Alumina-aluminum Titanate-titania Nanocomposite: Synthesis, Sintering Studies, Assessment Of Bioactivity And Its Mechanical And Electrical Properties

This thesis reports the development, synthesis and characterization of a ceramic-ceramic nanocomposite system for its possible application as structural and electronic biomaterial in the biomedical industry. The study selected and synthesized alumina-aluminum titanate-titania (Al2O3-Al2TiO5-TiO2) nanoceramic composite using a simple Sol-Gel technique, which can be easily reproduced. Aluminum propoxide and titanium propoxide were used as precursor chemicals. Propanol and 2- methoxy ethanol were used as solvent and stabilizer, respectively. Thermal analyses were performed for a systematic understanding of phase evolution from the synthesized gel. X-Ray diffraction technique was used to confirm the phase evolution, phase purity, crystallite size and crystal structure(s) of the phase(s). Calcination of the powder at low temperatures (700°C) leads to formation of Al2O3-TiO2 nanocomposite and at higher temperatures into Al2O3-Al2TiO5-TiO2 nanocomposite confirmed by XRD analysis. Electron microscopic techniques were used to investigate powder morphology, crystallite size and inter-planner spacing. High Resolution Transmission Electron Microscopy images of the calcined powder showed agglomerates of powder particles with particle size in 15-20 nm range. As-synthesized powder was uniaxially pressed into cylindrical pellets and sintered at elevated temperatures (1000-1400oC) to study the sintering behavior, densification characteristics, and measurement of mechanical and electrical properties and assessment of bioactivity. Phase transformation induced by the sintering process was analyzed by X-ray powder diffraction technique. The effects of nanosize of powder particles and multi-phases on densification, and mechanical and electrical properties were investigated. Vickers hardness and biaxial flexural strength tests were used to determine mechanical properties. Bioactivity of the nanocomposite was assessed in Simulated Body Fluid (SBF), which has the same ionic concentration as that of human plasma. Effects of biodegradation and change in mechanical properties of the composite when kept in SBF and maintained in a static condition were studied in terms of weight loss, change in the pH of the acellular solution and change in mechanical properties (hardness and biaxial strength). Scanning Electron Microscopy was used to observe the formation of apatite crystals on the surface of the nanocomposite specimens soaked in SBF. The results obtained throw light on biocompatibility and bioactivity of Al2TiO5 phase, which has not been reported so far in the literature to the best of our knowledge. Dielectric constant and dissipation factor of the sintered nanocomposite pellets were measured using HP 4284A impedance-capacitance-resistance meter and 16451 B dielectric test fixture at 1 MHz frequency. The effects of sintering time, temperature and phases present on the electrical properties were studied and are reported in the thesis

Simultaneous immunization with Omp25 and L7/L12 provides protection against brucellosis in mice

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A Bivalent Protein r-PAbxpB Comprising PA Domain IV and Exosporium Protein BxpB Confers Protection Against B. anthracis Spores and Toxin

Anthrax vaccines primarily relying only on protective antigen (PA), the cell binding component in anthrax toxins provide incomplete protection when challenged with spores of virulent encapsulated Bacillus anthracis strains. Alternatively, formaldehyde inactivated spores (FIS) or recombinant spore components generate anti-spore immune responses that inhibit the early stages of infection and augment the PA protective efficacy. In the present study domain IV of PA was spliced with exosporium antigen BxpB via a flexible G4S linker to generate a single functional antigen r-PAbxpB that was further assessed for its protective efficacy against anthrax toxins and spore infection. Immunization of mice with r-PAbxpB elicited significantly high titer antibodies comprising IgG1:IgG2a isotypes in 1:1 ratio, balanced up-regulation of both Th1 (IL2, IL12, IFN-γ) and Th2 (IL4, IL5, IL10) cytokines and high frequencies of CD4+ and CD8+ T cell subsets. The anti-r-PAbxpB antibodies significantly enhanced spore phagocytosis, and killing within macrophages; inhibited their germination to vegetative cells and completely neutralized the anthrax toxins as evidenced by the 100% protection in passive transfer studies. Active immunization with r-PAbxpB provided 100 and 83.3% protection in mice I.P. challenged with 5 × LD100 LD of toxins and 5 × 104 cfu/ml Ames spores, respectively while the sham immunized group succumbed to infection in 48 h. Therefore, the ability of r-PAbxpB to generate protective immune responses against both spores and toxin and provide significant protection suggests it as an efficient vaccine candidate against B. anthracis infection

Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer

Targeting the mitogen-activated protein kinase (MAPK) cascade in pancreatic ductal adenocarcinoma (PDAC) remains clinically unsuccessful. We aim to develop a MAPK inhibitor-based therapeutic combination with strong preclinical efficacy. Utilizing a reverse-phase protein array, we observe rapid phospho-activation of human epidermal growth factor receptor 2 (HER2) in PDAC cells upon pharmacological MAPK inhibition. Mechanistically, MAPK inhibitors lead to swift proteasomal degradation of dual-specificity phosphatase 6 (DUSP6). The carboxy terminus of HER2, containing a TEY motif also present in extracellular signal-regulated kinase 1/2 (ERK1/2), facilitates binding with DUSP6, enhancing its phosphatase activity to dephosphorylate HER2. In the presence of MAPK inhibitors, DUSP6 dissociates from the protective effect of the RING E3 ligase tripartite motif containing 21, resulting in its degradation. In PDAC patient-derived xenograft (PDX) models, combining ERK and HER inhibitors slows tumour growth and requires cytotoxic chemotherapy to achieve tumour regression. Alternatively, MAPK inhibitors with trastuzumab deruxtecan, an anti-HER2 antibody conjugated with cytotoxic chemotherapy, lead to sustained tumour regression in most tested PDXs without causing noticeable toxicity. Additionally, KRAS inhibitors also activate HER2, supporting testing the combination of KRAS inhibitors and trastuzumab deruxtecan in PDAC. This study identifies a rational and promising therapeutic combination for clinical testing in PDAC patients

Al2Tio5-Al2O3-Tio2 Nanocomposite: Structure, Mechanical Property And Bioactivity Studies

Novel biomaterials are of prime importance in tissue engineering. Here, we developed novel nanostructured Al2TiO5-Al 2O3-TiO2 composite as a biomaterial for bone repair. Initially, nanocrystalline Al2O3-TiO2 composite powder was synthesized by a sol-gel process. The powder was cold compacted and sintered at 1300-1500 °C to develop nanostructured Al 2TiO5-Al2O3-TiO2 composite. Nano features were retained in the sintered structures while the grains showed irregular morphology. The grain-growth and microcracking were prominent at higher sintering temperatures. X-ray diffraction peak intensity of β-Al2TiO5 increased with increasing temperature. β-Al2TiO5 content increased from 91.67% at 1300 °C to 98.83% at 1500 °C, according to Rietveld refinement. The density of β-Al2TiO5 sintered at 1300 °C, 1400 °C and 1500 °C were computed to be 3.668 g cm-3, 3.685 g cm -3 and 3.664 g cm-3, respectively. Nanocrystalline grains enhanced the flexural strength. The highest flexural strength of 43.2 MPa was achieved. Bioactivity and biomechanical properties were assessed in simulated body fluid. Electron microscopy confirmed the formation of apatite crystals on the surface of the nanocomposite. Spectroscopic analysis established the presence of Ca and P ions in the crystals. Results throw light on biocompatibility and bioactivity of β-Al2TiO5 phase, which has not been reported previously. © 2010 Elsevier Ltd. All rights reserved

Synthesis And Characterization Of Nanocrystalline Barium Strontium Titanate Powder Via Sol-Gel Processing

Barium Strontium Titanate (BST) solid solution is a strong candidate material for application in tunable ferroelectric devices. In this research, we have synthesized and characterized nanocrystalline BST (Ba0.7Sr 0.3TiO3) powder with average particle-diameter of 15 nm through a simple sol-gel process, using barium acetate, strontium acetate and titanium isopropoxide as the precursors. In this process, stoichiometric proportions of barium acetate and strontium acetate were dissolved in acetic acid followed by refluxing, and addition of titanium (IV) isopropoxide to form BST gel. The gel was analyzed using Differential Scanning Calorimetry (DSC) and Thermal Gravimetric Analysis (TGA). The as-formed gel was dried at 200 °C and then calcined in the temperature range of 400 to 800 °C for crystallization. Phase evolution during calcination was studied using X-ray diffraction (XRD) technique. Particle size, morphology and the lattice fringes of the calcined powder were characterized by high-resolution transmission electron microscopy (HR-TEM). To study the effects of sintering on BST nanopowder, green ceramic specimens were prepared by uniaxial compaction and then sintered at 950-1,100 °C under atmospheric conditions. Sintered specimens were analyzed for phase composition, grain size and geometric bulk density. © Springer Science+Business Media, LLC 2007

Synthesis, Densification, And Phase Evolution Studies Of Al2O3-Al2Tio5-Tio2 Nanocomposites And Measurement Of Their Electrical Properties

Alumina-aluminum titanate-titania (Al2O3-Al2TiO5-TiO2) nanocomposites were synthesized using alkoxide precursor solutions. Thermal analysis provided information on phase evolution from the as-synthesized gel with an increase in temperature. Calcination at 700°C led to the formation of an Al2O3-TiO2 nanocomposite, while at a higher temperature (1300°C) an Al2O3-Al2TiO5-TiO2 nanocomposite was formed. The nanocomposites were uniaxially compacted and sintered in a pressureless environment in air to study the densification behavior, grain growth, and phase evolution. The effects of nanosize particles on the crystal structure and densification of the nanocomposite have been discussed. The sintered nanocomposite structures were also characterized for dielectric properties. © 2007 The American Ceramic Society

Synthesis, Characterization And Measurements Of Electrical Properties Of Alumina-Titania Nano-Composites

In this study, we have synthesized and characterized nanocrystalline alumina-titania (Al2O3-TiO2) composites via a simple sol-gel process, using aluminum propoxide and titanium propoxide as precursor chemicals. Propanol and 2-methoxy ethanol were used as solvent and stabilizer, respectively. The as-formed gel was heat treated at 400°C, to obtain amorphous powder. The amorphous powder was subsequently calcined at 700°C and 900°C. Phase evolution, phase composition, crystal structure and crystallite-size of the synthesized powder were determined using X-ray diffraction (XRD) technique. Crystallite-size was further confirmed by high-resolution transmission electron microscopy (HR-TEM). HR-TEM results of powder calcined at 700°C showed agglomerates of powder particles, with particle-size in 15 - 20 nm range. The synthesized powder was uniaxially pressed using a steel mold and then sintered at elevated temperature (1000-1500°C) for densification study and electrical property measurements. XRD technique was used to study phase composition of the sintered pellets. Dielectric constant and dissipation factor of the sintered pellets were measured. The effects of sintering time, temperature and phases present on the electrical properties of the sintered pellets, were studied

Synthesis And Characterization Of Nanocrystalline Barium Strontium Titanate Ceramics

Nano-grained Barium Titanate based ceramics are of interest, for applications in ultra thin dielectric layers. In this work, we have synthesized nanocrystalline Barium Strontium Titanate (Ba0.7Sr 0.3TiO3) powder in the range of 15 - 25 nm using a simple sol-gel processing route. Barium acetate, strontium acetate and titanium isopropoxide were used as precursors. By varying the pH of the sol and the calcination temperature a simple sol-gel synthesis was developed which can be easily repeated. Thermal properties of the processed gel were determined using Differential Scanning Calorimetry and Thermogravimetric analysis. The Ba 0.7Sr0.3TiO3 gel obtained was dried at 200°C, to form powder and subsequently calcined in the temperature range of 400°C to 700°C for crystallization. X-Ray Diffraction technique was used to study the phase evolution and phase purity during synthesis. Crystallite size of the powder was also determined using X-ray diffraction patterns. XRD patterns showed variation in phase evolution as a function of pH of the solution. Scanning Electron Microcopy of the synthesized powder calcined at 700°C showed that the powder was in agglomerates, which were consisted of very fine particles. High Resolution Transmission Electron Microscopy (HR-TEM) results showed that the particle size of the Ba0.7Sr 0.3TiO3 powder obtained after calcination at 700°C was in the range 15-25 nm