Slievabawnogue Housing:Two Dwellings in A Disused Quarry

This project involves the construction of a dwelling in the outskirts of Dublin City. Situated in a disused quarry, the house act as an inhabited bridge, spanning between natural and man made outcrops, service structures and a shared entrance staircase. The houses language derives from the structure necessary to achieve these spans.
The section internally is modeled to present a variety of scales of spaces. More intimate living spaces and bedrooms occur in a lower, north-facing wing. Taller living spaces address the south.

Incorporating rainwater harvesting, wood-gasifying boilers, on site wind powered electrical generation, solar thermal panels and very high levels of insulation the houses are close to energy neutral. The fact that the house is constructed in massive timber construction means that 250 tonnes of carbon are sequestered in its construction. The design includes a 25yar replanting strategy to replace the existing coniferous-forested surrounds with native species in a coppiced planting strategy to allow ongoing fuel for the house, and cash crops to be sold on.

Located in an area of outstanding natural beauty the planning and design of the house involved research into patterns of rural development, the relationship between man made interventions and the natural landscape and the technology of the vernacular. This latter research forms part of the themes being explored under the Kevin Kieran Arts Council / OPW Bursary

Aims / Objectives Questions

1 To design and construct a low energy place to dwell.
2 To investigate the relationship between man-made interventions and new construction in an area of outstanding natural beauty.
3 To derive a language of construction that is contemporary in nature but refers to precedents embedded in the vernacular.
4 To develop a low-carbon form of construction that allows the construction of the house to act to sequester carbon
5 To make a contemporary addition in sympathy with the qualities of the existing site

A novel dual-fluorescence strategy for functionally validating microRNA targets in 3-prime untranslated regions: regulation of the inward rectifier potassium channel Kir2.1 by miR-212.

Gene targeting by microRNAs is important in health and disease. We developed a functional assay for identifying microRNA targets and applied it to the K+ channel Kir2.1 (KCNJ2) which is dysregulated in cardiac and vascular disorders. The 3'UTR was inserted downstream of the mCherry red fluorescent protein coding sequence in a mammalian expression plasmid. MicroRNA sequences were inserted into the pSM30 expression vector which provides enhanced green fluorescent protein as an indicator of microRNA expression. HEK293 cells were co-transfected with the mCherry-3'UTR plasmid and a pSM30-based plasmid with a microRNA insert. The principle of the assay is that functional targeting of the 3'UTR by the microRNA results in a decrease in the red/green fluorescence intensity ratio as determined by automated image analysis. The method was validated with miR-1, a known downregulator of Kir2.1 expression, and was used to investigate targeting of the Kir2.1 3'UTR by miR-212. Red/green ratio was lower in miR-212-expressing cells compared to non-targeting controls, an effect that was attenuated by mutating the predicted target site. MiR-212 also reduced inward rectifier current and Kir2.1 protein in HeLa cells. This novel assay has several advantages over traditional luciferase-based assays including larger sample size, amenability to time course studies and adaptability to high-throughput screening.

Ecological impacts of an invasive predator explained and predicted by comparative functional responses

Forecasting the ecological impacts of invasive species is a major challenge that has seen little progress, yet the development of robust predictive approaches is essential as new invasion threats continue to emerge. A common feature of ecologically damaging invaders is their ability to rapidly exploit and deplete resources. We thus hypothesized that the 'functional response' (the relationship between resource density and consumption rate) of such invasive species might be of consistently greater magnitude than those of taxonomically and/or trophically similar native species. Here, we derived functional responses of the predatory Ponto-Caspian freshwater 'bloody red' shrimp, Hemimysis anomala, a recent and ecologically damaging invader in Europe and N. America, in comparison to the local native analogues Mysis salemaai and Mysis diluviana in Ireland and Canada, respectively. This was conducted in a novel set of experiments involving multiple prey species in each geographic location and a prey species that occurs in both regions. The predatory functional responses of the invader were generally higher than those of the comparator native species and this difference was consistent across invaded regions. Moreover, those prey species characterized by the strongest and potentially de-stabilizing Type II functional responses in our laboratory experiments were the same prey species found to be most impacted by H. anomala in the field. The impact potential of H. anomala was further indicated when it exhibited similar or higher attack rates, consistently lower prey handling times and higher maximum feeding rates compared to those of the two Mysis species, formerly known as 'Mysis relicta', which itself has an extensive history of foodweb disruption in lakes to which it has been introduced. Comparative functional responses thus merit further exploration as a methodology for predicting severe community-level impacts of current and future invasive species and could be entered into risk assessment protocols.

eNOS overexpression exacerbates vascular closure in the obliterative phase of OIR and increases angiogenic drive in the subsequent proliferative stage

Purpose: In ischemic retinopathies, the misdirection of reparative angiogenesis away from the hypoxic retina leads to pathologic neovascularization. Thus, therapeutic strategies that reverse this trend would be extremely beneficial. Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) is an important mediator of vascular endothelial growth factor (VEGF) function facilitating vascular growth and maturation. However, in addition to NO, eNOS can also produce superoxide (O), exacerbating pathology. Here, our aim was to investigate the effect of eNOS overexpression on vascular closure and subsequent recovery of the ischemic retina.

Methods: Mice overexpressing eNOS-GFP were subjected to oxygen-induced retinopathy (OIR) and changes in retinal vascularization quantified. Background angiogenic drive was assessed during vascular development and in aortic rings. NOS activity was measured by Griess assay or conversion of radiolabeled arginine to citrulline, nitrotyrosine (NT), and superoxide by immunolabeling and dihydroethidium fluorescence and VEGF by ELISA.

Results: In response to hyperoxia, enhanced eNOS expression led to increased NOS-derived superoxide and dysfunctional NO production, NT accumulation, and exacerbated vessel closure associated with tetrahydrobiopterin (BH) insufficiency. Despite worse vaso-obliteration, eNOS overexpression resulted in elevated hypoxia-induced angiogenic drive, independent of VEGF production. This correlated with increased vascular branching similar to that observed in isolated aortas and during development. Enhanced recovery was also associated with neovascular tuft formation, which showed defective NO production and increased eNOS-derived superoxide and NT levels.

Conclusions: In hyperoxia, reduced BH bioavailability causes overexpressed eNOS to become dysfunctional, exacerbating vaso-obliteration. In the proliferative phase, however, eNOS has important prorepair functions enhancing angiogenic growth potential and recovery in ischemia. © 2012 The Association for Research in Vision and Ophthalmology, Inc.

Defects in acute responses to TLR4 in Btk-deficient mice result in impaired dendritic cell-induced IFN-γ production by natural killer cells

This study defines a critical role for Btk in regulating TLR4-induced crosstalk between antigen presenting cells (APCs) and natural killer (NK) cells. Reduced levels of IL-12, IL-18 and IFN-? were observed in Btk-deficient mice and ex vivo generated macrophages and dendritic cells (DCs) following acute LPS administration, whilst enhanced IL-10 production was observed. In addition, upregulation of activation markers and antigen presentation molecules on APCs was also impaired in the absence of Btk. APCs, by virtue of their ability to produce IL-12 and IL-18, are strong inducers of NK-derived IFN-?. Co-culture experiments demonstrate that Btk-deficient DCs were unable to drive wild-type or Btk-deficient NK cells to induce IFN-? production, whereas these responses could be restored by exogenous administration of IL-12 and IL-18. Thus Btk is a critical regulator of APC-induced NK cell activation by virtue of its ability to regulate IL-12 and IL-18 production in response to acute LPS administration.

Methodology for Validating Artifact Removal Techniques for Physiological Signals

Artifact removal from physiological signals is an essential component of the biosignal processing pipeline. The need for powerful and robust methods for this process has become particularly acute as healthcare technology deployment undergoes transition from the current hospital-centric setting toward a wearable and ubiquitous monitoring environment. Currently, determining the relative efficacy and performance of the multiple artifact removal techniques available on real world data can be problematic, due to incomplete information on the uncorrupted desired signal. The majority of techniques are presently evaluated using simulated data, and therefore, the quality of the conclusions is contingent on the fidelity of the model used. Consequently, in the biomedical signal processing community, there is considerable focus on the generation and validation of appropriate signal models for use in artifact suppression. Most approaches rely on mathematical models which capture suitable approximations to the signal dynamics or underlying physiology and, therefore, introduce some uncertainty to subsequent predictions of algorithm performance. This paper describes a more empirical approach to the modeling of the desired signal that we demonstrate for functional brain monitoring tasks which allows for the procurement of a ground truth signal which is highly correlated to a true desired signal that has been contaminated with artifacts. The availability of this ground truth, together with the corrupted signal, can then aid in determining the efficacy of selected artifact removal techniques. A number of commonly implemented artifact removal techniques were evaluated using the described methodology to validate the proposed novel test platform. © 2012 IEEE.