Managing an Unstable Housing Market

AbstractIn this paper it is intended to place the recent experience of the Irish housing market in the context of economic and property market cycles, how these interact over a property cycle and lessons from recent policy experience including interventions in the housing area. In spatial terms the currenthousing market can be seen as the result of an ad-hoc development led urban growth pattern which contributed to a dispersed development pattern with problems in oversupply. It is clear that alternative options exist to this approach and that evidence based management systems in terms of planning, development and financial decisions will be required to reduce the severity of future property market corrections. The incidence of rapidly increasing residential property prices has been a feature of many international economies in the past decade. This has resulted in house price surges and corrections across much of the industrialised world. Factors associated with such surges include growth in housing demand often supported by relaxed monetary policy stances, planning and zoning systems and fiscal regimes which encourage the investment in residential property acquisition anddevelopment. The falling prices for housing in Ireland in 2007-2010 nationally has created a stagnating effect with purchasers reluctant to enter the market while the price correction is worked through. In turn suppliers, construction interests and vendors are highly reluctant to accept lower bid prices in the market due to often unrealistic expectations created during the long boom. The result of oversupply is falling prices, reduced occupation demand and decreased investor demand, leading to lower building activity and profitability. In addition the banking and liquidity crisis have contributed to a radical deterioration in economic circumstances and increasing out-migration. As part of the Urban Environment Project at UCD this working paper considers the current evidence of a market correction and oversupply in the Dublin region and Ireland based on data available up to March 2010 including the authors’ working projections for 2010

Studies of Protein Function by Liquid Chromatography-Mass Spectrometry

Complete genomes of many organisms have been recorded using high throughput nucleic acid sequencing; however the intricate functions of the gene products remain largely undiscovered. As the most prominent technology for polypeptide sequence determination and quantification, mass spectrometry is used extensively to address questions regarding the behaviours of proteins in the biological context. The capacity of mass spectrometers to measure covalent modifications of amino acids is also of great value in the investigation of biological processes since specific reactive sites within proteins modulate their activity. Integration of liquid chromatography into mass spectrometry platforms has greatly improved sensitivity and throughput and is of particular benefit in the analysis of highly complex polypeptide mixtures. Studies of the behaviours of individual intracellular proteins in bacterial, plant and metazoan systems employing liquid chromatography-mass spectrometry are described herein. The phosphorylation of individual residues and resulting alterations in function were determined in GraR and VraR, two antibiotic resistance factors in Staphylococcus aureus. Three phosphosites of starch branching enzyme IIb which appear to regulate starch biosynthesis in Zea mays as well as kinases for which these sites are putative substrates were identified. Regulation of the multifunctional protein beta-catenin by p38 mitogen activated protein kinase was explored. Gene products with affinity for the highly conserved multifunctional protein beta-catenin, including several not previously known to interact, were identified from Rattus norvegicus smooth muscle cells. The specificity of peptide ion mass and peptide fragment ion mass relative to instrumental mass accuracy and the consequence for tandem-mass spectrometry-based quantification are explored in a separate chapter. In silico comparison of peptide ion/product ion mass pairs calculated from the human proteome revealed a range of mass redundancy from high to low simulated mass accuracy. Product ions from a single peptide sequence differ in their tendencies toward mass redundancy however no correlation between size and sequence specificity was apparent. This dissertation illustrates research into protein function conducted on three types of mass spectrometers and demonstrates some effects of liquid chromatographic and mass spectrometric performance on proteomic studies

Peptide macrocyclisation via intramolecular interception of visible-light-mediated desulfurisation

Synthetic methods that enable the macrocyclisation of peptides facilitate the development of effective therapeutic and diagnostic tools. Herein we report a peptide cyclisation strategy based on intramolecular interception of visible-light-mediated cysteine desulfurisation. This method allows cyclisation of unprotected peptides in an aqueous solution via the installation of a hydrocarbon linkage. We explore the limits of this chemistry using a range of model peptides of increasing length and complexity, including peptides of biological/therapeutic relevance. The method is applied to replace the native disulfide of the peptide hormone, oxytocin, with a proteolytically/redox-stable hydrocarbon, and internal macrocyclisation of an MCL-1-binding peptide

Translational recoding as a feedback controller : systems approaches reveal polyamine-specific effects on the antizyme ribosomal frameshift

Peer reviewedPublisher PD

Targeting Hypoxic Prostate Tumors Using the Novel Hypoxia-Activated Prodrug OCT1002 Inhibits Expression of Genes Associated with Malignant Progression

Purpose: To understand the role of hypoxia in prostate tumor progression and to evaluate the ability of the novel unidirectional hypoxia-activated prodrug OCT1002 to enhance the antitumor effect of bicalutamide. Experimental Design: The effect of OCT1002 on prostate cancer cells (LNCaP, 22Rv1, and PC3) was measured in normoxia and hypoxia in vitro. In vivo, tumor growth and lung metastases were measured in mice treated with bicalutamide, OCT1002, or a combination. Dorsal skin fold chambers were used to image tumor vasculature in vivo. Longitudinal gene expression changes in tumors were analyzed using PCR. Results: Reduction of OCT1002 to its active form (OCT1001) decreased prostate cancer cell viability. In LNCaP-luc spheroids, OCT1002 caused increased apoptosis and decreased clonogenicity. In vivo, treatment with OCT1002 alone, or with bicalutamide, showed significantly greater tumor growth control and reduced lung metastases compared with controls. Reestablishment of the tumor microvasculature following bicalutamide-induced vascular collapse is inhibited by OCT1002. Significantly, the upregulation of RUNX2 and its targets caused by bicalutamide alone was blocked by OCT1002. Conclusions: OCT1002 selectively targets hypoxic tumor cells and enhances the antitumor efficacy of bicalutamide. Furthermore, bicalutamide caused changes in gene expression, which indicated progression to a more malignant genotype; OCT1002 blocked these effects, emphasizing that more attention should be attached to understanding genetic changes that may occur during treatment. Early targeting of hypoxic cells with OCT1002 can provide a means of inhibiting prostate tumor growth and malignant progression. This is of importance for the design and refinement of existing androgen-deprivation regimens in the clinic

Modern paradigms for prostate cancer detection and management

Early detection and management of prostate cancer has evolved over the past decade, with a focus now on harm minimisation and reducing overdiagnosis and overtreatment, given the proven improvements in survival from randomised controlled trials. Multiparametric magnetic resonance imaging (mpMRI) is now an important aspect of the diagnostic pathway in prostate cancer, improving the detection of clinically significant prostate cancer, enabling accurate localisation of appropriate sites to biopsy, and reducing unnecessary biopsies in most patients with normal magnetic resonance imaging scans. Biopsies are now performed transperineally, substantially reducing the risk of post-procedure sepsis. Australian-led research has shown that prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has superior accuracy in the staging of prostate cancer than conventional imaging (CT and whole-body bone scan). Localised prostate cancer that is low risk (International Society for Urological Pathology [ISUP] grade 1, Gleason score 3 + 3 = 6; and ISUP grade group 2, Gleason score 3 + 4 = 7 with less than 10% pattern 4) can be offered active surveillance, reducing harms from overtreatment. Prostatectomy and definitive radiation remain the gold standard for localised intermediate and high risk disease. However, focal therapy is an emerging experimental treatment modality in Australia in carefully selected patients. The management of advanced prostate cancer treatment has evolved to now include several novel agents both in the metastatic hormone-sensitive and castration-resistant disease settings. Multimodal therapy with androgen deprivation therapy, additional systemic therapy and radiotherapy are often recommended. PSMA-based radioligand therapy has emerged as a treatment option for metastatic castration-resistant prostate cancer and is currently being evaluated in earlier disease states

Operating Room Fomites as Potential Sources for Microbial Transmission in Burns Theatres.

BACKGROUND: Burn patients are susceptible to healthcare-associated infections. Contaminated surfaces play a role in microbial transmission. This study aimed to quantify the degree of contamination of burns theatre fomites during routine clinical use. METHODS: The Patslide Patient Transfer Board (PAT slide) and operating table were investigated using two methods—bacterial swabs to culture viable organisms and adenosine triphosphate (ATP) swabs to measure biological material. Both items were sampled four times a day: before the first case, immediately after a case, immediately before the next case after cleaning and after the terminal clean. RESULTS: Among 82 bacterial samples, four organisms were isolated, including Staphylococcus aureus, Enterobacter cloacae (E. cloacae) x2 and Pseudomonas aeruginosa (P. aeruginosa), all from the PAT slide. The E. cloacae persisted after cleaning. In 9/82 swabs, the ATP count was >10 relative light units (RLU). In all cases where an organism was identified, the ATP count was >10 RLU. Hence the sensitivity and specificity of ATP > 10 RLU in detecting an organism were 100% and 94% respectively. CONCLUSIONS: Within burns theatres, there are instances of bacterial contamination on surfaces that persist despite cleaning. ATP luminometers as a point-of-care device may have a role in determining the cleanliness of surfaces, potentially minimizing onwards-bacterial transmission

Are power calculations useful? A multicentre neuroimaging study

There are now many reports of imaging experiments with small cohorts of typical participants that precede large-scale, often multicentre studies of psychiatric and neurological disorders. Data from these calibration experiments are sufficient to make estimates of statistical power and predictions of sample size and minimum observable effect sizes. In this technical note, we suggest how previously reported voxel-based power calculations can support decision making in the design, execution and analysis of cross-sectional multicentre imaging studies. The choice of MRI acquisition sequence, distribution of recruitment across acquisition centres, and changes to the registration method applied during data analysis are considered as examples. The consequences of modification are explored in quantitative terms by assessing the impact on sample size for a fixed effect size and detectable effect size for a fixed sample size. The calibration experiment dataset used for illustration was a precursor to the now complete Medical Research Council Autism Imaging Multicentre Study (MRC-AIMS). Validation of the voxel-based power calculations is made by comparing the predicted values from the calibration experiment with those observed in MRC-AIMS. The effect of non-linear mappings during image registration to a standard stereotactic space on the prediction is explored with reference to the amount of local deformation. In summary, power calculations offer a validated, quantitative means of making informed choices on important factors that influence the outcome of studies that consume significant resources

Utilisation of poultry litter as an energy feedstock

peer-reviewedThis paper examines poultry litter (PL) as a resource in fuel quality terms and illustrates how the small scale application of fluidised bed technology solves both energy and waste problems, while producing a nutrient rich ash. PL was found to have a higher heating value (HHV) of 18 GJ t−1 on a dry basis (db). On an as received basis (ar), it had an ash mass fraction of 9% and the elemental phosphorous content of the ash was 110 g kg−1. The resultant mineral matter can be utilised as a nutrient substitute for mineral fertiliser