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Normal human retinal development involves orderly generation of rods and cones by complex mechanisms. Cell-fate specification involves progenitor cell lineage and external signals such as soluble factors and cell-cell interactions. In most inherited human retinal degenerations, including retinitis pigmentosa, a mutant gene causes loss of visual function, death of mature rods, and eventually death of all cone subtypes. Only one inherited retinal disorder, the enhanced S cone syndrome (ESCS), shows increased visual function, involving the minority S (blue) cones, and decreased rod and L͞M (red͞green) cone function. This autosomal recessive disease is caused by mutations in NR2E3, a photoreceptor nuclear receptor transcription factor, and may result from abnormal cell-fate determination, leading to excess S cones at the expense of other photoreceptor subtypes. In 16 ESCS patients with the most common NR2E3 mutation, R311Q, we documented an abnormal ratio of S to L͞M cone function and progressive retinal degeneration. We studied the postmortem retina of an ESCS patient homozygous for NR2E3 R311Q. No rods were identified, but cones were increased approximately 2-fold, and 92% were S cones. Only 15% of the cones expressed L͞M cone opsin, and some coexpressed S cone opsin. The retina was disorganized, with densely packed cones intermixed with inner retinal neurons. The retina was also degenerate, retaining photoreceptors in only the central and far peripheral regions. These observations suggest a key role for NR2E3 in regulation of human photoreceptor development. Degeneration of the NR2E3 retina may result from defective development, known S cone fragility, or abnormal maintenance of mature photoreceptors. T he molecular events during development of invertebrate and vertebrate retinas are incompletely understood. The specification of rods and cones involves interactions of both intrinsic and extrinsic factors, including cell lineage, soluble factors, and local cell-cell interactions (1-3). These complex signaling pathways involve nuclear receptors, a superfamily of transcription factors that share structural features, including DNA and ligandbinding domains (4, 5). A human photoreceptor-specific nuclear receptor (PNR), NR2E3, is a member of the nuclear receptor subfamily II (6). Coexpression of NR2E3, CRX (cone-rod homeobox; ref. 7), and NRL (nuclear retina leucine zipper; ref. 8) in human Y79 retinoblastoma cells suggests that NR2E3 is a component of a photoreceptor transcription cascade in human retinal development (6).Mutations in NR2E3 (9, 10) cause a unique human retinal disease, the enhanced S cone syndrome (ESCS), initially described using psychophysical and electrophysiological methods (11). ESCS patients lack rod photoreceptor function, like other inherited retinal degenerations such as retinitis pigmentosa (12), but are unique because their S (blue) cones, normally a minority population (13), are more responsive to light than the usually more populous L͞M (red͞green) cones (11, 14-16). The retinal pathology ...

Recognition of the bilateral relationships between oral and systemic health will challenge physicians and dentists to work together closely in the future when managing patients with diabetes and periodontal disease.

AlloysTwo mechanisms are proposed for the limitation of strength in transformation-toughened zirconia ceramics: that the strength is limited by the critical stress to induce the tetragonalto-monoclinic zirconia phase transformation and that the inherent R-curve behavior of these materials limits the strength. Experimental evidence to support both mechanisms is presented which agrees tolerably well with theoretical predictions. However, for materials with larger initial flaws and higher toughness the experimental results favor the R-curve argument.

Cumulative survival rates for MS fixtures placed in one and two stages as well as one-stage TPS screws up to the 2- to 3-year follow-up examination were similar, indicating excellent clinical results. Radiographic measurements for changes in crestal bone loss were clinically insignificant for fixtures placed in one stage. For two-stage fixtures, maxillary changes were insignificant, whereas mandibular bone loss was statistically significant but clinically insignificant. Changes in crestal bone loss for TPS implants were statistically significant.

A plate with a semi-infinite crack is repaired by having reinforcing sheets bonded to its faces, and is subjected to a uniformly distributed tensile load at right-angles to the crack. It is shown that the crack extension force has a finite value, provided that the reinforced structure can still carry the load if the crack, instead of being semi-infinite, runs across the whole plate, cutting it in half. The case of a plate with a crack of finite length is considered next: the determination of the force is reduced to the solution of a Fredholm integral equation, from which the asymptotic behaviour for short cracks is deduced by the method of successive approximations. These results provide an upper bound to the force for arbitrary crack lengths. A comparison with numerical results suggests that this upper bound is sufficiently close to the actual value to be useful in practice. The residual thermal stress induced by the process of bonding, and the resulting force on a crack, are shown to depend sensitively on the nature of the constraint at the edges of the plate, as well as on the extent of the plate outside the heated region. A number of extensions to less idealized configurations are discussed.

The stress-free thermal strain corresponding to the temperature rise induced in a target by an incident laser pulse constitutes a volume source of ultrasound. In the present work, the appropriate point-source representation is derived by starting from a general representation theorem for volume sources. A formal solution for the double (Hankel–Laplace) transform of the displacement potentials is obtained for axially symmetric configurations, with the point-source lying within or on the surface of a half-space or a plate. The Cagniard-de Hoop technique is used to invert these double transforms. For the source on the surface of a half-space, detailed results are presented for the wave-front expansions, the displacement along the axis of symmetry and on the surface, the directivity pattern, and the partition of energy between longitudinal, transverse, and surface waves. For the source within or on the surface of a plate, only the epicentral displacement is considered in detail.

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