A combinatorial approach toward the generation of ambiphilic peptide-based inhibitors of protein:geranylgeranyl transferase-1

A combinatorial synthesis of oligopeptide analogues and their evaluation as protein:geranylgeranyl transferase inhibitors is presented. The combinatorial strategy is based on the random mutation, in each new generation, of one of any of the four amino acid building blocks of which the most effective compounds of the previous generation are assembled. In this way, a progressive improvement of the average inhibitory activity was observed until the fifth generation. The most active inhibitors were found to inhibit PGGT-1 in the low micromolar range (IC(50): 3.8-8.1 microM).     

The formation of fluorinated tetraphenylporphyrin nanoparticles via rapid expansion processes: RESS vs RESOLV

Organic nanoparticles of a fluorinated tetraphenylporphyrin (TBTPP) were produced by rapid expansion of supercritical CO(2) solutions into both air (RESS) and an aqueous receiving solution containing a stabilizing agent (RESOLV). The effect of processing conditions on both particle size and form was investigated. The size of the porphyrin nanoparticles produced via RESS increased in a well-behaved manner from 40 to 80 nm as the preexpansion temperature increased from 40 to 100 degrees C, independent of porphyrin concentration, degree of saturation, and preexpansion pressure. RESOLV of TBTPP + CO(2) solutions was investigated both for minimizing particle growth in the free jet and for the prevention of particle agglomeration. Anionic, nonionic, and polymeric stabilizing agents for the aqueous receiving solution were considered. Expansion into a 0.05 wt % SDS solution produced nanorods 50-100 nm in diameter with an aspect ratio of 3-5. RESOLV in a 0.025 wt % Pluronic F68 solution produced well-dispersed, individual, spherical nanoparticles averaging 23 +/- 10 to 32 +/- 10 nm in diameter, independent of the rapid expansion processing conditions selected. Furthermore, the resulting nanoparticle suspensions were stable, with particle sizes remaining unchanged after several months. However, some particle agglomeration occurred at higher (i.e., 1 wt % TBTPP in CO(2)) concentrations. Contact-angle measurements on solid TBTPP compacts with the tested receiving solutions indicate that a moderate wetting agent such as Pluronic F68 is most effective for preserving the size and form of the porphyrin nanoparticles produced by RESOLV. Finally, the fact that nanoparticles are produced from RESS of TBTPP, in contrast with other organics for which microparticles are produced, can be explained in terms of the high melting point of TBTPP (388 degrees C), which results in a solid-state diffusion coefficient of TBTPP low enough so that particle coalescence is significantly reduced in the free jet.     

Generalized nonlinear Schrödinger equation for dispersive susceptibility and permeability: application to negative index materials

A new generalized nonlinear Schr?dinger equation describing the propagation of ultrashort pulses in bulk media exhibiting frequency dependent dielectric susceptibility and magnetic permeability is derived and used to characterize wave propagation in a negative index material. The equation has new features that are distinct from ordinary materials (mu=1): the linear and nonlinear coefficients can be tailored through the linear properties of the medium to attain any combination of signs unachievable in ordinary matter, with significant potential to realize a wide class of solitary waves.     

Free Energy as a Geometric Invariant

The free energy plays a fundamental role in statistical and condensed matter physics. A related notion of free energy plays an important role in the study of hyperbolic dynamical systems. In this paper we introduce and study a natural notion of free energy for surfaces with variable negative curvature. This geometric free energy encodes a new type of marked length spectrum of closed geodesics, which lies between the well-known marked length spectrum (marked by the corresponding element of the fundamental group) and the unmarked length spectrum. We prove that the free energy parametrizes the boundary of the domain of convergence of a Poincaré series which also encodes this spectrum. We also show that this new length spectrum, or equivalently the geometric free energy, is not an isometry invariant. In the final section we use tools from multifractal analysis to effect a fine asymptotic comparison of word length and geodesic length of closed geodesics. We hope that our geometric understanding of free energy will provide new insight into this fundamental physical and dynamical quantity. The work of the second author was partially supported by a National Science Foundation grant DMS-0355180. This work was completed during a visit by the first author to Penn State as a Shapiro Fellow.     

Fast causal information transmission in a medium with a slow group velocity

It is widely believed that the velocity of information upsiloni encoded on an optical pulse is equal to the group velocity upsilong, at least when upsilong is less than the speed of light in vacuum c. On the other hand, several authors suggest that upsiloni=c, although the size of the signal traveling at this velocity may be small, thereby making it difficult to measure. Here, we measure upsiloni for pulses propagating through a resonant "slow-light" medium where upsilong approximately 0.006c. We find upsiloni=1.03c(+0.49c)-0.25c, or that upsiloni approximately 168upsilong, clearly demonstrating that the speed of information cannot be generally described by upsilong, but is characterized by its own velocity.     

Lamb wave tomography of pipe-like structures

Lamb waves are guided ultrasonic plate waves that can follow the curvature of pipe-like structures. By transmitting and receiving many helically propagating Lamb waves via longitudinal transducers in contact with the surface of a pipe, crosshole tomographic geometries can be mimicked and tomographic reconstructions performed in order to locate and size flaws. We describe here a meridional-array scheme which mimics a single line of transducers along the exterior surface of the pipe in the axial direction, and show proof of concept results on a pipe sample with an internal wall-thinning. We also demonstrate improved reconstructions for the other helical ultrasound tomography geometry where the transmitters and receivers lie along parallel circumferential rings. We find frequency compounding smoothes out some of the noise and artifacts that appear in the reconstructions.     

A finite-element model of the aperture method for determining the effective radiating area of physiotherapy treatment heads

This paper describes a theoretical study of the way in which a circular aperture placed in front of a plane-piston modifies the ultrasonic field it generates. Specifically, the radiated acoustic power transmitted by the aperture and the radiation force experienced by an absorbing target placed in the transmitted beam, are evaluated at a distance from the exit-side of the aperture. The calculations used a finite element (FE) method, in conjunction with a surface Helmholtz integral formulation to solve the fluid/structure interaction problem. The PAFEC (Program for Automatic Finite Element Computation) vibroacoustics software was used for the FE calculations and the implementation of the surface Helmholtz integral formulation method. Acoustic pressures and particle velocities were computed at required points, whilst accounting for the presence of the aperture in the medium, together with its dynamic properties when subjected to an incident sound field. This enabled the calculation of the radiation force on the absorber and its variation with the applied aperture diameter was investigated. As part of the validation process for the new FE aperture model, the ratio of radiation force to radiated acoustic power obtained using the FE method in the unapertured case, through the use of the Rayleigh integral, yielded good agreement with results obtained through an analytical solution. The study has been carried out to provide a better understanding of the factors affecting the measurement uncertainty for the aperture method of determining the effective radiating area (A(ER)) of physiotherapy ultrasound treatment heads.     

Simple and compact 1-Hz laser system via an improved mounting configuration of a reference cavity

We report an improved mounting configuration for a passive optical cavity used for laser frequency stabilization. The associated reduction of the vibration sensitivity of the effective cavity length has led to a simple and compact reference cavity system for laser stabilization at the level of 1 Hz linewidth.     

Determination of line strengths for selected transitions in the v2 band relative to the v1 and v5 bands of H2CO

The spectral line strengths in the v₂ band of H₂CO (segments spanning 1720-) have been determined relative to two sets of spectral line groups in the v₁ and v₅ band, using tunable diode laser spectroscopy. Simultaneous detection using a dual-diode instrument with a absorption cell was employed to assure identical H₂CO column density for the two spectral regions. The results in the selected regions of this study are in good agreement with the line positions and the relative intensities specified in an unpublished complete line listing for the v₂ band prepared by Linda Brown (see full text for reference). Based upon measurements of individual groups of spectral lines in the P, Q and R branches, the absolute band strength has been determined to be .     

Unified description of aging and rate effects in yield of glassy solids

The competing effects of slow structural relaxations (aging) and deformation at constant strain rate on the shear yield stress tau(y) of simple model glasses are examined using molecular simulations. At long times, aging leads to a logarithmic increase in density and tau(y). The yield stress also rises logarithmically with rate but shows a sharp transition in slope at a rate that decreases with increasing age. We present a simple phenomenological model that includes both intrinsic rate dependence and the change in properties with the total age of the system at yield. As predicted by the model, all data for each temperature collapse onto a universal curve.