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Quantitative comparison of FBP, EM, and Bayesian reconstruction algorithms for the IndyPET scanner.

We quantitatively compare filtered backprojection (FBP), expectation-maximization (EM), and Bayesian reconstruction algorithms as applied to the IndyPET scanner--a dedicated research scanner which has been developed for small and intermediate field of view imaging applications. In contrast to previous approaches that rely on Monte Carlo simulations, a key feature of our investigation is the use of an empirical system kernel determined from scans of line source phantoms. This kernel is incorporated into the forward model of the EM and Bayesian algorithms to achieve resolution recovery. Three data sets are used, data collected on the IndyPET scanner using a bar phantom and a Hoffman three-dimensional brain phantom, and simulated data containing a hot lesion added to a uniform background. Reconstruction quality is analyzed quantitatively in terms of bias-variance measures (bar phantom) and mean square error (lesion phantom). We observe that without use of the empirical system kernel, the FBP, EM, and Bayesian algorithms give similar performance. However, with the inclusion of the empirical kernel, the iterative algorithms provide superior reconstructions compared with FBP, both in terms of visual quality and quantitative measures. Furthermore, Bayesian methods outperform EM. We conclude that significant improvements in reconstruction quality can be realized by combining accurate models of the system response with Bayesian reconstruction algorithms.

Algorithms↗

Genus zero surface conformal mapping and its application to brain surface mapping.

We developed a general method for global conformal parameterizations based on the structure of the cohomology group of holomorphic one-forms for surfaces with or without boundaries (Gu and Yau, 2002), (Gu and Yau, 2003). For genus zero surfaces, our algorithm can find a unique mapping between any two genus zero manifolds by minimizing the harmonic energy of the map. In this paper, we apply the algorithm to the cortical surface matching problem. We use a mesh structure to represent the brain surface. Further constraints are added to ensure that the conformal map is unique. Empirical tests on magnetic resonance imaging (MRI) data show that the mappings preserve angular relationships, are stable in MRIs acquired at different times, and are robust to differences in data triangulation, and resolution. Compared with other brain surface conformal mapping algorithms, our algorithm is more stable and has good extensibility.

Algorithms↗

Spectral grouping using the Nyström method.

Spectral graph theoretic methods have recently shown great promise for the problem of image segmentation. However, due to the computational demands of these approaches, applications to large problems such as spatiotemporal data and high resolution imagery have been slow to appear. The contribution of this paper is a method that substantially reduces the computational requirements of grouping algorithms based on spectral partitioning making it feasible to apply them to very large grouping problems. Our approach is based on a technique for the numerical solution of eigenfunction problems known as the Nyström method. This method allows one to extrapolate the complete grouping solution using only a small number of samples. In doing so, we leverage the fact that there are far fewer coherent groups in a scene than pixels.

Algorithms↗

Crystal structure of rat alpha-parvalbumin at 1.05 Angstrom resolution.

The crystal structure of rat alpha-parvalbumin has been determined at 1.05 Angstrom resolution, using synchrotron data collected at Advanced Photon Source beamline 19-ID. After refinement with SHELX, employing anisotropic displacement parameters and riding hydrogen atoms, R = 0.132 and R(free) = 0.162. The average coordinate estimated standard deviations are 0.021 Angstrom and 0.038 Angstrom for backbone atoms and side-chain atoms, respectively. Besides providing a more precise view of the alpha-isoform than previously available, these data permit comparison with the 0.91 Angstrom structure determined for pike beta-parvalbumin. Visualization of the anisotropic displacement parameters as thermal ellipsoids yields insight into the atomic motion within the Ca(2+)-binding sites. The asymmetric unit includes three parvalbumin (PV) molecules. Interestingly, the EF site in one displays uncharacteristic flexibility. The ellipsoids for Asp-92 are particularly large and non-spherical, and the shape of the Ca(2+) ellipsoid implies significant vibrational motion perpendicular to the plane defined by the four y and z ligands. The relative dearth of crystal-packing interactions in this site suggests that the heightened flexibility may be the result of diminished intermolecular contacts. The implication is that, by impeding conformational mobility, crystal-packing forces may cause serious overestimation of EF-hand rigidity. The high quality of the data permitted 11 residues to be modeled in alternative side-chain conformations, including the two core residues, Ile-97 and Leu-105. The discrete disorder observed for Ile-97 may have functional ramifications, providing a mechanism for communicating binding status between the CD and EF binding loops and between the PV metal ion-binding domain and the N-terminal AB region.

Animals↗

Deleterious effects of beta-branched residues in the S1 specificity pocket of Streptomyces griseus proteinase B (SGPB): crystal structures of the turkey ovomucoid third domain variants Ile18I, Val18I, Thr18I, and Ser18I in complex with SGPB.

Turkey ovomucoid third domain (OMTKY3) is a canonical inhibitor of serine proteinases. Upon complex formation, the inhibitors fully exposed P1 residue becomes fully buried in the preformed cavity of the enzyme. All 20 P1 variants of OMTKY3 have been obtained by recombinant DNA technology and their equilibrium association constants have been measured with six serine proteinases. To rationalize the trends observed in this data set, high resolution crystal structures have been determined for OMTKY3 P1 variants in complex with the bacterial serine proteinase, Streptomyces griseus proteinase B (SGPB). Four high resolution complex structures are being reported in this paper; the three beta-branched variants, Ile18I, Val18I, and Thr18I, determined to 2.1, 1.6, and 1.7 A resolution, respectively, and the structure of the Ser18I variant complex, determined to 1.9 A resolution. Models of the Cys18I, Hse18I, and Ape18I variant complexes are also discussed. The beta-branched side chains are not complementary to the shape of the S1 binding pocket in SGPB, in contrast to that of the wild-type gamma-branched P1 residue for OMTKY3, Leu18I. Chi1 angles of approximately 40 degrees are imposed on the side chains of Ile18I, Val18I, and Thr18I within the S1 pocket. Dihedral angles of +60 degrees, -60 degrees, or 180 degrees are more commonly observed but 40 degrees is not unfavorable for the beta-branched side chains. Thr18I Ogamma1 also forms a hydrogen bond with Ser195 Ogamma in this orientation. The Ser18I side chain adopts two alternate conformations within the S1 pocket of SGPB, suggesting that the side chain is not stable in either conformation.

Amino Acid Substitution↗

1H and 31P spectroscopic imaging of epilepsy: spectroscopic and histologic correlations.

Although MRS measurements are useful in assessing the biochemical alterations underlying human epilepsy, to date their use has been limited primarily by three factors: (a) the lack of widespread methods and appropriate hardware for acquiring high-resolution spectroscopic imaging data, (b) difficulties in spectral interpretation associated with metabolic heterogeneity, and (c) difficulties in biological interpretation due to a lack of correlative histologic studies. In this work, we (a) describe approaches to overcome these hurdles, and (b) discuss the biological interpretation of the spectroscopic findings in TLE.

Adult↗

Multilocus interactions restrict gene introgression in interspecific populations of polyploid Gossypium (cotton).

Experimental advanced-generation backcross populations contain individuals with genomic compositions similar to those resulting from interspecific hybridization in nature. By applying a detailed restriction fragment length polymorphism (RFLP) map to 3662 BC3F2 plants derived from 24 different BC1 individuals of a cross between Gossypium hirsutum and G. barbadense, large and widespread deficiencies of donor (G. barbadense) chromatin were found, and seven independent chromosomal regions were entirely absent. This skewed chromatin transmission is best accounted for by multilocus epistatic interactions affecting chromatin transmission. The observed frequencies of two-locus genotypes were significantly different from Mendelian expectations about 26 times more often than could be explained by chance (P < or = 0.01). For identical pairs of loci, different two-locus genotypes occurred in excess in different BC3 families, implying the existence of higher-order interlocus interactions beyond the resolution of these data. Some G. barbadense markers occurred more frequently than expected by chance, indicating that genomic interactions do not always favor host chromatin. A preponderance of interspecific allelic interactions involved one locus each in the two different subgenomes of (allotetraploid) Gossypium, thus supporting several other lines of evidence suggesting that intersubgenomic interactions contribute to unique features that distinguish tetraploid cotton from its diploid ancestors.

Breeding↗

Phylogeny and biogeography of Croton alabamensis (Euphorbiaceae), a rare shrub from Texas and Alabama, using DNA sequence and AFLP data.

Croton alabamensis (Euphorbiaceae s.s.) is a rare plant species known from several populations in Texas and Alabama that have been assigned to var. texensis and var. alabamensis, respectively. We performed maximum parsimony, maximum likelihood, and Bayesian analyses of DNA sequences from the nuclear ribosomal internal transcribed spacer (ITS) and 5.8S regions and chloroplast trnL-trnF regions from collections of the two varieties of C. alabamensis and from outgroup taxa. C. alabamensis emerges alone on a long branch that is sister to Croton section Corylocroton and the Cuban endemic genus Moacroton. Molecular clock analysis estimates the split of C. alabamensis from its closest relatives in sect. Corylocroton at 41 million years ago, whereas the split of the two varieties of C. alabamensis occurred sometime in the Quaternary. Amplified fragment length polymorphism (AFLP) analyses were performed using two selective primer pairs on a larger sampling of accessions (22 from Texas, 17 from Alabama) to further discriminate phylogenetic structure and quantify genetic diversity. Using both neighbour joining and minimum evolution, the populations from the Cahaba and Black Warrior watersheds in Alabama form two well-separated groups, and in Texas, geographically distinct populations are recovered from Fort Hood, Balcones Canyonlands, and Pace Bend Park. Most of the molecular variance is accounted for by variance within populations. Approximately equal variance is found among populations within states and between states (varieties). Genetic distance between the Texas populations is significantly less than genetic distance between the Alabama populations. Both sequence and AFLP data support the same relationships between the varieties of C. alabamensis and their outgroup, while the AFLP data provide better resolution among the different geographical regions where C. alabamensis occurs. The conservation implications of these findings are discussed.

Alabama↗

Spatial clustering of malaria and associated risk factors during an epidemic in a highland area of western Kenya.

The epidemiology of malaria over small areas remains poorly understood, and this is particularly true for malaria during epidemics in highland areas of Africa, where transmission intensity is low and characterized by acute within and between year variations. We report an analysis of the spatial distribution of clinical malaria during an epidemic and investigate putative risk factors. Active case surveillance was undertaken in three schools in Nandi District, Western Kenya for 10 weeks during a malaria outbreak in May-July 2002. Household surveys of cases and age-matched controls were conducted to collect information on household construction, exposure factors and socio-economic status. Household geographical location and altitude were determined using a hand-held geographical positioning system and landcover types were determined using high spatial resolution satellite sensor data. Among 129 cases identified during the surveillance, which were matched to 155 controls, we identified significant spatial clusters of malaria cases as determined using the spatial scan statistic. Conditional multiple logistic regression analysis showed that the risk of malaria was higher in children who were underweight, who lived at lower altitudes, and who lived in households where drugs were not kept at home.

Adolescent↗

Noninvasive Evaluation of Aortic Valve Anatomy.

Although aortic valve anatomy is three-dimensionally complex, careful echocardiographic investigation can yield surgically relevant information. The promise of intravascular and transesophageal imaging is in yielding the raw data of sufficient resolution to make the three-dimensional reconstruction clinically meaningful. (ECHOCARDIOGRAPHY, Volume 13, May 1996)

Journal Article↗

The study of G-protein coupled receptor oligomerization with computational modeling and bioinformatics.

To achieve a structural context for the analysis of G-protein coupled receptor (GPCR) oligomers, molecular modeling must be used to predict the corresponding interaction interfaces. The task is complicated by the paucity of detailed structural data at atomic resolution, and the large number of possible modes in which the bundles of seven transmembrane (TM) segments of the interacting GPCR monomers can be packed together into dimers and/or higher-order oligomers. Approaches and tools offered by bioinformatics can be used to reduce the complexity of this task and, combined with computational modeling, can serve to yield testable predictions for the structural properties of oligomers. Most of the bioinformatics methods take advantage of the evolutionary relation that exists among GPCRs, as expressed in their sequences and measurable in the common elements of their structural and functional features. These common elements are responsible for the presence of detectable patterns of motifs and correlated mutations evident from the alignment of the sequences of these complex biological systems. The decoding of these patterns in terms of structural and functional determinants can provide indications about the most likely interfaces of dimerization/oligomerization of GPCRs. We review here the main approaches from bioinformatics, enhanced by computational molecular modeling, that have been used to predict likely interfaces of dimerization/oligomerization of GPCRs, and compare results from their application to rhodopsin-like GPCRs. A compilation of the most frequently predicted GPCR oligomerization interfaces points to specific regions of TMs 4-6.

Computational Biology↗

Surface-based atlases of cerebellar cortex in the human, macaque, and mouse.

This study describes surface reconstructions and associated flat maps that represent the highly convoluted shape of cerebellar cortex in three species: human, macaque, and mouse. The reconstructions were based on high-resolution structural MRI data obtained from other laboratories. The surface areas determined for the fiducial reconstructions are about 600 cm(2) for the human, 60 cm(2) for the macaque, and 0.8 cm(2) for the mouse. As expected from the ribbon-like pattern of cerebellar folding, the cerebellar flat maps are elongated along the axis parallel to the midline. However, the degree of elongation varies markedly across species. The macaque flat map is many times longer than its mean width, whereas the mouse flat map is only slightly elongated and the human map is intermediate in its aspect ratio. These cerebellar atlases, along with associated software for visualization and for mapping experimental data onto the atlas, are freely available to the neuroscience community (see http:/brainmap.wustl.edu).

Animals↗

Modulation transfer function of digitally reconstructed radiographs using helical computed tomography.

We have measured the modulation transfer function (MTF), at a distance from CT isocenter, in digitally reconstructed radiographs (DRR) using a bar pattern phantom for axial and helical data acquisitions. Spatial resolution in DRR increases for thinner slice thicknesses (43% at 1.6 lp/cm for 2 mm versus 16% for 5 mm). For the three slice thicknesses studied, the axial scanning mode provided better spatial resolution in DRR than helical scans performed at pitches > or = 1.5 (41% at 1.6 lp/cm for axial, 3 mm slice versus 18% for pitch = 2), but is similar to helical scans with pitch of 1. The reconstruction of overlapping slices from helical acquisitions of pitch = 1.5 results in spatial resolution of the DRR that is similar to that resulting from axial scans with contiguous reconstruction, but also results in the fine streaks known as "zebra" artifacts in the DRR.

Image Processing, Computer-Assisted↗

Satellite gravity measurements confirm accelerated melting of Greenland ice sheet.

Using time-variable gravity measurements from the Gravity Recovery and Climate Experiment (GRACE) satellite mission, we estimate ice mass changes over Greenland during the period April 2002 to November 2005. After correcting for the effects of spatial filtering and limited resolution of GRACE data, the estimated total ice melting rate over Greenland is -239 +/- 23 cubic kilometers per year, mostly from East Greenland. This estimate agrees remarkably well with a recent assessment of -224 +/- 41 cubic kilometers per year, based on satellite radar interferometry data. GRACE estimates in southeast Greenland suggest accelerated melting since the summer of 2004, consistent with the latest remote sensing measurements.

Journal Article↗

Seeing through the dust: martian crustal heterogeneity and links to the SNC meteorites.

Through the application of new analytical techniques to high spatial resolution imaging spectrometer data, the ferrous mineralogy of major volcanic terrains on Mars is shown to consist of significant fractions of both low- and high-calcium pyroxene. Changes in the relative abundances of these pyroxenes are observed for units of different age and morphology, even in regions with higher degrees of alteration and contamination from dust. Volcanic rocks with these characteristics are uncommon on Earth but are typical of the basaltic SNC meteorites (shergottites, nakhlites, and chassignites) thought to be from Mars. Thus, it is possible to infer, even through the veil of dust, that the SNC meteorites have mineralogic affinities to major volcanic provinces on Mars and are therefore truly representative of the heterogeneity observed on the surface of the "red planet".

Calcium↗

Hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi as a target for structure-based inhibitor design: crystallization and inhibition studies with purine analogs.

The hypoxanthine phosphoribosyltransferase (HPRT) from Trypanosoma cruzi is a potential target for enzyme structure-based inhibitor design, based on previous studies which indicate that these parasites lack the metabolic enzymes required for de novo synthesis of purine nucleotides. By using a bacterial complement selection system, 59 purine analogs were assayed for their interaction with the HPRTs from T. cruzi and Homo sapiens. Eight compounds were identified from the bacterial assay to have an affinity for the trypanosomal enzyme. Inhibition constants for four of these compounds against purified recombinant trypanosomal and human HPRTs were determined and compared. The results confirm that the recombinant system can be used to identify compounds which have affinity for the trypanosomal HPRT. Furthermore, the results provide evidence for the importance of chemical modifications at positions 6 and 8 of the purine ring in the binding of these compounds to the HPRTs. An accurate three-dimensional structure of the trypanosomal enzyme will greatly enhance our understanding of the interactions between HPRTs and these compounds. Toward this end, crystallization conditions for the trypanosomal HPRT and preliminary analysis of X-ray diffraction data to a resolution of 2 A is reported. These results represent significant progress toward a structure-based approach to the design of inhibitors of the HPRT of trypanosomes with the long-range goal of developing new drugs for the treatment of Chagas' disease.

Animals↗

Territrems, tremorgenic mycotoxins of Aspergillus terreus.

The tremorgenic mycotoxins isolated from Aspergillus terreus were given the trivial names territrem A and B instead of their previous designations of C1 and C2 respectively. High-resolution mass spectral data suggested the molecular formula of territrem A to be C28H30O9 and that of territrem B,C29H34O9. They were partially characterized by ultraviolet, infrared, proton magnetic resonance, and mass spectroscopy. The spectroscopic evidence indicated that their chemical structures were very similar. The procedures of purification were also revised for the complete separation of these two chemically related compounds.

Aspergillus↗

Protection against Pneumocystis carinii pneumonia by antibodies generated from either T helper 1 or T helper 2 responses.

To determine whether different antibody isotypes associated with T helper 1 (Th1) or Th2 responses are protective against Pneumocystis carinii, mice with disrupted interleukin 4 genes (IL-4(-/-) mice) or gamma interferon genes (IFN-gamma(-/-) mice) along with wild-type C57BL/6 mice were immunized intratracheally against P. carinii, depleted of T cells in vivo by use of monoclonal antibodies, and rechallenged intratracheally with 10(7) viable P. carinii organisms. Nearly all immunized mice resolved their lung P. carinii infections (limit of detection, log10 4.06) within 21 days of challenge even though they were depleted of T cells. Unimmunized mice depleted of T cells had significant lung infections (>log10 5.5) at day 21 post-P. carinii challenge. IFN-gamma(-/-) and wild-type mice developed P. carinii-specific immunoglobulin primarily of the immunoglobulin G1 (IgG1) subclass with relatively little P. carinii-specific IgG2a, IgG2b, or IgG3 in their sera, characteristic of a Th2-type response. In contrast, IL-4(-/-) mice had primarily an IgG2b P. carinii-specific antibody response in their sera with very little IgG1. Although IgG2b was the predominant isotype in IL-4(-/-) mice, optical density values of IgG2a and IgG3 were significantly higher in these mice (two and three times, respectively) than in IFN-gamma(-/-) mice, characteristic of a Th1-type response. Together, these data indicate that resolution of P. carinii infection can be mediated by specific antibody responses and that the antibody response can be either a predominantly Th1 or Th2 type. Furthermore, although wild-type mice mounted a Th2-like antibody response, IL-4(-/-) mice could resolve P. carinii pneumonia, indicating that resistance to P. carinii can occur in the absence of IL-4.

Animals↗