The expression of the ubiquitin ligase SIAH2 (seven in absentia homolog 2) is mediated through gene copy number in breast cancer and is associated with a basal-like phenotype and p53 expression

Introduction: The seven in absentia homolog 2 (SIAH2) protein plays a significant role in the hypoxic response by regulating the abundance of hypoxia-inducible factor-α; however, its role in breast carcinoma is unclear. We investigated the frequency and expression pattern of SIAH2 in two independent cohorts of sporadic breast cancers.Methods: Immunohistochemical evaluation of SIAH2protein expression was conducted in normal breast tissues and in tissue microarrays comprising ductal carcinoma in situ (DCIS) and a cohort of invasive breast carcinomas. Correlation analysis was performed between SIAH2 and clinicopathological variables and intrinsic breast cancer subgroups and validated in a cohort of 293 invasive ductal carcinomas. Promoter methylation, gene copy number and mRNA expression of SIAH2 were determined in a panel of basal-like tumors and cell lines.Results: There was a significant increase in nuclear SIAH2 expression from normal breast tissues through to DCIS and progression to invasive cancers. A significant inverse correlation was apparent between SIAH2 and estrogen receptor and progesterone receptor and a positive association with tumor grade, HER2, p53 and an intrinsic basal-like subtype. Logistic regression analysis confirmed the significant positive association between SIAH2 expression and the basal-like phenotype. No SIAH2 promoter methylation was identified, yet there was a significant correlation between SIAH2 mRNA and gene copy number. SIAH2-positive tumors were associated with a shorter relapse-free survival in univariate but not multivariate analysis.Conclusions: SIAH2 expression is upregulated in basal-like breast cancers via copy number changes and/or transcriptional activation by p53 and is likely to be partly responsible for the enhanced hypoxic drive through abrogation of the prolyl hydroxylases

Thin-plate rectangular weir with inlet shaft

Diplomová práce je rozdělena na literární rešerši a praktickou část (vlastní měření). Obsahem literární rešerše je popis přepadu přes tenkostěnný pravoúhlý přeliv. V praktické části je popsán model, měřicí přístroje a vlastní měření. Výsledkem je vyhodnocení průběhu dolní i horní obálky paprsku, stanovení součinitele přepadu, součinitele relativní délky šachty a určení mezní hodnoty relativní délky šachty pro neovlivnění tvaru přepadového paprsku.The thesis is divided into literary research and practical part (own measurement). The content of the literary research is a description of the flow over thin-plate rectangular weir. The practical part is focused on a description of the model, measuring equipment and measurement. The results are evaluation of lower and upper surface of nappe, determination of discharge coefficient, coefficient of relative length of shaft, limit value of relative length of shaft for uninfluenced shape of nappe.

Effects of magnitude and frequency of variations in external power output on simulated cycling time-trial performance

Mechanical models of cycling time-trial performance have indicated adverse effects of variations in external power output on overall performance times. Nevertheless, the precise influences of the magnitude and number of these variations over different distances of time trial are unclear. A hypothetical cyclist (body mass 70 kg, bicycle mass 10 kg) was studied using a mathematical model of cycling, which included the effects of acceleration. Performance times were modelled over distances of 4-40 km, mean power outputs of 200-600 W, power variation amplitudes of 5-15% and variation frequencies of 2-32 per time-trial. Effects of a "fast-start" strategy were compared with those of a constant-power strategy. Varying power improved 4-km performance at all power outputs, with the greatest improvement being 0.90 s for ± 15% power variation. For distances of 16.1, 20 and 40 km, varying power by ± 15% increased times by 3.29, 4.46 and 10.43 s respectively, suggesting that in long-duration cycling in constant environmental conditions, cyclists should strive to reduce power variation to maximise performance. The novel finding of the present study is that these effects are augmented with increasing event distance, amplitude and period of variation. These two latter factors reflect a poor adherence to a constant speed

Electrochemical analysis of microdroplet formation

This paper reports an electrochemical measurement system with a high-speed camera for observation of molecular transport phenomena at a water-oil (W/O) interface during microfluidic droplet formation. For demonstration of the system, currents corresponding to the transport of electrolyte ions to form the electrical double layer at the liquid interface were measured. Additionally, the high-speed camera observation revealed charge-effect on droplet stability during and/or just after the formation. This measurement system is expected to facilitate a full understanding of the droplet formation process