Expeditious method for the synthesis of novel 2,3,5,6-tetrahydrobenzo[g][1,3,5]oxadiazocine-4-thiones linked with isoxazole

Synthesis of novel 3-ary1-5-(3,5-dimethylisoxazol-4-y1)-2,3,5,6-tetrahydrobenzo[g][1,3,5]oxadiazocine-4-thiones 5 has been accomplished from 3,5-dimethylisoxazol-4-amine I by condensation with salicylaldehydes, followed by reduction, treatment with aryl isothiocyanates and subsequent smooth ring closure via acetal formation in the presence of formaldehyde.     

Lipophilicity in PK design: methyl, ethyl, futile

Lipophilicity, often expressed as distribution coefficients (log D) in octanol/water, is an important physicochemical parameter influencing processes such as oral absorption, brain uptake and various pharmacokinetic (PK) properties. Increasing log D values increases oral absorption, plasma protein binding and volume of distribution. However, more lipophilic compounds also become more vulnerable to P450 metabolism, leading to higher clearance. Molecular size and hydrogen bonding capacity are two other properties often considered as important for membrane permeation and pharmacokinetics. Interrelationships among these physicochemical properties are discussed. Increasing size (molecular weight) often gives higher potency, but inevitably also leads to either higher lipophilicity, and hence poorer dissolution/solubility, or to more hydrogen bonding capacity, which limits oral absorption. Differences in optimal properties between gastrointestinal absorption and uptake into the brain are addressed. Special attention is given to the desired lipophilicity of CNS drugs. In examples using -blockers, Ca channel antagonists and peptidic renin inhibitors we will demonstrate how potency and pharmacokinetic properties need to be balanced.     

Noise Path Synthesis with Nonlinear Joints

An efficient synthesis approach is developed which permits thecalculation of the steady-state frequency response of an assembly whichis comprised of linear components and nonlinear joints. Receptancematrices are used to characterize the linear components, which permitscondensation of the system to just the joint degrees-of-freedom.Furthermore, the calculated nonlinear joint forces are then used tostudy the power flow in the assembly, as well as detailed dynamicbehavior within the components. Integrated into the technique is acontinuation scheme which permits efficient parametric studies.     

横观各向同性层状场地对环形简谐荷载的位移响应

本文采用横观各同性层状粘弹性模型拟半空间上之的层状场地,用阻尼器取代其下部的半空间以吸收振动能量。     

Analytical Solutions for Partitioned Diffusion in Laminates: II. Harmonic Forcing Conditions

The migration of organic compounds in stratified media is of fundamental concern in environmental and chemical engineering research. The diffusive transport of volatile organic compounds through laminate systems is characterized by partitioning, i.e., the development of concentration discontinuities at the interfaces between the individual laminae. If the transport is governed by cyclic transients, the relevant equations can be written in terms of coupled systems of diffusion equations subject to sinusoidal boundary conditions. This paper solves these systems of equations to present new algebraic solutions for propagation of the sinusoidal modes through arbitrary (finite) numbers of contiguous one-dimensional laminae. Both Cartesian and radial coordinate systems are considered. Two independent formulations of the lamina interface matching conditions are considered, corresponding to (1) an instantaneous partitioning model and to (2) a mass-limited partitioning model. It is shown that sinusoidal components of the concentration solutions propagate dispersively throughout the laminates. This is manifested, for example, in changes in shape of concentration pulses as measured at different points in the laminate system. Algorithms for generating exact dispersion relations for partitioning laminates are given, and an experimental technique for studying interfacial dynamics via frequency domain measurements is proposed.     

Qualitative Theory and Identification of Dynamic System with One Degree of Freedom

Dynamic systems described by nonlinear differential equations of the second order are studied. It is assumed that certain preliminary information on the dissipative or elastic characteristics of systems is known. A new approach is demonstrated to obtaining full information on unknown or partially known characteristics of a system from measurements of not only displacements but also velocities and accelerations __________ Published in Prikladnaya Mekhanika, Vol. 41, No. 6, pp. 139–143, June 2005.     

Accurate Higher-Order Analytical Approximate Solutions to Large-Amplitude Oscillating Systems with a General Non-Rational Restoring Force

A new approximate analytical approach for accurate higher-order nonlinear solutions of oscillations with large amplitude is presented in this paper. The oscillatory system is subjected to a non-rational restoring force. This approach is built upon linearization of the governing dynamic equation associated with the method of harmonic balance. Unlike the classical harmonic balance method, simple linear algebraic equations instead of nonlinear algebraic equations are obtained upon linearization prior to harmonic balancing. This approach also explores large parameter regions beyond the classical perturbation methods which in principle are confined to problems with small parameters. It has significant contribution as there exist many nonlinear problems without small parameters. Through some examples in this paper, we establish the general approximate analytical formulas for the exact period and periodic solution which are valid for small as well as large amplitudes of oscillation.     

Identifying mode shapes and modal frequencies by operational modal analysis in the presence of harmonic excitation

Operational modal analysis techniques allow us to extract the modal properties of structures based on their response to non-measured stationary white noise, i.e., by considering only the system response to operational excitations. In this paper we outline a procedure to deduce modal parameters from operational response measurements. In particular, we discuss a novel approach to analyze operational responses due to unknown harmonic excitation in addition to noise. Structural eigenfrequencies and modal damping are computed using a modified least-squares complex exponential method. Once the poles of the system are identified, mode shapes are obtained by post-processing. The robustness and accuracy of the approach are illustrated by performing tests on a plate structure.     

New MnO–Nb(Ta)2O5 Phases Produced at High Pressures and Temperatures

Phase formation at high pressures and temperatures were studied in the MnO–Nb(Ta)₂O₅ system. New rhombohedral modifications of Mn₄Nb₂O₉ and Mn₄Ta₂O₉, two new modifications of MnTa₂O₆, and two modifications of Mn₂Ta₂O₇ were obtained. They were structurally identified.