X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis -acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.

Introduction: i Emulsions are metastable dispersions of two immisciblwere synthesized using methods adapted by Lae liquids that form an apparently homogeneous material (i.e. macroscopically). Without stabilizers, emulsions are intrinsically unstable and ultimately will separate into two different phases. 1 Although surfactants commonly stabilize emulsions, solid particles have also been demonstrated to be effective stabilizers producing systems called Pickering emulsions. 2-4 Based on the wettability of the particles, either oil-in-water or water-in-oil Pickering emulsions are formed. 3 Other advantages of Pickering emulsions include a significant increase in the emulsion's resistance to coalescence, increased energy barriers to eject particles from the emulsion interface (i.e. nearly irreversible adsorption), and decreased toxicity to living cells. 5-7 Consequently, Pickering emulsions can be used effectively in fields such as food science & engineering, oil recovery, cosmetics, and biomedical technologies. 6,8-12

Sono-photoacoustic (SPA) activation lowers the threshold of phase-change contrast agents by timing a laser shot to coincide with the arrival of an acoustic wave at a region of interest. The combination of photothermal heating from optical absorption and negative pressure from the acoustic wave greatly reduces the droplet’s combined vaporization threshold compared to using laser energy or acoustic energy alone. In previous studies, SPA imaging used a broadly illuminated optical pulse combined with plane wave acoustic pulses transmitted from a linear ultrasound array. Acoustic plane waves cover a wide lateral field of view, enabling direct visualization of the contrast agent distribution. In contrast, we demonstrate here that localized SPA activation is possible using electronically steered/focused ultrasound pulses. The focused SPA activation region is defined axially by the number of cycles in the acoustic pulse and laterally by the acoustic beam width. By reducing the spot size and enabling rapid electronic steering, complex activation patterns are possible, which may be particularly useful in therapeutic applications.

The swept-scan technique adopted in high-frequency ultrasound involves mechanically scanning a single-element transducer to acquire image data. Unlike conventional step scanning, where the image data are acquired at discrete positions, the swept-scan technique acquires the image data while the transducer is continuously moving. Such a scanning method is particularly advantageous for Doppler flow estimation because its frame rate is higher than that for the step-scan technique. However, the effects of the transducer motion on the accuracy of velocity estimation have not been studied comprehensively. This study employed a k-space approach to experimentally investigate the effects of swept scanning on both conventional Doppler axial velocity estimation and spectral-broadening-based lateral velocity estimation using a 45-MHz transducer. The results indicate that such effects must be corrected in order to obtain an accurate estimation of flow velocities.

Conventional ultrasound systems with fixed transmit and dynamic receive focusing suffer from limited depth of field and poor SNR uniformity. Based on fixed receive focusing, this paper proposes an SNR-dependent 2-D retrospective filtering technique to extend the depth of field, in which both the sidelobe energy and the filter energy are minimized simultaneously. According to the estimated SNR of the unfiltered image, the proposed 2-D filter can provide the optimal compromise between image quality and SNR while maintaining a moderate filter size. Simulations were performed to demonstrate the efficacy of the proposed technique. It has been shown that the proposed 2-D filter technique outperforms conventional 1-D lateral filter and classical 2-D Wiener filter in terms of both SNR and contrast resolution.