Post occupancy evaluation of buildings in a zero carbon city

This paper presents a methodology to monitor the performance of buildings in a Zero Carbon City from the occupant perspective. Masdar City in Abu Dhabi is hailed as the World's pioneering Zero Carbon Zero Waste city. The initial phase of construction is complete and the first students have moved into the residential quarters of the Masdar Institute of Science and Technology (MIST) in September 2010. Although the study monitors both Carbon and Waste, this paper outlines a Post Occupancy Evaluation (POE) to assess the resident's satisfaction and building performance at MIST. The research focuses on the role that user behaviour and satisfaction plays on energy efficiency. It is hoped that such an approach will allow building performance to be normalized for user behaviour and to examine how best to commission, explain and handover complex low energy developments to new residents. It is hoped that the residents' reaction and adaptation to the first Zero Carbon Zero Waste city will provide valuable insights that can be applied to future low energy developments

A Study of Erectile Dysfunction in Male Diabetes Patients and its Correlation with Platelet-Lymphocyte Ratio

Introduction: Erectile dysfunction (ED) constitutes a large burden on society given its high prevalence and impact on quality of life. Diabetes is a common cause of organic ED. Prevalence of ED in diabetes ranges from 35% to 85% depending on the study, versus 26% in general population. Platelet-lymphocyte ratio (PLR) has been detected as an important marker for inflammation. Some studies have identified its role in ED but more research is needed. Material and methods: It was a hospital-based prospective observational study. According to International Index of Erectile Function (IIEF)-5 questionnaire, patients were divided into 4 categories: mild ED with score 17 to 21, mild-to-moderate ED with score 12 to 16, moderate ED with score 8 to 11 and severe ED with score 1 to 7. Presence of ED and its severity was correlated with age, residence, duration of diabetes, glycemic status, lipid profile, PLR, complications, body mass index (BMI), etc. Results: Prevalence of ED in male diabetes patients was found to be 72.4%. Among 110 cases with ED, 8 had mild ED (7.2%), 27 had mild-to-moderate (24.5%), 27 had moderate ED (24.5%) and 48 had severe ED (43.6%). Prevalence of ED was found to be proportional to age. Majority of cases in ED group were those with long-standing diabetes. Correlation of ED with complication of diabetes, like nephropathy and retinopathy, was significant, whereas it was not significant with neuropathy. Significant correlation of ED was found with BMI and PLR. Conclusion: ED prevalence was high among the diabetes patients and it increased with age and duration of the disease. Presence of diabetic complications was significantly associated with ED. BMI was significantly associated with development of ED. PLR was significantly higher in ED group and closely related to severity of ED

Towards a better understanding of the full impact of the left digit effect on individual trading behaviour: unearthing a trading profit effect

Investors’ perceptions of price have been shown to be disproportionately affected by the left-most digit(s). However, a similar left digit effect (LDE) in relation to another important determinant of investors’ behaviour (i.e. trading profit) has not been explored. We examine over 7,314,570 million trades made by 25,766 individuals and find a LDE in profit that is 1.71 times stronger than that related to closing price; suggesting that individuals focus more on left digits in profit than price when deciding when to close a trade. In addition, we observe a positive synergistic relationship between the LDE related to profit and price, suggesting that its total influence may result in losses of billions of dollars per financial year for investors. We suggest that these results make a strong case for educating investors against this bias

Sustained low-dose treatment with the histone deacetylase inhibitor LBH589 induces terminal differentation of osteosarcoma cells

Histone deacetylase inhibitors (HDACi) were identified nearly four decades ago based on their ability to induce cellular differentiation. However, the clinical development of these compounds as cancer therapies has focused on their capacity to induce apoptosis in hematologic and lymphoid malignancies, often in combination with conventional cytotoxic agents. In many cases, HDACi doses necessary to induce these effects result in significant toxicity. Since osteosarcoma cells express markers of terminal osteoblast differentiation in response to DNA methyltransferase inhibitors, we reasoned that the epigenetic reprogramming capacity of HDACi might be exploited for therapeutic benefit. Here, we show that continuous exposure of osteosarcoma cells to low concentrations of HDACi LBH589 (Panobinostat) over a three-week period induces terminal osteoblast differentiation and irreversible senescence without inducing cell death. Remarkably, transcriptional profiling revealed that HDACi therapy initiated gene signatures characteristic of chondrocyte and adipocyte lineages in addition to marked upregulation of mature osteoblast markers. In a mouse xenograft model, continuous low dose treatment with LBH589 induced a sustained cytostatic response accompanied by induction of mature osteoblast gene expression. These data suggest that the remarkable capacity of osteosarcoma cells to differentiate in response to HDACi therapy could be exploited for therapeutic benefit without inducing systemic toxicity

Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature

Treating metastatic osteosarcoma (OS) remains a challenge in oncology. Current treatment strategies target the primary tumour rather than metastases and have a limited efficacy in the treatment of metastatic disease. Metastatic cells have specific features that render them less sensitive to therapy and targeting these features might enhance the efficacy of current treatment. A detailed study of the biological characteristics and behaviour of metastatic OS cells may provide a rational basis for innovative treatment strategies. The aim of this review is to give an overview of the biological changes in metastatic OS cells and the preclinical and clinical efforts targeting the different steps in OS metastases and how these contribute to designing a metastasis directed treatment for OS

The Role of Glypicans in Wnt Inhibitory Factor-1 Activity and the Structural Basis of Wif1's Effects on Wnt and Hedgehog Signaling

Proper assignment of cellular fates relies on correct interpretation of Wnt and Hedgehog (Hh) signals. Members of the Wnt Inhibitory Factor-1 (WIF1) family are secreted modulators of these extracellular signaling pathways. Vertebrate WIF1 binds Wnts and inhibits their signaling, but its Drosophila melanogaster ortholog Shifted (Shf) binds Hh and extends the range of Hh activity in the developing D. melanogaster wing. Shf activity is thought to depend on reinforcing interactions between Hh and glypican HSPGs. Using zebrafish embryos and the heterologous system provided by D. melanogaster wing, we report on the contribution of glypican HSPGs to the Wnt-inhibiting activity of zebrafish Wif1 and on the protein domains responsible for the differences in Wif1 and Shf specificity. We show that Wif1 strengthens interactions between Wnt and glypicans, modulating the biphasic action of glypicans towards Wnt inhibition; conversely, glypicans and the glypican-binding “EGF-like” domains of Wif1 are required for Wif1's full Wnt-inhibiting activity. Chimeric constructs between Wif1 and Shf were used to investigate their specificities for Wnt and Hh signaling. Full Wnt inhibition required the “WIF” domain of Wif1, and the HSPG-binding EGF-like domains of either Wif1 or Shf. Full promotion of Hh signaling requires both the EGF-like domains of Shf and the WIF domains of either Wif1 or Shf. That the Wif1 WIF domain can increase the Hh promoting activity of Shf's EGF domains suggests it is capable of interacting with Hh. In fact, full-length Wif1 affected distribution and signaling of Hh in D. melanogaster, albeit weakly, suggesting a possible role for Wif1 as a modulator of vertebrate Hh signaling

A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma

<p>Abstract</p> <p>Background</p> <p>Osteosarcoma (OS) is a bone malignancy which occurs primarily in adolescents. Since it occurs during a period of rapid growth, genes important in bone formation and growth are plausible modifiers of risk. Genes involved in DNA repair and ribosomal function may contribute to OS pathogenesis, because they maintain the integrity of critical cellular processes. We evaluated these hypotheses in an OS association study of genes from growth/hormone, bone formation, DNA repair, and ribosomal pathways.</p> <p>Methods</p> <p>We evaluated 4836 tag-SNPs across 255 candidate genes in 96 OS cases and 1426 controls. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI).</p> <p>Results</p> <p>Twelve SNPs in growth or DNA repair genes were significantly associated with OS after Bonferroni correction. Four SNPs in the DNA repair gene <it>FANCM </it>(ORs 1.9-2.0, <it>P </it>= 0.003-0.004) and 2 SNPs downstream of the growth hormone gene <it>GH1 </it>(OR 1.6, <it>P </it>= 0.002; OR 0.5, <it>P </it>= 0.0009) were significantly associated with OS. One SNP in the region of each of the following genes was significant: <it>MDM2</it>, <it>MPG</it>, <it>FGF2</it>, <it>FGFR3</it>, <it>GNRH2</it>, and <it>IGF1</it>.</p> <p>Conclusions</p> <p>Our results suggest that several SNPs in biologically plausible pathways are associated with OS. Larger studies are required to confirm our findings.</p

Sclerostin: Current Knowledge and Future Perspectives

In recent years study of rare human bone disorders has led to the identification of important signaling pathways that regulate bone formation. Such diseases include the bone sclerosing dysplasias sclerosteosis and van Buchem disease, which are due to deficiency of sclerostin, a protein secreted by osteocytes that inhibits bone formation by osteoblasts. The restricted expression pattern of sclerostin in the skeleton and the exclusive bone phenotype of good quality of patients with sclerosteosis and van Buchem disease provide the basis for the design of therapeutics that stimulate bone formation. We review here current knowledge of the regulation of the expression and formation of sclerostin, its mechanism of action, and its potential as a bone-building treatment for patients with osteoporosis