Rhinovirus-induced modulation of gene expression in bronchial epithelial cells from subjects with asthma.

Rhinovirus (RV) infections trigger asthma exacerbations. Genome-wide expression analysis of RV1A-infected primary bronchial epithelial cells from normal and asthmatic donors was performed to determine whether asthma is associated with a unique pattern of RV-induced gene expression. Virus replication rates were similar in cells from normal and asthmatic donors. Overall, RV downregulated 975 and upregulated 69 genes. Comparisons of transcriptional profiles generated from microarrays and confirmed by quantitative reverse transcription PCR and cluster analysis showed some up- and downregulated genes in asthma cells involved in immune responses (IL1B, IL1F9, IL24, and IFI44) and airway remodeling (LOXL2, MMP10, FN1). Notably, most of the asthma-related differences in RV-infected cells were also present in the cells before infection. These findings suggest that differences in RV-induced gene expression profiles of cells from normal and mild asthmatic subjects could affect the acute inflammatory response to RV, and subsequent airway repair and remodeling.

The best interests of the child in assisted human reproduction: the interplay between the state, professionals, and parents.

Developments in assisted human reproduction (AHR) have aroused considerable debate and interest around the world, with most governments accepting that they are matters of public policy. This politicization of AHR is explored in the context of a consideration of the oft-used term "the best interests of the child." This "rallying call" is frequently cited as the primary concern in the determination of policy. This article is based on the contention that it is important to examine the interplay between the three main groups directly influencing "best interest" outcomes for AHR offspring. These groups are the professionals, the parents, and the state. It seeks to examine how this high-sounding and well-meaning commitment is addressed, advanced, or ignored in the interplay of these groups.

Gradient-based iterative image reconstruction scheme for time-resolved optical tomography.

Currently available tomographic image reconstruction schemes for optical tomography (OT) are mostly based on the limiting assumptions of small perturbations and a priori knowledge of the optical properties of a reference medium. Furthermore, these algorithms usually require the inversion of large, full, ill-conditioned Jacobian matrixes. In this work a gradient-based iterative image reconstruction (GIIR) method is presented that promises to overcome current limitations. The code consists of three major parts: 1) A finite-difference, time-resolved, diffusion forward model is used to predict detector readings based on the spatial distribution of optical properties; 2) An objective function that describes the difference between predicted and measured data; 3) An updating method that uses the gradient of the objective function in a line minimization scheme to provide subsequent guesses of the spatial distribution of the optical properties for the forward model. The reconstruction of these properties is completed, once a minimum of this objective function is found. After a presentation of the mathematical background, two- and three-dimensional reconstruction of simple heterogeneous media as well as the clinically relevant example of ventricular bleeding in the brain are discussed. Numerical studies suggest that intraventricular hemorrhages can be detected using the GIIR technique, even in the presence of a heterogeneous background.

Epidermal trans-urocanic acid and the UV-A-induced photoaging of the skin.

The premature photoaging of the skin is mediated by the sensitization of reactive oxygen species after absorption of ultraviolet radiation by endogenous chromophores. Yet identification of UV-A-absorbing chromophores in the skin that quantitatively account for the action spectra of the physiological responses of photoaging has remained elusive. This paper reports that the in vitro action spectrum for singlet oxygen generation after excitation of trans-urocanic acid mimics the in vivo UV-A action spectrum for the photosagging of mouse skin. The data presented provide evidence suggesting that the UV-A excitation of trans-urocanic acid initiates chemical processes that result in the photoaging of skin.

Risk factors associated with Corynebacterium pseudotuberculosis infection in California horses.

A case-control study was designed using equine medical records from the UC Davis Veterinary Medical Teaching Hospital (VMTH) and data derived through a mailed survey. The objective was to evaluate the associations between horse demographics, horse-management factors, and equine Corynebacterium pseudotuberculosis infection in California. Horses admitted to the VMTH between July 1 1992 and June 30 1994 served as the study base for case identification and simple random sampling of 800 controls. A questionnaire was mailed to the owners of all horses enrolled in the study to collect data on demographics, management and health-related questions. A logistic-regression model containing age, outdoor activity level, other locations in California, insect-control measures, contact with other horses, and summer pasture was developed. The final model was adjusted for the suspected confounding variables admission type, regular teaching hospital patient and breed. Horses of age between 1 and 2 yrs and between 3 and 5 yrs, and horses in contact with other horses or horses on summer pasture had significantly increased odds (p < 0.05) of being diagnosed with C. pseudotuberculosis infection. The results support the hypotheses that the disease predominantly affects young-adult horses of all breeds and both sexes, and that management factors play an important role in occurrence of the disease. Since the existing serological test system is not reliable and destruction of infected animals is not feasible, the most-logical approach for disease prevention is the early identification and isolation of clinical cases and the implementation of management changes like improvement of stable hygiene and insect control and change of pasture practices.

The origin of the wavelength-dependent photoreactivity of trans-urocanic acid.

Two-color, pulsed-laser photoacoustic calorimetry is used to distinguish between multiple rotamer or electronic state contributions to the absorption spectrum of the epidermal chromophore trans-urocanic acid. The data definitively show that the wavelength-dependent photochemistry of trans-urocanic acid results from the presence of two distinct, weakly coupled electronic states absorbing between 264 nm and 310 nm.

Tomographic reconstruction using 3D deformable models.

We address the issue of reconstructing the shape of an object with uniform interior activity from a set of projections. We estimate directly from projection data the position of a triangulated surface describing the boundary of the object while incorporating prior knowledge about the unknown shape. This inverse problem is addressed in a Bayesian framework using the maximum a posteriori (MAP) estimate for the reconstruction. The derivatives needed for the gradient-based optimization of the model parameters are obtained using the adjoint differentiation technique. We present results from a numerical simulation of a dynamic cardiac imaging study. A first-pass exam is simulated with a numerical phantom of the right ventricle using the measured system response of the University of Arizona FASTSPECT imager, which consists of 24 detectors. We demonstrate the usefulness of our approach by reconstructing the shape of the ventricle from 10,000 counts. The comparison with an ML-EM result shows the usefulness of the deformable model approach.

Socioeconomic and demographic factors are associated with worldwide patterns of stunting and wasting of children.

We estimated the variability among nations in the prevalence of stunting and wasting, evaluated which national factors are associated with stunting and wasting and examined the relationship of stunting with wasting. The World Health Organization Global Database on Child Growth, a comprehensive conceptual model and a database of national factors were used with variance components and regression analyses. There was substantial variability among nations and among provinces within nations. Most national variability for stunting (76%) and wasting (66%) was explained by national factors and geographic region. Higher energy availability, female literacy and gross product were the most important factors associated with lower prevalence of stunting. The association of health expenditures and stunting differed by region. Higher immunization rate and, for Asia only, energy availability were the most important factors associated with lower prevalence of wasting. Regional differences in the relationship between stunting and wasting were accounted for by national factors. Some factors associated with stunting and wasting differ at the national level. Child malnutrition within a household is greatly influenced by issues at national and provincial levels, and intervention should be considered at all three levels.

Determinants of variability among nations in child growth.

This cross-national study aimed at understanding variability in growth among nations and its determinants. It examined the variability of growth among nations, the factors most important for explaining this variability, how these factors jointly determine growth, and the consistency of the patterns and relationships. A conceptual model was adapted from U. Jonsson. National data on height and weight of children, sex, ethnicity, and 15 social, economic, health, education, and political factors were combined from three secondary sources. A sequence of multiple linear regression models was used with three age groups: 1-2, 3-5, and 6-10 years. Substantial variability in growth among nations was seen in comparison to that within nations. Regression models with sex, ethnicity, food security, maternal and child care, and health services and environment explained a large percentage of this variability. Institutions, politics/ideology, economic structure, and potential resources contributed little additionally to the models. Ethnic differences among nations were observed and persisted even when models controlled for other factors, but should not necessarily be interpreted as genetic differences. Determinants for height, weight, and weight adjusted for height were somewhat different. Adjustment for only previous growth and sex explained about 90% of variability in growth, supporting the assumption that growth patterns are generally established early in life. As policy decisions and programmes addressing mild-to-moderate malnutrition are increasingly considered, the implications of cross-national variability in growth may assume greater importance. Future work should examine simultaneously the effects of national, community, family, and individual characteristics on growth using data from individuals in a number of nations.

Enzyme inhibitors: new and known polybrominated phenols and diphenyl ethers from four Indo-Pacific Dysidea sponges.

Extracts and pure compounds isolated from four samples of Dysidea sp. sponges collected from two geographically distinct regions of the Indo-Pacific (Chuuk Atoll and Fiji) were assayed against five different enzyme assays, four of which are relevant to anticancer drug discovery and one of which (15-lipoxygenase) may detect compounds significant in modulating the development of atherosclerotic plaque. The pure compounds that inhibited various enzymes were polybrominated phenols and polybrominated phenoxyphenols. Fourteen of these phenols were isolated, six of which were new compounds. A variety of the phenols inhibited inosine monophosphate dehydrogenase (IMPDH), guanosine monophosphate synthetase, and 15-lipoxygenase. No activity was observed with protein tyrosine kinase pp60v-src or matrix metalloprotease.

Solvent and temperature effects on the excited singlet state absorption of diphenylbutadiene.

Nanosecond excited state absorption spectra of all-trans-1,4-diphenyl-1,3-butadiene (DPB) and a rigid s-cis DPB analog, 1,4-diphenyl-1,3-cyclopentadiene, were obtained in several hydrocarbon solvents at room temperature and low temperatures. Analysis of the excited state absorption spectra of these two molecules suggests the presence of excited state s-cis rotamers in DPB at room temperature.

Optimization of the constrained Algebraic Reconstruction Technique for the performance of a variety of visual tasks.

This work demonstrates the application of a method to optimize image reconstruction algorithms on the basis of the performance of specific visual tasks that are to be accomplished using the reconstructed images. The evaluation of task performance is numerically realized by a Monte Carlo simulation of the complete imaging chain, including the final inference based on the reconstructions. Fundamental to this evaluation is that it yields an average response by consideration of many initial scenes. It is shown that the use of the nonnegativity constraint in the Algebraic Reconstruction Technique can significantly improve performance in situations where there is a severe lack of measurements when the relaxation factor is optimized. There is no indication in any of the cases studied hitherto that the nonnegativity constraint can improve performance in situations where the data are complete, but noisy. It is also shown that neither the rms error nor the L1 error in constrained reconstructions are good predictors of task performance.

In vivo validation of a thermodilution system designed to measure peripheral blood flow.

A 5F triple-lumen thermodilution catheter was evaluated in a canine vena cava model to determine whether this catheter and the thermodilution technique provide valid in vivo determinations of blood flow. Our ultimate goal is to develop methods for studying limb blood flow in humans. Seven dogs were studied. Blood flow was provided and regulated by a calibrated roller pump. Flow rate determinations by thermodilution were made over a range of 0.5 to 5.01 1/minute. Excellent correlation (r = 0.98, r2 = 0.96, P less than 0.01) was found between actual flow and flow measured by thermodilution. The mean (+/- SD) coefficient of variation for the thermodilution method was 9.97 +/- 5.72 per cent over the flow range tested. The coefficient of variation tended to be higher at low flow rates. The thermodilution technique with this catheter provides valid in vivo determinations of blood flow through large vessels. This technology can be rationally applied to the study of limb blood flow in humans.

Radiographic screen-film noise power spectrum: calibration and intercomparison.

The magnitude of a measurement of the noise power spectrum (NPS) of a radiographic screen-film system is affected by the light-scattering properties of the film studied and the optical characteristics of the micro-densitometer used to sample the image. To facilitate absolute NPS intercomparisons among laboratories, NPS in terms of instrument density must be converted to diffuse density. Conversion in terms of a Callier Q factor was found to be inadequate due to nonlinearity of the density response of the microdensitometer. By establishing instrument-to-diffuse density characteristic curves for the microdensitometers at two laboratories and correcting the NPS by the square of the slopes of these curves at the density of the image, good agreement was achieved for independent NPS measurements of a given film sample.

On the optimality of the filtered backprojection algorithm.

It is shown that under certain conditions the filtered backprojection algorithm produces a computed tomographic reconstruction for which the statistical accuracy attainable in the amplitude estimation of large-area objects meets the general lower bound derived by Tretiak. In this sense, filtered backprojection is an optimum algorithm.