Estimating Strength from Stiffness for Chemically Treated Soils

The central theme of this study is to identify strength-stiffness correlations for chemically treated subgrade soils in Indiana. This was done by conducting Unconfined Compression (UC) Tests and Resilient Modulus Tests for soils collected at three different sites—US-31, SR-37, and I-65. At each site, soil samples were obtained from 11 locations at 30 ft spacing. The soils were treated in the laboratory with cement, using the same proportions used for construction, and cured for 7 and 28 days before testing. Results from the UC tests were compared with the resilient modulus results that were available. No direct correlation was found between resilient modulus and UCS parameters for the soils investigated in this study. A brief statistical analysis of the results was conducted, and a simple linear regression model involving the soil characteristics (plasticity index, optimum moisture content and maximum dry density) along with UCS and resilient modulus parameters was proposed

Visualizing Structures in Confocal Microscopy Datasets Through Clusterization: A Case Study on Bile Ducts

Aiming at a better result from previous works, we employed some heuristics found in the literature to determine the appropriate parameters for the clustering. We proposed our methodology by adding some steps to be performed before the clustering phase: one step for pre-processing the volumetric dataset and another to analyzing candidate features to guide the clustering. In this latter aspect, we provide an interesting contribution: we have explored the gradient magnitude as a feature that allowed to extract relevant information from the density-based spatial clustering. Besides the fact that DBSCAN allows easy detection of noise points, an interesting result for both datasets was that the first and largest cluster found as significant for the visualization represents the structure of interest. In the red channel, this cluster represents the most prominent vessels, while in the green channel, the peribiliary glands were made more evident.Abstract—Three-dimensional datasets from biological tissues have increased with the evolution of confocal microscopy. Hepatology researchers have used confocal microscopy for investigating the microanatomy of bile ducts. Bile ducts are complex tubular tissues consisting of many juxtaposed microstructures with distinct characteristics. Since confocal images are difficult to segment because of the noise introduced during the specimen preparation, traditional quantitative analyses used in medical datasets are difficult to perform on confocal microscopy data and require extensive user intervention. Thus, the visual exploration and analysis of bile ducts pose a challenge in hepatology research, requiring different methods. This paper investigates the application of unsupervised machine learning to extract relevant structures from confocal microscopy datasets representing bile ducts. Our approach consists of pre-processing, clustering, and 3D visualization. For clustering, we explore the density-based spatial clustering for applications with noise (DBSCAN) algorithm, using gradient information for guiding the clustering. We obtained a better visualization of the most prominent vessels and internal structures.info:eu-repo/semantics/publishedVersio

Estimating Strength From Stiffness for Chemically Treated Soils

SPR-4420The central theme of this study is to identify strength-stiffness correlations for chemically treated subgrade soils in Indiana. This was done by conducting Unconfined Compression (UC) Tests and Resilient Modulus Tests for soils collected at three different sites\u2014US-31, SR-37, and I-65. At each site, soil samples were obtained from 11 locations at 30 ft spacing. The soils were treated in the laboratory with cement, using the same proportions used for construction, and cured for 7 and 28 days before testing. Results from the UC tests were compared with the resilient modulus results that were available. No direct correlation was found between resilient modulus and UCS parameters for the soils investigated in this study. A brief statistical analysis of the results was conducted, and a simple linear regression model involving the soil characteristics (plasticity index, optimum moisture content and maximum dry density) along with UCS and resilient modulus parameters was proposed

Staging of biliary atresia at diagnosis by molecular profiling of the liver

Abstract Background Young age at portoenterostomy has been linked to improved outcome in biliary atresia, but pre-existing biological factors may influence the rate of disease progression. In this study, we aimed to determine whether molecular profiling of the liver identifies stages of disease at diagnosis. Methods We examined liver biopsies from 47 infants with biliary atresia enrolled in a prospective observational study. Biopsies were scored for inflammation and fibrosis, used for gene expression profiles, and tested for association with indicators of disease severity, response to surgery, and survival at 2 years. Results Fourteen of 47 livers displayed predominant histological features of inflammation (N = 9) or fibrosis (N = 5), with the remainder showing similar levels of both simultaneously. By differential profiling of gene expression, the 14 livers had a unique molecular signature containing 150 gene probes. Applying prediction analysis models, the probes classified 29 of the remaining 33 livers into inflammation or fibrosis. Molecular classification into the two groups was validated by the findings of increased hepatic population of lymphocyte subsets or tissue accumulation of matrix substrates. The groups had no association with traditional markers of liver injury or function, response to surgery, or complications of cirrhosis. However, infants with an inflammation signature were younger, while those with a fibrosis signature had decreased transplant-free survival. Conclusions Molecular profiling at diagnosis of biliary atresia uncovers a signature of inflammation or fibrosis in most livers. This signature may relate to staging of disease at diagnosis and has implications to clinical outcomes.http://deepblue.lib.umich.edu/bitstream/2027.42/112492/1/13073_2010_Article_154.pd

HIF-1alpha-pathway activation in cholangiocytes of patients with biliary atresia : an immunohistochemical/molecular exploratory study

Background: Biliary atresia is a neonatal disease characterized by choledochal obstruction and progressive cholangiopathy requiring liver transplantation in most patients. Hypoxia-ischemia affecting the biliary epithelium may lead to biliary obstruction. We hypothesized that ischemic cholangiopathy involving disruption of the peribiliary vascular plexus could act as a triggering event in biliary atresia pathogenesis. Methods: Liver and porta hepatis paraffin-embedded samples of patients with biliary atresia or intrahepatic neonatal cholestasis (controls) were immunohistochemically evaluated for HIF-1alpha-nuclear signals. Frozen histological samples were analyzed for gene expression in molecular profiles associated with hypoxia-ischemia. Prospective clinical-laboratory and histopathological data of biliary atresia patients and controls were reviewed. Results: Immunohistochemical HIF-1alpha signals localized to cholangiocytes were detected exclusively in liver specimens from biliary atresia patients. In 37.5% of liver specimens, HIF-1alpha signals were observed in biliary structures involving progenitor cell niches and peribiliary vascular plexus. HIF-1alpha signals were also detected in biliary remnants of 81.8% of porta hepatis specimens. Increased gene expression of molecules linked to REDOX status, biliary proliferation, and angiogenesis was identified in biliary atresia liver specimens. In addition, there was a trend towards decreased GSR expression levels in the HIF-1alpha-positive group compared to the HIF-1alpha-negative group. Conclusion: Activation of the HIF-1alpha pathway may be associated with the pathogenesis of biliary atresia, and additional studies are necessary to confirm the significance of this finding. Ischemic cholangiopathy and REDOX status disturbance are putative explanations for HIF-1alpha activation. These findings may give rise to novel lines of clinical and therapeutic investigation in the BA field

Loss of interleukin-12 modifies the pro-inflammatory response but does not prevent duct obstruction in experimental biliary atresia

BACKGROUND: Livers of infants with biliary atresia and of neonatal mice infected with rotavirus (RRV) have increased expression of interferon-gamma (IFNγ) and interleukin (IL)-12. While the expression of IFNγ regulates the obstruction of extrahepatic bile ducts by lymphocytes, the role of IL-12 in the pathogenesis of biliary obstruction is unknown. Based on the role of IL-12 as a key proinflammatory cytokine, we hypothesized that loss of IL-12 prevents the obstruction of extrahepatic bile ducts. METHODS: IL12-knockout (IL-12KO) and wild type mice were injected with RRV or saline at day 1 of age and monitored for the development of symptoms. The cellular and molecular phenotypes were determined at days 3, 7, and 14 by real-time PCR and flow cytometry. RESULTS: RRV infection of IL-12KO mice resulted in growth failure, jaundice/acholic stools, and decreased survival similar to wild-type mice. IL-12KO mice had a remarkable neutrophil-rich portal inflammation and epithelial sloughing of extrahepatic bile ducts. Loss of IL-12 decreased but did not abolish the hepatic expression of IFNγ, displayed a remarkable increase in expression of TNFα, IFNα, IFNβ and decreased expression of IL-4 and IL-5. CONCLUSION: Loss of IL-12 did not modify the progression of bile duct obstruction in experimental biliary atresia. However, the inflammatory response was predominantly neutrophil-based and displayed a Th1 response in the absence of IL-12

Strength-Stiffness Correlations for Chemically Treated Soils

The central theme of the study is to identify strength-stiffness correlations for chemically treated subgrade soils in Indiana. This was done by conducting Unconfined Compression (UC) tests and resilient modulus tests for soils collected at three different sites, namely : US 31, SR 37 and I-65. At each site, soil samples were obtained from 11 locations at 30 ft spacing. The soils were treated in the laboratory with cement, using the same proportions used for construction, and cured for 7 and 28 days before testing. Results from the UC tests were compared with the resilient modulus results that were available. No direct correlation was found between resilient modulus and UCS parameters for the soils investigated in this study. A brief statistical analysis of the results was conducted, and a simple linear regression model involving the soil characteristics (plasticity index, optimum moisture content and maximum dry density) along with UCS and resilient modulus parameters was proposed

Gene expression signature for biliary atresia and a role for interleukin‐8 in pathogenesis of experimental disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107580/1/hep27045.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/107580/2/hep27045-sup-0001-suppinfo01.pd

Neonatal NK cells target the mouse duct epithelium via Nkg2d and drive tissue-specific injury in experimental biliary atresia

Biliary atresia is a neonatal obstructive cholangiopathy that progresses to end-stage liver disease. Although the etiology is unknown, a neonatal adaptive immune signature has been mechanistically linked to obstruction of the extrahepatic bile ducts. Here, we investigated the role of the innate immune response in the pathogenesis of biliary atresia. Analysis of livers of infants at diagnosis revealed that NK cells populate the vicinity of intrahepatic bile ducts and overexpress several genes involved in cytotoxicity. Using a model of rotavirus-induced biliary atresia in newborn mice, we found that activated NK cells also populated murine livers and were the most abundant cells in extrahepatic bile ducts at the time of obstruction. Rotavirus-primed hepatic NK cells lysed cholangiocytes in a contact- and Nkg2d-dependent fashion. Depletion of NK cells and blockade of Nkg2d each prevented injury of the duct epithelium after rotavirus infection, maintained continuity of duct lumen between the liver and duodenum, and enabled bile flow, despite the presence of virus in the tissue and the overexpression of proinflammatory cytokines. These findings identify NK cells as key initiators of cholangiocyte injury via Nkg2d and demonstrate that injury to the duct epithelium drives the phenotype of experimental biliary atresia