Downstream Branches Research Articles

107. Bacterial lipopolysaccharide-induced systemic inflammation alters cerebral blood flow: Relationship to prostaglandin and NO production

Delirium is a DSM-IVR diagnosis characterized by disturbed consciousness and changes in cognition over a short period of time. Cognition requires finely-regulated cerebral blood flow. Cerebral blood flow alterations may explain frequent delirium occurrence during bacterial sepsis. In the present work we studied the effect of systemic inflammation on cerebral blood flow. Magnetic resonance angiography revealed lower blood flow in the rostral part of the circle of Willis as well as in the middle and anterior cerebral arteries and downstream branches from 1 h after bacterial lipopolysaccharide (LPS) injection onwards as compared to saline administration. Two and a half hours after injection animals were killed and their brains analyzed for Nuclear Factor Kappa-B (NFkB) expression and for prostaglandin and NO production as enzymes for these vasoactive mediators are known to be upregulated by LPS. RT-PCR analyses showed increased expression of cyclooxygenase-2, prostaglandin E synthase and inducible NO synthase in the brains of LPS-treated animals. Immunohistochemistry indicated augmented nuclear NFkB in LPS-injected mice, but no frank increases in cyclooxygenase-2 protein or nitrotyrosine expression in the middle and anterior cerebral arteries. In conclusion, our work indicates that cerebral arterial blood flow is rapidly altered after intravenous bacterial LPS administration. The neuroimmune mechanisms underlying this effect remain elusive even though sustained changes in cerebral blood flow may involve prostaglandin and NO production.

Local mass transfer measurements for corals and other complex geometries using gypsum dissolution

A new method of measuring local mass transfer for highly complex geometries is demonstrated. The method combines gypsum dissolution and X-ray computed tomography (CT). An object coated in gypsum is CT scanned before and after exposure to fluid flow. Digital three-dimensional pre- and post-flow geometries are created using the CT data, and the local dissolution thickness is determined by subtracting the post-flow from the pre-flow object. The method is first demonstrated for cylinders in cross-flow and validated with mass and heat transfer data. The measurements agree with values from correlations reported in the literature when scaled using Reynolds, Sherwood, and Schmidt numbers. The method is then applied to measure local mass transfer for the complex geometry of a 0.75-scale branching scleractinian coral Stylophera pistillata. Local Sherwood numbers vary between nearly zero on the backward facing surfaces of the downstream branches of the coral and nearly 200 at the tips of the branches at the top of the coral. The upstream facing surfaces at radii between 20 and 70 % of the overall radius of the coral experience Sherwood numbers close to 100. The local measurements are integrated to produce a bulk mass transfer coefficient that lies within the range of previous bulk measurements in the literature for similar coral species. With this method, local mass transfer rates can be measured for complex objects in laboratory or natural in situ flow environments. These are geometries for which only bulk measurements were previously possible.

Aeroacoustics of T-junction merging flow

This paper reports a numerical study of the aeroacoustics of merging flow at T-junction. The primary focus is to elucidate the acoustic generation by the flow unsteadiness. The study is conducted by performing direct aeroacoustic simulation approach, which solves the unsteady compressible Navier-Stokes equations and the perfect gas equation of state simultaneously using the conservation element and solution element method. For practical flows, the Reynolds number based on duct width is usually quite high (>10(5)). In order to properly account for the effects of flow turbulence, a large eddy simulation methodology together with a wall modeling derived from the classical logarithm wall law is adopted. The numerical simulations are performed in two dimensions and the acoustic generation physics at different ratios of side-branch to main duct flow velocities VR (=0.5,0.67,1.0,2.0) are studied. Both the levels of unsteady interactions of merging flow structures and the efficiency of acoustic generation are observed to increase with VR. Based on Curle's analogy, the major acoustic source is found to be the fluctuating wall pressure induced by the flow unsteadiness occurred in the downstream branch. A scaling between the wall fluctuating force and the efficiency of the acoustic generation is also derived.

Differential unfolded protein response during Chikungunya and Sindbis virus infection: CHIKV nsP4 suppresses eIF2α phosphorylation

Chikungunya (CHIKV) and Sindbis (SINV) are arboviruses belonging to the alphavirus genus within the Togaviridae family. They cause frequent epidemics of febrile illness and long-term arthralgic sequelae that affect millions of people each year. Both viruses replicate prodigiously in infected patients and in vitro in mammalian cells, suggesting some level of control over the host cellular translational machinery that senses and appropriately directs the cell’s fate through the unfolded protein response (UPR). The mammalian UPR involves BIP (or GRP78), the master sensor in the endoplasmic reticulum (ER) together with the three downstream effector branches: inositol-requiring ser/thr protein kinase/endonuclease (IRE-1), PKR-like ER resident kinase (PERK) and activating transcription factor 6 (ATF-6). Through careful analysis of CHIKV and SINV infections in cell culture we found that the former selectively activates ATF-6 and IRE-1 branches of UPR and suppresses the PERK pathway. By separately expressing each of the CHIKV proteins as GFP-fusion proteins, we found that non-structural protein 4 (nsP4), which is a RNA-dependent-RNA polymerase, suppresses the serine-51 phosphorylation of eukaryotic translation initiation factor, alpha subunit (eIF2α), which in turn regulates the PERK pathway. This study provides insight into a mechanism by which CHIKV replication responds to overcome the host UPR machinery.

Effects of helical flow in one‐dimensional modelling of sediment distribution at river bifurcations

ABSTRACTComplex flow processes at river bifurcations and the influence of the layout of a bifurcation make it difficult to predict sediment distribution over the downstream branches in case bedload transport dominates. In one‐dimensional models we need a nodal point relationship that prescribes the distribution of sediment over the downstream branches. We have identified which factors need to be included in such a relationship for the division of bedload transport at bifurcations. Next, irrotational flow theory for idealized geometries has been used to derive a simple physics‐based nodal point relationship that accounts for the effects of helical flow in the situation that a channel takes off under an angle from a straight main channel. This first step towards a complete nodal point relationship is applicable to bedload transport situations if the flow is clearly curved and if there is no pronounced bed topography. The relationship has been tested against data from a unique set of laboratory measurements, numerical data and data from a scale model of the Rhine bifurcation at Pannerden in the Netherlands. We find that the derived model yields a reasonable prediction of the sediment division over the downstream branches, and yields better predictions than the Wang et al. model for the situation considered. Considering the relative complexity and limited accuracy of the nodal point relationship for the effect of helical flow alone, however, we conclude thatderiving a practical physics‐based 1‐D relationship including all relevant processes is not feasible. We therefore recommend 2‐D or 3‐D modelling for all cases in general where morphological evolution depends on the division of bedload transport at bifurcations. Copyright © 2012 John Wiley & Sons, Ltd.

Influence of Detailed Topography when Modeling Flows in Street Junction During Urban Flood

Floods in dense urban areas propagatemainly through the streets, where the flow can be locally affected by elements of urban topography. This study aims at assessing the need of integrating detailed topography in numerical models when simulating urban floods. Acoustic Doppler Velocimetry and Large Scale Particle Image Velocimetry measurements in an experimental three branch junction representing a city crossroad are used to calibrate a numerical model solving the 2D shallow water equations. A constant eddy viscosity model proves to be accurate enough to calculate velocity fields, but such model requires a fine calibration against experimental data. Simulations run with this calibrated model are performed to study the impact of obstacles and sidewalks representative of urban areas. It is found that obstacles located in the downstream branch can highly perturb the velocities distribution downstream of the junction, whereas obstacles located in the upstream branches have less influence. The presence of sidewalks results in reduced flow section and higher velocities, but additional effects occur within and downstream of the junction. Simulations presented here show the need of considering detailed topography and elements of urban furniture if local velocities have to be represented.

Regulation of the Hippo–YAP pathway by protease-activated receptors (PARs)

The Hippo signaling pathway plays a crucial role in tissue growth and tumorigenesis. Core components of the Hippo pathway include the MST1/2 and Lats1/2 kinases. Acting downstream from the Hippo pathway are the YAP/TAZ transcription coactivators, which are inhibited through phosphorylation by Lats. However, upstream signals that regulate the Hippo pathway have not been well delineated. Here we report that stimulation of protease-activated receptors (PARs) activates YAP/TAZ by decreasing phosphorylation and increasing nuclear localization. PAR1 acts through G(12/13) and Rho GTPase to inhibit the Lats1/2 kinase. Our observations establish thrombin as a physiological signal for the Hippo pathway and implicate Hippo-YAP as a key downstream signaling branch of PAR activation.

Functional coordination of the spread of vasodilations through skeletal muscle microvasculature: implications for blood flow control

We sought to understand the integrated vascular response to muscle contraction by determining how different branch orders of the terminal microvascular network respond to stimulation using a K(ATP) channel opener pinacidil (PIN) as a muscle contraction mimetic. Using the blood perfused, hamster cremaster preparation in situ, we locally micropipette-applied 10(-5) M PIN on the capillaries, Branch arteriole (third order, two branch orders up from the capillaries) and transverse arterioles (TA) (second order, three branch orders up from the capillaries) and observed different branch orders of the microvasculature to determine where the localized vasodilation spread throughout the terminal microvascular network. We observed that PIN stimulation of capillaries caused associated upstream vasodilation of the module inflow arteriole (MI) (fourth order, the terminal arteriole) (2.1 ± 0.4 μm), the associate Branch (1.4 ± 0.5 μm) and in the upstream direction on the TA (2.1 ± 0.5 μm). Vasodilation did not occur in all MIs (-0.2 ± 0.2 μm) from the vasodilated branch and did not go downstream on the TA (0.7 ± 0.4 μm). Branch stimulation caused upstream TA (3.3 ± 1.0 μm) and upstream Branch (1.7 ± 0.3 μm) vasodilation but not downstream TA (1.5 ± 0.6 μm) or downstream Branch (0.2 ± 0.3 μm) vasodilation. TA stimulation caused conducted responses in both directions and into all associated arteriolar Branches and MIs. The spread of the conducted response is dependent on the vascular branch order stimulated: capillary stimulation was most specific in its direction and TA stimulation was the least specific. Our data indicate that vascular branch order is important in determining the vascular response needed to direct blood flow to contracting skeletal muscle cells.

TGF-β-induced activation of mTOR complex 2 drives epithelial–mesenchymal transition and cell invasion

In cancer progression, carcinoma cells gain invasive behavior through a loss of epithelial characteristics and acquisition of mesenchymal properties, a process that can lead to epithelial–mesenchymal transition (EMT). TGF-β is a potent inducer of EMT, and increased TGF-β signaling in cancer cells is thought to drive cancer-associated EMT. Here, we examine the physiological requirement for mTOR complex 2 (mTORC2) in cells undergoing EMT. TGF-β rapidly induces mTORC2 kinase activity in cells undergoing EMT, and controls epithelial cell progression through EMT. By regulating EMT-associated cytoskeletal changes and gene expression, mTORC2 is required for cell migration and invasion. Furthermore, inactivation of mTORC2 prevents cancer cell dissemination in vivo. Our results suggest that the mTORC2 pathway is an essential downstream branch of TGF-β signaling, and represents a responsive target to inhibit EMT and prevent cancer cell invasion and metastasis.

Loss of flow mediated dilation accompanies endothelial dysfunction in the preconditioned state

To examine flow mediate dilation in the preconditioned state, terminal arteriolar junctions were observed in the hamster cheek pouch using intravital microscopy (pentobarbital 70mg/kg, N=28). Repeated occlusion of one downstream arteriolar branch induced dilation in both the unoccluded downstream branch B (where shear increased) and in the upstream feed F (where shear decreased). To test whether occlusion induced dilation was NO‐mediated, we applied nitro‐arginine (LNNA, 10‐5M) to either B or F (micropipette). LNNA prevented occlusion induced dilation in B (where shear increased) and not F. Thus dilation where shear increased is interpreted as flow mediated. To test whether occlusion induced dilation in F was propagated via gap junction (GJ) signals arising from B, 18‐alpha‐GA (10‐4M) was applied to either B or F. GJ inhibition blocked all dilation in F and none in B. Finally preconditioning induced pharmacologically with nitroprusside or b2‐adrenergic agonism (isoproterenol, ISO) caused endothelial dysfunction (bradykinin, acetylcholine). Occlusion in the preconditioned state caused the same flow changes in B or F, but no dilation. Local elevations in shear induce a local dilation and initiate a GJ mediated propagated dilation. Preconditioning inducing endothelial dysfunction includes absence of flow mediated dilation, and lack of GJ mediated propagated dilation. (NIH HL55492; AHA 0655908T)

Quantifying Transmission of Norovirus During an Outbreak

Healthcare workers are thought to play a role in nosocomial transmission of norovirus, but the level and direction of norovirus transmission between patients and healthcare workers in sustaining transmission during an outbreak have not been quantified. We developed a method for finding plausible transmission trees of who acquired their infection from whom. We applied the method to data from an outbreak of norovirus in 4 wards of a psychiatric institution in the Netherlands in 2008. The simulated transmission trees were based on serial intervals for time between symptom onsets, weighted for the number of days that healthcare workers were present. The obtained transmission trees were linked to the Barthel Index, a measure of patient reliance on healthcare in their basic daily activities. The dominant recognized transmission route was from patient to patient (64%), followed by patient to healthcare worker (29%). The overall estimated reproduction number for healthcare workers was low compared with patients (0.25 vs. 1.20; mean difference = 0.95 [95% confidence interval (CI) = 0.60 to 1.30]). The average number of all subsequent cases attributable to the downstream branch of one single infected healthcare worker in the transmission tree was 4.4 compared with 6.5 for cases attributable to one single infected patient (mean difference = 2.1 [95% CI = -4.7 to 8.9]). In the ward with patients requiring the highest level of care from healthcare workers, the attack rate among healthcare workers was highest. This approach provides a framework to quantify the magnitude and direction of transmission between healthcare workers and patients during a norovirus outbreak. The utility of this method in outbreaks of other infections and in different settings should be explored.

TGF-β-induced activation of mTOR complex 2 drives epithelial–mesenchymal transition and cell invasion

In cancer progression, carcinoma cells gain invasive behavior through a loss of epithelial characteristics and acquisition of mesenchymal properties, a process that can lead to epithelial-mesenchymal transition (EMT). TGF-β is a potent inducer of EMT, and increased TGF-β signaling in cancer cells is thought to drive cancer-associated EMT. Here, we examine the physiological requirement for mTOR complex 2 (mTORC2) in cells undergoing EMT. TGF-β rapidly induces mTORC2 kinase activity in cells undergoing EMT, and controls epithelial cell progression through EMT. By regulating EMT-associated cytoskeletal changes and gene expression, mTORC2 is required for cell migration and invasion. Furthermore, inactivation of mTORC2 prevents cancer cell dissemination in vivo. Our results suggest that the mTORC2 pathway is an essential downstream branch of TGF-β signaling, and represents a responsive target to inhibit EMT and prevent cancer cell invasion and metastasis.

Estimation of drag coefficient of a real tree considering the vertical stand structure of trunk, branches, and leaves

Drag coefficients of a real tree trunk and branch and the sheltering effects of an upstream trunk or branch on a downstream one in a linear arrangement with different spacings were investigated in detail. Willow and Robinia pseudoacacia, representative and invasive trees in Japanese rivers, respectively, were selected for the study. The drag coefficient of the real tree trunk started to decrease from a relatively low Reynolds number and was smaller than that of a smooth circular cylinder in the entire Reynolds number range investigated. Leaves increased the drag coefficient by around 40–100% in comparison to that of a branch alone and increased with increasing the area ratio of leaves and branches. The sheltering effects of an upstream branch increased with the existence of leaves. The drag coefficient of a downstream branch approached around 95% of that of a single branch with increasing Reynolds number, regardless of the presence of leaves. The moment for drag force of a whole tree was calculated for a strong wind event that overturned trees in the Arakawa River, Japan. The calculated value was compared with the experimental threshold values and was validated within a reasonable limit.

The effect of interacting downstream branches on saltwater intrusion in the Modaomen Estuary, China

In recent years, the increased pressure of saltwater intrusion in the Modaomen Estuary, one of the outlets in the Pearl River Delta (PRD), China, has threatened the freshwater supply for the surrounding regions. The estuary has complex geometry and bathymetry and branches into three waterways, Madaomen Waterway, Hongwan Waterway, and Hezhou Waterway, entering into the coastal sea. In this study, a three-dimensional baroclinic model (EFDC) was used to investigate salt transport among these branches and saltwater intrusion in the mainstem of the estuary. The salt transport at selected cross sections was decomposed into three components: advection, steady shear, and tidal oscillatory, following the method of Lerczak et al. (Lerczak, J.A., Geyer, W.R., Chant, R.J., 2006. Mechanisms driving the time-dependent salt flux in a partially stratified estuary. Journal of Physical Oceanography 36, 2296–2311). Results from this study indicate that the Hongwan Waterway serves as a salt source for the mainstem of the estuary, especially during spring tides, while the Hezhou Waterway mainly acts as a salt sink for the mainstem. The down-estuary wind increases the steady shear transport in the Modaomen Waterway and the advection transport in the Hongwan Waterway, which alters the saltwater intrusion in the estuary. Closure of the Hongwan and the Hezhou Waterways could result in a 20% decrease of saltwater intrusion in the estuary. These results provide scientific basis for water resource management in the region.

Evolution of a bifurcation in a meandering river with adjustable channel widths, Rhine delta apex, The Netherlands

ABSTRACTRivers may dramatically change course on a fluvial plain. Such an avulsion temporarily leads to two active channels connected at a bifurcation. Here we study the effect of dynamic meandering at the bifurcation and the effect of channel width adjustment to changing discharge in both downstream branches on the evolution of a bifurcation and coexisting channels. As an example, we reconstructed the last major avulsion at the Rhine delta apex.We combined historical and geological data to reconstruct a slowly developing avulsion process spanning 2000 years and involving channel width adjustment and meandering at the bifurcation. Based on earlier idealised models, we developed a one‐dimensional model for long‐term morphodynamic prediction of upstream channel and bifurcates connected at the bifurcation node. The model predicts flow and sediment partitioning at the node, including the effect of migrating meanders at the bifurcation and channel width adjustment.Bifurcate channel width adaptation to changing discharge partitioning dramatically slows the pacing of bifurcation evolution because the sediment balance for width adjustment and bed evolution are coupled. The model further shows that meandering at the bifurcation modulates channel abandonment or enlargement periodically. This explains hitherto unrecognised reactivation signals in the sedimentary record of the studied bifurcation meander belts, newly identified in our geological reconstruction. Historical maps show that bifurcation migration due to meander bend dynamics increases the bifurcation angle, which increases the rate of closure of one bifurcate.The combination of model and reconstruction identifies the relevant timescales for bifurcation evolution and avulsion duration. These are the time required to fill one downstream channel over one backwater length, the time to translate one meander wavelength downstream and, for strong river banks, the adaptation timescale to adjust channel width. The findings have relevance for all avulsions where channel width can adjust to changing discharge and where meandering occurs. Copyright © 2011 John Wiley & Sons, Ltd.

Experimental Microsphere Targeting in a Representative Hepatic Artery System

Recent work employing the computational fluid-particle modeling of the hepatic arteries has identified a correlation between particle release position and downstream branch distribution for direct tumor-targeting in radioembolization procedures. An experimental model has been constructed to evaluate the underlying simulation theory and determine its feasibility for future clinical use. A scaled model of a generalized hepatic system with a single inlet and five outlet branches was fabricated to replicate the fluid dynamics in the hepatic arteries of diseased livers. Assuming steady flow, neutrally buoyant microspheres were released from controlled locations within the inlet of the model and the resulting output distributions were recorded. Fluid and particle transport simulations were conducted with identical parameters. The resulting experimentally and simulation-derived microsphere distributions were compared. The experimental microsphere distribution exhibited a clear dependence on injection location that correlated very strongly with the computationally predicted results. Individual branch targeting was possible for each of the five outputs. The experimental results validate the simulation methodology for achieving targeted microsphere distributions in a known geometry under constant flow conditions.

Modelling and analyzing flow diversion in branching channels with symmetric geometry

AbstractThis paper aims at the investigation and analysis of numerical and laboratory modelling of flow in branched channels with symmetrical geometry and varying hydraulic conditions. Details of velocity and water‐level profiles in branching locations are discussed. In some low‐slop regions like plains, rivers may be branching; or in alluvial plains where the slop is low, meanders may appear. On the other hand, in the mountainous and semi‐mountainous areas with relatively steep slops, arterial rivers can be formed. Therefore, it is important to learn the behaviour of rivers in branching location and to simulate water flow in branching part of rivers.Details of two‐dimensional numerical model in a main channel and secondary downstream branches are explained and results are analysed and compared against experimental data. With respect to the numerical simulation, velocity and depth in different sections of laboratory model are calculated and the corresponding profiles are developed. The water‐level profiles are calculated and drawn using both the numerical and experimental models. Some long narrow eddies are predicted along internal bank of junction. The comparison of numerical and experimental models proves reasonable results for this research. Copyright © 2010 John Wiley & Sons, Ltd.

Dependence of Dendritic Growth on Convention with PFM Simulation

A binary alloy PFM (Phase-Field Model) which incorporates the flow field equations is constructed considering the dependence of microstructure on convention. Al-Cu binary alloy is investigated numerically based on the model, and the reasonable computational methods is studied for solving PFM, the effect of convention on dendritic growth and microsegregation patterns is implemented successfully. The computed results indicate that, the larger convention velocity U, the more developed the upstream dendritic branches is, and the more acutely the solute composition in the upstream dendritic solid fluctuates is. But the severity of microsegregation ahead of interface reduces. Nevertheless, the more undeveloped the downstream dendritic branches, the more acutely the solute composition in the the downstream dendritic solid fluctuates is, but the severity of microsegregation ahead of interface aggravates.

Prevention of transplant coronary artery disease by prenylation inhibitors

In this study we systematically dissect the prenylation pathway to better define the mechanism behind statin inhibition in chronic allograft rejection in heart transplants, or transplant coronary artery disease (TCAD). Utilizing a murine heterotopic heart transplant model, animals received daily treatments of either statin or selective isoprenoid blockade inhibitors to block the four major downstream branches of the mevalonate pathway. TCAD was assessed by morphometric analysis at Day 52. Graft-infiltrating cells, cytokine production, smooth muscle cell proliferation and migration and endothelial cell MHC II expression were detected on Day 7. Atorvastatin and two prenylation inhibitors, NE-10790 and manumycin A, significantly reduced TCAD lesions compared with untreated animals. Perillyl alcohol treatment resulted in a trend toward decreased luminal narrowing. Finally, zaragozic acid (cholesterol blockade only) did not alter TCAD severity. Statins and prenylation inhibitors reduced inflammatory cell allograft recruitment, but did not always correlate with TCAD reduction. Cytokine production was decreased in recipient spleens in all treatment groups. Both in vitro and in vivo IFN-γ-stimulated MHC II expression was decreased in a dose-dependent manner in the atorvastatin, perillyl alcohol and NE-10790 groups. In vitro smooth muscle cell proliferation was decreased in all treatment groups. Finally, in vitro smooth muscle cell migration was decreased in the atorvastatin, NE-10790 and manumycin A groups only. FPT and GGPT-2 (inhibition) are the key enzymes in the HGM-CoA reductase pathway and most influential in TCAD prevention. TCAD reduction is most closely related to smooth muscle cell migration, but not its anti-inflammatory properties.

Scour process due to symmetric dam spillways crossing jets

The presence of a dam in a river deeply modifies the natural dynamic process, including sediment transport, debris flow and flow regime occurring both in the upstream and in the downstream branches. Thus a dam cannot be considered as an isolated element in the context of a river, and the study of all the cited phenomena has to be conducted taking its presence into account. In particular, it affects both the global and the local river erosive mechanisms. Moreover, risk management policy considers, among other variables, that in all likelihood toe erosion is the one affecting dam failures. In this perspective, even the local scour phenomenon due to plunging jets assumes a particular importance for all river engineers and has to be carefully taken into consideration in order to prevent structural risks and to correctly design protection measurements downstream of hydraulic structures. Previous studies extensively analysed both scour geometry and flow features due to one single jet. The present paper aims to study both the flow features and the scour hole lengths in the case in which two symmetric crossing jets are used. In particular, experiments were conducted by varying hydraulic and geometric parameters: jet discharge, tailwater depth, jet vertical angle and the angle between the crossing jets. Moreover, it was experimentally proven that the vertical distance of the jet crossing point from the water surface deeply influences the scour hole length. A comparison of scour hole morphology due to an equivalent single jet geometric condition is also proposed, in order to understand under what conditions crossing jets reduce the scour depth.