Relative kinematics of the rib cage and abdomen during speech and nonspeech behaviors of 15-month-old children.

Speech motor control emerges in the neurophysiologic context of widely distributed, powerful coordinative mechanisms, including those mediating respiratory function. It is unknown, however, whether developing children are able to exploit the capabilities of neural circuits controlling homeostasis for the production of speech and voice. Speech and rest breathing were investigated in eleven 15-month-old children using inductance plethysmography (Respitrace). Rib cage and abdominal kinematics were studied using a time-varying correlational index of thoracoabdominal coupling (i.e., reflecting the synchrony of movement of the rib cage and abdomen) as well as simple classification of the moment-to-moment kinematic relationship of these two functional components (i.e., concurrent expansion or compression, or oppositional movement). Results revealed markedly different patterns of movement for rest breathing and speech breathing, although within types of vocalization (nonspeech vocalization, babbling, true word production) no differences were apparent. Whereas rest breathing was characterized by tight coupling of rib cage and abdominal movement (average correlation coefficients usually exceeded .90), speech breathing exhibited weak coupling (the correlation coefficient ranged widely, but averaged about .60). Furthermore, speech production by these toddlers included the occurrence of both rib cage and abdominal paradoxing, which are observed infrequently in adult speakers. These results fail to support the suggestion that speech emerges from the extant coordinative organization of rest breathing. Rather, even in its earliest stages breathing for speech and voice exhibits kinematic properties distinct from those of other observed behaviors.

Prediction of q-values and conformations of gadolinium chelates for magnetic resonance imaging.

For gadolinium chelates, we determined that there is a linear correlation between calculated solvent-accessible surface area and q-value, the number of rapidly exchanging water molecules directly bound to the gadolinium ion. A calibration curve was developed to predict q-value based on the solvent-accessible surface area of gadolinium. This predictive method was validated with the following gadolinium crystal structures: (ethylenediaminetetraacetic acid)-gadolinium(III) [Gd(EDTA)] [Templeton, L. K., Templeton, D. H., Zalkin, A., and Ruben, H. W. (1982) Anomalous Scattering by Praseodymium, Samarium, and Gadolinium and Structures of their Thylenediaminetetraacetate (EDTA) Salts. Acta Crystallogr., Sect. B 38, 2155], (1,4,7,10-tetraazacyclododecane-N,N',N' ',N' "-tetraacetic acid)-gadolinium(III) [Gd(DOTA)] [Dubost, J.-P., Leger, J.-M., Langlois, M.-H., Meyer, D., and Schaefer, M. (1991) Structure of a Magnetic Resonance Imaging Agent - The Gadolinium-DOTA Complex C(16)H(24)N(4)O(8)NaGd, 5H(2)O. C. R. Acad. Sci., Ser. 2 312, 349], (diethylenetriaminepentaacetic acid)-gadolinium(III) [Gd(DTPA)] [Stezowski, J. J., and Hoard, J. L. (1984) Heavy Metal Ionophores - Correlations Among Structural Parameters of Complexed Nonpeptide Polyamino Acids. Isr. J. Chem. 24, 323], (diethylenepenta-acetato)-gadolinium(III) [Gd(DTPA-BEA)] [Smith, P. H., Brainard, J. R., Morris, D. E., Jarvinen, G. D., and Ryan, R. R. (1989) Solution and Solid-State Characterization of Europium and Gadolinium Schiff-Base Complexes and Assessment of their Potential as Contrast Agents in Magnetic Resonance Imaging. J. Am. Chem. Soc. 111, 7437], and (1,7,13-triaza-4,10, 16-trioxacyclo-octadecane-N,N',N' '-triacetato)-gadolinium(III) [Gd(TTTA)] [Chen, D., Squattrito, P. J., Martell, A. E., and Clearfield, A. (1990) Synthesis and Crystal Structure of a 9-Coordinate Gadolinium(III) Complex of 1,7,13-Triaza-4,10, 16-Trioxacyclooctadecane-N,N',N' '-Tri-Acetic Acid. Inorg. Chem. 29, 4366]. Predicted q-values were in complete agreement with experimentally determined q-values. A genetic algorithm-based conformational search method was developed to generate valid 3D models for gadolinium chelates. The method was successfully tested on the following gadolinium chelates: Gd(EDTA) (Templeton et al., 1982), Gd(DOTA) (Dubost et al., 1991), Gd(DTPA-BEA) (Smith et al., 1989), Gd(TTTA) (Chen et al., 1990), Gd(triethylene glycol) [Rogers, R. D., Voss, E. J., and Etzenhouser, R. D. (1988) F-Element Crown Ether Complexes. 17. Synthetic and Structural Survey of Lanthanide Chloride Tiethylene Glycol Complexes. Inorg. Chem. 27, 533], and Gd(tetraethylene glycol) [Rogers, R. D., Etzenhouser, R. D., Murdoch, J. S., and Reyes, E. (1991) Macrocycle Complexation Chemistry. 35. Survey of the Complexation of the Open-Chain 15-Crown-5 Analogue tetraethylene Glycol with the Lanthanide Chlorides. Inorg. Chem. 30, 1445].

Prospective identification of biologically active structures by topomer shape similarity searching.

The principle of bioisosterism-similarly shaped molecules are more likely to share biological properties than are other molecules-has long helped to guide drug discovery. An algorithmic implementation of this principle, based on shape comparisons of a single rule-generated "topomer" conformation per molecule, had been found to be the descriptor most consistently predictive of similar biological properties, in retrospective studies, and also to be well-suited for searching large (>10(12)) "virtual libraries" of potential reaction products. Therefore a prospective trial of this shape similarity searching method was carried out, with synthesis of 425 compounds and testing of them for inhibition of binding of angiotensin II (A-II). The 63 compounds that were identified by shape searching as most similar to any of four query structures included all of the seven compounds found to be highly active, with none of the other 362 structures being highly active (p < 0.001). Additional consistent relations (p < 0.05) were found, among all 425 compounds, between the degree of shape similarity to the nearest query structure and the frequency of various levels of observed activity. Known "SAR" (rules specifying structural features required for A-II antagonism) were also regenerated within the biological data for the 63 shape similar structures.

Total synthesis of globotriaosylceramide (Gb3) and lysoglobotriaosylceramide (lysoGb3).

We have recently reported a highly efficient and stereocontrolled synthesis of globotriaosylceramide (Gb3, 1) in optically pure form. Key to our synthetic strategy was the implementation of the two-stage activation of thioglycosides for formation of the glycosidic bonds and the utilization of (2S, 3S, 4E)-2-azido-3-O-(tert-butyldimethylsilyl)-4-octadecen-1,3-di ol (9) as a sphingosine equivalent. The syntheses of Gb3 (1) and lysoGb3 (2) were achieved by stereocontrolled coupling of 2,3,4,6-tetra-O-benzyl-alpha-D-galactosyl fluoride (15) with phenyl O-(6-O-benzoyl-2,3-di-O-pivaloyl-beta-D-galactopyranosyl)- (1----4)-2,3,6-tri-O-pivaloyl-1-thio-beta-D-glucopyranoside (14) to form the P kappa antigen trisaccharide masked as a phenyl 1-thioglycoside at the reducing end. Thioglycoside 16 was converted into glycosyl fluoride 19, which was coupled to 9 in high yield. The coupled product 20 was converted into the title compounds 1 and 2 in four and three steps, respectively. This article presents the total synthesis of 1 and 2 in full experimental detail.