ILLICON Analysis of Ellingsrud Test Fill

The 50-m diameter test fill at Ellingsrud, Norway was constructed by NGI to determine preconsolidation pressure of a soft clay, mobilized under field conditions. The height of the fill was increased in four increments during 1972 to 1978. Settlement observations as well as pore water pressure measurements over a period of eleven years are used to evaluate predictions made by the ILLICON computer program. ILLICON analysis requires vertical profiles of compressibility and permeability parameters. The computed surface settlements are within 2 cm of the measured values during the first three loading stages. After the fourth loading, there is a larger range in the measured settlements, however, the computed values lie within the measured range. The computed pore water pressures are also in reasonable agreement with the observations. However, compressibility and permeability data for major depth intervals of the 24m soil profile are not available. Therefore, in spite of good agreement between prediction and field observation one cannot be completely certain whether the input parameters in fact represent the true condition of the soil

A large-strain radial consolidation theory for soft clays improved by vertical drains

A system of vertical drains with combined vacuum and surcharge preloading is an effective solution for promoting radial flow, accelerating consolidation. However, when a mixture of soil and water is deposited at a low initial density, a significant amount of deformation or surface settlement occurs. Therefore, it is necessary to introduce large-strain theory, which has been widely used to manage dredged disposal sites in one-dimensional theory, into radial consolidation theory. A governing equation based on Gibson's large-strain theory and Barron's free-strain theory incorporating the radial and vertical flows, the weight of the soil, variable hydraulic conductivity and compressibility during the consolidation process is therefore presented

KSHV G-protein coupled receptor vGPCR oncogenic signaling upregulation of Cyclooxygenase-2 expression mediates angiogenesis and tumorigenesis in Kaposi's sarcoma

Kaposi's sarcoma-associated herpesvirus (KSHV) vGPCR is a constitutively active G protein-coupled receptor that subverts proliferative and inflammatory signaling pathways to induce cell transformation in Kaposi's sarcoma. Cyclooxygenase-2 (COX-2) is an inflammatory mediator that plays a key regulatory role in the activation of tumor angiogenesis. Hereby we demonstrate, using two different transformed mouse models, and tumorigenic full KSHV genome-bearing cells, including KSHV-Bac16 based mutant system with a vGPCR deletion, that vGPCR upregulates COX-2 expression and activity, signaling through selective MAPK cascades. We show that vGPCR expression triggers signaling pathways that upregulate COX-2 levels due to a dual effect upon both its gene promoter region and, in mature mRNA, the 3'UTR region that control mRNA stability. Both events are mediated by signaling through ERK1/2 MAPK pathway. Inhibition of COX-2 in vGPCR-transformed cells impairs vGPCRdriven angiogenesis and treatment with the COX-2-selective inhibitory drug Celecoxib produces a significant decrease in tumor growth, pointing to COX-2 activity as critical for vGPCR oncogenicity in vivo and indicating that COX-2-mediated angiogenesis could play a role in KS tumorigenesis. These results, along with the overexpression of COX-2 in KS lesions, define COX-2 as a potential target for the prevention and treatment of KSHV-oncogenesis.Fil: Medina, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: D´Agostino, Agata. University Of Miami Miller School Of Medicine; Estados UnidosFil: Ma, Qi. University Of Miami Miller School Of Medicine; Estados UnidosFil: Eroles, Pilar. University Of Miami Miller School Of Medicine; Estados UnidosFil: Cavallin, Lucas. University Of Miami Miller School Of Medicine; Estados UnidosFil: Chiozzini, Chiara. Miller School Of Medicine; Estados UnidosFil: Sapochnik, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Cymeryng, Cora Betriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Hyjek, Elizabeth. University of Chicago; Estados UnidosFil: Cesarman, Ethel. Cornell University; Estados UnidosFil: Naipauer, Julian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Mesri, Enrique Alfredo. University Of Miami Miller School Of Medicine; Estados UnidosFil: Coso, Omar Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

Contribution of peat compaction to relative sea-level rise within Holocene deltas

Modern and forecasted flooding of deltas is accelerated by subsidence of Holocene deposits. Subsidence caused by tectonics, isostasy, sediment compaction and anthropogenic processes, combined with eustatic sea-level rise, results in drowning and increased flood risk within densely populated deltas. Many deltaic sedimentary successions include substantial amounts of peat, which is highly compressible compared to clay, silt and sand. Peat compaction, therefore, may contribute considerably to total delta subsidence. Existing studies are inadequate for quantifying peat compaction across deltas. We present a numerical peat compaction model calibrated with an extensive field dataset. The model quantifies spatial and temporal trends in peat compaction within fluvial-dominated Holocene flood basin sequences of different compositions. Subsidence due to peat compaction is highly variable in time and space, with local rates of up to 15 mm/yr, depending on sedimentary sequence. This is extremely important information for developing sound delta management strategies. Artificial groundwater table lowering may cause substantial additional subsidence. Subsidence due to peat compaction might even exceed estimates of relative sea-level rise, and thus, may seriously increase the risk of delta drowning and human vulnerability to floodin

Proteome Profiling Outperforms Transcriptome Profiling for Coexpression Based Gene Function Prediction

Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality of their gene products despite well-known limitations of this “guilt-by-association” (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome profiling data can outperform transcriptome profiling data for coexpression based gene function prediction has not been systematically investigated. Here, we address this question by constructing and analyzing mRNA and protein coexpression networks for three cancer types with matched mRNA and protein profiling data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses revealed a marked difference in wiring between the mRNA and protein coexpression networks. Whereas protein coexpression was driven primarily by functional similarity between coexpressed genes, mRNA coexpression was driven by both cofunction and chromosomal colocalization of the genes. Functionally coherent mRNA modules were more likely to have their edges preserved in corresponding protein networks than functionally incoherent mRNA modules. Proteomic data strengthened the link between gene expression and function for at least 75% of Gene Ontology (GO) biological processes and 90% of KEGG pathways. A web application Gene2Net (http://cptac.gene2net.org) developed based on the three protein coexpression networks revealed novel gene-function relationships, such as linking ERBB2 (HER2) to lipid biosynthetic process in breast cancer, identifying PLG as a new gene involved in complement activation, and identifying AEBP1 as a new epithelial-mesenchymal transition (EMT) marker. Our results demonstrate that proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Proteomics should be integrated if not preferred in gene function and human disease studies

Tiotropium inhibits proinflammatory microparticle generation by human bronchial and endothelial cells

Tiotropium is a muscarinic antagonist that reduces the risk of acute exacerbations of chronic obstructive pulmonary disease, possibly through an as yet incompletely characterized anti-inflammatory activity. We hypothesized that muscarinic activation of bronchial epithelial cells and endothelial cells causes the release of proinflammatory microparticles and that tiotropium inhibits the phenomenon. Microparticle generation was assessed by a functional assay, by flow cytometry and by NanoSight technology. Immortalized bronchial epithelial cells (16HBE) and umbilical vein endothelial cells were treated with acetylcholine in the presence of varying concentrations of tiotropium. Intracellular calcium concentration, extracellular regulated kinase phosphorylation and chemokine content in the conditioned media were assessed by commercial kits. Acetylcholine causes microparticle generation that is completely inhibited by tiotropium (50 pM). Microparticles generated by acetylcholine-stimulated cells increase the synthesis of proinflammatory mediators in an autocrine fashion. Acetylcholine-induced upregulation of microparticle generation is inhibited by an inhibitor of extracellular regulated kinase phosphorylation and by a phospholipase C inhibitor. Tiotropium blocks both extracellular regulated kinase phosphorylation and calcium mobilization, consistent with the hypothesis that the drug prevents microparticle generation through inhibition of these critical pathways. These results might contribute to explain the effect of tiotropium in reducing acute exacerbations of chronic obstructive pulmonary disease

A comparative study of different model families for the constitutive simulation of viscous clays

The simulation of the viscous behavior of some clays is of high importance in many geotechnical problems. The literature offers a vast amount of constitutive models able to simulate the rate dependence observed on these materials. Although most of thesemodels are calibrated to very similar experimental observations and share similar definitions ofmaterial parameters, some discrepancies of their response have been detected, which are related to their mathematical formulations. In this work, the causes of these discrepancies are carefully studied. To that end, four different model families are analyzed, namely, nonstationary flow surface (NSFS) models, viscoplasticity with overstress function (OVP), viscoplasticity with Norton\u27s power law (NVP), and visco-hypoplasticity (VHP). For the sake of a fair comparison, single constitutive models using the same set of material parameters, and following other requirements, are developed for each model family. Numerical implementations of the four resulting models are performed. Their response at different tests are carefully analyzed through simulation examples and direct examination of their constitutive equations. The set includes some basic tests at isotropic stress states and others as responses envelopes, undrained creep rupture, and an oedometer test with loading, unloading-reloading, creep, and relaxation. The article is concluded with some remarks about the observed discrepancies of these model families

Coadministration of Adenoviral Vascular Endothelial Growth Factor and Angiopoietin-1 Enhances Vascularization and Reduces Ventricular Remodeling in the Infarcted Myocardium of Type 1 Diabetic Rats

OBJECTIVE - Hyperglycemia impairs angiogenesis in response to ischemia, leading to ventricular remodeling. Although the effects of overexpressing angiogenic growth factors have been studied in inducing angiogenesis, the formation of functional vessels remains a challenge. The present study evaluates the reversal of diabetes-mediated impairment of angiogenesis in the infarcted diabetic rat myocardium by proangiogenic gene therapy. RESEARCH DESIGN AND METHODS - Ad.VEGF and Ad.Ang1 were intramyocardially administered in combination immediately after myocardial infarction to nondiabetic and diabetic rats. Ad.LacZ was similarly administered to the respective control groups. The hearts were excised for molecular and immunohistochemical analysis at predetermined time points. The myocardial function was measured by echocardiography 30 days after the intervention. RESULTS - We observed reduced fibrosis and increased capillary/arteriolar density along with reduced ventricular remodeling, as assessed by echocardiography in the treated diabetic animals compared with the nontreated diabetic controls. We also observed increased phosphorylated mitogen-activated protein kinase-activated protein kinase-2, 2 days after the treatment and increased expression of vascular endothelial growth factor (VEGF), Flk-1, angiopoietin-1 (Ang-1), Tie-2, and survivin, 4 days after treatment in the diabetic animals. Gel shift analysis revealed that the combination gene therapy stimulated the DNA binding activity of nuclear factor-κB in the diabetic animals. CONCLUSIONS - Our preclinical data demonstrate the efficacy of coadministration of adenoviral VEGF and Ang-1 in increasing angiogenesis and reducing ventricular remodeling in the infarcted diabetic myocardium. These unique results call for the initiation of a clinical trial to assess the efficacy of this therapeutic strategy in the treatment of diabetes-related human heart failure