Interaction of laser generated ultrasonic waves with wedge-shaped samples

Wedge-shaped samples can be used as a model of acoustic interactions with samples ranging from ocean wedges, to angled defects such as rolling contact fatigue, to thickness measurements of samples with non-parallel faces. We present work on laser generated ultrasonic waves on metal samples; one can measure the dominant Rayleigh-wave mode, but longitudinal and shear waves are also generated. We present calculations, models, and measurements giving the dependence of the arrival times and amplitudes of these modes on the wedge apex angle and the separation of generation and detection points, and hence give a measure of the wedge characteristics

The Effect of Crystallization on the Pulsations of White Dwarf Stars

We consider the pulsational properties of white dwarf star models with temperatures appropriate for the ZZ Ceti instability strip and with masses large enough that they should be substantially crystallized. Our work is motivated by the existence of a potentially crystallized DAV, BPM 37093, and the expectation that digital surveys in progress will yield many more such massive pulsators. A crystallized core makes possible a new class of oscillations, the torsional modes, although we expect these modes to couple at most weakly to any motions in the fluid and therefore to remain unobservable. The p-modes should be affected at the level of a few percent in period, but are unlikely to be present with observable amplitudes in crystallizing white dwarfs any more than they are in the other ZZ Ceti's. Most relevant to the observed light variations in white dwarfs are the g-modes. We find that the kinetic energy of these modes is effectively excluded from the crystallized cores of our models. As increasing crystallization pushes these modes farther out from the center, the mean period spacing between radial overtones increases substantially with the crystallized mass fraction. In addition, the degree and structure of mode trapping is affected. The fact that some periods are strongly affected by changes in the crystallized mass fraction while others are not suggests that we may be able to disentangle the effects of crystallization from those due to different surface layer masses.Comment: 18 pages, 5 figures, accepted on 1999 July 2 for publication in the Astrophysical Journa

A Majority of Solar Wind Intervals Support Ion-Driven Instabilities

We perform a statistical assessment of solar wind stability at 1 AU against ion sources of free energy using Nyquist's instability criterion. In contrast to typically employed threshold models which consider a single free-energy source, this method includes the effects of proton and He$^{2+}$ temperature anisotropy with respect to the background magnetic field as well as relative drifts between the proton core, proton beam, and He$^{2+}$ components on stability. Of 309 randomly selected spectra from the Wind spacecraft, $53.7\%$ are unstable when the ion components are modeled as drifting bi-Maxwellians; only $4.5\%$ of the spectra are unstable to long-wavelength instabilities. A majority of the instabilities occur for spectra where a proton beam is resolved. Nearly all observed instabilities have growth rates $\gamma$ slower than instrumental and ion-kinetic-scale timescales. Unstable spectra are associated with relatively-large He$^{2+}$ drift speeds and/or a departure of the core proton temperature from isotropy; other parametric dependencies of unstable spectra are also identified.Comment: 6 pages, 3 figures, 2 tables, accepted in Physical Review Letters; fixed typos in version

Ultra-short pulses in linear and nonlinear media

We consider the evolution of ultra-short optical pulses in linear and nonlinear media. For the linear case, we first show that the initial-boundary value problem for Maxwell's equations in which a pulse is injected into a quiescent medium at the left endpoint can be approximated by a linear wave equation which can then be further reduced to the linear short-pulse equation. A rigorous proof is given that the solution of the short pulse equation stays close to the solutions of the original wave equation over the time scales expected from the multiple scales derivation of the short pulse equation. For the nonlinear case we compare the predictions of the traditional nonlinear Schr\"odinger equation (NLSE) approximation which those of the short pulse equation (SPE). We show that both equations can be derived from Maxwell's equations using the renormalization group method, thus bringing out the contrasting scales. The numerical comparison of both equations to Maxwell's equations shows clearly that as the pulse length shortens, the NLSE approximation becomes steadily less accurate while the short pulse equation provides a better and better approximation

Guanabenz (Wytensin) selectively enhances uptake and efficacy of hydrophobically modified siRNAs

One of the major obstacles to the pharmaceutical success of oligonucleotide therapeutics (ONTs) is efficient delivery from the point of injection to the intracellular setting where functional gene silencing occurs. In particular, a significant fraction of internalized ONTs are nonproductively sequestered in endo-lysosomal compartments. Here, we describe a two-step, robust assay for high-throughput de novo detection of small bioactive molecules that enhance cellular uptake, endosomal escape, and efficacy of ONTs. Using this assay, we screened the LOPAC (Sigma-Aldrich) Library of Pharmacologically Active Compounds and discovered that Guanabenz acetate (Wytensin), an FDA-approved drug formerly used as an antihypertensive agent, is capable of markedly increasing the cellular internalization and target mRNA silencing of hydrophobically modified siRNAs (hsiRNAs), yielding a approximately 100-fold decrease in hsiRNA IC50 (from 132 nM to 2.4 nM). This is one of the first descriptions of a high-throughput small-molecule screen to identify novel chemistries that specifically enhance siRNA intracellular efficacy, and can be applied toward expansion of the chemical diversity of ONTs

5-Vinylphosphonate improves tissue accumulation and efficacy of conjugated siRNAs in vivo

5-Vinylphosphonate modification of siRNAs protects them from phosphatases, and improves silencing activity. Here, we show that 5-vinylphosphonate confers novel properties to siRNAs. Specifically, 5-vinylphosphonate (i) increases siRNA accumulation in tissues, (ii) extends duration of silencing in multiple organs and (iii) protects siRNAs from 5-to-3 exonucleases. Delivery of conjugated siRNAs requires extensive chemical modifications to achieve stability in vivo. Because chemically modified siRNAs are poor substrates for phosphorylation by kinases, and 5-phosphate is required for loading into RNA-induced silencing complex, the synthetic addition of a 5-phosphate on a fully modified siRNA guide strand is expected to be beneficial. Here, we show that synthetic phosphorylation of fully modified cholesterol-conjugated siRNAs increases their potency and efficacy in vitro, but when delivered systemically to mice, the 5-phosphate is removed within 2 hours. The 5-phosphate mimic 5-(E)-vinylphosphonate stabilizes the 5 end of the guide strand by protecting it from phosphatases and 5-to-3 exonucleases. The improved stability increases guide strand accumulation and retention in tissues, which significantly enhances the efficacy of cholesterol-conjugated siRNAs and the duration of silencing in vivo. Moreover, we show that 5-(E)-vinylphosphonate stabilizes 5 phosphate, thereby enabling systemic delivery to and silencing in kidney and heart