The deformability of double helical DNA is critical for its packaging in the cell, recognition by other molecules, and transient opening during biochemically important processes. Here, a complete set of sequence-dependent empirical energy functions suitable for describing such behavior is extracted from the f luctuations and correlations of structural parameters in DNA-protein crystal complexes. These elastic functions provide useful stereochemical measures of the local base step movements operative in sequencespecific recognition and protein-induced deformations. In particular, the pyrimidine-purine dimers stand out as the most variable steps in the DNA-protein complexes, apparently acting as f lexible ''hinges'' fitting the duplex to the protein surface. In addition to the angular parameters widely used to describe DNA deformations (i.e., the bend and twist angles), the translational parameters describing the displacements of base pairs along and across the helical axis are analyzed. The observed correlations of base pair bending and shearing motions are important for nonplanar folding of DNA in nucleosomes and other nucleoprotein complexes. The knowledge-based energies also offer realistic threedimensional models for the study of long DNA polymers at the global level, incorporating structural features beyond the scope of conventional elastic rod treatments and adding a new dimension to literal analyses of genomic sequences.In addition to the genetic message, DNA base sequence carries a multitude of other signals related to the manipulation of the long, thread-like molecule. Primary sequences of nucleic acid bases determine three-dimensional structures whose physical properties reflect the constituent residues. The existing library of solved DNA crystal structures (1), for example, reveals subtle sequence-dependent irregularities in the orientation and displacement of adjacent residues (2). Duplex stability under a given set of environmental conditions also depends to good approximation on the identity of the 10 nearest neighbor base pairs (3). The linear sequence of genetic information thus expands into a base sequence-dependent spatial and energetic code that governs the global organization of the double helix and its susceptibility to interactions with other molecules.Interest in understanding the physical properties of genomic DNA has prompted the development of new approaches to analyze and depict the sequence-dependent bending and twisting of neighboring base pairs. Studies of gel migration (4), chain cyclization kinetics (4, 5), and nucleosome phasing (6) have yielded a variety of sequence-dependent models to account for the observed data. Furthermore, collected oligonucleotide crystal structures show similar conformational trends (2), although there are discrepancies between the x-ray and solution assessments of the direction of bending at a few dimer steps (7,8). The solid state data additionally reveal sequence-dependent differences in the displacement of base pairs [see, e.g., Slide (2)], a ...

There was no significant difference in stage at presentation of renal cancer diagnosed in 1973 to 1985 compared with that diagnosed in 1986 to 1998. While the lack of a decrease in distant disease despite the increased detection of regional and localized renal cancer implies that a proportion of innocuous renal cancer cases may be detected by increased abdominal imaging, the increased incidence of renal cancer in all 3 categories indicates that other factors may also be contributing to the increasing incidence of renal cancer.

Telemarketers have a higher prevalence of voice problems than the control group. These problems affect productivity and are associated with modifiable risk factors. Evaluation of occupational voice disorders must encompass all of the determinants of health status, and treatment must focus on modifiable risk factors, not just the reduction of occupational vocal load.