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Surface orientation of 3,4,5-tris-substituted benzoic acid amphiphiles.

Regarding the molecular orientation on flat substrates, thin films have been studied of a series of wedge-shaped molecules (3,4,5-tris-substituted benzoate-benzo crown ether compounds) consisting of a hydrophobic outer rim and a polar group at the thin end which form columnar mesomorphic and crystalline structures. For most substrates studied here, autophobic dewetting is demonstrated to be caused by the formation of a monomolecular adlayer in which the molecules are oriented normal to the substrate surface with the hydrophobic tails directed away from the substrate. For thick films, this adlayer is shown to cause an "in-plane" orientation of the axis of the columnar state. An ordered in-plane oriented adlayer is observed only for highly ordered pyrolytic graphite as the substrate. In this case, specific interactions with the substrate cause formation of a well-ordered 2D pattern that might favor homeotropic orientation of the columnar structures but has to be optimized by further structural variation. The structure of the adsorbed monolayer is elucidated by combining contact angle measurements, plasmon resonance spectroscopy, and optical and scanning tunneling microscopy.

Journal Article↗

A comparison of algorithms for inference and learning in probabilistic graphical models.

Research into methods for reasoning under uncertainty is currently one of the most exciting areas of artificial intelligence, largely because it has recently become possible to record, store, and process large amounts of data. While impressive achievements have been made in pattern classification problems such as handwritten character recognition, face detection, speaker identification, and prediction of gene function, it is even more exciting that researchers are on the verge of introducing systems that can perform large-scale combinatorial analyses of data, decomposing the data into interacting components. For example, computational methods for automatic scene analysis are now emerging in the computer vision community. These methods decompose an input image into its constituent objects, lighting conditions, motion patterns, etc. Two of the main challenges are finding effective representations and models in specific applications and finding efficient algorithms for inference and learning in these models. In this paper, we advocate the use of graph-based probability models and their associated inference and learning algorithms. We review exact techniques and various approximate, computationally efficient techniques, including iterated conditional modes, the expectation maximization (EM) algorithm, Gibbs sampling, the mean field method, variational techniques, structured variational techniques and the sum-product algorithm ("loopy" belief propagation). We describe how each technique can be applied in a vision model of multiple, occluding objects and contrast the behaviors and performances of the techniques using a unifying cost function, free energy.

Algorithms↗

Structural diversity of domain superfamilies in the CATH database.

The CATH database of domain structures has been used to explore the structural variation of homologous domains in 294 well populated domain structure superfamilies, each containing at least three sequence diverse relatives. Our analyses confirm some previously detected trends relating sequence divergence to structural variation but for a much larger dataset and in some superfamilies the new data reveal exceptional structural variation. Use of a new algorithm (2DSEC) to analyse variability in secondary structure compositions across a superfamily sheds new light on how structures evolve. 2DSEC detects inserted secondary structures that embellish the core of conserved secondary structures found throughout the superfamily. Analysis showed that for 56% of highly populated superfamilies (>9 sequence diverse relatives), there are twofold or more increases in the numbers of secondary structures in some relatives. In some families fivefold increases occur, sometimes modifying the fold of the domain. Manual inspection of secondary structure insertions or embellishments in 48 particularly variable superfamilies revealed that although these insertions were usually discontiguous in the sequence they were often co-located in 3D resulting in a larger structural motif that often modified the geometry of the active site or the surface conformation promoting diverse domain partnerships and protein interactions. These observations, supported by automatic analysis of all well populated CATH families, suggest that accretion of small secondary structure insertions may provide a simple mechanism for evolving new functions in diverse relatives. Some layered domain architectures (e.g. mainly-beta and alpha-beta sandwiches) that recur highly in the genomes more frequently exploit these types of embellishments to modify function. In these architectures, aggregation occurs most often at the edges, top or bottom of the beta-sheets. Information on structural variability across domain superfamilies has been made available through the CATH Dictionary of Homologous Structures (DHS).

Amino Acid Sequence↗

Continuum secondary structure captures protein flexibility.

The DSSP program assigns protein secondary structure to one of eight states. This discrete assignment cannot describe the continuum of thermal fluctuations. Hence, a continuous assignment is proposed. Technically, the continuum results from averaging over ten discrete DSSP assignments with different hydrogen bond thresholds. The final continuous assignment for a single NMR model successfully reflected the structural variations observed between all NMR models in the ensemble. The structural variations between NMR models were verified to correlate with thermal motion; these variations were captured by the continuous assignments. Because the continuous assignment reproduces the structural variation between many NMR models from one single model, functionally important variation can be extracted from a single X-ray structure. Thus, continuous assignments of secondary structure may affect future protein structure analysis, comparison, and prediction.

Computer Systems↗

Finding an average core structure: application to the globins.

We present a procedure for automatically identifying from a set of aligned protein structures a subset of atoms with only a small amount of structural variation, i.e., a core. We apply this procedure to the globin family of proteins. Based purely on the results of the procedure, we show that the globin fold can be divided into two parts. The part with greater structural variation consists of the residues near the heme (the F helix and parts of the G and H helices), and the part with lesser structural variation (the core) forms a structural framework similar to that of the repressor protein (A, B, and E helices and remainder of the G and H helices). Such a division is consistent with many other structural and biochemical findings. In addition, we find further partitions within the core that may have biological significance. Finally, using the structural core of the globin family as a reference point, we have compared structural variation to sequence variation and shown that a core definition based on sequence conservation does not necessarily agree with one based on structural similarity.

Algorithms↗

Antigenic structure and variation of canine parvovirus type-2, feline panleukopenia virus, and mink enteritis virus.

The antigenic structure and variation of canine parvovirus type-2 (CPV), feline panleukopenia virus (FPV), mink enteritis virus (MEV), and a closely related virus of raccoons (RPV) was investigated using a panel of 13 monoclonal antibodies (mAb) formed against CPV and 8 mAb formed against FPV. Each mAb both neutralized and inhibited the hemagglutination of the homologous virus. All mAb tested immunoprecipitated the two capsid proteins. Five mAb were specific for the CPV isolates and one reacted with the FPV, MEV, and RV isolates, but not the CPV. Another mAb reacted only with certain FPV and MEV isolates. The remaining 14 mAb reacted with most parvoviral isolates from the four animal species. Antigenic variation was observed both within and between the parvovirus isolates from each species. The 12 MEV isolates could be grouped into three antigenic types based on their reactivity with the panel of mAb. Antigenic variants of either CPV or FPV were readily selected with several mAb. Analysis of these variant viruses by direct serological tests and competition radioimmune assays between different mAb revealed that the capsid surface contained at least two determinants, each being comprised of many different but overlapping epitopes.

Animals↗

An anatomical study of the sigmoid sulcus and related structures.

Variations in the shape and size of the sigmoid sulcus were investigated in 561 temporal bones (438 isolated temporal bones, 49 skull bases and 25 half skull bases) and measurements of related structures were made. Right-left differences were analysed. The sigmoid sulcus was significantly wider (12 mm) and longer (38 mm) in the skull bases, while no differences were observed in the isolated temporal bones. The distance from the most prominent point of the mastoid process to the Frankfort horizontal plane (FHP) was 33 mm; no right-left difference was found. The distance from the genu of the sigmoid sulcus to the external acoustic meatus was 24.06 mm on the right side and 24.74 mm on the left side and this difference is significant, being considerably longer on the left side. The jugular foramen diameter was 7.8 mm; no right-left difference was observed. The relationship of the mastoid air cells to the sulcus was analysed and air cells were found just behind the sulcus in 66% and behind and posterior to the sulcus in 5% of temporal bones.

Cranial Sinuses↗

Rapid emergence of novel antigenic and genetic variants of equine infectious anemia virus during persistent infection.

Previous results from our laboratory have demonstrated that equine infectious anemia virus displays structural variations in its surface glycoproteins and RNA genome during passage and chronic infections in experimentally infected Shetland ponies (Montelaro et al., J. Biol. Chem. 259:10539-10544, 1984; Payne et al., J. Gen. Virol. 65:1395-1399, 1984). The present study was undertaken to obtain an antigenic and biochemical characterization of equine infectious anemia virus isolates recovered from an experimentally infected pony during sequential disease episodes, each separated by intervals of only 4 to 8 weeks. The virus isolates could be distinguished antigenically by neutralization assays with serum from the infected pony and by Western blot analysis with a monoclonal antibody against the major surface glycoprotein gp90, thus demonstrating that novel antigenic variants of equine infectious anemia virus predominate during each clinical episode. The respective virion glycoproteins displayed different electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gels, indicating structural variation. Tryptic peptide and glycopeptide maps of the viral proteins of each virus isolate revealed biochemical alterations involving amino acid sequence and glycosylation patterns in the virion surface glycoproteins gp90 and gp45. In contrast, no structural variation was observed in the internal viral proteins pp15, p26, and p9 from any of the four virus isolates. Oligonucleotide mapping experiments revealed similar but unique RNase T1-resistant oligonucleotide fingerprints of the RNA genomes of each of the virus isolates. Localization of altered oligonucleotides for one virus isolate placed two of three unique oligonucleotides within the predicted env gene region of the genome, perhaps correlating with the structural variation observed in the envelope glycoproteins. Thus these results support the concept that equine infectious anemia virus is indeed capable of relatively rapid genomic variations during replication, some of which result in altered glycoprotein structures and antigenic variants which are responsible for the unique periodic disease nature observed in persistently infected animals. The findings of envelope specific differences in isolates of visna virus and of human T-cell lymphotropic virus III (acquired immune deficiency syndrome-related virus) suggest that this variation may be a common characteristic of the subfamily Lentivirinae.

Animals↗

Ultrastructural variations in frog muscles subjected to sciatectomy.

Fine structural variations in two different types of muscles of frog (Rana cyanophlictis) subjected to sciatectomy were studied electronmicroscopically. Gastrocnemius muscle showed marked myofibrillar disarray and degeneration due to sciatectomy, while sartorius muscle was relatively less affected. The extent of sciatectomy induced fine structural variation was in proportion to the degree of denervation atrophy (as reflected by loss of wet muscle weight) in these muscles. Differences in the degree of degenerative changes in atrophying muscles may be attributed to variations in fiber type composition and stretch effects imposed during swimming movements.

Animals↗

Chemical characterization of brominated flame retardants and identification of structurally representative compounds.

Three training sets were selected, each consisting of 10 structurally diverse compounds representative of brominated flame retardants (BFRs) that are either in use or have been used. Just three compounds account for nearly all the total production volume of BFRs. In the present study, however, the physicochemical characteristics of a far more structurally diverse set of 65 BFRs was explored using 15 molecular descriptors (including log P, constitutional counts, and semiempirical quantum mechanical parameters) and principal component analysis (PCA). The PCA generated an overview of the structural variation among BFRs, and certain compounds with unique physicochemical properties and specific clusters of compounds with distinct properties were identified. The training-set compounds were selected by applying the condensed information obtained from the PCA and statistical experimental design. The three training sets, which were designated as optimal, practical, and alternative, were selected either to maximize the structural variation (optimal) or to combine structural variation with practical advantages, such as ease of experimental handling and commercial availability (practical and alternative). Inclusion of the suggested compounds in assessments of the persistence, bioaccumulation, and toxicity properties of BFRs and related programs should help to increase our understanding of the effects and environmental fate of these compounds.

Bromine Compounds↗

Rheological properties of the anterior vaginal fluid from superovulated dairy heifers at estrus.

Anterior vaginal fluid samples were collected from 25 dairy heifers induced to superovulation at 12 to 20 hours after estrus detection. Thixotropy and flow behavior were evaluated. In samples from 19 heifers, structural variation was registered and the fluids were considered to be thixotropic; in the remaining samples (6 heifers), structural variation was not registered and the fluids were considered to be nonthixotropic. The mean estradiol concentration of the thixotropic fluids (20.8 pg/ml) was lower (P=0.0002) than of the nonthixotropic samples (56.7 pg/ml). All the nonthixotropic samples of anterior vaginal fluid exhibited Newtonian behavior. Of the 25 thixotropic anterior vaginal fluid samples, 10 exhibited Newtonian behavior while 9 exhibited non-Newtonian behavior. Heifers in which samples exhibited Newtonian behavior had a higher mean estradiol concentration (38.8 pg/ml; P=0.003) than heifers in which samples exhibited non-Newtonian behavior (12.8 pg/ml). Estradiol concentrations were correlated negatively (P=0.02) with the index of consistency (r = -0.46) and were not related to structural variation (P=0.08), although a certain tendency was shown. These results have shown that thixotropic and flow behavior measurements in the anterior vaginal fluid of superovulated estrous heifers vary over a wide range and even qualitatively. This variation is related to estrogen levels: Fluidity increases with increased plasma estrogen values, and the integrity of the gel structure tends toward elimination.

Journal Article↗

Gap junction structures. VI. Variation and conservation in connexon conformation and packing.

Correlation of structural changes in isolated gap junctions with the mechanism of channel gating is complicated by the effects of isolation procedures and the lack of a direct functional assay. The effect of variations in the isolation procedure are examined by comparison of the structures of gap junctions isolated by different protocols. X-ray diffraction data from over two hundren specimens are compared to provide a basis for identification of invariant aspects of the connexon structure and variable properties related either to functional switching or experimental modifications. We discuss the relationship between subunit tilt, lattice symmetry and packing, and membrane curvature and demonstrate that membrane curvature may be a natural consequence of the structure of the connexons and the patterns of interactions between them.

Animals↗

Variation in structure and location of VanA glycopeptide resistance elements among enterococci from a single patient.

Forty-six VanA glycopeptide-resistant enterococci (GRE) from a single patient were investigated for variation in structure and location of VanA resistance elements. Together with identification to species level and pulsed-field gel electrophoresis, these data divided the GRE into 10 groups and subgroups. Combining data in this manner appears helpful when investigating the epidemiology of GRE.

Bacterial Proteins↗

The mosaic structure of variation in the laboratory mouse genome.

Most inbred laboratory mouse strains are known to have originated from a mixed but limited founder population in a few laboratories. However, the effect of this breeding history on patterns of genetic variation among these strains and the implications for their use are not well understood. Here we present an analysis of the fine structure of variation in the mouse genome, using single nucleotide polymorphisms (SNPs). When the recently assembled genome sequence from the C57BL/6J strain is aligned with sample sequence from other strains, we observe long segments of either extremely high (approximately 40 SNPs per 10 kb) or extremely low (approximately 0.5 SNPs per 10 kb) polymorphism rates. In all strain-to-strain comparisons examined, only one-third of the genome falls into long regions (averaging >1 Mb) of a high SNP rate, consistent with estimated divergence rates between Mus musculus domesticus and either M. m. musculus or M. m. castaneus. These data suggest that the genomes of these inbred strains are mosaics with the vast majority of segments derived from domesticus and musculus sources. These observations have important implications for the design and interpretation of positional cloning experiments.

Albinism↗

Determining local conformational variations in DNA. Nuclear magnetic resonance structures of the DNA duplexes d(CGCCTAATCG) and d(CGTCACGCGC) generated using back-calculation of the nuclear Overhauser effect spectra, a distance geometry algorithm and constrained molecular dynamics.

Two-dimensional nuclear magnetic resonance (n.m.r.) spectroscopy and a variety of computational techniques have been used to generate three-dimensional structures of the two DNA duplexes d(CGCCTAATCG) and d(CGTCACGCGC). The central six base-pairs in these two decamers contain all ten dinucleotide pairs in DNA and thus, represent a model system for investigating how the local structure of DNA varies with base sequence. Resonance assignments were made for the non-exchangeable base protons and most of the C-1'-C-4' sugar protons in both decamers. Three-dimensional structures were generated using a distance geometry algorithm and these initial structures were refined by optimizing the fit of back-calculated spectra against the experimental two-dimensional nuclear Overhauser effect (NOE) spectra. This back-calculation procedure consists of calculating NOE cross relaxation rates for a given structure by solution of the Bloch equations, and directly accounts for spin diffusion effects. Use of this refinement procedure eliminates some assumptions that have been invoked when generating structures of DNA oligomers from n.m.r. data. Constrained energy minimization and constrained quenched molecular dynamics calculation were also performed on both decamers to help generate energetically favorable structures consistent with the experimental data. Analysis of the local conformational parameters of helical twist, helical rise, propeller twist, displacement and the alpha, beta, gamma, epison and zeta backbone torsion angles in these structures shows that these parameters span a large range of values relative to the X-ray data of nucleic acids. However, the glycosidic and pseudorotation angles are quite well defined in these structures. The implications that these results have for determination of local structural variations of DNA in solution, such as those predicted by Callidine's rules, are discussed. Our results differ significantly from some previous studies on determining local conformations of nucleic acids and comparisons with these studies are made.

Algorithms↗

Structure and variation in end-of-life discussions in the Surgical Intensive Care Unit.

The research reported here is an exploratory discourse analysis of a corpus of six end-of-life discussions in a Surgical Intensive Care Unit (SICU), describing the structure and variations of the four phases of an end-of-life discussion in terms of the function of each of these phases: the Opening (Phase 1), Description of Current Status (Phase 2), Holistic Decision Making (Phase 3), and Logistics of Dying (Phase 4). Of particular interest is Phase 2, in which the presentation of medical information culminates in an inferential summary statement that functions to establish the patient's status as terminal. We argue that it is Phase 2 that is crucial in the functional progression of an end-of-life discussion toward a decision to move from therapeutic to palliative care, since it is in Phase 2 that physicians and families interactionally achieve a consensus that allows a decision to withdraw or withhold further treatment, including life support, which would be futile and only prolong the patient's suffering. We show how two of the end-of-life discussions in the corpus that did not establish the terminal status of the patient in Phase 2 did not move to decision making in Phase 3.

Anthropology, Cultural↗

Site- and exercise-related variation in structure and function of cartilage from equine distal metacarpal condyle.

OBJECTIVE: Determine (1) the site-associated response of articular cartilage of the equine distal metacarpal condyle to training at a young age as assessed by changes in indentation stiffness and alterations in cartilage structure and composition, and (2) relationships between indentation stiffness and indices of cartilage structure and composition. METHOD: Experimental animals (n=6) were trained on a track (increasing exercise to 1km/day by 5 months); controls (n=6) were pasture-reared. Animals were euthanized at 18 months and four osteochondral samples were harvested per metacarpal condyle from dorsal-medial, dorsal-lateral, palmar-medial, and palmar-lateral aspects. Cartilage was analyzed for India ink staining (quantified as reflectance score (RS)), short-term indentation stiffness (sphere-ended, 0.4mm diameter), thickness, and biochemical composition. RESULTS: Cartilage structural, biochemical and biomechanical properties varied markedly with site in the joint. Sites just medial and just lateral to the sagittal ridge showed signs of early degeneration, with relatively low RS, indentation stiffness, and collagen content, and relatively high water content. Effects of exercise and side (left vs right) were not detected for any measure. Overall, indentation stiffness correlated positively with RS and collagen content, and inversely with thickness and water content. CONCLUSION: Gentle exercise-imposed mechanical stimulation did not markedly affect articular cartilage function or structure. However, the marked site-associated variation suggests that biomechanical environment can initiate degenerative changes in immature cartilage during joint growth and maturation.

Animals↗

Structural analysis of human Ia antigens reveals the existence of a fourth molecular subset distinct from DP, DQ, and DR molecules.

Structural analysis by two-dimensional peptide maps (2D-PM) of the human Ia molecular pool expressed on the cell surface of two distinct lymphoblastoid cell line, LG-2 and Raji, revealed the existence of a novel MHC class II molecular heterodimer that differs at the level of both alpha and beta subunits from the previously described DP, DQ, and DR antigens. These differences were also seen at the level of two-dimensional electrophoresis (2D-PAGE) of biosynthetically labeled intact molecules, although to a lesser extent, due to the intrinsic limitations of this technique in resolving fine structural differences. We have designated this new class II antigen as the fourth Ia subset. The fourth Ia subset seems to represent a small proportion of the human Ia pool. Comparative analysis by 2D-PM of the two cell lines showed the presence of structural variations in the alpha chains of the fourth Ia subset, suggesting the existence of polymorphism for these subunits. Cell surface iodination did not show appreciable labeling of the fourth subset beta chain in LG-2 cells, and this prevented analysis of the structural polymorphism of this subunit. Furthermore, for the first time, we have shown that DP alpha chains display distinct peptide maps in LG-2 and Raji cells, thus suggesting the presence of structural polymorphism for these Ia subunits also. The DQ1 alpha and beta allelic products present in LG-2 cells (DQ homozygous) did not show appreciable structural variation when compared with the homologous allelic products present in Raji cells (DQ heterozygous). Finally, we have confirmed the absence of polymorphism for the DR alpha subunits. By 2D-PM, relatively low structural variation was instead found for the highly polymorphic DR beta subunits expressed in the two cell lines, suggesting that cell surface iodination preferentially labels constant domains of DR beta chains.

Antibodies, Monoclonal↗