In vivo monitoring of multiple circulating cell populations using two-photon flow cytometry

To detect and quantify multiple distinct populations of cells circulating simultaneously in the blood of living animals, we developed a novel optical system for two-channel, two-photon flow cytometry in vivo. We used this system to investigate the circulation dynamics in live animals of breast cancer cells with low (MCF-7) and high (MDA-MB-435) metastatic potential, showing for the first time that two different populations of circulating cells can be quantified simultaneously in the vasculature of a single live mouse. We also non-invasively monitored a population of labeled, circulating red blood cells for more than two weeks, demonstrating that this technique can also quantify the dynamics of abundant cells in the vascular system for prolonged periods of time. These data are the first in vivo application of multichannel flow cytometry utilizing two-photon excitation, which will greatly enhance our capability to study circulating cells in cancer and other disease processes.     

Gain recovery dynamics and photon-driven transport in quantum cascade lasers

Quantum cascade lasers are semiconductor devices based on the interplay of perpendicular transport through the heterostructure and the intracavity lasing field. We employ femtosecond time-resolved pump-probe measurements to investigate the nature of the transport through the laser structure via the dynamics of the gain. The gain recovery is determined by the time-dependent transport of electrons through both the active regions and the superlattice regions connecting them. As the laser approaches and exceeds threshold, the component of the gain recovery due to the nonzero lifetime of the upper lasing state in the active region shows a dramatic reduction due to the onset of quantum stimulated emission; the drift of the electrons is thus driven by the cavity photon density. The gain recovery is qualitatively different from that in conventional lasers due to the superlattice transport in the cascade.     

Structural Determinants of the Binding and Activation of Estrogen Receptor α by Phenolic Thieno[2,3-d]pyrimidines

Synthetic, structural, and computational approaches were used to solve the puzzle as to how a phenolic nonsteroidal estrogen 1 with only a single H-bond to its receptor was more potent than an isomer 2 which formed an intricate network of H-bonds. Synthesis of a series of substituted phenols revealed that pK_a was not a determinant of estrogenic activity. First-principles calculation also failed to explain the difference in activity of 1 and 2 . Molecular dynamics revealed that 1 formed a more stable receptor complex compared to 2 , which may explain its increased activity despite forming fewer apparent H-bonds with the protein.     

Physical processes in azobenzene polymers on irradiation with polarized light

Azobenzenes can serve as model compounds for the study of transcis isomerization in more complex molecules. We have performed time-resolved spectroscopy in solutions containing free azobenzene chromophores and diols with a view to obtaining the energy levels and lifetimes of the excited states. A transition route based on experimental results for the theoretically calculated energy level scheme is proposed. Physical observations of surface relief in thin films of azobenzene polymers when irradiated with polarized light are reported. These include two beam polarization holographic observations and single beam transmission measurements through a mask, followed by atomic force microscope and profiler investigations. It is concluded that none of the prevalent theories can explain all the observed facts.