanoporous selective layer. Moreover, the economic materials and low-cost fabrication process of this membrane indicate its great potential for large-scale industrial applications.Keywords: membrane, inorganic nanofibers, oil/water separation, emulsions
Procedia PDF Downloads 172111 Facile Fabrication of TiO₂NT/Fe₂O₃@Ag₂CO₃ Nanocomposite and Its Highly Efficient Visible Light Photocatalytic and Antibacterial Activity
Authors: Amal A. Al-Kahlawy, Heba H. El-Maghrabi
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Due to the increasing need to environment protection in real time need to energize new materials are under extensive investigations. Between others, TiO2 nanotubes (TNTs) nanocomposite with iron oxide and silver carbonate, are promising alternatives as high-efficiency visible light photocatalyst due to their unique properties and their superior charge transport properties. Our efforts in this domain aim the construction of novel nanocomposite of TiO2NT/Fe2O3@Ag2CO3. The structure, surface morphology, chemical composition and optical properties were characterized by X-ray diffraction (XRD), Raman, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray spectrometer (EDS), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and UV–vis diffuse reflectance spectroscopy (DRS). XRD results confirm the interaction of TiO2-NT with iron oxide. This novel nanocomposite shows remarkably enhanced performance for phenol compounds photodegradation. The experimental data shows a promising photocatalytic activity. In particular, a maximum value of 450 mg/g was removed within 60 min at solar light irradiation with degradation efficiency of 99.5%. The high photocatalytic activity of the nanocomposite is found to be related to the increased adsorption toward chemical species, enhanced light absorption and efficient charge separation and transfer. Finally, the designed TiO2NT/Fe2O3@Ag2CO3 nanocomposite has a great degree of sustainability and could has a potential application for the industrial treatment of wastewater containing toxic organic materials.Keywords: nanocomposite, photocatalyst, solar energy, titanium dioxide nanotubes
Procedia PDF Downloads 247110 Forgeability Study of Medium Carbon Micro-Alloyed Forging Steel
Authors: M. I. Equbal, R. K. Ohdar, B. Singh, P. Talukdar
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Micro-alloyed steel components are used in automotive industry for the necessity to make the manufacturing process cycles shorter when compared to conventional steel by eliminating heat treatment cycles, so an important saving of costs and energy can be reached by reducing the number of operations. Micro-alloying elements like vanadium, niobium or titanium have been added to medium carbon steels to achieve grain refinement with or without precipitation strengthening along with uniform microstructure throughout the matrix. Present study reports the applicability of medium carbon vanadium micro-alloyed steel in hot forging. Forgeability has been determined with respect to different cooling rates, after forging in a hydraulic press at 50% diameter reduction in temperature range of 900-11000C. Final microstructures, hardness, tensile strength, and impact strength have been evaluated. The friction coefficients of different lubricating conditions, viz., graphite in hydraulic oil, graphite in furnace oil, DF 150 (Graphite, Water-Based) die lubricant and dry or without any lubrication were obtained from the ring compression test for the above micro-alloyed steel. Results of ring compression tests indicate that graphite in hydraulic oil lubricant is preferred for free forging and dry lubricant is preferred for die forging operation. Exceptionally good forgeability and high resistance to fracture, especially for faster cooling rate has been observed for fine equiaxed ferrite-pearlite grains, some amount of bainite and fine precipitates of vanadium carbides and carbonitrides. The results indicated that the cooling rate has a remarkable effect on the microstructure and mechanical properties at room temperature.Keywords: cooling rate, hot forging, micro-alloyed, ring compression
Procedia PDF Downloads 361109 Molecular Insights into the 5α-Reductase Inhibitors: Quantitative Structure Activity Relationship, Pre-Absorption, Distribution, Metabolism, and Excretion and Docking Studies
Authors: Richa Dhingra, Monika, Manav Malhotra, Tilak Raj Bhardwaj, Neelima Dhingra
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5-Alpha-reductases (5AR), a membrane bound, NADPH dependent enzyme and convert male hormone testosterone (T) into more potent androgen dihydrotestosterone (DHT). DHT is the required for the development and function of male sex organs, but its overproduction has been found to be associated with physiological conditions like Benign Prostatic Hyperplasia (BPH). Thus the inhibition of 5ARs could be a key target for the treatment of BPH. In present study, 2D and 3D Quantitative Structure Activity Relationship (QSAR) pharmacophore models have been generated for 5AR based on known inhibitory concentration (IC₅₀) values with extensive validations. The four featured 2D pharmacophore based PLS model correlated the topological interactions (–OH group connected with one single bond) (SsOHE-index); semi-empirical (Quadrupole2) and physicochemical descriptors (Mol. wt, Bromines Count, Chlorines Count) with 5AR inhibitory activity, and has the highest correlation coefficient (r² = 0.98, q² =0.84; F = 57.87, pred r² = 0.88). Internal and external validation was carried out using test and proposed set of compounds. The contribution plot of electrostatic field effects and steric interactions generated by 3D-QSAR showed interesting results in terms of internal and external predictability. The well validated 2D Partial Least Squares (PLS) and 3D k-nearest neighbour (kNN) models were used to search novel 5AR inhibitors with different chemical scaffold. To gain more insights into the molecular mechanism of action of these steroidal derivatives, molecular docking and in silico absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Studies have revealed the hydrophobic and hydrogen bonding of the ligand with residues Alanine (ALA) 63A, Threonine (THR) 60A, and Arginine (ARG) 456A of 4AT0 protein at the hinge region. The results of QSAR, molecular docking, in silico ADME studies provide guideline and mechanistic scope for the identification of more potent 5-Alpha-reductase inhibitors (5ARI).Keywords: 5α-reductase inhibitor, benign prostatic hyperplasia, ligands, molecular docking, QSAR
Procedia PDF Downloads 163108 Development of Positron Emission Tomography (PET) Tracers for the in-Vivo Imaging of α-Synuclein Aggregates in α-Synucleinopathies
Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi
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There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development
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