Computational Analysis Reveals a Critical Point Mutation in the N-Terminal Region of the Signaling Lymphocytic Activation Molecule Responsible for the Cross-Species Infection with Canine Distemper Virus

Infection of hosts by morbilliviruses is facilitated by the interaction between viral hemagglutinin (H-protein) and the signaling lymphocytic activation molecule (SLAM). Recently, the functional importance of the n-terminal region of human SLAM as a measles virus receptor was demonstrated. However, the functional roles of this region in the infection process by other morbilliviruses and host range determination remain unknown, partly because this region is highly flexible, which has hampered accurate structure determination of this region by X-ray crystallography. In this study, we analyzed the interaction between the H-protein from canine distemper virus (CDV-H) and SLAMs by a computational chemistry approach. Molecular dynamics simulations and fragment molecular orbital analysis demonstrated that the unique His28 in the N-terminal region of SLAM from Macaca is a key determinant that enables the formation of a stable interaction with CDV-H, providing a basis for CDV infection in Macaca. The computational chemistry approach presented should enable the determination of molecular interactions involving regions of proteins that are difficult to predict from crystal structures because of their high flexibility.     

Selective Propargylation of Carbonyl Compounds and Imines with Barium Reagents

A Barbier‐type regioselective propargylation of aldehydes and ketones with (3‐bromobut‐1‐ynyl)trimethylsilane has been achieved using reactive barium as a low‐valent metal in THF. Especially in the case of ketones, the corresponding homopropargylic alcohols form almost exclusively. In the reaction of α,β‐unsaturated carbonyl compounds, only 1,2‐adducts have been observed. This method is also applicable to propargylation of imines, and the corresponding homopropargylic amines are obtained regiospecifically in good yields with diastereomeric ratios of up to 87:13.     

Two-mass models of the vocal cords for natural sounding voice synthesis

Three new two-mass models of the vocal cords are treated. First, the features, structure, and differential equations of motion are described for each of the new models and compared with those of previous models. Second, performances of the models are discussed in terms of glottal volume flow, glottal area, radiated sound pressure, trajectories of mass movement, running spectra of the output sound pressure, and perceptual naturalness of the output sound. Finally, the major effects of glottal source-vocal tract interaction including skewing, truncation, and superposition are investigated, using one of the simplest types of two-mass models and two types of load representing the vocal tract.     

A compact optical heterodyne interferometer by optical integration and its application

A compact high-resolution optical heterodyne interferometer combining a two-frequency light module and a minute optical system is described. The light module, which generates two independent frequencies of light, is fabricated by proton exchange method on LiNbO₃ substrate. We report an experiment evaluating measurement accuracy using a micro-displacement measurement system which incorporates this interferometer. Results of the experiment with a standard thickness sample show high thermal stability with maximum measurement error of 1.8 nm at a temperature from 19°C to 33°C. The system was used to measure the hysteresis of a piezoelectric element for displacements of several nm, thereby making it possible to analyze the system quantitatively in practice.     

Spherical dye-doped silica particles

Organic dyes such as water soluble porphyrins were incorporated into monodispersed SiO₂ particles using the sol-gel technique (the Stober synthesis) and their monomeric and dimeric properties were investigated by aiming at the microcavity effect. Doping efficiencies of dyes into SiO₂ particles depended on dye's hydrophilic properties. The doping efficiency of a porphyrin, TTMAPP, decreased with increasing the nominal content in the starting solution and the doping content showed the maximum value of 1.6×10^–5 mol/g SiO₂. With increasing the TTMAPP content, spectra of doped particles were changed from dimeric to monomeric nature; the absorption peak due to dimers disappeared and halfwidth of absorption at Soret band decreased. This unusual change was caused by the decrease of particle sizes by dye doping. The TTMAPP-doped sample having monomeric spectrum showed the fluorescence life time of 8.5 nsec and photochemical hole burning at about 5 K.     

Effect of pressure on the solubilities ofo-,m- andp-xylene in water

The solubilities of o-, m- and p-xylene in water were measured at 25.0°C up to 250, 385, and 50 MPa, respectively. The solubility increased with increasing pressure up to 120 MPa (50 MPa for p-xylene) and then decreased. The reaction volumes, V^o accompanying the dissolution at 0.1 MPa were estimated as –3.6±0.5, –3.4±0.5, and –4.1±0.5 cm³-mol^–1 for o-, m-, and p-xylene, respectively, from the pressure dependences of the solubilities. The limiting partial molar volumes, of p- and o-xylene in water under high pressure were estimated from V^o and the molar volume of the xylene. The partial molar volumes decreased with increasing pressure. The reaction volume for the formation of intra-molecular pairwise hydrophobic interaction between the methyl groups, as proposed by Ben-Naim, is discussed for the V^o of p- and o-xylene at 0.1 MPa.     

Nonpeptide arginine vasopressin antagonists for both V1A and V2 receptors: synthesis and pharmacological properties of 4-(1,4,5,6-tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbonyl)benzanili de derivatives and 4'-(5,6-dihydro-4H-thiazolo[5,4-d][1]benzoazepine-6-carbonyl)benzanilid e derivatives

Arginine vasopressin (AVP) has a dual action mainly in the periphery, i.e., vasoconstriction and water reabsorption via V1A and V2 receptors; it may play a role in a number of diseases, including congestive heart failure (CHF), hypertension, renal disease, edema, and hyponatremia. We have attempted to develop a new series of orally active AVP antagonists for both V1A and V2 receptors based on the hypothesis that the blockade of both V1A and V2 receptors might be beneficial to CHF patients. In this report, a series of compounds structurally related to 4'-(1,4,5,6-tetrahydroimidazo[4,5-d][1]benzoazepine-6- carbonyl)benzanilide and 4'-(5,6-dihydro-4H- thiazolo[5,4-d][1]benzoazepine-6-carbonyl)benzanilide were synthesized and examined for AVP antagonist activity for both V1A and V2 receptors. As a result, it was found that the 4'-(1,4,5,6-tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbon yl)-2- phenylbenzanilide derivatives showed potent binding affinity for both V1A and V2 receptors. Especially, 4'-(2-methyl-1,4,5,6- tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbonyl)-2-phe nylbenzanilide monohydrochloride (18, YM087 = conivaptan hydrochloride) exhibited potent binding affinity and AVP antagonist activity, after intravenous administration, for both V1A and V2 receptors. Furthermore, YM087 exhibited the most potent oral activity for the V2 receptor. Details of the synthesis and pharmacological properties of this series are presented.     

Isomorphic electron orbitals for vibronic flexibility in a cyclopropenyl radical molecular device

Summary The vibronic character of this molecular device has been studied using isomorphic electron orbitals. The leading role of the softest vibrational mode for the electron transport process is stressed by the quantum mechanical treatment of the rearrangement operator. The theory was used to investigate the possible function of the soliton valve, which has been suggested as a switching tip. The electronic flexibility of the cyclopropenyl radical with respect to molecular vibrations, which is important for the function of the molecular device, is well characterized by the hardness and softness of the electron structure in terms of the orbital energy-occupation number correlation diagram.