Baroclinic geostrophic adjustment in a rotating circular basin

Baroclinic geostrophic adjustment in a rotating circular basin is investigated in a laboratory study. The adjustment process consists of a linear phase before advective and dissipative effects dominate the response for longer time. This work describes in detail the hydrodynamics and energetics of the linear phase of the adjustment process of a two-layer fluid from an initial step height discontinuity in the density interface DeltaH to a final response consisting of both geostrophic and fluctuating components. For a forcing lengthscale r(f) equal to the basin radius R-0, the geostrophic component takes the form of a basin-scale double gyre while the fluctuating component is composed of baroclinic Kelvin and Poincare waves. The Burger number S=R/r(f) (R is the baroclinic Rossby radius of deformation) and the dimensionless forcing amplitude epsilon = DeltaH/H-1 (H-1 is the upper-layer depth) characterize the response of the adjustment process. In particular, comparisons between analytical solutions and laboratory measurements indicate that for time tau: 1 < tau < S-1 (tau is time scaled by the inertial period 2pi/f), the basin-scale double gyre is established, followed by a period where the double gyre is sustained, given by S-1 < tau < 2epsilon(-1) for a moderate forcing and S-1 < tau < tau(D) for a weak forcing (tau(D) is the dimensionless dissipation timescale due to Ekman damping). The analytical solution is used to calculate the energetics of the baroclinic geostrophic adjustment. The results are found to compare well with previous studies with partitioning of energy between the geostrophic and fluctuating components exhibiting a strong dependence on S. Finally, the outcomes of this study are considered in terms of their application to lakes influenced by the rotation of the Earth

Confronting Grand Challenges in environmental fluid mechanics

Environmental fluid mechanics underlies a wealth of natural, industrial and, by extension, societal challenges. In the coming decades, as we strive towards a more sustainable planet, there are a wide range of grand challenge problems that need to be tackled, ranging from fundamental advances in understanding and modeling of stratified turbulence and consequent mixing, to applied studies of pollution transport in the ocean, atmosphere and urban environments. A workshop was organized in the Les Houches School of Physics in France in January 2019 with the objective of gathering leading figures in the field to produce a road map for the scientific community. Five subject areas were addressed: multiphase flow, stratified flow, ocean transport, atmospheric and urban transport, and weather and climate prediction. This article summarizes the discussions and outcomes of the meeting, with the intent of providing a resource for the community going forward

Confronting Grand Challenges in Environmental Fluid Dynamics

Environmental fluid dynamics underlies a wealth of natural, industrial and, by extension, societal challenges. In the coming decades, as we strive towards a more sustainable planet, there are a wide range of grand challenge problems that need to be tackled, ranging from fundamental advances in understanding and modeling of stratified turbulence and consequent mixing, to applied studies of pollution transport in the ocean, atmosphere and urban environments. A workshop was organized in the Les Houches School of Physics in France in January 2019 with the objective of gathering leading figures in the field to produce a road map for the scientific community. Five subject areas were addressed: multiphase flow, stratified flow, ocean transport, atmospheric and urban transport, and weather and climate prediction. This article summarizes the discussions and outcomes of the meeting, with the intent of providing a resource for the community going forward

Identification of Kinases Regulating Prostate Cancer Cell Growth Using an RNAi Phenotypic Screen

As prostate cancer progresses to castration-resistant disease, there is an increase in signal transduction activity. Most castration-resistant prostate tumors continue to express the androgen receptor (AR) as well as androgen-responsive genes, despite the near absence of circulating androgen in these patients. The AR is regulated not only by its cognate steroid hormone, but also by interactions with a constellation of co-regulatory and signaling molecules. Thus, the elevated signaling activity that occurs during progression to castration resistance can affect prostate cancer cell growth either through the AR or independent of the AR. In order to identify signaling pathways that regulate prostate cancer cell growth, we screened a panel of shRNAs targeting 673 human kinases against LNCaP prostate cancer cells grown in the presence and absence of hormone. The screen identified multiple shRNA clones against known and novel gene targets that regulate prostate cancer cell growth. Based on the magnitude of effect on growth, we selected six kinases for further study: MAP3K11, DGKD, ICK, CIT, GALK2, and PSKH1. Knockdown of these kinases decreased cell growth in both androgen-dependent and castration-resistant prostate cancer cells. However, these kinases had different effects on basal or androgen-induced transcriptional activity of AR target genes. MAP3K11 knockdown most consistently altered transcription of AR target genes, suggesting that MAP3K11 affected its growth inhibitory effect by modulating the AR transcriptional program. Consistent with MAP3K11 acting on the AR, knockdown of MAP3K11 inhibited AR Ser 650 phosphorylation, further supporting stress kinase regulation of AR phosphorylation. This study demonstrates the applicability of lentiviral-based shRNA for conducting phenotypic screens and identifies MAP3K11, DGKD, ICK, CIT, GALK2, and PSKH1 as regulators of prostate cancer cell growth. The thorough evaluation of these kinase targets will pave the way for developing more effective treatments for castration-resistant prostate cancer

A Heart-Hand Syndrome Gene: Tfap2b Plays a Critical Role in the Development and Remodeling of Mouse Ductus Arteriosus and Limb Patterning

BACKGROUND: Patent ductus arteriosus (PDA) is one of the most common forms of congenital heart disease. Mutations in transcription factor TFAP2B cause Char syndrome, a human disorder characterized by PDA, facial dysmorphysm and hand anomalies. Animal research data are needed to understand the mechanisms. The aim of our study was to elucidate the pathogenesis of Char syndrome at the molecular level. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression of Tfap2b during mouse development was studied, and newborns of Tfap2b-deficient mice were examined to identify phenotypes. Gel shift assays had been carried out to search for Tfap2 downstream genes. Promoters of candidate genes were cloned into a reporter construct and used to demonstrate their regulation by Tfap2b in cell transfection. In situ hybridizations showed that the murine transcription factor Tfap2b was expressed during the entire development of mouse ductus arteriosus. Histological examination of ductus arteriosus from Tfap2b knockout mice 6 hours after birth revealed that they were not closed. Consequently, the lungs of Tfap2b(-/-) mice demonstrated progressive congestion of the pulmonary capillaries, which was postulated to result secondarily from PDA. In addition, Tfap2b was expressed in the limb buds, particularly in the posterior limb field during development. Lack of Tfap2b resulted in bilateral postaxial accessory digits. Further study indicated that expressions of bone morphogenetic protein (Bmp) genes, which are reported to be involved in the limb patterning and ductal development, were altered in limb buds of Tfap2b-deficient embryos, due to direct control of Bmp2 and Bmp4 promoter activity by Tfap2b. CONCLUSIONS/SIGNIFICANCE: Tfap2b plays important roles in the development of mouse ductus arteriosus and limb patterning. Loss of Tfap2b results in altered Bmp expression that may cause the heart-limb defects observed in Tfap2b mouse mutants and Char syndrome patients. The Tfap2b knockout mouse may add to the very limited available animal models of PDA

Identification and structural analysis of the tripartite α-pore forming toxin of Aeromonas hydrophila

The alpha helical CytolysinA family of pore forming toxins (α-PFT) contains single, two, and three component members. Structures of the single component Eschericia coli ClyA and the two component Yersinia enterolytica YaxAB show both undergo conformational changes from soluble to pore forms, and oligomerization to produce the active pore. Here we identify tripartite α-PFTs in pathogenic Gram negative bacteria, including Aeromonas hydrophila (AhlABC). We show that the AhlABC toxin requires all three components for maximal cell lysis. We present structures of pore components which describe a bi-fold hinge mechanism for soluble to pore transition in AhlB and a contrasting tetrameric assembly employed by soluble AhlC to hide their hydrophobic membrane associated residues. We propose a model of pore assembly where the AhlC tetramer dissociates, binds a single membrane leaflet, recruits AhlB promoting soluble to pore transition, prior to AhlA binding to form the active hydrophilic lined pore

The Structure of Turbulence Across the Sediment-Water-Interface

An increasing body of literature indicates that turbulence is a major contributor to the exchange of mass and momentum across the sediment-water-interface (SWI). The permeability Reynolds number ReK = p Ku_=u is a key parameter describing the flow at the SWI, where K is the permeability of the porous medium. The dynamics of turbulence around the SWI are determined by the intricate interaction between the hydrodynamics and the sediment characteristics, however, traditional experimental techniques are hindered in accessing this region properly, making experimental data rare. In this work we describe novel experimental results, which combines refractive index matching (RIM) and particle tracking velocimetry (PTV), and capture the instantaneous velocity fields across the SWI, for two different values of ReK. The measurements enable us to evaluate the TKE budget, a key tool for understanding turbulent processes. The results show that for low ReK the TKEbudget is in good agreement with DNS results for an impermeable boundary. For the same permeability but larger ReK, the flow penetrates the interface and the TKE-budget shows turbulence is both produced and transported beyond the SWI and into the permeable medium. Unlike the low ReK case where at the interface only viscous diffusion and dissipation are dominant, in the high ReK case all terms in the TKE-budget are of importance

Development of a new risk-based framework to guide investment in water quality monitoring

An innovative framework for optimising investments in water quality monitoring has been developed for use by water and environmental agencies. By utilising historical data, investigating the accuracy of monitoring methods and considering the risk tolerance of the management agency, this new methodology calculates optimum water quality monitoring frequencies for individual water bodies. Such information can be applied to water quality constituents of concern in both engineered and natural water bodies and will guide the investment of monitoring resources. Here we present both the development of the framework itself and a proof of concept by applying it to the occurrence of hazardous cyanobacterial blooms in freshwater lakes. This application to existing data demonstrates the robustness of the approach and the capacity of the framework to optimise the allocation of both monitoring and mitigation resources. When applied to cyanobacterial blooms in the Swan Coastal Plain of Western Australia, we determined that optimising the monitoring regime at individual lakes could greatly alter the overall monitoring schedule for the region, rendering it more risk averse without increasing the amount of monitoring resources required. For water resources with high-density temporal data related to constituents of concern, a similar reduction in risk may be observed by applying the framework