Citations

It has previously been shown that acoustic ray paths in range-dependent ocean models exhibit chaotic behavior. Most of the investigations into the ray chaos phenomenon have been primarily numerical in nature. The objective of this report is to study theoretically the existence of ray chaos in a parabolic ray system with an analytically prescribed sound-speed model consisting of a double-channel profile perturbed by a typical periodic range-dependent disturbance. The perturbed Hamiltonian ray system is studied analytically via Melnikov’s method. It is shown that, under certain conditions, ray trajectories in some regions of the Poincaré section are equivalent to trajectories of the horseshoe map no matter how small the corresponding perturbation is. These conditions are sufficient for ray chaos and easily satisfied, thus explaining why double-channel propagation is very likely to exhibit chaotic behavior. [Work supported by CA43920 NIH.]

Earlier studies [P. J. Westervelt, J. Acoust. Soc. Am. 29, 199–203, 934–935 (1957)] of the mutual nonlinear interaction of two plane waves of sound with each other are extended to include the viscous effect. The viscous effect is considered both from the equations of motion and the equation of state of the medium. An analytical solution to the lowest order scattering process is obtained if the viscous effect of second order and higher can be neglected. In fact, it is shown that the scattered density ρs of two interacting plane waves having the frequencies ω1 and ω2, respectively, satisfies the following equation: ⧠2vρs=⧠2v{c0−2E12+[(2cosθ +B/A)/2ω1ω2 (1−cosθ)]∇2W12 +[DB(c20ω1ω2)−1 / 4A ×(1−cosθ)2]∇2(∂W12/∂t)+[DB(3+cosθ)/2Ac40 (1−cosθ)](∂V12/∂t)}, where E12, V12, and W12 are, respectively, the total, potential, and special defined energy densities, D is the sound diffusivity, B and A are nonlinearity parameters, θ is the intersecting angle, and ⧠2v is a modified d’Alembertian operator. [Work supported by CA43920 NIH.]

ABSTRACT HlyD, a member of the membrane fusion protein family, is essential for the secretion of the RTX hemolytic toxin HlyA from Escherichia coli . Random point mutations affecting HlyA secretion were obtained, distributed in most periplasmic regions of the HlyD molecule. Analysis of the secretion phenotypes of different mutants allowed the identification of regions in HlyD involved in different steps of HlyA translocation. Four mutants, V349-I, T85-I, V334-I and L165-Q, were conditionally defective, a phenotype shown to be linked to the presence of inhibitory concentrations of Ca 2+ in extracellular medium. Hly mutant T85-I was defective at an early stage in secretion, while mutants V334-I and L165-Q appeared to accumulate HlyA in the cell envelope, indicating a block at an intermediate step. Mutants V349-I, V334-I, and L165-Q were only partially defective in secretion, allowing significant levels of HlyA to be transported, but in the case of V349-I and L165-Q the HlyA molecules secreted showed greatly reduced hemolytic activity. Hemolysin molecules secreted from V349-I and V334-I are defective in normal folding and can be reactivated in vitro to the same levels as HlyA secreted from the wild-type translocator. Both V349-I and V334-I mutations mapped to the C-terminal lipoyl repeat motif, involved in the switching from the helical hairpin to the extended form of HlyD during assembly of the functional transport channel. These results suggest that HlyD is an integral component of the transport pathway, whose integrity is essential for the final folding of secreted HlyA into its active form.

Purpose To review the current utilization of diagnostic tests prescribed by the International Federation of Gynecology and Obstetrics (FIGO) clinical staging guidelines in the pretreatment work-up of invasive cervical cancer, and to compare the data with those of previous patterns of care studies. Patients and Methods This interdisciplinary American College of Radiology Imaging Network/Gynecologic Oncology Group prospective clinical trial was conducted between March 1, 2000, and November 11, 2002. Twenty-five participating institutions, all from the United States, enrolled a total of 208 patients. Only patients scheduled for surgery with biopsy-confirmed cervical cancer of clinical FIGO stage IB or higher were eligible. The patterns of care data analysis was based on 197 patients who met all inclusion criteria. The conventional FIGO-recommended tests used for pre-enrollment FIGO clinical stage classification were at the discretion of the treating physician; overall frequency of use was tabulated for each test. Results Use of cystoscopy (8.1%) and sigmoidoscopy or proctoscopy (8.6%) was significantly lower than in 1988 to 1989 (P < .0001 in each instance). Intravenous urography was used in only 1% of patients as compared with 42% in 1988 to 1989 and 91% in 1983. No patient included in the data analysis had barium enema or lymphangiography. Only 26.9% of patients had examination under anesthesia for FIGO clinical staging. Conclusion There is a large discrepancy between the diagnostic tests recommended by FIGO and the actual tests used for cervical cancer staging, suggesting a need to reassess the relevance of the FIGO guidelines to current clinical practice in the United States.

This paper presents a new method of inducing localized low-frequency acoustic energy in an object by remote sources. In this method two interacting high-power, high-frequency, ultrasound beams at two different frequencies are used. These beams are positioned to interact at the object’s surface (or any other impedance discontinuity inside the object). The result is a radiation force at the difference frequency, df, exerted in a small area defined by the beamwidths. Experiments are performed on a small steel needle and blocks of gelatin. To monitor the vibration, a high-frequency probing transducer is used in pulse echo mode with the beam aimed at the vibrating part of the object. This transducer shoots tone bursts at a rate much higher than df. Echoes are quadrature detected and the resulting in-phase and quadrature signals are recorded. These signals are used to calculate the phase of the returned echo which is shown to be proportional to the target displacement. In the experiments, the power beams were driven at 20 W each and df=10 Hz. Amplitude of the resulting vibrations were 5 μm for the gelatin block and 1.2 μm for the needle.

Log compression of A lines to produce B-scan images in clinical ultrasound imaging systems is a standard procedure to control the dynamic range of the images. The statistics of such compressed images in terms of underlying scatterer statistics have not been derived. The statistics are analyzed for partially formed speckle using a general K distribution model of envelope statistics to derive the density function for the log-compressed envelope. This density function is used to elucidate the relation between the moments of the compressed envelope, the compression parameters, and the statistics of the scatterers. The analysis shows that the mean of the log-compressed envelope is an increasing function of both the backscattered energy and the effective scatterer density. The variance of the log-compressed envelope is a decreasing function of the effective scatterer density and is independent of the backscattered energy.

Earlier studies [P. J. Westervelt, J. Acoust. Soc. Am. 29, 199–203, 934–935 (1957)] of the mutual nonlinear interaction of two plane waves of sound with each other are extended to include the viscous effect. The viscous effect is considered both from the equations of motion and the equation of state of the medium. An analytical solution to the lowest-order scattering process is obtained if the viscous effect of second order and higher can be neglected.

Purpose Surgical resection of liver-only metastases from colorectal cancer has undergone extensive evaluation and review. The use of neoadjuvant chemotherapy to improve the likelihood of resection in disease that is not optimally resectable has not been as well studied. Patients and Methods Patients with liver-only metastases from colorectal cancer deemed not optimally resectable by a surgeon with expertise in liver surgery received fluorouracil, leucovorin, and oxaliplatin (FOLFOX4). Patients were periodically reassessed for resectability. Surgical response was classified as completely resectable (S-CR), partially resectable (S-PR), or unresectable (S-UR). Study design specified the accrual of 39 patients, with two or more S-CRs considered evidence of promising activity with respect to increasing the S-CR rate. Results Forty-two of 44 patients were assessable for this analysis. Twenty-five patients (60%) had tumor reduction by serial imaging. Seventeen patients (40%) underwent surgery (S-CR, n = 14; S-PR, n = 1; and S-UR, n = 2) after a median of 6 months of chemotherapy. With a median postsurgical follow-up of 22 months (range, 13 to 32 months), 11 recurrences have occurred in the 15 S-CR and S-PR patients. Median survival time was 26 months. Conclusion Our data suggest that FOLFOX4 has a high response rate (complete response, partial response, or reduction) in patients with liver-only metastases from colorectal cancer, allowing for successful resection of disease in a portion of patients initially not judged to be optimally resectable. However, a high recurrence rate after surgery was observed, which, in 73% of patients, involved the liver. Further trials are indicated based on the promising results observed in this trial.

Frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) is caused by mutations in the gene encoding the microtubule-associated protein, tau. Some FTDP-17 mutations affect exon 10 splicing. To correct aberrant exon 10 splicing while retaining endogenous transcriptional control, we evaluated the feasibility of using spliceosome-mediated RNA trans-splicing (SMaRT) to reprogram tau mRNA. We designed a pre-trans-splicing molecule containing human tau exons 10 to 13 and a binding domain complementary to the 3′ end of tau intron 9. A minigene comprising tau exons 9, 10, and 11 and minimal flanking intronic sequences was used as a target. RT-PCR analysis of SH-SY5Y cells or COS cells cotransfected with a minigene and a pre-trans-splicing molecule using primers to opposite sides of the predicted splice junction generated products containing exons 9 to 13. Sequencing of the chimeric products showed that an exact exon 9–exon 10 junction had been created, thus demonstrating that tau RNA can be reprogrammed by trans-splicing. Furthermore, by using the same paradigm with a minigene containing full-length intronic sequences, we show that cis-splicing exclusion of exon 10 can be by-passed by trans-splicing and that conversion of exon 10 – tau RNA into exon 10 + tau RNA could be achieved with ≈34% efficiency. Our results demonstrate that an alternatively spliced exon can be replaced by trans-splicing and open the way to novel therapeutic applications of SMaRT for tauopathies and other disorders linked to aberrant alternative splicing.