The application of Wagner theory to idealised two-dimensional inertially dominated droplet impacts is extended to incorporate non-flat substrates that are continuous functions of distance along the surface. Mixed boundary value problems are solved for the displacement and velocity potentials for both a single impact with an asymmetric substrate and a pair of impacts. The droplet free-surface position and the pressure on the wetted surface are calculated, along with the load and moment on the substrate. For double impacts a void may be formed between the substrate and the droplet free surface. Double impacts are compared with a single asymmetric impact with one half of the equivalent substrate geometry to assess how the free surface, loads and moments are affected by the separation between impact sites. Interactions between symmetric double impacts enhance the liquid penetration between the impact sites and increase the load and moment on each substrate element compared with the corresponding single impact. The time taken for the void between droplet and substrate to become saturated is found assuming the gas pressure build-up and capillary forces are negligible, giving an estimate for the transition time from a partially wetted to a fully wetted surface close to the initial impact site. After the void becomes saturated, the subsequent free-surface evolution is determined and the effect of periodic roughness on the contact line evolution is calculated. For surfaces formed of an array of asperities, secondary impacts which both traps further voids and completely wet the surface are found.

ABSTRACT IMPACT: This study provides insight into how MED2 impacts the immune cells surrounding glioblastoma that help it to grow and spread; having a more complete understanding of how MED2 works will help us better develop therapies that may one day enter the clinic to improve patient outcomes in glioblastoma. OBJECTIVES/GOALS: The purpose of this study was to determine whether the phosphorylation state of the MED2 peptide impacts its biological activity in GBM and macrophages. MED2 variants include the phosphorylatable wild-type (MED2), pseudo-phosphorylated (MED2-PP), non-phosphorylatable (MED2-NP) and control length (CTL2) peptides. METHODS/STUDY POPULATION: MED2, MED2-NP, MED2-PP, and CTL2 were screened against a panel of molecularly characterized glioblastoma patient derived xenografts and IL4/13 stimulated M2-like THP-1 macrophages. The luminescent cell viability assay, CellTiter-Glo, was used to determine viability. RESULTS/ANTICIPATED RESULTS: The proneural lines XD456 and X1441 were highly sensitive to 5 µM MED2 and 5 µM MED2NP compared to 5 µM MED2PP (p<0.001). There was no statistically significant difference between untreated, 5 µM CTL2, and 5 µM MED2PP groups or between the MED2NP and MED2 treated groups. M2-like THP-1 macrophages were highly sensitive to 10 µM MED2NP compared to 10 µM CTL2 (p<0.01) and 10 µM MED2PP (p<0.01) No statistically significant difference was observed between untreated, 10 µM MED2, 10 µM MED2PP, and 10 µM CTL2 groups. DISCUSSION/SIGNIFICANCE OF FINDINGS: The phosphorylation state of MED2 determines its toxicity. When MED2 is phosphorylated, it is nontoxic to GBM or M2-like macrophages. The non-phosphorylatable version is toxic to both GBM and M2-like macrophages. The wild-type peptide is toxic to GBM but not M2-like macrophages, suggesting that MED2 may be phosphorylated in M2-like macrophages.

The use of spanwise wall oscillations to attenuate the growth of laminar streaks within the incompressible Blasius boundary layer is investigated. As in the case of the flow above a stationary flat plate, studied by Leib et al. (J. Fluid Mech., vol. 380, 1999, pp. 169–203), free-stream convected gusts interact with the boundary layer to drive the streak growth. Spanwise wall oscillations can either reduce or increase the total energy of the laminar streaks, depending upon the wall oscillation amplitude and frequency, as well as the free-stream gust properties. Reductions in streak energies of up to 90 % are obtained, indicating that spanwise wall oscillations are an effective technique for attenuating the laminar streak growth. Therefore they may suppress secondary boundary-layer instabilities and delay transition. The laminar boundary-layer base flow matches the Blasius profile in the streamwise and wall-normal directions, while in the spanwise direction a generalized version of the classical Stokes layer profile (generated by a wall oscillating beneath a quiescent fluid) occurs, which evolves downstream due to non-parallel flow effects. Via a Wentzel–Kramers–Brillouin–Jeffreys analysis, this generalized Stokes layer is shown to approach the classical Stokes layer in the limit of large downstream distances or high-frequency plate oscillations. The laminar streaks forced by the generalized and the classical Stokes flows differ significantly, which implies that the choice of the spanwise base flow may affect the secondary instability and transition in this flow. The analysis also proves that the use of the classical Stokes layer as spanwise base flow, as employed by Hack & Zaki (Phys. Fluids. vol. 24 (3), 2012, 034101), is inappropriate.

The role played by gas compressibility in gas-cushioned liquid–solid impacts is investigated within a viscous gas and inviscid liquid regime. A full analysis of the energy conservation in the gas is conducted for the first time, which indicates that both thermal diffusion across the gas film and viscous dissipation play an important role in gas cushioning once gas compression becomes significant. Consequently existing models of gas compressibility based on either an isothermal or an adiabatic equation of state for the gas do not fully reflect the physics associated with this phenomenon. Models incorporating thermal diffusion and viscous dissipation are presented, which are appropriate for length scales consistent with droplet impacts, and for larger scale liquid–solid impacts. The evolution of the free surface is calculated alongside the corresponding pressure, temperature and density profiles. These profiles indicate that a pocket of gas can become trapped during an impact. Differences between the new model and older models based on isothermal and adiabatic equations of state are discussed, along with predictions of the size of the trapped gas pocket.

Many journalists and politicians believe that during the Bush administration, a majority of Americans supported torture if they were assured that it would prevent a terrorist attack. As Mark Danner wrote in the April 2009 New York Review of Books, “Polls tend to show that a majority of Americans are willing to support torture only when they are assured that it will ‘thwart a terrorist attack.’” This view was repeated frequently in both left- and right-leaning articles and blogs, as well as in European papers (Sharrock 2008; Judd 2008; Koppelman 2009; Liberation 2008). There was a consensus, in other words, that throughout the years of the Bush administration, public opinion surveys tended to show a pro-torture American majority.