Estimating the probability of initiated cell death before tumor induction

The effects of cell toxicity are known to be inherent in carcinogenesis induced by radiation or chemical carcinogens. The event of cell death precludes tumor induction from occurring. A long standing problem is to estimate the proportion of initiated cells that die before tumor induction. No experimental techniques are currently available for directly gauging the rate of cell death over extended periods of time. The obstacle can be surmounted by newly developed theoretical methods of carcinogenesis modeling. In this paper, we apply such methods to published data on multiple lung tumors in mice receiving different schedules of urethane. Bioassays of this type play an important role in testing environmental chemicals for carcinogenic activity. Our estimates for urethane-induced carcinogenesis show that, unexpectedly, many initiated cells die early in the course of tumor promotion. We present numerical estimates for the probability of initiated cell death for different schedules (and doses) of urethane administration.

The role of London forces in defining noncentrosymmetric order of high dipole moment–high hyperpolarizability chromophores in electrically poled polymeric thin films

Graphs of second harmonic generation coefficients and electro-optic coefficients (measured by ellipsometry, attenuated total reflection, and two-slit interference modulation) as a function of chromophore number density (chromophore loading) are experimentally observed to exhibit maxima for polymers containing chromophores characterized by large dipole moments and polarizabilities. Modified London theory is used to demonstrated that this behavior can be attributed to the competition of chromophore-applied electric field and chromophore–chromophore electrostatic interactions. The comparison of theoretical and experimental data explains why the promise of exceptional macroscopic second-order optical nonlinearity predicted for organic materials has not been realized and suggests routes for circumventing current limitations to large optical nonlinearity. The results also suggest extensions of measurement and theoretical methods to achieve an improved understanding of intermolecular interactions in condensed phase materials including materials prepared by sequential synthesis and block copolymer methods.

Blood flow and oxygen delivery to human brain during functional activity: Theoretical modeling and experimental data

Coupling of cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) in physiologically activated brain states remains the subject of debates. Recently it was suggested that CBF is tightly coupled to oxidative metabolism in a nonlinear fashion. As part of this hypothesis, mathematical models of oxygen delivery to the brain have been described in which disproportionately large increases in CBF are necessary to sustain even small increases in CMRO2 during activation. We have explored the coupling of CBF and oxygen delivery by using two complementary methods. First, a more complex mathematical model was tested that differs from those recently described in that no assumptions were made regarding tissue oxygen level. Second, [15O] water CBF positron emission tomography (PET) studies in nine healthy subjects were conducted during states of visual activation and hypoxia to examine the relationship of CBF and oxygen delivery. In contrast to previous reports, our model showed adequate tissue levels of oxygen could be maintained without the need for increased CBF or oxygen delivery. Similarly, the PET studies demonstrated that the regional increase in CBF during visual activation was not affected by hypoxia. These findings strongly indicate that the increase in CBF associated with physiological activation is regulated by factors other than local requirements in oxygen.