Cosmological N-body simulations with suppressed variance

We present and test a method that dramatically reduces variance arising from the sparse sampling of wavemodes in cosmological simulations. The method uses two simulations which are fixed (the initial Fourier mode amplitudes are fixed to the ensemble average power spectrum) and paired (with initial modes exactly out of phase). We measure the power spectrum, monopole and quadrupole redshift-space correlation functions, halo mass function and reduced bispectrum at $z=1$. By these measures, predictions from a fixed pair can be as precise on non-linear scales as an average over 50 traditional simulations. The fixing procedure introduces a non-Gaussian correction to the initial conditions; we give an analytic argument showing why the simulations are still able to predict the mean properties of the Gaussian ensemble. We anticipate that the method will drive down the computational time requirements for accurate large-scale explorations of galaxy bias and clustering statistics, enabling more precise comparisons with theoretical models, and facilitating the use of numerical simulations in cosmological data interpretation

Subhalo abundance matching and assembly bias in the EAGLE simulation

Subhalo abundance matching (SHAM) is a widely used method to connect galaxies with dark matter structures in numerical simulations. SHAM predictions agree remarkably well with observations, yet they still lack strong theoretical support. We examine the performance, implementation, and assumptions of SHAM using the ‘Evolution and Assembly of Galaxies and their Environment’ (EAGLE) project simulations. We find that Vrelax, the highest value of the circular velocity attained by a subhalo while it satisfies a relaxation criterion, is the subhalo property that correlates most strongly with galaxy stellar mass (Mstar). Using this parameter in SHAM, we retrieve the real-space clustering of EAGLE to within our statistical uncertainties on scales greater than 2 Mpc for galaxies with 8.77 < log 10(Mstar[M⊙]) < 10.77. Conversely, clustering is overestimated by 30 per cent on scales below 2 Mpc for galaxies with 8.77 < log 10(Mstar[M⊙]) < 9.77 because SHAM slightly overpredicts the fraction of satellites in massive haloes compared to EAGLE. The agreement is even better in redshift space, where the clustering is recovered to within our statistical uncertainties for all masses and separations. Additionally, we analyse the dependence of galaxy clustering on properties other than halo mass, i.e. the assembly bias. We demonstrate assembly bias alters the clustering in EAGLE by 20  per cent and Vrelax captures its effect to within 15  per cent. We trace small differences in the clustering to the failure of SHAM as typically implemented, i.e. the Mstar assigned to a subhalo does not depend on (i) its host halo mass, (ii) whether it is a central or a satellite. In EAGLE, we find that these assumptions are not completely satisfied

Mortality rate of patients with asymptomatic primary biliary cirrhosis diagnosed at age 55 years or older is similar to that of the general population

Recent routine testing for liver function and anti-mitochondrial antibodies has increased the number of newly diagnosed patients with primary biliary cirrhosis (PBC). This study investigated the prognosis of asymptomatic PBC patients, focusing on age difference, to clarify its effect on the prognosis of PBC patients. The study was a systematic cohort analysis of 308 consecutive patients diagnosed with asymptomatic PBC. We compared prognosis between the elderly (55 years or older at the time of diagnosis) and the young patients (< 55 years). The mortality rate of the patients was also compared with that of an age- and gender-matched general population. The elderly patients showed a higher aspartate aminotransferase-to-platelet ratio, and lower alanine aminotransferase level than the young patients (P < 0.01 and P = 0.03, respectively). The two groups showed similar values for alkaline phosphatase and immunoglobulin M. Death in the young patients was more likely to be due to liver failure (71%), while the elderly were likely to die from other causes before the occurrence of liver failure (88%; P < 0.01), especially from malignancies (35%). The mortality rate of the elderly patients was not different from that of the age- and gender-matched general population (standardized mortality ratio, 1.1; 95% confidence interval, 0.6-1.7), although this rate was significantly higher than that of the young patients (P = 0.044). PBC often presents as more advanced disease in elderly patients than in the young. However, the mortality rate of the elderly patients is not different from that of an age- and gender-matched general population

M3G: Maximum Margin Microarray Gridding

<p>Abstract</p> <p>Background</p> <p>Complementary DNA (cDNA) microarrays are a well established technology for studying gene expression. A microarray image is obtained by laser scanning a hybridized cDNA microarray, which consists of thousands of spots representing chains of cDNA sequences, arranged in a two-dimensional array. The separation of the spots into distinct cells is widely known as microarray image gridding.</p> <p>Methods</p> <p>In this paper we propose M³G, a novel method for automatic gridding of cDNA microarray images based on the maximization of the margin between the rows and the columns of the spots. Initially the microarray image rotation is estimated and then a pre-processing algorithm is applied for a rough spot detection. In order to diminish the effect of artefacts, only a subset of the detected spots is selected by matching the distribution of the spot sizes to the normal distribution. Then, a set of grid lines is placed on the image in order to separate each pair of consecutive rows and columns of the selected spots. The optimal positioning of the lines is determined by maximizing the margin between these rows and columns by using a maximum margin linear classifier, effectively facilitating the localization of the spots.</p> <p>Results</p> <p>The experimental evaluation was based on a reference set of microarray images containing more than two million spots in total. The results show that M³G outperforms state of the art methods, demonstrating robustness in the presence of noise and artefacts. More than 98% of the spots reside completely inside their respective grid cells, whereas the mean distance between the spot center and the grid cell center is 1.2 pixels.</p> <p>Conclusions</p> <p>The proposed method performs highly accurate gridding in the presence of noise and artefacts, while taking into account the input image rotation. Thus, it provides the potential of achieving perfect gridding for the vast majority of the spots.</p

Influence of Prototropic Reactions on the Absorption and Fluorescence Spectra of Methyl p-dimethylaminobenzoate and Its Two Ortho Derivatives

The influence of prototropic reactions on the spectral characteristics of methyl p-dimethylaminobenzoate (I) and its o-methoxy (II) and o-hydroxy (III) derivatives has been studied using steady-state spectroscopic technique and quantum-chemical calculations. This study concerns the solvent-induced shift of the absorption, locally excited (LE) and intramolecular charge transfer (ICT) fluorescence bands in the neat tetrahydrofuran (THF) and its hydrochloric acid solutions at different HCl concentrations. On the basis of the experimental results and quantum-chemical calculations, it was shown that in a hydrochloric acid solution the studied molecules exist as a mixture of neutral, mono-, and dicationic forms. Additionally, the results of spectroscopic measurements were used to calculate, according to the Benesi-Hildebrand method, the equilibrium constants of protopropic reactions in the ground, S0, and excited, S1, states. Our findings predestine molecules I and II to be used as acid fluorescence probes in a region of 0–2.5 M of [H+] concentrations

Shortfalls and Solutions for Meeting National and Global Conservation Area Targets

Governments have committed to conserving 17% of terrestrial and 10% of marine environments globally, especially “areas of particular importance for biodiversity” through “ecologically representative” Protected Area (PA) systems or other “area-based conservation measures”, while individual countries have committed to conserve 3–50% of their land area. We estimate that PAs currently cover 14.6% of terrestrial and 2.8% of marine extent, but 59–68% of ecoregions, 77–78% of important sites for biodiversity, and 57% of 25,380 species have inadequate coverage. The existing 19.7 million km2 terrestrial PA network needs only 3.3 million km2 to be added to achieve 17% terrestrial coverage. However, it would require nearly doubling to achieve, costefficiently, coverage targets for all countries, ecoregions, important sites, and species. Poorer countries have the largest relative shortfalls. Such extensive and rapid expansion of formal PAs is unlikely to be achievable. Greater focus is therefore needed on alternative approaches, including community- and privately managed sites and other effective area-based conservation measures.We are grateful to the many individuals and organizations who contribute to the IUCN Red List of Threatened Species,WDPA, or to identification of IBAs or AZEs. We thank A. Bennett for help with data collation and N. Dulvy, W. Laurance, and D. Faith for helpful comments on an earlier draft. This work was supported by the Cambridge Conservation Initiative Collaborative Fund and Arcadia.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/conl.1215

Lactate Dehydrogenase-B Is Silenced by Promoter Methylation in a High Frequency of Human Breast Cancers

Objective: Under normoxia, non-malignant cells rely on oxidative phosphorylation for their ATP production, whereas cancer cells rely on Glycolysis; a phenomenon known as the Warburg effect. We aimed to elucidate the mechanisms contributing to the Warburg effect in human breast cancer. Experimental design: Lactate Dehydrogenase (LDH) isoenzymes were profiled using zymography. LDH-B subunit expression was assessed by reverse transcription PCR in cells, and by Immunohistochemistry in breast tissues. LDH-B promoter methylation was assessed by sequencing bisulfite modified DNA. Results: Absent or decreased expression of LDH isoenzymes 1-4, were seen in T-47D and MCF7 cells. Absence of LDH-B mRNA was seen in T-47D cells, and its expression was restored following treatment with the demethylating agent 5'Azacytadine. LDH-B promoter methylation was identified in T-47D and MCF7 cells, and in 25/ 25 cases of breast cancer tissues, but not in 5/ 5 cases of normal breast tissues. Absent immuno-expression of LDH-B protein (<10% cells stained), was seen in 23/ 26 (88%) breast cancer cases, and in 4/8 cases of adjacent ductal carcinoma in situ lesions. Exposure of breast cancer cells to hypoxia (1% O2), for 48 hours resulted in significant increases in lactate levels in both MCF7 (14.0 fold, p = 0.002), and T-47D cells (2.9 fold, p = 0.009), but not in MDA-MB-436 (-0.9 fold, p = 0.229), or MCF10AT (1.2 fold, p = 0.09) cells. Conclusions: Loss of LDH-B expression is an early and frequent event in human breast cancer occurring due to promoter methylation, and is likely to contribute to an enhanced glycolysis of cancer cells under hypoxia

MRCP compared to diagnostic ERCP for diagnosis when biliary obstruction is suspected: a systematic review

BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is an alternative to diagnostic endoscopic retrograde cholangiopancreatography (ERCP) for investigating biliary obstruction. The use of MRCP, a non-invasive procedure, may prevent the use of unnecessary invasive procedures. The aim of the study was to compare the findings of MRCP with those of ERCP by the computation of accuracy statistics. METHODS: Thirteen electronic bibliographic databases, covering biomedical, science, health economics and grey literature were searched. A systematic review of studies comparing MRCP to diagnostic ERCP in patients with suspected biliary obstruction was conducted. Sensitivity, specificity, likelihood ratios, acceptability and adverse events were reported. RESULTS: 25 studies were identified reporting several conditions including choledocholithiasis (18 studies), malignancy (four studies), obstruction (three studies), stricture (two studies) and dilatation (five studies). Three of the 18 studies reporting choledocholithiasis were excluded from the analysis due to lack of data, or differences in study design. The sensitivity for the 15 studies of choledocholithiasis ranged from 0.50 to 1.00 while specificity ranged from 0.83 to 1.00. The positive likelihood ratio ranged: from 5.44–47.72 and the negative likelihood ratio for the 15 studies ranged from 0.00–0.51. Significant heterogeneity was found across the 15 studies so the sensitivities and specificities were summarised by a Receiver Operating Characteristic (ROC) curve. For malignancy, sensitivity ranged from 0.81 to 0.94 and specificity from 0.92 to 1.00. Positive likelihood ratios ranged from 10.12 to 43 and negative likelihood ratios ranged from 0.15 to 0.21, although these estimates were less reliable. CONCLUSION: MRCP is a comparable diagnostic investigation in comparison to ERCP for diagnosing biliary obstruction