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The chemical mechanism for formation of electronically excited-state molecules from the thermal reaction of dimethyldioxetanone was studied. Light production in the presence of certain easily oxidized aromatic hydrocarbons was found not to conform to the classical mechanistic schemes for chemiexcitation. Detailed investigation of the dioxetanone s stem revealed light formation by the recently discovered, chemically initiated electron-exchange process. This result is extrapolated to bioluminescent systems. In particular, the key high-energy molecule involved in firefly luminescence, which has been identified as a dioxetanone, is postulated to form excited states as a result of intramolecular electron transfer from the phenoxythiazole moiety to the dioxetanone. Subsequent rapid decarboxylation results in direct formation of an excited singlet state of the emitting amide. Bioluminescent organisms are widely distributed throughout terrestrial and aquatic environments. Although the biological purpose of luminescence varies from species to species, the chemical mechanism for generation of the electronically excited state, which subsequently emits light, appears to be general in a wide variety of organisms. In nearly all of the bioluminescent processes that have been investigated, high-energy cyclic peroxide molecules are implicated as providing the energy necessary for excited state generation (1). In the study of bioluminescent mechanisms the central concerns have been: (i) identification of the molecule capable of undergoing a reaction with a free energy change sufficient to permit excited state generation, (ii) characterization of the emitting species, and (iii) identification of the molecular process that converts the high-energy reactant to an electronically excited product molecule.Our recent investigations (2) of chemiluminescence have led to the discovery of a general mechanism of excited state formation identified as chemically initiated electron exchange luminescence. Studies of exergonic chemical reactions that model bioluminescent systems now permit us to suggest that this mechanism is operative in the formation of electronically excited states in living organisms. The light-forming reaction of the North American firefly (Photinus pyralis) will serve as the prototypical case. The conclusions reached from this system are readily extended to other bioluminescent reactions.Many excellent studies of bioluminescence from the firefly have led to the characterization of the enzyme/substrate system involved in the light generation step (3). In summary, the substrate luciferin has been identified as 1 and independently synthesized. Reaction of 1 with oxygen in the presence of the enzyme luciferase generates a high-energy content molecule that has been identified as the dioxetanone (2) by 180 labeling studies (4, 5). In order to produce bioluminescence, 2 loses the The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "adv...

Purpose:To investigate the use of the whole-breast sound speed measurement as a marker of breast density (BD), a known risk factor for breast cancer. Methods: As part of an ongoing study of breast cancer detection, 249 patients were scanned with a clinical prototype that operates on the principles of ultrasound tomography. Typically, 40-100 sound speed tomograms were reconstructed from the scan data, corresponding to the entire volume of the breast of each patient. The data were used to estimate the volume averaged sound speed (VASS) of the breast for each patient. The corresponding mammograms were used to calculate mammographic percent density (MPD) using CUMULUS software. Film mammograms were available for 164 patients while 85 digital mammograms were available for the remaining patients. Standard statistical techniques were used to determine associations of breast sound speed with a variety of mammographic measures such as percent density, area of dense tissue, and area of nondense tissue. Furthermore, associations of breast sound speed with continuous variables such as age and weight and dichotomous variables such as parity and menopausal status were also assessed. Results: VASS was found to be significantly associated with MPD. The Spearman correlation coefficient (r s ) between VASS and MPD was found to be 0.77 and 0.71 for film and digital mammography, respectively. VASS was positively correlated with dense areas by mammography, both digital (r s = 0.46) and film (r s = 0.56). VASS was negatively associated with nondense area by mammography, both digital (r s = −0.58) and film (r s = −0.63). BD by all methods was less in postmenopausal than in premenopausal women. The MPD was lower in the postmenopausal group (by 6.6%, p < 0.08, for the digital group and 7.73%, p < 0.007, for the film group). The VASS was also lower in the postmenopausal group (by 15 m/s, p < 0.001 for the digital group and 8 m/s, p < 0.08, for the film group). The association of MPD with age was characterized with r s = −0.06 (p < 0.6) for digital mammography and r s = −0.53 (p < 0.002) for film mammography. For weight, the MPD associations were characterized by r s = −0.53 (p < 0.0001) for digital mammography and −0.38 (p < 0.0001) for film mammography. The association of VASS with age was r s = −0.33 (p < 0.002) for the digital group and −0.17 (p < 0.03) for the film group. For weight, the relationship was characterized with r s = −0.45 (p < 0.001) for the digital group and −0.37 (p < 0.0001) for the film group. Conclusions: The association between VASS and MPD is strong for both film and digital mammography, suggesting that VASS is a viable measure of breast density. This result sets the stage for future work that will focus on directly testing the association of VASS with breast cancer risk.