Effect of TiO2 Addition in Al2O3: Phase Evolution, Densification, Microstructure And Mechanical Properties

The thesis describes the effect of TiO2 additionin alumina on phase formation, densification, microstructure and mechanical properties of the composite.The ceramic composite were prepared with Al2O3 and TiO2 powder by solid state mixing route. The Al2O3–TiO2 powders contain 3, 5, 10, 13, 20, and 40 wt% of TiO2. Mixed powders were calcined at 1200oC.Calcinedpowders were uniaxially pressed into cylindrical pellets and rectangular bars, and sintered at 1600oC. X-ray powder diffraction technique was used to study the phase evolution in calcined powder and in sintered specimen. Scanning electron microscope (SEM) was used to find out the particle size and powder morphology of clacined power and microstructure of sintered sample. Flexural strength and Vickers hardness were measured on sintered sample. Calcined powder contains only alumina and titania phase. No intermediate phase was detected. In sintered sample Al2TiO5 phase was detected and its concentration increases with increases in TiO2 content.TiO2 phase was disappeared for high amount of TiO2 (20 and 40wt% addition) addition. It was found that low concentration of TiO2 (upto 10wt %) increases the density of the composite and further increase in TiO2concentration density decreases rapidly. Presence of Al2TiO5phase restricts the grain growth of alumina phase.Flexural strength and Vickers hardness of Al2O3-TiO2-Al2TiO5 composite is dependent on the content of TiO2 and the presence of Al2TiO5 phase

Autophosphorylation at serine 166 regulates RIP kinase 1-mediated cell death and inflammation

Receptor interacting protein kinase 1 (RIPK1) regulates cell death and inflammatory responses downstream of TNFR1 and other receptors, and has been implicated in the pathogenesis of inflammatory and degenerative diseases. RIPK1 kinase activity induces apoptosis and necroptosis, however the mechanisms and phosphorylation events regulating RIPK1-dependent cell death signaling remain poorly understood. Here we show that RIPK1 autophosphorylation at serine 166 plays a critical role for the activation of RIPK1 kinase-dependent apoptosis and necroptosis. Moreover, we show that S166 phosphorylation is required for RIPK1 kinase-dependent pathogenesis of inflammatory pathologies in vivo in four relevant mouse models. Mechanistically, we provide evidence that trans autophosphorylation at S166 modulates RIPK1 kinase activation but is not by itself sufficient to induce cell death. These results show that S166 autophosphorylation licenses RIPK1 kinase activity to induce downstream cell death signaling and inflammation, suggesting that S166 phosphorylation can serve as a reliable biomarker for RIPK1 kinase-dependent pathologies

Epithelial Cell Death and Inflammation in Skin

The presence of dying cells in inflamed tissues has been recognized since many years, but until recently cell death was considered primarily a consequence of inflammation. Recent data in mouse models suggest that cell death could provide a potent trigger of inflammation. The identification of necroptosis as a new type of regulated necrotic cell death that is induced by death receptors, toll like receptors and type I interferon receptor indicated that necroptosis could contribute to the proinflammatory properties of these receptors. This is particularly relevant to the skin, a tissue that provides a life-sustaining structural and immunological barrier with the environment and is constantly exposed to mechanical, chemical, and microbial insults. Studies in mouse models showed that sensitization of keratinocytes to apoptosis or necroptosis triggered by TNF and other stimuli causes severe chronic inflammatory skin lesions. In addition, keratinocyte death is a prominent histopathological feature of many inflammatory skin diseases, suggesting that death of epithelial cells could contribute to the pathogenesis of skin inflammation. Here we review recent studies in genetic mouse models providing evidence that keratinocyte death is a potent trigger of skin inflammation and discuss their potential relevance for human inflammatory skin diseases

Effect of scattering and electronic noise upon selection of detectors for Gamma Computerized Tomography

Computed tomography (CT) has become a vital tool in a variety of fields as a result of technological developments and continual improvement. High-quality CT images are desirable for image interpretation and obtaining information from CT images. A variety of things influence the CT image quality. Various research groups have investigated and attempted to improve image quality by examining noise/error associated with CT geometry. This study aims to select detectors for CT, which yield the least amount of noise in projection data. Three distinct gamma-ray detectors that are routinely used in CT have been compared in terms of scattering and electrical noise. The sensitivity of Kanpur Theorem-1 to scattering noise is demonstrated in this work and used to quantify the relative level of scattering noise. The detector measures the signal multiple times, and the standard deviation of the signal is used to calculate the electronic noise. It is observed that IC CsI(Tl) scintillation detector produces low electronic noise and relative scattering noise as compared to conventional electronic detectors; NaI(Tl) and HPGe.Comment: 12 pages, 7 figures, Table 1, 37 reference

The interplay of IKK, NF-kappa B and RIPK1 signaling in the regulation of cell death, tissue homeostasis and inflammation

Regulated cell death pathways have important functions in host defense and tissue homeostasis. Studies in genetic mouse models provided evidence that cell death could cause inflammation in different tissues. Inhibition of RIPK3-MLKL-dependent necroptosis by FADD and caspase-8 was identified as a key mechanism preventing inflammation in epithelial barriers. Moreover, the interplay between IKK/NF-kappa B and RIPK1 signaling was recognized as a critical determinant of tissue homeostasis and inflammation. NEMO was shown to regulate RIPK1 kinase activity-mediated apoptosis by NF-kappa B-dependent and -independent functions, which are critical for averting chronic tissue injury and inflammation in the intestine and the liver. In addition, RIPK1 was shown to exhibit kinase activity-independent functions that are essential for preventing cell death, maintaining tissue architecture and inhibiting inflammation. In the intestine, RIPK1 acts as a scaffold to prevent epithelial cell apoptosis and preserve tissue integrity. In the skin, RIPK1 functions via its RHIM to counteract ZBP1/DAI-dependent activation of RIPK3-MLKL-dependent necroptosis and inflammation. Collectively, these studies provided evidence that the regulation of cell death signaling plays an important role in the maintenance of tissue homeostasis, and suggested that cell death could be causally involved in the pathogenesis of inflammatory diseases

Macrophages in Skin Wounds: Functions and Therapeutic Potential

Macrophages regulate cutaneous wound healing by immune surveillance, tissue repair and remodelling. The depletion of dermal macrophages during the early and middle stages of wound healing has a detrimental impact on wound closure, characterised by reduced vessel density, fibroblast and myofibroblast proliferation, delayed re-epithelization and abated post-healing fibrosis and scar formation. However, in some animal species, oral mucosa and foetal life, cutaneous wounds can heal normally and remain scarless without any involvement of macrophages. These paradoxical observations have created much controversy on macrophages’ indispensable role in skin wound healing. Advanced knowledge gained by characterising macrophage subsets, their plasticity in switching phenotypes and molecular drivers provides new insights into their functional importance during cutaneous wound healing. In this review, we highlight the recent findings on skin macrophage subsets, their functional role in adult cutaneous wound healing and the potential benefits of targeting them for therapeutic use

RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation

Receptor-interacting protein kinase 1 (RIPK1) regulates cell death and inflammation through kinase-dependent and -independent functions(1-7). RIPK1 kinase activity induces caspase-8-dependent apoptosis and RIPK3 and mixed lineage kinase like (MLKL)-dependent necroptosis(8-13). In addition, RIPK1 inhibits apoptosis and necroptosis through kinase-independent functions, which are important for late embryonic development and the prevention of inflammation in epithelial barriers(14-18). The mechanism by which RIPK1 counteracts RIPK3-MLKL-mediated necroptosis has remained unknown. Here we show that RIPK1 prevents skin inflammation by inhibiting activation of RIPK3-MLKL-dependent necroptosis mediated by Z-DNA binding protein 1 (ZBP1, also known as DAI or DLM1). ZBP1 deficiency inhibited keratinocyte necroptosis and skin inflammation in mice with epidermis-specific RIPK1 knockout. Moreover, mutation of the conserved RIP homotypic interaction motif (RHIM) of endogenous mouse RIPK1 (RIPK1(mRHIM)) caused perinatal lethality that was prevented by RIPK3, MLKL or ZBP1 deficiency. Furthermore, mice expressing only RIPK1(mRHIM) in keratinocytes developed skin inflammation that was abrogated by MLKL or ZBP1 deficiency. Mechanistically, ZBP1 interacted strongly with phosphorylated RIPK3 in cells expressing RIPK1(mRHIM), suggesting that the RIPK1 RHIM prevents ZBP1 from binding and activating RIPK3. Collectively, these results show that RIPK1 prevents perinatal death as well as skin inflammation in adult mice by inhibiting ZBP1-induced necroptosis. Furthermore, these findings identify ZBP1 as a critical mediator of inflammation beyond its previously known role in antiviral defence and suggest that ZBP1 might be implicated in the pathogenesis of necroptosis-associated inflammatory diseases

Sharpin prevents skin inflammation by inhibiting TNFR1-induced keratinocyte apoptosis

Linear Ubiquitin chain Assembly Complex (LUBAC) is an E3 ligase complex that generates linear ubiquitin chains and is important for tumour necrosis factor (TNF) signaling activation. Mice lacking Sharpin, a critical subunit of LUBAC, spontaneously develop inflammatory lesions in the skin and other organs. Here we show that TNF receptor 1 (TNFR1)-associated death domain (TRADD)-dependent TNFR1 signaling in epidermal keratinocytes drives skin inflammation in Sharpin-deficient mice. Epidermis-restricted ablation of Fas-associated protein with death domain (FADD) combined with receptor-interacting protein kinase 3 (RIPK3) deficiency fully prevented skin inflammation, while single RIPK3 deficiency only delayed and partly ameliorated lesion development in Sharpin-deficient mice, showing that inflammation is primarily driven by TRADD- and FADD-dependent keratinocyte apoptosis while necroptosis plays a minor role. At the cellular level, Sharpin deficiency sensitized primary murine keratinocytes, human keratinocytes, and mouse embryonic fibroblasts to TNF-induced apoptosis. Depletion of FADD or TRADD in Sharpin-deficient HaCaT cells suppressed TNF-induced apoptosis, indicating the importance of FADD and TRADD in Sharpin-dependent anti-apoptosis signaling in keratinocytes