167 research outputs found
Integrodifferential Inequalities Arising in the Theory of Differential Equations
The goal of this paper is to achieve some new results related to integrodifferential inequalities of one independent variable which can be applied as a study of qualitative and quantitative properties of solutions of some nonlinear integral equations
THE ROLE OF INTEGRINS IN THE ACTIVATION OF FIBROBLASTS FROM SKIN, LUNG AND BREAST TISSUE
PhDFibroblasts are abundant mesenchymal cells present in all tissues in a quiescent state,
which contribute to wound healing when activated. Cytokine transforming growth
factor-β1 (TGF-β1) stimulates fibroblast-myofibroblast differentiation, which induces
extracellular matrix secretion, tissue contraction and promotes cancer cell migration.
Hence, chronic activity of stromal myofibroblasts correlates with a poor prognosis for
cancer and organ fibrosis patients. Therefore, modulating myofibroblast activity may
reduce the severity of these diseases. Previous research suggests blockade of
transmembrane integrin receptors expressed by fibroblasts prevents TGF-β1-
induced differentiation, indicating integrins are attractive therapeutic targets.
However, fibroblasts derived from different organs exhibit heterogeneity, although
their integrin expression and integrin-regulated differentiation has not been directly
compared. The aim of my research was 1) to understand and compare how integrins
regulate TGF-β1-induced activation of fibroblasts derived from normal skin, lung and
breast tissue; 2) to examine the global gene expression of TGF-β1-treated lung
fibroblasts; 3) to identify novel therapeutic targets that modulate TGF-β1-induced
activation of lung fibroblasts using a drug library.
qPCR showed skin, lung and breast fibroblasts differentially expressed TGF-β1-
induced activation markers, including ACTA2, FN1, TIMP3, CTGF and SERPINE1, in
addition to integrin genes for α1, α4, α11 and β3. Small-molecule inhibitors of αv
integrins only reduced the invasion of TGF-β1-exposed skin fibroblasts, but not lung
or breast fibroblasts. siRNA against α11, β3 and β5 decreased TGF-β1-induced
collagen contraction and activation marker expression in skin and lung fibroblasts,
while α1 siRNA prevented collagen contraction by breast fibroblasts only. RNA
sequencing of TGF-β1-treated lung fibroblasts revealed pro-inflammatory and profibrotic
pathways were significantly enriched, while screening TGF-β1-treated lung
fibroblasts with a FDA-approved drug library identified 46 hits that significantly
reduced α-smooth muscle actin and fibronectin expression.
Overall, genes are differentially expressed in TGF-β1-treated skin, lung and breast
fibroblasts, while different integrins in each fibroblast appear to regulate invasion,
TGF-β1-induced collagen contraction and gene expression. RNA sequencing revealed
TGF-β1 promotes the expression of a pro-tumour signature in lung fibroblasts and
several novel therapeutic targets that modulate the activation of lung fibroblasts
have been identified. Understanding these integrin-dependent and independent
mechanisms will facilitate the generation of myofibroblast-targeted treatments for
cancer and organ fibrosis.Biotechnology and Biological Sciences Research Council
(BBSRC) and GlaxoSmithKline
Root cause analysis (RCA) of fractured ASTM A53 carbon steel pipe at oil & gas company
Incident involving failures of ASTM A53 carbon steel (CS) pipe, connected to pressure safety valve (PSV) and carrying raw gas has caused serious supply disruption. This study was performed to identify the most probable cause of the pipe failure. It was conducted by reviewing the existing design, construction data and pipe material analysis using non-destructive techniques such as VT, PT, MT and UT along with metallographic, hardness and microscopic analysis. The investigation revealed that excessive material loss has occurred in both failure and its adjacent regions due to abrasive grinding, resulting in the formation of a through thickness flaw. These grindings were performed to accommodate the pre-installed piping spool to avoid alteration in the pipe position. RCA demonstrated that this rapid thinning of the steel pipe body later led to its failure. Metallurgical study using photomicrograph shows that the morphology of the steel material was consistent and did not show any evidence of internal corrosion or micro fractures. Further damage to the surface of already excessively reduced thickness occurred due to nominal pipe vibration and atmospheric effect during service. The research work described in the paper has a significant meaning to recognize the root cause of such failures in CS pipes and through given recommendations to eliminate future such happenings
Ethno-environmental knowledge as a tool to combat indoor air pollution in low income countries: a case study from rural communities in Pakistan
It has recently been estimated that 4 million deaths each year are associated with air pollution
originating from household solid fuel use. Interventions to reduce biomass fuel-related emissions
can yield a diverse stream of benefits including improved public health, socio-economic development,
reduced land degradation and climate change mitigation. This study investigates the use
of indigenous knowledge to inform interventions to combat indoor air pollution at a rural site in
the Punjab province of Pakistan. The results indicate that the majority of people using biomass
fuel had knowledge of its ill health effects. A range of methods were utilised to reduce indoor
smoke including cooking in open spaces, use of chimneys, better ventilation and use of dry fuel.
Education and housing type showed a statistically significant relationship with awareness of
methods to reduce indoor exposure to biomass smoke. These findings lend support to the notion
that communities have indigenous knowledge and their own methods to reduce exposure to
indoor smoke from biomass fuels; this knowledge can be used as tool to design and implement
sustainable intervention strategies to reduce the risk of exposure to indoor air pollution. It is
recommended that a community based intervention focusing on locally manufactured improved
stoves and better designed cooking spaces would be a suitable intervention in this region
Impact of COVID-19 on Ophthalmologists
Objectives: To determine the effects of COVID 19 pandemic on the professional lives of ophthalmologists
Methods: This cross sectional survey was conducted for 6 months in late 2020 and used google forms for data collection.
Results: Total 68 respondents gave their likert response for each of the 20 statements. No. %, median, mode and interquartile range, of all respondents likert sentiment for each statement, were calculated. Survey results showed general, ‘consent and consensus’.
Conclusion: Covid-19 has influenced professional lives of ophthalmologists
Meshfree numerical approach for some time-space dependent order partial differential equations in porous media
In this article, the meshfree radial basis function method based on the Gaussian function is proposed for some time-space dependent fractional order partial differential equation (PDE) models. These PDE models have significant applications in chemical engineering and physical science. Some main advantages of the proposed method are that it is easy to implement, and the output response is quick and highly accurate, especially in the higher dimension. In this method, the time-dependent derivative terms are treated by Caputo fractional derivative while space-dependent derivative terms are treated by Riesz, Riemann-Liouville, and Grünwald-Letnikov derivatives. The proposed method is tested on some numerical examples and the accuracy is analyzed by
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