MEASUREMENT OF THE SHORTEST PATH LENGTH; DISTANCE ESTIMATION WITHIN THE 3D BORDERS OF A TISSUE OF INTEREST

Volume data, such as 3D reconstructions from histological sections orMRI and CT data, are commonly used in studies in biology and medicine. The quantification of morphological parameters and changes within a region of interest is a key concern in such studies. Specifically, it is often required to measure the distance between two points. These distance measurements have to follow a track through the tissue when measuring in sheetlike or contorted organs like the developing heart. A tool was developed that enables this kind of distance measurements. Three existing neighborhood estimators were compared; two of Verwer and one of Kiryati, all originally designed to compute chamfer distances in data sets with isotropic, cubic voxels. The estimators were therefore adjusted to handle non-isotropic data sets. Moreover, the shortest path along a track within a given tissue was calculated. The measurement of known distances, through a simplified model of an early heart tube, with anisotropic voxels was used decide which of the three estimators should be implemented. The observed Root Mean Square (RMS) errors were similar to the ones reported in literature in the unrestrained isotropic case. The adjusted Verwer estimator measuring in a 53 neighborhood performed best by far with the lowest mean and RMS errors

Особливості синтаксичної організації художньої прози Редьярда Кіплінга

Статья посвящена исследованию синтаксических конструкций, с помощью которых в художественной прозе Редьярда Киплинга отображаются особенности английской и индийской культур.Стаття присвячена дослідженню синтаксичних конструкцій, за допомогою яких у художній прозі Редьярда Кіплінга відображено особливості англійської та індійської культур.The article is dedicated to the investigation of the main syntactic constractions with the help of which in the prose of Rudyard Kipling there are depicted the peculiarities of English and Indian cultures

Proton Pump Inhibitor Use, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients:Results From the TransplantLines Biobank and Cohort Study

Rationale &amp; Objective: Prior studies report that the use of proton pump inhibitors (PPIs) can adversely affect gut microbiota and gastrointestinal uptake of micronutrients, in particular iron and magnesium, and are used frequently by kidney transplant recipients. Altered gut microbiota, iron deficiency, and magnesium deficiency have been implicated in the pathogenesis of chronic fatigue. Therefore, we hypothesized that PPI use may be an important and underappreciated cause of fatigue and reduced health-related quality of life (HRQoL) in this population. Study Design: Cross-sectional study. Setting &amp; Participants: Kidney transplant recipients (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study. Exposure: PPI use, PPI type, PPI dosage, and duration of PPI use. Outcome: Fatigue and HRQoL, assessed using the validated Checklist Individual Strength 20 Revised questionnaire and Short Form-36 questionnaire. Analytical Approach: Logistic and linear regression. Results: We included 937 kidney transplant recipients (mean age 56 ± 13 years, 39% female) at a median of 3 (1-10) years after transplantation. PPI use was associated with fatigue severity (regression coefficient 4.02, 95% CI, 2.18 to 5.85, P &lt; 0.001), a higher risk of severe fatigue (OR 2.05, 95% CI, 1.48 to 2.84, P &lt; 0.001), lower physical HRQoL (regression coefficient −8.54, 95% CI, −11.54 to −5.54, P &lt; 0.001), and lower mental HRQoL (regression coefficient −4.66, 95% CI, −7.15 to −2.17, P &lt; 0.001). These associations were independent of potential confounders including age, time since transplantation, history of upper gastrointestinal disease, antiplatelet therapy, and the total number of medications. They were present among all individually assessed PPI types and were dose dependent. Duration of PPI exposure was only associated with fatigue severity. Limitations: Residual confounding and inability to assess causal relationships. Conclusions: PPI use is independently associated with fatigue and lower HRQoL among kidney transplant recipients. PPI use might be an easily accessible target for alleviating fatigue and improving HRQoL among kidney transplant recipients. Further studies examining the effect of PPI exposure in this population are warranted. Plain-Language Summary: In this observational study, we investigated the association of proton pump inhibitors with fatigue and health-related quality of life among kidney transplant recipients. Our data showed that proton pump inhibitors were independently associated with fatigue severity, severe fatigue, and lower physical and mental health-related quality of life. These associations were present among all individually assessed proton pump inhibitor types and were dose dependent. While we await future studies on this topic, proton pump inhibitor use might be an easily accessible target for alleviating fatigue and improving health-related quality of life among kidney transplant recipients.</p

Growth of the developing mouse heart: An interactive qualitative and quantitative 3D atlas

Analysis of experiments aimed at understanding the genetic mechanisms of differentiation and growth of the heart, calls for detailed insights into cardiac growth and proliferation rate of myocytes and their precursors. Such insights in mouse heart development are currently lacking. We quantitatively assessed the 3D patterns of proliferation in the forming mouse heart and in the adjacent splanchnic mesoderm, from the onset of heart formation till the developed heart at late gestation. These results are presented in an interactive portable document format (Suppl. PDF) to facilitate communication and understanding. We show that the mouse splanchnic mesoderm is highly proliferative, and that the proliferation rate drops upon recruitment of cells into the cardiac lineage. Concomitantly, the proliferation rate locally increases at the sites of chamber formation, generating a regionalized proliferation pattern. Quantitative analysis shows a gradual decrease in proliferation rate of the ventricular walls with progression of development, and a base-to-top decline in proliferation rate in the trabecules. Our data offers clear insights into the growth and morphogenesis of the mouse heart and shows that in early development the phases of tube formation and chamber formation overlap. The resulting interactive quantitative 3D atlas of cardiac growth and morphogenesis provides a resource for interpretation of mechanistic studies. (C) 2012 Elsevier Inc. All rights reserve

EMERGE: a flexible modelling framework to predict genomic regulatory elements from genomic signatures

Regulatory DNA elements, short genomic segments that regulate gene expression, have been implicated in developmental disorders and human disease. Despite this clinical urgency, only a small fraction of the regulatory DNA repertoire has been confirmed through reporter gene assays. The overall success rate of functional validation of candidate regulatory elements is low. Moreover, the number and diversity of datasets from which putative regulatory elements can be identified is large and rapidly increasing. We generated a flexible and user-friendly tool to integrate the information from different types of genomic datasets, e.g. ATAC-seq, ChIP-seq, conservation, aiming to increase the ease and success rate of functional prediction. To this end, we developed the EMERGE program that merges all datasets that the user considers informative and uses a logistic regression framework, based on validated functional elements, to set optimal weights to these datasets. ROC curve analysis shows that a combination of datasets leads to improved prediction of tissue-specific enhancers in human, mouse and Drosophila genomes. Functional assays based on this prediction can be expected to have substantially higher success rates. The resulting integrated signal for prediction of functional elements can be plotted in a build-in genome browser or exported for further analysi

Image cytometry: protocols for 2D and 3D quantification in microscopic images

Microscopy-based imaging is booming and the need for tools to retrieve quantitative data from images is urgent. This book provides simple but reliable tools to generate valid quantitative gene expression data, at the mRNA, protein and activity level, from microscopic images in relation to structures in cells, tissues and organs in 2D and 3D. Volumes, areas, lengths and numbers of cells and tissues can be calculated and related to these gene expression data while preserving the 2D and 3D morphology. Image cytometry thus provides a comprehensive toolkit to study molecular processes and structural changes at the level of cells and tissue