Geometry of lines and degeneracy loci of morphisms of vector bundles

Corrado Segre played a leading role in the foundation of line geometry. We survey some recent results on degeneracy loci of morphisms of vector bundles where he still is of profound inspiration.Comment: 10 pages. To appear in the proceedings of the conference "Homage to Corrado Segre

Regression of left ventricular mass following conversion from conventional hemodialysis to thrice weekly in-centre nocturnal hemodialysis

<p>Abstract</p> <p>Background</p> <p>Increased left ventricular mass (LVM) is associated with adverse outcomes in patients receiving chronic hemodialysis. Among patients receiving conventional hemodialysis (CHD, 3×/week, 4 hrs/session), we evaluated whether dialysis intensification with in-centre nocturnal hemodialysis (INHD, 3×/week, 7-8 hrs/session in the dialysis unit) was associated with regression of LVM.</p> <p>Methods</p> <p>We conducted a retrospective cohort study of CHD recipients who converted to INHD and received INHD for at least 6 months. LVM on the first echocardiogram performed at least 6 months post-conversion was compared to LVM pre-conversion. In a secondary analysis, we examined echocardiograms performed at least 12 months after starting INHD. The effect of conversion to INHD on LVM over time was also evaluated using a longitudinal analysis that incorporated all LVM data on patients with 2 or more echocardiograms.</p> <p>Results</p> <p>Thirty-seven patients were eligible for the primary analysis. Mean age at conversion was 49 ± 12 yrs and 30% were women. Mean pre-conversion LVM was 219 ± 66 g and following conversion, LVM declined by 32 ± 58 g (p = 0.002). Among patients whose follow-up echocardiogram occurred at least 12 months following conversion, LVM declined by 40 ± 56 g (p = 0.0004). The rate of change of LVM decreased significantly from 0.4 g/yr before conversion, to -11.7 g/yr following conversion to INHD (p < 0.0001).</p> <p>Conclusion</p> <p>Conversion to INHD is associated with a significant regression in LVM, which may portend a more favourable cardiovascular outcome. Our preliminary findings support the need for randomized controlled trials to definitively evaluate the cardiovascular effects of INHD.</p

The read-across hypothesis and environmental risk assessment of pharmaceuticals

This article is made available through the Brunel Open Access Publishing Fund. Copyright © 2013 American Chemical Society.Pharmaceuticals in the environment have received increased attention over the past decade, as they are ubiquitous in rivers and waterways. Concentrations are in sub-ng to low μg/L, well below acute toxic levels, but there are uncertainties regarding the effects of chronic exposures and there is a need to prioritise which pharmaceuticals may be of concern. The read-across hypothesis stipulates that a drug will have an effect in non-target organisms only if the molecular targets such as receptors and enzymes have been conserved, resulting in a (specific) pharmacological effect only if plasma concentrations are similar to human therapeutic concentrations. If this holds true for different classes of pharmaceuticals, it should be possible to predict the potential environmental impact from information obtained during the drug development process. This paper critically reviews the evidence for read-across, and finds that few studies include plasma concentrations and mode of action based effects. Thus, despite a large number of apparently relevant papers and a general acceptance of the hypothesis, there is an absence of documented evidence. There is a need for large-scale studies to generate robust data for testing the read-across hypothesis and developing predictive models, the only feasible approach to protecting the environment.BBSRC Industrial Partnership Award BB/ I00646X/1 and BBSRC Industrial CASE Partnership Studentship BB/I53257X/1 with AstraZeneca Safety Health and Environment Research Programme

An immunohistochemical perspective of PPARβ and one of its putative targets PDK1 in normal ovaries, benign and malignant ovarian tumours

Peroxisome proliferator-activated receptor β (PPARβ) is a member of the nuclear hormone receptor family and is a ligand-activated transcription factor with few known molecular targets including 3-phosphoinositide-dependent protein kinase 1(PDK1). In view of the association of PPARβ and PDK1 with cancer, we have examined the expression of PPARβ and PDK1 in normal ovaries and different histological grades of ovarian tumours. Normal ovaries, benign, borderline, grades 1, 2 and 3 ovarian tumours of serous, muciuous, endometrioid, clear cell and mixed subtypes were analysed by immunohistochemistry for PPARβ and PDK1 expression. All normal ovarian tissues, benign, borderline and grade 1 tumours showed PPARβ staining localised in the epithelium and stroma. Staining was predominantly nuclear, but some degree of cytoplasmic staining was also evident. Approximately 20% of grades 2 and 3 tumours lacked PPARβ staining, whereas the rest displayed some degree of nuclear and cytoplasmic staining of the scattered epithelium and stroma. The extent of epithelial and stromal PPARβ staining was significantly different among the normal and the histological grades of tumours (χ2=59.25, d.f.=25, P<0.001; χ2=64.48, d.f.=25, P<0.001). Significantly different staining of PPARβ was observed in the epithelium and stroma of benign and borderline tumours compared with grades 1, 2 and 3 tumours (χ2=11.28, d.f.=4, P<0.05; χ2=16.15, d.f.=4, P<0.005). In contrast, PDK1 immunostaining was absent in 9 out of 10 normal ovaries. Weak staining for PDK1 was observed in one normal ovary and 40% of benign ovarian tumours. All borderline and malignant ovarian tumours showed positive cytoplasmic and membrane PDK1 staining. Staining of PDK1 was confined to the epithelium and the blood vessels, and no apparent staining of the stroma was evident. Significantly different PDK1 staining was observed between the benign/borderline and malignant ovarian tumours (χ2=22.45, d.f.=5, P<0.001). In some borderline and high-grade tumours, staining of the reactive stroma was also evident. Our results suggest that unlike the colon, the endometrial, head and neck carcinomas, overexpression of PPARβ does not occur in ovarian tumours. However, overexpression of PDK1 was evident in borderline and low- to high-grade ovarian tumours and is consistent with its known role in tumorigenesis

Expression of PPARδ in multistage carcinogenesis of the colorectum: implications of malignant cancer morphology

Whether peroxisome proliferator-activated receptor (PPAR) δ is a good target for the chemoprevention and/or treatment of colorectal cancer (CRC) remains controversial. Our goal was to examine PPARδ expression in multistage carcinogenesis of the colorectum and to assess the relevance of PPARδ in CRC. Immunohistochemical analysis indicated that PPARδ expression increased from normal mucosa to adenomatous polyps to CRC. In cancer tissues, the PPARδ protein was accumulated only in those cancer cells with highly malignant morphology, as represented by a large-sized nucleus, round-shaped nucleus, and presence of clear nucleoli. Interestingly, the cancer tissue often contained both PPARδ-positive and -negative areas, each retaining their respective specific morphological features. Moreover, this pattern persisted even when PPARδ-positive and -negative cells were aligned next to each other within a single cancer nest or gland and was present in the majority of CRC cases. Immunohistochemistry for Ki-67 proliferation marker showed no significant correlation between Ki-67 and PPARδ in CRC samples. Based on Western blot analysis and quantitative RT–PCR, high PPARδ protein expression correlated with high PPARδ mRNA levels. Peroxisome proliferator-activated receptor δ may have a supporting role in tumorigenesis, and the close association between PPARδ expression and malignant morphology of CRC cells suggests a pivotal role in cancer tissue

The Organic Food Premium: A Local Assessment in the UK

The present study combines stated and revealed preferences in order to estimate the hypothetical bias of a sample of organic food consumers from Canterbury in the UK. It uses contingent valuation and hedonic pricing to compare stated and revealed preferences and employs the Almost Ideal Demand System to estimate the elasticity of organic products. The results show that the average price premium is fairly large (approximately 10%). They also demonstrate, crucially, that the size of this estimate is encouragingly similar whether a willingness-to-pay or hedonic pricing method is used. The estimated elasticity of organic products is on average above one, suggesting an elastic response to pricing policy in the present sample. Desirable next steps and potential policy applications for future research are also discussed

PPARδ Activation Acts Cooperatively with 3-Phosphoinositide-Dependent Protein Kinase-1 to Enhance Mammary Tumorigenesis

Peroxisome proliferator-activated receptorδ (PPARδ) is a transcription factor that is associated with metabolic gene regulation and inflammation. It has been implicated in tumor promotion and in the regulation of 3-phosphoinositide-dependent kinase-1 (PDK1). PDK1 is a key regulator of the AGC protein kinase family, which includes the proto-oncogene AKT/PKB implicated in several malignancies, including breast cancer. To assess the role of PDK1 in mammary tumorigenesis and its interaction with PPARδ, transgenic mice were generated in which PDK1 was expressed in mammary epithelium under the control of the MMTV enhancer/promoter region. Transgene expression increased pT308AKT and pS9GSK3β, but did not alter phosphorylation of mTOR, 4EBP1, ribosomal protein S6 and PKCα. The transgenic mammary gland also expressed higher levels of PPARδ and a gene expression profile resembling wild-type mice maintained on a diet containing the PPARδ agonist, GW501516. Both wild-type and transgenic mice treated with GW501516 exhibited accelerated rates of tumor formation that were more pronounced in transgenic animals. GW501516 treatment was accompanied by a distinct metabolic gene expression and metabolomic signature that was not present in untreated animals. GW501516-treated transgenic mice expressed higher levels of fatty acid and phospholipid metabolites than treated wild-type mice, suggesting the involvement of PDK1 in enhancing PPARδ-driven energy metabolism. These results reveal that PPARδ activation elicits a distinct metabolic and metabolomic profile in tumors that is in part related to PDK1 and AKT signaling