Hydrodynamic Forces on Inundated Bridge Decks

The hydrodynamic forces experienced by an inundated bridge deck have great importance in the design of bridges. Specifically, the drag force, lift force, and the moment acting on the bridge deck under various levels of inundation and a range of flow conditions influence the design and construction of the bridge. This report explores the forces acting on bridges in two ways. First, through physical experimentation on scaled-down bridge deck models tested in a flume and then with computational fluid dynamics (CFD) simulation models. Three bridge deck prototypes were used for the experimentation: a typical six-girder highway bridge deck, a three-girder deck, and a streamlined deck designed to better withstand the hydraulic forces. The forces (expressed as nondimensional force coefficients) on each of the bridge deck shapes were measured in the laboratory with an ultra-precise force balance under a range of inundation scenarios (including partial inundation) and at four different velocities characterized by Froude numbers in the range of 0.16 to 0.32. CFD modeling was performed using both the Fluent® and STAR-CD® software packages. The CFD models were calibrated to the flow conditions of the six-girder bridge, and these same conditions were used for the other two bridge shapes. A range of model options were tested including two-dimensional versus three-dimensional models, different mesh resolutions, boundary conditions, and turbulence models; their effect on the accuracy of results and processing efficiency were noted. Fitting equations were generated to create an envelope around the experimental data and create design charts for each of the bridge types and force coefficients. Finally, the CFD models, though they can match some of the general behavior of experimental models in terms of the relationship between inundation ratio and force measured at the bridge, do not yet faithfully reproduce the critical values of the hydraulic forces and show very little response to velocity. The CFD simulations seem promising as a method to test bridge designs, but more research is needed before complex designs can be tested wholly in the CFD realm. However, the design charts from the experimental results should be a valuable tool for the bridge designer in a wide range of design applications

Networking erythropoiesis

Recent findings and technological advances provide insight into how a few transcription factors work together in complex ways to orchestrate red blood cell differentiation

LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice

Mammalian oocytes are arrested at prophase I until puberty when hormonal signals induce the resumption of meiosis I and progression to meiosis II. Meiotic progression is controlled by CDK1 activity and is accompanied by dynamic epigenetic changes. Although the signalling pathways regulating CDK1 activity are well defined, the functional significance of epigenetic changes remains largely unknown. Here we show that LSD1, a lysine demethylase, regulates histone H3 lysine 4 di-methylation (H3K4me2) in mouse oocytes and is essential for meiotic progression. Conditional deletion of Lsd1 in growing oocytes results in precocious resumption of meiosis and spindle and chromosomal abnormalities. Consequently, most Lsd1-null oocytes fail to complete meiosis I and undergo apoptosis. Mechanistically, upregulation of CDC25B, a phosphatase that activates CDK1, is responsible for precocious meiotic resumption and also contributes to subsequent spindle and chromosomal defects. Our findings uncover a functional link between LSD1 and the major signalling pathway governing meiotic progression

Targeted Disruption of the EZH2/EED Complex Inhibits EZH2-dependent Cancer

Enhancer of zeste homolog2 (EZH2) is the histone lysine N-methyltransferase component of the Polycomb repressive complex 2 (PRC2), which in conjunction with embryonic ectoderm development (EED) and suppressor of zeste 12 homolog (SUZ12), regulates cell lineage determination and homeostasis. Enzymatic hyperactivity has been linked to aberrant repression of tumor suppressor genes in diverse cancers. Here, we report the development of stabilized alpha-helix of EZH2 (SAH-EZH2) peptides that selectively inhibit H3 Lys27 trimethylation by dose-responsively disrupting the EZH2/EED complex and reducing EZH2 protein levels, a mechanism distinct from that reported for small molecule EZH2 inhibitors targeting the enzyme catalytic domain. MLL-AF9 leukemia cells, which are dependent on PRC2, undergo growth arrest and monocyte/macrophage differentiation upon treatment with SAH-EZH2, consistent with observed changes in expression of PRC2-regulated, lineage-specific marker genes. Thus, by dissociating the EZH2/EED complex, we pharmacologically modulate an epigenetic “writer” and suppress PRC2-dependent cancer cell growth

Calibration of erodibility testing devices for bridge design support

In order to promote bridge safety under flood conditions, the U. S. Federal Highway Administration (FHWA) has been developing more reliable bridge scour evaluation methods that take into account bridge site specific flow conditions and stream bed material properties. The FHWA is currently developing two such devices: the Ex-situ Scour Testing Device (ESTD) and the laboratory version of an In-situ Scour Testing Device (Lab-ISTD), both test erodibility of stream bed material under specific flow conditions. To maintain portability and robustness, the Lab-ISTD has evolved into a compact cylindrical device that uses a radial flow pattern towards the center of the device to mobilize the foundation material and carrying it away. In this study the previously calibrated ESTD is used as a reference to characterize the performance of the Lab-ISTD, and therefore establish a calibration procedure that enables the Lab-ISTD to produce necessary parameters for better bridge scour evaluation and foundation design

Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturation

Here, we describe that lysine-specific demethylase 1 (Lsd1/KDM1a), which demethylates histone H3 on Lys4 or Lys9 (H3K4/K9), is an indispensible epigenetic governor of hematopoietic differentiation. Integrative genomic analysis, combining global occupancy of Lsd1, genome-wide analysis of its substrates H3K4 monomethylation and dimethylation, and gene expression profiling, reveals that Lsd1 represses hematopoietic stem and progenitor cell (HSPC) gene expression programs during hematopoietic differentiation. We found that Lsd1 acts at transcription start sites, as well as enhancer regions. Loss of Lsd1 was associated with increased H3K4me1 and H3K4me2 methylation on HSPC genes and gene derepression. Failure to fully silence HSPC genes compromised differentiation of hematopoietic stem cells as well as mature blood cell lineages. Collectively, our data indicate that Lsd1-mediated concurrent repression of enhancer and promoter activity of stem and progenitor cell genes is a pivotal epigenetic mechanism required for proper hematopoietic maturation. DOI: http://dx.doi.org/10.7554/eLife.00633.00