Correction of through-plane deformation artifacts in stimulated echo acquisition mode cardiac imaging.

Attempts to use a stimulated echo acquisition mode (STEAM) in cardiac imaging are impeded by imaging artifacts that result in signal attenuation and nulling of the cardiac tissue. In this work, we present a method to reduce this artifact by acquiring two sets of stimulated echo images with two different demodulations. The resulting two images are combined to recover the signal loss and weighted to compensate for possible deformation-dependent intensity variation. Numerical simulations were used to validate the theory. Also, the proposed correction method was applied to in vivo imaging of normal volunteers (n = 6) and animal models with induced infarction (n = 3). The results show the ability of the method to recover the lost myocardial signal and generate artifact-free black-blood cardiac images.

Mechanisms and evolutionary patterns of mammalian and avian dosage compensation.

As a result of sex chromosome differentiation from ancestral autosomes, male mammalian cells only contain one X chromosome. It has long been hypothesized that X-linked gene expression levels have become doubled in males to restore the original transcriptional output, and that the resulting X overexpression in females then drove the evolution of X inactivation (XCI). However, this model has never been directly tested and patterns and mechanisms of dosage compensation across different mammals and birds generally remain little understood. Here we trace the evolution of dosage compensation using extensive transcriptome data from males and females representing all major mammalian lineages and birds. Our analyses suggest that the X has become globally upregulated in marsupials, whereas we do not detect a global upregulation of this chromosome in placental mammals. However, we find that a subset of autosomal genes interacting with X-linked genes have become downregulated in placentals upon the emergence of sex chromosomes. Thus, different driving forces may underlie the evolution of XCI and the highly efficient equilibration of X expression levels between the sexes observed for both of these lineages. In the egg-laying monotremes and birds, which have partially homologous sex chromosome systems, partial upregulation of the X (Z in birds) evolved but is largely restricted to the heterogametic sex, which provides an explanation for the partially sex-biased X (Z) expression and lack of global inactivation mechanisms in these lineages. Our findings suggest that dosage reductions imposed by sex chromosome differentiation events in amniotes were resolved in strikingly different ways.

Flow structures at an idealized bifurcation : a numerical experiment

River bifurcations are key nodes within braided river systems controlling the flow and sediment partitioning and therefore the dynamics of the river braiding process. Recent research has shown that certain geometrical configurations induce instabilities that lead to downstream mid-channel bar formation and the formation of bifurcations. However, we currently have a poor understanding of the flow division process within bifurcations and the flow dynamics in the downstream bifurcates, both of which are needed to understand bifurcation stability. This paper presents results of a numerical sensitivity experiment undertaken using computational fluid dynamics (CFD) with the purpose of understanding the flow dynamics of a series of idealized bifurcations. A geometric sensitivity analysis is undertaken for a range of channel slopes (0.005 to 0.03), bifurcation angles (22 degrees to 42 degrees) and a restricted set of inflow conditions based upon simulating flow through meander bends with different curvature on the flow field dynamics through the bifurcation. The results demonstrate that the overall slope of the bifurcation affects the velocity of flow through the bifurcation and when slope asymmetry is introduced, the flow structures in the bifurcation are modified. In terms of bifurcation evolution the most important observation appears to be that once slope asymmetry is greater than 0.2 the flow within the steep bifurcate shows potential instability and the potential for alternate channel bar formation. Bifurcation angle also defines the flow structures within the bifurcation with an increase in bifurcation angle increasing the flow velocity down both bifurcates. However, redistributive effects of secondary circulation caused by upstream curvature can very easily counter the effects of local bifurcation characteristics. Copyright (C) 2011 John Wiley & Sons, Ltd.

Identification of different heart tissues from MRI C-SENC images using an unsupervised multi-stage fuzzy clustering technique.

PURPOSE: To objectively characterize different heart tissues from functional and viability images provided by composite-strain-encoding (C-SENC) MRI. MATERIALS AND METHODS: C-SENC is a new MRI technique for simultaneously acquiring cardiac functional and viability images. In this work, an unsupervised multi-stage fuzzy clustering method is proposed to identify different heart tissues in the C-SENC images. The method is based on sequential application of the fuzzy c-means (FCM) and iterative self-organizing data (ISODATA) clustering algorithms. The proposed method is tested on simulated heart images and on images from nine patients with and without myocardial infarction (MI). The resulting clustered images are compared with MRI delayed-enhancement (DE) viability images for determining MI. Also, Bland-Altman analysis is conducted between the two methods. RESULTS: Normal myocardium, infarcted myocardium, and blood are correctly identified using the proposed method. The clustered images correctly identified 90 +/- 4% of the pixels defined as infarct in the DE images. In addition, 89 +/- 5% of the pixels defined as infarct in the clustered images were also defined as infarct in DE images. The Bland-Altman results show no bias between the two methods in identifying MI. CONCLUSION: The proposed technique allows for objectively identifying divergent heart tissues, which would be potentially important for clinical decision-making in patients with MI.

Combining protein identification and quantification: C-terminal isotope-coded tagging using sulfanilic acid.

Two methods of differential isotopic coding of carboxylic groups have been developed to date. The first approach uses d0- or d3-methanol to convert carboxyl groups into the corresponding methyl esters. The second relies on the incorporation of two 18O atoms into the C-terminal carboxylic group during tryptic digestion of proteins in H(2)18O. However, both methods have limitations such as chromatographic separation of 1H and 2H derivatives or overlap of isotopic distributions of light and heavy forms due to small mass shifts. Here we present a new tagging approach based on the specific incorporation of sulfanilic acid into carboxylic groups. The reagent was synthesized in a heavy form (13C phenyl ring), showing no chromatographic shift and an optimal isotopic separation with a 6 Da mass shift. Moreover, sulfanilic acid allows for simplified fragmentation in matrix-assisted laser desorption/ionization (MALDI) due the charge fixation of the sulfonate group at the C-terminus of the peptide. The derivatization is simple, specific and minimizes the number of sample treatment steps that can strongly alter the sample composition. The quantification is reproducible within an order of magnitude and can be analyzed either by electrospray ionization (ESI) or MALDI. Finally, the method is able to specifically identify the C-terminal peptide of a protein by using GluC as the proteolytic enzyme.

High-throughput SELEX SAGE method for quantitative modeling of transcription-factor binding sites.

The ability to determine the location and relative strength of all transcription-factor binding sites in a genome is important both for a comprehensive understanding of gene regulation and for effective promoter engineering in biotechnological applications. Here we present a bioinformatically driven experimental method to accurately define the DNA-binding sequence specificity of transcription factors. A generalized profile was used as a predictive quantitative model for binding sites, and its parameters were estimated from in vitro-selected ligands using standard hidden Markov model training algorithms. Computer simulations showed that several thousand low- to medium-affinity sequences are required to generate a profile of desired accuracy. To produce data on this scale, we applied high-throughput genomics methods to the biochemical problem addressed here. A method combining systematic evolution of ligands by exponential enrichment (SELEX) and serial analysis of gene expression (SAGE) protocols was coupled to an automated quality-controlled sequence extraction procedure based on Phred quality scores. This allowed the sequencing of a database of more than 10,000 potential DNA ligands for the CTF/NFI transcription factor. The resulting binding-site model defines the sequence specificity of this protein with a high degree of accuracy not achieved earlier and thereby makes it possible to identify previously unknown regulatory sequences in genomic DNA. A covariance analysis of the selected sites revealed non-independent base preferences at different nucleotide positions, providing insight into the binding mechanism.

Cost-effectiveness analysis of a European primary-care physician training in smoking cessation counseling.

BACKGROUND: Physician training in smoking cessation counseling has been shown to be effective as a means to increase quit success. We assessed the cost-effectiveness ratio of a smoking cessation counseling training programme. Its effectiveness was previously demonstrated in a cluster randomized, control trial performed in two Swiss university outpatients clinics, in which residents were randomized to receive training in smoking interventions or a control educational intervention. DESIGN AND METHODS: We used a Markov simulation model for effectiveness analysis. This model incorporates the intervention efficacy, the natural quit rate, and the lifetime probability of relapse after 1-year abstinence. We used previously published results in addition to hospital service and outpatient clinic cost data. The time horizon was 1 year, and we opted for a third-party payer perspective. RESULTS: The incremental cost of the intervention amounted to US$2.58 per consultation by a smoker, translating into a cost per life-year saved of US$25.4 for men and 35.2 for women. One-way sensitivity analyses yielded a range of US$4.0-107.1 in men and US$9.7-148.6 in women. Variations in the quit rate of the control intervention, the length of training effectiveness, and the discount rate yielded moderately large effects on the outcome. Variations in the natural cessation rate, the lifetime probability of relapse, the cost of physician training, the counseling time, the cost per hour of physician time, and the cost of the booklets had little effect on the cost-effectiveness ratio. CONCLUSIONS: Training residents in smoking cessation counseling is a very cost-effective intervention and may be more efficient than currently accepted tobacco control interventions.