An imaging system that can display both the amplitude and phase maps of internal vibration in soft tissues for forced low-frequency vibration is described. In this method, low-frequency sinusoidal vibration of frequency under several hundred hertz is applied from the surface of the sample and the resulting movement in it is measured from the Doppler frequency shift of the simultaneously transmitted probe ultrasonic waves. Basic experiments are carried out by using 3.0-MHz ultrasonic waves. The two-dimensional maps of the amplitude and phase of internal vibration are shown, and the velocities of vibration are measured for some samples as well as in vivo.

Further development of the potent carborane-containing estrogenic agonists described here, having a new skeletal structure and unique characteristics, should yield novel therapeutic agents, especially selective estrogen receptor modulators. Furthermore, the suitability of the spherical carborane cage for binding to the cavity of the estrogen receptor-alpha ligand-binding domain should provide a basis for a similar approach to developing novel ligands for other steroid receptors.

Introduction.The carboranes (dicarba-closo-dodecaboranes) 1 exhibit remarkable thermal stability, are resistant to attack by most types of reagents, and are generally biologically inactive. Their icosahedral geometry, in which the carbon and boron atoms are hexacoordinated, accounts for these unusual properties, which make such molecules and their carbon and boron derivatives uniquely suitable for several specialized applications, including synthesis of polymers for hightemperature use and neutron-shielding purposes. 2 In the field of medical and pharmaceutical sciences, incorporation of large numbers of boron atoms into tumor cells for boron neutron capture therapy (BNCT) 3 has attracted much interest in recent years. For this purpose, various compounds have been synthesized by adding carborane units to nucleic acids, 4 amino acids, 5 etc. In contrast, little attention has been paid to the possible use of carboranes as components of biologically active molecules. The exceptionally hydrophobic character and spherical geometry of carboranes may allow their use as a hydrophobic pharmacophore in biologically active molecules which interact hydrophobically with receptors. Recently, we have reported the first example of design, synthesis, and biological evaluation of retinoids containing a carborane cage as a hydrophobic pharmacophore. 6 In this article, we describe the synthesis and biological evaluation of novel carboranecontaining estrogenic agonists which are more potent than 17β-estradiol.Estrogen (17β-estradiol, 1) is an important hormone that mediates a wide variety of cellular responses through its binding to a specific nuclear estrogen receptor (ER). The hormone-bound ER forms an active dimer, which functions as a transcription factor that mediates biological response by binding to specific promoter elements of DNA to initiate gene transcription. Compounds that either induce or inhibit cellular estrogen responses have potential value as biochemical tools and candidates for drug development.

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Microobject manipulation using ultrasonic waves is expected to play important roles in constructing future drug or gene delivery systems. The acoustic radiation force, which is applied to microobjects, traps the objects at the desired position. A microjet, which is produced by bubble explosion under high-intensity ultrasonic waves, creates microholes through the cell membrane (sonoporation), which is considered as a sophisticated method of improving the doses of drugs or genes injected into a tissue. Aiming at increasing the trapping force in micro bubble manipulation using ultrasonic waves, we have proposed a novel method based on the self-organization of microbubbles. This method uses seed bubbles in order to trap the target bubbles. In this study, the proposed method is applied to yeast cell trapping using ultrasonic waves. An ultrasonic wave contrast agent (Levovist; Shering A.G., Germany) is used as a seed bubble. It is shown that the number of trapped yeast cells depends on the preparation of the yeast cells. In order to evaluate the result, two additional experiments are carried out by changing the internal gas of the seed bubbles and by using bubbles with a polymer shell.

Microbubble manipulation by acoustic radiation force may play an important role in future drug delivery systems, because the required bubble manipulations, such as bubble trapping at the desired position and payload release by bubble destruction using a high-intensity ultrasonic wave, are controlled by ultrasonic waves. In this paper, a novel method of microbubble trapping by bubble nonlinear oscillation is proposed. Two ultrasonic waves, which have a harmonic frequency relation, are used in order to generate the force for trapping bubbles. The first wave is a pumping wave, which has a relatively high sound pressure. This wave is used for inducing the nonlinear oscillation of bubbles. The second wave is a control wave, whose frequency is set to be the harmonic frequency of the nonlinear bubble oscillation. The pressure gradient of the control wave in conjunction with the harmonic component of nonlinear oscillation generates the Bjerknes force applied to bubbles. This force forms multiple traps with a narrow separation for bubbles, which flow into the cross area of the two ultrasonic waves.

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