Quantitative determination of the mineral distribution in different collagen zones of calcifying tendon using high voltage electron microscopic tomography

High voltage electron microscopic tomography was used to make the first quantitative determination of the distribution of mineral between different regions of collagen fibrils undergoing early calcification in normal leg tendons of the domestic turkey, Meleagris gallopavo. The tomographic 3-D reconstruction was computed from a tilt series of 61 different views spanning an angular range of +/- 60 degrees in 2 degrees intervals. Successive applications of an interactive computer operation were used to mask the collagen banding pattern of either hole or overlap zones into separate versions of the reconstruction. In such 3-D volumes, regions specified by the mask retained their original image density while the remaining volume was set to background levels. This approach was also applied to the mineral crystals present in the same volumes to yield versions of the 3-D reconstructions that were masked for both the crystal mass and the respective collagen zones. Density profiles from these volumes contained a distinct peak corresponding only to the crystal mass. A comparison of the integrated density of this peak from each profile established that 64% of the crystals observed were located in the collagen hole zones and 36% were found in the overlap zones. If no changes in crystal stability occur once crystals are formed, this result suggests the possibilities that nucleation of mineral is preferentially and initially associated with the hole zones, nucleation occurs more frequently in the hole zones, the rate of crystal growth is more rapid in the hole zones, or a combination of these alternatives. All lead to the conclusion that the overall accumulation of mineral mass is predominant in the collagen hole zones compared to overlap zones during early collagen fibril calcification.     

Estimating the lifetime utilization rate of radiotherapy in cancer patients: the Multicohort Current Utilization Table (MCUT) method

Extensive research has been carried out to establish the appropriate proportion of cancer patients requiring radiotherapy at some point during their illness. However, it is difficult to compare the actual rates against the appropriate rate, because calculating the actual rates requires life-long follow up of cancer patients. We have developed a method, referred to as the Multicohort Current Utilization Table (MCUT) method, to estimate the predicted lifetime utilization rates based on current medical practice. We implemented the method in SAS as a macro, and validated it by comparing the predicted and the actual utilization rates of radiotherapy in lung, breast, and prostate cancer cases diagnosed in Ontario, Canada. The MCUT method could be used to predict lifetime utilization rate of any medical services.     

Mie scattering from a sonoluminescing air bubble in water

A single bubble of air in water can emit pulses of blue-white light that have durations of less than 50 ps while it is oscillating in an acoustic standing wave. The emission is called sonoluminescence. A knowledge of the bubble diameter throughout the cycle, and in particular near the time of sonoluminescence emission, can provide important information about the phenomenon. A new Mie scattering technique is developed to determine the size of the bubble through its expansion and collapse during the acoustic cycle. The technique does not rely on an independent means of calibration or on accurate measurements of the scattered intensity.     

Experimental investigation of the self- and N(2)-broadened continuum within the ν(2) band of water vapor

We present an experimental study of the self- and N(2)-broadened H(2) O continuum in microwindows within the ν(2) fundamental centered at ~1600 cm(-1). The continuum is derived from transmission spectra recorded at room temperature with a BOMEM Fourier transform spectrometer at a resolution of ~0.040 cm(-1). Although we find general agreement with previous studies, our results suggest that there is significant near-wing super-Lorentzian behavior that produces a highly wave-number-dependent structure in the continuum as it is currently defined.     

Biomarkers in pediatrics: children as biomarker orphans

Biomarkers have enormous potential to improve patient care by establishing tests of diagnosis, prognosis, and treatment effects. Successfully translating a biomarker from discovery to clinical application demands high-quality discovery research and high-quality clinical studies for biomarker validation; however, there are additional challenges that face biomarker research in pediatrics. There are also additional characteristics of pediatric medicine that make biomarker research especially needed. This review focuses on the fundamentals of biomarkers, the additional considerations needed for applying biomarker research to children, and recommendations for advancing pediatric biomarker research.     

Age-related differences in warning symbol comprehension and training effectiveness: effects of familiarity, complexity, and comprehensibility

Age-related changes in selective attention, inhibitory efficiency, and the ability to form new associations suggest that older adults may have greater difficulty with more complex and less comprehensible symbols. We examined comprehension of symbols varying in terms of ratings of familiarity, complexity, and comprehensibility, by younger (aged 18-35) and older (aged 55-70) adults. It was found that older adults have greater difficulty than younger adults in comprehending warning symbols and that accident scenario training improves comprehension. Regression analyses indicated that familiarity and comprehensibility were important in determining performance on the pre-training comprehension test by both younger and older adults. However, training eliminated the effects of stimulus characteristics for younger adults, while older adults' comprehension continued to be significantly influenced by comprehensibility. We suggest that symbol design incorporates cues to knowledge to facilitate the linkage between new knowledge (i.e. the warning symbol) and relevant knowledge in long-term memory. Statement of Relevance: Symbol characteristics play an important role in age-related differences in warning symbol comprehension. To optimise comprehension by older adults, symbols should have a clear relationship with areal-world referent. Alternatively, symbol design could incorporate cues to knowledge to facilitate the linkage between new knowledge and relevant knowledge in long-term memory.     

Halogenated ligands and their interactions with amino acids: implications for structure-activity and structure-toxicity relationships

The properties of chemicals are rooted in their molecular structure. It follows that structural analysis of specific interactions between ligands and biomolecules at the molecular level is invaluable for defining structure-activity relationships (SARs) and structure-toxicity relationships (STRs). This study has elucidated the structural and molecular basis of interactions of biomolecules with alkyl and aryl halides that are extensively used as components in many commercial pesticides, disinfectants, and drugs. We analyzed the protein structures deposited in Protein Data Bank (PDB) for structural information associated with interactions between halogenated ligands and proteins. This analysis revealed distinct patterns with respect to the nature and structural characteristics of halogen interactions with specific types of atoms and groups in proteins. Fluorine had the highest propensity of interactions for glycine, while chlorine for leucine, bromine for arginine, and iodine for lysine. Chlorine, bromine and iodine had the lowest propensity of interactions for cysteine, while fluorine had a lowest propensity for proline. These trends for highest propensity shifted towards the hydrophobic residues for all the halogens when only interactions with the side chain were considered. Halogens had equal propensities of interaction for the halogen bonding partners (nitrogen and oxygen atoms), albeit with different geometries. The optimal angle for interactions with halogens was approximately 120 degrees for oxygen atoms, and approximately 96 degrees for nitrogen atoms. The distance distributions of halogens with various amino acids were mostly bimodal, and the angle distributions were unimodal. Insights gained from this study have implications for the rational design of safer drugs and commercially important chemicals.