Global Stability Analysis of Compressible Leading-Edge Flow on a Swept Wing

International audienceThe global hydrodynamic stability of compressible leading-edge flow on a swept wing is addressed using Krylov-based iterative methods in conjunction with direct numerical simulations (DNS). Such a global hydrodynamic stability solver enables the analysis of complex fluid behavior by extracting global stability information directly from numerical simulations. Applying the DNS-based stability approach, unstable boundary-layer modes of the crossflow type and amplified as well as weakly-damped acoustic modes have been computed for a supersonic flow configuration. A parameter study reveals that, depending on the spanwise disturbance wavenumber β, boundary-layer modes or acoustic modes represent the dominant instability mechanism for the investigated parameter choices. Furthermore, the results of the present work clearly demonstrate the necessity of a global stability analysis to comprehensively understand the stability of swept leading-edge flow

Force-induced calcium concentration change and focal adhesion translocation : effects of force amplitude and frequency

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2004.Includes bibliographical references (p. 63-66).Vascular endothelial cells rapidly sense and transduce external forces into biological signals through a process known as mechanotransduction. Numerous biological processes are involved in mechanotransduction, including calcium signaling and activation of focal adhesion sites, but little is known about how cells initially sense changes in the external mechanical environment. In order to examine the rapid mechanosensing thresholds involved with mechanotransduction, calcium concentration changes and focal adhesion site translocations were observed with fluorescent microscopy by labeling intracellular calcium with Fluo-3 calcium dye and by infecting cells with GFP-paxillin fusion proteins. Monitoring calcium concentration changes proved unreliable for determining mechanotransduction thresholds, while a non-graded, time dependent ([similar to] minutes) steady load threshold for mechanotransduction was established between 0.90 and 1.45 nN for focal adhesion site activation. Activation was greatest near the point of forcing (< 7.5 [mu]m), indicating that shear forces imposed on the apical cell membrane transmit non-uniformly to the basal cell surface and that focal adhesion sites may function as individual mechanosensors responding to local levels of force. Results from a while applying nN-level magnetic trap shear forces to the cell apex via integrin-linked magnetic beads. Both biological responses were monitored continuum, viscoelastic finite element model of magnetocytometry that represented experimental focal adhesion attachments provided support for a non-uniform force transmission to basal surface focal adhesion sites. Frequency variation between 0.1 and 50 Hz altered focal adhesion translocation and(cont.) resulted in a biphasic response minimized at 1.0 Hz. Furthermore, applying the tyrosine kinase inhibitors genistein and PP2, a specific Src family kinase inhibitor, resulted in differential effects on force-induced translocation. These results highlight the mutual importance of force transmission and biochemical signaling in focal adhesion mechanotransduction.by Peter J. Mack.S.M

Defining critical endothelial-dependent events

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2008.Includes bibliographical references (p. 98-101).Coronary heart disease (CHD) is a major health concern for Americans and people worldwide. Arteriogenesis, an adaptive remodeling process in which pre-existing collateral arterioles remodel to form large diameter conductance arteries, has received recent attention for its therapeutic potential in treating CHD, but the mechanisms regulating the process remain incompletely understood. In particular, little is known about how collateral flow, and the resulting effect of shear stress acting along the collateral vessel wall, regulates coronary collateralization. This Thesis combines a series of experimental systems to define the responses evoked in endothelial cells exposed to hemodynamic waveforms characteristic of coronary collateral vessels and the subsequent paracrine effects on smooth muscle cells. Initially, a lumped parameter model of the human coronary collateral circulation was used to simulate normal (NCC) and adaptive remodeling (ACC) coronary collateral shear stress waveforms. These waveforms were then applied to cultured human endothelial cells (EC) and the resulting differences in EC gene expression were assessed by genome-wide transcriptional profiling, identifying genes distinctly regulated by collateral flow, including genes important for endothelial-smooth muscle interactions. In particular, the transcription factor KLF2 was upregulated by the ACC waveform and several of its downstream targets displayed the expected modulation, including the downregulation of Connective tissue growth factor (CTGF). Moreover, delivery of endothelial conditioned medium generated throughout the collateral flow experiments to culture smooth muscle cells (SMC) resulted in the modulation of SMC genes related to vessel maturation and stabilization. In the second part of this Thesis, the effect of endothelial KLF2 expression on SMC migration was characterized using a 3D microfluidic assay capable of monitoring SMC migration in co-culture with EC. Using this 3D system, it was found that KLF2-expressing EC co-cultured with SMC significantly reduce SMC migration compared to control EC and that this reduction can be rescued by delivery of soluble CTGF.(cont.) Collectively, these results demonstrate that the shear stress generated by collateral flow evokes distinct EC gene expression profiles and functional phenotypes that subsequently influence vascular events important for adaptive remodeling and provides experimental evidence supporting efforts directed at investigating endothelial KLF2 as a molecular target for therapeutic arteriogenesis.by Pater J. Mack.Ph.D

Dissolved iron transport pathways in the Ross Sea : influence of tides and horizontal resolution in a regional ocean model

© The Author(s), 2016. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Journal of Marine Systems 166 (2017): 73-86, doi:10.1016/j.jmarsys.2016.10.008.Phytoplankton production in the Ross Sea is regulated by the availability of dissolved iron (dFe), a limiting micro-nutrient, whose sources include Circumpolar Deep Water, sea ice melt, glacial melt, and benthic sources (sediment efflux and remineralization). We employ a passive tracer dye to model the benthic dFe sources and track pathways from deep areas of the continental shelf to the surface mixed layer in simulations with and without tidal forcing, and at 5 and 1.5km horizontal resolution. This, combined with dyes for each of the other dFe sources, provides an estimate of total dFe supply to surface waters. We find that tidal forcing increases the amount of benthic dye that covers the banks on the continental shelf. Calculations of mixed layer depth to define the surface ocean give similar average values over the shelf, but spatial patterns differ between simulations, particularly along the ice shelf front. Benthic dFe supply in simulations shows an increase with tidal forcing and a decrease with higher resolution. The changes in benthic dFe supply control the difference in total supply between simulations. Overall, the total dFe supply from simulations varies from 5.60 to 7.95 μmol m-2 yr-1, with benthic supply comprising 32-50%, comparing well with recent data and model synthesis. We suggest that including tides and using high horizontal resolution is important, especially when considering spatial variability of iron supply on the Ross Sea shelf.The authors acknowledge funding from NSF's Antarctic Research Program 496 (ODU: ANT-0944174; WHOI: ANT-0094165)

Optical conductivity in doped manganites with planar x2^2-y2^2 orbital order

We investigate a planar model for the ferromagnetic (FM) phase of manganites, which develops orbital order of $e_g$ electrons with x$^2$-y$^2$-symmetry at low temperature. The dynamic structure factor of orbital excitations and the optical conductivity $\sigma(\omega)$ are studied with help of a finite-temperature diagonalization method. Our calculations provide a theoretical prediction for $\sigma(\omega)$ for the 2D FM state and are of possible relevance for the recently found A-type phase of manganites at high doping which consists of FM layers coupled antiferromagnetically. In the x$^2$-y$^2$ ordered regime $\sigma(\omega)$ shows both a Drude peak and a gapped incoherent absorption due to a gap in the orbital excitations.Comment: 5 pages, 5 figures, to appear in Phys. Rev. Let

Double exchange magnets: Spin-dynamics in the paramagnetic phase

The electronic structure of perovskite manganese oxides is investigated in terms of a Kondo lattice model with ferromagnetic Hund coupling and antiferromagnetic exchange between $t_{2g}$-spins using a finite temperature diagonalization technique. Results for the dynamic structure factor are consistent with recent neutron scattering experiments for the bilayer manganite La$_{1.2}$Sr$_{1.8}$Mn$_2$O$_7$ . The susceptibility shows Curie-Weiss behaviour and is used to derive a phase diagram. In the paramagnetic phase carriers are characterized as ferromagnetic polarons in an antiferromagnetic spin liquid.Comment: Revtex, 4 pages with 5 postscript figures include

Mining Disaggregase Sequence Space to Safely Counter TDP-43, FUS, and α-Synuclein Proteotoxicity.

Hsp104 is an AAA+ protein disaggregase, which can be potentiated via diverse mutations in its autoregulatory middle domain (MD) to mitigate toxic misfolding of TDP-43, FUS, and α-synuclein implicated in fatal neurodegenerative disorders. Problematically, potentiated MD variants can exhibit off-target toxicity. Here, we mine disaggregase sequence space to safely enhance Hsp104 activity via single mutations in nucleotide-binding domain 1 (NBD1) or NBD2. Like MD variants, NBD variants counter TDP-43, FUS, and α-synuclein toxicity and exhibit elevated ATPase and disaggregase activity. Unlike MD variants, non-toxic NBD1 and NBD2 variants emerge that rescue TDP-43, FUS, and α-synuclein toxicity. Potentiating substitutions alter NBD1 residues that contact ATP, ATP-binding residues, or the MD. Mutating the NBD2 protomer interface can also safely ameliorate Hsp104. Thus, we disambiguate allosteric regulation of Hsp104 by several tunable structural contacts, which can be engineered to spawn enhanced therapeutic disaggregases with minimal off-target toxicity

Illusory perceptions of space and time preserve cross-saccadic perceptual continuity

When voluntary saccadic eye movements are made to a silently ticking clock, observers sometimes think that the second hand takes longer than normal to move to its next position. For a short period, the clock appears to have stopped (chronostasis). Here we show that the illusion occurs because the brain extends the percept of the saccadic target backwards in time to just before the onset of the saccade. This occurs every time we move the eyes but it is only perceived when an external time reference alerts us to the phenomenon. The illusion does not seem to depend on the shift of spatial attention that accompanies the saccade. However, if the target is moved unpredictably during the saccade, breaking perception of the target's spatial continuity, then the illusion disappears. We suggest that temporal extension of the target's percept is one of the mechanisms that 'fill in' the perceptual 'gap' during saccadic suppression. The effect is critically linked to perceptual mechanisms that identify a target's spatial stability

Orbital dynamics in ferromagnetic transition metal oxides

We consider a model of strongly correlated $e_g$ electrons interacting by superexchange orbital interactions in the ferromagnetic phase of LaMnO$_3$. It is found that the classical orbital order with alternating occupied $e_g$ orbitals has a full rotational symmetry at orbital degeneracy, and the excitation spectrum derived using the linear spin-wave theory is gapless. The quantum (fluctuation) corrections to the order parameter and to the ground state energy restore the cubic symmetry of the model. By applying a uniaxial pressure orbital degeneracy is lifted in a tetragonal field and one finds an orbital-flop phase with a gap in the excitation spectrum. In two dimensions the classical order is more robust near the orbital degeneracy point and quantum effects are suppressed. The orbital excitation spectra obtained using finite temperature diagonalization of two-dimensional clusters consist of a quasiparticle accompanied by satellite structures. The orbital waves found within the linear spin-wave theory provide an excellent description of the dominant pole of these spectra.Comment: 13 pages, 12 figures, to appear in Phys. Rev.

G2A Signaling Dampens Colitic Inflammation via Production of IFN-γ

Proinflammatory consequences have been described for lysophosphatidylcholine, a lipid product of cellular injury, signaling via the G protein–coupled receptor G2A on myeloid and lymphoid inflammatory cells. This prompted the hypothesis that genetic deletion of G2A would limit intestinal inflammation in a mouse model of colitis induced by dextran sodium sulfate. Surprisingly, G2A2/2 mice exhibited significantly worsened colitis compared with wild-type mice, as demonstrated by disease activity, colon shortening, histology, and elevated IL-6 and IL-5 in colon tissues. Investigation of inflammatory cells recruited to inflamed G2A2/2 colons showed significantly more TNF-a+ and Ly6ChiMHCII2 proinflammatory monocytes and eosinophils than in wild-type colons. Both monocytes and eosinophils were pathogenic as their depletion abolished the excess inflammation in G2A2/2 mice. G2A2/2 mice also had less IFN-g in inflamed colon tissues than wild-type mice. Fewer CD4+ lymphocytes were recruited to inflamed G2A2/2 colons, and fewer colonic lymphocytes produced IFN-g upon ex vivo stimulation. Administration of IFN-g to G2A2/2 mice during dextran sodium sulfate exposure abolished the excess colitic inflammation and reduced colonic IL-5 and eosinophil numbers to levels seen in wild-type mice. Furthermore, IFN-g reduced the numbers of TNF-a+ monocyte and enhanced their maturation from Ly6ChiMHCII2 to Ly6CintMHCII+ . Taken together, the data suggest that G2A signaling serves to dampen intestinal inflammation via the production of IFN-g, which, in turn, enhances monocyte maturation to a less inflammatory program and ultimately reduces eosinophil-induced injury of colonic tissues