Assessment of angiogenesis: implications for ultrasound imaging

In this paper, the fundamentals of tumor angiogenesis and the implications for ultrasound imaging will be described. Twenty-eight athymic nude mice were implanted with the human melanoma cell lines DB-1 or MW-9 (14 mice/group). Ultrasound contrast agents were injected in the tail veins. Power Doppler and pulse inversion harmonic imaging (PI-HI) was performed (in real time and intermittently). Ultrasound results were compared to immunohistochemical stains for endothelial cells (CD31), vascular endothelial growth factor (VEGF), and cyclooxygenase-2 (COX-2). Linear regression analysis indicated statistically significant correlations between percent area stained with COX-2 and with VEGF relative to power Doppler (p<0.05) and intermittent PI-HI (p<0.05) measures of tumor neovascularity in the MW-9 and the DB-1 mice, respectively. Preliminary results from a human trial of the anti-angiogenic drug Angiostatin (Entremed, Rockville, MD) showed tumor volumes increased in two patients, while the vascularity remained virtually unchanged. Conversely, in three patients with diminished tumor volumes vascularity increased by 38%. In conclusion, contrast enhanced ultrasound imaging of tumor neovascularity may provide noninvasive markers of angiogenesis and may become a useful tool for monitoring anti-angiogenic therapies in vivo.     

Multichip vertical-external-cavity surface-emitting lasers: a coherent power scaling scheme

We propose an efficient coherent power scaling scheme, the multichip vertical-external-cavity surface-emitting laser (VECSEL), in which the waste heat generated in the active region is distributed on multi-VECSEL chips such that the pump level at the thermal rollover is significantly increased. The advantages of this laser are discussed, and the development and demonstration of a two-chip VECSEL operating around 970 nm with over 19 W of output power is presented.     

Fluorescence lifetime imaging of molecular rotors to map microviscosity in cells

Fluorescence liftime imaging （FLIM） of modified hydrophobic bodipy dyes that act as fluorescent molecular rotors shows that the fluorescence lifetime of these probes is a function of the microviscosity of their environment. Incubating cells with these dyes, we find a punctate and continuous distribution of the dye in cells. The viscosity value obtained in what appears to be endocytotic vesicles in living cells is around 100 times higher than that of water and of cellular cytoplasm.Time-resolved fluorescence anisotropy measurements also yield rotational correlation times consistent with large microviscosity values. In this way, we successfully develop a practical and versatile approach to map the microviscosity in cells based on imaging fluorescent molecular rotors.     

Measurement and modeling of three-dimensional sound intensity variations due to shallow-water internal waves

Broadband acoustic data (30-160 Hz) from the SWARM'95 experiment are analyzed to investigate acoustic signal variability in the presence of ocean internal waves. Temporal variations in the intensity of the received signals were observed over periods of 10 to 15 min. These fluctuations are synchronous in depth and are dependent upon the water column variability. They can be explained by significant horizontal refraction taking place when the orientation of the acoustic track is nearly parallel to the fronts of the internal waves. Analyses based on the equations of vertical modes and horizontal rays and on a parabolic equation in the horizontal plane are carried out and show interesting frequency-dependent behavior of the intensity. Good agreement is obtained between theoretical calculations and experimental data.     

Field-cycled PEDRI imaging of free radicals with detection at 450 mT

This paper describes the design, construction and use of a field-cycled proton-electron double-resonance imaging (FC-PEDRI) system for the detection and imaging of free radicals. The unique feature of this imager is its use of a 450-mT detection magnetic field in order to achieve good image quality and sensitivity. The detection magnetic field is provided by a superconducting magnet, giving high stability and homogeneity. Field cycling is implemented by switching on and off the current in an internal, coaxial, resistive secondary magnet that partially cancels the superconducting magnet's field at the sample; the secondary magnet is actively shielded to avoid eddy currents. EPR irradiation takes place at approximately 5 mT, following which the field is switched to 450 mT in 40 ms for NMR signal detection. Full details of the imager's subsystems are given, and experiments to image the distribution of stable free radical contrast agents in phantoms and in anesthetized rats are described.     

Stereochemical analysis of ferrocene and the uncertainty of fluorescence XAFS data

Methods for the quantification of statistically valid measures of the uncertainties associated with X‐ray absorption fine structure (XAFS) data obtained from dilute solutions using fluorescence measurements are developed. Experimental data obtained from 10 mM solutions of the organometallic compound ferrocene, Fe(C₅H₅)₂, are analysed within this framework and, following correction for various electronic and geometrical factors, give robust estimates of the standard errors of the individual measurements. The reliability of the refinement statistics of standard current XAFS structure approaches that do not include propagation of experimental uncertainties to assess subtle structural distortions is assessed in terms of refinements obtained for the staggered and eclipsed conformations of the C₅H₅ rings of ferrocene. Standard approaches (XFIT, IFEFFIT) give refinement statistics that appear to show strong, but opposite, preferences for the different conformations. Incorporation of experimental uncertainties into an IFEFFIT‐like analysis yield refinement statistics for the staggered and eclipsed forms of ferrocene which show a far more realistic preference for the eclipsed form which accurately reflects the reliability of the analysis. Moreover, the more strongly founded estimates of the refined parameter uncertainties allow more direct comparison with those obtained by other techniques. These XAFS‐based estimates of the bond distances have accuracies comparable with those obtained using single‐crystal diffraction techniques and are superior in terms of their use in comparisons of experimental and computed structures.     

Synthetic gene network for entraining and amplifying cellular oscillations

We present a model for a synthetic gene oscillator and consider the coupling of the oscillator to a periodic process that is intrinsic to the cell. We investigate the synchronization properties of the coupled system, and show how the oscillator can be constructed to yield a significant amplification of cellular oscillations. We reduce the driven oscillator equations to a normal form, and analytically determine the amplification as a function of the strength of the cellular oscillations. The ability to couple naturally occurring genetic oscillations to a synthetically designed network could lead to possible strategies for entraining and/or amplifying oscillations in cellular protein levels.     

Binary-black-hole encounters, gravitational bursts, and maximum final spin

The spin of the final black hole in the coalescence of nonspinning black holes is determined by the "residual" orbital angular momentum of the binary. This residual momentum consists of the orbital angular momentum that the binary is not able to shed in the process of merging. We study the angular momentum radiated, the spin of the final black hole, and the gravitational bursts in a sequence of equal mass encounters. The initial orbital configurations range from those producing an almost direct infall to others leading to numerous orbits before infall, with multiple bursts of radiation. Our sequence consists of orbits with fixed impact parameter. What varies is the initial linear momentum of the black holes. For this sequence, the final black hole of mass M_{h} gets a maximum spin parameter a/M_{h} approximately 0.823, with this maximum occurring for initial orbital angular momentum L/M_{h};{2} approximately 1.176.