Rationally Designed Semisynthetic Natural Product Analogues for Stabilization of 14‐3‐3 Protein–Protein Interactions

The natural product family of fusicoccanes are stabilizers of 14‐3‐3 mediated protein–protein interactions (PPIs), some of which possess antitumor activity. In this study, the first use of molecular dynamics (MD) to rationally design PPI stabilizers with increased potency is presented. Synthesis of a focused library, with subsequent characterization by fluorescence polarization, mutational studies, and X‐ray crystallography confirmed the power of the MD‐based design approach, revealing the potential for an additional hydrogen bond with the 14‐3‐3 protein to lead to significantly increased potency. Additionally, these compounds exert their action in a cellular environment with increased potency. The newly found polar interaction could provide an anchoring point for new small‐molecule PPI stabilizers. These results facilitate the development of fusicoccanes towards drugs or tool compounds, as well as allowing the study of the fundamental principles behind PPI stabilization.     

High-speed separation system of randomly suspended single living cells by laser trap and dielectrophoresis

We developed a new system for random separation of a single microorganism, such as a living cell and a microbe, in the microfluidic device under the microscope by integrating the laser-trapping force and dielectrophoretic (DEP) force. An arbitrarily selected single microbe could be isolated in a microchannel, despite the presence of a large number of microbes in solution. Once the target microbe is trapped at the focal point of the laser, we can easily realize exclusion of excess microbes around the target by controlling the electric field, while keeping the target trapped by the laser at the focal point. To realize an efficient separation system, we proposed a new separation cell and produced it by microfabrication. Flow speed in the microchannel is adjusted and balanced to realize high-speed and high-purity extraction of the target. Some preliminary experiments are conducted to show the effectiveness. The target is trapped by the laser, transported, and is taken out from the extraction port. Total separation time is less than 20 s. Our method is extremely useful in the pure cultivation of the cell and will be a promising method for biologists in screening useful microbes.     

Amphiphilic block and statistical copolymers with pendant glucose residues: Controlled synthesis by living cationic polymerization and the effect of copolymer architecture on their properties

Amphiphilic block and statistical copolymers of vinyl ethers (VEs) with pendant glucose residues were synthesized by the living cationic polymerization of isobutyl VE (IBVE) and a VE carrying 1,2:5,6‐di‐O‐isopropylidene‐D ‐glucose (IpGlcVE), followed by deprotection. The block copolymer was prepared by a two‐stage sequential block copolymerization, whereas the statistical copolymer was obtained by the copolymerization of a mixture of the two monomers. The monomer reactivity ratios estimated with the statistical copolymerization were r₁ (IBVE) = 1.65 and r₂ (IpGlcVE) = 1.15. The obtained statistical copolymers were nearly uniform with the comonomer composition along the main chain. Both the block and statistical copolymers had narrow molecular weight distributions (weight‐average molecular weight/number‐average molecular weight ∼ 1.1). Gel permeation chromatography, static light scattering, and spin–lattice relaxation time measurements in a selective solvent revealed that the block copolymer formed multimolecular micelles, possibly with a hydrophobic poly(IBVE) core and a glucose‐carrying poly(VE) shell, whereas the statistical copolymer with nearly the same molecular weight and segment composition was molecularly dispersed in solution. The surface properties of the solvent‐cast films of the block and statistical copolymer were also investigated with the contact‐angle measurement. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 459–467, 2001     

Dense orbits of automorphisms and compactness of groups

It is proved, by using topological properties, that when a group automorphism of a locally compact totally disconnected group is ergodic under the Haar measure, the group is compact. The result is an answer for Halmos's question that has remained open for the totally disconnected case.     

On progressively truncated maximum likelihood estimators

Summary The basic regularity conditions pertaining to the asymptotic theory of progressively truncated likelihood functions and maximum likelihood estimators are considered, and the uniform strong consistency and weak convergence of progressively truncated maximum likelihood estimators are studied systematically. Work done during the first author's visit (as a visiting scholar) to the University of North Carolina at Chapel Hill, supported by the Ministry of Education of the Japanese Government. Work supported by the (U.S.) National Heart, Lung and Blood Institute, Contact NIH-NHLBI-F1-2243-L.     

Convergence Properties of the Regularized Newton Method for the Unconstrained Nonconvex Optimization

The regularized Newton method (RNM) is one of the efficient solution methods for the unconstrained convex optimization. It is well-known that the RNM has good convergence properties as compared to the steepest descent method and the pure Newton’s method. For example, Li, Fukushima, Qi and Yamashita showed that the RNM has a quadratic rate of convergence under the local error bound condition. Recently, Polyak showed that the global complexity bound of the RNM, which is the first iteration k such that ‖∇ f(x _k )‖≤ε, is O(ε ⁻⁴), where f is the objective function and ε is a given positive constant. In this paper, we consider a RNM extended to the unconstrained “nonconvex” optimization. We show that the extended RNM (E-RNM) has the following properties. (a) The E-RNM has a global convergence property under appropriate conditions. (b) The global complexity bound of the E-RNM is O(ε ⁻²) if ∇ ² f is Lipschitz continuous on a certain compact set. (c) The E-RNM has a superlinear rate of convergence under the local error bound condition.     

A large deviation principle for (r,p)-capacities on the Wiener space

Summary We formulate and prove a large deviation principle for the (r, p)-capacity on an abstract Wiener space. As an application, we obtain a sharpening of Strassen's law of the iterated logarithm in terms of the capacity.     

Complete Enumeration of Small Realizable Oriented Matroids

Enumeration of all combinatorial types of point configurations and polytopes is a fundamental problem in combinatorial geometry. Although many studies have been done, most of them are for 2-dimensional and non-degenerate cases. Finschi and Fukuda (Discrete Comput Geom 27:117–136, 2002) published the first database of oriented matroids including degenerate (i.e., non-uniform) ones and of higher ranks. In this paper, we investigate algorithmic ways to classify them in terms of realizability, although the underlying decision problem of realizability checking is NP-hard. As an application, we determine all possible combinatorial types (including degenerate ones) of 3-dimensional configurations of 8 points, 2-dimensional configurations of 9 points, and 5-dimensional configurations of 9 points. We also determine all possible combinatorial types of 5-polytopes with nine vertices.     

Proton acceleration to 40 MeV using a high intensity, high contrast optical parametric chirped-pulse amplification/Ti:sapphire hybrid laser system

Using a high-contrast (10(10):1) and high-intensity (10(21) W/cm(2)) laser pulse with the duration of 40 fs from an optical parametric chirped-pulse amplification/Ti:sapphire laser, a 40 MeV proton bunch is obtained, which is a record for laser pulse with energy less than 10 J. The efficiency for generation of protons with kinetic energy above 15 MeV is 0.1%.     

Electronic structure of BaTiO3 using resonant X-ray emission spectroscopy at the Ba-L3 and Ti-K absorption edges

We have studied the electronic properties of the ferroelectric barium titanate BaTiO₃ using two complementary bulk-sensitive spectroscopic probes, resonant X-ray emission spectroscopy (RXES) and X-ray absorption spectroscopy in the partial fluorescence mode (PFY-XAS) at the Ba-L₃ and Ti-K absorption edges. Contrary to a previous study, we found no fine structure in the pre-edge area of the PFY-XAS spectrum at the Ba-L₃ edge, and no temperature-induced spectral change was observed between room temperature and 150 °C. This result is not supportive of the possible presence of the displacement around Ba²⁺ at the Curie temperature. RXES spectra were measured at the Ti-K edge for BaTiO₃, along with SrTiO₃ and La-doped metallic SrTiO₃. The photon energy of the emission peak is found to be nearly constant throughout the absorption edge for all three compounds. We deduce the Ti 3d states to have a delocalized character, in contrast with the Ba 5d states, a property which is consistent with the proposed scenario of the formation of electric dipoles in BaTiO₃.