712 research outputs found
Buckling design of stringer-stiffened conical shells in compression
No full textThe buckling strength of conical shells subjected to axial compression may be increased by means of meridional stiffeners (stringers). Unlike stiffened cylinders, only limited research has been carried out and no design provisions exist for stringer-stiffened cones. In this paper, a design procedure for such cones is developed based on an equivalent cylinder approach. Design criteria for both local (shell panel) and global (stiffened panel) buckling modes are proposed. In the absence of experimental results, a numerical parametric study is then presented to assess the design proposal. By using finite-element models, linear and nonlinear analyses are performed to quantify critical design aspects and to calibrate buckling strength predictions derived from the design proposal
The Trials and Tribulations of an Unpaid, Overworked Writer : The MTV College Stringer Program
No full textii, 72 p.The author describes her experience as the local college stringer for the Kalamazoo/Battle Creek area in Winter 1998
Chemotherapy-induced mucositis: the role of the gastrointestinal microbiome and toll-like receptors
No full textAlimentary mucositis is a major clinical problem. Patients with mucositis are at significantly increased risk of infection and are often hospitalized for prolonged periods. More importantly, these patients often have to undergo reductions in their cytotoxic therapy, which may lead to reduced survival. Unfortunately, there are very limited therapeutic options for mucositis and no effective prevention. The human gut microbiome is receiving increased attention as a key player in the pathogenesis of alimentary mucositis with recent literature suggesting that changes in bacteria lead to mucositis. The bacteria which are found throughout the gut are tightly regulated by the toll-like receptor (TLR) family which currently has 13 known members. TLRs play a critical role in gut homeostasis and bacterial regulation. Furthermore, TLRs play a critical role in the regulation of nuclear factor kappa B, a key regulator of alimentary mucositis. However to date, no research has clearly identified a link between TLRs and alimentary mucositis. This critical literature review seeks to correct this.Daniel W. Thorpe, Andrea M. Stringer and Rachel J. Gibso
Selection of housekeeping genes for gene expression studies in a rat model of irinotecan-induced mucositis
No full textBackground/Aims: Mucositis is the term used to describe damage caused by chemotherapy to mucous membranes of the alimentary tract. RT-PCR has recently been utilised to determine the molecular events that occur in mucositis. As this method relies on the use of a validated endogenous control, this study aims to validate commonly used housekeeping genes in an irinotecan-induced mucositis model.
Methods: Rats were administered irinotecan and sacrificed at different time points, in particular 1, 24, 72 and 144 h following treatment. Histopathological damage was assessed by haematoxylin and eosin staining. RT-PCR was used to evaluate the expression of 11 housekeeping genes. Expression stability was determined by the Normfinder program. Matrix metalloproteinase 2 was used as a target gene to validate the appropriateness of the top-ranking housekeeping gene.
Results: For normalisation to multiple housekeeping genes, the most stable combination across all time points in the jejunum was Ywhaz/UBC and in the colon UBC/β-actin. SDHA and GAPDH were the most variable genes in the jejunum and colon where they were 4.4 and 3.2 fold upregulated following irinotecan, respectively.
Conclusions: For normalisation of irinotecan-induced mucositis gene expression studies, a combination of Ywhaz/UBC and UBC/β-actin should be used in the jejunum and colon, respectively. UBC is the most favourable if restricted to a single housekeeping gene across all time points.Noor Al-Dasooqi, Joanne M. Bowen, Rachel J. Gibson, Richard M. Logan, Andrea M. Stringer, Dorothy M. Keef
Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis
No full textBackground: Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Methods: Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Results: Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Conclusions: Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.Zhi Yi Ong, Rachel J. Gibson, Joanne M. Bowen, Andrea M. Stringer, Jocelyn M. Darby, Richard M. Logan, Ann S.J. Yeoh, Dorothy M. Keef
The Influence of Radial Edge Constraint on the Stability of Stiffened Conical Shells in Compression
No full textUsing finite element analysis, the non-linear behaviour of thin stringer-stiffened cones under axial compression is studied. In particular, various alternatives in specifying edge conditions are presented and the sensitivity natives in specifying edge conditions are presented and the sensitivity of the response to the radial edge constraint is examined in detail. It is shown that both the initial stiffness and the limit load cart be severely reduced if radial edge displacements are not constrained and that, in this case, linear eigenvalue results can be misleading. Analogies are drawn between the cone and the more commonly encountered cylindrical shell. The implications of these results for experimental studies and for the development of design formulations are discussed
Chemotherapy-induced modifications to gastrointestinal microflora: Evidence and implications of change
No full text© 2009 Bentham Science Publishers Ltd.Mucositis is a common side effect of chemotherapy which remains poorly understood. Despite advances in the understanding of oral and small intestinal mucositis over recent years, large intestinal mucositis, including diarrhoea, has not been well defined and the underlying mechanisms of the condition are yet to be established. The majority of the literature available concerning large intestinal mucositis is based on clinical observations, with very little basic research existing. However, from the little research conducted, it is likely that the intestinal microflora play a role in the development of chemotherapy-induced mucositis. This review will explore the potentially important relationship between intestinal microflora and the subsequent development of chemotherapy-induced mucositis.Andrea M. Stringer, Rachel J. Gibson, Joanne M. Bowen and Dorothy M.K. Keef
Numerical modelling of crack growth profiles in integral skin-stringer panels
No full textIntegral (monolithic) structures can play a significant role in high efficiency structural design. According to the current technological manufacture methods, integral structures have an impact on fabrication cost and on weight reduction. However, until now, some critical aspects have limited the use of these structures. Conventional structures with mechanical or chemical (by adhesion) joints are advantageous because of their damage tolerant and fail safe behaviour. The presence of two separate parts, skins and stringers, guarantee the structural integrity of the component when propagating defects and cracks are present and are thus the key factor in aircraft structures. Focusing our attention on aircraft related structures, the aim of this paper is to show the application of numerical methodologies to evaluate the behaviour of integrally machined skin-stringer panels in the presence of propagating cracks. The described activity resulted from the Analytical Round Robin on Crack Growth and Residual Strength Prediction in Integral Structures proposed by ASTM Task Group E08.04.05 while different FE approaches for a single type integral panel with a propagating crack have been introduced in this paper. The crack growth evaluation based on the numerical models agrees well with the experimental results
Kinetics and regional specificity of irinotecan-induced gene expression in the gastrointestinal tract
No full textData source: Supplementary data, http://www.sciencedirect.com/science/article/pii/S0300483X09006428#appd002Gastrointestinal toxicity remains a significant and dose-limiting complication of cancer treatment. While the pathophysiology is becoming clearer, considerable gaps in the knowledge remain surrounding the timing and site-specific gene changes which occur in response to insult. As such, this study aimed to assess gene expression profiles in a number of regions along the gastrointestinal tract following treatment with the chemotherapy agent, irinotecan, and correlate them with markers of cell death and tissue damage. Data analysis of microarray results found that genes involved in apoptosis, mitogen activated kinase (MAPK) signalling and inflammation were upregulated within 6 h, while genes involved in cell proliferation, wound healing and blood vessel formation were upregulated at later time points up to 72 h. Cell death was significantly increased at 6 and 24 h, and the stomach showed the lowest severity of overt tissue damage. Real time PCR of MAPK signalling pathway genes found that the jejunum and colon had significantly increased expression in a number of genes at 72 h, where as the stomach was unchanged. These results indicate that overall severity of tissue damage may be determined by precisely timed target gene responses specific to each region. Therapeutic targeting of key gene responses at the appropriate time point may prove to be effective for prevention of chemotherapy-induced gastrointestinal damage.Joanne M. Bowen, Anna Tsykin, Andrea M. Stringer, Richard M. Logan, Rachel J. Gibson and Dorothy M.K. Keefehttp://www.elsevier.com/wps/find/journaldescription.cws_home/505518/description#descriptio
Anti-inflammatory cytokines: important immunoregulatory factors contributing to chemotherapy-induced gastrointestinal mucositis
No full text“Mucositis” is the clinical term used to describe ulceration and damage of the mucous membranes of the entire gastrointestinal tract (GIT) following cytotoxic cancer chemotherapy and radiation therapy common symptoms include abdominal pain, bloating, diarrhoea, vomiting, and constipation resulting in both a significant clinical and financial burden. Chemotherapeutic drugs cause upregulation of stress response genes including NFκB, that in turn upregulate the production of proinflammatory cytokines such as interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). These proinflammatory cytokines are responsible for initiating inflammation in response to tissue injury. Anti-inflammatory cytokines and specific cytokine inhibitors are also released to limit the sustained or excessive inflammatory reactions. In the past decade, intensive research has determined the role of proinflammatory cytokines in development of mucositis. However, a large gap remains in the knowledge of the role of anti-inflammatory cytokines in the setting of chemotherapy-induced mucositis. This critical paper will highlight current literature available relating to what is known regarding the development of mucositis, including the molecular mechanisms involved in inducing inflammation particularly with respect to the role of proinflammatory cytokines, as well as provide a detailed discussion of why it is essential to consider extensive research in the role of anti-inflammatory cytokines in chemotherapy-induced mucositis so that effective targeted treatment strategies can be developed.Masooma Sultani, Andrea M. Stringer, Joanne M. Bowen and Rachel J. Gibso
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