Prediagnostic Plasma Vitamin D Metabolites and Mortality among Patients with Prostate Cancer

Laboratory evidence suggests that vitamin D might influence prostate cancer prognosis.We examined the associations between prediagnostic plasma levels of 25(OH)vitamin D [25(OH)D] and 1,25(OH)(2) vitamin D [1,25(OH)(2)D] and mortality among 1822 participants of the Health Professionals Follow-up Study and Physicians' Health Study who were diagnosed with prostate cancer. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of total mortality (n = 595) and lethal prostate cancer (death from prostate cancer or development of bone metastases; n = 202). In models adjusted for age at diagnosis, BMI, physical activity, and smoking, we observed a HR of 1.22 (95% CI: 0.97, 1.54) for total mortality, comparing men in the lowest to the highest quartile of 25(OH)D. There was no association between 1,25(OH)(2)D and total mortality. Men with the lowest 25(OH)D quartile were more likely to die of their cancer (HR: 1.59; 95% CI: 1.06, 2.39) compared to those in the highest quartile (P(trend) = 0.006). This association was largely explained by the association between low 25(OH)D levels and advanced cancer stage and higher Gleason score, suggesting that these variables may mediate the influence of 25(OH)D on prognosis. The association also tended to be stronger among patients with samples collected within five years of cancer diagnosis. 1,25(OH)(2)D levels were not associated with lethal prostate cancer.Although potential bias of less advanced disease due to more screening activity among men with high 25(OH)D levels cannot be ruled out, higher prediagnostic plasma 25(OH)D might be associated with improved prostate cancer prognosis

A methodology for speeding up matrix vector multiplication for single/multi-core architectures

In this paper, a new methodology for computing the Dense Matrix Vector Multiplication, for both embedded (processors without SIMD unit) and general purpose processors (single and multi-core processors, with SIMD unit), is presented. This methodology achieves higher execution speed than ATLAS state-of-the-art library (speedup from 1.2 up to 1.45). This is achieved by fully exploiting the combination of the software (e.g., data reuse) and hardware parameters (e.g., data cache associativity) which are considered simultaneously as one problem and not separately, giving a smaller search space and high-quality solutions. The proposed methodology produces a different schedule for different values of the (i) number of the levels of data cache; (ii) data cache sizes; (iii) data cache associativities; (iv) data cache and main memory latencies; (v) data array layout of the matrix and (vi) number of cores

Circulating vitamin D, vitamin D-related genetic variation, and risk of fatal prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

BACKGROUND: Evidence from experimental animal and cell line studies supports a beneficial role for vitamin D in prostate cancer (PCa). Although the results from human studies have been mainly null for overall PCa risk, there may be a benefit for survival. This study assessed the associations of circulating 25-hydroxyvitamin D (25(OH)D) and common variations in key vitamin D-related genes with fatal PCa. METHODS: In a large cohort consortium, 518 fatal cases and 2986 controls with 25(OH)D data were identified. Genotyping information for 91 single-nucleotide polymorphisms (SNPs) in 7 vitamin D-related genes (vitamin D receptor, group-specific component, cytochrome P450 27A1 [CYP27A1], CYP27B1, CYP24A1, CYP2R1, and retinoid X receptor α) was available for 496 fatal cases and 3577 controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of 25(OH)D and SNPs with fatal PCa. The study also tested for 25(OH)D-SNP interactions among 264 fatal cases and 1169 controls. RESULTS: No statistically significant relationship was observed between 25(OH)D and fatal PCa (OR for extreme quartiles, 0.86; 95% CI, 0.65-1.14; P for trend = .22) or the main effects of the SNPs and fatal PCa. There was evidence suggesting that associations of several SNPs, including 5 related to circulating 25(OH)D, with fatal PCa were modified by 25(OH)D. Individually, these associations did not remain significant after multiple testing; however, the P value for the set-based test for CYP2R1 was .002. CONCLUSIONS: Statistically significant associations were not observed for either 25(OH)D or vitamin D-related SNPs with fatal PCa. The effect modification of 25(OH)D associations by biologically plausible genetic variation may deserve further exploration

Current challenges in software solutions for mass spectrometry-based quantitative proteomics

This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

Comparison of Insertional RNA Editing in Myxomycetes

RNA editing describes the process in which individual or short stretches of nucleotides in a messenger or structural RNA are inserted, deleted, or substituted. A high level of RNA editing has been observed in the mitochondrial genome of Physarum polycephalum. The most frequent editing type in Physarum is the insertion of individual Cs. RNA editing is extremely accurate in Physarum; however, little is known about its mechanism. Here, we demonstrate how analyzing two organisms from the Myxomycetes, namely Physarum polycephalum and Didymium iridis, allows us to test hypotheses about the editing mechanism that can not be tested from a single organism alone. First, we show that using the recently determined full transcriptome information of Physarum dramatically improves the accuracy of computational editing site prediction in Didymium. We use this approach to predict genes in the mitochondrial genome of Didymium and identify six new edited genes as well as one new gene that appears unedited. Next we investigate sequence conservation in the vicinity of editing sites between the two organisms in order to identify sites that harbor the information for the location of editing sites based on increased conservation. Our results imply that the information contained within only nine or ten nucleotides on either side of the editing site (a distance previously suggested through experiments) is not enough to locate the editing sites. Finally, we show that the codon position bias in C insertional RNA editing of these two organisms is correlated with the selection pressure on the respective genes thereby directly testing an evolutionary theory on the origin of this codon bias. Beyond revealing interesting properties of insertional RNA editing in Myxomycetes, our work suggests possible approaches to be used when finding sequence motifs for any biological process fails

Right Scaling for Right Pricing: A Case Study on Total Cost of Ownership Measurement for Cloud Migration

Cloud computing promises traditional enterprises and independent software vendors a myriad of advantages over on-premise installations including cost, operational and organizational efficiencies. The decision to migrate software configured for on-premise delivery to the cloud requires careful technical consideration and planning. In this chapter, we discuss the impact of right-scaling on the cost modelling for migration decision making and price setting of software for commercial resale. An integrated process is presented for measuring total cost of ownership, taking in to account IaaS/PaaS resource consumption based on forecast SaaS usage levels. The process is illustrated with a real world case study

Long term in-vivo studies of a photo-oxidized bovine osteochondral transplant in sheep

BACKGROUND: Articular cartilage has limited capacity to repair. Defects greater than 3 mm heal with formation of inferior fibrous cartilage. Therefore, many attempts have been made to find the ideal graft for larger cartilage lesions. Different grafts, such as untreated or cryopreserved osteochondral transplants, have been used with variable success. METHODS: Photo-oxidized osteochondral grafts were implanted in both femoral condyles of one ovine knee. Untreated xenogeneic and autogeneic grafts served as controls. Three groups of 8 sheep each were formed and they were sacrificed 6, 12 or 18 months after surgery. RESULTS: The macroscopic evaluation of the condyle and graft showed a well-maintained cartilage surface in most grafts at all time points. However, the host cartilage matrix deteriorated considerably in all xenogeneic, most autogeneic and fewer of the photo-oxidized grafts at 12 and 18 months, respectively. The blue colour of the photo-oxidized grafts resulting from the process of photo-oxidation was visible in all grafts at 6 months, had diminished at 12 months and had completely disappeared at 18 months after surgery. Histologically a loss of matrix staining was almost never noticed in untreated xenografts, transiently at 6 months in photo-oxidized grafts and increased at 12 and 18 months. Fusion between graft and host cartilage could be seen in photo-oxidized grafts at 12 and 18 months, but was never seen in autografts and xenografts. CONCLUSIONS: The photo-oxidation of osteochondral grafts and its use as transplant appears to have a beneficial effect on cartilage and bone remodelling. Osteochondral grafts pre-treated with photo-oxidation may be considered for articular cartilage replacement and therefore may delay artificial joint replacements in human patients