高島教授の景気政策 : 『租税・公債・通貨新論』

新刊批

Angiotensin II Receptor Subtypes and Cardiac Function

All the components of the renin-angiotensin system have been identified in the heart including the angiotensin II receptor subtypes AT1 and AT2 In the normal human heart, there is a decreasing receptor density from the right atrium to the left ventricle. In right atrial membranes prepared from pathological hearts, the percentage of AT1 receptor decreases with the severity of cardiac dysfunction whereas that of AT2 receptor increases. Treatment of hypertrophic rats with AT1 receptor antagonists inhibits cardiac hypertrophy and reverses the increase receptor density, indicating involvement of this Ang II receptor subtype. The role of the AT2 receptor is still largely unknown but it may be involved in cell growth and proliferation. The cloning of both AT1 and AT2 receptors as well as the availability of potent and selective antagonists will help us to understand better the functional role of Angiotensin II in cardiovascular disorder

Hybrid Newton-type method for a class of semismooth equations

In this paper, we present a hybrid method for the solution of a class of composite semismooth equations encountered frequently in applications. The method is obtained by combining a generalized finite-difference Newton method to an inexpensive direct search method. We prove that, under standard assumptions, the method is globally convergent with a local rate of convergence which is superlinear or quadratic. We report also several numerical results obtained applying the method to suitable reformulations of well-known nonlinear complementarity problem

The Blue Straggler population in the globular cluster M53 (NGC5024): a combined HST, LBT, CFHT study

We used a proper combination of multiband high-resolution and wide field multi-wavelength observations collected at three different telescopes (HST, LBT and CFHT) to probe Blue Straggler Star (BSS) populations in the globular cluster M53. Almost 200 BSS have been identified over the entire cluster extension. The radial distribution of these stars has been found to be bimodal (similarly to that of several other clusters) with a prominent dip at ~60'' (~2 r_c) from the cluster center. This value turns out to be a factor of two smaller than the radius of avoidance (r_avoid, the radius within which all the stars of ~1.2 M_sun have sunk to the core because of dynamical friction effects in an Hubble time). While in most of the clusters with a bimodal BSS radial distribution, r_avoid has been found to be located in the region of the observed minimum, this is the second case (after NGC6388) where this discrepancy is noted. This evidence suggests that in a few clusters the dynamical friction seems to be somehow less efficient than expected. We have also used this data base to construct the radial star density profile of the cluster: this is the most extended and accurate radial profile ever published for this cluster, including detailed star counts in the very inner region. The star density profile is reproduced by a standard King Model with an extended core (~25'') and a modest value of the concentration parameter (c=1.58). A deviation from the model is noted in the most external region of the cluster (at r>6.5' from the center). This feature needs to be further investigated in order to address the possible presence of a tidal tail in this cluster.Comment: 25 pages, 9 figures, accepted for publication on Ap

Electronic sculpting of ligand-GPCR subtype selectivity:the case of angiotensin II

GPCR subtypes possess distinct functional and pharmacological profiles, and thus development of subtype-selective ligands has immense therapeutic potential. This is especially the case for the angiotensin receptor subtypes AT1R and AT2R, where a functional negative control has been described and AT2R activation highlighted as an important cancer drug target. We describe a strategy to fine-tune ligand selectivity for the AT2R/AT1R subtypes through electronic control of ligand aromatic-prolyl interactions. Through this strategy an AT2R high affinity (<i>K</i>_i = 3 nM) agonist analogue that exerted 18,000-fold higher selectivity for AT2R versus AT1R was obtained. We show that this compound is a negative regulator of AT1R signaling since it is able to inhibit MCF-7 breast carcinoma cellular proliferation in the low nanomolar range

Wide and deep near-UV (360nm) galaxy counts and the extragalactic background light with the Large Binocular Camera

Deep multicolour surveys are the main tool to explore the formation and evolution of the faint galaxies which are beyond the spectroscopic limit with the present technology. The photometric properties of these faint galaxies are usually compared with current renditions of semianalytical models to provide constraints on the fundamental physical processes involved in galaxy formation and evolution, namely the mass assembly and the star formation. Galaxy counts over large sky areas in the near-UV band are important because they are difficult to obtain given the low efficiency of near-UV instrumentation, even at 8m class telescopes. A large instrumental field of view helps in minimizing the biases due to the cosmic variance. We have obtained deep images in the 360nm U band provided by the blue channel of the Large Binocular Camera at the prime focus of the Large Binocular Telescope. We have derived over an area of ~0.4 sq. deg. the galaxy number counts down to U=27 in the Vega system (corresponding to U=27.86 in the AB system) at a completeness level of 30% reaching the faintest current limit for this wavelength and sky area. The shape of the galaxy counts in the U band can be described by a double power-law, the bright side being consistent with the shape of shallower surveys of comparable or greater areas. The slope bends over significantly at U>23.5 ensuring the convergence of the contribution by star forming galaxies to the EBL in the near-UV band to a value which is more than 70% of the most recent upper limits derived for this band. We have jointly compared our near-UV and K band counts collected from the literature with few selected hierarchical CDM models emphasizing critical issues in the physical description of the galaxy formation and evolution.Comment: Accepted for publication in A&A. Uses aa.cls, 9 pages, 4 figures. Citations update

Small Molecules with Similar Structures Exhibit Agonist, Neutral Antagonist or Inverse Agonist Activity toward Angiotensin II Type 1 Receptor

Small differences in the chemical structures of ligands can be responsible for agonism, neutral antagonism or inverse agonism toward a G-protein-coupled receptor (GPCR). Although each ligand may stabilize the receptor conformation in a different way, little is known about the precise conformational differences. We synthesized the angiotensin II type 1 receptor blocker (ARB) olmesartan, R239470 and R794847, which induced inverse agonism, antagonism and agonism, respectively, and then investigated the ligand-specific changes in the receptor conformation with respect to stabilization around transmembrane (TM)3. The results of substituted cysteine accessibility mapping studies support the novel concept that ligand-induced changes in the conformation of TM3 play a role in stabilizing GPCR. Although the agonist-, neutral antagonist and inverse agonist-binding sites in the AT1 receptor are similar, each ligand induced specific conformational changes in TM3. In addition, all of the experimental data were obtained with functional receptors in a native membrane environment (in situ)