Analysis of Regional Mechanics in Canine Lung Injury Using Forced Oscillations and 3D Image Registration

Acute lung injury is characterized by heterogeneity of regional mechanical properties, which is thought to be correlated with disease severity. The feasibility of using respiratory input impedance ($Z_{rs}$) and computed tomographic (CT) image registration for assessing parenchymal mechanical heterogeneity was evaluated. In six dogs, measurements of ($Z_{rs}$) before and after oleic acid injury at various distending pressures were obtained, followed by whole lung CT scans. Each ($Z_{rs}$) spectrum was fit with a model incorporating variable distributions of regional compliances. CT image pairs at different inflation pressures were matched using an image registration algorithm, from which distributions of regional compliances from the resulting anatomic deformation fields were computed. Under baseline conditions, average model compliance decreased with increasing inflation pressure, reflecting parenchymal stiffening. After lung injury, these average compliances decreased at each pressure, indicating derecruitment, alveolar flooding, or alterations in intrinsic tissue elastance. However, average compliance did not change as inflation pressure increased, consistent with simultaneous recruitment and strain stiffening. Image registration revealed peaked distributions of regional compliances, and that small portions of the lung might undergo relative compression during inflation. The authors conclude that assessments of lung function using ($Z_{rs}$) combined with the structural alterations inferred from image registration provide unique but complementary information on the mechanical derangements associated with lung injury

Comparison of Image Registration Based Measures of Regional Lung Ventilation from Dynamic Spiral CT with Xe-CT

Purpose: Regional lung volume change as a function of lung inflation serves as an index of parenchymal and airway status as well as an index of regional ventilation and can be used to detect pathologic changes over time. In this article, we propose a new regional measure of lung mechanics --- the specific air volume change by corrected Jacobian. Methods: 4DCT and Xe-CT data sets from four adult sheep are used in this study. Nonlinear, 3D image registration is applied to register an image acquired near end inspiration to an image acquired near end expiration. Approximately 200 annotated anatomical points are used as landmarks to evaluate registration accuracy. Three different registration-based measures of regional lung mechanics are derived and compared: the specific air volume change calculated from the Jacobian (SAJ); the specific air volume change calculated by the corrected Jacobian (SACJ); and the specific air volume change by intensity change (SAI). Results: After registration, the mean registration error is on the order of 1 mm. For cubical ROIs in cubes with size 20 mm $\times$ 20 mm $\times$ 20 mm, the SAJ and SACJ measures show significantly higher correlation (linear regression, average $r^2=0.75$ and $r^2=0.82$) with the Xe-CT based measure of specific ventilation (sV) than the SAI measure. For ROIs in slabs along the ventral-dorsal vertical direction with size of 150 mm $\times$ 8 mm $\times$ 40 mm, the SAJ, SACJ, and SAI all show high correlation (linear regression, average $r^2=0.88$, $r^2=0.92$ and $r^2=0.87$) with the Xe-CT based sV without significant differences when comparing between the three methods. Conclusion: Given a deformation field by an image registration algorithm, significant differences between the SAJ, SACJ, and SAI measures were found at a regional level compared to the Xe-CT sV in four sheep that were studied

High-resolution three-dimensional hybrid MRI + low dose CT vocal tract modeling:A cadaveric pilot study

SummaryObjectivesMRI based vocal tract models have many applications in voice research and education. These models do not adequately capture bony structures (e.g. teeth, mandible), and spatial resolution is often relatively low in order to minimize scanning time. Most MRI sequences achieve 3D vocal tract coverage at gross resolutions of 2 mm3 within a scan time of <20 seconds. Computed tomography (CT) is well suited for vocal tract imaging, but is infrequently used due to the risk of ionizing radiation. In this cadaveric study, a single, extremely low-dose CT scan of the bony structures is blended with accelerated high-resolution (1 mm3) MRI scans of the soft tissues, creating a high-resolution hybrid CT-MRI vocal tract model.MethodsMinimum CT dosages were determined and a custom 16-channel airway receiver coil for accelerated high (1 mm3) resolution MRI was evaluated. A rigid body landmark based partial volume registration scheme was then applied to the images, creating a hybrid CT-MRI model that was segmented in Slicer.ResultsUltra-low dose CT produced images with sufficient quality to clearly visualize the bone, and exposed the cadaver to 0.06 mSv. This is comparable to atmospheric exposures during a round trip transatlantic flight. The custom 16-channel vocal tract coil produced acceptable image quality at 1 mm3 resolution when reconstructed from ∼6 fold undersampled data. High (1 mm3) resolution MR imaging of short (<10 seconds) sustained sounds was achieved. The feasibility of hybrid CT-MRI vocal tract modeling was successfully demonstrated using the rigid body landmark based partial volume registration scheme. Segmentations of CT and hybrid CT-MRI images provided more detailed 3D representations of the vocal tract than 2 mm3 MRI based segmentations.ConclusionsThe method described in this study indicates that high-resolution CT and MR image sets can be combined so that structures such as teeth and bone are accurately represented in vocal tract reconstructions. Such scans will aid learning and deepen understanding of anatomical features that relate to voice production, as well as furthering knowledge of the static and dynamic functioning of individual structures relating to voice production

Can phylogeny predict chemical diversity and potential medicinal activity of plants? A case study of amaryllidaceae

Background During evolution, plants and other organisms have developed a diversity of chemical defences, leading to the evolution of various groups of specialized metabolites selected for their endogenous biological function. A correlation between phylogeny and biosynthetic pathways could offer a predictive approach enabling more efficient selection of plants for the development of traditional medicine and lead discovery. However, this relationship has rarely been rigorously tested and the potential predictive power is consequently unknown.Results We produced a phylogenetic hypothesis for the medicinally important plant subfamily Amaryllidoideae (Amaryllidaceae) based on parsimony and Bayesian analysis of nuclear, plastid, and mitochondrial DNA sequences of over 100 species. We tested if alkaloid diversity and activity in bioassays related to the central nervous system are significantly correlated with phylogeny and found evidence for a significant phylogenetic signal in these traits, although the effect is not strong.Conclusions Several genera are non-monophyletic emphasizing the importance of using phylogeny for interpretation of character distribution. Alkaloid diversity and in vitro inhibition of acetylcholinesterase (AChE) and binding to the serotonin reuptake transporter (SERT) are significantly correlated with phylogeny. This has implications for the use of phylogenies to interpret chemical evolution and biosynthetic pathways, to select candidate taxa for lead discovery, and to make recommendations for policies regarding traditional use and conservation priorities.<br /

Numerical Simulations of Penetration and Overshoot in the Sun

We present numerical simulations of convective overshoot in a two-dimensional model of the solar equatorial plane. The simulated domain extends from 0.001 R_sun to 0.93 R_sun, spanning both convective and radiative regions. We show that convective penetration leads to a slightly extended, mildly subadiabatic temperature gradient beneath the convection zone below which there is a rapid transition to a strongly subadiabatic region. A slightly higher temperature is maintained in the overshoot region by adiabatic heating from overshooting plumes. This enhanced temperature may partially account for the sound speed discrepancy between the standard solar model and helioseismology. Simulations conducted with tracer particles suggest that a fully mixed region exists down to at least 0.687 R_sun.Comment: 24 pages, 8 figures, submitted to Ap

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants

Cys2-His2 zinc finger proteins (ZFPs) are the largest group of transcription factors in higher metazoans. A complete characterization of these ZFPs and their associated target sequences is pivotal to fully annotate transcriptional regulatory networks in metazoan genomes. As a first step in this process, we have characterized the DNA-binding specificities of 129 zinc finger sets from Drosophila using a bacterial one-hybrid system. This data set contains the DNA-binding specificities for at least one encoded ZFP from 70 unique genes and 23 alternate splice isoforms representing the largest set of characterized ZFPs from any organism described to date. These recognition motifs can be used to predict genomic binding sites for these factors within the fruit fly genome. Subsets of fingers from these ZFPs were characterized to define their orientation and register on their recognition sequences, thereby allowing us to define the recognition diversity within this finger set. We find that the characterized fingers can specify 47 of the 64 possible DNA triplets. To confirm the utility of our finger recognition models, we employed subsets of Drosophila fingers in combination with an existing archive of artificial zinc finger modules to create ZFPs with novel DNA-binding specificity. These hybrids of natural and artificial fingers can be used to create functional zinc finger nucleases for editing vertebrate genomes

Controlled depolymerisation, as assessed by analytical ultracentrifugation, of low molecular weight chitosan for potential use in archaeological conservation

The heterogeneity and molecular weight of a chitosan of low molecular weight (molar mass) and low degree of acetylation (0.1), for potential use as a consolidant for decayed archaeological wood, has been examined by sedimentation velocity and sedimentation equilibriumin the analytical ultracentrifuge before and after depolymerisation. Sedimentation velocity before polymerisation revealed a uniform distribution of sedimentation coefficient with little concentration dependence. SEDFIT-MSTAR analysis revealed a weight average molecular weight Mw of (14.2 + 1.2) kDa, and polydispersity index of ~ 1.2. Further analysis using MULTISIG revealed a distribution of material between 2-20 kDa and consistent with the weight average Mw. Controlled depolymerisation using hydrogen peroxide and UV in an acetic acid medium reduced this to (4.9 + 0.7) kDa, with a similar polydispersity. The depolymerised material appears to be within the range that has been predicted to fully penetrate into archaeological wood. The consequences for this and the use of the analytical ultracentrifuge in wood conservation strategies is considered

Evaluation Research and Institutional Pressures: Challenges in Public-Nonprofit Contracting

This article examines the connection between program evaluation research and decision-making by public managers. Drawing on neo-institutional theory, a framework is presented for diagnosing the pressures and conditions that lead alternatively toward or away the rational use of evaluation research. Three cases of public-nonprofit contracting for the delivery of major programs are presented to clarify the way coercive, mimetic, and normative pressures interfere with a sound connection being made between research and implementation. The article concludes by considering how public managers can respond to the isomorphic pressures in their environment that make it hard to act on data relating to program performance.This publication is Hauser Center Working Paper No. 23. The Hauser Center Working Paper Series was launched during the summer of 2000. The Series enables the Hauser Center to share with a broad audience important works-in-progress written by Hauser Center scholars and researchers