Impact of Tumour Epithelial Subtype on Circulating MicroRNAs in Breast Cancer Patients

While a range of miRNAs have been shown to be dysregulated in the circulation of patients with breast cancer, little is known about the relationship between circulating levels and tumour characteristics. The aim of this study was to analyse alterations in circulating miRNA expression during tumour progression in a murine model of breast cancer, and to detemine the clinical relevance of identified miRNAs at both tissue and circulating level in patient samples. Athymic nude mice received a subcutaneous or mammary fat pad injection of MDA-MB-231 cells. Blood sampling was performed at weeks 1, 3 and 6 following tumour induction, and microRNA extracted. MicroRNA microArray analysis was performed comparing samples harvested at week 1 to those collected at week 6 from the same animals. Significantly altered miRNAs were validated across all murine samples by RQ-PCR (n = 45). Three miRNAs of interest were then quantified in the circulation(n = 166) and tissue (n = 100) of breast cancer patients and healthy control individuals. MicroArray-based analysis of murine blood samples revealed levels of 77 circulating microRNAs to be changed during disease progression, with 44 demonstrating changes .2-fold. Validation across all samples revealed miR-138 to be significantly elevated in the circulation of animals during disease development, with miR-191 and miR-106a levels significantly decreased. Analysis of patient tissue and blood samples revealed miR-138 to be significantly up-regulated in the circulation of patients with breast cancer, with no change observed in the tissue setting. While not significantly changed overall in breast cancer patients compared to controls, circulating miR-106a and miR-191 were significantly decreased in patients with basal breast cancer. In tissue, both miRNAs were significantly elevated in breast cancer compared to normal breast tissue. The data demonstrates an impact of tumour epithelial subtype on circulating levels of miRNAs, and highlights divergent miRNA profiles between tissue and blood samples from breast cancer patients

Automatisierte Planung von digitalen Hochgeschwindigkeitsnetzen

Der Ausbau von digitalen Hochgeschwindigkeitsnetzen ist gekennzeichnet durch neuartige Anforderungen an den Planungsprozess. Diese Anforderungen erfordern wiederum den Einsatz von neuartigen Paradigmen, die eine effiziente und zugleich genaue Planung von flächendeckenden Glasfasernetzen ermöglichen. Hierbei können wiederkehrende Planungsaufgaben durch eine gezielte computergestützte Automatisierung effizienter und genauer ausgeführt, als es mit bisherigen Planungskonzepten möglich ist. Dieses Arbeitspapier beschreibt die computergestützte Ausführung eines Planungsprozesses auf Basis von fünf grundlegenden, iterativen Planungsschritten und gibt Empfehlungen für eine effiziente und genaue Planung von Glasfasernetzen. Der hier vorgestellte Ansatz ermöglicht es Netzbetreibern und Investoren, den Ausbau beliebiger Siedlungs- und Gewerbegebiete auf der zuverlässigen Basis von belastbarem Faktenwissen wirtschaftlich zu priorisieren

Modeling demand response in the residential sector for the provision of reserves

2012 IEEE Power & Energy Society General Meeting. New Energy Horizons - Opportunities and Challenges, , San Diego, CAPenetrations of variable renewable generation are increasing globally. While this trend is creating challenges for power systems, improved communication technologies are providing opportunities for the demand side to play a role in meeting some of these challenges. Commercial and industrial customers have long participated in demand response, but residential demand response is a largely untapped resource. Smart grid solutions provide the residential sector with the potential to respond to the systems needs over short time scales. A number of residential loads are well suited to providing reserves with minimal impact on consumers. In this paper the potential response from the residential sector in a heating dominated climate is estimated by modeling relevant responsive loads. The potential response is significant (6% of system demand on average). The aggregate interruptible load is expected to fall by approximately 19% by 2020. The modeling captures the daily and seasonal variations of the available resource.Science Foundation IrelandDeposited by bulk impor

miR-191 levels in (A) Circulation and (B) tissue of Breast Cancer Patients and healthy controls.

<p>Levels in breast cancer patients were further subdivided based on epithelial subtype of the disease. * denotes outliers.</p

Top ten microRNAs demonstrating greatest changes in circulating levels in animals from week 1 to week 6 during tumour progression.

<p>Top ten microRNAs demonstrating greatest changes in circulating levels in animals from week 1 to week 6 during tumour progression.</p

Clinicopathological characteristics of patients from whom blood samples were harvested for analysis of circulating microRNAs.

<p>Clinicopathological characteristics of patients from whom blood samples were harvested for analysis of circulating microRNAs.</p

Validation of changes in circulating levels of microRNAs identified using microArray analysis in murine blood samples at week1, week 3 and week 6 following tumour induction (A) Circulating miR-138 (B) Circulating miR-191 (C) Circulating miR-106a.

<p>* denotes outliers.</p

Selection of 44 microRNAs found to be commonly dysregulated in the circulation of 4/5 animals as tumours progressed.

<p>Selection of 44 microRNAs found to be commonly dysregulated in the circulation of 4/5 animals as tumours progressed.</p

Impact of Tumour Epithelial Subtype on Circulating microRNAs in Breast Cancer Patients

While a range of miRNAs have been shown to be dysregulated in the circulation of patients with breast cancer, little is known about the relationship between circulating levels and tumour characteristics. The aim of this study was to analyse alterations in circulating miRNA expression during tumour progression in a murine model of breast cancer, and to detemine the clinical relevance of identified miRNAs at both tissue and circulating level in patient samples. Athymic nude mice received a subcutaneous or mammary fat pad injection of MDA-MB-231 cells. Blood sampling was performed at weeks 1, 3 and 6 following tumour induction, and microRNA extracted. MicroRNA microArray analysis was performed comparing samples harvested at week 1 to those collected at week 6 from the same animals. Significantly altered miRNAs were validated across all murine samples by RQ-PCR (n = 45). Three miRNAs of interest were then quantified in the circulation(n = 166) and tissue (n = 100) of breast cancer patients and healthy control individuals. MicroArray-based analysis of murine blood samples revealed levels of 77 circulating microRNAs to be changed during disease progression, with 44 demonstrating changes >2-fold. Validation across all samples revealed miR-138 to be significantly elevated in the circulation of animals during disease development, with miR-191 and miR-106a levels significantly decreased. Analysis of patient tissue and blood samples revealed miR-138 to be significantly up-regulated in the circulation of patients with breast cancer, with no change observed in the tissue setting. While not significantly changed overall in breast cancer patients compared to controls, circulating miR-106a and miR-191 were significantly decreased in patients with basal breast cancer. In tissue, both miRNAs were significantly elevated in breast cancer compared to normal breast tissue. The data demonstrates an impact of tumour epithelial subtype on circulating levels of miRNAs, and highlights divergent miRNA profiles between tissue and blood samples from breast cancer patients