Physical Models of Atmospheric Boundary Layer Flows: Some Developments and Recent Applications

Experimental studies on wind engineering require the use of different types of physical models of boundary layer flows. Small-scale models obtained in a wind tunnel, for example, attempt to reproduce real atmosphere phenomena like wind loads on structures and pollutant dispersion by the mean flow and turbulent mixing. The quality of the scale model depends on the similarity between the laboratory-generated flow and the atmospheric flow. Different types of neutral atmospheric boundary layer (ABL) including full-depth and part-depth simulations are experimentally evaluated. The Prof. Jacek Gorecki wind tunnel of the UNNE, Argentina, and the Prof. Joaquim Blessmann closed-return wind tunnel of the UFRGS, Brazil, were used to obtain the experimental data. Finally, some recent wind engineering applications of this type of physical wind models are shown

Modelagem Numérica do Vento Atmosférico pelo Método de Decomposição Espectral

Modelagem numérica do vento atmosférico pelo métodode decomposição espectra

Wind Tunnel Experiments on Turbulent Boundary Layer Flows

The knowledge and experimental development of boundary layer turbulent flows is extremely important in applications related to the building aerodynamics, wind comfort, atmospheric dispersion, and even aeronautics. The Aerodynamic Laboratories of the UFRGS and UNNE have been making joint activities related to wind engineering such as those mentioned earlier for more than 25 years. In this work, a compilation of different experiments on turbulent boundary layer flows realized in these both laboratories is carried out. The characteristics of flows that develop on a smooth surface of the wind tunnel are experimentally evaluated. Then, reduced-scale models of atmospheric boundary layer flows are analyzed including the effects of turbulence generators and surface roughness. Special attention on the behavior of the turbulent parameters in the case of experimental studies using low mean velocity is paid. Finally, some comments referring to recent studies on thermal effects in turbulent boundary layer flows and the development of reduced-scale models of convective flows are included

A RAB5/RAB4 recycling circuitry induces a proteolytic invasive program and promotes tumor dissemination

The mechanisms by which tumor cells metastasize and the role of endocytic proteins in this process are not well understood. We report that overexpression of the GTPase RAB5A, a master regulator of endocytosis, is predictive of aggressive behavior and metastatic ability in human breast cancers. RAB5A is necessary and sufficient to promote local invasion and distant dissemination of various mammary and nonmammary tumor cell lines, and this prometastatic behavior is associated with increased intratumoral cell motility. Specifically, RAB5A is necessary for the formation of invadosomes, membrane protrusions specialized in extracellular matrix (ECM) degradation. RAB5A promotes RAB4- and RABENOSYN-5-dependent endo/exocytic cycles (EECs) of critical cargos (membrane-type 1 matrix metalloprotease [MT1-MMP] and \u3b23 integrin) required for invadosome formation in response to motogenic stimuli. This trafficking circuitry is necessary for spatially localized hepatocyte growth factor (HGF)/MET signaling that drives invasive, proteolysis-dependent chemotaxis in vitro and for conversion of ductal carcinoma in situ to invasive ductal carcinoma in vivo. Thus, RAB5A/RAB4 EECs promote tumor dissemination by controlling a proteolytic, mesenchymal invasive program

Evidence of Distinct Tumour-Propagating Cell Populations with Different Properties in Primary Human Hepatocellular Carcinoma

Increasing evidence that a number of malignancies are characterised by tumour cell heterogeneity has recently been published, but there is still a lack of data concerning liver cancers. The aim of this study was to investigate and characterise tumour-propagating cell (TPC) compartments within human hepatocellular carcinoma (HCC).After long-term culture, we identified three morphologically different tumour cell populations in a single HCC specimen, and extensively characterised them by means of flow cytometry, fluorescence microscopy, karyotyping and microarray analyses, single cell cloning, and xenotransplantation in NOD/SCID/IL2Rγ/⁻ mice.The primary cell populations (hcc-1, -2 and -3) and two clones generated by means of limiting dilutions from hcc-1 (clone-1/7 and -1/8) differently expressed a number of tumour-associated stem cell markers, including EpCAM, CD49f, CD44, CD133, CD56, Thy-1, ALDH and CK19, and also showed different doubling times, drug resistance and tumorigenic potential. Moreover, we found that ALDH expression, in combination with CD44 or Thy-1 negativity or CD56 positivity identified subpopulations with a higher clonogenic potential within hcc-1, hcc-2 and hcc-3 primary cell populations, respectively. Karyotyping revealed the clonal evolution of the cell populations and clones within the primary tumour. Importantly, the primary tumour cell population with the greatest tumorigenic potential and drug resistance showed more chromosomal alterations than the others and contained clones with epithelial and mesenchymal features.Individual HCCs can harbor different self-renewing tumorigenic cell types expressing a variety of morphological and phenotypical markers, karyotypic evolution and different gene expression profiles. This suggests that the models of hepatic carcinogenesis should take into account TPC heterogeneity due to intratumour clonal evolution

Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34- cell population with intrinsic resistance to imatinib.

We show the molecular and functional characterization of a novel population of lineage-negative CD34-negative (Lin–CD34–) hematopoietic stem cells from chronic myelogenous leukemia (CML) patients at diagnosis. Molecular karyotyping and quantitative analysis of BCR-ABL transcript demonstrated that approximately one-third of CD34– cells are leukemic. CML Lin–CD34– cells showed kinetic quiescence and limited clonogenic capacity. However, stroma-dependent cultures induced CD34 expression on some cells and cell cycling, and increased clonogenic activity and expression of BCR-ABL transcript. Lin–CD34– cells showed hematopoietic cell engraftment rate in 2 immunodeficient mouse strains similar to Lin-CD34+ cells, whereas endothelial cell engraftment was significantly higher. Gene expression profiling revealed the down-regulation of cell-cycle arrest genes and genes involved in antigen presentation and processing, while the expression of genes related to tumor progression, such as angiogenic factors, was strongly up-regulated compared with normal counterparts. Phenotypic analysis confirmed the significant down-regulation of HLA class I and II molecules in CML Lin–CD34– cells. Imatinib mesylate did not reduce fusion transcript levels, BCR-ABL kinase activity, and clonogenic efficiency of CML Lin–CD34– cells in vitro. Moreover, leukemic CD34– cells survived exposure to BCR-ABL inhibitors in vivo. Thus, we identified a novel CD34– leukemic stem cell subset in CML with peculiar molecular and functional characteristics