Pycortex: an interactive surface visualizer for fMRI.

Surface visualizations of fMRI provide a comprehensive view of cortical activity. However, surface visualizations are difficult to generate and most common visualization techniques rely on unnecessary interpolation which limits the fidelity of the resulting maps. Furthermore, it is difficult to understand the relationship between flattened cortical surfaces and the underlying 3D anatomy using tools available currently. To address these problems we have developed pycortex, a Python toolbox for interactive surface mapping and visualization. Pycortex exploits the power of modern graphics cards to sample volumetric data on a per-pixel basis, allowing dense and accurate mapping of the voxel grid across the surface. Anatomical and functional information can be projected onto the cortical surface. The surface can be inflated and flattened interactively, aiding interpretation of the correspondence between the anatomical surface and the flattened cortical sheet. The output of pycortex can be viewed using WebGL, a technology compatible with modern web browsers. This allows complex fMRI surface maps to be distributed broadly online without requiring installation of complex software

A universal reference sample derived from clone vector for improved detection of differential gene expression

BACKGROUND: Using microarrays by co-hybridizing two samples labeled with different dyes enables differential gene expression measurements and comparisons across slides while controlling for within-slide variability. Typically one dye produces weaker signal intensities than the other often causing signals to be undetectable. In addition, undetectable spots represent a large problem for two-color microarray designs and most arrays contain at least 40% undetectable spots even when labeled with reference samples such as Stratagene's Universal Reference RNAs™. RESULTS: We introduce a novel universal reference sample that produces strong signal for all spots on the array, increasing the average fraction of detectable spots to 97%. Maximizing detectable spots on the reference image channel also decreases the variability of microarray data allowing for reliable detection of smaller differential gene expression changes. The reference sample is derived from sequence contained in the parental EST clone vector pT7T3D-Pac and is called vector RNA (vRNA). We show that vRNA can also be used for quality control of microarray printing and PCR product quality, detection of hybridization anomalies, and simplification of spot finding and segmentation tasks. This reference sample can be made inexpensively in large quantities as a renewable resource that is consistent across experiments. CONCLUSION: Results of this study show that vRNA provides a useful universal reference that yields high signal for almost all spots on a microarray, reduces variation and allows for comparisons between experiments and laboratories. Further, it can be used for quality control of microarray printing and PCR product quality, detection of hybridization anomalies, and simplification of spot finding and segmentation tasks. This type of reference allows for detection of small changes in differential expression while reference designs in general allow for large-scale multivariate experimental designs. vRNA in combination with reference designs enable systems biology microarray experiments of small physiologically relevant changes

Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction.

BackgroundThe extracellular matrix plays an important role in tissue regeneration. We investigated whether extracellular matrix protein fragments could be targeted with antibodies to ischemically injured myocardium to promote angiogenesis and myocardial repair.Methodology/principal findingsFour peptides, 2 derived from fibronectin and 2 derived from Type IV Collagen, were assessed for in vitro and in vivo tendencies for angiogenesis. Three of the four peptides--Hep I, Hep III, RGD--were identified and shown to increase endothelial cell attachment, proliferation, migration and cell activation in vitro. By chemically conjugating these peptides to an anti-myosin heavy chain antibody, the peptides could be administered intravenously and specifically targeted to the site of the myocardial infarction. When administered into Sprague-Dawley rats that underwent ischemia-reperfusion myocardial infarction, these peptides produced statistically significantly higher levels of angiogenesis and arteriogenesis 6 weeks post treatment.Conclusions/significanceWe demonstrated that antibody-targeted ECM-derived peptides alone can be used to sufficiently alter the extracellular matrix microenvironment to induce a dramatic angiogenic response in the myocardial infarct area. Our results indicate a potentially new non-invasive strategy for repairing damaged tissue, as well as a novel tool for investigating in vivo cell biology

Microvessel Density and Clinicopathologic Characteristics in Hepatocellular Carcinoma With and Without Cirrhosis

Angiogenesis is essential to the survival, growth, invasion, and metastasis of various human solid tumors. We compared the microvessel density (MVD) and clinicopathologic features of two different groups of hepatocellular carcinoma (HCC), namely HCC with cirrhosis (HCC-C) and without cirrhosis (HCC-NC). A tissue microarray composed of 20 normal livers, 20 cirrhotic livers, tumor and adjacent background non-neoplastic liver tissues from 20 HCC-C and 20 HCC-NC were constructed and stained immunohistochemically with antibodies against the antigen CD34. The MVD was determined by the measurement of the area and density of CD34 positive sinusoidal endothelial cells using the Image Pro Plus software. There was a trend of increased MVD in cirrhotic liver compared to normal liver and in cirrhotic background non-neoplastic liver adjacent to the tumor compared to the non-cirrhotic background non-neoplastic liver. Tumor tissue of HCC-C and HCC-NC both showed significantly higher MVD than their adjacent background non-neoplastic liver tissue. There was no statistical difference in MVD between HCC-C and HCC-NC. A higher value of MVD was seen in tumors of intermediate size (5–10 cm), high histologic grade, the presence of lymphvascular space invasion, and the underlying etiology of hepatitis C and alcoholic steatohepatitis. This data indicates that MVD may play an important role in liver carcinogenesis and neoplastic progression. The difference in clinical behavior between HCC-C and HCC-NC does not seem to be associated with differences in tumor MVD. Objective measurement of MVD using standardized computer software could potentially be used as a clinical marker to predict patients’ prognosis

Assessing the effect of reducing agents on the selective catalytic reduction of NO<inf>x</inf> over Ag/Al<inf>2</inf>O<inf>3</inf> catalysts

The selective catalytic reduction (SCR) of NOx in the presence of different reducing agents over Ag/Al2O3 prepared by wet impregnation was investigated by probing catalyst activity and using NMR relaxation time analysis.We gratefully acknowledge funding for this work from the EPSRC CASTech grant (EP/G012156/1). Carmine D’Agostino would like to acknowledge Wolfson College, Cambridge, for supporting his research activities. The authors would also like to thank Dr Jonathan Mitchell for useful discussions.This is the final version of the article. It first appeared from RSC via http://dx.doi.org/10.1039/C5CY01508

Accelerated coronary vascular disease in the heart transplant patient: Coronary arteriographic findings

AbstractAnnual coronary arteriograms have been obtained from all heart transplant recipients at Stanford University Medical Center since 1969. Angiographic lesions in 81 transplant patients exhibiting coronary vascular disease were classified into three categories: type A, discrete or tubular stenoses; type B, diffuse concentric narrowing; and type C, narrowed irregular vessels with occluded branches. The 81 arteriograms showing transplant coronary vascular disease were contrasted with 32 from nontransplant patients with coronary artery disease analyzed in a similar fashion.The nontransplant angiograms showed 178 lesions, all of type A (discrete or tubular) morphology, 75% of which were located in primary epicardial coronary vessels and 25% in secondary branch vessels. In the patients with transplant coronary vascular disease, 349 (76%) of 461 lesions were type A: 57% in primary vessels, 42% in secondary branches and 1.4% in tertiary branches. Of the 112 type B and C lesions (diffuse narrowing, tapering and obliteration), 25% were in primary vessels, 44% in secondary vessels and 31% in tertiary branches (p < 0.05 for patients with transplant coronary vascular disease versus patients with nontransplant coronary artery disease). Total vessel occlusion was found in proximal or middle vessel segments in 96% and distally in 4% of patients with “ordinary” coronary artery disease versus 49% distally in patients with transplant coronary disease (p < 0.002). In the presence of total vessel occlusion, collateral vessels were poor or absent in 92% of transplant versus 7% of nontransplant patients with coronary disease (p < 0.002).Therefore, coronary artery disease in transplant patients represents a mixture of typical atheromatous lesions and unique transplant-related progressive distal obliterative disease that occurs without collateral vessel development

The MBD7 complex promotes expression of methylated transgenes without significantly altering their methylation status.

DNA methylation is associated with gene silencing in eukaryotic organisms. Although pathways controlling the establishment, maintenance and removal of DNA methylation are known, relatively little is understood about how DNA methylation influences gene expression. Here we identified a METHYL-CpG-BINDING DOMAIN 7 (MBD7) complex in Arabidopsis thaliana that suppresses the transcriptional silencing of two LUCIFERASE (LUC) reporters via a mechanism that is largely downstream of DNA methylation. Although mutations in components of the MBD7 complex resulted in modest increases in DNA methylation concomitant with decreased LUC expression, we found that these hyper-methylation and gene expression phenotypes can be genetically uncoupled. This finding, along with genome-wide profiling experiments showing minimal changes in DNA methylation upon disruption of the MBD7 complex, places the MBD7 complex amongst a small number of factors acting downstream of DNA methylation. This complex, however, is unique as it functions to suppress, rather than enforce, DNA methylation-mediated gene silencing

The SCottish Alcoholic Liver disease Evaluation: a population-level matched cohort study of hospital-based costs, 1991-2011

Studies assessing the costs of alcoholic liver disease are lacking. We aimed to calculate the costs of hospitalisations before and after diagnosis compared to population controls matched by age, sex and socio-economic deprivation. We aimed to use population level data to identify a cohort of individuals hospitalised for the first time with alcoholic liver disease in Scotland between 1991 and 2011.Incident cases were classified by disease severity, sex, age group, socio-economic deprivation and year of index admission. 5 matched controls for every incident case were identified from the Scottish population level primary care database. Hospital costs were calculated for both cases and controls using length of stay from morbidity records and hospital-specific daily rates by specialty. Remaining lifetime costs were estimated using parametric survival models and predicted annual costs. 35,208 incident alcoholic liver disease hospitalisations were identified. Mean annual hospital costs for cases were 2.3 times that of controls pre diagnosis (£804 higher) and 10.2 times (£12,774 higher) post diagnosis. Mean incident admission cost was £6,663. Remaining lifetime cost for a male, 50-59 years old, living in the most deprived area diagnosed with acoholic liver disease was estimated to be £65,999 higher than the matched controls (£12,474 for 7.43 years remaining life compared to £1,224 for 21.8 years). In Scotland, alcoholic liver disease diagnosis is associated with significant increases in admissions to hospital both before and after diagnosis. Our results provide robust population level estimates of costs of alcoholic liver disease for the purposes of health-care delivery, planning and future cost-effectiveness analyses