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Heparan sulfate (HS) glycosaminoglycans are widely expressed on the mammalian cell surfaces and extracellular matrices and play important roles in a variety of cell functions. Studies on the structure–activity relationships of HS have long been hampered by the challenges in obtaining chemically defined HS structures with unique sulfation patterns. Here, we report a new approach to HS glycomimetics based on iterative assembly of clickable disaccharide building blocks that mimic the disaccharide repeating units of native HS. Variably sulfated clickable disaccharides were facilely assembled into a library of mass spec-sequenceable HS-mimetic oligomers with defined sulfation patterns by solution-phase iterative syntheses. Microarray and surface plasmon resonance (SPR) binding assays corroborated molecular dynamics (MD) simulations and confirmed that these HS-mimetic oligomers bind protein fibroblast growth factor 2 (FGF2) in a sulfation-dependent manner consistent with that of the native HS. This work established a general approach to HS glycomimetics that can potentially serve as alternatives to native HS in both fundamental research and disease models. 

In this article we show that the Euler equations, when linearized around a low frequency perturbation to Couette flow, exhibit norm inflation in Gevrey-type spaces as time tends to infinity. Thus, echo chains are shown to be a (secondary) linear instability mechanism. Furthermore, we develop a more precise analysis of cancellations in the resonance mechanism, which yields a modified exponent in the high frequency regime. This allows us, in addition, to remove a logarithmic constraint on the perturbations present in prior works by Bedrossian, Deng and Masmoudi, and to construct solutions which are initially in a Gevrey class for which the velocity asymptotically converges in Sobolev regularity but diverges in Gevrey regularity.

 

Abstract A fundamental question in wave turbulence theory is to understand how the wave kinetic equation describes the long-time dynamics of its associated nonlinear dispersive equation. Formal derivations in the physics literature, dating back to the work of Peierls in 1928, suggest that such a kinetic description should hold (for well-prepared random data) at a large kinetic time scale $T_{\mathrm {kin}} \gg 1$ and in a limiting regime where the size L of the domain goes to infinity and the strength $\alpha $ of the nonlinearity goes to $0$ (weak nonlinearity). For the cubic nonlinear Schrödinger equation, $T_{\mathrm {kin}}=O\left (\alpha ^{-2}\right )$ and $\alpha $ is related to the conserved mass $\lambda $ of the solution via $\alpha =\lambda ^2 L^{-d}$ . In this paper, we study the rigorous justification of this monumental statement and show that the answer seems to depend on the particular scaling law in which the $(\alpha , L)$ limit is taken, in a spirit similar to how the Boltzmann–Grad scaling law is imposed in the derivation of Boltzmann’s equation. In particular, there appear to be two favourable scaling laws: when $\alpha $ approaches $0$ like $L^{-\varepsilon +}$ or like $L^{-1-\frac {\varepsilon }{2}+}$ (for arbitrary small $\varepsilon $ ), we exhibit the wave kinetic equation up to time scales $O(T_{\mathrm {kin}}L^{-\varepsilon })$ , by showing that the relevant Feynman-diagram expansions converge absolutely (as a sum over paired trees). For the other scaling laws, we justify the onset of the kinetic description at time scales $T_*\ll T_{\mathrm {kin}}$ and identify specific interactions that become very large for times beyond $T_*$ . In particular, the relevant tree expansion diverges absolutely there. In light of those interactions, extending the kinetic description beyond $T_*$ toward $T_{\mathrm {kin}}$ for such scaling laws seems to require new methods and ideas.