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The first total synthesis of (+)-tanzawaic acid B, a natural polyketide bearing a pentadienoic ester and octalin moiety, has been accomplished. The synthetic improvement from previous synthetic conditions facilitated our gram-scale synthesis of the chiral octalin that possesses seven stereogenic centers and that is the core skeleton of almost all of the tanzawaic acid family.

The first total synthesis of (+)-tanzawaic acid B, a natural polyketide bearing a pentadienoic ester and octalin moiety, has been accomplished. The synthetic improvement from previous synthetic conditions facilitated our gram-scale synthesis of the chiral octalin that possesses seven stereogenic centers and that is the core skeleton of almost all of the tanzawaic acid family.

We propose a robust approach to recovering jointly sparse signals in the presence of outliers. The robust recovery task is cast as a convex optimization problem involving a minimax concave loss function (which is weakly convex) and a strongly convex regularizer (which ensures the overall convexity). The use of the nonconvex loss makes the problem difficult to solve directly by the convex optimization methods even with the well-established firm shrinkage. We circumvent this difficulty by reformulating the problem via the Moreau decomposition so that the objective function becomes a sum of convex functions that can be minimized by the primal-dual splitting method. The parameter designs/ranges for the present specific case are derived to ensure the convergence. We demonstrate the remarkable robustness of the proposed approach against outliers by extensive simulations to the application of multi-lead electrocardiogram as well as synthetic data.

We present an efficient mathematical framework based on the linearly-involved Moreau-enhanced-over-subspace (LiMES) model. Two concrete applications are considered: sparse modeling and robust regression. The popular minimax concave (MC) penalty for sparse modeling subtracts, from the $\ell_1$ norm, its Moreau envelope, inducing nearly unbiased estimates and thus yielding remarkable performance enhancements. To extend it to underdetermined linear systems, we propose the projective minimax concave penalty using the projection onto the input subspace, where the Moreau-enhancement effect is restricted to the subspace for preserving the overall convexity. We also present a novel concept of stable outlier-robust regression which distinguishes noise and outlier explicitly. The LiMES model encompasses those two specific examples as well as two other applications: stable principal component pursuit and robust classification. The LiMES function involved in the model is an ``additively nonseparable'' weakly convex function but is defined with the Moreau envelope returning the minimum of a ``separable'' convex function. This mixed nature of separability and nonseparability allows an application of the LiMES model to the underdetermined case with an efficient algorithmic implementation. Two linear/affine operators play key roles in the model: one corresponds to the projection mentioned above and the other takes care of robust regression/classification. A necessary and sufficient condition for convexity of the smooth part of the objective function is studied. Numerical examples show the efficacy of LiMES in applications to sparse modeling and robust regression., Comment: 17 pages, 10 fugures, journal paper

形態: カラー図版あり, Physical characteristics: Original contains color illustrations, Accepted: 2018-04-16, 資料番号: PA1810060000

Most gastrointestinal stromal tumours (GISTs) are caused by constitutively active mutations in Kit tyrosine kinase. The drug imatinib, a specific Kit inhibitor, improves the prognosis of metastatic GIST patients, but these patients become resistant to the drug by acquiring secondary mutations in the Kit kinase domain. We recently reported that a Kit mutant causes oncogenic signals only on the Golgi apparatus in GISTs. In this study, we show that in GIST, 2-methylcoprophilinamide (M-COPA, also known as "AMF-26"), an inhibitor of biosynthetic protein trafficking from the endoplasmic reticulum (ER) to the Golgi, suppresses Kit autophosphorylation at Y703/Y721/Y730/Y936, resulting in blockade of oncogenic signalling. Results of our M-COPA treatment assay show that Kit Y703/Y730/Y936 in the ER are dephosphorylated by protein tyrosine phosphatases (PTPs), thus the ER-retained Kit is unable to activate downstream molecules. ER-localized Kit Y721 is not phosphorylated, but not due to PTPs. Importantly, M-COPA can inhibit the activation of the Kit kinase domain mutant, resulting in suppression of imatinib-resistant GIST proliferation. Our study demonstrates that Kit autophosphorylation is spatio-temporally regulated and may offer a new strategy for treating imatinib-resistant GISTs.

In this study, we evaluate the influence of fault parameters on the ground motion characteristics and building response characteristics in the near-fault region, in order to develop the seismic design load for the Uemachi fault. We simulate ground motions in near-fault region changing several fault parameters using 3D-FDM. As results, the following conclusions are obtained. 1)Background of fault have little effect to near-fault pulse-like ground motion in the period range T>1.25s. 2)Peak ground velocity is affected by asperity size, rupture velocity, rise time, upper depth of asperity. 3)The pulse period on sedimentary layers depends on that of the bedrock and predominant periods of sedimentary layers. 4)The region where we should consider the influence of pulselike ground motions depends on the ratio of natural periods of buildings and pulse periods of the ground motion.

In recent inland shallow earthquakes, pulse-like ground motions have been observed which subsequently caused severe damage to buildings. However, the response of buildings to pulse-like ground motions has not been sufficiently characterized yet. In this study, we investigate the effect of pulse-like ground motions on the design of structures and define the maximum response of an undamped singledegree-of-freedom (SDOF) system subjected to a sinusoidal pulse as a function of natural period. In addition, design response spectra for pulse-like ground motions are proposed.

It is suggested that the pulse-like ground motions, in the near-fault region, have great impact on the building seismic design. However, the theoretical study on the building response to the pulse-like ground motions input is not sufficiently clarified yet. In this study, the time at maximum response is theoretically evaluated as important factor. Based on that, the theoretical solutions of response spectra, with single-degree-of-freedom system subject to the sinusoidal pulse input, are performed. In addition, we suggested the damping-modification-factor, in accordance with the time at maximum response and the pulse wave period - building period relations.

Post-processing functions are used to reduce the imperfectness of physical random number generators. At FSE '07, Dichtl considered the case where the physical random number generator outputs independent bits that have a constant bias, and the post-processing function has fixed input and output lengths. In this paper, we first present a number of bounds on deg(n,m), which is a measure of the reduction of biases with n-bit input and m-bit output post-processing functions. We next show the exact values of deg(n,m) for a large class of (n,m) such that 1 ≤ m ≤ n ≤ 16, by using the bounds on deg(n,m) and a computer simulation. We finally discuss how we have derived these numerical values.

Techniques for the production of three kinds of 192Ir sources, i.e. hairpin, single-pin and seed, for brachytherapy were developed in Japan Atomic Energy Research Institute. Platinumiridium, alloy wire sheathed with platinum tube in advance were irradiated by the JRR-2 or JRR-3 reactor. The platinum tube cuts off beta-rays so as to minimize unnecessary radiation exposure to patients. Irradiation conditions were determined to obtain the radioactivity of 0.74 GBq (20 mCi) for a hairpin, 0.37 GBq (10 mCi) for a single-pin and 0.37 X 10(-1) GBq (1 mCi) for a seed, respectively, at the end of irradiation. Fluctuation in the linear distribution of the radioactivity along the hairpin source or the single-pin source was small enough on the viewpoint of its application. No significant impurity or surface contamination was observed in the source produced with pre-encapsulation. Seed targets were loaded in a polyethylene tube so as to be suitable for the new treatment technique of tumor. Irradiation of seed targets, packed alternately with nylon spacers in a polyethylene tube, was found to be satisfactory for preparing ribbon sources.