Shen, Feng
Cheng, Lan
Douglas, Andrew E.
Riobo, Natalia A.
Smoothened (Smo) is a 7-transmembrane protein essential to the activation of Gli transcription factors (Gli) by hedgehog morphogens. The structure of Smo implies interactions with heterotrimeric G proteins, but the degree to which G proteins participate in the actions of hedgehogs remains controversial. We posit that the G(i) family of G proteins provides to hedgehogs the ability to expand well beyond the bounds of Gli. In this regard, we evaluate here the efficacy of Smo as it relates to the activation of Gi, by comparing Smo with the 5-hydroxytryptamine(1A) (5-HT1A) receptor, a quintessential G(i)-coupled receptor. We find that with use of [S-35]guanosine 5'-(3-O-thio) triphosphate, first, with forms of G(i) endogenous to human embryonic kidney (HEK)-293 cells made to express epitopetagged receptors and, second, with individual forms of G alpha(i) fused to the C terminus of each receptor, Smo is equivalent to the 5-HT1A receptor in the assay as it relates to capacity to activate Gi. This finding is true regardless of subtype of G(i) (e. g., G(i2), G(o), and G(z)) tested. We also find that Smo endogenous to HEK-293 cells, ostensibly through inhibition of adenylyl cyclase, decreases intracellular levels of cAMP. The results indicate that Smo is a receptor that can engage not only Gli but also other more immediate effectors.
Gibbs sampling also known as Glauber dynamics is a popular technique for sampling high dimensional distributions defined on graphs. Of special interest is the behavior of Gibbs sampling on the Erdős–R茅nyi random graph G(n, d/n), where each edge is chosen independently with probability d/n and d is fixed. While the average degree in G(n, d/n) is d(1−o(1)), it contains many nodes of degree of order (log n) / (log log n). The existence of nodes of almost logarithmic degrees implies that for many natural distributions defined on G(n, d/n) such as uniform coloring (with a constant number of colors) or the Ising model at any fixed inverse temperature β, the mixing time of Gibbs sampling is at least n 1+Ω(1 / log log n) with high probability. High degree nodes pose a technical challenge in proving polynomial time mixing of the dynamics for many models including coloring. Almost all known sufficient conditions in terms of number of colors needed for rapid mixing of Gibbs samplers are stated in terms of the maximum degree of the underlying graph. In this work we consider sampling q-colorings and show that for every d < ∞ there exists q(d) < ∞ such that for all q ≥ q(d) the mixing time of the Gibbs sampling on G(n, d/n) is polynomial in n with high probability. Our results are the first polynomial time mixing results proven for the coloring model on G(n, d/n) for d > 1 where the number of colors does not depend on n. They also provide a rare example where one can prove a polynomial time mixing of Gibbs sampler in a situation where the actual mixing time is slower than npolylog(n). In previous work we have shown that similar results hold for the ferromagnetic Ising model. However, the proof for the Ising model crucially relied on monotonicity arguments and the “Weitz tree”, both of which have no counterparts in the coloring setting. Our proof presented here exploits in novel ways the local treelike structure of Erdős–R茅nyi random graphs, block dynamics, spatial decay properties and coupling arguments. Our results give the first polynomial-time algorithm to approximately sample colorings on G(n, d/n) with a constant number of colors. They extend to much more general families of graphs which are sparse in some average sense and to much more general interactions. In particular, they apply to any graph for which there exists an α > 0 such that every vertex v of the graph has a neighborhood N(v) of radius O(log n) in which the induced sub-graph is the union of a tree and at most O(1) edges and where each simple path Γ of length O(log n) satisfies 氓u 脦 G氓v 鹿 uad(u,v) = O(log n){\sum_{u \in \Gamma}\sum_{v \neq u}\alpha^{d(u,v)} = O({\rm log} n)} . The results also generalize to the hard-core model at low fugacity and to general models of soft constraints at high temperatures.
Asymmetric first total synthesis of eudistomidins G, H. and I, tetrahydro-beta-carboline alkaloids from the Okinawan marine tunicate Eudistoma glaucus, has been accomplished with the Bischler-Napieralski reaction and the Noyori catalytic asymmetric hydrogen-transfer reaction. The absolute configurations of eudistomidins G, H, and! were confirmed from comparison of the H-1 and C-13 NMR, and CD spectral data of synthetic and natural eudistomidins G, H, and I, respectively. (C) 2012 Elsevier Ltd. All rights reserved.
Asymmetric first total synthesis of eudistomidins G, H, and I, tetrahydro-β-carboline alkaloids from the Okinawan marine tunicate Eudistoma glaucus, has been accomplished with the Bischler-Napieralski reaction and the Noyori catalytic asymmetric hydrogen-transfer reaction. The absolute configurations of eudistomidins G, H, and I were confirmed from comparison of the 1H and 13C NMR, and CD spectral data of synthetic and natural eudistomidins G, H, and I, respectively.
S Sturm
K Blaum
B Schabinger
A Wagner
W Quint
G Werth
Individual hydrogen- and lithium-like ions with medium nuclear charge Z are confined in a cylindrical triple Penning trap for nearly unlimited time under well-controlled conditions in a small volume in space. We present progress in a project to determine the magnetic moment of the electron bound in Si13+ and Ca19+ and their Li-like counterparts. This serves for testing bound-state quantum electrodynamic calculations. Significant technical improvements will allow for higher precision than in the previous similar experiments on C5+ and O7+.
Let a linear algebraic group G act on an algebraic variety X. Classification of all these actions, in particular birational classification, is of great interest. A complete classification related to Galois cohomologies of the group G was established. Another important question is reducibility, in some sense, of this action to an action of G on an affine variety. It has been shown that if the stabilizer of a typical point under the action of a reductive group G on a variety X is reductive, then X is birationally isomorphic to an affine variety [`(X)] \bar X with stable action of G. In this paper, I show that if a typical orbit of the action of G is quasiaffine, then the variety X is birationally isomorphic to an affine variety [`(X)] \bar X .