On the Use of Matrix-Free Shift-Invert Strategies For Global Flow Instability Analysis

A novel time-stepping shift-invert algorithm for linear stability analysis of laminar flows in complex geometries is presented. This method, based on a Krylov subspace iteration, enables the solution of complex non-symmetric eigenvalue problems in a matrix-free framework. Validations and comparisons to the classical exponential method have been performed in three different cases: (i) stenotic flow, (ii) backward-facing step and (iii) lid-driven swirling flow. Results show that this new approach speeds up the required Krylov subspace iterations and has the capability of converging to specific parts of the global spectrum. It is shown that, although the exponential method remains the method of choice if leading eigenvalues are sought, the performance of the present method could be dramatically improved with the use of a preconditioner. In addition, as opposed to other methods, this strategy can be directly applied to any time-stepper, regardless of the temporal or spatial discretization of the latter.

Global Stability Analysis of a Compressible Turbulent Flow around a High-Lift Configuration

The purpose of this work is to analyze a complex high lift configuration for which significant regions of separated flow are present. Current state of the art methods have some diffculty to predict the origin and the progression of this separated flow when increasing the angle of attack. The mechanisms responsible for the maximum lift limit on multi-element wing con?gurations are not clear; this stability analysis could help to understand the physics behind the phenomenon and to find a relation between the flow separation and the instability onset. The methodology presented herein consists in the computation of a steady base flow solution based on a finite volume discretization and a proposal of the solution for a generalized eigenvalue problem corresponding to the perturbed and linearized problem. The eigenvalue problem has been solved with the Arnoldi iterative method, one of the Krylov subspace projection methods. The described methodology was applied to the NACA0012 test case in subsonic and in transonic conditions and, finally, for the first time to the authors knowledge, on an industrial multi-component geometry, such as the A310 airfoil, in order to identify low frequency instabilities related to the separation. One important conclusion is that for all the analyzed geometries, one unstable mode related to flow separation appears for an angle of attack greater than the one correspondent to the maximum lift coe?cient condition. Finally, an adjoint study was carried out in order to evaluate the receptivity and the structural sensitivity of the geometries, giving an indication of the domain region that could be modified resulting in the biggest change of the flowfield.

Transverse galloping at low Reynolds numbers

The possibility of transverse galloping of a square cylinder at low Reynolds numbers (Re≤200Re≤200, so that the flow is presumably laminar) is analysed. Transverse galloping is here considered as a one-degree-of-freedom oscillator subjected to fluid forces, which are described by using the quasi-steady hypothesis (time-averaged data are extracted from previous numerical simulations). Approximate solutions are obtained by means of the method of Krylov-Bogoliubov, with two major conclusions: (i) a square cylinder cannot gallop below a Reynolds number of 159 and (ii) in the range 159≤Re≤200159≤Re≤200 the response exhibits no hysteresis.

A general method to design dominant negatives to B-HLHZip proteins that abolish DNA binding

We describe a method to design dominant-negative proteins (D-N) to the basic helix–loop–helix–leucine zipper (B-HLHZip) family of sequence-specific DNA binding transcription factors. The D-Ns specifically heterodimerize with the B-HLHZip dimerization domain of the transcription factors and abolish DNA binding in an equimolar competition. Thermal denaturation studies indicate that a heterodimer between a Myc B-HLHZip domain and a D-N consisting of a 12-amino acid sequence appended onto the Max dimerization domain (A-Max) is −6.3 kcal⋅mol−1 more stable than the Myc:Max heterodimer. One molar equivalent of A-Max can totally abolish the DNA binding activity of a Myc:Max heterodimer. This acidic extension also has been appended onto the dimerization domain of the B-HLHZip protein Mitf, a member of the transcription factor enhancer binding subfamily, to produce A-Mitf. The heterodimer between A-Mitf and the B-HLHZip domain of Mitf is −3.7 kcal⋅mol−1 more stable than the Mitf homodimer. Cell culture studies show that A-Mitf can inhibit Mitf-dependent transactivation both in acidic extension and in a dimerization-dependent manner. A-Max can inhibit Myc-dependent foci formation twice as well as the Max dimerization domain (HLHZip). This strategy of producing D-Ns may be applicable to other B-HLHZip or B-HLH proteins because it provides a method to inhibit the DNA binding of these transcription factors in a dimerization-specific manner.

Hsp90 Is Required for Pheromone Signaling in Yeast

The heat-shock protein 90 (Hsp90) is a cytosolic molecular chaperone that is highly abundant even at normal temperature. Specific functions for Hsp90 have been proposed based on the characterization of its interactions with certain transcription factors and kinases including Raf in vertebrates and flies. We therefore decided to address the role of Hsp90 for MAP kinase pathways in the budding yeast, an organism amenable to both genetic and biochemical analyses. We found that both basal and induced activities of the pheromone-signaling pathway depend on Hsp90. Signaling is defective in strains expressing low levels or point mutants of yeast Hsp90 (Hsp82), or human Hsp90β instead of the wild-type protein. Ste11, a yeast equivalent of Raf, forms complexes with wild-type Hsp90 and depends on Hsp90 function for accumulation. For budding yeast, Ste11 represents the first identified endogenous “substrate” of Hsp90. Moreover, Hsp90 functions in steroid receptor and pheromone signaling can be genetically separated as the Hsp82 point mutant T525I and the human Hsp90β are specifically defective for the former and the latter, respectively. These findings further corroborate the view that molecular chaperones must also be considered as transient or stable components of signal transduction pathways.

Heat shock protein hsp90 regulates dioxin receptor function in vivo.

The dioxin (aryl hydrocarbon) receptor is a ligand-dependent basic helix-loop-helix (bHLH) factor that binds to xenobiotic response elements of target promoters upon heterodimerization with the bHLH partner factor Arnt. Here we have replaced the bHLH motif of the dioxin receptor with a heterologous DNA-binding domain to create fusion proteins that mediate ligand-dependent transcriptional enhancement in yeast (Saccharomyces cerevisiae). Previously, our experiments indicated that the ligand-free dioxin receptor is stably associated with the 90-kDa heat shock protein, hsp90. To investigate the role of hsp90 in dioxin signaling we have studied receptor function in a yeast strain where hsp90 expression can be down-regulated to about 5% relative to wild-type levels. At low levels of hsp90, ligand-dependent activation of the chimeric dioxin receptor construct was almost completely inhibited, whereas the activity of a similar chimeric construct containing the structurally related Arnt factor was not affected. Moreover, a chimeric dioxin receptor construct lacking the central ligand- and hsp90-binding region of the receptor showed constitutive transcriptional activity in yeast that was not impaired upon down-regulation of hsp90 expression levels. Thus, these data suggest that hsp90 is a critical determinant of conditional regulation of dioxin receptor function in vivo via the ligand-binding domain.

Fostering Change: Toward Understanding, Valuing, and Informing the Therapeutic Role of Foster Parents

Foster parents have the potential to effect lasting therapeutic change through their role with the children they temporarily foster. Therapists working with foster parents can understand, support, and inform foster parents in their role based on a commonality that exists between the roles of therapists and foster parents. Similarities at different stages of both the therapeutic and foster parenting relationships are addressed, as well as the use of these relationships in a therapeutic manner. Advantages (for foster parents, foster children, therapists, and the foster care system) of articulating the foster parenting relationship through the lens of the therapeutic relationship are also discussed. Future research into the experience of foster parents in their role will be essential in creating an effective and sustainable system of care for vulnerable children.

Phase relationships between orbital forcing and the composition of air trapped in Antarctic ice cores

Orbital tuning is central for ice core chronologies beyond annual layer counting, available back to 60 ka (i.e. thousands of years before 1950) for Greenland ice cores. While several complementary orbital tuning tools have recently been developed using δ¹⁸Oatm, δO₂⁄N₂ and air content with different orbital targets, quantifying their uncertainties remains a challenge. Indeed, the exact processes linking variations of these parameters, measured in the air trapped in ice, to their orbital targets are not yet fully understood. Here, we provide new series of δO₂∕N₂ and δ¹⁸Oatm data encompassing Marine Isotopic Stage (MIS) 5 (between 100 and 160 ka) and the oldest part (340–800 ka) of the East Antarctic EPICA Dome C (EDC) ice core. For the first time, the measurements over MIS 5 allow an inter-comparison of δO₂∕N₂ and δ¹⁸Oatm records from three East Antarctic ice core sites (EDC, Vostok and Dome F). This comparison highlights some site-specific δO₂∕N₂ variations. Such an observation, the evidence of a 100 ka periodicity in the δO₂∕N₂ signal and the difficulty to identify extrema and mid-slopes in δO2∕N2 increase the uncertainty associated with the use of δO₂∕N₂ as an orbital tuning tool, now calculated to be 3–4 ka. When combining records of δ¹⁸Oatm and δO₂∕N₂ from Vostok and EDC, we find a loss of orbital signature for these two parameters during periods of minimum eccentricity (∼ 400 ka, ∼ 720–800 ka). Our data set reveals a time-varying offset between δO₂∕N₂ and δ¹⁸Oatm records over the last 800 ka that we interpret as variations in the lagged response of δ¹⁸Oatm to precession. The largest offsets are identified during Terminations II, MIS 8 and MIS 16, corresponding to periods of destabilization of the Northern polar ice sheets. We therefore suggest that the occurrence of Heinrich–like events influences the response of δ¹⁸Oatm to precession.

Mineralogical composition of the upper 300m of Hole 302-M0002A

During the Arctic Coring Expedition (ACEX), a 428-m-thick sequence of Upper Cretaceous to Quaternary sediments was penetrated. The mineralogical composition of the upper 300 m of this sequence is presented here for the first time. Heavy and clay mineral associations indicate a major and consistent shift in provenance, from the Barents-Kara - western Laptev Sea region, characterized by presence of common clinopyroxene, to the eastern Laptev-East Siberian seas in the upper part of the section, characterized by common hornblende (amphibole). Sea ice originating from the latter source region must have survived at least one summer melt cycle in order to reach the ACEX drill site, if considering modern sea ice trajectories and velocities. This shift in mineral assemblages probably represents the onset of a perennial sea ice cover in the Arctic Ocean, which occurred at about 13 Ma, thus suggesting a coeval freeze in the Arctic and Antarctic regions.