The impact of density and atomic composition on the dosimetric response of various detectors in small photon radiation fields is characterized using a 'density-correction' factor, F(detector), defined as the ratio of Monte Carlo calculated doses delivered to water and detector voxels located on-axis, 5 cm deep in a water phantom with a SSD of 100 cm. The variation of F(detector) with field size has been computed for detector voxels of various materials and densities. For ion chambers and solid-state detectors, the well-known variation of F(detector) at small field sizes is shown to be due to differences between the densities of detector active volumes and water, rather than differences in atomic number. However, associated changes in the measured shapes of small-field profiles offset these variations in F(detector), so that integral doses measured using the different detectors are quite similar, at least for slit fields. Since changes in F(detector) with field size arise primarily from differences between the densities of the detector materials and water, ideal small-field relative dosimeters should have small active volumes and water-like density.

Bar-headed geese (Anser indicus) fly at up to 9,000 m elevation during their migration over the Himalayas, sustaining high metabolic rates in the severe hypoxia at these altitudes. We investigated the evolution of cardiac energy metabolism and O(2) transport in this species to better understand the molecular and physiological mechanisms of high-altitude adaptation. Compared with low-altitude geese (pink-footed geese and barnacle geese), bar-headed geese had larger lungs and higher capillary densities in the left ventricle of the heart, both of which should improve O(2) diffusion during hypoxia. Although myoglobin abundance and the activities of many metabolic enzymes (carnitine palmitoyltransferase, citrate synthase, 3-hydroxyacyl-coA dehydrogenase, lactate dehydrogenase, and pyruvate kinase) showed only minor variation between species, bar-headed geese had a striking alteration in the kinetics of cytochrome c oxidase (COX), the heteromeric enzyme that catalyzes O(2) reduction in oxidative phosphorylation. This was reflected by a lower maximum catalytic activity and a higher affinity for reduced cytochrome c. There were small differences between species in messenger RNA and protein expression of COX subunits 3 and 4, but these were inconsistent with the divergence in enzyme kinetics. However, the COX3 gene of bar-headed geese contained a nonsynonymous substitution at a site that is otherwise conserved across vertebrates and resulted in a major functional change of amino acid class (Trp-116 → Arg). This mutation was predicted by structural modeling to alter the interaction between COX3 and COX1. Adaptations in mitochondrial enzyme kinetics and O(2) transport capacity may therefore contribute to the exceptional ability of bar-headed geese to fly high.

Coordinated development of brain stem and spinal target neurons is pivotal for the emergence of a precisely functioning locomotor system. Signals that match the development of these far-apart regions of the central nervous system may be redeployed during spinal cord regeneration. Here we show that descending dopaminergic projections from the brain promote motor neuron generation at the expense of V2 interneurons in the developing zebrafish spinal cord by activating the D4a receptor, which acts on the hedgehog pathway. Inhibiting this essential signal during early neurogenesis leads to a long-lasting reduction of motor neuron numbers and impaired motor responses of free-swimming larvae. Importantly, during successful spinal cord regeneration in adult zebrafish, endogenous dopamine promotes generation of spinal motor neurons, and dopamine agonists augment this process. Hence, we describe a supraspinal control mechanism for the development and regeneration of specific spinal cell types that uses dopamine as a signal.

Accurate characterization of small-field dosimetry requires measurements to be made with precisely aligned specialized detectors and is thus time consuming and error prone. This work explores measurement differences between detectors by using a Monte Carlo model matched to large-field data to predict properties of smaller fields. Measurements made with a variety of detectors have been compared with calculated results to assess their validity and explore reasons for differences. Unshielded diodes are expected to produce some of the most useful data, as their small sensitive cross sections give good resolution whilst their energy dependence is shown to vary little with depth in a 15 MV linac beam. Their response is shown to be constant with field size over the range 1-10 cm, with a correction of 3% needed for a field size of 0.5 cm. BEAMnrc has been used to create a 15 MV beam model, matched to dosimetric data for square fields larger than 3 cm, and producing small-field profiles and percentage depth doses (PDDs) that agree well with unshielded diode data for field sizes down to 0.5 cm. For fields sizes of 1.5 cm and above, little detector-to-detector variation exists in measured output factors, however for a 0.5 cm field a relative spread of 18% is seen between output factors measured with different detectors-values measured with the diamond and pinpoint detectors lying below that of the unshielded diode, with the shielded diode value being higher. Relative to the corrected unshielded diode measurement, the Monte Carlo modeled output factor is 4.5% low, a discrepancy that is probably due to the focal spot fluence profile and source occlusion modeling. The large-field Monte Carlo model can, therefore, currently be used to predict small-field profiles and PDDs measured with an unshielded diode. However, determination of output factors for the smallest fields requires a more detailed model of focal spot fluence and source occlusion.