To Investigate and Fabricate Melt Processed Biomaterials Exhibiting Shape Recovery Properties

The purpose of this research was to produce and characterise novel hybrid biomaterials. Currently, there is a research gap in the area of producing hybrid biomaterials with shape memory properties for use in the fields of bioengineering or biomedical devices. This research will provide the initial results for a novel hybrid biomaterial that could be further researched for use in a biomedical device. In this study, melt extrusion methods were applied to the hybrid polymers. Three characterisation methods were employed within this work: mechanical (tensile) testing, shape recovery, and in vitro (trypsin) degradation. Across the three characterisation methods, PCL:PLA 30:70WT% 20% PEG-200 plasticised hybrid fibres were found to outperform the other materials reported in this thesis. Three key findings resulted from this research. The melt extrusion method used proved to be successful. PCL:PLA hybrid fibres could be produced consistently. Both glycerol and PEG-200 plasticisers used within this work were found to improve the blend properties of the hybrids. A total of 65% of tested hybrid fibres exhibited shape recovery when tested at a temperature of 37.5°C. The overall results of this study indicate that the hybrid materials produced here need to undergo further testing prior to use in biomedical applications

Linking Anomalous Behaviour with Stellar Properties: An Unsupervised Exploration of TESS Light Curves

With the upcoming plethora of astronomical time-domain datasets and surveys, anomaly detection as a way to discover new types of variable stars and transients has inspired a new wave of research. Yet, the fundamental definition of what constitutes an anomaly and how this depends on the overall properties of the population of light curves studied remains a discussed issue. Building on a previous study focused on Kepler light curves, we present an analysis that uses the Unsupervised Random Forest to search for anomalies in TESS light curves. We provide a catalogue of anomalous light curves, classify them according to their variability characteristics and associate their anomalous nature to any particular evolutionary stage or astrophysical configuration. For anomalies belonging to known classes (e.g. eclipsing binaries), we have investigated which physical parameters drive the anomaly score. We find a combination of unclassified anomalies and objects of a known class with outlying physical configurations, such as rapid pulsators, deep eclipsing binaries of long periods, and irregular light curves due to obscuration in YSOs. Remarkably, we find that the set of anomalous types differ between the Kepler and TESS datasets, indicating that the overall properties of the parent population are an important driver of anomalous behaviour.Comment: 23 pages, 26 figures. Submitted to MNRA

Probabilistic evaluation tankship damage in collision events.

CIVINS (Civilian Institutions) Thesis documenthttp://www.archive.org/details/probabilisticeva00crakCIVIN

Exploring Molecular Links between Obesity and Breast Cancer

Obesity is associated with a high risk of incidence of, and mortality for, postmenopausal breast cancer. Despite this well-established link, the molecular and mechanistic basis of the obesity and breast cancer association still remains unclear. In obesity research, genetic variation due to copy number differences has become increasingly popular. The salivary amylase gene, AMY1, is well-known for its extensive copy number variation (CNV) in the human genome and has previously been correlated with a genetic predisposition toward obesity; however, research surrounding this association is controversial. Despite an established relationship between obesity and breast cancer risk, the recently reported genetic association between AMY1 CNV and obesity has not yet been examined in normal and obese breast cancer patients. Furthermore, gene expression changes in breast tumours from obese women remain poorly characterised. We hypothesise that obese breast cancer patients are associated with (1) low AMY1 copy number and (2) differential expression of candidate genes in the breast tumour. This study included 55 post-menopausal breast cancer patients from The Cancer Society Tissue Bank, with a BMI (body mass index)> 30 (obese; n=28) or BMI < 25 (healthy; n=27). Quantitative PCR (qPCR) assessment of germline AMY1 copy number status from blood showed that obese breast cancer patients have a lower average copy number of AMY1 compared to normal weight patients. Examining breast tumour expression profiles of obese and non-obese patients from two published studies, identified four candidate genes (GRIA2, DUSP4, NR2F1, and ADH1B) shared between both studies. Analysis of gene expression data from The Cancer Genome Atlas (TCGA) indicated that these four genes are differentially expressed within clinically relevant breast tumour subtypes characterised by oestrogen receptor, progesterone receptor and HER2 status. qPCR analysis of each candidate gene within our study cohort showed that the average expression of GRIA2, DUSP4, NR2F1 and ADH1B was lower in obese compared to healthy breast tumours, but these results were not statistically significant. My study indicated that BMI may be associated with lower germline copy number of AMY1 in post-menopausal breast cancer patients; however, further work with a larger cohort is needed to establish if GRIA2, DUSP4, NR2F1 and ADH1B are associated with obesity related breast cancer

Biologically and acoustically compatible chamber for studying ultrasound-mediated delivery of therapeutic compounds

Ultrasound (US), in combination with microbubbles, has been found to be a potential alternative to viral therapies for transfecting biological cells. The translation of this technique to the clinical environment, however, requires robust and systematic optimization of the acoustic parameters needed to achieve a desired therapeutic effect. Currently, a variety of different devices have been developed to transfect cells in vitro, resulting in a lack of standardized experimental conditions and difficulty in comparing results from different laboratories. To overcome this limitation, we propose an easy-to-fabricate and cost-effective device for application in US-mediated delivery of therapeutic compounds. It comprises a commercially available cell culture dish coupled with a silicon-based "lid" developed in-house that enables the device to be immersed in a water bath for US exposure. Described here are the design of the device, characterization of the sound field and fluid dynamics inside the chamber and an example protocol for a therapeutic delivery experiment

Local and systemic effects of adipocyte-secreted factors in breast cancer

Breast cancer is a complex disease that, once developed, progresses in response to multiple environmental factors, including local microenvironmental factors within the breast and systemic markers in circulation. Obesity affects one third of all New Zealand adults and is known to negatively impact breast cancer outcomes. Epidemiological studies have shown obese women with breast cancer have increased risk of recurrence and metastasis, poorer pathological response rates to chemotherapy, and worse overall survival. The biological mechanisms underlying these associations are complex and not yet completely understood. Cancer associated adipocytes (CAA) are fat cells located within close proximity to breast tumour cells. In vitro, CAA promote breast cancer cell migration, invasion, and resistance to therapy. Analysis of gene expression in breast cancer cells co-cultured with CAA has identified a number of genes which may be supporting disease progression. To further assess the influence of CAA on breast cancer cells, we identified and quantified changes in global protein abundance induced in breast cancer cells co-cultured with human breast adipocytes (CAA), and evaluated these changes by identifying key molecules and pathways that were significantly altered. Global differences in relative protein expression in MCF-7 (ER+, PR+, HER2-) and MDA-MB-231 (ER-, PR-, HER2-) breast cancer cells co-cultured with, or without, mature breast adipocytes in a transwell co-culture system, were measured using isobaric tags for relative and absolute quantification (iTRAQ) labelling and liquid chromatography tandem mass spectrometry (LC-MS/MS). In both control and co-cultured samples, a total of 1,126 proteins and 1,218 proteins were identified in MCF-7 and MDA-MB-231 breast cancer cells, respectively. Relative to controls, 85 proteins in MCF-7 cells (32 upregulated, 53 downregulated) and 63 proteins in MDA-MB-231 cells (51 upregulated, 12 downregulated) were differentially abundant by 1.5-fold or greater in co-cultured cells. Co-culture with CAA caused an enriched upregulation of tricarboxylic acid (TCA) cycle proteins in MCF-7 cells and glycolysis proteins in MDA-MB-231 cells. The glycolytic protein, phosphoglycerate kinase 1 (PGK1), was the only protein that was upregulated by more than 1.5-fold in both MCF-7 and MDA-MB-231 cells co-cultured with CAA. PGK1 is a kinase enzyme that plays an important role in the glycolytic pathway. In women with breast cancer, increased PGK1 expression in the tumour has been identified as a predictor of poor patient survival and marker of resistance to paclitaxel. As metabolic co-operation between adipocytes and breast cancer cells is a key mechanism promoting breast tumour progression, we investigated PGK1 overexpression in vitro. The transient transfection model for in vitro PGK1 overexpression utilised in this study induced differential effects in MCF-7 and MDA-MB-231 breast cancer cells. PGK1 overexpression increased sensitivity to chemotherapy in MCF-7 cells. Whereas, cell proliferation and viability were decreased, and conditioned media lactate concentrations were increased, in GFP and PGK1 expressing plasmid transfected MDA-MB-231 cells. In silico analysis showed PGK1 expression was higher in HER2 enriched compared to triple negative breast cancer cells, and was upregulated in HER2 overexpressing (HER2+) compared to HER2- breast tumours, suggesting that PGK1 expression may be particularly relevant to HER2+ breast cancers. Obesity is characterised by a state of low-grade chronic systemic inflammation. Breast cancer chemotherapies are predominantly metabolised in liver hepatocytes by cytochrome P450 (CYP) drug metabolising enzymes. Inflammatory cytokines have been shown to downregulate expression and activity of CYP enzymes in vitro. Additionally, CYP genotype-phenotype discordance has been observed in patients with advanced cancer. To investigate whether obesity-associated circulating inflammatory cytokines influence in vivo activity of CYP enzymes in women receiving chemotherapy for breast cancer, we carried out an exploratory patient study that recruited seven non-obese and five obese women receiving adriamycin-cyclophosphamide (AC) and paclitaxel chemotherapy for stage II or III breast cancer. During chemotherapy, serum levels of B-cell activating factor (BAFF), growth and differentiation factor 15 (GDF-15) and monocyte chemoattractant protein 1 (MCP-1) increased, whereas interleukin 10 (IL-10) levels decreased. Importantly, changes in the levels of circulating inflammatory cytokines during chemotherapy were not associated with differences in body morphometry or voluntary physical activity levels. Activity of the CYP enzymes (CYP2C9, CYP2C19, CYP2D6, and CYP3A4), measured using the ‘Inje’ probe drug cocktail, were largely unchanged over the course of chemotherapy, although varied between participants. However, increased serum MCP-1 levels correlated with decreased CYP3A4 activity during chemotherapy, and this finding provides preliminary evidence that circulating inflammatory cytokines may negatively influence CYP-mediated chemotherapy metabolism in women undergoing treatment for breast cancer. This study has provided, for the first time, an extensive list of breast cancer cell protein abundance alterations induced by co-culture with CAA, which can be used as a comprehensive platform for future investigations. Moreover, this study has validated, for the first time, the feasibility of using the ‘Inje’ cocktail to measure CYP activity in women receiving chemotherapy for breast cancer, and in doing so, has provided preliminary evidence to support the concept that changes in circulating inflammatory cytokines during chemotherapy treatment may impact CYP activity, and thus, chemotherapy metabolism in some patients

Delayed recovery of coronary resistive vessel function after coronary angioplasty

AbstractObjectives. The aim of this study was to use Doppler catheterization and sequential dynamic positron emission tomography (PET) to investigate the role and time course of abnormal coronary resistive vessel function in the impairment of the coronary vasodilator response (maximal/basal coronary blood flow) after successful coronary angioplasty.Background. The coronary vasodilator response may be impaired immediately after coronary angioplasty, despite successful dilation of a flow-limiting stenosis.Methods. Twelve men (mean age 52 ± 10 years) with singlevessel coronary artery disease and normal left ventricular function were studied. The coronary vasodilator response to intravenous dipyridamole (0.5 mg·kg−1over 4 min) was determined from intracoronary Doppler measurement of coronary How velocity, before and after successful angioplasty. Basal and maximal myocardial blood flow in the angioplasty region and a normal region were determined in nine patients with positron emission tomography with H215O at 1 day (PET1), 7 days (PET2) and 3 months (PET3) after angioplasty.Results. The coronary vasodilator response, measured by Doppler catheterization, was similar before and immediately after angioplasty, 1.63 ± 0.41 and 1.62 ± 0.55, respectively (p = NS). After angioplasty, in seven of nine patients without restenosis, basal myocardial blood flow at PET1, PET2and PET3was 0.98 ± 0.16, 0.94 ± 0.09 and 0.99 ± 0.13 ml·min−1·g−1, respectively, in the remote region and 1.19 ± 0.23 (p < 0.01 vs. remote region), 1.17 ± 0.19 (p < 0.01 vs. remote region) and 1.10 ± 0.08 ml·min-1·g−1(p = NS vs. remote region), respectively, in the angioplasty region. Myocardial blood flow after dipyridamole at PET1, PET2and PET3was 3.04 ± 0.68, 3.00 ± 0.71 and 3.00 ± 0.60 ml·ml·min−1g−1, respectively, in the remote region and 2.11 ± 0.80 (p < 0.01 vs. remote region), 2.28 ± 0.73 (p = NS vs. remote region) and 3.06 ± 0.86 ml · min−1· g−1(p = NS vs. remote region), respectively, in the angioplasty region. The coronary vasodilator response at PET1, PET2and PET3was 3.15 ± 0.85, 3.18 ± 0.68 and 3.08 ± 0.75, respectively, in the remote region and 1.80 ± 0.68 (p < 0.01 vs. remote region), 1.94 ± 0.49 (p < 0.01 vs. remote region) and 2.77 ± 0.74 (p = NS vs. remote region), respectively, in the angioplasty region.Conclusions. After successful angioplasty, basal myocardial blood flow is increased for ≥7 days in the angioplasty region, with a reduction in the dipyridamole · induced increase in maximal myocardial blood flow for ≥24 h after the procedure. Thus, the coronary vasodilator response is impaired for ≥7 days after angioplasty, indicating that there is abnormal resistive vessel function in the coronary vascular bed distal to a coronary artery stenosis that persists for 7 days to 3 months

Pericardial Disease in Cancer Patients

Purpose of review: To understand the variety of conditions in which the pericardium may be affected in cancer patients. // Recent findings: Cancer may affect the pericardium directly (primary cancer; uncommon) or through metastases (commoner). Cancer treatment (chemotherapy and radiotherapy) may affect the pericardium leading to pericarditis and myopericarditis. Pericardial effusions, tamponade and constrictive pericarditis are complications that can also occur. A variety of techniques (predominantly cardiac imaging related) are used to make the diagnosis with the treatment strategy dependent on whether the pericardial disease is due to cancer or as a result of cancer treatment. // Summary: A variety of pericardial diseases may be caused by cancer and cancer treatment. Determining the aetiology and providing effective treatment can often be challenging