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Sample records for extended phenotypes structure

  1. Allelic variants of the amylose extender mutation of maize demonstrate phenotypic variation in starch structure resulting from modified protein–protein interactions

    PubMed Central

    Liu, Fushan; Ahmed, Zaheer; Lee, Elizabeth A.; Donner, Elizabeth; Liu, Qiang; Ahmed, Regina; Morell, Matthew K.; Emes, Michael J.; Tetlow, Ian J.

    2012-01-01

    amylose extender (ae−) starches characteristically have modified starch granule morphology resulting from amylopectin with reduced branch frequency and longer glucan chains in clusters, caused by the loss of activity of the major starch branching enzyme (SBE), which in maize endosperm is SBEIIb. A recent study with ae− maize lacking the SBEIIb protein (termed ae1.1 herein) showed that novel protein–protein interactions between enzymes of starch biosynthesis in the amyloplast could explain the starch phenotype of the ae1.1 mutant. The present study examined an allelic variant of the ae− mutation, ae1.2, which expresses a catalytically inactive form of SBEIIb. The catalytically inactive SBEIIb in ae1.2 lacks a 28 amino acid peptide (Val272–Pro299) and is unable to bind to amylopectin. Analysis of starch from ae1.2 revealed altered granule morphology and physicochemical characteristics distinct from those of the ae1.1 mutant as well as the wild-type, including altered apparent amylose content and gelatinization properties. Starch from ae1.2 had fewer intermediate length glucan chains (degree of polymerization 16–20) than ae1.1. Biochemical analysis of ae1.2 showed that there were differences in the organization and assembly of protein complexes of starch biosynthetic enzymes in comparison with ae1.1 (and wild-type) amyloplasts, which were also reflected in the composition of starch granule-bound proteins. The formation of stromal protein complexes in the wild-type and ae1.2 was strongly enhanced by ATP, and broken by phosphatase treatment, indicating a role for protein phosphorylation in their assembly. Labelling experiments with [γ-32P]ATP showed that the inactive form of SBEIIb in ae1.2 was phosphorylated, both in the monomeric form and in association with starch synthase isoforms. Although the inactive SBEIIb was unable to bind starch directly, it was strongly associated with the starch granule, reinforcing the conclusion that its presence in the

  2. Could the Extended Phenotype Extend to the Cellular and Subcellular Levels in Insect-Induced Galls?

    PubMed Central

    Carneiro, Renê Gonçalves da Silva; Pacheco, Priscilla; Isaias, Rosy Mary dos Santos

    2015-01-01

    Neo-ontogenesis of plant galls involves redifferentiation of host plant tissues to express new phenotypes, when new cell properties are established via structural-functional remodeling. Herein, Psidium cattleianum leaves and Nothotrioza cattleiani galls are analyzed by developmental anatomy, cytometry and immunocytochemistry of cell walls. We address hypothesis-driven questions concerning the organogenesis of globoid galls in the association of P. cattleianum - N. cattleianum, and P. myrtoides - N. myrtoidis. These double co-generic systems represent good models for comparing final gall shapes and cell lineages functionalities under the perspective of convergent plant-dependent or divergent insect-induced characteristics. Gall induction, and growth and development are similar in both galls, but homologous cell lineages exhibit divergent degrees of cell hypertrophy and directions of elongation. Median cortical cells in P. cattleianum galls hypertrophy the most, while in P. myrtoides galls there is a centrifugal gradient of cell hypertrophy. Cortical cells in P. cattleianum galls tend to anisotropy, while P. myrtoidis galls have isotropically hypertrophied cells. Immunocytochemistry evidences the chemical identity and functional traits of cell lineages: epidermal cells walls have homogalacturonans (HGAs) and galactans, which confer rigidity to sites of enhanced cell division; oil gland cell walls have arabinogalactan proteins (AGPs) that help avoiding cell death; and parenchyma cell walls have HGAs, galactans and arabinans, which confer porosity. Variations in such chemical identities are related to specific sites of hypertrophy. Even though the double co-generic models have the same macroscopic phenotype, the globoid morphotype, current analyses indicate that the extended phenotype of N. cattleiani is substantiated by cellular and subcellular specificities. PMID:26053863

  3. The social and ecological costs of an ‘over-extended' phenotype

    PubMed Central

    Maguire, Sean M.; Hofmann, Hans A.; Kohda, Masanori

    2016-01-01

    Extended phenotypes offer a unique opportunity to experimentally manipulate and identify sources of selection acting on traits under natural conditions. The social cichlid fish Neolamprologus multifasciatus builds nests by digging up aquatic snail shells, creating an extended sexual phenotype that is highly amenable to experimental manipulation through addition of extra shells. Here, we find sources of both positive sexual selection and opposing natural selection acting on this trait; augmenting shell nests increases access to mates, but also increases social aggression and predation risk. Increasing the attractiveness of one male also changed social interactions throughout the social network and altered the entire community structure. Manipulated males produced and received more displays from neighbouring females, who also joined augmented male territories at higher rates than unmanipulated groups. However, males in more attractive territories received more aggression from neighbouring males, potentially as a form of social policing. We also detected a significant ecological cost of the ‘over-extended' phenotype; heterospecific predators usurped augmented nests at higher rates, using them as breeding sites and displacing residents. Using these natural experiments, we find that both social and ecological interactions generate clear sources of selection mediating the expression of an extended phenotype in the wild. PMID:26740619

  4. The social and ecological costs of an 'over-extended' phenotype.

    PubMed

    Jordan, Lyndon Alexander; Maguire, Sean M; Hofmann, Hans A; Kohda, Masanori

    2016-01-13

    Extended phenotypes offer a unique opportunity to experimentally manipulate and identify sources of selection acting on traits under natural conditions. The social cichlid fish Neolamprologus multifasciatus builds nests by digging up aquatic snail shells, creating an extended sexual phenotype that is highly amenable to experimental manipulation through addition of extra shells. Here, we find sources of both positive sexual selection and opposing natural selection acting on this trait; augmenting shell nests increases access to mates, but also increases social aggression and predation risk. Increasing the attractiveness of one male also changed social interactions throughout the social network and altered the entire community structure. Manipulated males produced and received more displays from neighbouring females, who also joined augmented male territories at higher rates than unmanipulated groups. However, males in more attractive territories received more aggression from neighbouring males, potentially as a form of social policing. We also detected a significant ecological cost of the 'over-extended' phenotype; heterospecific predators usurped augmented nests at higher rates, using them as breeding sites and displacing residents. Using these natural experiments, we find that both social and ecological interactions generate clear sources of selection mediating the expression of an extended phenotype in the wild. PMID:26740619

  5. Stellar structures in Extended Gravity

    NASA Astrophysics Data System (ADS)

    Capozziello, S.; De Laurentis, M.

    2016-09-01

    Stellar structures are investigated by considering the modified Lané-Emden equation coming out from Extended Gravity. In particular, this equation is obtained in the Newtonian limit of f ( R) -gravity by introducing a polytropic relation between the pressure and the density into the modified Poisson equation. The result is an integro-differential equation, which, in the limit f ( R) → R , becomes the standard Lané-Emden equation usually adopted in the stellar theory. We find the radial profiles of gravitational potential by solving for some values of the polytropic index. The solutions are compatible with those coming from General Relativity and could be physically relevant in order to address peculiar and extremely massive objects.

  6. The life of a dead ant: the expression of an adaptive extended phenotype.

    PubMed

    Andersen, Sandra B; Gerritsma, Sylvia; Yusah, Kalsum M; Mayntz, David; Hywel-Jones, Nigel L; Billen, Johan; Boomsma, Jacobus J; Hughes, David P

    2009-09-01

    Specialized parasites are expected to express complex adaptations to their hosts. Manipulation of host behavior is such an adaptation. We studied the fungus Ophiocordyceps unilateralis, a locally specialized parasite of arboreal Camponotus leonardi ants. Ant-infecting Ophiocordyceps are known to make hosts bite onto vegetation before killing them. We show that this represents a fine-tuned fungal adaptation: an extended phenotype. Dead ants were found under leaves, attached by their mandibles, on the northern side of saplings approximately 25 cm above the soil, where temperature and humidity conditions were optimal for fungal growth. Experimental relocation confirmed that parasite fitness was lower outside this manipulative zone. Host resources were rapidly colonized and further secured by extensive internal structuring. Nutritional composition analysis indicated that such structuring allows the parasite to produce a large fruiting body for spore production. Our findings suggest that the osmotrophic lifestyle of fungi may have facilitated novel exploitation strategies. PMID:19627240

  7. Pathophysiology of protein aggregation and extended phenotyping in filaminopathy

    PubMed Central

    Serdaroglu-Oflazer, Piraye; Leber, Yvonne; Odgerel, Zagaa; van der Ven, Peter F. M.; Olivé, Montse; Ferrer, Isidro; Onipe, Adekunle; Mihaylov, Mariya; Bilbao, Juan M.; Lee, Hee S.; Höhfeld, Jörg; Djinović-Carugo, Kristina; Kong, Kester; Tegenthoff, Martin; Peters, Sören A.; Stenzel, Werner; Vorgerd, Matthias; Goldfarb, Lev G.; Fürst, Dieter O.

    2012-01-01

    Mutations in FLNC cause two distinct types of myopathy. Disease associated with mutations in filamin C rod domain leading to expression of a toxic protein presents with progressive proximal muscle weakness and shows focal destructive lesions of polymorphous aggregates containing desmin, myotilin and other proteins in the affected myofibres; these features correspond to the profile of myofibrillar myopathy. The second variant associated with mutations in the actin-binding domain of filamin C is characterized by weakness of distal muscles and morphologically by non-specific myopathic features. A frameshift mutation in the filamin C rod domain causing haploinsufficiency was also found responsible for distal myopathy with some myofibrillar changes but no protein aggregation typical of myofibrillar myopathies. Controversial data accumulating in the literature require re-evaluation and comparative analysis of phenotypes associated with the position of the FLNC mutation and investigation of the underlying disease mechanisms. This is relevant and necessary for the refinement of diagnostic criteria and developing therapeutic approaches. We identified a p.W2710X mutation in families originating from ethnically diverse populations and re-evaluated a family with a p.V930_T933del mutation. Analysis of the expanded database allows us to refine clinical and myopathological characteristics of myofibrillar myopathy caused by mutations in the rod domain of filamin C. Biophysical and biochemical studies indicate that certain pathogenic mutations in FLNC cause protein misfolding, which triggers aggregation of the mutant filamin C protein and subsequently involves several other proteins. Immunofluorescence analyses using markers for the ubiquitin–proteasome system and autophagy reveal that the affected muscle fibres react to protein aggregate formation with a highly increased expression of chaperones and proteins involved in proteasomal protein degradation and autophagy. However

  8. Pathophysiology of protein aggregation and extended phenotyping in filaminopathy.

    PubMed

    Kley, Rudolf A; Serdaroglu-Oflazer, Piraye; Leber, Yvonne; Odgerel, Zagaa; van der Ven, Peter F M; Olivé, Montse; Ferrer, Isidro; Onipe, Adekunle; Mihaylov, Mariya; Bilbao, Juan M; Lee, Hee S; Höhfeld, Jörg; Djinović-Carugo, Kristina; Kong, Kester; Tegenthoff, Martin; Peters, Sören A; Stenzel, Werner; Vorgerd, Matthias; Goldfarb, Lev G; Fürst, Dieter O

    2012-09-01

    Mutations in FLNC cause two distinct types of myopathy. Disease associated with mutations in filamin C rod domain leading to expression of a toxic protein presents with progressive proximal muscle weakness and shows focal destructive lesions of polymorphous aggregates containing desmin, myotilin and other proteins in the affected myofibres; these features correspond to the profile of myofibrillar myopathy. The second variant associated with mutations in the actin-binding domain of filamin C is characterized by weakness of distal muscles and morphologically by non-specific myopathic features. A frameshift mutation in the filamin C rod domain causing haploinsufficiency was also found responsible for distal myopathy with some myofibrillar changes but no protein aggregation typical of myofibrillar myopathies. Controversial data accumulating in the literature require re-evaluation and comparative analysis of phenotypes associated with the position of the FLNC mutation and investigation of the underlying disease mechanisms. This is relevant and necessary for the refinement of diagnostic criteria and developing therapeutic approaches. We identified a p.W2710X mutation in families originating from ethnically diverse populations and re-evaluated a family with a p.V930_T933del mutation. Analysis of the expanded database allows us to refine clinical and myopathological characteristics of myofibrillar myopathy caused by mutations in the rod domain of filamin C. Biophysical and biochemical studies indicate that certain pathogenic mutations in FLNC cause protein misfolding, which triggers aggregation of the mutant filamin C protein and subsequently involves several other proteins. Immunofluorescence analyses using markers for the ubiquitin-proteasome system and autophagy reveal that the affected muscle fibres react to protein aggregate formation with a highly increased expression of chaperones and proteins involved in proteasomal protein degradation and autophagy. However, there

  9. Extending the phenotypic spectrum of RBFOX1 deletions: Sporadic focal epilepsy.

    PubMed

    Lal, Dennis; Pernhorst, Katharina; Klein, Karl Martin; Reif, Philipp; Tozzi, Rossana; Toliat, Mohammad R; Winterer, Georg; Neubauer, Bernd; Nürnberg, Peter; Rosenow, Felix; Becker, Felicitas; Lerche, Holger; Kunz, Wolfram S; Kurki, Mitja I; Hoffmann, Per; Becker, Albert J; Perucca, Emilio; Zara, Federico; Sander, Thomas; Weber, Yvonne G

    2015-09-01

    Partial deletions of the RBFOX1 gene encoding the neuronal splicing regulator have been reported in a range of neurodevelopmental diseases including idiopathic/genetic generalized epilepsy (IGE/GGE), childhood focal epilepsy, and self-limited childhood benign epilepsy with centrotemporal spikes (BECTS, rolandic epilepsy), and autism. The protein regulates alternative splicing of many neuronal transcripts involved in the homeostatic control of neuronal excitability. Herein, we examined whether structural deletions affecting RBFOX1 exons confer susceptibility to common forms of juvenile and adult focal epilepsy syndromes. We screened 807 unrelated patients with sporadic focal epilepsy, and we identified seven hemizygous exonic RBFOX1 deletions in patients with sporadic focal epilepsy (0.9%) in comparison to one deletion found in 1,502 controls. The phenotypes of the patients carrying RBFOX1 deletions comprise magnetic resonance imaging (MRI)-negative epilepsy of unknown etiology with frontal and temporal origin (n = 5) and two patients with temporal lobe epilepsy with hippocampal sclerosis. The epilepsies were largely pharmacoresistant but not associated with intellectual disability. Our study extends the phenotypic spectrum of RBFOX1 deletions as a risk factor for focal epilepsy and suggests that exonic RBFOX1 deletions are involved in the broad spectrum of focal and generalized epilepsies. PMID:26174448

  10. Identifying Heritable Brain Phenotypes in an Extended Pedigree of Vervet Monkeys

    PubMed Central

    Melega, William P.; Service, Susan K.; Lee, Chris; Chen, Kelly; Tu, Zhuowen; Jorgensen, Matthew J.; Fairbanks, Lynn A.; Cantor, Rita M.; Freimer, Nelson B.; Woods, Roger P.

    2009-01-01

    The area and volume of brain structural features, as assessed by high-resolution 3D magnetic resonance imaging (MRI), are among the most heritable measures relating to the human central nervous system. We have conducted MRI scanning of all available monkeys over 2 years of age (n=357) from the extended multigenerational pedigree of the Vervet Research Colony (VRC). Using a combination of automated and manual segmentation we have quantified several correlated but distinct brain structural phenotypes. The estimated heritabilities (h2) for these measures in the VRC are higher than those reported previously for such features in humans or in other non human primates (NHP): total brain volume (h2=0.99, standard error (se)=0.06), cerebral volume (h2=0.98, se=0.06), cerebellar volume (h2=0.86, se=0.09), hippocampal volume (h2=0.95, se=0.07) and corpus callosum cross-sectional areas (h2=0.87, se=0.07). These findings indicate that, in the controlled environment and with the inbreeding structure of the VRC, additive genetic factors account for almost all of the observed variance in brain structure, and suggest the potential of the VRC for genetic mapping of quantitative trait loci (QTL) underlying such variance. PMID:19261882

  11. Morphogenesis of an extended phenotype: four-dimensional ant nest architecture.

    PubMed

    Minter, Nicholas J; Franks, Nigel R; Brown, Katharine A Robson

    2012-03-01

    Animals produce a variety of structures to modify their environments adaptively. Such structures represent extended phenotypes whose development is rarely studied. To begin to rectify this, we used micro-computed tomography (CT) scanning and time-series experiments to obtain the first high-resolution dataset on the four-dimensional growth of ant nests. We show that extrinsic features within the environment, such as the presence of planes between layers of sediment, influence the architecture of Lasius flavus nests, with ants excavating horizontal tunnels along such planes. Intrinsically, the dimensions of the tunnels are associated with individual colonies, the dynamics of excavation can be explained by negative feedback and the angular distribution of tunnels is probably a result of local competition among tunnels for miners. The architecture and dynamics of ant nest excavation therefore result from local interactions of ants with one another and templates inherent in the environment. The influence of the environment on the form of structures has been documented across both biotic and abiotic domains. Our study opens up the utility of CT scanning as a technique for observing the morphogenesis of such structures. PMID:21849386

  12. Morphogenesis of an extended phenotype: four-dimensional ant nest architecture

    PubMed Central

    Minter, Nicholas J.; Franks, Nigel R.; Robson Brown, Katharine A.

    2012-01-01

    Animals produce a variety of structures to modify their environments adaptively. Such structures represent extended phenotypes whose development is rarely studied. To begin to rectify this, we used micro-computed tomography (CT) scanning and time-series experiments to obtain the first high-resolution dataset on the four-dimensional growth of ant nests. We show that extrinsic features within the environment, such as the presence of planes between layers of sediment, influence the architecture of Lasius flavus nests, with ants excavating horizontal tunnels along such planes. Intrinsically, the dimensions of the tunnels are associated with individual colonies, the dynamics of excavation can be explained by negative feedback and the angular distribution of tunnels is probably a result of local competition among tunnels for miners. The architecture and dynamics of ant nest excavation therefore result from local interactions of ants with one another and templates inherent in the environment. The influence of the environment on the form of structures has been documented across both biotic and abiotic domains. Our study opens up the utility of CT scanning as a technique for observing the morphogenesis of such structures. PMID:21849386

  13. Discovering phenotypic causal structure from nonexperimental data.

    PubMed

    Otsuka, J

    2016-06-01

    The evolutionary potential of organisms depends on how their parts are structured into a cohesive whole. A major obstacle for empirical studies of phenotypic organization is that observed associations among characters usually confound different causal pathways such as pleiotropic modules, interphenotypic causal relationships and environmental effects. The present article proposes causal search algorithms as a new tool to distinguish these different modes of phenotypic integration. Without assuming an a priori structure, the algorithms seek a class of causal hypotheses consistent with independence relationships holding in observational data. The technique can be applied to discover causal relationships among a set of measured traits and to distinguish genuine selection from spurious correlations. The former application is illustrated with a biological data set of rat morphological measurements previously analysed by Cheverud et al. (Evolution 1983, 37, 895). PMID:27007864

  14. Altering an extended phenotype reduces intraspecific male aggression and can maintain diversity in cichlid fish

    PubMed Central

    Croft, Guy E.; Joyce, Domino A.

    2013-01-01

    Reduced male aggression towards different phenotypes generating negative frequency-dependent intrasexual selection has been suggested as a mechanism to facilitate the invasion and maintenance of novel phenotypes in a population. To date, the best empirical evidence for the phenomenon has been provided by laboratory studies on cichlid fish with different colour polymorphisms. Here we experimentally tested the hypothesis in a natural population of Lake Malawi cichlid fish, in which males build sand-castles (bowers) to attract females during seasonal leks. We predicted that if bower shape plays an important role in male aggressive interactions, aggression among conspecific males should decrease when their bower shape is altered. Accordingly, we allocated randomly chosen bowers in a Nyassachromis cf. microcephalus lek into three treatments: control, manipulated to a different shape, and simulated manipulation. We then measured male behaviours and bower shape before and after these treatments. We found that once bower shape was altered, males were involved in significantly fewer aggressive interactions with conspecific males than before manipulation. Mating success was not affected. Our results support the idea that an extended phenotype, such as bower shape, can be important in maintaining polymorphic populations. Specifically, reduced male conspecific aggression towards males with different extended phenotypes (here, bower shapes) may cause negative frequency-dependent selection, allowing the invasion and establishment of a new phenotype (bower builder). This could help our understanding of mechanisms of diversification within populations, and in particular, the overall diversification of bower shapes within Lake Malawi cichlids. PMID:24349896

  15. A molecular genetic study of autism and related phenotypes in extended pedigrees

    PubMed Central

    2013-01-01

    Background Efforts to uncover the risk genotypes associated with the familial nature of autism spectrum disorder (ASD) have had limited success. The study of extended pedigrees, incorporating additional ASD-related phenotypes into linkage analysis, offers an alternative approach to the search for inherited ASD susceptibility variants that complements traditional methods used to study the genetics of ASD. Methods We examined evidence for linkage in 19 extended pedigrees ascertained through ASD cases spread across at least two (and in most cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non-ASD individuals, the broad autism phenotype) and more narrowly defined components of these phenotypes, e.g., social and repetitive behavior, pragmatic language, and anxiety, were examined. The overarching goal was to maximize the aggregate information available on the maximum number of individuals and to disaggregate syndromic phenotypes in order to examine the genetic underpinnings of more narrowly defined aspects of ASD behavior. Results Results reveal substantial between-family locus heterogeneity and support the importance of previously reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen in the ASD analyses, show evidence for linkage to the broad autism phenotype (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety, pragmatic language, and social behavior) showing linkage to regions overlapping with the compound BAP phenotype. Whereas 'repetitive behavior’, showing the strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2-24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected with other compound or narrow phenotypes examined in this study. Conclusions These results provide support for the presence of key features underlying the complexity of the genetic architecture of ASD: substantial between-family locus heterogeneity, that the BAP appears

  16. Extending Injury- and Disease-Resistant CNS Phenotypes by Repetitive Epigenetic Conditioning

    PubMed Central

    Gidday, Jeffrey M.

    2015-01-01

    Significant reductions in the extent of acute injury in the CNS can be achieved by exposure to different preconditioning stimuli, but the duration of the induced protective phenotype is typically short-lasting, and thus is deemed as limiting its clinical applicability. Extending the period over which such adaptive epigenetic changes persist – in effect, expanding conditioning’s “therapeutic window” – would significantly broaden the potential applications of such a treatment approach in patients. The frequency of the conditioning stimulus may hold the key. While transient (1–3 days) protection against CNS ischemic injury is well established preclinically following a single preconditioning stimulus, repetitively presenting preconditioning stimuli extends the duration of ischemic tolerance by many weeks. Moreover, repetitive intermittent postconditioning enhances post-ischemic recovery metrics and improves long-term survival. Intermittent conditioning is also efficacious for preventing or delaying injury in preclinical models of chronic neurodegenerative disease, and for promoting long-lasting functional improvements in a number of other pathologies as well. Although the detailed mechanisms underlying these protracted kinds of neuroplasticity remain largely unstudied, accumulating empirical evidence supports the contention that all of these adaptive phenotypes are epigenetically mediated. Going forward, additional preclinical demonstrations of the ability to induce sustained beneficial phenotypes that reduce the burden of acute and chronic neurodegeneration, and experimental interrogations of the regulatory constructs responsible for these epigenetic responses, will accelerate the identification of not only efficacious but also practical, adaptive epigenetics-based treatments for individuals with neurological disease. PMID:25784897

  17. Extending injury- and disease-resistant CNS phenotypes by repetitive epigenetic conditioning.

    PubMed

    Gidday, Jeffrey M

    2015-01-01

    Significant reductions in the extent of acute injury in the CNS can be achieved by exposure to different preconditioning stimuli, but the duration of the induced protective phenotype is typically short-lasting, and thus is deemed as limiting its clinical applicability. Extending the period over which such adaptive epigenetic changes persist - in effect, expanding conditioning's "therapeutic window" - would significantly broaden the potential applications of such a treatment approach in patients. The frequency of the conditioning stimulus may hold the key. While transient (1-3 days) protection against CNS ischemic injury is well established preclinically following a single preconditioning stimulus, repetitively presenting preconditioning stimuli extends the duration of ischemic tolerance by many weeks. Moreover, repetitive intermittent postconditioning enhances post-ischemic recovery metrics and improves long-term survival. Intermittent conditioning is also efficacious for preventing or delaying injury in preclinical models of chronic neurodegenerative disease, and for promoting long-lasting functional improvements in a number of other pathologies as well. Although the detailed mechanisms underlying these protracted kinds of neuroplasticity remain largely unstudied, accumulating empirical evidence supports the contention that all of these adaptive phenotypes are epigenetically mediated. Going forward, additional preclinical demonstrations of the ability to induce sustained beneficial phenotypes that reduce the burden of acute and chronic neurodegeneration, and experimental interrogations of the regulatory constructs responsible for these epigenetic responses, will accelerate the identification of not only efficacious but also practical, adaptive epigenetics-based treatments for individuals with neurological disease. PMID:25784897

  18. Nanodosimetric track structure in homogeneous extended beams.

    PubMed

    Conte, V; Moro, D; Colautti, P; Grosswendt, B

    2015-09-01

    Physical aspects of particle track structure are important in determining the induction of clustered damage in relevant subcellular structures like the DNA and higher-order genomic structures. The direct measurement of track-structure properties of ionising radiation is feasible today by counting the number of ionisations produced inside a small gas volume. In particular, the so-called track-nanodosimeter, installed at the TANDEM-ALPI accelerator complex of LNL, measures ionisation cluster-size distributions in a simulated subcellular structure of dimensions 20 nm, corresponding approximately to the diameter of the chromatin fibre. The target volume is irradiated by pencil beams of primary particles passing at specified impact parameter. To directly relate these measured track-structure data to radiobiological measurements performed in broad homogeneous particle beams, these data can be integrated over the impact parameter. This procedure was successfully applied to 240 MeV carbon ions and compared with Monte Carlo simulations for extended fields. PMID:25848108

  19. Angle-resolved photoemission extended fine structure

    SciTech Connect

    Barton, J.J.

    1985-03-01

    Measurements of the Angle-Resolved Photoemission Extended Fine Structure (ARPEFS) from the S(1s) core level of a c(2 x 2)S/Ni(001) are analyzed to determine the spacing between the S overlayer and the first and second Ni layers. ARPEFS is a type of photoelectron diffraction measurement in which the photoelectron kinetic energy is swept typically from 100 to 600 eV. By using this wide range of intermediate energies we add high precision and theoretical simplification to the advantages of the photoelectron diffraction technique for determining surface structures. We report developments in the theory of photoelectron scattering in the intermediate energy range, measurement of the experimental photoemission spectra, their reduction to ARPEFS, and the surface structure determination from the ARPEFS by combined Fourier and multiple-scattering analyses. 202 refs., 67 figs., 2 tabs.

  20. EXTENDED CULTURE OF MACROPHAGES FROM DIFFERENT SOURCES AND MATURATION RESULTS IN A COMMON M2 PHENOTYPE

    PubMed Central

    Chamberlain, Lisa M.; Holt-Casper, Dolly; Gonzalez-Juarrero, Mercedes; Grainger, David W.

    2015-01-01

    Inflammatory responses to biomaterials heavily influence the environment surrounding implanted devices, often producing foreign body reactions. The macrophage is a key immunomodulatory cell type consistently associated with implanted biomaterials and routinely employed in short term in vitro cell studies of biomaterials aiming to reproduce host responses. Inconsistencies within these studies, including differently sourced cells, different durations of culture, and assessment of different activation markers, lead to many conflicting results in vitro that confound consistency and conclusions. We hypothesize that different experimentally popular monocyte-macrophage cell types have intrinsic in vitro culture-specific differences that yield conflicting results. Recent studies demonstrate changes in cultured macrophage cytokine expression over time, leading to the hypothesis that changes in macrophage phenotype also occur in response to extended culture. Here, macrophage cells of different transformed and primary-derived origins were cultured for 21 days on model polymer biomaterials. Cell type-based differences in morphology and cytokine/chemokine expression as well as changes in cell surface biomarkers associated with differentiation stage, activation state, and adhesion were compared. Results reflect consistent macrophage development towards an M2 phenotype via up-regulation of the macrophage mannose receptor for all cell types following 21-day extended culture. Significantly, implanted biomaterials experiencing the foreign body response and encapsulation in vivo often elicit a shift towards an analogous M2 macrophage phenotype. In vitro “default” of macrophage cultures, regardless of lineage, to this M2 state in the presence of biomaterials at long culture periods is not recognized but has important implications to in vitro modeling of in vivo host response. PMID:25684281

  1. Extended culture of macrophages from different sources and maturation results in a common M2 phenotype.

    PubMed

    Chamberlain, Lisa M; Holt-Casper, Dolly; Gonzalez-Juarrero, Mercedes; Grainger, David W

    2015-09-01

    Inflammatory responses to biomaterials heavily influence the environment surrounding implanted devices, often producing foreign-body reactions. The macrophage is a key immunomodulatory cell type consistently associated with implanted biomaterials and routinely used in short-term in vitro cell studies of biomaterials aiming to reproduce host responses. Inconsistencies within these studies, including differently sourced cells, different durations of culture, and assessment of different activation markers, lead to many conflicting results in vitro that confound consistency and conclusions. We hypothesize that different experimentally popular monocyte-macrophage cell types have intrinsic in vitro culture-specific differences that yield conflicting results. Recent studies demonstrate changes in cultured macrophage cytokine expression over time, leading to the hypothesis that changes in macrophage phenotype also occur in response to extended culture. Here, macrophage cells of different transformed and primary-derived origins were cultured for 21 days on model polymer biomaterials. Cell type-based differences in morphology and cytokine/chemokine expression as well as changes in cell surface biomarkers associated with differentiation stage, activation state, and adhesion were compared. Results reflect consistent macrophage development toward an M2 phenotype via up-regulation of the macrophage mannose receptor for all cell types following 21-day extended culture. Significantly, implanted biomaterials experiencing the foreign-body response and encapsulation in vivo often elicit a shift toward an analogous M2 macrophage phenotype. In vitro "default" of macrophage cultures, regardless of lineage, to this M2 state in the presence of biomaterials at long culture periods is not recognized, but has important implications to in vitro modeling of in vivo host response. PMID:25684281

  2. Extended Solar System Structures Observed by WISE

    NASA Astrophysics Data System (ADS)

    Sykes, Mark V.; Masci, Frank; Cutri, Roc; Walker, Russell; Mainzer, Amy; Bauer, James; Stevenson, Rachel; Tricarico, Pasquale

    2014-11-01

    Extended structures associated with recent asteroid collisions and comets were detected by the Infrared Astronomical Satellite, which conducted the first survey of the thermal emission of the sky in 1983. Twenty-seven years later, the Wide-field Infrared Survey Explorer (WISE), conducted a more sensitive survey of the sky at wavelengths spanning the shorter IRAS bandpasses and detected many of these same structures. Initial identifications include asteroid dust bands associated with collisions giving rise to the Karin and Beagle clusters within the Koronis and Themis asteroid families, respectively. An additional pair of bands is associated with the collision giving rise to the Veritas asteroid family. Comet trails associated with short-period comets have also been observed. Type 2 trails, detected by IRAS and possibly associated with asteroid collisions within the past few thousand years, have yet to be identified. Because WISE is significantly more sensitive than IRAS in the mid-infrared, it has detected some trails extending much further over their orbits and will greatly expand the catalog of trails detected in addition to those observed by IRAS and Spitzer (the latter by targeted observations). WISE and the yet more sensitive NEOCAM survey telescope will provide important insights into the recent collisional history of the asteroid belt and the nature and evolution of comets.

  3. Extended region of nodulation genes in Rhizobium meliloti 1021. I. Phenotypes of Tn5 insertion mutants

    SciTech Connect

    Swanson, J.A.; Tu, J.K.; Ogawa, J.; Sanga, R.; Fisher, R.F.; Long, S.R.

    1987-10-01

    Rhizobium meliloti Nod/sup -/ mutant WL131, a derivative of wild-type strain 102F51, was complemented by a clone bank of wild-type R. meliloti 1021 DNA, and clone pRmJT5 was recovered. Transfer of pRmJT5 conferred alfalfa nodulation on other Rhizobium species, indicating a role in host range determination for pRmJT5. Mutagenesis of pRmJT5 revealed several segments in which transposon insertion causes delay in nodulation, and/or marked reduction of the number of nodules formed on host alfalfa plants. The set of mutants indicated five regions in which nod genes are located; one mutant, nod-216, is located in a region not previously reported to encode a nodulation gene. Other mutant phenotypes correlated with the positions of open reading frames for nodH, nodF and nodE, and with a 2.2-kb EcoRI fragment. A mutant in nodG had no altered phenotype in this strain. One nodulation mutant was shown to be a large deletion of the common nod gene region. The authors present a discussion comparing the various studies made on this extended nod gene region.

  4. Detection of extended-spectrum β-lactamases in Klebsiella pneumoniae: comparison of phenotypic characterization methods

    PubMed Central

    Ejaz, Hasan; ul-Haq, Ikram; Mahmood, Saqib; Zafar, Aizza; Mohsin Javed, Muhammad

    2013-01-01

    Objective: Extended-spectrum β-lactamase producing K. pneumoniae is a serious threat to the patients. This manuscript shows the comparison of phenotypic characterization methods used for ESBL K. pneumoniae and frequency distribution of these isolates in various clinical samples. Methodology: Eleven different types of pathological samples collected on various time intervals were analyzed. K. pneumoniae were identified with API 20E system (bioMerieux) and initial screening of ESBL K. pneumoniae was performed using the ceftazidime antimicrobial disc. Double-disc synergy test (DDST) and CLSI confirmatory test were compared for the phenotypic detection of ESBL K. pneumoniae. Results: A total number of 214 ESBL producing K. pneumoniae were isolated from various clinical samples. Frequency distribution of ESBL producing K. pneumoniae was found to be highest among blood 117 (54.7%) and urine 46 (21.5%) samples. Data regarding the use of various interventions among these patients showed most common presence of intravenous line 209 (97.7%) and urinary catheters 46 (21.5%). Comparison of DDST and CLSI confirmatory test showed that the DDST detected 145 (67.8%) isolates while 213 (99.5%) ESBL K. pneumoniae were characterized by CLSI confirmatory test. Conclusion: The use of CLSI confirmatory test is very efficient in the early detection of ESBL K. pneumoniae especially when the facilities for molecular characterization are not available. PMID:24353625

  5. Next-generation Sequencing Extends the Phenotypic Spectrum for LCA5 Mutations: Novel LCA5 Mutations in Cone Dystrophy.

    PubMed

    Chen, Xue; Sheng, Xunlun; Sun, Xiantao; Zhang, Yuxin; Jiang, Chao; Li, Huiping; Ding, Sijia; Liu, Yani; Liu, Wenzhou; Li, Zili; Zhao, Chen

    2016-01-01

    We aim to characterize the clinical features and genetic causes for two affected siblings from a Chinese family with cone dystrophy (CD). Two patients and four unaffected family members were recruited and received complete ophthalmic examinations. Genomic DNA was isolated from the peripheral blood samples from all patients. Targeted next-generation sequencing (NGS) approach followed by intrafamilal cosegregation and in silico analyses were employed to determine the genetic defects. Ophthalmic evaluations finalized the clinical diagnosis of CD for the two patients in this family, both of whom presented macular atrophy with no remarkable changes in the peripheral retina. Comprehensive genetic screening approach revealed biallelic missense mutations in the Leber congenital amaurosis 5 (LCA5) gene, p.[Ala212Pro];[Tyr441Cys], as disease causative for this family. Both mutations were novel. The first substitution was predicted to eliminate a hydrogen bond and alter the tertiary structure of lebercilin, protein encoded by LCA5. We for the first time report novel biallelic LCA5 mutations in causing CD. Our study extends the phenotypic and genotypic spectrums for LCA5-associated retinopathies and better illustrates its genotype-phenotype correlations, which would help with better genetic diagnosis, prognosis, and personalized treatment for CD patients. PMID:27067258

  6. Next-generation Sequencing Extends the Phenotypic Spectrum for LCA5 Mutations: Novel LCA5 Mutations in Cone Dystrophy

    PubMed Central

    Chen, Xue; Sheng, Xunlun; Sun, Xiantao; Zhang, Yuxin; Jiang, Chao; Li, Huiping; Ding, Sijia; Liu, Yani; Liu, Wenzhou; Li, Zili; Zhao, Chen

    2016-01-01

    We aim to characterize the clinical features and genetic causes for two affected siblings from a Chinese family with cone dystrophy (CD). Two patients and four unaffected family members were recruited and received complete ophthalmic examinations. Genomic DNA was isolated from the peripheral blood samples from all patients. Targeted next-generation sequencing (NGS) approach followed by intrafamilal cosegregation and in silico analyses were employed to determine the genetic defects. Ophthalmic evaluations finalized the clinical diagnosis of CD for the two patients in this family, both of whom presented macular atrophy with no remarkable changes in the peripheral retina. Comprehensive genetic screening approach revealed biallelic missense mutations in the Leber congenital amaurosis 5 (LCA5) gene, p.[Ala212Pro];[Tyr441Cys], as disease causative for this family. Both mutations were novel. The first substitution was predicted to eliminate a hydrogen bond and alter the tertiary structure of lebercilin, protein encoded by LCA5. We for the first time report novel biallelic LCA5 mutations in causing CD. Our study extends the phenotypic and genotypic spectrums for LCA5-associated retinopathies and better illustrates its genotype-phenotype correlations, which would help with better genetic diagnosis, prognosis, and personalized treatment for CD patients. PMID:27067258

  7. Think laterally: horizontal gene transfer from symbiotic microbes may extend the phenotype of marine sessile hosts

    PubMed Central

    Degnan, Sandie M.

    2014-01-01

    Since the origin of the animal kingdom, marine animals have lived in association with viruses, prokaryotes and unicellular eukaryotes, often as symbionts. This long and continuous interaction has provided ample opportunity not only for the evolution of intimate interactions such as sharing of metabolic pathways, but also for horizontal gene transfer (HGT) of non-metazoan genes into metazoan genomes. The number of demonstrated cases of inter-kingdom HGT is currently small, such that it is not yet widely appreciated as a significant player in animal evolution. Sessile marine invertebrates that vertically inherit bacterial symbionts, that have no dedicated germ line, or that bud or excise pluripotent somatic cells during their life history may be particularly receptive to HGT from their symbionts. Closer scrutiny of the growing number of genomes being accrued for these animals may thus reveal HGT as a regular source of novel variation that can function to extend the host phenotype metabolically, morphologically, or even behaviorally. Taxonomic identification of symbionts will help to address the intriguing question of whether past HGT events may constrain contemporary symbioses. PMID:25477875

  8. Targeted next-generation sequencing extends the phenotypic and mutational spectrums for EYS mutations

    PubMed Central

    Gu, Shun; Tian, Yuanyuan; Chen, Xue

    2016-01-01

    Purpose We aim to determine genetic lesions with a phenotypic correlation in four Chinese families with autosomal recessive retinitis pigmentosa (RP). Methods Medical histories were carefully reviewed. All patients received comprehensive ophthalmic evaluations. The next-generation sequencing (NGS) approach targeting a panel of 205 retinal disease–relevant genes and 15 candidate genes was selectively performed on probands from the four recruited families for mutation detection. Online predictive software and crystal structure modeling were also applied to test the potential pathogenic effects of identified mutations. Results Of the four families, two were diagnosed with RP sino pigmento (RPSP). Patients with RPSP claimed to have earlier RP age of onset but slower disease progression. Five mutations in the eyes shut homolog (EYS) gene, involving two novel (c.7228+1G>A and c.9248G>A) and three recurrent mutations (c.4957dupA, c.6416G>A and c.6557G>A), were found as RP causative in the four families. The missense variant c.5093T>C was determined to be a variant of unknown significance (VUS) due to the variant’s colocalization in the same allele with the reported pathogenic mutation c.6416G>A. The two novel variants were further confirmed absent in 100 unrelated healthy controls. Online predictive software indicated potential pathogenicity of the three missense mutations. Further, crystal structural modeling suggested generation of two abnormal hydrogen bonds by the missense mutation p.G2186E (c.6557G>A) and elongation of its neighboring β-sheet induced by p.G3083D (c.9248G>A), which could alter the tertiary structure of the eys protein and thus interrupt its physicochemical properties. Conclusions Taken together, with the targeted NGS approach, we reveal novel EYS mutations and prove the efficiency of targeted NGS in the genetic diagnoses of RP. We also first report the correlation between EYS mutations and RPSP. The genotypic-phenotypic relationship in all

  9. The structure of phenotypic personality traits.

    PubMed

    Goldberg, L R

    1993-01-01

    This personal historical article traces the development of the Big-Five factor structure, whose growing acceptance by personality researchers has profoundly influenced the scientific study of individual differences. The roots of this taxonomy lie in the lexical hypothesis and the insights of Sir Francis Galton, the prescience of L. L. Thurstone, the legacy of Raymond B. Cattell, and the seminal analyses of Tupes and Christal. Paradoxically, the present popularity of this model owes much to its many critics, each of whom tried to replace it, but failed. In reaction, there have been a number of attempts to assimilate other models into the five-factor structure. Lately, some practical implications of the emerging consensus can be seen in such contexts as personnel selection and classification. PMID:8427480

  10. Extended phenotypes in a boy and his mother with oto-palato-digital-syndrome type II.

    PubMed

    Kaissi, Ali Al; Kraschl, Raimund; Kaulfersch, Wilhelm; Grill, Franz; Ganger, Rudolf

    2015-09-01

    We describe additional phenotypic features in a boy and his mother. Both manifested the phenotypic/genotypic correlation of oto-palato-digital syndrome type II. The mother's radiographs showed wormian bones of the skull, and paranasal bossing, her feet showed bilateral fusion of the cuboid with the lateral cuneiform bone with subsequent development of metatarsus varus associated with dysplastic distal phalanges. PMID:26401283

  11. Arrhythmogenic Cardiomyopathy: Electrical and Structural Phenotypes

    PubMed Central

    Akdis, Deniz; Brunckhorst, Corinna; Duru, Firat

    2016-01-01

    This overview gives an update on the molecular mechanisms, clinical manifestations, diagnosis and therapy of arrhythmogenic cardiomyopathy (ACM). ACM is mostly hereditary and associated with mutations in genes encoding proteins of the intercalated disc. Three subtypes have been proposed: the classical right-dominant subtype generally referred to as ARVC/D, biventricular forms with early biventricular involvement and left-dominant subtypes with predominant LV involvement. Typical symptoms include palpitations, arrhythmic (pre)syncope and sudden cardiac arrest due to ventricular arrhythmias, which typically occur in athletes. At later stages, heart failure may occur. Diagnosis is established with the 2010 Task Force Criteria (TFC). Modern imaging tools are crucial for ACM diagnosis, including both echocardiography and cardiac magnetic resonance imaging for detecting functional and structural alternations. Of note, structural findings often become visible after electrical alterations, such as premature ventricular beats, ventricular fibrillation (VF) and ventricular tachycardia (VT). 12-lead ECG is important to assess for depolarisation and repolarisation abnormalities, including T-wave inversions as the most common ECG abnormality. Family history and the detection of causative mutations, mostly affecting the desmosome, have been incorporated in the TFC, and stress the importance of cascade family screening. Differential diagnoses include idiopathic right ventricular outflow tract (RVOT) VT, sarcoidosis, congenital heart disease, myocarditis, dilated cardiomyopathy, athlete’s heart, Brugada syndrome and RV infarction. Therapeutic strategies include restriction from endurance and competitive sports, β-blockers, antiarrhythmic drugs, heart failure medication, implantable cardioverter-defibrillators and endocardial/epicardial catheter ablation. PMID:27617087

  12. Arrhythmogenic Cardiomyopathy: Electrical and Structural Phenotypes.

    PubMed

    Akdis, Deniz; Brunckhorst, Corinna; Duru, Firat; Saguner, Ardan M

    2016-08-01

    This overview gives an update on the molecular mechanisms, clinical manifestations, diagnosis and therapy of arrhythmogenic cardiomyopathy (ACM). ACM is mostly hereditary and associated with mutations in genes encoding proteins of the intercalated disc. Three subtypes have been proposed: the classical right-dominant subtype generally referred to as ARVC/D, biventricular forms with early biventricular involvement and left-dominant subtypes with predominant LV involvement. Typical symptoms include palpitations, arrhythmic (pre)syncope and sudden cardiac arrest due to ventricular arrhythmias, which typically occur in athletes. At later stages, heart failure may occur. Diagnosis is established with the 2010 Task Force Criteria (TFC). Modern imaging tools are crucial for ACM diagnosis, including both echocardiography and cardiac magnetic resonance imaging for detecting functional and structural alternations. Of note, structural findings often become visible after electrical alterations, such as premature ventricular beats, ventricular fibrillation (VF) and ventricular tachycardia (VT). 12-lead ECG is important to assess for depolarisation and repolarisation abnormalities, including T-wave inversions as the most common ECG abnormality. Family history and the detection of causative mutations, mostly affecting the desmosome, have been incorporated in the TFC, and stress the importance of cascade family screening. Differential diagnoses include idiopathic right ventricular outflow tract (RVOT) VT, sarcoidosis, congenital heart disease, myocarditis, dilated cardiomyopathy, athlete's heart, Brugada syndrome and RV infarction. Therapeutic strategies include restriction from endurance and competitive sports, β-blockers, antiarrhythmic drugs, heart failure medication, implantable cardioverter-defibrillators and endocardial/epicardial catheter ablation. PMID:27617087

  13. Extended phenotypes in a boy and his mother with oto-palato-digital-syndrome type II

    PubMed Central

    Kaissi, Ali Al; Kraschl, Raimund; Kaulfersch, Wilhelm; Grill, Franz; Ganger, Rudolf

    2015-01-01

    Key Clinical Message We describe additional phenotypic features in a boy and his mother. Both manifested the phenotypic/genotypic correlation of oto-palato-digital syndrome type II. The mother′s radiographs showed wormian bones of the skull, and paranasal bossing, her feet showed bilateral fusion of the cuboid with the lateral cuneiform bone with subsequent development of metatarsus varus associated with dysplastic distal phalanges. PMID:26401283

  14. Structural Phenotyping of Stem Cell-Derived Cardiomyocytes

    PubMed Central

    Pasqualini, Francesco Silvio; Sheehy, Sean Paul; Agarwal, Ashutosh; Aratyn-Schaus, Yvonne; Parker, Kevin Kit

    2015-01-01

    Summary Structural phenotyping based on classical image feature detection has been adopted to elucidate the molecular mechanisms behind genetically or pharmacologically induced changes in cell morphology. Here, we developed a set of 11 metrics to capture the increasing sarcomere organization that occurs intracellularly during striated muscle cell development. To test our metrics, we analyzed the localization of the contractile protein α-actinin in a variety of primary and stem-cell derived cardiomyocytes. Further, we combined these metrics with data mining algorithms to unbiasedly score the phenotypic maturity of human-induced pluripotent stem cell-derived cardiomyocytes. PMID:25733020

  15. Introduction: Dissipative localized structures in extended systems

    NASA Astrophysics Data System (ADS)

    Tlidi, Mustapha; Taki, Majid; Kolokolnikov, Theodore

    2007-09-01

    Localized structures belong to the class of dissipative structures found far from equilibrium. Contributions from the most representative groups working on a various fields of natural science such as biology, chemistry, plant ecology, mathematics, optics, and laser physics are presented. The aim of this issue is to gather specialists from these fields towards a cross-fertilization among these active areas of research and thereby to present an overview of the state of art in the formation and the characterization of dissipative localized structures. Nonlinear optics and laser physics have an important part in this issue because of potential applications in information technology. In particular, localized structures could be used as "bits" for parallel information storage and processing.

  16. HMG Nuclear Proteins: Linking Chromatin Structure to Cellular Phenotype

    PubMed Central

    Reeves, Raymond

    2009-01-01

    I. Summary Although the three families of mammalian HMG proteins (HMGA, HMGB and HMGN) participate in many of the same nuclear processes, each family plays its own unique role in modulating chromatin structure and regulating genomic function. This review focuses on the similarities and differences in the mechanisms by which the different HMG families impact chromatin structure and influence cellular phenotype. The biological implications of having three architectural transcription factor families with complementary, but partially overlapping, nuclear functions are discussed. PMID:19748605

  17. A folding algorithm for extended RNA secondary structures

    PubMed Central

    zu Siederdissen, Christian Höner; Bernhart, Stephan H.; Stadler, Peter F.; Hofacker, Ivo L.

    2011-01-01

    Motivation: RNA secondary structure contains many non-canonical base pairs of different pair families. Successful prediction of these structural features leads to improved secondary structures with applications in tertiary structure prediction and simultaneous folding and alignment. Results: We present a theoretical model capturing both RNA pair families and extended secondary structure motifs with shared nucleotides using 2-diagrams. We accompany this model with a number of programs for parameter optimization and structure prediction. Availability: All sources (optimization routines, RNA folding, RNA evaluation, extended secondary structure visualization) are published under the GPLv3 and available at www.tbi.univie.ac.at/software/rnawolf/. Contact: choener@tbi.univie.ac.at PMID:21685061

  18. Novel TTC37 Mutations in a Patient with Immunodeficiency without Diarrhea: Extending the Phenotype of Trichohepatoenteric Syndrome.

    PubMed

    Rider, Nicholas L; Boisson, Bertrand; Jyonouchi, Soma; Hanson, Eric P; Rosenzweig, Sergio D; Cassanova, Jean-Laurent; Orange, Jordan S

    2015-01-01

    Unbiased genetic diagnosis has increasingly associated seemingly unrelated somatic and immunological phenotypes. We report a male infant who presented within the first year of life with physical growth impairment, feeding difficulties, hyperemesis without diarrhea, and abnormal hair findings suggestive of trichorrhexis nodosa. With advancing age, moderate global developmental delay, susceptibility to frequent viral illnesses, otitis media, and purulent conjunctivitis were identified. Because of the repeated infections, an immunological evaluation was pursued and identified impaired antibody memory responses following pneumococcal vaccine administration. Immunoglobulin replacement therapy and nutritional support were employed as mainstays of therapy. The child is now aged 12 years and still without diarrhea. Whole exome sequencing identified compound heterozygous mutations in the TTC37 gene, a known cause of the trichohepatoenteric syndrome (THES). This case extends the known phenotype of THES and defines a potential subset for inclusion as an immune overlap syndrome. PMID:25688341

  19. Novel TTC37 Mutations in a Patient with Immunodeficiency without Diarrhea: Extending the Phenotype of Trichohepatoenteric Syndrome

    PubMed Central

    Rider, Nicholas L.; Boisson, Bertrand; Jyonouchi, Soma; Hanson, Eric P.; Rosenzweig, Sergio D.; Casanova, Jean-Laurent; Orange, Jordan S.

    2015-01-01

    Unbiased genetic diagnosis has increasingly associated seemingly unrelated somatic and immunological phenotypes. We report a male infant who presented within the first year of life with physical growth impairment, feeding difficulties, hyperemesis without diarrhea, and abnormal hair findings suggestive of trichorrhexis nodosa. With advancing age, moderate global developmental delay, susceptibility to frequent viral illnesses, otitis media, and purulent conjunctivitis were identified. Because of the repeated infections, an immunological evaluation was pursued and identified impaired antibody memory responses following pneumococcal vaccine administration. Immunoglobulin replacement therapy and nutritional support were employed as mainstays of therapy. The child is now aged 12 years and still without diarrhea. Whole exome sequencing identified compound heterozygous mutations in the TTC37 gene, a known cause of the trichohepatoenteric syndrome (THES). This case extends the known phenotype of THES and defines a potential subset for inclusion as an immune overlap syndrome. PMID:25688341

  20. Sexual and natural selection in the evolution of extended phenotypes: the use of green nesting material in starlings.

    PubMed

    Rubalcaba, J G; Polo, V; Maia, R; Rubenstein, D R; Veiga, J P

    2016-08-01

    Although sexual selection is typically considered the predominant force driving the evolution of ritualized sexual behaviours, natural selection may also play an important and often underappreciated role. The use of green aromatic plants among nesting birds has been interpreted as a component of extended phenotype that evolved either via natural selection due to potential sanitary functions or via sexual selection as a signal of male attractiveness. Here, we compared both hypotheses using comparative methods in starlings, a group where this behaviour is widespread. We found that the use of green plants was positively related to male-biased size dimorphism and that it was most likely to occur among cavity-nesting species. These results suggest that this behaviour is likely favoured by sexual selection, but also related to its sanitary use in response to higher parasite loads in cavities. We speculate that the use of green plants in starlings may be facilitated by cavity nesting and was subsequently co-opted as a sexual signal by males. Our results represent an example of how an extended phenotypic component of males becomes sexually selected by females. Thus, both natural selection and sexual selection are necessary to fully understand the evolution of ritualized behaviours involved in courtship. PMID:27168035

  1. Cosmetics as a feature of the extended human phenotype: modulation of the perception of biologically important facial signals.

    PubMed

    Etcoff, Nancy L; Stock, Shannon; Haley, Lauren E; Vickery, Sarah A; House, David M

    2011-01-01

    Research on the perception of faces has focused on the size, shape, and configuration of inherited features or the biological phenotype, and largely ignored the effects of adornment, or the extended phenotype. Research on the evolution of signaling has shown that animals frequently alter visual features, including color cues, to attract, intimidate or protect themselves from conspecifics. Humans engage in conscious manipulation of visual signals using cultural tools in real time rather than genetic changes over evolutionary time. Here, we investigate one tool, the use of color cosmetics. In two studies, we asked viewers to rate the same female faces with or without color cosmetics, and we varied the style of makeup from minimal (natural), to moderate (professional), to dramatic (glamorous). Each look provided increasing luminance contrast between the facial features and surrounding skin. Faces were shown for 250 ms or for unlimited inspection time, and subjects rated them for attractiveness, competence, likeability and trustworthiness. At 250 ms, cosmetics had significant positive effects on all outcomes. Length of inspection time did not change the effect for competence or attractiveness. However, with longer inspection time, the effect of cosmetics on likability and trust varied by specific makeup looks, indicating that cosmetics could impact automatic and deliberative judgments differently. The results suggest that cosmetics can create supernormal facial stimuli, and that one way they may do so is by exaggerating cues to sexual dimorphism. Our results provide evidence that judgments of facial trustworthiness and attractiveness are at least partially separable, that beauty has a significant positive effect on judgment of competence, a universal dimension of social cognition, but has a more nuanced effect on the other universal dimension of social warmth, and that the extended phenotype significantly influences perception of biologically important signals at first

  2. Cosmetics as a Feature of the Extended Human Phenotype: Modulation of the Perception of Biologically Important Facial Signals

    PubMed Central

    Etcoff, Nancy L.; Stock, Shannon; Haley, Lauren E.; Vickery, Sarah A.; House, David M.

    2011-01-01

    Research on the perception of faces has focused on the size, shape, and configuration of inherited features or the biological phenotype, and largely ignored the effects of adornment, or the extended phenotype. Research on the evolution of signaling has shown that animals frequently alter visual features, including color cues, to attract, intimidate or protect themselves from conspecifics. Humans engage in conscious manipulation of visual signals using cultural tools in real time rather than genetic changes over evolutionary time. Here, we investigate one tool, the use of color cosmetics. In two studies, we asked viewers to rate the same female faces with or without color cosmetics, and we varied the style of makeup from minimal (natural), to moderate (professional), to dramatic (glamorous). Each look provided increasing luminance contrast between the facial features and surrounding skin. Faces were shown for 250 ms or for unlimited inspection time, and subjects rated them for attractiveness, competence, likeability and trustworthiness. At 250 ms, cosmetics had significant positive effects on all outcomes. Length of inspection time did not change the effect for competence or attractiveness. However, with longer inspection time, the effect of cosmetics on likability and trust varied by specific makeup looks, indicating that cosmetics could impact automatic and deliberative judgments differently. The results suggest that cosmetics can create supernormal facial stimuli, and that one way they may do so is by exaggerating cues to sexual dimorphism. Our results provide evidence that judgments of facial trustworthiness and attractiveness are at least partially separable, that beauty has a significant positive effect on judgment of competence, a universal dimension of social cognition, but has a more nuanced effect on the other universal dimension of social warmth, and that the extended phenotype significantly influences perception of biologically important signals at first

  3. Phenotyping structural abnormalities in mouse embryos using high-resolution episcopic microscopy

    PubMed Central

    Weninger, Wolfgang J.; Geyer, Stefan H.; Martineau, Alexandrine; Galli, Antonella; Adams, David J.; Wilson, Robert; Mohun, Timothy J.

    2014-01-01

    The arrival of simple and reliable methods for 3D imaging of mouse embryos has opened the possibility of analysing normal and abnormal development in a far more systematic and comprehensive manner than has hitherto been possible. This will not only help to extend our understanding of normal tissue and organ development but, by applying the same approach to embryos from genetically modified mouse lines, such imaging studies could also transform our knowledge of gene function in embryogenesis and the aetiology of developmental disorders. The International Mouse Phenotyping Consortium is coordinating efforts to phenotype single gene knockouts covering the entire mouse genome, including characterising developmental defects for those knockout lines that prove to be embryonic lethal. Here, we present a pilot study of 34 such lines, utilising high-resolution episcopic microscopy (HREM) for comprehensive 2D and 3D imaging of homozygous null embryos and their wild-type littermates. We present a simple phenotyping protocol that has been developed to take advantage of the high-resolution images obtained by HREM and that can be used to score tissue and organ abnormalities in a reliable manner. Using this approach with embryos at embryonic day 14.5, we show the wide range of structural abnormalities that are likely to be detected in such studies and the variability in phenotypes between sibling homozygous null embryos. PMID:25256713

  4. Association between brain structure and phenotypic characteristics in pedophilia.

    PubMed

    Poeppl, Timm B; Nitschke, Joachim; Santtila, Pekka; Schecklmann, Martin; Langguth, Berthold; Greenlee, Mark W; Osterheider, Michael; Mokros, Andreas

    2013-05-01

    Studies applying structural neuroimaging to pedophiles are scarce and have shown conflicting results. Although first findings suggested reduced volume of the amygdala, pronounced gray matter decreases in frontal regions were observed in another group of pedophilic offenders. When compared to non-sexual offenders instead of community controls, pedophiles revealed deficiencies in white matter only. The present study sought to test the hypotheses of structurally compromised prefrontal and limbic networks and whether structural brain abnormalities are related to phenotypic characteristics in pedophiles. We compared gray matter volume of male pedophilic offenders and non-sexual offenders from high-security forensic hospitals using voxel-based morphometry in cross-sectional and correlational whole-brain analyses. The significance threshold was set to p < .05, corrected for multiple comparisons. Compared to controls, pedophiles exhibited a volume reduction of the right amygdala (small volume corrected). Within the pedophilic group, pedosexual interest and sexual recidivism were correlated with gray matter decrease in the left dorsolateral prefrontal cortex (r = -.64) and insular cortex (r = -.45). Lower age of victims was strongly associated with gray matter reductions in the orbitofrontal cortex (r = .98) and angular gyri bilaterally (r = .70 and r = .93). Our findings of specifically impaired neural networks being related to certain phenotypic characteristics might account for the heterogeneous results in previous neuroimaging studies of pedophilia. The neuroanatomical abnormalities in pedophilia seem to be of a dimensional rather than a categorical nature, supporting the notion of a multifaceted disorder. PMID:23399486

  5. Comparison of nine phenotypic methods for detection of extended-spectrum beta-lactamase production by Enterobacteriaceae.

    PubMed

    Garrec, Hélène; Drieux-Rouzet, Laurence; Golmard, Jean-Louis; Jarlier, Vincent; Robert, Jérôme

    2011-03-01

    The detection of extended-spectrum β-lactamase-producing (ESBL) bacteria is of importance for infection control and epidemiological surveillance. We aimed to compare phenotypic methods available in the routine laboratory and to evaluate two-step strategies using these methods for the detection of ESBL-positive Enterobacteriaceae. Two methods used for routine susceptibility testing (Vitek2 and disk diffusion methods) and seven methods designed for the detection of ESBL production (ESBL Etests, combination disks, double-disk synergy [DDS] methods on Mueller-Hinton [MH] agar and cloxacillin-containing MH agar, and the Cica-Beta test) were tested against 107 strains of Enterobacteriaceae not susceptible to extended-spectrum cephalosporins. All strains were screened for the presence of acquired ESBL-encoding genes by PCR, and the PCR result was considered the gold standard for evaluation of the other test methods. Among the 107 strains, 52 (49%) were ESBL positive. With Vitek2, sensitivities were the highest when using extended cards (73% to 79%), but 25% to 31% of the strains yielded indeterminate results. For the disk diffusion method, sensitivities were the highest (96%) when testing at least cefotaxime, cefepime, and a third compound (ceftazidime, cefpodoxime, or aztreonam). For the specific methods, specificities ranged from 62% (ceftazidime ESBL Etest) to 100% (DDS using a disk spacing of 20 mm). When a method designed for ESBL detection was used on strains considered ESBL negative or with an indeterminate result by a first routine susceptibility method, sensitivities reached 100% for a majority of combinations. In conclusion, two-step strategies using phenotypic methods available in most clinical laboratories may reach a sensitivity of 100% for ESBL detection among a large panel of species, including AmpC producers, providing a sensible choice of tests. PMID:21248086

  6. Structural genomic variation in childhood epilepsies with complex phenotypes

    PubMed Central

    Helbig, Ingo; Swinkels, Marielle E M; Aten, Emmelien; Caliebe, Almuth; van 't Slot, Ruben; Boor, Rainer; von Spiczak, Sarah; Muhle, Hiltrud; Jähn, Johanna A; van Binsbergen, Ellen; van Nieuwenhuizen, Onno; Jansen, Floor E; Braun, Kees P J; de Haan, Gerrit-Jan; Tommerup, Niels; Stephani, Ulrich; Hjalgrim, Helle; Poot, Martin; Lindhout, Dick; Brilstra, Eva H; Møller, Rikke S; Koeleman, Bobby PC

    2014-01-01

    A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened for CNVs. MRI findings including acquired or developmental lesions and patient characteristics were subdivided and analyzed in subgroups. MRI data were available for 88.3% of patients, of whom 41.6% had abnormal MRI findings. Eighty-eight rare CNVs were discovered in 71 out of 222 patients (31.9%). Segregation of all identified variants could be assessed in 42 patients, 11 of which were de novo. The frequency of all structural variants and de novo variants was not statistically different between patients with or without MRI abnormalities or MRI subcategories. Patients with dysmorphic features were more likely to carry a rare CNV. Genome-wide screening methods for rare CNVs may provide clues for the genetic etiology in patients with a broader range of epilepsies than previously anticipated, including in patients with various brain anomalies detectable by MRI. Performing genome-wide screens for rare CNVs can be a valuable contribution to the routine diagnostic workup in patients with a broad range of childhood epilepsies. PMID:24281369

  7. A novel GABRG2 mutation, p.R136*, in a family with GEFS+ and extended phenotypes.

    PubMed

    Johnston, Ann J; Kang, Jing-Qiong; Shen, Wangzhen; Pickrell, William O; Cushion, Thomas D; Davies, Jeffrey S; Baer, Kristin; Mullins, Jonathan G L; Hammond, Carrie L; Chung, Seo-Kyung; Thomas, Rhys H; White, Cathy; Smith, Phil E M; Macdonald, Robert L; Rees, Mark I

    2014-04-01

    Genetic mutations in voltage-gated and ligand-gated ion channel genes have been identified in a small number of Mendelian families with genetic generalised epilepsies (GGEs). They are commonly associated with febrile seizures (FS), childhood absence epilepsy (CAE) and particularly with generalised or genetic epilepsy with febrile seizures plus (GEFS+). In clinical practice, despite efforts to categorise epilepsy and epilepsy families into syndromic diagnoses, many generalised epilepsies remain unclassified with a presumed genetic basis. During the systematic collection of epilepsy families, we assembled a cohort of families with evidence of GEFS+ and screened for variations in the γ2 subunit of the γ-aminobutyric acid (GABA) type A receptor gene (GABRG2). We detected a novel GABRG2(p.R136*) premature translation termination codon in one index-case from a two-generation nuclear family, presenting with an unclassified GGE, a borderline GEFS+ phenotype with learning difficulties and extended behavioural presentation. The GABRG2(p.R136*) mutation segregates with the febrile seizure component of this family's GGE and is absent in 190 healthy control samples. In vitro expression assays demonstrated that γ2(p.R136*) subunits were produced, but had reduced cell-surface and total expression. When γ2(p.R136*) subunits were co-expressed with α1 and β2 subunits in HEK 293T cells, GABA-evoked currents were reduced. Furthermore, γ2(p.R136*) subunits were highly-expressed in intracellular aggregations surrounding the nucleus and endoplasmic reticulum (ER), suggesting compromised receptor trafficking. A novel GABRG2(p.R136*) mutation extends the spectrum of GABRG2 mutations identified in GEFS+ and GGE phenotypes, causes GABAA receptor dysfunction, and represents a putative epilepsy mechanism. PMID:24407264

  8. Atomic Structure and Properties of Extended Defects in Silicon

    SciTech Connect

    Buczko, R.; Chisholm, M.F.; Kaplan, T.; Maiti, A.; Mostoller, M.; Pantelides, S.T.; Pennycook, S.J.

    1998-10-15

    The Z-contrast technique represents a new approach to high-resolution electron microscopy allowing for the first time incoherent imaging of materials on the atomic scale. The key advantages of the technique, an intrinsically higher resolution limit and directly interpretable, compositionally sensitive imaging, allow a new level of insight into the atomic configurations of extended defects in silicon. This experimental technique has been combined with theoretical calculations (a combination of first principles, tight binding, and classical methods) to extend this level of insight by obtaining the energetic and electronic structure of the defects.

  9. Structured light illumination for extended resolution in fluorescence microscopy

    NASA Astrophysics Data System (ADS)

    Fedosseev, R.; Belyaev, Y.; Frohn, J.; Stemmer, A.

    2005-03-01

    During the last two decades fluorescence microscopy has become a powerful experimental tool in modern biology. Resolution of optical microscopes is limited by the diffraction nature of light and amounts to approximately 200 nm for point objects imaged with green light and high-NA objectives. Recently, several successful attempts have been made to break the resolution limit of microscopes. One of them is the so-called harmonic excitation light microscopy. 2D structured illumination produced by four interfering laser beams improves the lateral resolution by a factor of 2 to reach 100 nm. Structured illumination extends optical resolution since spatial frequencies beyond the classical cut-off frequency are brought into the passband of the optical microscope by frequency mixing. The extended passband is reconstructed computationally from several images acquired with shifted illumination patterns. Here we discuss an extension towards high resolution imaging of thick specimens by combining 2D structured illumination with deconvolution techniques.

  10. Extended X-ray absorption fine structure of bimetallic nanoparticles

    PubMed Central

    2011-01-01

    Summary Electronic and magnetic properties strongly depend on the structure of the material, especially on the crystal symmetry and chemical environment. In nanoparticles, the break of symmetry at the surface may yield different physical properties with respect to the corresponding bulk material. A useful tool to investigate the electronic structure, magnetic behaviour and local crystallographic structure is X-ray absorption spectroscopy. In this review, recent developments in the field of extended X-ray absorption fine structure measurements and in the analysis methods for structural investigations of bimetallic nanoparticles are highlighted. The standard analysis based on Fourier transforms is compared to the relatively new field of wavelet transforms that have the potential to outperform traditional analysis, especially in bimetallic alloys. As an example, the lattice expansion and inhomogeneous alloying found in FePt nanoparticles is presented, and this is discussed below in terms of the influence of employed density functional theory calculations on the magnetic properties. PMID:21977436

  11. Baculovirus-induced tree-top disease: how extended is the role of egt as a gene for the extended phenotype?

    PubMed

    Ros, Vera I D; van Houte, Stineke; Hemerik, Lia; van Oers, Monique M

    2015-01-01

    Many parasites alter host behaviour to enhance their chance of transmission. Recently, the ecdysteroid UDP-glucosyl transferase (egt) gene from the baculovirus Lymantria dispar multiple nucleopolyhedrovirus (LdMNPV) was identified to induce tree-top disease in L. dispar larvae. Infected gypsy moth larvae died at elevated positions (hence the term tree-top disease), which is thought to promote dissemination of the virus to lower foliage. It is, however, unknown whether egt has a conserved role among baculoviruses in inducing tree-top disease. Here, we studied tree-top disease induced by the baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) in two different host insects, Trichoplusia ni and Spodoptera exigua, and we investigated the role of the viral egt gene therein. AcMNPV induced tree-top disease in both T. ni and S. exigua larvae, although in S. exigua a moulting-dependent effect was seen. Those S. exigua larvae undergoing a larval moult during the infection process died at elevated positions, while larvae that did not moult after infection died at low positions. For both T. ni and S. exigua, infection with a mutant AcMNPV lacking egt did not change the position where the larvae died. We conclude that egt has no highly conserved role in inducing tree-top disease in lepidopteran larvae. The conclusion that egt is a 'gene for an extended phenotype' is therefore not generally applicable for all baculovirus-host interactions. We hypothesize that in some baculovirus-host systems (including LdMNPV in L. dispar), an effect of egt on tree-top disease can be observed through indirect effects of egt on moulting-related climbing behaviour. PMID:25443568

  12. Extended structures and physicochemical properties of uranyl-organic compounds.

    PubMed

    Wang, Kai-Xue; Chen, Jie-Sheng

    2011-07-19

    The ability of uranium to undergo nuclear fission has been exploited primarily to manufacture nuclear weapons and to generate nuclear power. Outside of its nuclear physics, uranium also exhibits rich chemistry, and it forms various compounds with other elements. Among the uranium-bearing compounds, those with a uranium oxidation state of +6 are most common and a particular structural unit, uranyl UO(2)(2+) is usually involved in these hexavalent uranium compounds. Apart from forming solids with inorganic ions, the uranyl unit also bonds to organic molecules to generate uranyl-organic coordination materials. If appropriate reaction conditions are employed, uranyl-organic extended structures (1-D chains, 2-D layers, and 3-D frameworks) can be obtained. Research on uranyl-organic compounds with extended structures allows for the exploration of their rich structural chemistry, and such studies also point to potential applications such as in materials that could facilitate nuclear waste disposal. In this Account, we describe the structural features of uranyl-organic compounds and efforts to synthesize uranyl-organic compounds with desired structures. We address strategies to construct 3-D uranyl-organic frameworks through rational selection of organic ligands and the incorporation of heteroatoms. The UO(2)(2+) species with inactive U═O double bonds usually form bipyramidal polyhedral structures with ligands coordinated at the equatorial positions, and these polyhedra act as primary building units (PBUs) for the construction of uranyl-organic compounds. The geometry of the uranyl ions and the steric arrangements and functionalities of organic ligands can be exploited in the the design of uranyl--organic extended structures, We also focus on the investigation of the promising physicochemical properties of uranyl-organic compounds. Uranyl-organic materials with an extended structure may exhibit attractive properties, such as photoluminescence, photocatalysis

  13. A Novel GABRG2 Mutation, p.R136*, in a family with GEFS+ and extended phenotypes

    PubMed Central

    Shen, Wangzhen; Pickrell, William O.; Cushion, Thomas D.; Davies, Jeffrey S.; Baer, Kristin; Mullins, Jonathan G.L.; Hammond, Carrie L.; Chung, Seo-Kyung; Thomas, Rhys H.; White, Cathy; Smith, Phil E.M.

    2014-01-01

    Genetic mutations in voltage-gated and ligand-gated ion channel genes have been identified in a small number of Mendelian families with genetic generalised epilepsies (GGEs). They are commonly associated with febrile seizures (FS), childhood absence epilepsy (CAE) and particularly with generalised or genetic epilepsy with febrile seizures plus (GEFS+). In clinical practice, despite efforts to categorise epilepsy and epilepsy families into syndromic diagnoses, many generalised epilepsies remain unclassified with a presumed genetic basis. During the systematic collection of epilepsy families, we assembled a cohort of families with evidence of GEFS+ and screened for variations in the γ2 subunit of the γ-aminobutyric acid (GABA) type A receptor gene (GABRG2). We detected a novel GABRG2(p.R136*) premature translation termination codon in one index-case from a two-generation nuclear family, presenting with an unclassified GGE, a borderline GEFS+ phenotype with learning difficulties and autism spectrum disorder (ASD). The GABRG2(p.R136*) mutation segregates with the febrile seizure component of this family's GGE and is absent in 190 healthy control samples. In vitro expression assays demonstrated that γ2(p.R136*) subunits were produced, but had reduced cell-surface and total expression. When γ2(p.R136*) subunits were co-expressed with α1 and β2 subunits in HEK 293T cells, GABA–evoked currents were reduced. Furthermore, γ2(p.R136*) subunits were highly-expressed in intracellular aggregations surrounding the nucleus and endoplasmic reticulum (ER), suggesting compromised receptor trafficking. A novel GABRG2(p.R136*) mutation extends the spectrum of GABRG2 mutations identified in GEFS+ and GGE phenotypes, causes GABAA receptor dysfunction, and represents a putative epilepsy mechanism. PMID:24407264

  14. X , Y , and Z waves: extended structures in nonlinear lattices.

    PubMed

    Kevrekidis, P G; Gagnon, J; Frantzeskakis, D J; Malomed, B A

    2007-01-01

    We propose a new type of waveforms in two-dimensional (2D) and three-dimensional (3D) discrete media-multilegged extended nonlinear structures (ENSs), built as arrays of lattice solitons (tiles and stones, in the 2D and 3D cases, respectively). We study the stability of the tiles and stones analytically, and then extend them numerically to complete ENS forms for both 2D and 3D lattices, aiming to single out stable ENSs. The predicted patterns can be realized in Bose-Einstein condensates trapped in deep optical lattices, crystals built of microresonators, and 2D photonic crystals. In the latter case, the patterns provide for a technique for writing reconfigurable virtual partitions in multipurpose photonic devices. PMID:17358275

  15. Concomitant Hamiltonian and topological structures of extended magnetohydrodynamics

    NASA Astrophysics Data System (ADS)

    Lingam, Manasvi; Miloshevich, George; Morrison, Philip J.

    2016-07-01

    The paper describes the unique geometric properties of ideal magnetohydrodynamics (MHD), and demonstrates how such features are inherited by extended MHD, viz. models that incorporate two-fluid effects (the Hall term and electron inertia). The generalized helicities, and other geometric expressions for these models are presented in a topological context, emphasizing their universal facets. Some of the results presented include: the generalized Kelvin circulation theorems; the existence of two Lie-dragged 2-forms; and two concomitant helicities that can be studied via the Jones polynomial, which is widely utilized in Chern-Simons theory. The ensuing commonality is traced to the existence of an underlying Hamiltonian structure for all the extended MHD models, exemplified by the presence of a unique noncanonical Poisson bracket, and its associated energy.

  16. X , Y , and Z waves: Extended structures in nonlinear lattices

    NASA Astrophysics Data System (ADS)

    Kevrekidis, P. G.; Gagnon, J.; Frantzeskakis, D. J.; Malomed, B. A.

    2007-01-01

    We propose a new type of waveforms in two-dimensional (2D) and three-dimensional (3D) discrete media-multilegged extended nonlinear structures (ENSs), built as arrays of lattice solitons (tiles and stones, in the 2D and 3D cases, respectively). We study the stability of the tiles and stones analytically, and then extend them numerically to complete ENS forms for both 2D and 3D lattices, aiming to single out stable ENSs. The predicted patterns can be realized in Bose-Einstein condensates trapped in deep optical lattices, crystals built of microresonators, and 2D photonic crystals. In the latter case, the patterns provide for a technique for writing reconfigurable virtual partitions in multipurpose photonic devices.

  17. The extended phenotypes of marine symbioses: ecological and evolutionary consequences of intraspecific genetic diversity in coral–algal associations

    PubMed Central

    Parkinson, John E.; Baums, Iliana B.

    2014-01-01

    Reef-building corals owe much of their success to a symbiosis with dinoflagellate microalgae in the genus Symbiodinium. In this association, the performance of each organism is tied to that of its partner, and together the partners form a holobiont that can be subject to selection. Climate change affects coral reefs, which are declining globally as a result. Yet the extent to which coral holobionts will be able to acclimate or evolve to handle climate change and other stressors remains unclear. Selection acts on individuals and evidence from terrestrial systems demonstrates that intraspecific genetic diversity plays a significant role in symbiosis ecology and evolution. However, we have a limited understanding of the effects of such diversity in corals. As molecular methods have advanced, so too has our recognition of the taxonomic and functional diversity of holobiont partners. Resolving the major components of the holobiont to the level of the individual will help us assess the importance of intraspecific diversity and partner interactions in coral–algal symbioses. Here, we hypothesize that unique combinations of coral and algal individuals yield functional diversity that affects not only the ecology and evolution of the coral holobiont, but associated communities as well. Our synthesis is derived from reviewing existing evidence and presenting novel data. By incorporating the effects of holobiont extended phenotypes into predictive models, we may refine our understanding of the evolutionary trajectory of corals and reef communities responding to climate change. PMID:25202306

  18. A tractable genotype–phenotype map modelling the self-assembly of protein quaternary structure

    PubMed Central

    Greenbury, Sam F.; Johnston, Iain G.; Louis, Ard A.; Ahnert, Sebastian E.

    2014-01-01

    The mapping between biological genotypes and phenotypes is central to the study of biological evolution. Here, we introduce a rich, intuitive and biologically realistic genotype–phenotype (GP) map that serves as a model of self-assembling biological structures, such as protein complexes, and remains computationally and analytically tractable. Our GP map arises naturally from the self-assembly of polyomino structures on a two-dimensional lattice and exhibits a number of properties: redundancy (genotypes vastly outnumber phenotypes), phenotype bias (genotypic redundancy varies greatly between phenotypes), genotype component disconnectivity (phenotypes consist of disconnected mutational networks) and shape space covering (most phenotypes can be reached in a small number of mutations). We also show that the mutational robustness of phenotypes scales very roughly logarithmically with phenotype redundancy and is positively correlated with phenotypic evolvability. Although our GP map describes the assembly of disconnected objects, it shares many properties with other popular GP maps for connected units, such as models for RNA secondary structure or the hydrophobic-polar (HP) lattice model for protein tertiary structure. The remarkable fact that these important properties similarly emerge from such different models suggests the possibility that universal features underlie a much wider class of biologically realistic GP maps. PMID:24718456

  19. Integrative phenomics reveals insight into the structure of phenotypic diversity in budding yeast

    PubMed Central

    Skelly, Daniel A.; Merrihew, Gennifer E.; Riffle, Michael; Connelly, Caitlin F.; Kerr, Emily O.; Johansson, Marnie; Jaschob, Daniel; Graczyk, Beth; Shulman, Nicholas J.; Wakefield, Jon; Cooper, Sara J.; Fields, Stanley; Noble, William S.; Muller, Eric G.D.; Davis, Trisha N.; Dunham, Maitreya J.; MacCoss, Michael J.; Akey, Joshua M.

    2013-01-01

    To better understand the quantitative characteristics and structure of phenotypic diversity, we measured over 14,000 transcript, protein, metabolite, and morphological traits in 22 genetically diverse strains of Saccharomyces cerevisiae. More than 50% of all measured traits varied significantly across strains [false discovery rate (FDR) = 5%]. The structure of phenotypic correlations is complex, with 85% of all traits significantly correlated with at least one other phenotype (median = 6, maximum = 328). We show how high-dimensional molecular phenomics data sets can be leveraged to accurately predict phenotypic variation between strains, often with greater precision than afforded by DNA sequence information alone. These results provide new insights into the spectrum and structure of phenotypic diversity and the characteristics influencing the ability to accurately predict phenotypes. PMID:23720455

  20. Plasmon coupling in extended structures: Graphene superlattice nanoribbon arrays

    NASA Astrophysics Data System (ADS)

    Rodrigo, Daniel; Low, Tony; Farmer, Damon B.; Altug, Hatice; Avouris, Phaedon

    2016-03-01

    Interaction between localized plasmons in isolated proximal nanostructures is a well-studied phenomenon. Here we explore plasmon-plasmon interactions in connected extended systems. Such systems can now be easily produced experimentally using graphene. However, the mechanisms of plasmonic interactions in extended systems are not well understood. We employ finite-element methods to study these interactions in graphene superlattice nanoribbon arrays with a periodically modulated electrochemical potential or number of layers. We find a rich variation in the resulting plasmonic resonances depending on the dimensions, the electrochemical potentials (doping), and the separation of the nanoribbon segments, and we demonstrate the involvement of both transverse and longitudinal plasmon-plasmon interactions. For example, unlike predictions based on the well-known "orbital hybridization model," the energies of the resulting hybrid plasmonic resonances in the extended system can lie between the energies of the plasmons in the individual components. Our results demonstrate that the plasmonic spectra of graphene superlattice structures can be easily adjusted, continuously tuned, and used to enhance optical fields in the infrared and terahertz regions of the electromagnetic spectrum.

  1. Structure of the extended emission in the infrared celestial background

    SciTech Connect

    Price, S.D.

    1988-01-01

    The extended infrared celestial emission is due to three main sources: zodiacal dust, large discrete objects in the galaxy, and interstellar dust. As viewed from earth orbit, the thermal reradiation of sunlight absorbed by dust in the solar system produces a pervasive IR background that peaks roughly along the ecliptic plane, where the density of dust is highest. Much-smaller-scale structure was also observed in both the visual and infrared. Between 7 and 30 micrometers, H II regions are the brightest discrete objects in the galaxy. An additional emission mechanism is needed, however, to account for the shorter-wavelength observations. The galactic sources combine along the line of sight to produce an intense band of emission, centered on the galactic plane. Structure in all of these backgrounds creates a clutter problem for an orbiting IR telescope.

  2. Exploring the Extended Structure of the Sculptor Dwarf Spheroidal Galaxy

    NASA Astrophysics Data System (ADS)

    Westfall, K. B.; Ostheimer, J. C.; Frinchaboy, P. M.; Patterson, R. J.; Majewski, S. R.; Kunkel, W. E.

    2000-12-01

    We have undertaken a large area (>3 deg2) survey of the Sculptor dSph using the 1-m Swope telescope. The region surveyed includes roughly 1 deg2 centered on the Sculptor core, with the remaining survey area extending to the east and stretching to almost twice the tidal radius (rt=76.5m) to the northeast and southeast. We have imaged in the Washington M,T2 and DDO51 filters, a combination that allows us to discriminate dwarf and giant stars based on the gravity sensitivity of DDO51. The extended structure of Sculptor can be mapped via those stars selected both as giant stars and as having a combination of M and M-T2 consistent with the red giant branch of Sculptor. We also make use of the areal distribution of blue horizontal branch stars, which delineate the extended structure of Sculptor relatively well in this field at high Galactic latitude. Using the HYDRA spectrograph on the Blanco 4-m, we have obtained more than a dozen radial velocities for candidate Sculptor stars that we have identified well outside (1) the core radius, and (2) the radii explored by previous surveys. A preliminary conclusion from our work so far is that Sculptor does not show as extensive a population of extratidal stars as we have identified in similar work we have conducted around the Carina (Majewski et al. 2000, AJ, 119, 760) and Ursa Minor (Palma et al. 2000, BAAS) dwarf galaxies. Indeed, if a lack of significant extended material around Sculptor is borne out by further study over more area and other position angles, then an interesting correlation begins to emerge: Among four galaxies we have surveyed in this way (Car, UMi, Leo II, and Scl), the relative fraction of the dSph's found outside the nominal tidal radius appears to correlate with the published values of M/L. This may suggest that the derived masses for the dwarf spheroidals may be systematically overestimated to a degree set by the amount of dynamical non-equilibrium in the system. This work was supported by NSF, NASA, the

  3. Structural Modeling Insights into Human VKORC1 Phenotypes

    PubMed Central

    Czogalla, Katrin J.; Watzka, Matthias; Oldenburg, Johannes

    2015-01-01

    Vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) catalyses the reduction of vitamin K and its 2,3-epoxide essential to sustain γ-carboxylation of vitamin K-dependent proteins. Two different phenotypes are associated with mutations in human VKORC1. The majority of mutations cause resistance to 4-hydroxycoumarin- and indandione-based vitamin K antagonists (VKA) used in the prevention and therapy of thromboembolism. Patients with these mutations require greater doses of VKA for stable anticoagulation than patients without mutations. The second phenotype, a very rare autosomal-recessive bleeding disorder caused by combined deficiency of vitamin K dependent clotting factors type 2 (VKCFD2) arises from a homozygous Arg98Trp mutation. The bleeding phenotype can be corrected by vitamin K administration. Here, we summarize published experimental data and in silico modeling results in order to rationalize the mechanisms of VKA resistance and VKCFD2. PMID:26287237

  4. The extended structure of the dwarf irregular galaxy Sagittarius

    NASA Astrophysics Data System (ADS)

    Beccari, G.; Bellazzini, M.; Fraternali, F.; Battaglia, G.; Perina, S.; Sollima, A.; Oosterloo, T. A.; Testa, V.; Galleti, S.

    2014-10-01

    We present a detailed study of the stellar and H i structure of the dwarf irregular galaxy Sagittarius. We use new deep and wide field photometry to trace the surface brightness profile of the galaxy out to ≃5.0' (corresponding to ≃1600 pc) and down to μV ≃ 30.0 mag/arcsec2, thus showing that the stellar body of the galaxy is much more extended than previously believed, and it is similarly (or more) extended than the overall H i distribution. The whole major-axis profile is consistent with a pure exponential, with a scale radius of ≃340 pc. The surface density maps reveal that the distribution of old and intermediate-age stars is smooth and remarkably flattened out to its edges, while the associated H i has a much rounder shape, is off-centred and presents multiple density maxima and a significant hole. No clear sign of systemic rotation is detectable in the complex H i velocity field. No metallicity gradient is detected in the old and intermediate age population of the galaxy, and we confirm that this population has a much more extended distribution than young stars (age ≲ 1 Gyr). Based on data obtained with the European Southern Observatory Very Large Telescope, Paranal, Chile, under the Program 089.D-0052(A).Table of stellar photometry (IN6) is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/570/A78

  5. FOURIER ANALYSIS OF EXTENDED FINE STRUCTURE WITH AUTOREGRESSIVE PREDICTION

    SciTech Connect

    Barton, J.; Shirley, D.A.

    1985-01-01

    Autoregressive prediction is adapted to double the resolution of Angle-Resolved Photoemission Extended Fine Structure (ARPEFS) Fourier transforms. Even with the optimal taper (weighting function), the commonly used taper-and-transform Fourier method has limited resolution: it assumes the signal is zero beyond the limits of the measurement. By seeking the Fourier spectrum of an infinite extent oscillation consistent with the measurements but otherwise having maximum entropy, the errors caused by finite data range can be reduced. Our procedure developed to implement this concept applies autoregressive prediction to extrapolate the signal to an extent controlled by a taper width. Difficulties encountered when processing actual ARPEFS data are discussed. A key feature of this approach is the ability to convert improved measurements (signal-to-noise or point density) into improved Fourier resolution.

  6. Structure of the extended emission in the infrared celestial background

    SciTech Connect

    Price, S.D.

    1986-09-30

    The extended emission in the infrared celestial background may be divided into three main components: the zodiacal background, the large discrete sources in the galaxy, and the interstellar dust. The zodiacal background is due to the thermal reradiation of sunlight absorbed by the dust in the solar system. An earth-orbiting infrared telescope will detect the diffuse emission from this dust in all directions with maximum intensity lying roughly along the ecliptic plane where the density of dust is highest. Structure with scale lengths of 10/sup 0/ was measured in both the visual and infrared; finer structure was detected in the infrared by the Infrared Astronomy Satellite. H II regions, areas of ionized gas mixed with and surrounded by dust, are the brightest discrete objects in the galaxy in the long wavelength infrared re-emitted in the infrared with a range of temperatures characteristic of the thermal equilibrium for the surroundings of the dust. The emission from the interstellar dust produces a filimentary structured background, the infrared cirrus. The observed far-infrared color temperature of about 20-35K for the cirrus is consistent with emission-form graphite and silicate grains which absorb the interstellar radiation field. The much-larger LWIR color temperature is likely due to a greater abundance of sub-micron particles in the interstellar medium and, perhaps, from band emission due to polycyclic aromatic hydrocarbons. These galactic planes have full width at half maxima of about 2/sup 0/.

  7. The extended evolutionary synthesis: its structure, assumptions and predictions

    PubMed Central

    Laland, Kevin N.; Uller, Tobias; Feldman, Marcus W.; Sterelny, Kim; Müller, Gerd B.; Moczek, Armin; Jablonka, Eva; Odling-Smee, John

    2015-01-01

    Scientific activities take place within the structured sets of ideas and assumptions that define a field and its practices. The conceptual framework of evolutionary biology emerged with the Modern Synthesis in the early twentieth century and has since expanded into a highly successful research program to explore the processes of diversification and adaptation. Nonetheless, the ability of that framework satisfactorily to accommodate the rapid advances in developmental biology, genomics and ecology has been questioned. We review some of these arguments, focusing on literatures (evo-devo, developmental plasticity, inclusive inheritance and niche construction) whose implications for evolution can be interpreted in two ways—one that preserves the internal structure of contemporary evolutionary theory and one that points towards an alternative conceptual framework. The latter, which we label the ‘extended evolutionary synthesis' (EES), retains the fundaments of evolutionary theory, but differs in its emphasis on the role of constructive processes in development and evolution, and reciprocal portrayals of causation. In the EES, developmental processes, operating through developmental bias, inclusive inheritance and niche construction, share responsibility for the direction and rate of evolution, the origin of character variation and organism–environment complementarity. We spell out the structure, core assumptions and novel predictions of the EES, and show how it can be deployed to stimulate and advance research in those fields that study or use evolutionary biology. PMID:26246559

  8. Coupled and extended quintessence: Theoretical differences and structure formation

    NASA Astrophysics Data System (ADS)

    Pettorino, Valeria; Baccigalupi, Carlo

    2008-05-01

    The case of a coupling between dark energy and matter [coupled quintessence (CQ)] or gravity [extended quintessence (EQ)] has recently attracted a deep interest and has been widely investigated both in the Einstein and in the Jordan frames (EF, JF), within scalar-tensor theories. Focusing on the simplest models proposed so far, in this paper we study the relation existing between the two scenarios, isolating the Weyl scaling which allows one to express them in the EF and JF. Moreover, we perform a comparative study of the behavior of linear perturbations in both scenarios, which turn out to behave in a markedly different way. In particular, while the clustering is enhanced in the considered CQ models with respect to the corresponding quintessence ones where the coupling is absent and to the ordinary cosmologies with a cosmological constant and cold dark matter (ΛCDM), structures in EQ models may grow slower. This is likely to have direct consequences on the inner properties of nonlinear structures, like cluster concentration, as well as on the weak lensing shear on large scales. Finally, we specialize our study for interfacing linear dynamics and N-body simulations in these cosmologies, giving a recipe for the corrections to be included in N-body codes in order to take into account the modifications to the expansion rate, growth of structures, and strength of gravity.

  9. The extended evolutionary synthesis: its structure, assumptions and predictions.

    PubMed

    Laland, Kevin N; Uller, Tobias; Feldman, Marcus W; Sterelny, Kim; Müller, Gerd B; Moczek, Armin; Jablonka, Eva; Odling-Smee, John

    2015-08-22

    Scientific activities take place within the structured sets of ideas and assumptions that define a field and its practices. The conceptual framework of evolutionary biology emerged with the Modern Synthesis in the early twentieth century and has since expanded into a highly successful research program to explore the processes of diversification and adaptation. Nonetheless, the ability of that framework satisfactorily to accommodate the rapid advances in developmental biology, genomics and ecology has been questioned. We review some of these arguments, focusing on literatures (evo-devo, developmental plasticity, inclusive inheritance and niche construction) whose implications for evolution can be interpreted in two ways—one that preserves the internal structure of contemporary evolutionary theory and one that points towards an alternative conceptual framework. The latter, which we label the 'extended evolutionary synthesis' (EES), retains the fundaments of evolutionary theory, but differs in its emphasis on the role of constructive processes in development and evolution, and reciprocal portrayals of causation. In the EES, developmental processes, operating through developmental bias, inclusive inheritance and niche construction, share responsibility for the direction and rate of evolution, the origin of character variation and organism-environment complementarity. We spell out the structure, core assumptions and novel predictions of the EES, and show how it can be deployed to stimulate and advance research in those fields that study or use evolutionary biology. PMID:26246559

  10. Population structure and genotype-phenotype associations in a collection of oat landraces and historic cultivars.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Population structure and genetic architecture of phenotypic traits in oat (Avena sativa L.) remain relatively under-researched compared to other small grain species. This study explores the historic context of current elite germplasm, including phenotypic and genetic characterization, with a partic...

  11. Understanding the Phenotypic Structure of Adult Retrospective ADHD Symptoms during Childhood in the United States

    ERIC Educational Resources Information Center

    Ranby, Krista W.; Boynton, Marcella H.; Kollins, Scott H.; McClernon, F. Joseph; Yang, Chongming; Fuemmeler, Bernard F.

    2012-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous disorder, and the phenotypic structure comprising inattentive and hyperactive-impulsive type symptoms has been the focus of a growing body of recent research. Methodological studies are needed to better characterize phenotypes to advance research as well as clinical…

  12. Visibility of Extended Coronal Structures and CMEs in the EUV

    NASA Astrophysics Data System (ADS)

    Schanche, Nicole; Golub, Leon

    2014-06-01

    Extended coronal structures around active regions and coronal mass ejections (CMEs) have often been seen in the extreme-ultraviolet (EUV) channels to the full extent of the AIA and SWAP field of views 1.3 and 1.7 Rsun). Using off-pointed comet data in AIA we sum a large number of frames to evaluate the off-limb distance to which streamers can be detected. For CMEs, we compared the events classified as halo CMEs in the white-light LASCO CACTus catalog from July-September 2013 to the AIA and SWAP data collected around those events. We discovered that roughly 80% of events could be seen in the EUV using both regular and running difference movies, with the most effective channels being the 193 and 304Å channels. By projecting out the signal strength of several of these events, we conclude that these EUV events can in many cases be detected to over 2.5 Rsun. A larger field-of-view telescope would make it possible to track the development of these structures and events from the disk out to several solar radii, complementing the traditional white-light methods.

  13. The extended interacting wind structure of Eta Carinae

    NASA Astrophysics Data System (ADS)

    Gull, T. R.; Nielsen, K. E.; Corcoran, M. F.; Madura, T. I.; Owocki, S. P.; Russell, C. M. P.; Hillier, D. J.; Hamaguchi, K.; Kober, G. V.; Weis, K.; Stahl, O.; Okazaki, A. T.

    2009-07-01

    The highly eccentric binary system, η Car, provides clues to the transition of massive stars from hydrogen-burning via the CNO cycle to a helium-burning evolutionary state. The fast-moving wind of η Car B creates a cavity in η Car A's slower, but more massive, stellar wind, providing an in situ probe. The Hubble Space Telescope/Space Telescope Imaging Spectrograph (HST/STIS), with its high spatial and spectral resolutions, is well matched to follow temporal spatial and velocity variations of multiple wind features. We use observations obtained across 1998-2004 to produce a rudimentary three-dimensional model of the wind interaction in the η Car system. Broad (+/-500 km s-1) [FeII] emission line structures extend 0.7arcsec (~1600 au) from the stellar core. In contrast, [FeIII], [ArIII], [NeIII] and [SIII] lines extend only 0.3arcsec (700 au) from NE to SW and are blue shifted from -500 to +200 km s-1. All observed spectral features vary with the 5.54-year orbital period. The highly ionized, forbidden emission disappears during the low state, associated with periastron passage. The high-ionization emission originates in the outer wind interaction region that is directly excited by the far-ultraviolet radiation from η Car B. The HST/STIS spectra reveal a time-varying, distorted paraboloidal structure, caused by the interaction of the massive stellar winds. The model and observations are consistent with the orbital plane aligned with the skirt of the Homunculus. However, the axis of the distorted paraboloid, relative to the major axis of the binary orbit, is shifted in a prograde rotation along the plane, which projected on the sky is from NE to NW. Based on observations made with the National Aeronautics and Space Agency/European Space Agency (NASA/ESA) HST. Support for Programme numbers 7302, 8036, 8483, 8619, 9083, 9337, 9420, 9973, 10957 and 11273 was provided by NASA directly to the Space Telescope Imaging Spectrograph Science Team and through grants from the

  14. Leber Congenital Amaurosis: Genotypes and Retinal Structure Phenotypes.

    PubMed

    Jacobson, Samuel G; Cideciyan, Artur V; Huang, Wei Chieh; Sumaroka, Alexander; Nam, Hyun Ju; Sheplock, Rebecca; Schwartz, Sharon B

    2016-01-01

    Leber congenital amaurosis (LCA) patients of 10 known genotypes (n = 24; age range, 3-25 years) were studied clinically and by optical coherence tomography (OCT). Comparisons were made between OCT results across the horizontal meridian (central 60(o)) of the patients. Three patterns were identified. First, there were LCA genotypes with unusual and readily identifiable patterns, such as near normal outer nuclear layer (ONL) across the central retina or severely dysplastic retina. Second, there were genotypes with well-formed foveal architecture but only residual central islands of normal or reduced ONL thickness. Third, some genotypes showed central ONL losses or dysmorphology suggesting early macular disease or foveal maldevelopment. Objective in vivo morphological features could complement other phenotypic characteristics and help guide genetic testing of LCA patients or at least permit a differential diagnosis of genotypes to be made in the clinic. PMID:26427408

  15. The MARK-AGE phenotypic database: Structure and strategy.

    PubMed

    Moreno-Villanueva, María; Kötter, Tobias; Sindlinger, Thilo; Baur, Jennifer; Oehlke, Sebastian; Bürkle, Alexander; Berthold, Michael R

    2015-11-01

    In the context of the MARK-AGE study, anthropometric, clinical and social data as well as samples of venous blood, buccal mucosal cells and urine were systematically collected from 3337 volunteers. Information from about 500 standardised questions and about 500 analysed biomarkers needed to be documented per individual. On the one hand handling with such a vast amount of data necessitates the use of appropriate informatics tools and the establishment of a database. On the other hand personal information on subjects obtained as a result of such studies has, of course, to be kept confidential, and therefore the investigators must ensure that the subjects' anonymity will be maintained. Such secrecy obligation implies a well-designed and secure system for data storage. In order to fulfil the demands of the MARK-AGE study we established a phenotypic database for storing information on the study subjects by using a doubly coded system. PMID:25817205

  16. Extended Kalman filter based structural damage detection for MR damper controlled structures

    NASA Astrophysics Data System (ADS)

    Jin, Chenhao; Jang, Shinae; Sun, Xiaorong; Jiang, Zhaoshuo; Christenson, Richard

    2016-04-01

    The Magneto-rheological (MR) dampers have been widely used in many building and bridge structures against earthquake and wind loadings due to its advantages including mechanical simplicity, high dynamic range, low power requirements, large force capacity, and robustness. However, research about structural damage detection methods for MR damper controlled structures is limited. This paper aims to develop a real-time structural damage detection method for MR damper controlled structures. A novel state space model of MR damper controlled structure is first built by combining the structure's equation of motion and MR damper's hyperbolic tangent model. In this way, the state parameters of both the structure and MR damper are added in the state vector of the state space model. Extended Kalman filter is then used to provide prediction for state variables from measurement data. The two techniques are synergistically combined to identify parameters and track the changes of both structure and MR damper in real time. The proposed method is tested using response data of a three-floor MR damper controlled linear building structure under earthquake excitation. The testing results show that the adaptive extended Kalman filter based approach is capable to estimate not only structural parameters such as stiffness and damping of each floor, but also the parameters of MR damper, so that more insights and understanding of the damage can be obtained. The developed method also demonstrates high damage detection accuracy and light computation, as well as the potential to implement in a structural health monitoring system.

  17. Combinatorial phenotypic screen uncovers unrecognized family of extended thiourea inhibitors with copper-dependent anti-staphylococcal activity.

    PubMed

    Dalecki, Alex G; Malalasekera, Aruni P; Schaaf, Kaitlyn; Kutsch, Olaf; Bossmann, Stefan H; Wolschendorf, Frank

    2016-04-01

    The continuous rise of multi-drug resistant pathogenic bacteria has become a significant challenge for the health care system. In particular, novel drugs to treat infections of methicillin-resistant Staphylococcus aureus strains (MRSA) are needed, but traditional drug discovery campaigns have largely failed to deliver clinically suitable antibiotics. More than simply new drugs, new drug discovery approaches are needed to combat bacterial resistance. The recently described phenomenon of copper-dependent inhibitors has galvanized research exploring the use of metal-coordinating molecules to harness copper's natural antibacterial properties for therapeutic purposes. Here, we describe the results of the first concerted screening effort to identify copper-dependent inhibitors of Staphylococcus aureus. A standard library of 10 000 compounds was assayed for anti-staphylococcal activity, with hits defined as those compounds with a strict copper-dependent inhibitory activity. A total of 53 copper-dependent hit molecules were uncovered, similar to the copper independent hit rate of a traditionally executed campaign conducted in parallel on the same library. Most prominent was a hit family with an extended thiourea core structure, termed the NNSN motif. This motif resulted in copper-dependent and copper-specific S. aureus inhibition, while simultaneously being well tolerated by eukaryotic cells. Importantly, we could demonstrate that copper binding by the NNSN motif is highly unusual and likely responsible for the promising biological qualities of these compounds. A subsequent chemoinformatic meta-analysis of the ChEMBL chemical database confirmed the NNSNs as an unrecognized staphylococcal inhibitor, despite the family's presence in many chemical screening libraries. Thus, our copper-biased screen has proven able to discover inhibitors within previously screened libraries, offering a mechanism to reinvigorate exhausted molecular collections. PMID:26935206

  18. Population structure of deep-sea chemolithoautotrophs: identification of phenotypic and genotypic correlations

    NASA Astrophysics Data System (ADS)

    Mino, S.; Nakagawa, S.; Sawabe, T.; Miyazaki, J.; Makita, H.; Nunoura, T.; Yamamoto, M.; Takai, K.

    2012-12-01

    Deep-sea hydrothermal fields are areas on the seafloor of high biological productivity fueled primarily by microbial chemosynthesis. Chemolithoautotrophic Epsilonproteobacteria and Persephonella with an ability to utilize inorganic substrates such as elemental sulfur and hydrogen are important members in wide range of temperature conditions in deep-sea hydrothermal vents. However, little is known about their population genetic structure such as intraspecific genetic diversity, distribution pattern, and phenotypic characteristics. Previously, using genetic approach based on multi-locus sequence analysis (MLSA), we clarified that Epsilonproteobacteria Group A, B, F, and Persephonella populations were geographically separated, and Epsilonproteobacteria appeared to diverge by mutation rather than recombination. Contrary to genetic evidence for allopatric segregation in deep-sea chemoautotrophs, however, phenotypic evidence has never been found. In addition, analyzing such a phenotypic characteristic may lead to a better understanding of the interactions microbes have with their environment. In this study, we present a metabolomic approach based on matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) to reveal phenotypic biogeographical discrimination. We demonstrated the whole-cell MALDI-TOF MS method on Epsilonproteobacteria and Persephonella populations. These chemoautotrophic strains used in this study were isolated from chimney structures, vent fluids, and hydrothermal sediments. These hydrothermal samples were collected from geographically separated hydrothermal areas of the South Mariana Trough, Okinawa Trough and Central Indian Ridge. Based on mass peaks (signal/noise >10) within the m/z range of 2000-14000, phenotypic analysis was carried out by cluster analysis. The result of phenotypic analysis was compared with the genotypic clusters. The whole-cell MALDI-TOF MS revealed that Persephonella population was identified to

  19. Simple surface structure determination from Fourier transforms of angle-resolved photoemission extended fine structure

    SciTech Connect

    Zheng, Y. |; Shirley, D.A.

    1995-02-01

    The authors show by Fourier analyses of experimental data, with no further treatment, that the positions of all the strong peaks in Fourier transforms of angle-resolved photoemission extended fine structure (ARPEFS) from adsorbed surfaces can be explicitly predicted from a trial structure with an accuracy of about {+-} 0.3 {angstrom} based on a single-scattering cluster model together with the concept of a strong backscattering cone, and without any additional analysis. This characteristic of ARPEFS Fourier transforms can be developed as a simple method for determining the structures of adsorbed surfaces to an accuracy of about {+-} 0.1 {angstrom}.

  20. Evaluation of high temperature structural adhesives for extended service

    NASA Technical Reports Server (NTRS)

    Hendricks, C. L.; Hill, S. G.

    1984-01-01

    High temperature stable adhesive systems were evaluated for potential Supersonic Cruise Research (SCR) vehicle applications. The program was divided into two major phases: Phase I 'Adhesive Screening' evaluated eleven selected polyimide (PI) and polyphenylquinoxaline (PPQ) adhesive resins using eight different titanium (6Al-4V) adherend surface preparations; Phase II 'Adhesive Optimization and Characterization' extensively evaluated two adhesive systems, selected from Phase I studies, for chemical characterization and environmental durability. The adhesive systems which exhibited superior thermal and environmental bond properties were LARC-TPI polyimide and polyphenylquinoxaline both developed at NASA Langley. The latter adhesive system did develop bond failures at extended thermal aging due primarily to incompatibility between the surface preparation and the polymer. However, this study did demonstrate that suitable adhesive systems are available for extended supersonic cruise vehicle design applications.

  1. Can structural neuroimaging be used to define phenotypes and course of schizophrenia?

    PubMed

    Kerns, John G; Lauriello, John

    2012-09-01

    This article examines whether structural neuroimaging measures have been found to predict outcome in schizophrenia and whether changes in neuroimaging measures have been found to correlate with poor outcome in the disorder. Overall, there is little compelling evidence that structural neuroimaging measures in either first-episode or chronic patients predict future outcome. Progressive brain changes might reflect a neuroimaging phenotype associated with a worse course of the disorder. At the same time, there are many fruitful avenues that future research could take in an attempt to better predict future outcome or to identify specific imaging phenotypes associated with outcome. PMID:22929870

  2. Voltage-gated potassium channel antibody-related encephalopathy: a case which may extend the documented phenotype of this condition

    PubMed Central

    Scott, Janet T; Scally, Caroline; Peden, Norman; Macleod, Malcolm

    2012-01-01

    A 51-year-old man presented with a focal epileptic, fluctuating encephalopathy. Antibodies to voltage-gated potassium channels (VGKC-Abs) were detected in his serum. Several features of this case were different from those previously reported in VGKC-Ab-associated encephalitis, illustrating that it may have a broader phenotype than previously documented. These features were: excess hepatic iron deposits without cirrhosis, reduced consciousness and fluctuating neurological signs. Previous history included personality change, depression, type 2 diabetes mellitus, pupil sparing third nerve palsy and epilepsy secondary to a head injury. He had never drunk alcohol and had recovered from a similar episode 4 years previously. Both episodes resolved after approximately 2 months. The cerebrospinal fluid had a raised protein content but no organisms. The patient was heterozygous for C282Y and negative for H63D mutations excluding classical idiopathic haemochromatosis. He recovered with supportive care to his premorbid level of health. PMID:22693327

  3. Band structures extending to very high spin in Xe126

    NASA Astrophysics Data System (ADS)

    Rønn Hansen, C.; Sletten, G.; Hagemann, G. B.; Herskind, B.; Jensen, D. R.; Bringel, P.; Engelhardt, C.; Hübel, H.; Neußer-Neffgen, A.; Singh, A. K.; Carpenter, M. P.; Janssens, R. V. F.; Khoo, T. L.; Lauritsen, T.; Bednarczyk, P.; Byrski, T.; Curien, D.; Benzoni, G.; Bracco, A.; Camera, F.; Leoni, S.; Clark, R. M.; Fallon, P.; Korichi, A.; Roccaz, J.; Maj, A.; Wilson, J. N.; Lisle, J. C.; Steinhardt, T.; Thelen, O.; Ødegård, S. W.

    2007-09-01

    High-spin states in Xe126 have been populated in the Se82(Ca48,4n)Xe126 reaction in two experiments, one at the VIVITRON accelerator in Strasbourg using the Euroball detector array, and a subsequent one with ATLAS at Argonne using the Gammasphere Ge-detector array. Levels and assignments made previously for Xe126 up to I=20 have been confirmed and extended. Four regular bands extending to a spin of almost I=60, which are interpreted as two pairs of signature partners with opposite parity, are identified for the first time. The α = 0 partner of each pair is connected to the lower-lying levels, whereas the two α = 1 partners remain floating. A fractional Doppler shift analysis of transitions in the strongest populated (π,α)=(-,0) band provides a value of 5.20.50.4 b for the transition quadrupole moment, which can be related to a minimum in the potential-energy surface calculated by the ULTIMATE CRANKER cranked shell-model code at ɛ≈0.35 and γ≈5°. The four lowest bands calculated for this minimum compare well with the two signature pairs experimentally observed over a wide spin range. A sharp upbend at ℏω~1170 keV is interpreted as a crossing with a band involving the j15/2 neutron orbital, for which pairing correlations are expected to be totally quenched. The four long bands extend to within ˜5 spin units of a crossing with an yrast line defined by calculated hyperdeformed transitions and will serve as important stepping stones into the spin region beyond 60ħ for future experiments.

  4. Structural and functional genome analysis using extended chromatin

    SciTech Connect

    Heaf, T.; Ward, D.C.

    1994-09-01

    Highly extended linear chromatin fibers (ECFs) produced by detergent and high-salt lysis and stretching of nuclear chromatin across the surface of a glass slide can by hybridized over physical distances of at least several Mb. This allows long-range FISH analysis of the human genome with excellent DNA resolution (<10 kb/{mu}m). The insertion of Alu elements which are more than 50-fold underrepresented in centromeres can be seen within and near long tandem arrays of alpha-satellite DNA. Long tracts of trinucleotide repeats, i.e. (CCA){sub n}, can be localized within larger genomic regions. The combined application of BrdU incorporation and ECFs allows one to study the spatio-temporal distribution of DNA replication sites in finer detail. DNA synthesis occurs at multiple discrete sites within Mb arrays of alpha-satellite. Replicating DNA is tightly associated with the nuclear matrix and highly resistant to stretching out, while ECFs containing newly replicated DNA are easily released. Asynchrony in replication timing is accompanied by differences in condensation of homologous DNA segments. Extended chromatin reveals differential packaging of active and inactive DNA. Upon transcriptional inactivation by AMD, the normally compact rRNA genes become much more susceptible to decondensation procedures. By extending the chromatin from pachytene spermatocytes, meiotic pairing and genetic exchange between homologs can be visualized directly. Histone depletion by high salt and detergent produces loop chromatin surrounding the nuclear matrix in a halo-like fashion. DNA halos can be used to map nuclear matrix attachment sites in somatic cells and in mature sperm. Alpha-satellite containing DNA loops appear to be attached to the sperm-cell matrix by CENP-B boxes, short 17 bp sequences found in a subset of alpha satellite monomers. Sperm telomeres almost always appear as hybridization doublets, suggesting the presence of already replicated chromosome ends.

  5. Structure and composition of the courtship phenotype in the bird of paradise Parotia lawesii (Aves: Paradisaeidae).

    PubMed

    Scholes, Edwin

    2008-01-01

    Ethology is rooted in the idea that behavior is composed of discrete units and sub-units that can be compared among taxa in a phylogenetic framework. This means that behavior, like morphology and genes, is inherently modular. Yet, the concept of modularity is not well integrated into how we envision the behavioral components of phenotype. Understanding ethological modularity, and its implications for animal phenotype organization and evolution, requires that we construct interpretive schemes that permit us to examine it. In this study, I describe the structure and composition of a complex part of the behavioral phenotype of Parotia lawesii Ramsay, 1885--a bird of paradise (Aves: Paradisaeidae) from the forests of eastern New Guinea. I use archived voucher video clips, photographic ethograms, and phenotype ontology diagrams to describe the modular units comprising courtship at various levels of integration. Results show P. lawesii to have 15 courtship and mating behaviors (11 males, 4 females) hierarchically arranged within a complex seven-level structure. At the finest level examined, male displays are comprised of 49 modular sub-units (elements) differentially employed to form more complex modular units (phases and versions) at higher-levels of integration. With its emphasis on hierarchical modularity, this study provides an important conceptual framework for understanding courtship-related phenotypic complexity and provides a solid basis for comparative study of the genus Parotia. PMID:18359213

  6. Multivariate genetic analysis of brain structure in an extended twin design.

    PubMed

    Posthuma, D; de Geus, E J; Neale, M C; Hulshoff Pol, H E; Baaré WEC; Kahn, R S; Boomsma, D

    2000-07-01

    The hunt for genes influencing behavior may be aided by the study of intermediate phenotypes for several reasons. First, intermediate phenotypes may be influenced by only a few genes, which facilitates their detection. Second, many intermediate phenotypes can be measured on a continuous quantitative scale and thus can be assessed in affected and unaffected individuals. Continuous measures increase the statistical power to detect genetic effects (Neale et al., 1994), and allow studies to be designed to collect data from informative subjects such as extreme concordant or discordant pairs. Intermediate phenotypes for discrete traits, such as psychiatric disorders, can be neurotransmitter levels, brain function, or structure. In this paper we conduct a multivariate analysis of data from 111 twin pairs and 34 additional siblings on cerebellar volume, intracranial space, and body height. The analysis is carried out on the raw data and specifies a model for the mean and the covariance structure. Results suggest that cerebellar volume and intracranial space vary with age and sex. Brain volumes tend to decrease slightly with age, and males generally have a larger brain volume than females. The remaining phenotypic variance of cerebellar volume is largely genetic (88%). These genetic factors partly overlap with the genetic factors that explain variance in intracranial space and body height. The applied method is presented as a general approach for the analysis of intermediate phenotypes in which the effects of correlated variables on the observed scores are modeled through multivariate analysis. PMID:11206086

  7. Correlates across the Structural, Functional, and Molecular Phenotypes of Fragile X Syndrome

    ERIC Educational Resources Information Center

    Beckel-Mitchener, Andrea; Greenough, William T.

    2004-01-01

    Fragile X syndrome (FXS) is characterized by a pattern of morphological, functional, and molecular characteristics with, in at least some cases, apparent relationships among phenotypic features at different levels. Gross morphology differences in the sizes of some human brain regions are accompanied by fine structural alterations in the shapes and…

  8. Rubinstein-Taybi syndrome type 2: report of nine new cases that extend the phenotypic and genotypic spectrum.

    PubMed

    Hamilton, Mark J; Newbury-Ecob, Ruth; Holder-Espinasse, Muriel; Yau, Shu; Lillis, Suzanne; Hurst, Jane A; Clement, Emma; Reardon, William; Joss, Shelagh; Hobson, Emma; Blyth, Moira; Al-Shehhi, Maryam; Lynch, Sally A; Suri, Mohnish

    2016-10-01

    Rubinstein-Taybi syndrome (RTS) is an autosomal dominant neurodevelopmental disorder characterized by growth deficiency, broad thumbs and great toes, intellectual disability and characteristic craniofacial appearance. Mutations in CREBBP account for around 55% of cases, with a further 8% attributed to the paralogous gene EP300. Comparatively few reports exist describing the phenotype of Rubinstein-Taybi because of EP300 mutations. Clinical and genetic data were obtained from nine patients from the UK and Ireland with pathogenic EP300 mutations, identified either by targeted testing or by exome sequencing. All patients had mild or moderate intellectual impairment. Behavioural or social difficulties were noted in eight patients, including three with autistic spectrum disorders. Typical dysmorphic features of Rubinstein-Taybi were only variably present. Additional observations include maternal pre-eclampsia (2/9), syndactyly (3/9), feeding or swallowing issues (3/9), delayed bone age (2/9) and scoliosis (2/9). Six patients had truncating mutations in EP300, with pathogenic missense mutations identified in the remaining three. The findings support previous observations that microcephaly, maternal pre-eclampsia, mild growth restriction and a mild to moderate intellectual disability are key pointers to the diagnosis of EP300-related RTS. Variability in the presence of typical facial features of Rubinstein-Taybi further highlights clinical heterogeneity, particularly among patients identified by exome sequencing. Features that overlap with Floating-Harbor syndrome, including craniofacial dysmorphism and delayed osseous maturation, were observed in three patients. Previous reports have only described mutations predicted to cause haploinsufficiency of EP300, whereas this cohort includes the first described pathogenic missense mutations in EP300. PMID:27465822

  9. Extended B cell phenotype in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional study.

    PubMed

    Mensah, F; Bansal, A; Berkovitz, S; Sharma, A; Reddy, V; Leandro, M J; Cambridge, G

    2016-05-01

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous condition of unknown aetiology characterized by multiple symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months. Recently, two clinical trials of B cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms. A possible but undefined role for B cells has therefore been proposed. Studies of the relative percentages of B cell subsets in patients with ME/CFS have not revealed any reproducible differences from healthy controls (HC). In order to explore whether more subtle alterations in B cell subsets related to B cell differentiation exist in ME/CFS patients we used flow cytometry to immunophenotype CD19(+) B cells. The panel utilized immunoglobulin (Ig)D, CD27 and CD38 (classical B cell subsets) together with additional markers. A total of 38 patients fulfilling Canadian, Centre for Disease Control and Fukuda ME/CFS criteria and 32 age- and sex-matched HC were included. We found no difference in percentages of classical subsets between ME/CFS patients and HC. However, we observed an increase in frequency (P < 0·01) and expression (MFI; P = 0·03) of CD24 on total B cells, confined to IgD(+) subsets. Within memory subsets, a higher frequency of CD21(+) CD38(-) B cells (>20%) was associated with the presence of ME/CFS [odds ratio: 3·47 (1·15-10·46); P = 0·03] compared with HC, and there was a negative correlation with disease duration. In conclusion, we identified possible changes in B cell phenotype in patients with ME/CFS. These may reflect altered B cell function and, if confirmed in other patient cohorts, could provide a platform for studies based on clinical course or responsiveness to rituximab therapy. PMID:26646713

  10. Trade-Offs in Relative Limb Length among Peruvian Children: Extending the Thrifty Phenotype Hypothesis to Limb Proportions

    PubMed Central

    Pomeroy, Emma; Stock, Jay T.; Stanojevic, Sanja; Miranda, J. Jaime; Cole, Tim J.; Wells, Jonathan C. K.

    2012-01-01

    Background and Methods Both the concept of ‘brain-sparing’ growth and associations between relative lower limb length, childhood environment and adult disease risk are well established. Furthermore, tibia length is suggested to be particularly plastic under conditions of environmental stress. The mechanisms responsible are uncertain, but three hypotheses may be relevant. The ‘thrifty phenotype’ assumes that some components of growth are selectively sacrificed to preserve more critical outcomes, like the brain. The ‘distal blood flow’ hypothesis assumes that blood nutrients decline with distance from the heart, and hence may affect limbs in relation to basic body geometry. Temperature adaptation predicts a gradient of decreased size along the limbs reflecting decreasing tissue temperature/blood flow. We examined these questions by comparing the size of body segments among Peruvian children born and raised in differentially stressful environments. In a cross-sectional sample of children aged 6 months to 14 years (n = 447) we measured head circumference, head-trunk height, total upper and lower limb lengths, and zeugopod (ulna and tibia) and autopod (hand and foot) lengths. Results Highland children (exposed to greater stress) had significantly shorter limbs and zeugopod and autopod elements than lowland children, while differences in head-trunk height were smaller. Zeugopod elements appeared most sensitive to environmental conditions, as they were relatively shorter among highland children than their respective autopod elements. Discussion The results suggest that functional traits (hand, foot, and head) may be partially protected at the expense of the tibia and ulna. The results do not fit the predictions of the distal blood flow and temperature adaptation models as explanations for relative limb segment growth under stress conditions. Rather, our data support the extension of the thrifty phenotype hypothesis to limb growth, and suggest that certain

  11. Structural and Genetic Assessment of the ABCA4-Associated Optical Gap Phenotype

    PubMed Central

    Nõupuu, Kalev; Lee, Winston; Zernant, Jana; Tsang, Stephen H.; Allikmets, Rando

    2014-01-01

    Purpose. To investigate the developmental stages and genetic etiology of the optical gap phenotype in recessive Stargardt disease (STGD1). Methods. Single and longitudinal data points from 15 patients, including four sibling pairs, exhibiting an optical gap phenotype on spectral-domain optical coherence tomography (SD-OCT) with confirmed disease-causing ABCA4 alleles were retrospectively analyzed. Fundus images with corresponding SD-OCT scans were collected with a confocal scanning laser ophthalmoscope. Structural phenotypes were assigned to three developmental stages according to SD-OCT. The ABCA4 gene was screened in all patients. Results. At least two disease-causing ABCA4 variants where identified in each patient; all except one (91%) were compound heterozygous for the p.G1961E mutation. All patients exhibited structural findings on SD-OCT that grouped into three progressive developmental stages over several years. Stage 1 was characterized by mild disruptions of the ellipsoid zone (EZ) band over the fovea. Stage 2 was a progressive expansion of the EZ band loss resulting in an empty lesion devoid of photoreceptors. Stage 3 observed a structural collapse of the inner retinal layers into the optical gap space leading to involvement and atrophy of the RPE thereafter. Conclusions. The optical gap phenotype in STGD1 can be structurally divided into three progressive stages spanning several years. This particular phenotype also appears to be highly associated with the p.G1961E mutation of ABCA4. Taken together, it appears that a focal loss of photoreceptors sequentially precedes RPE dysfunction in the early development of ABCA4-associated optical gap lesions. PMID:25301883

  12. Extending the lifespan of nuclear power plant structures

    SciTech Connect

    Naus, D.J.; Oland, C.B.; Ellingwood, B.

    1995-04-01

    By the end of this decade, 63 of the 111 commercial nuclear power plants in the United States will be more than 20 years old, with some nearing the end of their 40-year operating license term. Faced with the prospect of having to replace lost generating capacity from other sources and substantial shutdown and decommissioning costs, many utilities are expected to apply to continue the service of their plants past the initial licensing period. In support of such applications, evidence should be provided that the capacity of the safety-related systems and structures to mitigate potential extreme events has not deteriorated unacceptably due to either aging or environmental stressor effects during the previous service history.

  13. Phosphorenes with Non-Honeycomb Structures: A Much Extended Family

    NASA Astrophysics Data System (ADS)

    Wu, Menghao; Fu, Huahua; Zhou, Ling; Yao, Kailun; Zeng, Xiao Cheng; Huazhong University of Science; Technology Team; University of Nebraska-Lincoln Team

    We predict a new class of monolayer phosphorous allotropes, namely, ɛ-P, ζ-P, η-P and θ-P. Distinctly different from the monolayer α-P (black) and previously predicted β-P (Phys. Rev. Lett. 112, 176802 (2014)), γ-P and δ-P (Phys. Rev. Lett. 113, 046804 (2014)) with buckled honeycomb lattice, the new allotropes are composed of P4 square or P5 pentagon units that favor tricoordination for P atoms. The new four phases, together with 5 hybrid phases, are confirmed stable by first-principles calculations. In particularly, the θ-P is shown to be equally stable as the α-P (black) and more stable than all previously reported phosphorene allotropes. Prediction of nonvolatile ferroelastic switching and structural transformation among different phases under strains points out their potential applications via strain engineering. MHW was supported by start-up fund from Huazhong University of Science and Technology.

  14. The Extended Granin Family: Structure, Function, and Biomedical Implications

    PubMed Central

    Bartolomucci, Alessandro; Possenti, Roberta; Mahata, Sushil K.; Fischer-Colbrie, Reiner; Loh, Y. Peng

    2011-01-01

    The chromogranins (chromogranin A and chromogranin B), secretogranins (secretogranin II and secretogranin III), and additional related proteins (7B2, NESP55, proSAAS, and VGF) that together comprise the granin family subserve essential roles in the regulated secretory pathway that is responsible for controlled delivery of peptides, hormones, neurotransmitters, and growth factors. Here we review the structure and function of granins and granin-derived peptides and expansive new genetic evidence, including recent single-nucleotide polymorphism mapping, genomic sequence comparisons, and analysis of transgenic and knockout mice, which together support an important and evolutionarily conserved role for these proteins in large dense-core vesicle biogenesis and regulated secretion. Recent data further indicate that their processed peptides function prominently in metabolic and glucose homeostasis, emotional behavior, pain pathways, and blood pressure modulation, suggesting future utility of granins and granin-derived peptides as novel disease biomarkers. PMID:21862681

  15. Evaluation of high temperature structural adhesives for extended service

    NASA Technical Reports Server (NTRS)

    Hill, S. G.; Peters, P. D.; Hendricks, C. L.

    1982-01-01

    The evaluation, selection, and demonstration of structural adhesive systems for supersonic cruise research applications, and establishment of environmental durability of selected systems for up to 20,000 hours is described. Ten candidate adhesives were initially evaluated. During screening and evaluation, these candidates were narrowed to three of the most promising for environmental durability testing. The three adhesives were LARC-13, PPQ, and NR056X. The LARC-13 was eliminated because of a lack of stability at 505 K. The NRO56X was removed from the market. The LARC-TPI was added after preliminary evaluation and an abbreviated screening test. Only PPQ and LARC-TPI remained as the reasonable candidates late into the durability testing. Large area bond panels were fabricated to demonstrate the processibility of the selected systems. Specifications were prepared to assure control over critical material and process parameters. Surface characterization concentrated primarily upon titanium surface treatments of 10 volt chronic acid anodize, 5 volt chromic acid anodize and PASA-JELL. Failure analysis was conducted on lap shear adhesive bond failures which occurred in PPQ and LARC-13 test specimens after 10,000 hours at 505 K.

  16. Divergent immune responses to house dust mite lead to distinct structural-functional phenotypes.

    PubMed

    Johnson, Jill R; Swirski, Filip K; Gajewska, Beata U; Wiley, Ryan E; Fattouh, Ramzi; Pacitto, Stephanie R; Wong, Jonathan K; Stämpfli, Martin R; Jordana, Manel

    2007-09-01

    Asthma is a chronic airway inflammatory disease that encompasses three cardinal processes: T helper (Th) cell type 2 (Th2)-polarized inflammation, bronchial hyperreactivity, and airway wall remodeling. However, the link between the immune-inflammatory phenotype and the structural-functional phenotype remains to be fully defined. The objective of these studies was to evaluate the relationship between the immunologic nature of chronic airway inflammation and the development of abnormal airway structure and function in a mouse model of chronic asthma. Using IL-4-competent and IL-4-deficient mice, we created divergent immune-inflammatory responses to chronic aeroallergen challenge. Immune-inflammatory, structural, and physiological parameters of chronic allergic airway disease were evaluated in both strains of mice. Although both strains developed airway inflammation, the profiles of the immune-inflammatory responses were markedly different: IL-4-competent mice elicited a Th2-polarized response and IL-4-deficient mice developed a Th1-polarized response. Importantly, this chronic Th1-polarized immune response was not associated with airway remodeling or bronchial hyperresponsiveness. Transient reconstitution of IL-4 in IL-4-deficient mice via an airway gene transfer approach led to partial Th2 repolarization and increased bronchial hyperresponsiveness, along with full reconstitution of airway remodeling. These data show that distinct structural-functional phenotypes associated with chronic airway inflammation are strictly dependent on the nature of the immune-inflammatory response. PMID:17586699

  17. Phenotypic variation and water selection potential in the stem structure of invasive alligator weed

    NASA Astrophysics Data System (ADS)

    Du, Leshan; Yang, Beifen; Guan, Wenbin; Li, Junmin

    2016-02-01

    The morphological and anatomical characteristics of stems have been found to be related to drought resistance in plants. Testing the phenotypic selection of water availability on stem anatomical traits would be useful for exploring the evolutionary potential of the stem in response to water availability. To test the phenotypic variation of the stem anatomical traits of an invasive plant in response to water availability, we collected a total of 320 individuals of Alternanthera philoxeroides from 16 populations from terrestrial and aquatic habitats in 8 plots in China and then analyzed the variation, differentiation, plasticity and selection potential of water availability on the stem anatomical traits. We found that except for the thickness of the cortex, all of the examined phenotypic parameters of the A. philoxeroides stem were significantly and positively correlated with soil water availability. The phenotypic differentiation coefficient for all of the anatomical structural parameters indicated that most of the variation existed between habitats within the same plot, whereas there was little variation among plots or among individuals within the same habitat except for variation in the thickness of the cortex. A significant phenotypic plasticity response to water availability was found for all of the anatomical traits of A. philoxeroides stem except for the thickness of the cortex. The associations between fitness and some of the anatomical traits, such as the stem diameter, the cortex area-to-stem area ratio, the pith cavity area-to-stem area ratio and the density of vascular bundles, differed with heterogeneous water availability. In both the aquatic and terrestrial habitats, no significant directional selection gradient was found for the stem diameter, the cortex area-to-stem area ratio or the density of vascular bundles. These results indicated that the anatomical structure of the A. philoxeroides stem may play an important role in the adaptation to changes

  18. Plant phenotyping using multi-view stereo vision with structured lights

    NASA Astrophysics Data System (ADS)

    Nguyen, Thuy Tuong; Slaughter, David C.; Maloof, Julin N.; Sinha, Neelima

    2016-05-01

    A multi-view stereo vision system for true 3D reconstruction, modeling and phenotyping of plants was created that successfully resolves many of the shortcomings of traditional camera-based 3D plant phenotyping systems. This novel system incorporates several features including: computer algorithms, including camera calibration, excessive-green based plant segmentation, semi-global stereo block matching, disparity bilateral filtering, 3D point cloud processing, and 3D feature extraction, and hardware consisting of a hemispherical superstructure designed to hold five stereo pairs of cameras and a custom designed structured light pattern illumination system. This system is nondestructive and can extract 3D features of whole plants modeled from multiple pairs of stereo images taken at different view angles. The study characterizes the systems phenotyping performance for 3D plant features: plant height, total leaf area, and total leaf shading area. For plants having specified leaf spacing and size, the algorithms used in our system yielded satisfactory experimental results and demonstrated the ability to study plant development where the same plants were repeatedly imaged and phenotyped over the time.

  19. Effects of grazer presence on genetic structure of a phenotypically diverse diatom population.

    PubMed

    Sjöqvist, C; Kremp, A; Lindehoff, E; Båmstedt, U; Egardt, J; Gross, S; Jönsson, M; Larsson, H; Pohnert, G; Richter, H; Selander, E; Godhe, A

    2014-01-01

    Studies of predator-prey systems in both aquatic and terrestrial environments have shown that grazers structure the intraspecific diversity of prey species, given that the prey populations are phenotypically variable. Populations of phytoplankton have traditionally considered comprising only low intraspecific variation, hence selective grazing as a potentially structuring factor of both genetic and phenotypic diversity has not been comprehensively studied. In this study, we compared strain specific growth rates, production of polyunsaturated aldehydes, and chain length of the marine diatom Skeletonema marinoi in both grazer and non-grazer conditions by conducting monoclonal experiments. Additionally, a mesocosm experiment was performed with multiclonal experimental S. marinoi populations exposed to grazers at different levels of copepod concentration to test effects of grazer presence on diatom diversity in close to natural conditions. Our results show that distinct genotypes of a geographically restricted population exhibit variable phenotypic traits relevant to grazing interactions such as chain length and growth rates. Grazer presence affected clonal richness and evenness of multiclonal Skeletonema populations in the mesocosms, likely in conjunction with intrinsic interactions among the diatom strains. Only the production of polyunsaturated aldehydes was not affected by grazer presence. Our findings suggest that grazing can be an important factor structuring diatom population diversity in the sea and emphasize the importance of considering clonal differences when characterizing species and their role in nature. PMID:24272280

  20. Structural and Functional Aspects of Extended-Spectrum AmpC Cephalosporinases.

    PubMed

    Powers, Rachel A

    2016-01-01

    β-lactam antibiotics have revolutionized modern medicine, but resistance to these drugs is a major public health crisis. Traditionally, class C β-lactamases were referred to as cephalosporinases due to their substrate preference for this particular class of β-lactams. However, the emergence of AmpC enzymes with extended-spectrum activity (extended-spectrum cephalosporinases or ESACs) is particularly worrisome, especially given that most clinical β-lactamase inhibitors are ineffective against these enzymes. This review summarizes structures of several extended spectrum class C β-lactamases and analyzes the structure-function relationship observed among them. PMID:26073861

  1. Phenotypic detection of extended spectrum β-lactamase and Amp-C β-lactamase producing clinical isolates in a Tertiary Care Hospital: A preliminary study

    PubMed Central

    Sageerabanoo, S.; Malini, A.; Mangaiyarkarasi, T.; Hemalatha, G.

    2015-01-01

    Background: Production of β-lactamase enzymes by Gram-negative bacteria is the most common mechanism to acquire drug resistance to β-lactam antibiotics. Limitations in detecting extended spectrum β-lactamases (ESBL) and Amp-C β-lactamases have contributed to the uncontrolled spread of bacterial resistance and are of significant clinical concern. Materials and Methods: A total of 148 samples was selected on the basis of resistance against third-generation cephalosporin for screening ESBLs and Amp-C β-lactamases production. These multidrug-resistant strains were phenotypically screened for ESBL production by phenotypic confirmatory disc diffusion test and double disc synergy test. Modified three-dimensional method was used for Amp-C β-lactamases detection. Result: Among the 148 isolates, 82 (55.40%) were ESBL producers, and 115 (77.70%) were Amp-C β-lactamases producers. Co-existence of ESBL and Amp-C was observed in 70 (47.29%) isolates. Escherichia coli was the most common ESBL and Amp-C β-lactamase producer. All ESBL producers were highly resistant to ciprofloxacin (83.10%), cotrimoxazole (95.27%), and gentamicin (89.18%). However, these bacterial strains were sensitive to imipenem 146 (98.64%) and piperacillin/tazobactam 143 (96.62%). Conclusion: Our study showed that ESBL producing organisms were not only resistant to cephalosporins but also to other group of drugs and also that multiple mechanisms play a role in drug resistance among Gram-negative bacteria. PMID:26283835

  2. Structural Properties of Gene Promoters Highlight More than Two Phenotypes of Diabetes

    PubMed Central

    Guja, Cristian

    2015-01-01

    Genome-wide association studies (GWAS) published in the last decade raised the number of loci associated with type 1 (T1D) and type 2 diabetes (T2D) to more than 50 for each of these diabetes phenotypes. The environmental factors seem to play an important role in the expression of these genes, acting through transcription factors that bind to promoters. Using the available databases we examined the promoters of various genes classically associated with the two main diabetes phenotypes. Our comparative analyses have revealed significant architectural differences between promoters of genes classically associated with T1D and T2D. Nevertheless, five gene promoters (about 16%) belonging to T1D and six gene promoters (over 19%) belonging to T2D have shown some intermediary structural properties, suggesting a direct relationship to either LADA (Latent Autoimmune Diabetes in Adults) phenotype or to non-autoimmune type 1 phenotype. The distribution of these promoters in at least three separate classes seems to indicate specific pathogenic pathways. The image-based patterns (DNA patterns) generated by promoters of genes associated with these three phenotypes support the clinical observation of a smooth link between specific cases of typical T1D and T2D. In addition, a global distribution of these DNA patterns suggests that promoters of genes associated with T1D appear to be evolutionary more conserved than those associated with T2D. Though, the image based patterns obtained by our method might be a new useful parameter for understanding the pathogenetic mechanism and the diabetogenic gene networks. PMID:26379145

  3. Linking amphibian call structure to the environment: the interplay between phenotypic flexibility and individual attributes.

    PubMed

    Ziegler, Lucía; Arim, Matías; Narins, Peter M

    2011-05-01

    The structure of the environment surrounding signal emission produces different patterns of degradation and attenuation. The expected adjustment of calls to ensure signal transmission in an environment was formalized in the acoustic adaptation hypothesis. Within this framework, most studies considered anuran calls as fixed attributes determined by local adaptations. However, variability in vocalizations as a product of phenotypic expression has also been reported. Empirical evidence supporting the association between environment and call structure has been inconsistent, particularly in anurans. Here, we identify a plausible causal structure connecting environment, individual attributes, and temporal and spectral adjustments as direct or indirect determinants of the observed variation in call attributes of the frog Hypsiboas pulchellus. For that purpose, we recorded the calls of 40 males in the field, together with vegetation density and other environmental descriptors of the calling site. Path analysis revealed a strong effect of habitat structure on the temporal parameters of the call, and an effect of site temperature conditioning the size of organisms calling at each site and thus indirectly affecting the dominant frequency of the call. Experimental habitat modification with a styrofoam enclosure yielded results consistent with field observations, highlighting the potential role of call flexibility on detected call patterns. Both, experimental and correlative results indicate the need to incorporate the so far poorly considered role of phenotypic plasticity in the complex connection between environmental structure and individual call attributes. PMID:22479134

  4. Phenotype, Sex of Rearing, Gender Re-Assignment, and Response to Medical Treatment in Extended Family Members with a Novel Mutation in the SRD5A2 Gene.

    PubMed

    Deeb, Asma; Al Suwaidi, Hana; Ibukunoluwa, Fakunle; Attia, Salima

    2016-06-01

    Deficiency of steroid 5-alpha reductase-2 (5ARD2) is an inborn error of metabolism causing a disorder of sexual differentiation. It is caused by a mutation in the SRD5A2 gene in which various mutation types have been reported. Affected individuals have a broad spectrum of presentation ranging from normal female-appearing genitalia, cliteromegaly, microphallus, hypospadias, to completely male-appearing genitalia. We report an extended Emirati family with 11 affected members. The family displayed various phenotypes on presentation leading to different sex of rearing. Some family members were reassigned gender at various stages of life. The index case was born with severe undervirilization with bilaterally palpable gonads and was raised as male from birth. He had a 46,XY karyotype and a high testosterone/dihydrotestosterone ratio. Genetic investigation revealed a novel homozygous deletion of exon 2 of the SRD5A2 gene. Both parents were found to be carriers for the gene deletion. The patient had masculinizing surgery and a course of topical dihydrotestosterone. No beneficial effect of the hormone application was noted over 3 months and the treatment was discontinued. The findings on this kindred indicate that deletion of exon 2 in the SRD5A2 gene causes various degrees of genital ambiguity leading to different sex of rearing in affected family members. Gender reassignment may be done at various ages even in conservative communities like the Gulf region. PMID:27086719

  5. Mutations of the AMH type II receptor in two extended families with persistent Müllerian duct syndrome: lack of phenotype/genotype correlation.

    PubMed

    Abduljabbar, Mohammad; Taheini, Khalid; Picard, Jean-Yves; Cate, Richard L; Josso, Nathalie

    2012-01-01

    Our goal was to compare phenotype and genotype in two extended Middle-Eastern families affected by persistent Müllerian duct syndrome due to mutations of the type II anti-Müllerian hormone receptor (AMHR-II). The first, consanguineous, family consisted of 6 boys and 2 girls, the second consisted of 4 girls and 2 boys. In family I, 4 boys and 1 girl were homozygous for a stop mutation in the 9th exon of AMHR-II, removing part of the intracellular domain of the protein. In family II, 1 girl and 1 boy were homozygous for a transversion changing conserved histidine 254 into a glutamine. Both homozygous girls were normal. In the homozygous males, the degree of development of Müllerian derivatives was variable. The uterus was well developed in 2 boys of family I and in the patient from family II; however, in 1 subject from family I, Müllerian derivatives were undetectable. Taken together, the diversity of clinical symptoms within the same sibship and the lack of correlation between the development of the Müllerian derivatives and the severity of the molecular defects suggest highly variable penetrance of the abnormal alleles and/or the existence of other genetic or epigenetic modifiers of gene expression. PMID:22584735

  6. Phenotypic and Molecular Characterisation of Extended-Spectrum Beta-Lactamase Producing Escherichia coli Obtained from Animal Fecal Samples in Ado Ekiti, Nigeria

    PubMed Central

    Olowe, Olugbenga Adekunle; Adewumi, Olufunmilayo; Odewale, Gbolabo; Ojurongbe, Olusola; Adefioye, Olusolabomi Jose

    2015-01-01

    Production of extended-spectrum β-lactamases (ESBLs) producing E. coli in animals and different methods of identifications from Ado Ekiti, Ekiti State, Nigeria, were investigated. Three hundred and fifty fecal samples, collected from apparently healthy cattle and pigs, were cultured and identified following standard procedures. ESBL phenotypic detection was carried out using combination disc test, double disc synergism test, and ESBL brilliance agar screening. Molecular detection of TEM, SHV, and CTX-M genes was carried out using standard molecular method. One hundred and fourteen E. coli isolates were recovered from the 350 samples processed, out of which 72 (63.2%) isolates were positive for ESBLs with multiple resistance to the antibiotics used. Eighty-one (71%) isolates were positive for ESBL by combination disc test, 90 (78.9%) were positive for double disc synergism test, and 93 (81.6%) were positive for ESBL brilliance agar. TEM and CTX-M genes were detected in 48 (42.1%) and 51 (44.7%) isolates, respectively. SHV gene was not detected in any of the isolates while TEM and CTX-M were detected in 33 (28.9%) isolates. This study showed high resistance of E. coli to antibiotics, particularly to the third generation cephalosporins. Regular monitoring and regulated use of antibiotics in livestock should be encouraged. PMID:26417371

  7. Population Structure and Genotype–Phenotype Associations in a Collection of Oat Landraces and Historic Cultivars

    PubMed Central

    Winkler, Louisa R.; Michael Bonman, J.; Chao, Shiaoman; Admassu Yimer, B.; Bockelman, Harold; Esvelt Klos, Kathy

    2016-01-01

    Population structure and genetic architecture of phenotypic traits in oat (Avena sativa L.) remain relatively under-researched compared to other small grain species. This study explores the historic context of current elite germplasm, including phenotypic and genetic characterization, with a particular focus on identifying under-utilized areas. A diverse panel of cultivated oat accessions was assembled from the USDA National Small Grains Collection to represent a gene pool relatively unaffected by twentieth century breeding activity and unlikely to have been included in recent molecular studies. The panel was genotyped using an oat iSelect 6K beadchip SNP array. The final dataset included 759 unique individuals and 2,715 polymorphic markers. Some population structure was apparent, with the first three principal components accounting for 38.8% of variation and 73% of individuals belonging to one of three clusters. One cluster with high genetic distinctness appears to have been largely overlooked in twentieth century breeding. Classification and phenotype data provided by the Germplasm Resources Information Network were evaluated for their relationship to population structure. Of the structuring variables evaluated, improvement status (cultivar or landrace) was relatively unimportant, indicating that landraces and cultivars included in the panel were all sampled from a similar underlying population. Instead, lemma color and region of origin showed the strongest explanatory power. An exploratory association mapping study of the panel using a subset of 2,588 mapped markers generated novel indications of genomic regions associated with awn frequency, kernels per spikelet, lemma color, and panicle type. Further results supported previous findings of loci associated with barley yellow dwarf virus tolerance, crown rust (caused by Puccinia coronata f. sp. avenae) resistance, days to anthesis, and growth habit (winter/spring). In addition, two novel loci were identified for

  8. Population Structure and Genotype-Phenotype Associations in a Collection of Oat Landraces and Historic Cultivars.

    PubMed

    Winkler, Louisa R; Michael Bonman, J; Chao, Shiaoman; Admassu Yimer, B; Bockelman, Harold; Esvelt Klos, Kathy

    2016-01-01

    Population structure and genetic architecture of phenotypic traits in oat (Avena sativa L.) remain relatively under-researched compared to other small grain species. This study explores the historic context of current elite germplasm, including phenotypic and genetic characterization, with a particular focus on identifying under-utilized areas. A diverse panel of cultivated oat accessions was assembled from the USDA National Small Grains Collection to represent a gene pool relatively unaffected by twentieth century breeding activity and unlikely to have been included in recent molecular studies. The panel was genotyped using an oat iSelect 6K beadchip SNP array. The final dataset included 759 unique individuals and 2,715 polymorphic markers. Some population structure was apparent, with the first three principal components accounting for 38.8% of variation and 73% of individuals belonging to one of three clusters. One cluster with high genetic distinctness appears to have been largely overlooked in twentieth century breeding. Classification and phenotype data provided by the Germplasm Resources Information Network were evaluated for their relationship to population structure. Of the structuring variables evaluated, improvement status (cultivar or landrace) was relatively unimportant, indicating that landraces and cultivars included in the panel were all sampled from a similar underlying population. Instead, lemma color and region of origin showed the strongest explanatory power. An exploratory association mapping study of the panel using a subset of 2,588 mapped markers generated novel indications of genomic regions associated with awn frequency, kernels per spikelet, lemma color, and panicle type. Further results supported previous findings of loci associated with barley yellow dwarf virus tolerance, crown rust (caused by Puccinia coronata f. sp. avenae) resistance, days to anthesis, and growth habit (winter/spring). In addition, two novel loci were identified for

  9. Packaging and structural phenotype of brome mosaic virus capsid protein with altered N-terminal {beta}-hexamer structure

    SciTech Connect

    Wispelaere, Melissanne de; Chaturvedi, Sonali; Wilkens, Stephan; Rao, A.L.N.

    2011-10-10

    The first 45 amino acid region of brome mosaic virus (BMV) capsid protein (CP) contains RNA binding and structural domains that are implicated in the assembly of infectious virions. One such important structural domain encompassing amino acids {sup 28}QPVIV{sup 32}, highly conserved between BMV and cowpea chlorotic mottle virus (CCMV), exhibits a {beta}-hexamer structure. In this study we report that alteration of the {beta}-hexamer structure by mutating {sup 28}QPVIV{sup 32} to {sup 28}AAAAA{sup 32} had no effect either on symptom phenotype, local and systemic movement in Chenopodium quinoa and RNA profile of in vivo assembled virions. However, sensitivity to RNase and assembly phenotypes distinguished virions assembled with CP subunits having {beta}-hexamer from those of wild type. A comparison of 3-D models obtained by cryo electron microscopy revealed overall similar structural features for wild type and mutant virions, with small but significant differences near the 3-fold axes of symmetry.

  10. Extended Structures in RNA Folding Intermediates Are Due to Nonnative Interactions Rather than Electrostatic Repulsion

    SciTech Connect

    Baird, Nathan J.; Gong, Haipeng; Zaheer, Syed S.; Freed, Karl F.; Pan, Tao; Sosnick, Tobin R.

    2010-05-25

    RNA folding occurs via a series of transitions between metastable intermediate states for Mg{sup 2+} concentrations below those needed to fold the native structure. In general, these folding intermediates are considerably less compact than their respective native states. Our previous work demonstrates that the major equilibrium intermediate of the 154-residue specificity domain (S-domain) of the Bacillus subtilis RNase P RNA is more extended than its native structure. We now investigate two models with falsifiable predictions regarding the origins of the extended intermediate structures in the S-domains of the B. subtilis and the Escherichia coli RNase P RNA that belong to different classes of P RNA and have distinct native structures. The first model explores the contribution of electrostatic repulsion, while the second model probes specific interactions in the core of the folding intermediate. Using small-angle X-ray scattering and Langevin dynamics simulations, we show that electrostatics plays only a minor role, whereas specific interactions largely account for the extended nature of the intermediate. Structural contacts in the core, including a nonnative base pair, help to stabilize the intermediate conformation. We conclude that RNA folding intermediates adopt extended conformations due to short-range, nonnative interactions rather than generic electrostatic repulsion of helical domains. These principles apply to other ribozymes and riboswitches that undergo functionally relevant conformational changes.

  11. Neurocognition in the Extended Psychosis Phenotype: Performance of a Community Sample of Adolescents With Psychotic Symptoms on the MATRICS Neurocognitive Battery

    PubMed Central

    Cannon, Mary

    2013-01-01

    Neurocognitive dysfunction is well established in psychosis, but recent work suggests that processing speed deficits might represent a particularly important cognitive deficit. A number of significant confounds, however, such as disease chronicity and antipsychotic medication use, have been shown to affect processing speed, causing debate as to the core cognitive features of psychosis. We adopted a novel strategy of testing neurocognitive performance in the “extended psychosis phenotype,” involving community-based adolescents who are not clinically psychotic but who report psychotic symptoms and who are at increased risk of psychosis in adulthood. This allows investigation of the earliest cognitive factors associated with psychosis risk, while excluding potential confounds such as disease chronicity and antipsychotic use. A population sample of 212 school-going adolescents aged 11–13 years took part in this study. Psychotic symptoms were assessed using the psychosis section of the Schedule for Affective Disorders and Schizophrenia. Neurocognition was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus neurocognitive battery. Adolescents with psychotic symptoms performed significantly more poorly on 3 processing speed tasks: Trail Making Test-A (F = 3.3, P < .05), Trail Making Test-B (F = 3.1, P < .05), and digit symbol coding task (F = 7.0, P < .001)—as well as on a nonverbal working memory (spatial span) task (F = 3.2, P < .05). Our findings support the idea that neurocognitive impairment, and processing speed impairment in particular, is a core feature of psychosis risk. This group likely demonstrates some of the earliest cognitive impairments associated with psychosis vulnerability.Key words: epidemiology/adolescents/cognition PMID:22927672

  12. Structural studies of molecular and metallic overlayers using angle- resolved photoemission extended fine structure

    SciTech Connect

    Huang, Z.

    1992-10-01

    Angle-resolved photoemission extended fine structure (ARPEFS) was used to study molecular and metallic overlayers on metal surfaces through analysis of p2mg(2{times}1)CO/Ni(110) and the p(2{times}2)K/Ni(111) adsorption. For the dense p2mg(2{times}1)CO/Ni(110) surface layer, photoemission intensities from C 1s level were measured in three directions at photoelectron kinetic energies 60-400 eV. Using multiple-scattering spherical-wave (MSSW) modeling, it was found that CO molecules are adsorbed on short-bridge sites, with adjacent CO along the [110] direction displaced alternatively in opposite directions towards the [001] azimuths to form a zigzag chain geometry. The tilt angle is 16{plus_minus}2{degree} from the surface normal for the direction linking the C atom and the center of the Ni bridge. The carbon C-Ni interatomic distance was determined to be 1.94{plus_minus}0.02{Angstrom}. The first- to second-layer spacing of Ni is 1.27{plus_minus}0.04{Angstrom}, up from 1.10{Angstrom} for the clean Ni(110) surface, but close to the 1.25{Angstrom} Ni interlayer spacing in the bulk. The C-O bond length and tilt angle were varied within small ranges (1.10--1.20{Angstrom} and 15--23{degrees}) in our MSSW simulations. Best agreement between experiment and simulations was achieved at 1.16{Angstrom} and 19{degrees}. This yields an O-O distance of 2.95{Angstrom} for the two nearest CO molecules, (van der Waals` radius {approximately} 1.5 {Angstrom} for oxygen). Two different partial-wave phase-shifts were used in MSSW, and structural results from both are in very good agreement. For the p(2{times}2)K/Ni(111) overlayer, ARPEFS {chi}(k) curves from K 1s level measured along [111] and [771] at 130K showed that the K atoms are preferentially adsorbed on the atop sites, in agreement with a LEED study of the same system.

  13. Structural studies of molecular and metallic overlayers using angle- resolved photoemission extended fine structure

    SciTech Connect

    Huang, Z.

    1992-10-01

    Angle-resolved photoemission extended fine structure (ARPEFS) was used to study molecular and metallic overlayers on metal surfaces through analysis of p2mg(2[times]1)CO/Ni(110) and the p(2[times]2)K/Ni(111) adsorption. For the dense p2mg(2[times]1)CO/Ni(110) surface layer, photoemission intensities from C 1s level were measured in three directions at photoelectron kinetic energies 60-400 eV. Using multiple-scattering spherical-wave (MSSW) modeling, it was found that CO molecules are adsorbed on short-bridge sites, with adjacent CO along the [110] direction displaced alternatively in opposite directions towards the [001] azimuths to form a zigzag chain geometry. The tilt angle is 16[plus minus]2[degree] from the surface normal for the direction linking the C atom and the center of the Ni bridge. The carbon C-Ni interatomic distance was determined to be 1.94[plus minus]0.02[Angstrom]. The first- to second-layer spacing of Ni is 1.27[plus minus]0.04[Angstrom], up from 1.10[Angstrom] for the clean Ni(110) surface, but close to the 1.25[Angstrom] Ni interlayer spacing in the bulk. The C-O bond length and tilt angle were varied within small ranges (1.10--1.20[Angstrom] and 15--23[degrees]) in our MSSW simulations. Best agreement between experiment and simulations was achieved at 1.16[Angstrom] and 19[degrees]. This yields an O-O distance of 2.95[Angstrom] for the two nearest CO molecules, (van der Waals' radius [approximately] 1.5 [Angstrom] for oxygen). Two different partial-wave phase-shifts were used in MSSW, and structural results from both are in very good agreement. For the p(2[times]2)K/Ni(111) overlayer, ARPEFS [chi](k) curves from K 1s level measured along [111] and [771] at 130K showed that the K atoms are preferentially adsorbed on the atop sites, in agreement with a LEED study of the same system.

  14. Novel Intronic RNA Structures Contribute to Maintenance of Phenotype in Saccharomyces cerevisiae

    PubMed Central

    Hooks, Katarzyna B.; Naseeb, Samina; Parker, Steven; Griffiths-Jones, Sam; Delneri, Daniela

    2016-01-01

    The Saccharomyces cerevisiae genome has undergone extensive intron loss during its evolutionary history. It has been suggested that the few remaining introns (in only 5% of protein-coding genes) are retained because of their impact on function under stress conditions. Here, we explore the possibility that novel noncoding RNA structures (ncRNAs) are embedded within intronic sequences and are contributing to phenotype and intron retention in yeast. We employed de novo RNA structure prediction tools to screen intronic sequences in S. cerevisiae and 36 other fungi. We identified and validated 19 new intronic RNAs via RNA sequencing (RNA-seq) and RT-PCR. Contrary to the common belief that excised introns are rapidly degraded, we found that, in six cases, the excised introns were maintained intact in the cells. In another two cases we showed that the ncRNAs were further processed from their introns. RNA-seq analysis confirmed that introns in ribosomal protein genes are more highly expressed when they contain predicted RNA structures. We deleted the novel intronic RNA structure within the GLC7 intron and showed that this region, rather than the intron itself, is responsible for the cell’s ability to respond to salt stress. We also showed a direct association between the in cis presence of the intronic RNA and GLC7 expression. Overall, these data support the notion that some introns may have been maintained in the genome because they harbor functional RNA structures. PMID:27194751

  15. Phenotypic and Causal Structure of Conduct Disorder in the Broader Context of Prevalent Forms of Psychopathology

    PubMed Central

    Lahey, Benjamin B.; Waldman, Irwin D.

    2011-01-01

    Background A better understanding of the nature and etiology of conduct disorder (CD) can inform nosology and vice-versa. We posit that any prevalent form of psychopathology, including CD, can be best understood if it is studied in the context of other correlated forms of child and adolescent psychopathology using formal models to guide inquiry. Methods Review of both cross-sectional and longitudinal studies of the place of CD in the phenotypic and causal structure of prevalent psychopathology, with an emphasis on similarities and differences between CD and oppositional defiant disorder (ODD). Papers were located using Web of Science by topic searches with no restriction on year of publication. Results Although some important nosologic questions remain unanswered, the dimensional phenotype of CD is well defined. CD differs from other disorders in its correlates, associated impairment, and course. Nonetheless, it is robustly correlated with many other prevalent dimensions of psychopathology both concurrently and predictively, including both other “externalizing” disorders and some “internalizing” disorders. Based on emerging evidence, we hypothesize that these concurrent and predictive correlations result primarily from widespread genetic pleiotropy, with some genetic factors nonspecifically influencing risk for multiple correlated dimensions of psychopathology. In contrast, environmental influences mostly act to differentiate dimensions of psychopathology from one another both concurrently and over time. CD and ODD share half of their genetic influences, but their genetic etiologies are distinct in other ways. Unlike most other dimensions of psychopathology, half of the genetic influences on CD appear to be unique to CD. In contrast, ODD broadly shares nearly all of its genetic influences with other disorders and has little unique genetic variance. Conclusions CD is a relatively distinct syndrome at both phenotypic and etiologic levels, but much is revealed

  16. Individual fitness and phenotypic selection in age-structured populations with constant growth rates

    PubMed Central

    Moorad, Jacob A.

    2013-01-01

    Powerful multiple regression-based approaches are commonly used to measure the strength of phenotypic selection, which is the statistical association between individual fitness and trait values. Age structure and overlapping generations complicate determinations of individual fitness, contributing to the popularity of alternative methods for measuring natural selection that do not depend upon such measures. The application of regression-based techniques for measuring selection in these situations requires a demographically appropriate, conceptually sound, and observable measure of individual fitness. It has been suggested that Fisher’s reproductive value applied to an individual at its birth is such a definition. Here I offer support for this assertion by showing that multiple regression applied to this measure and vital rates (age-specific survival and fertility rates) yields the same selection gradients for vital rates as those inferred from Hamilton’s classical results. I discuss how multiple regressions, applied to individual reproductive value at birth, can be used efficiently to estimate measures of phenotypic selection that are problematic for sensitivity analyses. These include nonlinear selection, components of the opportunity for selection, and multi-level selection. PMID:24933826

  17. Thermal Expansion Behaviour of Silver Examined by Extended X-Ray Absorption Fine Structure Spectroscopy

    SciTech Connect

    Dubiel, M.; Chasse, A.; Haug, J.; Schneider, R.; Kruth, H.

    2007-02-02

    EXAFS (extended X-ray absorption fine structure) investigations are reported concerning the thermal expansion behaviour of silver in an extended range of temperature from 10 K to about 950 K measured in transmission mode. Both the ratio method and an EXAFS fitting procedure were applied to reveal the temperature dependence of EXAFS parameters. Models based on quantum and classical thermodynamic perturbation theory have been used to interpret experimental data and compared to XRD (X-ray diffraction) results of bulk silver material. The description of thermodynamic data of thermal expansion of silver in the complete range of temperature by EXAFS Spectroscopy was successful by first calculations using third order quantum perturbation theory.

  18. Where Is the Extended Phenotype in the Wild? The Community Composition of Arthropods on Mature Oak Trees Does Not Depend on the Oak Genotype

    PubMed Central

    Gossner, Martin M.; Brändle, Martin; Brandl, Roland; Bail, Johannes; Müller, Jörg; Opgenoorth, Lars

    2015-01-01

    Through a series of common garden experiments, it has been shown that heritable phenotypic differences between individual trees can affect arthropod communities. However, field studies under heterogeneous environmental conditions remain rare. In the present study, we investigated the genetic constitution of 121 mature oak host trees at different trophic levels from 10 sites across Bavaria, southern Germany and their associated insect communities. A total of 23,576 individuals representing 395 species of beetles and true bugs were evaluated. In particular, we determined whether the composition of arthropod communities is related to the oak genotype and whether the strength of the relationships decreases from lower to higher trophic levels, such as for phytophagous, xylophagous, zoophagous, and mycetophagous species. The genetic differentiation of oaks was assessed using eight microsatellite markers. We found no significant influence of the oak genotype on neither the full beetle and true bug community nor on any of the analyzed trophic guilds. In contrast, the community composition of the insects was highly related to the space and climate, such that the community similarity decreased with increases in spatial distance and climatic differences. The relationship with space and climate was much stronger in beetles than in true bugs, particularly in mycetophagous species. Our results suggest that spatial processes override the genetic effects of the host plant in structuring arthropod communities on oak trees. Because we used neutral markers, we cannot exclude the possibility that trait-specific markers may reveal a genetic imprint of the foundation tree species on the composition of the arthropod community. However, based on the strength of the spatial patterns in our data set, we assume that genetic differences among oaks are less important in the structuring of arthropod communities. Future whole-genome studies are required to draw a final conclusion. PMID:25635387

  19. On implementation of the extended interior penalty function. [optimum structural design

    NASA Technical Reports Server (NTRS)

    Cassis, J. H.; Schmit, L. A., Jr.

    1976-01-01

    The extended interior penalty function formulation is implemented. A rational method for determining the transition between the interior and extended parts is set forth. The formulation includes a straightforward method for avoiding design points with some negative components, which are physically meaningless in structural analysis. The technique, when extended to problems involving parametric constraints, can facilitate closed form integration of the penalty terms over the most important parts of the parameter interval. The method lends itself well to the use of approximation concepts, such as design variable linking, constraint deletion and Taylor series expansions of response quantities in terms of design variables. Examples demonstrating the algorithm, in the context of planar orthogonal frames subjected to ground motion, are included.

  20. Optical coherence tomography for live phenotypic analysis of embryonic ocular structures in mouse models

    NASA Astrophysics Data System (ADS)

    Larina, Irina V.; Syed, Saba H.; Sudheendran, Narendran; Overbeek, Paul A.; Dickinson, Mary E.; Larin, Kirill V.

    2012-08-01

    Mouse models of ocular diseases provide a powerful resource for exploration of molecular regulation of eye development and pre-clinical studies. Availability of a live high-resolution imaging method for mouse embryonic eyes would significantly enhance longitudinal analyses and high-throughput morphological screening. We demonstrate that optical coherence tomography (OCT) can be used for live embryonic ocular imaging throughout gestation. At all studied stages, the whole eye is within the imaging distance of the system and there is a good optical contrast between the structures. We also performed OCT eye imaging in the embryonic retinoblastoma mouse model Pax6-SV40 T-antigen, which spontaneously forms lens and retinal lesions, and demonstrate that OCT allows us to clearly differentiate between the mutant and wild type phenotypes. These results demonstrate that OCTin utero imaging is a potentially useful tool to study embryonic ocular diseases in mouse models.

  1. Interacting Thin Film Systems Probed by Electron Induced Extended Fine Structure

    NASA Astrophysics Data System (ADS)

    Idzerda, Yves Ulrich

    In order to obtain information on the structure and dynamics of various systems including interacting thin films, it is necessary to be able to measure local structure information with surface sensitivity. Three techniques of Electron Induced Extended Fine Structure (EIEFS), the electron analog of Extended X-ray Absorption Fine Structure (EXAFS), are described, compared, and applied to thin film systems. Surface Extended Electron Loss Fine Structure (SEELFS), Extended Appearence Potential Fine Structure (EAPFS) and Auger-Monitored Extended Fine Structure (AMEFS), are all local structure probes with varying degrees of surface sensitivity, and all yield similar information. Our results show that each technique can be measured by commercially available electron optics, SEELFS and AMEFS by either a cylindrical mirror analyzer (CMA) or by low energy electron diffraction (LEED) optics and EAPFS by the LEED optics. We have addressed questions concerning proper phase shifts for the analysis, short data ranges, required use of undifferentiated data, and experimental difficulties. Investigations of carbon, oxygen, sodium, potassium, cesium, and sulfur on Cu(111) and titanium on silicon demonstrate that SEELFS is applicable to single monolayer coverages of very low Z adsorbates and thin films. Many of the theoretical difficulties surrounding the analysis of SEELFS can be circumvented by the use of standards and the ratio technique analysis developed for EXAFS. We also find in our studies of silicon, titanium, and aluminum oxide that systems with plasmon losses in the region of interest cannot be analyzed, but systems with other characteristic losses which are very sharp or very broad can be. Examination of EAPFS shows that it is more surface sensitive and is applicable to single monolayer coverages (of a broader range of elements than SEELFS) and thin films. Unfortunately, EAPFS is not applicable to single crystal systems with low electron binding energies where diffraction

  2. CHANDRA EVIDENCE FOR EXTENDED X-RAY STRUCTURE IN RY Tau

    SciTech Connect

    Skinner, Stephen L.; Audard, Marc; Guedel, Manuel E-mail: marc.audard@unige.ch

    2011-08-10

    We report results of a sensitive Chandra ACIS-S observation of the classical T Tauri star RY Tau. Previous studies have shown that it drives a spectacular bipolar jet whose blueshifted component is traced optically along P.A. {approx} 295{sup 0} at separations of 1.''5-31'' from the star. Complex X-ray emission is revealed, including a very soft non-variable spectral component (some of which may originate in shocks), a superhot flaring component (T {approx}> 100 MK), and faint extended structure near the star. The structure is visible in deconvolved images and extends northwestward out to a separation of 1.''7, overlapping the inner part of the optical jet. Image analysis suggests that most of the extension is real, but some contamination by point-spread-function-induced structure within the central arcsecond may be present. The predicted temperature for a shock-heated jet based on jet speed and shock speed estimates from optical measurements is too low to explain the extended X-ray structure. Either higher speed material within the jet has escaped optical detection or other mechanisms besides shock heating are involved. Alternative mechanisms that could produce higher temperature plasma at small offsets to the northwest of RY Tau include magnetic heating in the jet, hot plasmoids ejected at high speeds, or X-ray emission from a putative close companion whose presence has been inferred from Hipparcos variations.

  3. DETERMINING THE NATURE OF THE EXTENDED H I STRUCTURE AROUND LITTLE THINGS DWARF GALAXY NGC 1569

    SciTech Connect

    Johnson, Megan

    2013-06-15

    This work presents an extended, neutral hydrogen emission map around Magellanic-type dwarf irregular galaxy (dIm) NGC 1569. In the spring of 2010, the Robert C. Byrd Green Bank Telescope was used to map a 9 Degree-Sign Multiplication-Sign 2 Degree-Sign region in H I line emission that includes NGC 1569 and IC 342 as well as two other dwarf galaxies. The primary objective for these observations was to search for structures potentially connecting NGC 1569 with IC 342 group members in order to trace previous interactions and thus, provide an explanation for the starburst and peculiar kinematics prevalent in NGC 1569. A large, half-degree diameter H I cloud was detected that shares the same position and velocity as NGC 1569. Also, two long structures were discovered that are reminiscent of intergalactic filaments extending out in a V-shaped manner from NGC 1569 toward UGCA 92, a nearby dwarf galaxy. These filamentary structures extend for about 1. Degree-Sign 5, which is 77 kpc at NGC 1569. There is a continuous velocity succession with the 0. Degree-Sign 5 H I cloud, filaments, and main body of the galaxy. The 0. Degree-Sign 5 H I cloud and filamentary structures may be foreground Milky Way, but are suggestive as possible remnants of an interaction between NGC 1569 and UGCA 92. The data also show two tidal tails extending from UGCA 86 and IC 342, respectively. These structures may be part of a continuous H I bridge but more data are needed to determine if this is the case.

  4. Ultrasonic array imaging of multilayer structures using full matrix capture and extended phase shift migration

    NASA Astrophysics Data System (ADS)

    Wu, Haiteng; Chen, Jian; Yang, Keji; Hu, Xuxiao

    2016-04-01

    Multilayer structures have been widely used in industrial fields, and non-destructive evaluation of these structures is of great importance to assure their quality and performance. Recently, ultrasonic array imaging using full matrix capture, e.g. the total focusing method (TFM), has been shown to increase sensitivity to small defects and improve imaging resolution in homogeneous media. However, it cannot be applied to multilayer structures directly, due to the sound velocity variation in different layers and because refraction occurs at layer interfaces, which gives rise to difficulties in determining the propagation path and time. To overcome these problems, an extended phase shift migration (EPSM) is proposed for the full matrix imaging of multilayer structures in this paper. Based on the theory of phase shift migration for monostatic pulse-echo imaging, full matrix imaging using EPSM is derived by extrapolating the wavefields in both transmission and reception, and extended to the multilayer case. The performance of the proposed algorithm is evaluated by full matrix imaging of a two-layer structure with side-drilled holes conducted both in the simulation and the experiment. The results verify that the proposed algorithm is capable of full matrix imaging of a layered structure with a high resolution and signal-to-noise ratio. For comparison, full matrix imaging using the TFM with root-mean-squared velocity is also performed, and the results demonstrate that the proposed algorithm is superior to the TFM in improving both the image quality and resolution.

  5. Family Structure and Adolescent Alcohol Use Problems: Extending Popular Explanations to American Indiansc

    PubMed Central

    Eitle, Tamela McNulty; Johnson-Jennings, Michelle; Eitle, David J.

    2013-01-01

    Competing explanations of the relationship between family structure and alcohol use problems are examined using a sample of American Indian adolescents from the National Longitudinal Study of Adolescent Health. Living in a single-parent family is found to be a marker for the unequal distribution of stress exposure and parental alcohol use, but the effects of other family structures like non-parent families and the presence of under 21-year-old extended family or non-family members emerge or remain as risk or protective factors for alcohol use problems after a consideration of SES, family processes, peer socialization, and social stress. In particular, a non-parent family structure that has not been considered in prior research emerged as a protective family structure for American Indian adolescent alcohol use problems. PMID:24014896

  6. A testosterone-related structural brain phenotype predicts aggressive behavior from childhood to adulthood.

    PubMed

    Nguyen, Tuong-Vi; McCracken, James T; Albaugh, Matthew D; Botteron, Kelly N; Hudziak, James J; Ducharme, Simon

    2016-01-01

    Structural covariance, the examination of anatomic correlations between brain regions, has emerged recently as a valid and useful measure of developmental brain changes. Yet the exact biological processes leading to changes in covariance, and the relation between such covariance and behavior, remain largely unexplored. The steroid hormone testosterone represents a compelling mechanism through which this structural covariance may be developmentally regulated in humans. Although steroid hormone receptors can be found throughout the central nervous system, the amygdala represents a key target for testosterone-specific effects, given its high density of androgen receptors. In addition, testosterone has been found to impact cortical thickness (CTh) across the whole brain, suggesting that it may also regulate the structural relationship, or covariance, between the amygdala and CTh. Here, we examined testosterone-related covariance between amygdala volumes and whole-brain CTh, as well as its relationship to aggression levels, in a longitudinal sample of children, adolescents, and young adults 6-22 years old. We found: (1) testosterone-specific modulation of the covariance between the amygdala and medial prefrontal cortex (mPFC); (2) a significant relationship between amygdala-mPFC covariance and levels of aggression; and (3) mediation effects of amygdala-mPFC covariance on the relationship between testosterone and aggression. These effects were independent of sex, age, pubertal stage, estradiol levels and anxious-depressed symptoms. These findings are consistent with prior evidence that testosterone targets the neural circuits regulating affect and impulse regulation, and show, for the first time in humans, how androgen-dependent organizational effects may regulate a very specific, aggression-related structural brain phenotype from childhood to young adulthood. PMID:26431805

  7. Drug Repositioning by Kernel-Based Integration of Molecular Structure, Molecular Activity, and Phenotype Data

    PubMed Central

    Wang, Yongcui; Chen, Shilong; Deng, Naiyang; Wang, Yong

    2013-01-01

    Computational inference of novel therapeutic values for existing drugs, i.e., drug repositioning, offers the great prospect for faster and low-risk drug development. Previous researches have indicated that chemical structures, target proteins, and side-effects could provide rich information in drug similarity assessment and further disease similarity. However, each single data source is important in its own way and data integration holds the great promise to reposition drug more accurately. Here, we propose a new method for drug repositioning, PreDR (Predict Drug Repositioning), to integrate molecular structure, molecular activity, and phenotype data. Specifically, we characterize drug by profiling in chemical structure, target protein, and side-effects space, and define a kernel function to correlate drugs with diseases. Then we train a support vector machine (SVM) to computationally predict novel drug-disease interactions. PreDR is validated on a well-established drug-disease network with 1,933 interactions among 593 drugs and 313 diseases. By cross-validation, we find that chemical structure, drug target, and side-effects information are all predictive for drug-disease relationships. More experimentally observed drug-disease interactions can be revealed by integrating these three data sources. Comparison with existing methods demonstrates that PreDR is competitive both in accuracy and coverage. Follow-up database search and pathway analysis indicate that our new predictions are worthy of further experimental validation. Particularly several novel predictions are supported by clinical trials databases and this shows the significant prospects of PreDR in future drug treatment. In conclusion, our new method, PreDR, can serve as a useful tool in drug discovery to efficiently identify novel drug-disease interactions. In addition, our heterogeneous data integration framework can be applied to other problems. PMID:24244318

  8. Allosteric and hyperekplexic mutant phenotypes investigated on an α1 glycine receptor transmembrane structure

    PubMed Central

    Moraga-Cid, Gustavo; Sauguet, Ludovic; Huon, Christèle; Malherbe, Laurie; Girard-Blanc, Christine; Petres, Stéphane; Murail, Samuel; Taly, Antoine; Baaden, Marc; Delarue, Marc; Corringer, Pierre-Jean

    2015-01-01

    The glycine receptor (GlyR) is a pentameric ligand-gated ion channel (pLGIC) mediating inhibitory transmission in the nervous system. Its transmembrane domain (TMD) is the target of allosteric modulators such as general anesthetics and ethanol and is a major locus for hyperekplexic congenital mutations altering the allosteric transitions of activation or desensitization. We previously showed that the TMD of the human α1GlyR could be fused to the extracellular domain of GLIC, a bacterial pLGIC, to form a functional chimera called Lily. Here, we overexpress Lily in Schneider 2 insect cells and solve its structure by X-ray crystallography at 3.5 Å resolution. The TMD of the α1GlyR adopts a closed-channel conformation involving a single ring of hydrophobic residues at the center of the pore. Electrophysiological recordings show that the phenotypes of key allosteric mutations of the α1GlyR, scattered all along the pore, are qualitatively preserved in this chimera, including those that confer decreased sensitivity to agonists, constitutive activity, decreased activation kinetics, or increased desensitization kinetics. Combined structural and functional data indicate a pore-opening mechanism for the α1GlyR, suggesting a structural explanation for the effect of some key hyperekplexic allosteric mutations. The first X-ray structure of the TMD of the α1GlyR solved here using GLIC as a scaffold paves the way for mechanistic investigation and design of allosteric modulators of a human receptor. PMID:25730860

  9. Structural and functional roles of the N- and C-terminal extended modules in channelrhodopsin-1.

    PubMed

    Doi, Satoko; Mori, Arisa; Tsukamoto, Takashi; Reissig, Louisa; Ihara, Kunio; Sudo, Yuki

    2015-09-26

    Channelrhodopsins have become a focus of interest because of their ability to control neural activity by light, used in a technology called optogenetics. The channelrhodopsin in the eukaryote Chlamydomonas reinhardtii (CrChR-1) is a light-gated cation channel responsible for motility changes upon photo-illumination and a member of the membrane-embedded retinal protein family. Recent crystal structure analysis revealed that CrChR-1 has unique extended modules both at its N- and C-termini compared to other microbial retinal proteins. This study reports the first successful expression of a ChR-1 variant in Escherichia coli as a holoprotein: the ChR-1 variant lacking both the N- and C-termini (CrChR-1_82-308). However, compared to ChR-1 having the extended modules (CrChR-1_1-357), truncation of the termini greatly altered the absorption maximum and photochemical properties, including the pKa values of its charged residues around the chromophore, the reaction rates in the photocycle and the photo-induced ion channeling activity. The results of some experiments regarding ion transport activity suggest that CrChR-1_82-308 has a proton channeling activity even in the dark. On the basis of these results, we discuss the structural and functional roles of the N- and C-terminal extended modules in CrChR-1. PMID:26098533

  10. The red extended structure of IC 10, the nearest blue compact galaxy

    NASA Astrophysics Data System (ADS)

    Gerbrandt, Stephanie A. N.; McConnachie, Alan W.; Irwin, Mike

    2015-11-01

    The Local Group starburst galaxy IC 10 is the closest example of a blue compact galaxy. Here, we use optical gi imaging from Canada-France-Hawaii Telescope/MegaCam and near infrared JHK imaging from United Kingdom Infrared Telescope/Wide Field Camera to conduct a comprehensive survey of the structure of IC 10. We examine the spatial distribution of its resolved young, intermediate and old stellar populations to large radius and low effective surface brightness levels. Akin to other dwarfs with multiple populations of different ages, stellar populations of decreasing average age are increasingly concentrated in this galaxy. We find that the young, starbursting population and the asymptotic giant branch population are both offset from the geometric centre of the older red giant branch (RGB) population by a few hundred parsecs, implying that the younger star formation occurred significantly away from the centre of the galaxy. The RGB population traces an extended structure that is typical of blue compact galaxies, with an effective radius of ˜5.75 arcmin (˜1.25 kpc). These measurements show that IC 10 is much more extended than has previously been realized, and this blue compact galaxy is one of the most extended dwarf galaxies in the Local Group. The outermost isophotes of this galaxy are very regular in shape and essentially circular in morphology. Based on this analysis, we do not find any evidence to suggest that IC 10 has undergone a recent, significant, interaction with an unknown companion.

  11. Split mandrel versus split sleeve coldworking: Dual methods for extending the fatigue life of metal structures

    NASA Astrophysics Data System (ADS)

    Rodman, Geoffrey A.; Creager, Matthew

    1994-09-01

    It is common practice to use split sleeve coldworking of fastener holes as a means of extending the fatigue life of metal structures. In search of lower manufacturing costs, the aerospace industry is examining the split mandrel (sleeveless) coldworking process as an alternative method of coldworking fastener holes in metal structures. The split mandrel process (SpM) significantly extends the fatigue life of metal structures through the introduction of a residual compressive stress in a manner that is very similar to the split sleeve system (SpSl). Since the split mandrel process is significantly less expensive than the split sleeve process and more adaptable to robotic automation, it will have a notable influence upon other new manufacture of metal structures which require coldworking a significant number of holes, provided the aerospace community recognizes that the resulting residual stress distributions and fatigue life improvement are the same for both processes. Considerable testing has validated the correctness of that conclusion. The findings presented in this paper represent the results of an extensive research and development program, comprising data collected from over 400 specimens fabricated from 2024-T3 and 7075-T651 aluminum alloys in varied configurations, which quantify the benefits (fatigue enhancement and cost savings) of automating a sleeveless coldworking system.

  12. Split mandrel versus split sleeve coldworking: Dual methods for extending the fatigue life of metal structures

    NASA Technical Reports Server (NTRS)

    Rodman, Geoffrey A.; Creager, Matthew

    1994-01-01

    It is common practice to use split sleeve coldworking of fastener holes as a means of extending the fatigue life of metal structures. In search of lower manufacturing costs, the aerospace industry is examining the split mandrel (sleeveless) coldworking process as an alternative method of coldworking fastener holes in metal structures. The split mandrel process (SpM) significantly extends the fatigue life of metal structures through the introduction of a residual compressive stress in a manner that is very similar to the split sleeve system (SpSl). Since the split mandrel process is significantly less expensive than the split sleeve process and more adaptable to robotic automation, it will have a notable influence upon other new manufacture of metal structures which require coldworking a significant number of holes, provided the aerospace community recognizes that the resulting residual stress distributions and fatigue life improvement are the same for both processes. Considerable testing has validated the correctness of that conclusion. The findings presented in this paper represent the results of an extensive research and development program, comprising data collected from over 400 specimens fabricated from 2024-T3 and 7075-T651 aluminum alloys in varied configurations, which quantify the benefits (fatigue enhancement and cost savings) of automating a sleeveless coldworking system.

  13. Novel Method for Measuring Structure and Semantic Similarity of XML Documents Based on Extended Adjacency Matrix

    NASA Astrophysics Data System (ADS)

    Zhang, Xue-Liang; Yang, Ting; Fan, Bao-Quan; Wang, Xu; Wei, Jin-Mao

    Similarity measurement of XML documents is crucial to meet various needs of approximate searches and document classifications in XML-oriented applications. Some methods have been proposed for this purpose. Nevertheless, few methods can be elegantly exploited to depict structure and semantic information and hence to effectively measure the similarity of XML documents. In this paper, we present a new method of computing the structure and semantic similarity of XML documents based on extended adjacency matrix(EAM). Different from a general adjacency matrix, in an EAM, the structure information of not only the adjacent layers but also the ancestor-descendant layers can be stored. For measuring the similarity of two XML documents, the proposed method firstly stores the structure and semantic information in two extended adjacency matrices(M1, M2). Then it computes similarity of the two documents through cos(M1, M2) Experimental results on bench-mark data show that the method holds high efficiency and accuracy.

  14. Metal-organic extended 2D structures: Fe-PTCDA on Au(111).

    PubMed

    Alvarez, Lucía; Peláez, Samuel; Caillard, Renaud; Serena, Pedro A; Martín-Gago, José A; Méndez, Javier

    2010-07-30

    In this work we combine organic molecules of 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) with iron atoms on an Au (111) substrate in ultra-high vacuum conditions at different temperatures. By means of scanning tunnelling microscopy (STM) we study the formation of stable 2D metal-organic structures. We show that at certain growth conditions (temperature, time and coverage) stable 'ladder-like' nanostructures are obtained. These are the result of connecting together two metal-organic chains through PTCDA molecules placed perpendicularly, as rungs of a ladder. These structures, stable up to 450 K, can be extended in a 2D layer covering the entire surface and presenting different rotation domains. STM images at both polarities show a contrast reversal between the two molecules at the unit cell. By means of density functional theory (DFT) calculations, we confirm the stability of these structures and that their molecular orbitals are placed separately at the different molecules. PMID:20603531

  15. Structural damage detection using extended Kalman filter combined with statistical process control

    NASA Astrophysics Data System (ADS)

    Jin, Chenhao; Jang, Shinae; Sun, Xiaorong

    2015-04-01

    Traditional modal-based methods, which identify damage based upon changes in vibration characteristics of the structure on a global basis, have received considerable attention in the past decades. However, the effectiveness of the modalbased methods is dependent on the type of damage and the accuracy of the structural model, and these methods may also have difficulties when applied to complex structures. The extended Kalman filter (EKF) algorithm which has the capability to estimate parameters and catch abrupt changes, is currently used in continuous and automatic structural damage detection to overcome disadvantages of traditional methods. Structural parameters are typically slow-changing variables under effects of operational and environmental conditions, thus it would be difficult to observe the structural damage and quantify the damage in real-time with EKF only. In this paper, a Statistical Process Control (SPC) is combined with EFK method in order to overcome this difficulty. Based on historical measurements of damage-sensitive feathers involved in the state-space dynamic models, extended Kalman filter (EKF) algorithm is used to produce real-time estimations of these features as well as standard derivations, which can then be used to form control ranges for SPC to detect any abnormality of the selected features. Moreover, confidence levels of the detection can be adjusted by choosing different times of sigma and number of adjacent out-of-range points. The proposed method is tested using simulated data of a three floors linear building in different damage scenarios, and numerical results demonstrate high damage detection accuracy and light computation of this presented method.

  16. XPD Helicase Structures and Activities: Insights into the Cancer and Aging Phenotypes from XPD Mutations

    SciTech Connect

    Tainer, John; Fan, Li; Fuss, Jill O.; Cheng, Quen J.; Arvai, Andrew S.; Hammel, Michal; Roberts, Victoria A.; Cooper, Priscilla K.; Tainer, John A.

    2008-06-02

    Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicase activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.

  17. XPD Helicase Structures And Activities: Insights Into the Cancer And Aging Phenotypes From XPD Mutations

    SciTech Connect

    Fan, L.; Fuss, J.O.; Cheng, Q.J.; Arvai, A.S.; Hammel, M.; Roberts, V.A.; Cooper, P.K.; Tainer, J.A.

    2009-05-18

    Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicase activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.

  18. Gene duplication of type-B ARR transcription factors systematically extends transcriptional regulatory structures in Arabidopsis

    PubMed Central

    Choi, Seung Hee; Hyeon, Do Young; Lee, ll Hwan; Park, Su Jin; Han, Seungmin; Lee, In Chul; Hwang, Daehee; Nam, Hong Gil

    2014-01-01

    Many of duplicated genes are enriched in signaling pathways. Recently, gene duplication of kinases has been shown to provide genetic buffering and functional diversification in cellular signaling. Transcription factors (TFs) are also often duplicated. However, how duplication of TFs affects their regulatory structures and functions of target genes has not been explored at the systems level. Here, we examined regulatory and functional roles of duplication of three major ARR TFs (ARR1, 10, and 12) in Arabidopsis cytokinin signaling using wild-type and single, double, and triple deletion mutants of the TFs. Comparative analysis of gene expression profiles obtained from Arabidopsis roots in wild-type and these mutants showed that duplication of ARR TFs systematically extended their transcriptional regulatory structures, leading to enhanced robustness and diversification in functions of target genes, as well as in regulation of cellular networks of target genes. Therefore, our results suggest that duplication of TFs contributes to robustness and diversification in functions of target genes by extending transcriptional regulatory structures. PMID:25425016

  19. Structure Theory for Extended Kepler-Coulomb 3D Classical Superintegrable Systems

    NASA Astrophysics Data System (ADS)

    Kalnins, Ernie G.; Miller, Willard, Jr.

    2012-06-01

    The classical Kepler-Coulomb system in 3 dimensions is well known to be 2nd order superintegrable, with a symmetry algebra that closes polynomially under Poisson brackets. This polynomial closure is typical for 2nd order superintegrable systems in 2D and for 2nd order systems in 3D with nondegenerate (4-parameter) potentials. However the degenerate 3-parameter potential for the 3D extended Kepler-Coulomb system (also 2nd order superintegrable) is an exception, as its quadratic symmetry algebra doesn't close polynomially. The 3D 4-parameter potential for the extended Kepler-Coulomb system is not even 2nd order superintegrable. However, Verrier and Evans (2008) showed it was 4th order superintegrable, and Tanoudis and Daskaloyannis (2011) showed that in the quantum case, if a second 4th order symmetry is added to the generators, the double commutators in the symmetry algebra close polynomially. Here, based on the Tremblay, Turbiner and Winternitz construction, we consider a! n infinite class of classical extended Kepler-Coulomb 3- and 4-parameter systems indexed by a pair of rational numbers (k1,k2) and reducing to the usual systems when k1=k2=1. We show these systems to be superintegrable of arbitrarily high order and work out explicitly the structure of the symmetry algebras determined by the 5 basis generators we have constructed. We demonstrate that the symmetry algebras close rationally; only for systems admitting extra discrete symmetries is polynomial closure achieved. Underlying the structure theory is the existence of raising and lowering constants of the motion, not themselves polynomials in the momenta, that can be employed to construct the polynomial symmetries and their structure relations.

  20. Local structure of NiAl compounds investigated by extended X-ray absorption fine-structure spectroscopy.

    PubMed

    Tian, J S; Han, G M; Wei, H; Jin, T; Dargusch, M S

    2012-07-01

    The local structures of pure NiAl and Ti-, Co-doped NiAl compounds have been obtained utilizing extended X-ray absorption fine-structure (EXAFS) spectroscopy. The results provide experimental evidence that Ni antisite defects exist in the Ni-rich NiAl compounds. The site preference of Ti and Co has been confirmed. Ti occupies the Al sublattice, while Co occupies the Ni sublattice. The structure parameters obtained by EXAFS were consistent with the X-ray diffraction results. Owing to the precipitation of α-Cr, the local structure of NiAl-Cr has not been obtained, making the site preference of Cr unclear. PMID:22713881

  1. Phenotypic covariance structure and its divergence for acoustic mate attraction signals among four cricket species

    PubMed Central

    Bertram, Susan M; Fitzsimmons, Lauren P; McAuley, Emily M; Rundle, Howard D; Gorelick, Root

    2012-01-01

    The phenotypic variance–covariance matrix (P) describes the multivariate distribution of a population in phenotypic space, providing direct insight into the appropriateness of measured traits within the context of multicollinearity (i.e., do they describe any significant variance that is independent of other traits), and whether trait covariances restrict the combinations of phenotypes available to selection. Given the importance of P, it is therefore surprising that phenotypic covariances are seldom jointly analyzed and that the dimensionality of P has rarely been investigated in a rigorous statistical framework. Here, we used a repeated measures approach to quantify P separately for populations of four cricket species using seven acoustic signaling traits thought to enhance mate attraction. P was of full or almost full dimensionality in all four species, indicating that all traits conveyed some information that was independent of the other traits, and that phenotypic trait covariances do not constrain the combinations of signaling traits available to selection. P also differed significantly among species, although the dominant axis of phenotypic variation (pmax) was largely shared among three of the species (Acheta domesticus, Gryllus assimilis, G. texensis), but different in the fourth (G. veletis). In G. veletis and A. domesticus, but not G. assimilis and G. texensis, pmax was correlated with body size, while pmax was not correlated with residual mass (a condition measure) in any of the species. This study reveals the importance of jointly analyzing phenotypic traits. PMID:22408735

  2. Improved self-absorption correction for extended x-ray absorption fine-structure measurements

    SciTech Connect

    Booth, C.H.; Bridges, F.

    2003-06-04

    Extended x-ray absorption fine-structure (EXAFS) data collected in the fluorescence mode are susceptible to an apparent amplitude reduction due to the self-absorption of the fluorescing photon by the sample before it reaches a detector. Previous treatments have made the simplifying assumption that the effect of the EXAFS on the correction term is negligible, and that the samples are in the thick limit. We present a nearly exact treatment that can be applied for any sample thickness or concentration, and retains the EXAFS oscillations in the correction term.

  3. Surface extended x-ray absorption fine structure of low-Z absorbates using fluorescence detection

    SciTech Connect

    Stoehr, J.; Kollin, E.B.; Fischer, D.A.; Hastings, J.B.; Zaera, F.; Sette, F.

    1985-05-01

    Comparison of x-ray fluorescence yield (FY) and electron yield surface extended x-ray absorption fine structure spectra above the S K-edge for c(2 x 2) S on Ni(100) reveals an order of magnitude higher sensitivity of the FY technique. Using FY detection, thiophene (C/sub 4/H/sub 4/S) chemisorption on Ni(100) is studied with S coverages down to 0.08 monolayer. The molecule dissociates at temperatures as low as 100K by interaction with fourfold hollow Ni sites. Blocking of these sites by oxygen leaves the molecule intact.

  4. Structured Extended Finite Element Methods of Solids Defined by Implicit Surfaces

    SciTech Connect

    Belytschko, T; Mish, K; Moes, N; Parimi, C

    2002-11-17

    A paradigm is developed for generating structured finite element models from solid models by means of implicit surface definitions. The implicit surfaces are defined by radial basis functions. Internal features, such as material interfaces, sliding interfaces and cracks are treated by enrichment techniques developed in the extended finite element method (X-FEM). Methods for integrating the weak form for such models are proposed. These methods simplify the generation of finite element models. Results presented for several examples show that the accuracy of this method is comparable to standard unstructured finite element methods.

  5. A Phenotypic Structure and Neural Correlates of Compulsive Behaviors in Adolescents

    PubMed Central

    Montigny, Chantale; Castellanos-Ryan, Natalie; Whelan, Robert; Banaschewski, Tobias; Barker, Gareth J.; Büchel, Christian; Gallinat, Jürgen; Flor, Herta; Mann, Karl; Paillère-Martinot, Marie-Laure; Nees, Frauke; Lathrop, Mark; Loth, Eva; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Schumann, Gunter; Smolka, Michael N.; Struve, Maren; Robbins, Trevor W.; Garavan, Hugh; Conrod, Patricia J.

    2013-01-01

    Background A compulsivity spectrum has been hypothesized to exist across Obsessive-Compulsive disorder (OCD), Eating Disorders (ED), substance abuse (SA) and binge-drinking (BD). The objective was to examine the validity of this compulsivity spectrum, and differentiate it from an externalizing behaviors dimension, but also to look at hypothesized personality and neural correlates. Method A community-sample of adolescents (N=1938; mean age 14.5 years), and their parents were recruited via high-schools in 8 European study sites. Data on adolescents’ psychiatric symptoms, DSM diagnoses (DAWBA) and substance use behaviors (AUDIT and ESPAD) were collected through adolescent- and parent-reported questionnaires and interviews. The phenotypic structure of compulsive behaviors was then tested using structural equation modeling. The model was validated using personality variables (NEO-FFI and TCI), and Voxel-Based Morphometry (VBM) analysis. Results Compulsivity symptoms best fit a higher-order two factor model, with ED and OCD loading onto a compulsivity factor, and BD and SA loading onto an externalizing factor, composed also of ADHD and conduct disorder symptoms. The compulsivity construct correlated with neuroticism (r=0.638; p≤0.001), conscientiousness (r=0.171; p≤0.001), and brain gray matter volume in left and right orbitofrontal cortex, right ventral striatum and right dorsolateral prefrontal cortex. The externalizing factor correlated with extraversion (r=0.201; p≤0.001), novelty-seeking (r=0.451; p≤0.001), and negatively with gray matter volume in the left inferior and middle frontal gyri. Conclusions Results suggest that a compulsivity spectrum exists in an adolescent, preclinical sample and accounts for variance in both OCD and ED, but not substance-related behaviors, and can be differentiated from an externalizing spectrum. PMID:24244633

  6. [POLYMORPHISM IN THE PHENOTYPIC STRUCTURE OF A POPULATION OF TAIGA TICK AND ITS EPIDEMIOLOGICAL SIGNIFICANCE].

    PubMed

    Morozov, I M; Alekseev, A N; Dubinina, E V; Nikitin, A Ya; Melnikova, O V; Andaev, E I

    2015-01-01

    The paper presents the results of 10-year (2005-2014) observations of an Ixodespersulcatus Schulze population. The purpose of this investigation was to trace long-term changes in the structure of the taiga tick population from the proportion of specimens with external skeletal anomalies and to assess a relationship between the pattern of imago phenotypic variation and the virus percentage of a carrier. There were a total of reports of the external skeletal structure of 1123 females gathered from plants to a flag in an area at 43 km from the Baikal Road connecting Irkutsk and the settlement of Listvyanka (Irkutsk Region). The proportion of specimens with anomalies averaged 37.8 +/- 1.88%. Four-to-seven varying anomalies were annually recorded. There was a preponderance of scutum impairment (an average of 17.0 +/- 3.08% of all females) that was a conglomerate of prominences and indentations along the entire clypeus surface and that was denoted P9. The nature of a change in the proportion of ticks with two anomalies (average monthly registration rate, 2.5 +/- 0.66%) is exhibited by three-year high-frequency oscillations whereas the specimens with P9 anomalies fail to show so clear cycling. The percentage of virus-containing taiga ticks was individually determined estimating the level of tick-borne encephalitis virus antigen by an enzyme immunoassay. A total of 4022 ticks were examined. The male and female data were pooled. There was a positive correlation between the change in the proportion of females with P9 anomaly and the infection of ticks in the examined population (Spearman's correlation coefficient, 0.88; P < 0.01). This supports the earlier observation of the greater epidemiological significance of the imago of a taiga tick with external skeletal anomalies particularly with considerably marked ones. PMID:26720971

  7. The CATH database: an extended protein family resource for structural and functional genomics

    PubMed Central

    Pearl, F. M. G.; Bennett, C. F.; Bray, J. E.; Harrison, A. P.; Martin, N.; Shepherd, A.; Sillitoe, I.; Thornton, J.; Orengo, C. A.

    2003-01-01

    The CATH database of protein domain structures (http://www.biochem.ucl.ac.uk/bsm/cath_new) currently contains 34 287 domain structures classified into 1383 superfamilies and 3285 sequence families. Each structural family is expanded with domain sequence relatives recruited from GenBank using a variety of efficient sequence search protocols and reliable thresholds. This extended resource, known as the CATH-protein family database (CATH-PFDB) contains a total of 310 000 domain sequences classified into 26 812 sequence families. New sequence search protocols have been designed, based on these intermediate sequence libraries, to allow more regular updating of the classification. Further developments include the adaptation of a recently developed method for rapid structure comparison, based on secondary structure matching, for domain boundary assignment. The philosophy behind CATHEDRAL is the recognition of recurrent folds already classified in CATH. Benchmarking of CATHEDRAL, using manually validated domain assignments, demonstrated that 43% of domains boundaries could be completely automatically assigned. This is an improvement on a previous consensus approach for which only 10–20% of domains could be reliably processed in a completely automated fashion. Since domain boundary assignment is a significant bottleneck in the classification of new structures, CATHEDRAL will also help to increase the frequency of CATH updates. PMID:12520050

  8. A 200 V silicon-on-sapphire LDMOS structure with a step oxide extended field plate

    NASA Astrophysics Data System (ADS)

    Roig, J.; Flores, D.; Rebollo, J.; Hidalgo, S.; Millan, J.

    2004-02-01

    Fabrication of power integrated circuits on silicon-on-sapphire (SOS) substrates has rarely been considered before. Hence, there is a lack of research in lateral power devices integrated on SOS. Self-heating effects in existing silicon-on-insulator (SOI) lateral power devices degrade the device performance and their reliability. Use of SOS substrates could alleviate these problems though they would require a different approach in lateral power device engineering. This paper purposes a new power SOS LDMOS structure with reduced transient self-heating effects and enhanced current capability compared to the conventional SOI counterpart. The proposed lateral power structure integrated on SOS substrates is analyzed by electro-thermal simulations. The field plate is enlarged (extended field plate (EFP)) along the drift region, reaching the drain region. The EFP includes an oxide step which improves the "on-state resistance-breakdown voltage" trade-off ( RONxS- Vbr).

  9. Local vibrational properties of GaAs studied by extended X-ray absorption fine structure.

    PubMed

    Ahmed, S I; Aquilanti, G; Novello, N; Olivi, L; Grisenti, R; Fornasini, P

    2013-10-28

    Extended X-ray absorption fine structure (EXAFS) has been measured at both the K edges of gallium and arsenic in GaAs, from 14 to 300 K, to investigate the local vibrational and thermodynamic behaviour in terms of bond expansion, parallel, and perpendicular mean square relative displacements and third cumulant. The separate analysis of the two edges allows a self-consistent check of the results and suggests that a residual influence of Ga EXAFS at the As edge cannot be excluded. The relation between bond expansion, lattice expansion, and expansion due to anharmonicity of the effective potential is quantitatively clarified. The comparison with previous EXAFS results on other crystals with the diamond or zincblende structure shows that the values of a number of parameters determined from EXAFS are clearly correlated with the fractional ionicity and with the strength and temperature interval of the lattice negative expansion. PMID:24182054

  10. Extending the ICRF to Higher Radio Frequencies: Imaging and Source Structure

    NASA Technical Reports Server (NTRS)

    Boboltz, David A.; Fey, Alan L.; Charlot, Patrick; Fomalont, Edward B.; Lanyi, Gabor E.; Zhang, Li-Wei

    2004-01-01

    We present imaging results and source structure analysis of extragalactic radio sources observed using the Very Long Baseline Array (VLBA) at 24 GHz and 43 GHz as part of an ongoing NASA, USNO, NRAO and Bordeaux Observatory collaboration to extend the International Celestial Reference Frame (ICRF) to higher radio frequencies. The K/Q-band image database now includes images of 108 sources at 43 GHz (Q-braid) and images of 230 sources at 24 GHz (K-band). Preliminary analysis of the observations taken to date shows that the sources are generally more compact as one goes from the ICRF frequency of 8.4 GHz to 24 GHz. This result is consistent with the standard theory of compact extragalactic radio sources and suggests that reference frames defined at these higher radio frequencies will be less susceptible to the effects of intrinsic source structure than those defined at lower frequencies.

  11. An extended structure-based model based on a stochastic eddy-axis evolution equation

    NASA Technical Reports Server (NTRS)

    Kassinos, S. C.; Reynolds, W. C.

    1995-01-01

    We have proposed and implemented an extension of the structure-based model for weak deformations. It was shown that the extended model will correctly reduce to the form of standard k-e models for the case of equilibrium under weak mean strain. The realizability of the extended model is guaranteed by the method of its construction. The predictions of the proposed model were very good for rotating homogeneous shear flows and for irrotational axisymmetric contraction, but were seriously deficient in the case of plane strain and axisymmetric expansion. We have concluded that the problem behind these difficulties lies in the algebraic constitutive equation relating the Reynolds stresses to the structure parameters rather than in the slow model developed here. In its present form, this equation assumes that under irrotational strain the principal axes of the Reynolds stresses remain locked onto those of the eddy-axis tensor. This is correct in the RDT limit, but inappropriate under weaker mean strains, when the non-linear eddy-eddy interactions tend to misalign the two sets of principal axes and create some non-zero theta and gamma.

  12. Structure of a lipid-bound extended synaptotagmin indicates a role in lipid transfer.

    PubMed

    Schauder, Curtis M; Wu, Xudong; Saheki, Yasunori; Narayanaswamy, Pradeep; Torta, Federico; Wenk, Markus R; De Camilli, Pietro; Reinisch, Karin M

    2014-06-26

    Growing evidence suggests that close appositions between the endoplasmic reticulum (ER) and other membranes, including appositions with the plasma membrane (PM), mediate exchange of lipids between these bilayers. The mechanisms of such exchange, which allows lipid transfer independently of vesicular transport, remain poorly understood. The presence of a synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain, a proposed lipid-binding module, in several proteins localized at membrane contact sites has raised the possibility that such domains may be implicated in lipid transport. SMP-containing proteins include components of the ERMES complex, an ER–mitochondrial tether, and the extended synaptotagmins (known as tricalbins in yeast), which are ER–PM tethers. Here we present at 2.44 Å resolution the crystal structure of a fragment of human extended synaptotagmin 2 (E-SYT2), including an SMP domain and two adjacent C2 domains. The SMP domain has a β-barrel structure like protein modules in the tubular-lipid-binding (TULIP) superfamily. It dimerizes to form an approximately 90-Å-long cylinder traversed by a channel lined entirely with hydrophobic residues, with the two C2A–C2B fragments forming arched structures flexibly linked to the SMP domain. Importantly, structural analysis complemented by mass spectrometry revealed the presence of glycerophospholipids in the E-SYT2 SMP channel, indicating a direct role for E-SYTs in lipid transport. These findings provide strong evidence for a role of SMP-domain-containing proteins in the control of lipid transfer at membrane contact sites and have broad implications beyond the field of ER-to-PM appositions. PMID:24847877

  13. Three-dimensional structure of the extended solar magnetic field and the sunspot cycle variation in cosmic ray intensity

    NASA Technical Reports Server (NTRS)

    Svalgaard, L.; Wilcox, J. M.

    1976-01-01

    A principal cause for the eleven-year sunspot cycle variation in the primary cosmic ray intensity observed at earth may be a variation in the solid angle of the heliosphere occupied by the extended solar polar magnetic field. Galactic cosmic rays have relatively easy access to the inner solar system through the regular extended solar polar fields, and relatively difficult access through the irregular extended solar sector structure fields.

  14. The Relative Influence of Competition and Prey Defenses on the Phenotypic Structure of Insectivorous Bat Ensembles in Southern Africa

    PubMed Central

    Schoeman, M. Corrie; Jacobs, David S.

    2008-01-01

    Deterministic filters such as competition and prey defences should have a strong influence on the community structure of animals such as insectivorous bats that have life histories characterized by low fecundity, low predation risk, long life expectancy, and stable populations. We investigated the relative influence of these two deterministic filters on the phenotypic structure of insectivorous bat ensembles in southern Africa. We used null models to simulate the random phenotypic patterns expected in the absence of competition or prey defences and analysed the deviations of the observed phenotypic pattern from these expected random patterns. The phenotypic structure at local scales exhibited non-random patterns consistent with both competition and prey defense hypotheses. There was evidence that competition influenced body size distribution across ensembles. Competition also influenced wing and echolocation patterns in ensembles and in functional foraging groups with high species richness or abundance. At the same time, prey defense filters influenced echolocation patterns in two species-poor ensembles. Non-random patterns remained evident even after we removed the influence of body size from wing morphology and echolocation parameters taking phylogeny into account. However, abiotic filters such as geographic distribution ranges of small and large-bodied species, extinction risk, and the physics of flight and sound probably also interacted with biotic filters at local and/or regional scales to influence the community structure of sympatric bats in southern Africa. Future studies should investigate alternative parameters that define bat community structure such as diet and abundance to better determine the influence of competition and prey defences on the structure of insectivorous bat ensembles in southern Africa. PMID:19005563

  15. The structure of the genotype-phenotype map strongly constrains the evolution of non-coding RNA.

    PubMed

    Dingle, Kamaludin; Schaper, Steffen; Louis, Ard A

    2015-12-01

    The prevalence of neutral mutations implies that biological systems typically have many more genotypes than phenotypes. But, can the way that genotypes are distributed over phenotypes determine evolutionary outcomes? Answering such questions is difficult, in part because the number of genotypes can be hyper-astronomically large. By solving the genotype-phenotype (GP) map for RNA secondary structure (SS) for systems up to length L = 126 nucleotides (where the set of all possible RNA strands would weigh more than the mass of the visible universe), we show that the GP map strongly constrains the evolution of non-coding RNA (ncRNA). Simple random sampling over genotypes predicts the distribution of properties such as the mutational robustness or the number of stems per SS found in naturally occurring ncRNA with surprising accuracy. Because we ignore natural selection, this strikingly close correspondence with the mapping suggests that structures allowing for functionality are easily discovered, despite the enormous size of the genetic spaces. The mapping is extremely biased: the majority of genotypes map to an exponentially small portion of the morphospace of all biophysically possible structures. Such strong constraints provide a non-adaptive explanation for the convergent evolution of structures such as the hammerhead ribozyme. These results present a particularly clear example of bias in the arrival of variation strongly shaping evolutionary outcomes and may be relevant to Mayr's distinction between proximate and ultimate causes in evolutionary biology. PMID:26640651

  16. An Incompletely Penetrant Novel Mutation in COL7A1 Causes Epidermolysis Bullosa Pruriginosa and Dominant Dystrophic Epidermolysis Bullosa Phenotypes in an Extended Kindred

    PubMed Central

    Yang, Catherine S; Lu, Yin; Farhi, Anita; Nelson-Williams, Carol; Kashgarian, Michael; Glusac, Earl J; Lifton, Richard P; Antaya, Richard J; Choate, Keith A

    2012-01-01

    Epidermolysis bullosa pruriginosa (EBP) is a rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by intense pruritus, nodular or lichenoid lesions, and violaceous linear scarring, most prominently on the extensor extremities. Remarkably, identical mutations in COL7A1, which encodes an anchoring fibril protein present at the dermal–epidermal junction, can cause both DEB and EBP with either autosomal dominant or recessive inheritance. We present one family with both dystrophic and pruriginosa phenotypes of epidermolysis bullosa. The proband is a 19-year-old Caucasian woman who initially presented in childhood with lichenoid papules affecting her extensor limbs and intense pruritus consistent with EBP. Her maternal grandmother saw a dermatologist for similar skin lesions that developed without any known triggers at age 47 and mostly resolved spontaneously after approximately 10 years. The proband’s younger brother developed a small crop of pruritic papules on his elbows, dorsal hands, knees, and ankles at age 13. Her second cousin once removed, however, reported a mild blistering disease without pruritus consistent with DEB. Genetic sequencing of the kindred revealed a single dominant novel intron 47 splice site donor G>A mutation, c.4668 + 1 G>A, which we predict leads to exon skipping. Incomplete penetrance is confirmed in her clinically unaffected mother, who carries the same dominant mutation. The wide diversity of clinical phenotypes with one underlying genotype demonstrates that COL7A1 mutations are incompletely penetrant and strongly suggests that other genetic and environmental factors influence clinical presentation. PMID:22515571

  17. Evolutionary Conservation and Network Structure Characterize Genes of Phenotypic Relevance for Mitosis in Human

    PubMed Central

    del Sol, Antonio

    2012-01-01

    The impact of gene silencing on cellular phenotypes is difficult to establish due to the complexity of interactions in the associated biological processes and pathways. A recent genome-wide RNA knock-down study both identified and phenotypically characterized a set of important genes for the cell cycle in HeLa cells. Here, we combine a molecular interaction network analysis, based on physical and functional protein interactions, in conjunction with evolutionary information, to elucidate the common biological and topological properties of these key genes. Our results show that these genes tend to be conserved with their corresponding protein interactions across several species and are key constituents of the evolutionary conserved molecular interaction network. Moreover, a group of bistable network motifs is found to be conserved within this network, which are likely to influence the network stability and therefore the robustness of cellular functioning. They form a cluster, which displays functional homogeneity and is significantly enriched in genes phenotypically relevant for mitosis. Additional results reveal a relationship between specific cellular processes and the phenotypic outcomes induced by gene silencing. This study introduces new ideas regarding the relationship between genotype and phenotype in the context of the cell cycle. We show that the analysis of molecular interaction networks can result in the identification of genes relevant to cellular processes, which is a promising avenue for future research. PMID:22577488

  18. Extended-resolution structured illumination imaging of endocytic and cytoskeletal dynamics

    PubMed Central

    Li, Dong; Shao, Lin; Chen, Bi-Chang; Zhang, Xi; Zhang, Mingshu; Moses, Brian; Milkie, Daniel E.; Beach, Jordan R.; Hammer, John A.; Pasham, Mithun; Kirchhausen, Tomas; Baird, Michelle A.; Davidson, Michael W.; Xu, Pingyong; Betzig, Eric

    2015-01-01

    Super-resolution fluorescence microscopy is distinct among nanoscale imaging tools in its ability to image protein dynamics in living cells. Structured illumination microscopy (SIM) stands out in this regard because of its high speed and low illumination intensities, but typically offers only a twofold resolution gain. We extended the resolution of live-cell SIM through two approaches: ultrahigh numerical aperture SIM at 84-nanometer lateral resolution for more than 100 multicolor frames, and nonlinear SIM with patterned activation at 45- to 62-nanometer resolution for approximately 20 to 40 frames. We applied these approaches to image dynamics near the plasma membrane of spatially resolved assemblies of clathrin and caveolin, Rab5a in early endosomes, and a-actinin, often in relationship to cortical actin. In addition, we examined mitochondria, actin, and the Golgi apparatus dynamics in three dimensions. PMID:26315442

  19. Extended x-ray absorption fine structure of NaBr and Ge at high pressure

    SciTech Connect

    Ingalls, R.; Crozier, E.D.; Whitmore, J.E.; Seary, A.J.; Tranquada, J.M.

    1980-06-01

    The x-ray absorption spectra of Ge and of Br in NaBr have been measured to pressures of 52 and 21 kbars, respectively, in a boron carbide and diamond anvil cell in which pressure was measured via the ruby-fluorescence technique. Although Bragg peaks from the diamond anvil reduced the accuracy, atomic spacings in both materials could be determined by extended x-ray absorption fine-structure (EXAFS) analysis. Changes in the nearest-neighbor separations in NaBr, and Ge to at least 40 kbars, agreed with literature values, indicating that the EXAFS phase shifts are quite insensitive to such pressures. In addition the near-edge peak positions in the NaBr spectra appeared to readily shift with pressure, which suggests that NaBr may be quite suitable as a pressure standard in future work of this type.

  20. New classes of integrals inherent in the mathematical structure of extended equations describing superconducting systems

    NASA Astrophysics Data System (ADS)

    Gonczarek, Ryszard; Krzyzosiak, Mateusz; Gonczarek, Adam; Jacak, Lucjan

    2015-06-01

    In this paper, we discuss the mathematical structure of the s-wave superconducting gap and other quantitative characteristics of superconducting systems. In particular, we evaluate and discuss integrals inherent in fundamental equations describing superconducting systems. The results presented here extend the approach formulated by Abrikosov and Maki, which was restricted to the first-order expansion. A few infinite families of integrals are derived and allow us to express the fundamental equations by means of analytic formulas. They can be then exploited in order to find some quantitative characteristics of superconducting systems by the method of successive approximations. We show that the results can be applied to some modern formalisms in order to study high-Tc superconductors and other superconducting materials of the new generation.

  1. ADVANCED IMAGING. Extended-resolution structured illumination imaging of endocytic and cytoskeletal dynamics.

    PubMed

    Li, Dong; Shao, Lin; Chen, Bi-Chang; Zhang, Xi; Zhang, Mingshu; Moses, Brian; Milkie, Daniel E; Beach, Jordan R; Hammer, John A; Pasham, Mithun; Kirchhausen, Tomas; Baird, Michelle A; Davidson, Michael W; Xu, Pingyong; Betzig, Eric

    2015-08-28

    Super-resolution fluorescence microscopy is distinct among nanoscale imaging tools in its ability to image protein dynamics in living cells. Structured illumination microscopy (SIM) stands out in this regard because of its high speed and low illumination intensities, but typically offers only a twofold resolution gain. We extended the resolution of live-cell SIM through two approaches: ultrahigh numerical aperture SIM at 84-nanometer lateral resolution for more than 100 multicolor frames, and nonlinear SIM with patterned activation at 45- to 62-nanometer resolution for approximately 20 to 40 frames. We applied these approaches to image dynamics near the plasma membrane of spatially resolved assemblies of clathrin and caveolin, Rab5a in early endosomes, and α-actinin, often in relationship to cortical actin. In addition, we examined mitochondria, actin, and the Golgi apparatus dynamics in three dimensions. PMID:26315442

  2. Asymmetric Dust Jets and Extended Structure of 22P/Kopff Observed During 2009 Appearance

    NASA Astrophysics Data System (ADS)

    Hanayama, Hidekazu; Ishiguro, Masateru; Watanabe, Jun-Ichi; Sarugaku, Yuki; Fukushima, Hideo; Miyaji, Takeshi; Yanagisawa, Kenshi; Kuroda, Daisuke; Yoshida, Michitoshi; Ohta, Kouji; Nobuyuki, Kawai

    2012-12-01

    22P/Kopff images were taken with Multicolor Imaging Telescopes for Survey and Monstrous Explosions (MITSuME) 3ch simultaneous CCD cameras on the Ishigakijima astronomical observatory 105-cm telescope and a 2kCCD camera on the Kiso 105-cm Schmidt telescope from 2009 August to December after the passage of its perihelion on 2009 May 25. We confirmed that the near-nuclear fan-shaped jet structure extended toward the south. Whereas we detected a dust trail structure on the project orbit of the parent nucleus, we could not confirm the obvious neck-line structure. We deduced a pole orientation of (αp1, δp1) = (302°±30°, 62°±10°) or (αp1, δp1) = (122°±30°, -62°±10°) in the case of prograde or retrograde rotation, based on the fan-shaped jet. In addition, we conducted a model simulation of the dust orbital evolution, and found that the observed dust morphology of the fan-shaped jet and dust trail can well explain the dust emission near the south polar region. Finally, we conclude that the surface of 22P/Kopff is becoming largely dormant, but the polar region is still active, as we saw in the Deep Space 1 image of 19P/Borrelly.

  3. Crystal Structure of a Super Leucine Zipper an Extended Two-Stranded Super Long Coiled Coil

    SciTech Connect

    J Diao

    2011-12-31

    Coiled coil is a ubiquitous structural motif in proteins, with two to seven alpha helices coiled together like the strands of a rope, and coiled coil folding and assembly is not completely understood. A GCN4 leucine zipper mutant with four mutations of K3A, D7A, Y17W, and H18N has been designed, and the crystal structure has been determined at 1.6 {angstrom} resolution. The peptide monomer shows a helix trunk with short curved N- and C-termini. In the crystal, two monomers cross in 35{sup o} and form an X-shaped dimer, and each X-shaped dimer is welded into the next one through sticky hydrophobic ends, thus forming an extended two-stranded, parallel, super long coiled coil rather than a discrete, two-helix coiled coil of the wild-type GCN4 leucine zipper. Leucine residues appear at every seventh position in the super long coiled coil, suggesting that it is an extended super leucine zipper. Compared to the wild-type leucine zipper, the N-terminus of the mutant has a dramatic conformational change and the C-terminus has one more residue Glu 32 determined. The mutant X-shaped dimer has a large crossing angle of 35{sup o} instead of 18{sup o} in the wild-type dimer. The results show a novel assembly mode and oligomeric state of coiled coil, and demonstrate that mutations may affect folding and assembly of the overall coiled coil. Analysis of the formation mechanism of the super long coiled coil may help understand and design self-assembling protein fibers.

  4. Quinolone-Resistant Escherichia coli O127a:K63 Serotype with an Extended-Spectrum-Beta-Lactamase Phenotype from a Food Poisoning Outbreak in China

    PubMed Central

    Hao, Rongzhang; Qiu, Shaofu; Yang, Guang; Su, Wenli; Song, Lixue; Zhang, Jia; Chen, Jiaxu; Jia, Leili; Wang, Ligui

    2012-01-01

    We report an atypical enteropathogenic Escherichia coli O127a:K63 strain with resistance to quinolones and extended-spectrum cephalosporins isolated from a 2010 food poisoning outbreak involving 112 adults in China. Two resistance genes [blaCTX-M-15, aac(6′)-Ib-c] and five mutations (two in gyrA, two in parC, one in parE) coexisted in this enteropathogenic E. coli strain. PMID:22553233

  5. Structural characterization of alkaline hydrogen peroxide pretreated grasses exhibiting diverse lignin phenotypes

    PubMed Central

    2012-01-01

    Background For cellulosic biofuels processes, suitable characterization of the lignin remaining within the cell wall and correlation of quantified properties of lignin to cell wall polysaccharide enzymatic deconstruction is underrepresented in the literature. This is particularly true for grasses which represent a number of promising bioenergy feedstocks where quantification of grass lignins is particularly problematic due to the high fraction of p-hydroxycinnamates. The main focus of this work is to use grasses with a diverse range of lignin properties, and applying multiple lignin characterization platforms, attempt to correlate the differences in these lignin properties to the susceptibility to alkaline hydrogen peroxide (AHP) pretreatment and subsequent enzymatic deconstruction. Results We were able to determine that the enzymatic hydrolysis of cellulose to to glucose (i.e. digestibility) of four grasses with relatively diverse lignin phenotypes could be correlated to total lignin content and the content of p-hydroxycinnamates, while S/G ratios did not appear to contribute to the enzymatic digestibility or delignification. The lignins of the brown midrib corn stovers tested were significantly more condensed than a typical commercial corn stover and a significant finding was that pretreatment with alkaline hydrogen peroxide increases the fraction of lignins involved in condensed linkages from 88–95% to ~99% for all the corn stovers tested, which is much more than has been reported in the literature for other pretreatments. This indicates significant scission of β-O-4 bonds by pretreatment and/or induction of lignin condensation reactions. The S/G ratios in grasses determined by analytical pyrolysis are significantly lower than values obtained using either thioacidolysis or 2DHSQC NMR due to presumed interference by ferulates. Conclusions It was found that grass cell wall polysaccharide hydrolysis by cellulolytic enzymes for grasses exhibiting a diversity of

  6. New insights into the phenotypic covariance structure of the anthropoid cranium.

    PubMed

    Makedonska, Jana

    2014-12-01

    In complex organisms, suites of non-random, highly intercorrelated phenotypic traits, organized according to their developmental history and forming semi-autonomous units (i.e. modules), have the potential to impose constraints on morphological diversification or to improve evolvability. Because of its structural, developmental and functional complexity, the cranium is arguably one of the best models for studying the interplay between developmental history and the need for various parts of a structure to specialize in different functions. This study evaluated the significance of two specific types of developmental imprints in the adult anthropoid cranium, those imposed by ossification pattern (i.e. ossification with and without a pre-existing cartilaginous phase) and those imposed by tissue origin (i.e. tissues derived principally from neural-crest vs. those derived from paraxial mesoderm). Specifically, this study tests the hypothesis that the face and the basicranium form two distinct modules with higher within-unit trait integration magnitudes compared with the cranium as a whole. Data on 12 anthropoid primate species were collected in the form of 20 three-dimensional landmarks digitized on cranial surface models that sample the basicranium as well as regions of functional importance during feeding [corrected]. The presence of a significant modularity imprint in the adult cranium was assessed using a between-region within-species comparison of multivariate correlations (RV coefficients) obtained with partial least-squares, using within-module within-species eigenvalue variance (EV), and using cluster analyses and non-metric multidimensional scaling. In addition to addressing the validity of the cranial modularity hypothesis in anthropoids, this study addressed methodological aspects of the interspecific comparison of morphological integration, namely the effect of sample size and the effect of landmark number on integration magnitudes. Two methodological

  7. A DEEPER LOOK AT LEO IV: STAR FORMATION HISTORY AND EXTENDED STRUCTURE

    SciTech Connect

    Sand, David J.; Seth, Anil; Olszewski, Edward W.; Zaritsky, Dennis; Willman, Beth; Kallivayalil, Nitya

    2010-07-20

    We present MMT/Megacam imaging of the Leo IV dwarf galaxy in order to investigate its structure and star formation history, and to search for signs of association with the recently discovered Leo V satellite. Based on parameterized fits, we find that Leo IV is round, with {epsilon} < 0.23 (at the 68% confidence limit) and a half-light radius of r{sub h} {approx_equal} 130 pc. Additionally, we perform a thorough search for extended structures in the plane of the sky and along the line of sight. We derive our surface brightness detection limit by implanting fake structures into our catalog with stellar populations identical to that of Leo IV. We show that we are sensitive to stream-like structures with surface brightness {mu}{sub r} {approx}< 29.6 mag arcsec{sup -2}, and at this limit we find no stellar bridge between Leo IV (out to a radius of {approx}0.5 kpc) and the recently discovered, nearby satellite Leo V. Using the color-magnitude fitting package StarFISH, we determine that Leo IV is consistent with a single age ({approx}14 Gyr), single metallicity ([Fe/H] {approx} -2.3) stellar population, although we cannot rule out a significant spread in these values. We derive a luminosity of M{sub V} = -5.5 {+-} 0.3. Studying both the spatial distribution and frequency of Leo IV's 'blue plume' stars reveals evidence for a young ({approx}2 Gyr) stellar population which makes up {approx}2% of its stellar mass. This sprinkling of star formation, only detectable in this deep study, highlights the need for further imaging of the new Milky Way satellites along with theoretical work on the expected, detailed properties of these possible 'reionization fossils'.

  8. Extended X-ray absorption fine structure study of mixed-ligand copper(II) complexes having analogous structures

    NASA Astrophysics Data System (ADS)

    Gaur, Abhijeet; Shrivastava, B. D.; Srivastava, Krishna; Prasad, J.

    2013-02-01

    X-ray absorption fine structure spectra have been studied at the Cu K-edge in five mixed-ligand copper(II) complexes, viz., [Cu(L-glu)(bipy)] 1, [Cu(L-glu)(phen) (H2O)].3H2O 2, [Cu(L-tyro)(bipy)(ClO4)].2H2O 3, [Cu(L-phen)(bipy)(H2O)] (ClO4) 4, and [Cu(L-tyro)(phen)(H2O)] (ClO4).1.5H2O 5 (where L-glu = L-glutamate dianion, L-tyro = L-tyrosinate anion, bipy = 2,2'-bipyridine, and phen =1,10-phenanthroline), having essentially the same structure. The crystallographic data are available for all the complexes using which five theoretical models have been generated. Firstly, extended X-ray absorption fine structure (EXAFS) data of each complex has been analyzed using its own theoretical model and the results obtained are found to be comparable with the crystallographic results. Then, the EXAFS data of each complex has been analyzed using the theoretical models of the remaining four of these complexes. For each complex, the structural parameters obtained by fitting EXAFS data with theoretical models of the four remaining complexes have been found to be comparable with those obtained by fitting its own theoretical model. Thus, it has been found that if the crystal structure is not available for a complex, then the crystal structure of similar or analogous complex can be used satisfactorily for generating the theoretical model for the EXAFS data analysis of that complex, even if different ligands are attached to the central metal atom. On the basis of EXAFS data analysis, the coordination geometries around the central metal ions in these complexes have been depicted.

  9. Free-energy landscape of mechanically unfolded model proteins: Extended Jarzinsky versus inherent structure reconstruction

    NASA Astrophysics Data System (ADS)

    Luccioli, Stefano; Imparato, Alberto; Torcini, Alessandro

    2008-09-01

    The equilibrium free-energy landscape of off-lattice model heteropolymers as a function of an internal coordinate, namely the end-to-end distance, is reconstructed from out-of-equilibrium steered molecular dynamics data. This task is accomplished via two independent methods: By employing an extended version of the Jarzynski equality and the inherent structure formalism. A comparison of the free energies estimated with these two schemes with equilibrium results obtained via the umbrella sampling technique reveals a good quantitative agreement among all the approaches in a range of temperatures around the “folding transition” for the two examined sequences. In particular, for the sequence with good foldability properties, the mechanically induced structural transitions can be related to thermodynamical aspects of folding. Moreover, for the same sequence the knowledge of the landscape profile allows for a good estimation of the lifetimes of the native configuration for temperatures ranging from the folding to the collapse temperature. For the random sequence, mechanical and thermal unfolding appear to follow different paths along the landscape.

  10. Spatial phenotypic and genetic structure of threespine stickleback (Gasterosteus aculeatus) in a heterogeneous natural system, Lake Mývatn, Iceland

    PubMed Central

    Millet, Antoine; Kristjánsson, Bjarni K; Einarsson, Árni; Räsänen, Katja

    2013-01-01

    Eco-evolutionary responses of natural populations to spatial environmental variation strongly depend on the relative strength of environmental differences/natural selection and dispersal/gene flow. In absence of geographic barriers, as often is the case in lake ecosystems, gene flow is expected to constrain adaptive divergence between environments – favoring phenotypic plasticity or high trait variability. However, if divergent natural selection is sufficiently strong, adaptive divergence can occur in face of gene flow. The extent of divergence is most often studied between two contrasting environments, whereas potential for multimodal divergence is little explored. We investigated phenotypic (body size, defensive structures, and feeding morphology) and genetic (microsatellites) structure in threespine stickleback (Gasterosteus aculeatus) across five habitat types and two basins (North and South) within the geologically young and highly heterogeneous Lake Mývatn, North East Iceland. We found that (1) North basin stickleback were, on average, larger and had relatively longer spines than South basin stickleback, whereas (2) feeding morphology (gill raker number and gill raker gap width) differed among three of five habitat types, and (3) there was only subtle genetic differentiation across the lake. Overall, our results indicate predator and prey mediated phenotypic divergence across multiple habitats in the lake, in face of gene flow. PMID:24223263

  11. Ovarian structures and uterine environment are associated with phenotypic and genetic merit for performance in lactating dairy cows.

    PubMed

    Fitzgerald, A M; Ryan, D P; Carthy, T R; Evans, R D; Berry, D P

    2014-12-01

    The objective of this study was to estimate the association between detailed reproductive phenotypes for cows categorized as divergent for phenotypic and genetic performance. The hypothesis was that higher yielding animals, either phenotypically or genetically, would have compromised ovarian and uterine reproductive performance. Detailed reproductive traits including multiple ovulations, cystic ovarian structures, corpus luteum (CL) presence, and uterine environment were available on 9675 ultrasound records from 8174 dairy lactating cows, calved between 10 and 70 days. Cows were categorized, within parity, into low, average, or high for each of the performance traits. There was a greater likelihood of multiple ovulations in cows with greater phenotypic yields (odds ratio: 1.53-1.81) and greater genetic merit for yield (odds ratio: 1.31-1.59) relative to lower performing contemporaries. After adjustment for genetic merit, a similar trend of increased odds (odds ratio: 1.29-1.87) of multiple ovulations in higher yielding cows was observed compared with the lowest yielding category. There was no association between either phenotypic milk composition or genetic merit for milk composition with the likelihood of multiple ovulations. The likelihood of cystic ovarian structures was highest in cows with greatest phenotypic milk yields (odds ratio: 2.75-3.24), greater genetic merit for milk yield (odds ratio: 1.30-1.51), and even after adjustment for genetic merit there was a greater likelihood of cystic ovarian structures in cows with the highest milk yields (odds ratio: 2.71-2.95), compared with cows in the lowest category for each of the milk traits. Cows with average phenotypic milk yields were more likely to have a CL, compared with the lowest yielding category (odds ratio: 1.20-1.23), and these associations remained after adjustment for genetic merit of the trait. The likelihood of CL presence was highest in cows with the lowest genetic merit for milk. Lower fat

  12. Structural Analysis of Freshwater-Cultured Pearls with Different Lusters Using the Extended X-Ray Absorption Fine Structure Technique

    NASA Astrophysics Data System (ADS)

    Monarumit, N.; Noirawee, N.; Phlayrahan, A.; Promdee, K.; Won-in, K.; Satitkune, S.

    2016-05-01

    The quality of freshwater-cultured pearls (Chamberlainia hainesiana) is determined by their luster, which is related to the content of the two CaCO3 mineral phases: aragonite and vaterite. The atomic structures of pearl samples were analyzed by the extended X-ray absorption fine structure (EXAFS) technique using synchrotron radiation to compare the atomic environment and atomic bonding around Ca atoms of high- and low-luster pearls. The Ca K-edge EXAFS spectra of the pearl samples were determined and interpreted in terms of the photoelectron wave number and the distance between Ca atoms and neighboring atoms. From the results, the wave oscillation of high-luster pearls is less than that of low-luster pearls. This indicates the presence of the aragonite phase in high-luster pearls and a combination of aragonite and vaterite phases in low-luster pearls, especially in the fi rst and second shells of Ca atoms. It can be concluded that the different lusters of freshwater-cultured pearls are related to the different CaCO3 phases in their structures.

  13. The local structure factor near an interface; beyond extended capillary-wave models.

    PubMed

    Parry, A O; Rascón, C; Evans, R

    2016-06-22

    We investigate the local structure factor S (z;q) at a free liquid-gas interface in systems with short-ranged intermolecular forces and determine the corrections to the leading-order, capillary-wave-like, Goldstone mode divergence of S (z;q) known to occur for parallel (i.e. measured along the interface) wavevectors [Formula: see text]. We show from explicit solution of the inhomogeneous Ornstein-Zernike equation that for distances z far from the interface, where the profile decays exponentially, S (z;q) splits unambiguously into bulk and interfacial contributions. On each side of the interface, the interfacial contributions can be characterised by distinct liquid and gas wavevector dependent surface tensions, [Formula: see text] and [Formula: see text], which are determined solely by the bulk two-body and three-body direct correlation functions. At high temperatures, the wavevector dependence simplifies and is determined almost entirely by the appropriate bulk structure factor, leading to positive rigidity coefficients. Our predictions are confirmed by explicit calculation of S (z;q) within square-gradient theory and the Sullivan model. The results for the latter predict a striking temperature dependence for [Formula: see text] and [Formula: see text], and have implications for fluctuation effects. Our results account quantitatively for the findings of a recent very extensive simulation study by Höfling and Dietrich of the total structure factor in the interfacial region, in a system with a cut-off Lennard-Jones potential, in sharp contrast to extended capillary-wave models which failed completely to describe the simulation results. PMID:27115774

  14. An extended structure-function model and its application to the analysis of solar wind intermittency

    NASA Technical Reports Server (NTRS)

    Tu, C.-Y.; Marsch, E.; Rosenbauer, H.

    1995-01-01

    An extended structure-function model is developed by including the new effect in the p-model of Meneveau and Sreenivasan (1987a), i.e., that the averaged energy cascade rate changes with scale, a situation which has been found to prevail in non-fully-developed turbulence in the inner solar wind. This model is useful for the small-scale fluctuations in the inner heliosphere, where the turbulence is not fully developed and cannot be explained quantitatively by any of the previous intermittency turbulence models. With two model parameters, the intrinsic index of the energy spectrum, alpha and the fragmentation fraction p, the model can fit, for the first time, all the observed scaling exponents of the structure functions, which are calculated for time lags ranging from 81 seconds to 0.7 hours from the Helios solar wind data. From the cases we studied we can establish for p neither a clear radial evolution trend, nor a solar-wind-speed, or stream-structure dependence, or a systematic anisotropy for both the flow velocity and magnetic field component fluctuations. Generally, p has values between 0. 7 and 0.8. However, in some cases in low-speed wind p has somewhat higher values for the magnetic components, especially for the radial component. In high-speed wind, the inferred intrinsic spectral indices (alpha) of the velocity and magnetic field components are about equal, while the experimental spectral indices derived from the observed power spectra differ. The magnetic index is somewhat larger than the index of the velocity spectrum. For magnetic fluctuations in both high- and low-speed winds, the intrinsic exponent alpha has values which are near 1.5, while the observed spectral exponent has much higher values.

  15. The local structure factor near an interface; beyond extended capillary-wave models

    NASA Astrophysics Data System (ADS)

    Parry, A. O.; Rascón, C.; Evans, R.

    2016-06-01

    We investigate the local structure factor S (zq) at a free liquid–gas interface in systems with short-ranged intermolecular forces and determine the corrections to the leading-order, capillary-wave-like, Goldstone mode divergence of S (zq) known to occur for parallel (i.e. measured along the interface) wavevectors q\\to 0 . We show from explicit solution of the inhomogeneous Ornstein–Zernike equation that for distances z far from the interface, where the profile decays exponentially, S (zq) splits unambiguously into bulk and interfacial contributions. On each side of the interface, the interfacial contributions can be characterised by distinct liquid and gas wavevector dependent surface tensions, {σ l}(q) and {σg}(q) , which are determined solely by the bulk two-body and three-body direct correlation functions. At high temperatures, the wavevector dependence simplifies and is determined almost entirely by the appropriate bulk structure factor, leading to positive rigidity coefficients. Our predictions are confirmed by explicit calculation of S (zq) within square-gradient theory and the Sullivan model. The results for the latter predict a striking temperature dependence for {σ l}(q) and {σg}(q) , and have implications for fluctuation effects. Our results account quantitatively for the findings of a recent very extensive simulation study by Höfling and Dietrich of the total structure factor in the interfacial region, in a system with a cut-off Lennard-Jones potential, in sharp contrast to extended capillary-wave models which failed completely to describe the simulation results.

  16. Item-Level Psychometrics of the Glasgow Outcome Scale: Extended Structured Interviews.

    PubMed

    Hong, Ickpyo; Li, Chih-Ying; Velozo, Craig A

    2016-04-01

    The Glasgow Outcome Scale-Extended (GOSE) structured interview captures critical components of activities and participation, including home, shopping, work, leisure, and family/friend relationships. Eighty-nine community dwelling adults with mild-moderate traumatic brain injury (TBI) were recruited (average = 2.7 year post injury). Nine items of the 19 items were used for the psychometrics analysis purpose. Factor analysis and item-level psychometrics were investigated using the Rasch partial-credit model. Although the principal components analysis of residuals suggests that a single measurement factor dominates the measure, the instrument did not meet the factor analysis criteria. Five items met the rating scale criteria. Eight items fit the Rasch model. The instrument demonstrated low person reliability (0.63), low person strata (2.07), and a slight ceiling effect. The GOSE demonstrated limitations in precisely measuring activities/participation for individuals after TBI. Future studies should examine the impact of the low precision of the GOSE on effect size. PMID:27504879

  17. Fine-structure constant constraints on dark energy. II. Extending the parameter space

    NASA Astrophysics Data System (ADS)

    Martins, C. J. A. P.; Pinho, A. M. M.; Carreira, P.; Gusart, A.; López, J.; Rocha, C. I. S. A.

    2016-01-01

    Astrophysical tests of the stability of fundamental couplings, such as the fine-structure constant α , are a powerful probe of new physics. Recently these measurements, combined with local atomic clock tests and Type Ia supernova and Hubble parameter data, were used to constrain the simplest class of dynamical dark energy models where the same degree of freedom is assumed to provide both the dark energy and (through a dimensionless coupling, ζ , to the electromagnetic sector) the α variation. One caveat of these analyses was that it was based on fiducial models where the dark energy equation of state was described by a single parameter (effectively its present day value, w0). Here we relax this assumption and study broader dark energy model classes, including the Chevallier-Polarski-Linder and early dark energy parametrizations. Even in these extended cases we find that the current data constrains the coupling ζ at the 1 0-6 level and w0 to a few percent (marginalizing over other parameters), thus confirming the robustness of earlier analyses. On the other hand, the additional parameters are typically not well constrained. We also highlight the implications of our results for constraints on violations of the weak equivalence principle and improvements to be expected from forthcoming measurements with high-resolution ultrastable spectrographs.

  18. Consider neuromusculoskeletal redundancy and extended proprioception when designing smart structures to interface with humans

    NASA Astrophysics Data System (ADS)

    Winters, Jack M.

    1996-05-01

    Despite many well-intentioned attempts to utilize state-of-the-art advanced control systems technology to design contact devices such as powered orthoses, there have been more failures than successes. In part this is due to our limited understanding of neuromechanical function, and of how to optimally design human-technology interfaces. This paper develops a theoretical foundation for mechanical impedance and postural stability for large-scale human systems, and for the analysis and design of human-technology contact interfaces. We start with four basic presuppositions: redundancy is a fundamental feature of biosystem design, muscle actuators possess intrinsic nonlinear stiffness which can be modulated, mechanical interaction between the human and an environment is fundamentally bicausal, and objects with certain properties can become almost a natural extension of the human body. We then develop the key concepts of intimate contact and extended proprioception, and provide examples of how these principles can be applied to practical problems in orthotics, focusing on posture-assist technologies. Finally, suggestions are put forward for applying smart materials and structures to innovative orthotic design.

  19. Extended Kalman filtering for the detection of damage in linear mechanical structures

    NASA Astrophysics Data System (ADS)

    Liu, X.; Escamilla-Ambrosio, P. J.; Lieven, N. A. J.

    2009-09-01

    This paper addresses the problem of assessing the location and extent of damage in a vibrating structure by means of vibration measurements. Frequency domain identification methods (e.g. finite element model updating) have been widely used in this area while time domain methods such as the extended Kalman filter (EKF) method, are more sparsely represented. The difficulty of applying EKF in mechanical system damage identification and localisation lies in: the high computational cost, the dependence of estimation results on the initial estimation error covariance matrix P(0), the initial value of parameters to be estimated, and on the statistics of measurement noise R and process noise Q. To resolve these problems in the EKF, a multiple model adaptive estimator consisting of a bank of EKF in modal domain was designed, each filter in the bank is based on different P(0). The algorithm was iterated by using the weighted global iteration method. A fuzzy logic model was incorporated in each filter to estimate the variance of the measurement noise R. The application of the method is illustrated by simulated and real examples.

  20. Computational extended magneto-hydrodynamical study of shock structure generated by flows past an obstacle

    SciTech Connect

    Zhao, Xuan; Seyler, C. E.

    2015-07-15

    The magnetized shock problem is studied in the context where supersonic plasma flows past a solid obstacle. This problem exhibits interesting and important phenomena such as a bow shock, magnetotail formation, reconnection, and plasmoid formation. This study is carried out using a discontinuous Galerkin method to solve an extended magneto-hydrodynamic model (XMHD). The main goals of this paper are to present a reasonably complete picture of the properties of this interaction using the MHD model and then to compare the results to the XMHD model. The inflow parameters, such as the magnetosonic Mach number M{sub f} and the ratio of thermal pressure to magnetic pressure β, can significantly affect the physical structures of the flow-obstacle interaction. The Hall effect can also significantly influence the results in the regime in which the ion inertial length is numerically resolved. Most of the results presented are for the two-dimensional case; however, two three-dimensional simulations are presented to make a connection to the important case in which the solar wind interacts with a solid body and to explore the possibility of performing scaled laboratory experiments.

  1. Enhanced traveling wave amplification of co-planar slow wave structure by extended phase-matching

    SciTech Connect

    Palm, Andrew; Sirigiri, Jagadishwar; Shin, Young-Min

    2015-09-15

    The electron beam co-propagating with slow waves in a staggered double grating array (SDGA) efficiently amplifies millimeter and sub-millimeter waves over a wide spectrum. Our theoretical and numerical analyses show that the power amplification in the fundamental passband is enhanced by the extended beam-wave phase-matching. Particle-in-cell simulations on the SDGA slow wave structure, designed with 10.4 keV and 50–100 mA sheet beam, indicate that maintaining beam-wave synchronization along the entire length of the circuit improves the gain by 7.3% leading to a total gain of 28 dB, corresponding to 62 W saturated power at the middle of operating band, and a 3-dB bandwidth of 7 GHz with 10.5% at V-band (73.5 GHz center frequency) with saturated peak power reaching 80 W and 28 dB at 71 GHz. These results also show a reasonably good agreement with analytic calculations based on Pierce small signal gain theory.

  2. Emulsification of partially miscible liquids using colloidal particles: nonspherical and extended domain structures.

    PubMed

    Clegg, Paul S; Herzig, Eva M; Schofield, Andrew B; Egelhaaf, Stefan U; Horozov, Tommy S; Binks, Bernard P; Cates, Michael E; Poon, Wilson C K

    2007-05-22

    We present microscopy studies of particle-stabilized emulsions with unconventional morphologies. The emulsions comprise pairs of partially miscible fluids and are stabilized by colloids. Alcohol-oil mixtures are employed; silica colloids are chemically modified so that they have partial wettability. We create our morphologies by two distinct routes: starting with a conventional colloid-stabilized emulsion or starting in the single-fluid phase with the colloids dispersed. In the first case temperature cycling leads to the creation of extended fluid domains built around some of the initial fluid droplets. In the second case quenching into the demixed region leads to the formation of domains which reflect the demixing kinetics. The structures are stable due to a jammed, semisolid, multilayer of colloids on the liquid-liquid interface. The differing morphologies reflect the roles in formation of the arrested state of heterogeneous and homogeneous nucleation and spinodal decomposition. The latter results in metastable, bicontinuous emulsions with frozen interfaces, at least for the thin-slab samples, investigated here. PMID:17439257

  3. Correlative nanoscale 3D imaging of structure and composition in extended objects.

    PubMed

    Xu, Feng; Helfen, Lukas; Suhonen, Heikki; Elgrabli, Dan; Bayat, Sam; Reischig, Péter; Baumbach, Tilo; Cloetens, Peter

    2012-01-01

    Structure and composition at the nanoscale determine the behavior of biological systems and engineered materials. The drive to understand and control this behavior has placed strong demands on developing methods for high resolution imaging. In general, the improvement of three-dimensional (3D) resolution is accomplished by tightening constraints: reduced manageable specimen sizes, decreasing analyzable volumes, degrading contrasts, and increasing sample preparation efforts. Aiming to overcome these limitations, we present a non-destructive and multiple-contrast imaging technique, using principles of X-ray laminography, thus generalizing tomography towards laterally extended objects. We retain advantages that are usually restricted to 2D microscopic imaging, such as scanning of large areas and subsequent zooming-in towards a region of interest at the highest possible resolution. Our technique permits correlating the 3D structure and the elemental distribution yielding a high sensitivity to variations of the electron density via coherent imaging and to local trace element quantification through X-ray fluorescence. We demonstrate the method by imaging a lithographic nanostructure and an aluminum alloy. Analyzing a biological system, we visualize in lung tissue the subcellular response to toxic stress after exposure to nanotubes. We show that most of the nanotubes are trapped inside alveolar macrophages, while a small portion of the nanotubes has crossed the barrier to the cellular space of the alveolar wall. In general, our method is non-destructive and can be combined with different sample environmental or loading conditions. We therefore anticipate that correlative X-ray nano-laminography will enable a variety of in situ and in operando 3D studies. PMID:23185554

  4. Characterization of basin concrete in support of structural integrity demonstration for extended storage

    SciTech Connect

    Duncan, A.

    2014-09-30

    Concrete core samples from C basin were characterized through material testing and analysis to verify the design inputs for structural analysis of the L Basin and to evaluate the type and extent of changes in the material condition of the concrete under extended service for fuel storage. To avoid the impact on operations, core samples were not collected from L area, but rather, several concrete core samples were taken from the C Basin prior to its closure. C basin was selected due to its similar environmental exposure and service history compared to L Basin. The microstructure and chemical composition of the concrete exposed to the water was profiled from the water surface into the wall to evaluate the impact and extent of exposure. No significant leaching of concrete components was observed. Ingress of carbonation or deleterious species was determined to be insignificant. No evidence of alkali-silica reactions (ASR) was observed. Ettringite was observed to form throughout the structure (in air voids or pores); however, the sulfur content was measured to be consistent with the initial concrete that was used to construct the facility. Similar ettringite trends were observed in the interior segments of the core samples. The compressive strength of the concrete at the mid-wall of the basin was measured, and similar microstructural analysis was conducted on these materials post compression testing. The microstructure was determined to be similar to near-surface segments of the core samples. The average strength was 4148 psi, which is well-above the design strength of 2500 psi. The analyses showed that phase alterations and minor cracking in a microstructure did not affect the design specification for the concrete.

  5. Correlative Nanoscale 3D Imaging of Structure and Composition in Extended Objects

    PubMed Central

    Xu, Feng; Helfen, Lukas; Suhonen, Heikki; Elgrabli, Dan; Bayat, Sam; Reischig, Péter; Baumbach, Tilo; Cloetens, Peter

    2012-01-01

    Structure and composition at the nanoscale determine the behavior of biological systems and engineered materials. The drive to understand and control this behavior has placed strong demands on developing methods for high resolution imaging. In general, the improvement of three-dimensional (3D) resolution is accomplished by tightening constraints: reduced manageable specimen sizes, decreasing analyzable volumes, degrading contrasts, and increasing sample preparation efforts. Aiming to overcome these limitations, we present a non-destructive and multiple-contrast imaging technique, using principles of X-ray laminography, thus generalizing tomography towards laterally extended objects. We retain advantages that are usually restricted to 2D microscopic imaging, such as scanning of large areas and subsequent zooming-in towards a region of interest at the highest possible resolution. Our technique permits correlating the 3D structure and the elemental distribution yielding a high sensitivity to variations of the electron density via coherent imaging and to local trace element quantification through X-ray fluorescence. We demonstrate the method by imaging a lithographic nanostructure and an aluminum alloy. Analyzing a biological system, we visualize in lung tissue the subcellular response to toxic stress after exposure to nanotubes. We show that most of the nanotubes are trapped inside alveolar macrophages, while a small portion of the nanotubes has crossed the barrier to the cellular space of the alveolar wall. In general, our method is non-destructive and can be combined with different sample environmental or loading conditions. We therefore anticipate that correlative X-ray nano-laminography will enable a variety of in situ and in operando 3D studies. PMID:23185554

  6. A surface extended X-ray absorption fine structure study of tellurium adsorbed onto Si(100)

    NASA Astrophysics Data System (ADS)

    Burgess, S. R.; Cowie, B. C. C.; Wilks, S. P.; Dunstan, P. R.; Dunscombe, C. J.; Williams, R. H.

    1996-09-01

    The adsorption of tellurium on Si(100) has been studied using surface extended X-ray adsorption fine structure (SEXAFS) and X-ray standing wave spectroscopy (XSW). This particular system is of interest due to its potential applicability in the surfactant aided growth of CdHgTeCdTeSi(100) based infra-red detectors. The Te/Si(100) structure was generated by depositing a thick layer (˜ 100 Å) of CdTe onto a clean Si (2 × 1) double domain surface, and annealing the sample to 350°C. This resulted is a ˜ 1 ML Te terminated surface where the (2 × 1) reconstruction was lost in favour of a (1 × 1) symmetry. X-ray absorption of the Te L 3 edge ( E = 4341 eV), with a photon energy range of 4440-4700 eV, was probed using a total yield detection scheme. The SEXAFS results indicated that the Te atoms sat in 2-fold bridge sites directly above a fourth layer Si atom. The corresponding bond length was measured to be 2.52 ± 0.05 Å. The XSW measurements of the (400) reflection gave a coherent position of 1.63 ± 0.03 Å and a coherent fraction of 0.65. This is consistent with the breaking of the SiSi dimers and thus could be an example of the phenomena of adsorbate-induced dereconstruction of the surface. These results are compared with those of Bennet et al. who examined a similar system using soft X-ray photoemission (SXPS) and the STM study of Yoshikawa et al.

  7. Extended-X-ray-absorption-fine-structure investigations of zinc in 5-aminolaevulinate dehydratase.

    PubMed Central

    Hasnain, S S; Wardell, E M; Garner, C D; Schlösser, M; Beyersmann, D

    1985-01-01

    The zinc co-ordination in 5-aminolaevulinate dehydratase (5-aminolaevulinate hydro-lyase, EC 4.2.1.24) was investigated by recording and interpreting the extended X-ray-absorption fine structure (e.x.a.f.s.) associated with the zinc K-edge. The enzyme has a molecular mass of 280 000 Da and consists of eight subunits of 35 000 Da each; the samples studied contained approx. 1 g-atom of zinc/mol of subunit. Four forms of the enzyme were investigated and details of the zinc environment were elucidated, as follows. In the native enzyme, zinc is considered to be co-ordinated to three sulphur atoms at 0.228(2)nm [2.28(2)A] and a lower-Z atom at 0.192(5)nm [1.92(5)A] (if nitrogen) or 0.189(5)nm [1.89(5)A] (if oxygen). Reaction of the enzyme with the inhibitor 2-bromo-3-(imidazol-5-yl)propionic acid produced significant changes in the e.x.a.f.s., the nature of which are consistent with co-ordination by about three sulphur atoms at 0.222(2)nm [2.22(2)A], a nitrogen atom at 0.193(5)nm [1.93(5)A] and a nitrogen atom from the inhibitor at 0.214(5)nm [2.14(5)A]. Inactivation of the enzyme by air-oxidation of essential thiol groups and binding of the substrate produce slight changes in the e.x.a.f.s. consistent with slight re-arrangement of ligands with additional lighter ligands (nitrogen or oxygen). These results, when combined with previous findings, are taken to indicate that zinc has a structural rather than a direct catalytic role in 5-aminolaevulinate dehydratase. PMID:4062868

  8. The electronic structure of Fe2+ in reaction centers from Rhodopseudomonas sphaeroides. II. Extended x-ray fine structure studies.

    PubMed Central

    Eisenberger, P; Okamura, M Y; Feher, G

    1982-01-01

    Extended x-ray absorption fine structure (EXAFS) studies were performed on reaction centers (RC) of the photosynthetic bacterium Rhodopseudomonas sphaeroides R-26. RC containing two, one, and no quinones (2Q, 1Q, 0Q) samples were studied. The average ligand distance of the first coordination shell was determined to be 2.10 +/- 0.02 A with a more distant shell at 4.14 +/- 0.05 A. The Fe2+ site in RC was found to have a very large structural disorder parameter, from which a spread in ligand distance per iron site of approximately +/- 0.1 A was deduced. The most likely coordination number of the first shell is six, with a mixture of oxygens and nitrogens as ligands. The edge absorption results are consistent with the Fe2+ being in distorted octahedral environment. The EXAFS spectra of the 2Q and 1Q samples with and without O-phenanthroline were found to be the same. This indicates that either the secondary quinone and o-phenanthroline do not bind to Fe2+ or that they replace an equivalent ligand. The 0Q sample showed a 12% decrease in the EXAFS amplitude, which was restored upon addition of o-phenanthroline. These results can be explained by either a loss of a ligand or a severe conformational change when the primary quinone was removed. PMID:6977381

  9. Evolutionary dynamics of phenotype-structured populations: from individual-level mechanisms to population-level consequences

    NASA Astrophysics Data System (ADS)

    Chisholm, Rebecca H.; Lorenzi, Tommaso; Desvillettes, Laurent; Hughes, Barry D.

    2016-08-01

    Epigenetic mechanisms are increasingly recognised as integral to the adaptation of species that face environmental changes. In particular, empirical work has provided important insights into the contribution of epigenetic mechanisms to the persistence of clonal species, from which a number of verbal explanations have emerged that are suited to logical testing by proof-of-concept mathematical models. Here, we present a stochastic agent-based model and a related deterministic integrodifferential equation model for the evolution of a phenotype-structured population composed of asexually-reproducing and competing organisms which are exposed to novel environmental conditions. This setting has relevance to the study of biological systems where colonising asexual populations must survive and rapidly adapt to hostile environments, like pathogenesis, invasion and tumour metastasis. We explore how evolution might proceed when epigenetic variation in gene expression can change the reproductive capacity of individuals within the population in the new environment. Simulations and analyses of our models clarify the conditions under which certain evolutionary paths are possible and illustrate that while epigenetic mechanisms may facilitate adaptation in asexual species faced with environmental change, they can also lead to a type of "epigenetic load" and contribute to extinction. Moreover, our results offer a formal basis for the claim that constant environments favour individuals with low rates of stochastic phenotypic variation. Finally, our model provides a "proof of concept" of the verbal hypothesis that phenotypic stability is a key driver in rescuing the adaptive potential of an asexual lineage and supports the notion that intense selection pressure can, to an extent, offset the deleterious effects of high phenotypic instability and biased epimutations, and steer an asexual population back from the brink of an evolutionary dead end.

  10. The C9ORF72 expansion mutation: gene structure, phenotypic and diagnostic issues.

    PubMed

    Woollacott, Ione O C; Mead, Simon

    2014-03-01

    The discovery of the C9ORF72 hexanucleotide repeat expansion in 2011 and the immediate realisation of a remarkably high prevalence in both familial and sporadic frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) triggered an explosion of interest in studies aiming to define the associated clinical and investigation phenotypes and attempts to develop technologies to measure more accurately the size of the repeat region. This article reviews progress in these areas over the subsequent 2 years, focussing on issues directly relevant to the practising physician. First, we summarise findings from studies regarding the global prevalence of the expansion, not only in FTLD and ALS cases, but also in other neurological diseases and its concurrence with other genetic mutations associated with FTLD and ALS. Second, we discuss the variability in normal repeat number in cases and controls and the theories regarding the relevance of intermediate and pathological repeat number for disease risk and clinical phenotype. Third, we discuss the usefulness of various features within the FTLD and ALS clinical phenotype in aiding differentiation between cases with and without the C9ORF72 expansion. Fourth, we review clinical investigations used to identify cases with the expansion, including neuroimaging and cerebrospinal fluid markers, and describe the mechanisms and limitations of the various diagnostic laboratory techniques used to quantify repeat number in cases and controls. Finally, we discuss the issues surrounding accurate clinical and technological diagnosis of patients with FTLD and/or ALS associated with the C9ORF72 expansion, and outline areas for future research that might aid better diagnosis and genetic counselling of patients with seemingly sporadic or familial FTLD or ALS and their relatives. PMID:24515836

  11. Structure and development of old-growth, unmanaged second-growth, and extended rotation Pinus resinosa forests in Minnesota, USA

    USGS Publications Warehouse

    Silver, Emily J.; D'Amato, Anthony W.; Fraver, Shawn; Palik, Brian J.; Bradford, John B.

    2013-01-01

    The structure and developmental dynamics of old-growth forests often serve as important baselines for restoration prescriptions aimed at promoting more complex structural conditions in managed forest landscapes. Nonetheless, long-term information on natural patterns of development is rare for many commercially important and ecologically widespread forest types. Moreover, the effectiveness of approaches recommended for restoring old-growth structural conditions to managed forests, such as the application of extended rotation forestry, has been little studied. This study uses several long-term datasets from old growth, extended rotation, and unmanaged second growth Pinus resinosa (red pine) forests in northern Minnesota, USA, to quantify the range of variation in structural conditions for this forest type and to evaluate the effectiveness of extended rotation forestry at promoting the development of late-successional structural conditions. Long-term tree population data from permanent plots for one of the old-growth stands and the extended rotation stands (87 and 61 years, respectively) also allowed for an examination of the long-term structural dynamics of these systems. Old-growth forests were more structurally complex than unmanaged second-growth and extended rotation red pine stands, due in large part to the significantly higher volumes of coarse woody debris (70.7 vs. 11.5 and 4.7 m3/ha, respectively) and higher snag basal area (6.9 vs. 2.9 and 0.5 m2/ha, respectively). In addition, old-growth forests, although red pine-dominated, contained a greater abundance of other species, including Pinus strobus, Abies balsamea, and Picea glauca relative to the other stand types examined. These differences between stand types largely reflect historic gap-scale disturbances within the old-growth systems and their corresponding structural and compositional legacies. Nonetheless, extended rotation thinning treatments, by accelerating advancement to larger tree diameter

  12. Detection of Healthcare-Related Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Transmission Events Using Combined Genetic and Phenotypic Epidemiology

    PubMed Central

    Boers, Stefan A.; Jansen, Ruud; Hays, John P.; Goessens, Wil H. F.; Vos, Margreet C.

    2016-01-01

    Background Since the year 2000 there has been a sharp increase in the prevalence of healthcare-related infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. However, the high community prevalence of ESBL-producing E. coli isolates means that many E. coli typing techniques may not be suitable for detecting E. coli transmission events. Therefore, we investigated if High-throughput MultiLocus Sequence Typing (HiMLST) and/or Raman spectroscopy were suitable techniques for detecting recent E. coli transmission events. Methods This study was conducted from January until December 2010 at Erasmus University Medical Center, Rotterdam, the Netherlands. Isolates were typed using HiMLST and Raman spectroscopy. A genetic cluster was defined as two or more patients carrying identical isolates. We used predefined definitions for epidemiological relatedness to assess healthcare-related transmission. Results We included 194 patients; strains of 112 patients were typed using HiMLST and strains of 194 patients were typed using Raman spectroscopy. Raman spectroscopy identified 16 clusters while HiMLST identified 10 clusters. However, no healthcare-related transmission events were detected. When combining data from both typing techniques, we identified eight clusters (n = 34 patients), as well as 78 patients with a non-cluster isolate. However, we could not detect any healthcare-related transmission in these 8 clusters. Conclusions Although clusters were genetically detected using HiMLST and Raman spectroscopy, no definite epidemiological relationships could be demonstrated which makes the possibility of healthcare-related transmission events highly unlikely. Our results suggest that typing of ESBL-producing E. coli using HiMLST and/or Raman spectroscopy is not helpful in detecting E. coli healthcare-related transmission events. PMID:27463231

  13. Structural and Functional Concepts in Current Mouse Phenotyping and Archiving Facilities

    PubMed Central

    Kollmus, Heike; Post, Rainer; Brielmeier, Markus; Fernández, Julia; Fuchs, Helmut; McKerlie, Colin; Montoliu, Lluis; Otaegui, Pedro J; Rebelo, Manuel; Riedesel, Hermann; Ruberte, Jesús; Sedlacek, Radislav; de Angelis, Martin Hrabě; Schughart, Klaus

    2012-01-01

    Collecting and analyzing available information on the building plans, concepts, and workflow from existing animal facilities is an essential prerequisite for most centers that are planning and designing the construction of a new animal experimental research unit. Here, we have collected and analyzed such information in the context of the European project Infrafrontier, which aims to develop a common European infrastructure for high-throughput systemic phenotyping, archiving, and dissemination of mouse models. A team of experts visited 9 research facilities and 3 commercial breeders in Europe, Canada, the United States, and Singapore. During the visits, detailed data of each facility were collected and subsequently represented in standardized floor plans and descriptive tables. These data showed that because the local needs of scientists and their projects, property issues, and national and regional laws require very specific solutions, a common strategy for the construction of such facilities does not exist. However, several basic concepts were apparent that can be described by standardized floor plans showing the principle functional units and their interconnection. Here, we provide detailed information of how individual facilities addressed their specific needs by using different concepts of connecting the principle units. Our analysis likely will be valuable to research centers that are planning to design new mouse phenotyping and archiving facilities. PMID:23043807

  14. Structural and functional concepts in current mouse phenotyping and archiving facilities.

    PubMed

    Kollmus, Heike; Post, Rainer; Brielmeier, Markus; Fernández, Julia; Fuchs, Helmut; McKerlie, Colin; Montoliu, Lluis; Otaegui, Pedro J; Rebelo, Manuel; Riedesel, Hermann; Ruberte, Jesús; Sedlacek, Radislav; de Angelis, Martin Hrabě; Schughart, Klaus

    2012-07-01

    Collecting and analyzing available information on the building plans, concepts, and workflow from existing animal facilities is an essential prerequisite for most centers that are planning and designing the construction of a new animal experimental research unit. Here, we have collected and analyzed such information in the context of the European project Infrafrontier, which aims to develop a common European infrastructure for high-throughput systemic phenotyping, archiving, and dissemination of mouse models. A team of experts visited 9 research facilities and 3 commercial breeders in Europe, Canada, the United States, and Singapore. During the visits, detailed data of each facility were collected and subsequently represented in standardized floor plans and descriptive tables. These data showed that because the local needs of scientists and their projects, property issues, and national and regional laws require very specific solutions, a common strategy for the construction of such facilities does not exist. However, several basic concepts were apparent that can be described by standardized floor plans showing the principle functional units and their interconnection. Here, we provide detailed information of how individual facilities addressed their specific needs by using different concepts of connecting the principle units. Our analysis likely will be valuable to research centers that are planning to design new mouse phenotyping and archiving facilities. PMID:23043807

  15. Structural and Theoretical Studies Indicate that the Cylindrical Protease ClpP Samples Extended and Compact Conformations

    SciTech Connect

    Kimber, Matthew S.; Yu, Angela Yeou Hsiung; Borg, Mikael; Leung, Elisa; Chan, Hue Sun; Houry, Walid A.

    2010-09-21

    The highly conserved ClpP protease consists of two heptameric rings that interact by the interdigitation of an {alpha}-helix {beta} strand handle domain motif to form a tetradecameric cylinder. We previously proposed that protease dynamics results in the temporary unstructuring of interacting pairs of handle domains, opening transient equatorial side pores that allow for peptide egress. Here, we report the structure of an Escherichia coli ClpP mutant in which each opposing pair of protomers is linked by a disulfide bond. This structure resembles the compact structures of Streptococcus pneumoniae, Mycobacterium tuberculosis, and Plasmodium falciparum ClpPs, rather than the active, extended structures that have previously been determined for E. coli ClpPs. The structural data, along with normal mode analysis, support a model whereby the ClpP cylinder switches dynamically between an active extended state required for substrate degradation and an inactive compact state allowing peptide product release.

  16. The Mud Hills, Mojave Desert, California: Structure, stratigraphy and sedimentology of a rapidly extended terrane

    SciTech Connect

    Ingersoll, R.V.; Devaney, K.A.; Geslin, J.K.; Cavazza, W.; Diamond, D.S.; Jagiello, K.J.; Marsaglia, K.M.; Paylor, E.D. II; Short, P.F. . Dept. of Earth and Space Sciences)

    1993-04-01

    The Mud Hills exposes synorogenic breccia (Mud Hills Fm.) deposited during the final stages of crustal extension of the upper plate above the Waterman Hills detachment (20--18 Ma). Previous workers have misinterpreted fault contacts as stratigraphic contacts, and have developed intricate pseudostratigraphy to explain their observations. The authors' detailed mapping, combined with stratigraphic and sedimentologic data, documents that the volcaniclastic Pickhandle Fm. is conformably overlain by the plutoniclastic Mud Hills Fm., with no interfingering. Repetition of these south-dipping lithologic units is due to imbricate, north-dipping listric faults. These relations are demonstrated by the systematic northward v''ing of fault contacts and southward v''ing of stratigraphic contacts. Stratigraphic dip decreases upsection, which is consistent with incremental rotation of basinal strata simultaneously with deposition. Most of the Mud Hills Fm. consists of rock-avalanche breccia and megabreccia derived from granodiorite, which is identical to basement exposed beneath the Pickhandle and Jackhammer Fms. to the north. The Mud Hills Fm. was derived from now-buried granodiorite of a stranded upper-plate block to the south, as demonstrated by northward paleocurrents, facies relations and the presence of fine-grained units close to the presumed master fault (as is typical of half-graben sedimentation). Unconformably overlying the Mud Hills Fm. is the Owl Conglomerate (Barstow Fm.), which has mixed provenance with southward paleocurrents; the Owl Conglomerate was derived from residual highlands after extension ceased. Integration of structural, stratigraphic and sedimentologic information is essential for correct reconstruction of highly extended terranes.

  17. Effects of Highly Conserved Major Histocompatibility Complex (MHC) Extended Haplotypes on Iron and Low CD8+ T Lymphocyte Phenotypes in HFE C282Y Homozygous Hemochromatosis Patients from Three Geographically Distant Areas

    PubMed Central

    Barton, James C.; Thorstensen, Ketil; Morais, Sandra; da Silva, Berta M.; Pinto, Jorge P.; Vieira, Cristina P.; Vieira, Jorge; Acton, Ronald T.; Porto, Graça

    2013-01-01

    Hereditary Hemochromatosis (HH) is a recessively inherited disorder of iron overload occurring commonly in subjects homozygous for the C282Y mutation in HFE gene localized on chromosome 6p21.3 in linkage disequilibrium with the human leukocyte antigen (HLA)-A locus. Although its genetic homogeneity, the phenotypic expression is variable suggesting the presence of modifying factors. One such genetic factor, a SNP microhaplotype named A-A-T, was recently found to be associated with a more severe phenotype and also with low CD8+T-lymphocyte numbers. The present study aimed to test whether the predictive value of the A-A-T microhaplotype remained in other population settings. In this study of 304 HH patients from 3 geographically distant populations (Porto, Portugal 65; Alabama, USA 57; Nord-Trøndelag, Norway 182), the extended haplotypes involving A-A-T were studied in 608 chromosomes and the CD8+ T-lymphocyte numbers were determined in all subjects. Patients from Porto had a more severe phenotype than those from other settings. Patients with A-A-T seemed on average to have greater iron stores (p = 0.021), but significant differences were not confirmed in the 3 separate populations. Low CD8+ T-lymphocytes were associated with HLA-A*03-A-A-T in Porto and Alabama patients but not in the greater series from Nord-Trøndelag. Although A-A-T may signal a more severe iron phenotype, this study was unable to prove such an association in all population settings, precluding its use as a universal predictive marker of iron overload in HH. Interestingly, the association between A-A-T and CD8+ T-lymphocytes, which was confirmed in Porto and Alabama patients, was not observed in Nord-Trøndelag patients, showing that common HLA haplotypes like A*01–B*08 or A*03–B*07 segregating with HFE/C282Y in the three populations may carry different messages. These findings further strengthen the relevance of HH as a good disease model to search for novel candidate loci associated with

  18. Phenotypic, Ultra-Structural, and Functional Characterization of Bovine Peripheral Blood Dendritic Cell Subsets

    PubMed Central

    Sei, Janet J.; Ochoa, Amanda S.; Bishop, Elizabeth; Barlow, John W.; Golde, William T.

    2014-01-01

    Dendritic cells (DC) are multi-functional cells that bridge the gap between innate and adaptive immune systems. In bovine, significant information is lacking on the precise identity and role of peripheral blood DC subsets. In this study, we identify and characterize bovine peripheral blood DC subsets directly ex vivo, without further in vitro manipulation. Multi-color flow cytometric analysis revealed that three DC subsets could be identified. Bovine plasmacytoid DC were phenotypically identified by a unique pattern of cell surface protein expression including CD4, exhibited an extensive endoplasmic reticulum and Golgi apparatus, efficiently internalized and degraded exogenous antigen, and were the only peripheral blood cells specialized in the production of type I IFN following activation with Toll-like receptor (TLR) agonists. Conventional DC were identified by expression of a different pattern of cell surface proteins including CD11c, MHC class II, and CD80, among others, the display of extensive dendritic protrusions on their plasma membrane, expression of very high levels of MHC class II and co-stimulatory molecules, efficient internalization and degradation of exogenous antigen, and ready production of detectable levels of TNF-alpha in response to TLR activation. Our investigations also revealed a third novel DC subset that may be a precursor of conventional DC that were MHC class II+ and CD11c−. These cells exhibited a smooth plasma membrane with a rounded nucleus, produced TNF-alpha in response to TLR-activation (albeit lower than CD11c+ DC), and were the least efficient in internalization/degradation of exogenous antigen. These studies define three bovine blood DC subsets with distinct phenotypic and functional characteristics which can be analyzed during immune responses to pathogens and vaccinations of cattle. PMID:25295753

  19. Specific domain structures control abscisic acid-, salicylic acid-, and stress-mediated SIZ1 phenotypes.

    PubMed

    Cheong, Mi Sun; Park, Hyeong Cheol; Hong, Mi Ju; Lee, Jiyoung; Choi, Wonkyun; Jin, Jing Bo; Bohnert, Hans J; Lee, Sang Yeol; Bressan, Ray A; Yun, Dae-Jin

    2009-12-01

    SIZ1 (for yeast SAP and MIZ1) encodes the sole ortholog of mammalian PIAS (for protein inhibitor of activated STAT) and yeast SIZ SUMO (for small ubiquitin-related modifier) E3 ligases in Arabidopsis (Arabidopsis thaliana). Four conserved motifs in SIZ1 include SAP (for scaffold attachment factor A/B/acinus/PIAS domain), PINIT (for proline-isoleucine-asparagine-isoleucine-threonine), SP-RING (for SIZ/PIAS-RING), and SXS (for serine-X-serine, where X is any amino acid) motifs. SIZ1 contains, in addition, a PHD (for plant homeodomain) typical of plant PIAS proteins. We determined phenotypes of siz1-2 knockout mutants transformed with SIZ1 alleles carrying point mutations in the predicted domains. Domain SP-RING is required for SUMO conjugation activity and nuclear localization of SIZ1. Salicylic acid (SA) accumulation and SA-dependent phenotypes of siz1-2, such as diminished plant size, heightened innate immunity, and abscisic acid inhibition of cotyledon greening, as well as SA-independent basal thermotolerance were not complemented by the altered SP-RING allele of SIZ1. The SXS domain also controlled SA accumulation and was involved in greening and expansion of cotyledons of seedlings germinated in the presence of abscisic acid. Mutations of the PHD zinc finger domain and the PINIT motif affected in vivo SUMOylation. Expression of the PHD and/or PINIT domain mutant alleles of SIZ1 in siz1-2 promoted hypocotyl elongation in response to sugar and light. The various domains of SIZ1 make unique contributions to the plant's ability to cope with its environment. PMID:19837819

  20. Decentralized identification of nonlinear structure under strong ground motion using the extended Kalman filter and unscented Kalman filter

    NASA Astrophysics Data System (ADS)

    Tao, Dongwang; Li, Hui; Ma, Qiang

    2016-04-01

    Complete structure identification of complicate nonlinear system using extend Kalman filter (EKF) or unscented Kalman filter (UKF) may have the problems of divergence, huge computation and low estimation precision due to the large dimension of the extended state space for the system. In this article, a decentralized identification method of hysteretic system based on the joint EKF and UKF is proposed. The complete structure is divided into linear substructures and nonlinear substructures. The substructures are identified from the top to the bottom. For the linear substructure, EKF is used to identify the extended space including the displacements, velocities, stiffness and damping coefficients of the substructures, using the limited absolute accelerations and the identified interface force above the substructure. Similarly, for the nonlinear substructure, UKF is used to identify the extended space including the displacements, velocities, stiffness, damping coefficients and control parameters for the hysteretic Bouc-Wen model and the force at the interface of substructures. Finally a 10-story shear-type structure with multiple inter-story hysteresis is used for numerical simulation and is identified using the decentralized approach, and the identified results are compared with those using only EKF or UKF for the complete structure identification. The results show that the decentralized approach has the advantage of more stability, relative less computation and higher estimation precision.

  1. Devices with extended area structures for mass transfer processing of fluids

    DOEpatents

    TeGrotenhuis, Ward E.; Wegeng, Robert S.; Whyatt, Greg A.; King, David L.; Brooks, Kriston P.; Stenkamp, Victoria S.

    2009-04-21

    A microchannel device includes several mass transfer microchannels to receive a fluid media for processing at least one heat transfer microchannel in fluid communication with a heat transfer fluid defined by a thermally conductive wall, and at several thermally conductive fins each connected to the wall and extending therefrom to separate the mass transfer microchannels from one another. In one form, the device may optionally include another heat transfer microchannel and corresponding wall that is positioned opposite the first wall and has the fins and the mass transfer microchannels extending therebetween.

  2. The Matchmaker Exchange API: automating patient matching through the exchange of structured phenotypic and genotypic profiles.

    PubMed

    Buske, Orion J; Schiettecatte, François; Hutton, Benjamin; Dumitriu, Sergiu; Misyura, Andriy; Huang, Lijia; Hartley, Taila; Girdea, Marta; Sobreira, Nara; Mungall, Chris; Brudno, Michael

    2015-10-01

    Despite the increasing prevalence of clinical sequencing, the difficulty of identifying additional affected families is a key obstacle to solving many rare diseases. There may only be a handful of similar patients worldwide, and their data may be stored in diverse clinical and research databases. Computational methods are necessary to enable finding similar patients across the growing number of patient repositories and registries. We present the Matchmaker Exchange Application Programming Interface (MME API), a protocol and data format for exchanging phenotype and genotype profiles to enable matchmaking among patient databases, facilitate the identification of additional cohorts, and increase the rate with which rare diseases can be researched and diagnosed. We designed the API to be straightforward and flexible in order to simplify its adoption on a large number of data types and workflows. We also provide a public test data set, curated from the literature, to facilitate implementation of the API and development of new matching algorithms. The initial version of the API has been successfully implemented by three members of the Matchmaker Exchange and was immediately able to reproduce previously identified matches and generate several new leads currently being validated. The API is available at https://github.com/ga4gh/mme-apis. PMID:26255989

  3. SOS1 Mutations in Noonan Syndrome: Molecular Spectrum, Structural Insights on Pathogenic Effects, and Genotype–Phenotype Correlations

    PubMed Central

    Lepri, Francesca; De Luca, Alessandro; Stella, Lorenzo; Rossi, Cesare; Baldassarre, Giuseppina; Pantaleoni, Francesca; Cordeddu, Viviana; Williams, Bradley J; Dentici, Maria L; Caputo, Viviana; Venanzi, Serenella; Bonaguro, Michela; Kavamura, Ines; Faienza, Maria F; Pilotta, Alba; Stanzial, Franco; Faravelli, Francesca; Gabrielli, Orazio; Marino, Bruno; Neri, Giovanni; Silengo, Margherita Cirillo; Ferrero, Giovanni B; Torrrente, Isabella; Selicorni, Angelo; Mazzanti, Laura; Digilio, Maria C; Zampino, Giuseppe; Dallapiccola, Bruno; Gelb, Bruce D; Tartaglia, Marco

    2011-01-01

    Noonan syndrome (NS) is among the most common nonchromosomal disorders affecting development and growth. NS is caused by aberrant RAS-MAPK signaling and is genetically heterogeneous, which explains, in part, the marked clinical variability documented for this Mendelian trait. Recently, we and others identified SOS1 as a major gene underlying NS. Here, we explored further the spectrum of SOS1 mutations and their associated phenotypic features. Mutation scanning of the entire SOS1 coding sequence allowed the identification of 33 different variants deemed to be of pathological significance, including 16 novel missense changes and in-frame indels. Various mutation clusters destabilizing or altering orientation of regions of the protein predicted to contribute structurally to the maintenance of autoinhibition were identified. Two previously unappreciated clusters predicted to enhance SOS1's recruitment to the plasma membrane, thus promoting a spatial reorientation of domains contributing to inhibition, were also recognized. Genotype–phenotype analysis confirmed our previous observations, establishing a high frequency of ectodermal anomalies and a low prevalence of cognitive impairment and reduced growth. Finally, mutation analysis performed on cohorts of individuals with nonsyndromic pulmonic stenosis, atrial septal defects, and ventricular septal defects excluded a major contribution of germline SOS1 lesions to the isolated occurrence of these cardiac anomalies. Hum Mutat 32:760–772, 2011. © 2011 Wiley-Liss, Inc. PMID:21387466

  4. Tissue phenotype depends on reciprocal interactions between the extracellular matrix and the structural organization of the nucleus

    SciTech Connect

    Lelie'vre, S.A.; Weaver, V.M.; Nickerson, J.A.; Larabell, C.A.; Bhaumik, A.; Petersen, O.W.; Bissell, M.J.

    1998-08-14

    What determines the nuclear organization within a cell and whether this organization itself can impose cellular function within a tissue remains unknown. To explore the relationship between nuclear organization and tissue architecture and function, we used a model of human mammary epithelial cell acinar morphogenesis. When cultured within a reconstituted basement membrane (rBM), HMT-3522 cells form polarized and growth-arrested tissue-like acini with a central lumen and deposit an endogenous BM. We show that rBM-induced morphogenesis is accompanied by relocalization of the nuclear matrix proteins NuMA, splicing factor SRm160, and cell cycle regulator Rb. These proteins had distinct distribution patterns specific for proliferation, growth arrest, and acini formation, whereas the distribution of the nuclear lamina protein, lamin B, remained unchanged. NuMA relocalized to foci, which coalesced into larger assemblies as morphogenesis progressed. Perturbation of histone acetylation in the acini by trichostatin A treatment altered chromatin structure, disrupted NuMA foci, and induced cell proliferation. Moreover, treatment of transiently permeabilized acini with a NuMA antibody led to the disruption of NuMA foci, alteration of histone acetylation, activation of metalloproteases, and breakdown of the endogenous BM. These results experimentally demonstrate a dynamic interaction between the extracellular matrix, nuclear organization, and tissue phenotype. They further show that rather than passively ref lecting changes in gene expression, nuclear organization itself can modulate the cellular and tissue phenotype.

  5. Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals

    PubMed Central

    Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C.; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M.; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

    2014-01-01

    The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry. PMID:25254375

  6. Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals.

    PubMed

    Ruiz-Linares, Andrés; Adhikari, Kaustubh; Acuña-Alonzo, Victor; Quinto-Sanchez, Mirsha; Jaramillo, Claudia; Arias, William; Fuentes, Macarena; Pizarro, María; Everardo, Paola; de Avila, Francisco; Gómez-Valdés, Jorge; León-Mimila, Paola; Hunemeier, Tábita; Ramallo, Virginia; Silva de Cerqueira, Caio C; Burley, Mari-Wyn; Konca, Esra; de Oliveira, Marcelo Zagonel; Veronez, Mauricio Roberto; Rubio-Codina, Marta; Attanasio, Orazio; Gibbon, Sahra; Ray, Nicolas; Gallo, Carla; Poletti, Giovanni; Rosique, Javier; Schuler-Faccini, Lavinia; Salzano, Francisco M; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; Balding, David; Gonzalez-José, Rolando

    2014-09-01

    The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry. PMID:25254375

  7. Viroids: From Genotype to Phenotype Just Relying on RNA Sequence and Structural Motifs

    PubMed Central

    Flores, Ricardo; Serra, Pedro; Minoia, Sofía; Di Serio, Francesco; Navarro, Beatriz

    2012-01-01

    As a consequence of two unique physical properties, small size and circularity, viroid RNAs do not code for proteins and thus depend on RNA sequence/structural motifs for interacting with host proteins that mediate their invasion, replication, spread, and circumvention of defensive barriers. Viroid genomes fold up on themselves adopting collapsed secondary structures wherein stretches of nucleotides stabilized by Watson–Crick pairs are flanked by apparently unstructured loops. However, compelling data show that they are instead stabilized by alternative non-canonical pairs and that specific loops in the rod-like secondary structure, characteristic of Potato spindle tuber viroid and most other members of the family Pospiviroidae, are critical for replication and systemic trafficking. In contrast, rather than folding into a rod-like secondary structure, most members of the family Avsunviroidae adopt multibranched conformations occasionally stabilized by kissing-loop interactions critical for viroid viability in vivo. Besides these most stable secondary structures, viroid RNAs alternatively adopt during replication transient metastable conformations containing elements of local higher-order structure, prominent among which are the hammerhead ribozymes catalyzing a key replicative step in the family Avsunviroidae, and certain conserved hairpins that also mediate replication steps in the family Pospiviroidae. Therefore, different RNA structures – either global or local – determine different functions, thus highlighting the need for in-depth structural studies on viroid RNAs. PMID:22719735

  8. Effect of extended line defects on thermal conduction of carbon nanotubes: analyzing phonon structures by band unfolding

    NASA Astrophysics Data System (ADS)

    Huang, Huaqing

    2015-08-01

    We theoretically investigate the effect of extended line defects (ELDs) on thermal transport properties of carbon nanotubes (CNTs) using nonequilibrium Green’s function method. Our study shows that the thermal conductance of CNTs with ELDs can be 25% lower than that of pristine CNTs. By extending the application of the recently developed unfolding method for electronic structures to phonon spectra, we find that the unfolded phonon bands of defected CNTs are split with obvious gap opening, leading to lower phonon transmissions. Further phonon local density of states analysis reveals that the change of bonding configuration near the ELD in defected CNTs can tail the degree of phonon localization. Our results indicate that introducing ELDs might be an efficient way to control thermal conduction of CNTs. The extended unfolding method for phonon systems, found to be efficient in this work, is expected to be applicable to other systems with densely folded phonon bands.

  9. Pre-adsorbed type-I collagen structure-dependent changes in osteoblastic phenotype

    SciTech Connect

    Hanagata, Nobutaka . E-mail: HANAGATA.Nobutaka@nims.go.jp; Takemura, Taro; Monkawa, Akira; Ikoma, Toshiyuki; Tanaka, Junzo

    2006-06-16

    Type-I collagen is the most abundant extracellular matrix in bones and modulates various functions of osteoblasts. We prepared two different structures of type-I collagen on tissue culture grade polystylene (TCPS) surfaces, one is feltwork structure of filamentous molecules from acid solutions (ACs) and the other is network structure of fibrils from neutral solutions (NCs), to examine effects of the structures on the maturation process of osteoblast-like cells. No significant differences of cell proliferation were observed between TCPS and ACs, but NCs delayed the proliferation. In initial cell attachment, the cells on ACs had tense lamellipodia with sharp tips, while those on NCs had loose lamellipodia. No detectable differences in levels of expressed integrin {alpha}{sub 2}- and {alpha}{sub 5}-subunits were observed between the structures. Although the matrix mineralization in NCs was also delayed in comparison with TCPS and ACs, fully mineralized levels in NCs were the same as those of TCPS and ACs. In addition, although we examined the effects of densities of pre-adsorbed collagen molecules on osteoblast maturation, the effects were less serious than those of the structures. This study suggests that the structures of collagen affect proliferation and mineralization of osteoblast-like cells.

  10. Triplet excitons as sensitive spin probes for structure analysis of extended defects in microcrystalline silicon

    NASA Astrophysics Data System (ADS)

    Meier, Christoph; Teutloff, Christian; Behrends, Jan; Bittl, Robert; Astakhov, Oleksandr; Lips, Klaus

    2016-07-01

    Electrically detected magnetic resonance (EDMR) spectroscopy is employed to study the influence of triplet excitons on the photocurrent in state-of-the-art microcrystalline silicon thin-film solar cells. These triplet excitons are used as sensitive spin probes for the investigation of their electronic and nuclear environment in this mixed-phase material. According to low-temperature EDMR results obtained from solar cells with different extended defects in the crystallites of microcrystalline silicon that give rise to shallow states in the silicon band gap. The excitons possess a rather delocalized wave function, couple to electron spins in conduction band tail states nearby, and take part in a spin-dependent recombination process. Our study shows that extended defects such as grain boundaries or stacking faults in the crystalline part of the material act as charge carrier traps that can influence the material conductivity.

  11. Superconducting extended objects and applications to the phase structure of quantum chromodynamics

    NASA Astrophysics Data System (ADS)

    Skagerstam, B.-S.; Stern, A.

    1982-03-01

    In a previous work the dynamics of relativistic extended objects (i.e., strings, shells, etc.) coupled to Abelian or non-Abelian gauge fields was developed. The extended objects possessed an electriclike current which was defined in the associated Lie algebra of the gauge group under consideration. In the present paper, the interaction between the extended objects and gauge fields is slightly modified so that the objects behave like superconductors. By this we mean (a) the electrical conductivity is infinite and (b) for objects other than strings, a magnetic shielding or Meissner effect (with zero penetration depth) is present. Both (a) and (b) are features which occur in the classical description of the system. We also develop the dynamics for a system which is dual to the one described above. That is, instead of possessing an electric current, the objects here carry a magnetic current (Abelian or non-Abelian). Furthermore, the magnetic conductivity is infinite, and for objects other than strings an electric shielding or "dual" Meissner effect is present. The systems developed here contain Dirac's extended electron model and the MIT bag model as special cases. The former coincides with the description of an electrically charged shell. In the latter, we verify that the dynamics of a cavity within a (magnetic) superconducting vacuum is identical to that of a glueball in the MIT bag. This agrees with the view that the true quantum-chromodynamic (QCD) vacuum may be in a magnetic superconducting phase, and that the "dual" Meissner effect may be relevant for the confinement question. We also examine the possibility of the QCD vacuum being in an electric (or conventional) superconducting phase and a mixed superconducting phase, and comment on the confinement question for these two cases.

  12. Phenotypes in phylogeography: Species’ traits, environmental variation, and vertebrate diversification

    PubMed Central

    Bell, Rayna C.; Mason, Nicholas A.

    2016-01-01

    Almost 30 y ago, the field of intraspecific phylogeography laid the foundation for spatially explicit and genealogically informed studies of population divergence. With new methods and markers, the focus in phylogeography shifted to previously unrecognized geographic genetic variation, thus reducing the attention paid to phenotypic variation in those same diverging lineages. Although phenotypic differences among lineages once provided the main data for studies of evolutionary change, the mechanisms shaping phenotypic differentiation and their integration with intraspecific genetic structure have been underexplored in phylogeographic studies. However, phenotypes are targets of selection and play important roles in species performance, recognition, and diversification. Here, we focus on three questions. First, how can phenotypes elucidate mechanisms underlying concordant or idiosyncratic responses of vertebrate species evolving in shared landscapes? Second, what mechanisms underlie the concordance or discordance of phenotypic and phylogeographic differentiation? Third, how can phylogeography contribute to our understanding of functional phenotypic evolution? We demonstrate that the integration of phenotypic data extends the reach of phylogeography to explain the origin and maintenance of biodiversity. Finally, we stress the importance of natural history collections as sources of high-quality phenotypic data that span temporal and spatial axes. PMID:27432983

  13. Phenotypes in phylogeography: Species' traits, environmental variation, and vertebrate diversification.

    PubMed

    Zamudio, Kelly R; Bell, Rayna C; Mason, Nicholas A

    2016-07-19

    Almost 30 y ago, the field of intraspecific phylogeography laid the foundation for spatially explicit and genealogically informed studies of population divergence. With new methods and markers, the focus in phylogeography shifted to previously unrecognized geographic genetic variation, thus reducing the attention paid to phenotypic variation in those same diverging lineages. Although phenotypic differences among lineages once provided the main data for studies of evolutionary change, the mechanisms shaping phenotypic differentiation and their integration with intraspecific genetic structure have been underexplored in phylogeographic studies. However, phenotypes are targets of selection and play important roles in species performance, recognition, and diversification. Here, we focus on three questions. First, how can phenotypes elucidate mechanisms underlying concordant or idiosyncratic responses of vertebrate species evolving in shared landscapes? Second, what mechanisms underlie the concordance or discordance of phenotypic and phylogeographic differentiation? Third, how can phylogeography contribute to our understanding of functional phenotypic evolution? We demonstrate that the integration of phenotypic data extends the reach of phylogeography to explain the origin and maintenance of biodiversity. Finally, we stress the importance of natural history collections as sources of high-quality phenotypic data that span temporal and spatial axes. PMID:27432983

  14. Structure of the ERM protein moesin reveals the FERM domain fold masked by an extended actin binding tail domain.

    PubMed

    Pearson, M A; Reczek, D; Bretscher, A; Karplus, P A

    2000-04-28

    The ezrin-radixin-moesin (ERM) protein family link actin filaments of cell surface structures to the plasma membrane, using a C-terminal F-actin binding segment and an N-terminal FERM domain, a common membrane binding module. ERM proteins are regulated by an intramolecular association of the FERM and C-terminal tail domains that masks their binding sites. The crystal structure of a dormant moesin FERM/tail complex reveals that the FERM domain has three compact lobes including an integrated PTB/PH/ EVH1 fold, with the C-terminal segment bound as an extended peptide masking a large surface of the FERM domain. This extended binding mode suggests a novel mechanism for how different signals could produce varying levels of activation. Sequence conservation suggests a similar regulation of the tumor suppressor merlin. PMID:10847681

  15. In situ mapping of the effect of additional mutations on starch granule structure in amylose-extender (ae) maize kernels.

    PubMed

    Liu, Dongli; Wellner, Nikolaus; Parker, Mary L; Morris, Victor J; Cheng, Fang

    2015-03-15

    Optical (KI/I2-staining, polarised) and FTIR microscopy has been used to monitor starch granule structure within wild-type (wt), GEMS-0067 and waxy-amylose-extender (wx-ae) maize mutant kernels. In the GEMS-0067 mutant containing the high amylose modifier (HAM) gene(s) plus the recessive ae gene, structural heterogeneity characteristic of the ae mutation was reduced markedly. However, enhanced variation in granule shape and size was observed distributed spatially within the kernel, which appears to be related to new heterogeneity in internal starch granule structure. In wx-ae starch mutants the ae gene led to heterogeneity of starch granule structure equivalent to that in single ae mutants, plus new structural heterogeneity coincident with novel induced variation in granule size and shape. PMID:25542125

  16. Abnormalities in the basement membrane structure promote basal keratinocytes in the epidermis of hypertrophic scars to adopt a proliferative phenotype

    PubMed Central

    YANG, SHAOWEI; SUN, YEXIAO; GENG, ZHIJUN; MA, KUI; SUN, XIAOYAN; FU, XIAOBING

    2016-01-01

    The majority of studies on scar formation have mainly focused on the dermis and little is known of the involvement of the epidermis. Previous research has demonstrated that the scar tissue-derived keratinocytes are different from normal cells at both the genetic and cell biological levels; however, the mechanisms responsible for the fundamental abnormalities in keratinocytes during scar development remain elusive. For this purpose, in this study, we used normal, wound edge and hypertrophic scar tissue to examine the morphological changes which occur during epidermal regeneration as part of the wound healing process and found that the histological structure of hypertrophic scar tissues differed from that of normal skin, with a significant increase in epidermal thickness. Notably, staining of the basement membrane (BM) appeared to be absent in the scar tissues. Moreover, immunofluorescence staining for cytokeratin (CK)10, CK14, CK5, CK19 and integrin-β1 indicated the differential expression of cell markers in the epidermal keratinocytes among the normal, wound edge and hypertrophic scar tissues, which corresponded with the altered BM structures. By using a panel of proteins associated with BM components, we validated our hypothesis that the BM plays a significant role in regulating the cell fate decision of epidermal keratinocytes during skin wound healing. Alterations in the structure of the BM promote basal keratinocytes to adopt a proliferative phenotype both in vivo and in vitro. PMID:26986690

  17. Stereomicroscopic 3D-pattern profiling of murine and human intestinal inflammation reveals unique structural phenotypes

    PubMed Central

    Rodriguez-Palacios, Alex; Kodani, Tomohiro; Kaydo, Lindsey; Pietropaoli, Davide; Corridoni, Daniele; Howell, Scott; Katz, Jeffry; Xin, Wei; Pizarro, Theresa T.; Cominelli, Fabio

    2015-01-01

    Histology is fundamental to assess two-dimensional intestinal inflammation; however, inflammatory bowel diseases (IBDs) are often indistinguishable microscopically on the basis of mucosal biopsies. Here, we use stereomicroscopy (SM) to rapidly profile the entire intestinal topography and assess inflammation. We examine the mucosal surface of >700 mice (encompassing >16 strains and various IBD-models), create a profiling catalogue of 3D-stereomicroscopic abnormalities and demonstrate that mice with comparable histological scores display unique sub-clusters of 3D-structure-patterns of IBD pathology, which we call 3D-stereoenterotypes, and which are otherwise indiscernible histologically. We show that two ileal IBD-stereoenterotypes (‘cobblestones' versus ‘villous mini-aggregation') cluster separately within two distinct mouse lines of spontaneous ileitis, suggesting that host genetics drive unique and divergent inflammatory 3D-structural patterns in the gut. In humans, stereomicroscopy reveals ‘liquefaction' lesions and hierarchical fistulous complexes, enriched with clostridia/segmented filamentous bacteria, running under healthy mucosa in Crohn's disease. We suggest that stereomicroscopic (3D-SMAPgut) profiling can be easily implemented and enable the comprehensive study of inflammatory 3D structures, genetics and flora in IBD. PMID:26154811

  18. Exploring Optically Compact Dwarf Galaxies for Kinematic Structures and Extended HI Halos

    NASA Astrophysics Data System (ADS)

    Most, Hans; Cannon, J. M.; Salzer, J. J.; Rosenberg, J. L.

    2012-01-01

    We present Very Large Array H I spectral line and optical imaging of eight optically compact (optical radii <1 kpc), star-forming dwarf galaxies. These galaxies were chosen because of their optically compact stellar distributions, faint blue magnitudes, ongoing star formation, and relative proximity. The sample includes ADBS 113845+2008, which was found to have an HI halo that extends nearly 40 optical scale lengths from the stellar body (Cannon et al. 2009). Using this larger sample, we are working to discern if the "giant gas disk" dwarf galaxy is common or rare. We are also exploring the kinematics and dark matter contents of each of the sample galaxies.

  19. Extended line defects in BN, GaN, and AlN semiconductor materials: Graphene-like structures

    NASA Astrophysics Data System (ADS)

    Camacho-Mojica, Dulce C.; López-Urías, Florentino

    2016-05-01

    The extended line defect (ELD) mimicking grain boundaries in two-dimensional systems is theoretically investigated in BN, GaN, and AlN semiconductor materials with a single layer honeycomb structure. The ELD consists of octagonal-square membered rings. Density functional calculations of the electronic density of states, scanning tunneling microscopy and transmission electron microscopy image simulations are analyzed. Our results revealed that the ELDs are stable in all considered monolayers. In addition, electronic density of states calculations demonstrated that in gap states are emerged when ELD is incorporated into the honeycomb structures. Finally, results on armchair nanoribbons with bare-edges and hydrogenated edges are discussed.

  20. Extended Bis(benzothia)quinodimethanes and Their Dications: From Singlet Diradicaloids to Isoelectronic Structures of Long Acenes.

    PubMed

    Dong, Shaoqiang; Herng, Tun Seng; Gopalakrishna, Tullimilli Y; Phan, Hoa; Lim, Zheng Long; Hu, Pan; Webster, Richard D; Ding, Jun; Chi, Chunyan

    2016-08-01

    Extended bis(benzothia)quinodimethanes and their dications were synthesized as stable species. The neutral compounds mainly have a quinoidal structure in the ground state but show increased diradical character with extension of the central quinodimethane unit. The dications exhibit similar electronic absorption spectra, NMR spectra, NICS values, and diatropic ring currents to their aromatic all-carbon acene analogues and thus can be regarded as genuine isoelectronic structures of pentacene, hexacene, and heptacene, respectively. Our research gave some insights into the design and synthesis of stable longer acene analogues. PMID:27356244

  1. Displacive phase-transition of cuprite Ag2O revealed by extended x-ray absorption fine structure

    NASA Astrophysics Data System (ADS)

    Sanson, Andrea

    2016-08-01

    The low-temperature phase-transition of silver oxide (Ag2O) has been investigated by extended x-ray absorption fine structure (EXAFS) spectroscopy as a function of temperature. The thermal evolution of the local structure around Ag atoms has been determined. In particular, below the phase-transition temperature at ∼35 K, a progressive splitting of the Ag-Ag next-nearest-neighbor distances is observed. This definitely supports the idea that the phase-transition of Ag2O is due to displacive disorder of the Ag atoms.

  2. Developing Neuroimaging Phenotypes of the Default Mode Network in PTSD: Integrating the Resting State, Working Memory, and Structural Connectivity

    PubMed Central

    Philip, Noah S.; Carpenter, S. Louisa; Sweet, Lawrence H.

    2014-01-01

    Complementary structural and functional neuroimaging techniques used to examine the Default Mode Network (DMN) could potentially improve assessments of psychiatric illness severity and provide added validity to the clinical diagnostic process. Recent neuroimaging research suggests that DMN processes may be disrupted in a number of stress-related psychiatric illnesses, such as posttraumatic stress disorder (PTSD). Although specific DMN functions remain under investigation, it is generally thought to be involved in introspection and self-processing. In healthy individuals it exhibits greatest activity during periods of rest, with less activity, observed as deactivation, during cognitive tasks, e.g., working memory. This network consists of the medial prefrontal cortex, posterior cingulate cortex/precuneus, lateral parietal cortices and medial temporal regions. Multiple functional and structural imaging approaches have been developed to study the DMN. These have unprecedented potential to further the understanding of the function and dysfunction of this network. Functional approaches, such as the evaluation of resting state connectivity and task-induced deactivation, have excellent potential to identify targeted neurocognitive and neuroaffective (functional) diagnostic markers and may indicate illness severity and prognosis with increased accuracy or specificity. Structural approaches, such as evaluation of morphometry and connectivity, may provide unique markers of etiology and long-term outcomes. Combined, functional and structural methods provide strong multimodal, complementary and synergistic approaches to develop valid DMN-based imaging phenotypes in stress-related psychiatric conditions. This protocol aims to integrate these methods to investigate DMN structure and function in PTSD, relating findings to illness severity and relevant clinical factors. PMID:25046537

  3. Structural and biochemical changes underlying a keratoderma-like phenotype in mice lacking suprabasal AP1 transcription factor function

    PubMed Central

    Rorke, E A; Adhikary, G; Young, C A; Rice, R H; Elias, P M; Crumrine, D; Meyer, J; Blumenberg, M; Eckert, R L

    2015-01-01

    Epidermal keratinocyte differentiation on the body surface is a carefully choreographed process that leads to assembly of a barrier that is essential for life. Perturbation of keratinocyte differentiation leads to disease. Activator protein 1 (AP1) transcription factors are key controllers of this process. We have shown that inhibiting AP1 transcription factor activity in the suprabasal murine epidermis, by expression of dominant-negative c-jun (TAM67), produces a phenotype type that resembles human keratoderma. However, little is understood regarding the structural and molecular changes that drive this phenotype. In the present study we show that TAM67-positive epidermis displays altered cornified envelope, filaggrin-type keratohyalin granule, keratin filament, desmosome formation and lamellar body secretion leading to reduced barrier integrity. To understand the molecular changes underlying this process, we performed proteomic and RNA array analysis. Proteomic study of the corneocyte cross-linked proteome reveals a reduction in incorporation of cutaneous keratins, filaggrin, filaggrin2, late cornified envelope precursor proteins, hair keratins and hair keratin-associated proteins. This is coupled with increased incorporation of desmosome linker, small proline-rich, S100, transglutaminase and inflammation-associated proteins. Incorporation of most cutaneous keratins (Krt1, Krt5 and Krt10) is reduced, but incorporation of hyperproliferation-associated epidermal keratins (Krt6a, Krt6b and Krt16) is increased. RNA array analysis reveals reduced expression of mRNA encoding differentiation-associated cutaneous keratins, hair keratins and associated proteins, late cornified envelope precursors and filaggrin-related proteins; and increased expression of mRNA encoding small proline-rich proteins, protease inhibitors (serpins), S100 proteins, defensins and hyperproliferation-associated keratins. These findings suggest that AP1 factor inactivation in the suprabasal

  4. Structural and biochemical changes underlying a keratoderma-like phenotype in mice lacking suprabasal AP1 transcription factor function.

    PubMed

    Rorke, E A; Adhikary, G; Young, C A; Rice, R H; Elias, P M; Crumrine, D; Meyer, J; Blumenberg, M; Eckert, R L

    2015-01-01

    Epidermal keratinocyte differentiation on the body surface is a carefully choreographed process that leads to assembly of a barrier that is essential for life. Perturbation of keratinocyte differentiation leads to disease. Activator protein 1 (AP1) transcription factors are key controllers of this process. We have shown that inhibiting AP1 transcription factor activity in the suprabasal murine epidermis, by expression of dominant-negative c-jun (TAM67), produces a phenotype type that resembles human keratoderma. However, little is understood regarding the structural and molecular changes that drive this phenotype. In the present study we show that TAM67-positive epidermis displays altered cornified envelope, filaggrin-type keratohyalin granule, keratin filament, desmosome formation and lamellar body secretion leading to reduced barrier integrity. To understand the molecular changes underlying this process, we performed proteomic and RNA array analysis. Proteomic study of the corneocyte cross-linked proteome reveals a reduction in incorporation of cutaneous keratins, filaggrin, filaggrin2, late cornified envelope precursor proteins, hair keratins and hair keratin-associated proteins. This is coupled with increased incorporation of desmosome linker, small proline-rich, S100, transglutaminase and inflammation-associated proteins. Incorporation of most cutaneous keratins (Krt1, Krt5 and Krt10) is reduced, but incorporation of hyperproliferation-associated epidermal keratins (Krt6a, Krt6b and Krt16) is increased. RNA array analysis reveals reduced expression of mRNA encoding differentiation-associated cutaneous keratins, hair keratins and associated proteins, late cornified envelope precursors and filaggrin-related proteins; and increased expression of mRNA encoding small proline-rich proteins, protease inhibitors (serpins), S100 proteins, defensins and hyperproliferation-associated keratins. These findings suggest that AP1 factor inactivation in the suprabasal

  5. Expanding the SHOC2 Mutation Associated Phenotype of Noonan Syndrome with Loose Anagen Hair: Structural Brain Anomalies and Myelofibrosis

    PubMed Central

    Gripp, Karen W.; Zand, Dina J.; Demmer, Laurie; Anderson, Carol E.; Dobyns, William B.; Zackai, Elaine H.; Denenberg, Elizabeth; Jenny, Kim; Stabley, Deborah L.; Sol-Church, Katia

    2013-01-01

    Noonan syndrome is a heterogenous rasopathy typically presenting with short stature, characteristic facial features, cardiac abnormalities including pulmonic valve stenosis, ASD and hypertrophic cardiomyopathy (HCM), cryptorchidism, ectodermal abnormalities and learning differences. The phenotype is variable, and limited genotype phenotype correlation exists with SOS1 mutations often associated with normal cognition and stature, RAF1 mutations entailing a high HCM risk, and certain PTPN11 mutations predisposing to juvenile myelomonocytic leukemia. The recently identified SHOC2 mutation (p.Ser2Gly) causes Noonan syndrome with loose anagen hair. We report five patients with this mutation. All had skin hyperpigmentation, sparse light colored hair, increased fine wrinkles, ligamentous laxity, developmental delay and 4/4 had a structural cardiac anomaly. Hypotonia and macrocephaly occurred in 4/5 (80%); 3/5 (60%) had polyhydramnios, increased birth weight or required use of a feeding tube. Distinctive brain abnormalities included relative megalencephaly and enlarged subarachnoid spaces suggestive of benign external hydrocephalus, and a relatively small posterior fossa as indicated by a vertical tentorium. The combination of a large brain with a small posterior fossa likely resulted in the high rate of cerebellar tonsillar ectopia (3/4) (75%). Periventricular nodular heterotopia was seen in one patient with a thick and dysplastic corpus callosum. We report on the first hematologic neoplasm, myelofibrosis, in a 2-year-old patient with SHOC2 mutation. Myelofibrosis is exceedingly rare in children and young adults. The absence of a somatic JAK2 mutation, seen in the majority of patients with myelofibrosis, is noteworthy as it suggests that germline or somatic SHOC2 mutations are causally involved in myelofibrosis. PMID:23918763

  6. OpenMx: An Open Source Extended Structural Equation Modeling Framework

    ERIC Educational Resources Information Center

    Boker, Steven; Neale, Michael; Maes, Hermine; Wilde, Michael; Spiegel, Michael; Brick, Timothy; Spies, Jeffrey; Estabrook, Ryne; Kenny, Sarah; Bates, Timothy; Mehta, Paras; Fox, John

    2011-01-01

    OpenMx is free, full-featured, open source, structural equation modeling (SEM) software. OpenMx runs within the "R" statistical programming environment on Windows, Mac OS-X, and Linux computers. The rationale for developing OpenMx is discussed along with the philosophy behind the user interface. The OpenMx data structures are introduced--these…

  7. Extended X-ray absorption fine structure of the [Fe]-hydrogenase Hmd active site

    NASA Astrophysics Data System (ADS)

    Salomone-Stagni, Marco; Vogt, Sonja; Shima, Seigo; Meyer-Klaucke, Wolfram

    2009-11-01

    Hydrogenases are enzymes that catalyze the reversible oxidation of molecular hydrogen. Although their structure and catalytic mechanism are of considerable applied interest as models for the development of efficient catalysts for hydrogen fueled processes, the understanding of how hydrogenases react with H2 is only in its infancy. Two of the three known types of hydrogenases are iron-sulfur proteins that contain a dinuclear metal center, either [NiFe] or [FeFe]. In contrast, [Fe]-hydrogenase is the only mononuclear hydrogenase and thus a perfect system for studying the structural and electronic determinants of these enzymes. Here we summarize recent improvements in modeling based on the EXAFS signal and the geometric structure of this metalloenzyme in its as isolated or reconstituted form. The individual contributions to the EXAFS resulting in two different structural models are presented and discussed. Inspired by the new crystal structure, we show an advanced EXAFS model for the enzyme from Methanothermobacter marburgensis.

  8. Extended Aging Theories for Predictions of Safe Operational Life of Critical Airborne Structural Components

    NASA Technical Reports Server (NTRS)

    Ko, William L.; Chen, Tony

    2006-01-01

    The previously developed Ko closed-form aging theory has been reformulated into a more compact mathematical form for easier application. A new equivalent loading theory and empirical loading theories have also been developed and incorporated into the revised Ko aging theory for the prediction of a safe operational life of airborne failure-critical structural components. The new set of aging and loading theories were applied to predict the safe number of flights for the B-52B aircraft to carry a launch vehicle, the structural life of critical components consumed by load excursion to proof load value, and the ground-sitting life of B-52B pylon failure-critical structural components. A special life prediction method was developed for the preflight predictions of operational life of failure-critical structural components of the B-52H pylon system, for which no flight data are available.

  9. Family Structure, Maternal Dating, and Sexual Debut: Extending the Conceptualization of Instability.

    PubMed

    Zito, Rena Cornell; De Coster, Stacy

    2016-05-01

    Family structure influences the risk of early onset of sexual intercourse. This study proposes that the family structures associated with risk-single-mother, step-parent, and cohabiting-influence early sexual debut due to family instability, including shifts in family structure and maternal dating, which can undermine parental control and transmit messages about the acceptability of nonmarital sex. Previous research has not considered maternal dating as a component of family instability, assuming single mothers who date and those who do not date experience comparable levels of family disruption and transmit similar messages about the acceptability of nonmarital sex. Hypotheses are assessed using logistic regression models predicting the odds of early onset of sexual intercourse among 9959 respondents (53 % female, 47 % male) from the National Longitudinal Study of Adolescent to Adult Health. Respondents were ages 12-17 at the first wave of data collection and 18-26 at the third wave, when respondents reported the age at which they first had sexual intercourse. Results show that maternal dating is a source of family instability with repercussions for early sexual debut. Parental control and permissive attitudes towards teenage sex and pregnancy link at-risk family structures and maternal dating to early sexual initiation among females, though these variables do not fully explain family structure and maternal dating effects. Among males, the influence of maternal dating on early sexual debut is fully explained by the learning of permissive sexual attitudes. PMID:26951507

  10. Synthesis, structure, characterization and fluorescent properties of Ag+ complexes with extended π⋯π interactions

    NASA Astrophysics Data System (ADS)

    Huang, Ting-Hong; Yan, Jie; Yang, Hu; Qiang, Liu; Du, Huai-Ming

    2015-12-01

    Two mixed-ligand Ag (I) complexes, [Ag2(Phterpy)2(NO3)2(dppe)]·CH3CN (1) and [Ag4(Phterpy)2(NO3)2(dppp)2](NO3)2·6H2O (2) (dppe = 1, 2-bis (diphenylphosphino) ethane, dppp = 1, 3-bis (diphenylphosphino) propane, Phterpy = 4‧-phenyl-2, 2‧:6‧, 2″-terpyridine), have been synthesized and structurally characterized by IR, 1H-NMR, 31P-NMR, elemental analysis and X-ray crystal structure analysis. Structural analysis reveals that the change of bridging ligands from dppe to dppp lead to the formation of centrosymmetric cations [Ag2(Phterpy)2(NO3)2(dppe)] and [Ag4(Phterpy)2 (NO3)2(dppp)2]2+, especially complex 2 containing two independent centrosymmetric tetramers with the central (obligate) Ag2O2 planes. Complexes 1 and 2 consist of the 1D infinite chains, with different variations in π-stacking patterns. Crystal structure of 1 contains 1D infinite chains constructed by π⋯π interactions between Phterpy, while 2 is built by π⋯π interaction of phenylene rings from dppp. All these reveal that the change of phosphine ligands might be the key of construction of different types of polynuclear structures and 1D π-stacking chain. Moreover, the solid-state emission spectra of complexes 1 and 2 display broad emission bands at 420-600 nm.

  11. Damage Characterization Using the Extended Finite Element Method for Structural Health Management

    NASA Technical Reports Server (NTRS)

    Krishnamurthy, Thiagarajan; Gallegos, Adam M.

    2011-01-01

    The development of validated multidisciplinary Integrated Vehicle Health Management (IVHM) tools, technologies, and techniques to enable detection, diagnosis, prognosis, and mitigation in the presence of adverse conditions during flight will provide effective solutions to deal with safety related challenges facing next generation aircraft. The adverse conditions include loss of control caused by environmental factors, actuator and sensor faults or failures, and damage conditions. A major concern in these structures is the growth of undetected damage/cracks due to fatigue and low velocity foreign impact that can reach a critical size during flight, resulting in loss of control of the aircraft. Hence, development of efficient methodologies to determine the presence, location, and severity of damage/cracks in critical structural components is highly important in developing efficient structural health management systems.

  12. High Sensitivity Combined with Extended Structural Coverage of Labile Compounds via Nanoelectrospray Ionization at Subambient Pressures

    SciTech Connect

    Cox, Jonathan T.; Kronewitter, Scott R.; Shukla, Anil K.; Moore, Ronald J.; Smith, Richard D.; Tang, Keqi

    2014-10-07

    Subambient pressure ionization with nanoelectrospray (SPIN) has proven to be effective in producing ions with high efficiency and transmitting them to low pressures for high sensitivity mass spectrometry (MS) analysis. Here we present evidence that not only does the SPIN source improve MS sensitivity but also allows for gentler ionization conditions. The gentleness of a conventional heated capillary electrospray ionization (ESI) source and the SPIN source was compared by the liquid chromatography mass spectrometry (LC-MS) analysis of colominic acid. Colominic acid is a mixture of sialic acid polymers of different lengths containing labile glycosidic linkages between monomer units necessitating a gentle ion source. By coupling the SPIN source with high resolution mass spectrometry and using advanced data processing tools, we demonstrate much extended coverage of sialic acid polymer chains as compared to using the conventional ESI source. Additionally we show that SPIN-LC-MS is effective in elucidating polymer features with high efficiency and high sensitivity previously unattainable by the conventional ESI-LC-MS methods.

  13. Phenotype characterization of embryoid body structures generated by a crystal comet effect tail in an intercellular cancer collision scenario

    PubMed Central

    Diaz, Jairo A; Murillo, Mauricio F

    2012-01-01

    Cancer is, by definition, the uncontrolled growth of autonomous cells that eventually destroy adjacent tissues and generate architectural disorder. However, this concept cannot be totally true. In three well documented studies, we have demonstrated that cancer tissues produce order zones that evolve over time and generate embryoid body structures in a space-time interval. The authors decided to revise the macroscopic and microscopic material in well-developed malignant tumors in which embryoid bodies were identified to determine the phenotype characterization that serves as a guideline for easy recognition. The factors responsible for this morphogenesis are physical, bioelectric, and magnetic susceptibilities produced by crystals that act as molecular designers for the topographic gradients that guide the surrounding silhouette and establish tissue head-tail positional identities. The structures are located in amniotic-like cavities and show characteristic somite-like embryologic segmentation. Immunophenotypic study has demonstrated exclusion factor positional identity in relation to enolase-immunopositive expression of embryoid body and human chorionic gonadotropin immunopositivity exclusion factor expression in the surrounding tissues. The significance of these observations is that they can also be predicted by experimental image data collected by the Large Hadron Collider (LHC) accelerator at the European Organization for Nuclear Research, in which two-beam subatomic collision particles in the resulting debris show hyperorder domains similar to those identified by us in intercellular cancer collisions. Our findings suggest that we are dealing with true reverse biologic system information in an activated collective cancer stem cell memory, in which physics participates in the elaboration of geometric complexes and chiral biomolecules that serve to build bodies with embryoid print as it develops during gestation. Reversal mechanisms in biology are intimately

  14. Structural Equation Modelling of Multiple Facet Data: Extending Models for Multitrait-Multimethod Data

    ERIC Educational Resources Information Center

    Bechger, Timo M.; Maris, Gunter

    2004-01-01

    This paper is about the structural equation modelling of quantitative measures that are obtained from a multiple facet design. A facet is simply a set consisting of a finite number of elements. It is assumed that measures are obtained by combining each element of each facet. Methods and traits are two such facets, and a multitrait-multimethod…

  15. Extending the Multiple-Goal Perspective to Tertiary Classroom Goal Structures

    ERIC Educational Resources Information Center

    James, Vennessa H.; Yates, Shirley M.

    2007-01-01

    The multiple-goal perspective has recently been applied to teacher behaviours in primary school classrooms through experimental intervention (Linnenbrink, 2005) and objective observation (Sideridis, 2005). However, there is evidence suggesting that rather than centered only on teacher behaviour, classroom goal structures are a whole class feature…

  16. Evaluation of high temperature structural adhesives for extended service, phase 5

    NASA Technical Reports Server (NTRS)

    Hendricks, C. L.; Hill, S. G.; Hale, J. N.; Dumars, W. G.

    1987-01-01

    The evaluation of 3 experimental polymers from NASA-Langley and a commercially produced polymer from Mitsui Toatsu Chemicals as high temperature structural adhesives is presented. A polyphenylquinoxaline (PPQ), polyimide (STPI/LaRC-2), and a polyarylene ether (PAE-SO2) were evaluated as metal-to-metal adhesives. Lap shear, crack extension, and climbing drum peel specimens were fabricated from all three polymers and tested after thermal, combined thermal/humidity, and stressed hydraulic fluid (Skydrol) exposure. The fourth polymer, LARC-TPI was evaluated as an adhesive for titanium honeycomb sandwich structure. All three experimental polymers performed well as metal-to-metal adhesives from 219 K (-65 F) to 505 K (450 F), including humidity exposure. Structural adhesive strength was also maintained at 505 K for a minimum of 3000 hours. LaRC-TPI was evaluated as a high temperature (505 K) adhesive for titanium honeycomb sandwich structure. The LaRC-TPI bonding process development concentrated on improving the honeycomb core-to-skin bond. The most promising approach of those evaluated combined a LaRC-TPI polymer solution with a semi-crystalline LaRC-TPI powder for adhesive film fabrication and fillet formation.

  17. First-principles simulations of extended phosphorus oxynitride structures in LiPON glasses

    NASA Astrophysics Data System (ADS)

    Du, Yaojun; Holzwarth, N. A. W.

    2009-03-01

    The thin film electrolyte LiPON, having the composition of Li3+xPO4-yNz with x=3z-2y, was developed at Oak Ridge National Lab in the 1990's for use in solid state batteries and related applications. In an effort to understand and to optimize properties of this electrolyte material, we expanded previous studies of isolated defects in crystalline Li3PO4 to focus on more complicated phosphate structures based on combinations of tetrahedral P-O bonds and bridging P-O-P bonds. For example, crystalline LiPO3 and P2O5 are composed of phosphate structures with linear and branched chains, respectively. Both these and related structures derived from substituting O with N and adjusting mobile Li ion concentrations approximate components found in LiPON films.^2 In the simulated structures, we find that N is energetically more stable at bridging bond sites than at tetrahedral sites by 2-3 eV and that the Li ion migration energies are 0.5-0.6 eV, similar to values measured in LiPON films.

  18. EB1 regulates attachment of Ska1 with microtubules by forming extended structures on the microtubule lattice.

    PubMed

    Thomas, Geethu E; Bandopadhyay, K; Sutradhar, Sabyasachi; Renjith, M R; Singh, Puja; Gireesh, K K; Simon, Steny; Badarudeen, Binshad; Gupta, Hindol; Banerjee, Manidipa; Paul, Raja; Mitra, J; Manna, Tapas K

    2016-01-01

    Kinetochore couples chromosome movement to dynamic microtubules, a process that is fundamental to mitosis in all eukaryotes but poorly understood. In vertebrates, spindle-kinetochore-associated (Ska1-3) protein complex plays an important role in this process. However, the proteins that stabilize Ska-mediated kinetochore-microtubule attachment remain unknown. Here we show that microtubule plus-end tracking protein EB1 facilitates Ska localization on microtubules in vertebrate cells. EB1 depletion results in a significant reduction of Ska1 recruitment onto microtubules and defects in mitotic chromosome alignment, which is also reflected in computational modelling. Biochemical experiments reveal that EB1 interacts with Ska1, facilitates Ska1-microtubule attachment and together stabilizes microtubules. Structural studies reveal that EB1 either with Ska1 or Ska complex forms extended structures on microtubule lattice. Results indicate that EB1 promotes Ska association with K-fibres and facilitates kinetochore-microtubule attachment. They also implicate that in vertebrates, chromosome coupling to dynamic microtubules could be mediated through EB1-Ska extended structures. PMID:27225956

  19. EB1 regulates attachment of Ska1 with microtubules by forming extended structures on the microtubule lattice

    PubMed Central

    Thomas, Geethu E.; Bandopadhyay, K.; Sutradhar, Sabyasachi; Renjith, M. R.; Singh, Puja; Gireesh, K. K.; Simon, Steny; Badarudeen, Binshad; Gupta, Hindol; Banerjee, Manidipa; Paul, Raja; Mitra, J.; Manna, Tapas K.

    2016-01-01

    Kinetochore couples chromosome movement to dynamic microtubules, a process that is fundamental to mitosis in all eukaryotes but poorly understood. In vertebrates, spindle-kinetochore-associated (Ska1–3) protein complex plays an important role in this process. However, the proteins that stabilize Ska-mediated kinetochore-microtubule attachment remain unknown. Here we show that microtubule plus-end tracking protein EB1 facilitates Ska localization on microtubules in vertebrate cells. EB1 depletion results in a significant reduction of Ska1 recruitment onto microtubules and defects in mitotic chromosome alignment, which is also reflected in computational modelling. Biochemical experiments reveal that EB1 interacts with Ska1, facilitates Ska1-microtubule attachment and together stabilizes microtubules. Structural studies reveal that EB1 either with Ska1 or Ska complex forms extended structures on microtubule lattice. Results indicate that EB1 promotes Ska association with K-fibres and facilitates kinetochore-microtubule attachment. They also implicate that in vertebrates, chromosome coupling to dynamic microtubules could be mediated through EB1-Ska extended structures. PMID:27225956

  20. Extended Functional Groups (EFG): An Efficient Set for Chemical Characterization and Structure-Activity Relationship Studies of Chemical Compounds.

    PubMed

    Salmina, Elena S; Haider, Norbert; Tetko, Igor V

    2015-01-01

    The article describes a classification system termed "extended functional groups" (EFG), which are an extension of a set previously used by the CheckMol software, that covers in addition heterocyclic compound classes and periodic table groups. The functional groups are defined as SMARTS patterns and are available as part of the ToxAlerts tool (http://ochem.eu/alerts) of the On-line CHEmical database and Modeling (OCHEM) environment platform. The article describes the motivation and the main ideas behind this extension and demonstrates that EFG can be efficiently used to develop and interpret structure-activity relationship models. PMID:26703557

  1. Nine new phosphorene polymorphs with non-honeycomb structures: a much extended family.

    PubMed

    Wu, Menghao; Fu, Huahua; Zhou, Ling; Yao, Kailun; Zeng, Xiao Cheng

    2015-05-13

    We predict a new class of monolayer phosphorus allotropes, namely, ε-P, ζ-P, η-P, and θ-P. Distinctly different from the monolayer α-P (black) and previously predicted β-P (Phys. Rev. Lett. 2014, 112, 176802), γ-P, and δ-P (Phys. Rev. Lett. 2014, 113, 046804) with buckled honeycomb lattice, the new allotropes are composed of P4 square or P5 pentagon units that favor tricoordination for P atoms. The new four polymorphs, together with five additional hybrid polymorphs, greatly enrich the phosphorene structures, and their stabilities are confirmed by first-principles calculations. In particular, the θ-P is shown to be equally stable as the α-P (black) and more stable than all previously reported phosphorene polymorphs. Prediction of nonvolatile ferroelastic switching and structural transformation among different polymorphs under strains points out their potential applications via strain engineering. PMID:25844524

  2. Surface structure of an invariant manifold of a Halo Orbit (extended abstract)

    NASA Technical Reports Server (NTRS)

    Hirani, Anil N.; Lo, Martin W.

    2005-01-01

    We extract the surface structure of the unstable invariant manifold tube projected into position space, of a halo orbit near L2. We do this by using transversal planes to intersect trajectories that approximate the tube. From these intersection points we construct spline-interpolated cross section curves which give a good idea of the structure of the tube. For example, we show that, for the value of (mu) we use, the tube pinches, develops a self-intersection, develops loop-inside-tube structure, pinches some more, and so on. We also construct surfaces made of quadrilaterals and triangles from these cross-sections. The transversal planes are obtained by taking planes orthogonal to a curve that follows the general shape of the tube. One such curve we use, is the unstable invariant manifold of the equilibrium point L2 itself. In another example, we take a circle that follows the tube, as the curve for finding planes transversal to the tube. Our method is complementary to the method of taking cross-sections of constant time (the isochronous method), as used by some other researchers. The isochronous method is good at revealing the temporal structure of trajectories on a tube. However, due to the unequal speeds of different trajectories, it is harder to use for long length surface extraction. In contrast, using our method, we show cross-sections of the tube through an angular extent of nearly (pi) during which the tube becomes extremely convoluted. We also show that tubes of different energies, that start out in certain ordering, do not obey the ordering after a while. Our work is motivated by applications to space mission design.

  3. Different mutations at V363 MAPT codon are associated with atypical clinical phenotypes and show unusual structural and functional features.

    PubMed

    Rossi, Giacomina; Bastone, Antonio; Piccoli, Elena; Morbin, Michela; Mazzoleni, Giulia; Fugnanesi, Valeria; Beeg, Marten; Del Favero, Elena; Cantù, Laura; Motta, Simona; Salsano, Ettore; Pareyson, Davide; Erbetta, Alessandra; Elia, Antonio Emanuele; Del Sorbo, Francesca; Silani, Vincenzo; Morelli, Claudia; Salmona, Mario; Tagliavini, Fabrizio

    2014-02-01

    Microtubule-associated protein tau gene (MAPT) is one of the major genes linked to frontotemporal lobar degeneration, a group of neurodegenerative diseases clinically, pathologically, and genetically heterogeneous. In particular, MAPT mutations give rise to the subgroup of tauopathies. The pathogenetic mechanisms underlying the MAPT mutations so far described are the decreased ability of tau protein to promote microtubule polymerization (missense mutations) or the altered ratio of tau isoforms (splicing mutations), both leading to accumulation of hyperphosphorylated filamentous tau protein. Following a genetic screening of patients affected by frontotemporal lobar degeneration, we identified 2 MAPT mutations, V363I and V363A, leading to atypical clinical phenotypes, such as posterior cortical atrophy. We investigated in vitro features of the recombinant mutated tau isoforms and revealed unusual functional and structural characteristics such as an increased ability to promote microtubule polymerization and a tendency to form oligomeric instead of filamentous aggregates. Thus, we disclosed a greater than expected complexity of abnormal features of mutated tau isoforms. Overall our findings suggest a high probability that these mutations are pathogenic. PMID:24018212

  4. Type IV Pilus Proteins Form an Integrated Structure Extending from the Cytoplasm to the Outer Membrane

    PubMed Central

    Li, Chengyun; Wallace, Regina A.; Black, Wesley P.; Li, Yue-zhong; Yang, Zhaomin

    2013-01-01

    The bacterial type IV pilus (T4P) is the strongest biological motor known to date as its retraction can generate forces well over 100 pN. Myxococcus xanthus, a δ-proteobacterium, provides a good model for T4P investigations because its social (S) gliding motility is powered by T4P. In this study, the interactions among M. xanthus T4P proteins were investigated using genetics and the yeast two-hybrid (Y2H) system. Our genetic analysis suggests that there is an integrated T4P structure that crosses the inner membrane (IM), periplasm and the outer membrane (OM). Moreover, this structure exists in the absence of the pilus filament. A systematic Y2H survey provided evidence for direct interactions among IM and OM proteins exposed to the periplasm. For example, the IM lipoprotein PilP interacted with its cognate OM protein PilQ. In addition, interactions among T4P proteins from the thermophile Thermus thermophilus were investigated by Y2H. The results indicated similar protein-protein interactions in the T4P system of this non-proteobacterium despite significant sequence divergence between T4P proteins in T. thermophilus and M. xanthus. The observations here support the model of an integrated T4P structure in the absence of a pilus in diverse bacterial species. PMID:23922942

  5. Exciton Localization in Extended π-Electron Systems: Comparison of Linear and Cyclic Structures.

    PubMed

    Thiessen, Alexander; Würsch, Dominik; Jester, Stefan-S; Aggarwal, A Vikas; Idelson, Alissa; Bange, Sebastian; Vogelsang, Jan; Höger, Sigurd; Lupton, John M

    2015-07-30

    We employ five π-conjugated model materials of different molecular shape-oligomers and cyclic structures-to investigate the extent of exciton self-trapping and torsional motion of the molecular framework following optical excitation. Our studies combine steady state and transient fluorescence spectroscopy in the ensemble with measurements of polarization anisotropy on single molecules, supported by Monte Carlo simulations. The dimer exhibits a significant spectral red shift within ∼100 ps after photoexcitation which is attributed to torsional relaxation. This relaxation mechanism is inhibited in the structurally rigid macrocyclic analogue. However, both systems show a high degree of exciton localization but with very different consequences: while, in the macrocycle, the exciton localizes randomly on different parts of the ring, scrambling polarization memory, in the dimer, localization leads to a deterministic exciton position with luminescence characteristics of a dipole. Monte Carlo simulations allow us to quantify the structural difference between the emitting and absorbing units of the π-conjugated system in terms of disorder parameters. PMID:26035080

  6. Crystal Structures of Lys-63-linked tri- and di-ubiquitin Reveal a Highly Extended Chain Architecture

    SciTech Connect

    Weeks, S.; Grasty, K; Hernandez-Cuebas, L; Loll, P

    2009-01-01

    The covalent attachment of different types of poly-ubiquitin chains signal different outcomes for the proteins so targeted. For example, a protein modified with Lys-48-linked poly-ubiquitin chains is targeted for proteasomal degradation, whereas Lys-63-linked chains encode nondegradative signals. The structural features that enable these different types of chains to encode different signals have not yet been fully elucidated. We report here the X-ray crystal structures of Lys-63-linked tri- and di-ubiquitin at resolutions of 2.3 and 1.9 {angstrom}, respectively. The tri- and di-ubiquitin species adopt essentially identical structures. In both instances, the ubiquitin chain assumes a highly extended conformation with a left-handed helical twist; the helical chain contains four ubiquitin monomers per turn and has a repeat length of {approx}110 {angstrom}. Interestingly, Lys-48 ubiquitin chains also adopt a left-handed helical structure with a similar repeat length. However, the Lys-63 architecture is much more open than that of Lys-48 chains and exposes much more of the ubiquitin surface for potential recognition events. These new crystal structures are consistent with the results of solution studies of Lys-63 chain conformation, and reveal the structural basis for differential recognition of Lys-63 versus Lys-48 chains.

  7. Analysis and design for inelastic structural response of extended pile shaft foundations in laterally spreading ground during earthquakes

    NASA Astrophysics Data System (ADS)

    Khosravifar, Arash

    Experiences from past earthquakes have shown that lateral spreading associated with liquefaction of cohesionless soils can be a cause of severe damage to bridge foundations. Large diameter extended pile shafts can be an effective bridge foundation choice for areas subjected to lateral spreading because they offer greater stiffness and strength relative to the magnitude of lateral spreading loads that can develop against them. A limited degree of plastic hinging below the ground surface may be allowable in design of extended pile shafts. Issues for design for extended pile shafts include: (a) how to estimate the demands due to superstructure inertia and lateral spreading in liquefied soils, and (b) how to combine these two loads in estimating the local and global inelastic demands on the structure. Studies of the response of pile foundations and pile-supported structures in liquefiable soils using physical models, numerical models, and case studies have provided the basis for a number of design recommendations. The guidance is, however, quite varied regarding how lateral spreading and superstructure inertial loads should be combined in design. To answer the above questions a series of Nonlinear Dynamic Finite Element Analyses (NDA) have been performed to investigate inelastic response of extended pile shafts subjected to liquefaction-induced lateral spreading, covering a range of soil, pile, and ground motion conditions. The results of NDA were first used to show that combined effects of lateral spreading and superstructure inertia produce larger demands than are produced by either loading case alone, such that the combined demand cannot be enveloped by analyzing the two load cases separately. The results were then used to evaluate current equivalent static analysis (ESA) method (Caltrans, 2008), with the relatively poor agreement illustrating the limitations of methods that do not combine the two loads. The results of NDA parametric study were then used to develop

  8. Profiling functions of ectomycorrhizal diversity and root structuring in seedlings of Norway spruce (Picea abies) with fast- and slow-growing phenotypes.

    PubMed

    Velmala, Sannakajsa M; Rajala, Tiina; Heinonsalo, Jussi; Taylor, Andy F S; Pennanen, Taina

    2014-01-01

    We studied the role of taxonomical and functional ectomycorrhizal (ECM) fungal diversity in root formation and nutrient uptake by Norway spruce (Picea abies) seedlings with fast- and slow-growing phenotypes. Seedlings were grown with an increasing ECM fungal diversity gradient from one to four species and sampled before aboveground growth differences between the two phenotypes were apparent. ECM fungal colonization patterns were determined and functional diversity was assayed via measurements of potential enzyme activities of eight exoenzymes probably involved in nutrient mobilization. Phenotypes did not vary in their receptiveness to different ECM fungal species. However, seedlings of slow-growing phenotypes had higher fine-root density and thus more condensed root systems than fast-growing seedlings, but the potential enzyme activities of ectomycorrhizas did not differ qualitatively or quantitatively. ECM species richness increased host nutrient acquisition potential by diversifying the exoenzyme palette. Needle nitrogen content correlated positively with high chitinase activity of ectomycorrhizas. Rather than fast- and slow-growing phenotypes exhibiting differing receptiveness to ECM fungi, our results suggest that distinctions in fine-root structuring and in the belowground growth strategy already apparent at early stages of seedling development may explain later growth differences between fast- and slow-growing families. PMID:24117652

  9. Quantifying seascape structure: Extending terrestrial spatial pattern metrics to the marine realm

    USGS Publications Warehouse

    Wedding, L.M.; Christopher, L.A.; Pittman, S.J.; Friedlander, A.M.; Jorgensen, S.

    2011-01-01

    Spatial pattern metrics have routinely been applied to characterize and quantify structural features of terrestrial landscapes and have demonstrated great utility in landscape ecology and conservation planning. The important role of spatial structure in ecology and management is now commonly recognized, and recent advances in marine remote sensing technology have facilitated the application of spatial pattern metrics to the marine environment. However, it is not yet clear whether concepts, metrics, and statistical techniques developed for terrestrial ecosystems are relevant for marine species and seascapes. To address this gap in our knowledge, we reviewed, synthesized, and evaluated the utility and application of spatial pattern metrics in the marine science literature over the past 30 yr (1980 to 2010). In total, 23 studies characterized seascape structure, of which 17 quantified spatial patterns using a 2-dimensional patch-mosaic model and 5 used a continuously varying 3-dimensional surface model. Most seascape studies followed terrestrial-based studies in their search for ecological patterns and applied or modified existing metrics. Only 1 truly unique metric was found (hydrodynamic aperture applied to Pacific atolls). While there are still relatively few studies using spatial pattern metrics in the marine environment, they have suffered from similar misuse as reported for terrestrial studies, such as the lack of a priori considerations or the problem of collinearity between metrics. Spatial pattern metrics offer great potential for ecological research and environmental management in marine systems, and future studies should focus on (1) the dynamic boundary between the land and sea; (2) quantifying 3-dimensional spatial patterns; and (3) assessing and monitoring seascape change. ?? Inter-Research 2011.

  10. Extending motifs in lithiocuprate chemistry: unexpected structural diversity in thiocyanate complexes.

    PubMed

    Peel, Andrew J; Hedidi, Madani; Bentabed-Ababsa, Ghenia; Roisnel, Thierry; Mongin, Florence; Wheatley, Andrew E H

    2016-04-14

    The new area of lithio(thiocyanato)cuprates has been developed. Using inexpensive, stable and safe CuSCN for their preparation, these complexes revealed Lipshutz-type dimeric motifs with solvent-dependent point group identities; planar, boat-shaped and chair shaped conformers are seen in the solid state. In solution, both Lipshutz-type and Gilman structures are clearly seen. Since the advent in 2007 of directed ortho cupration, effort has gone into understanding the structure-reactivity effects of amide ligand variation in and alkali metal salt abstraction from Lipshutz-type cuprates such as (TMP)2Cu(CN)Li2(THF) 1 (TMP = 2,2,6,6-tetramethylpiperidide). The replacement of CN(-) with SCN(-) is investigated presently as a means of improving the safety of lithium cuprates. The synthesis and solid state structural characterization of reference cuprate (TMP)2Cu(CN)Li2(THP) 8 (THP = tetrahydropyran) precedes that of the thiocyanate series (TMP)2Cu(SCN)Li2(L) (L = OEt29, THF 10, THP 11). For each of 9-11, preformed TMPLi was combined with CuSCN (2 : 1) in the presence of sub-stoichiometric Lewis base (0.5 eq. wrt Li). The avoidance of Lewis basic solvents incurs formation of the unsolvated Gilman cuprate (TMP)2CuLi 12, whilst multidimensional NMR spectroscopy has evidenced the abstraction of LiSCN from 9-11 in hydrocarbon solution and the in situ formation of Gilman reagents. The synthetic utility of 10 is established in the selective deprotometalation of chloropyridine substrates, including effecting transition metal-free homocoupling in 51-69% yield. PMID:26554572

  11. Extended fine structures in the electron energy loss spectrum of InAs

    NASA Technical Reports Server (NTRS)

    Schowengerdt, F. D.; Grunthaner, F. J.

    1988-01-01

    The possibility of using electron energy loss fine structure (EELFS) for the characterization of thin pseudomorphic quantum wells of InAs and GaAs(100) is investigated. It is shown that the EELFS technique can yield reliable radial distribution functions for bulk InAs, provided beam-induced sample degradation is controlled stringently. Additional improvements in the data collection procedures, including better control of the sample condition, are required as well as more detailed work on separating contributions from multiple edges in the data analysis.

  12. Ligand effects on the structures of extended networks of dicyanamide-containing transition-metal ions.

    PubMed

    Armentano, Donatella; De Munno, Giovanni; Guerra, Francesca; Julve, Miguel; Lloret, Francesc

    2006-06-12

    The structural characterization of a series of complexes of formula [M(dca)2L]n, where dca = dicyanamide, L = 1,10-phenanthroline (phen) [1-4] and 2,9-dimethylphenanthroline (2,9-dmphen) [9-12], and M = Mn (1 and 9), Fe (2 and 10), Co (3 and 11), and Ni (4 and 12), has revealed the effect of the presence of the methyl substituents of L on the resulting network. The structure of [Mn(dca)2(phen)]n (1), which is identical to those of 2-4, together with the investigation of its magnetic properties in the temperature range of 77-300 K were reported elsewhere. The use of the 4,7-dimethylphenanthroline (4,7-dmphen) as the co-ligand yielded a series of compounds of formula [M(dca)2(4,7-dmphen)]n [M = Mn (5), Fe (6), Co (7), and Ni (8)], which are isostructural with 1-4. Compounds containing phen (1-4) and 4,7-dmphen (5-8) are made of two-dimensional grids of metal atoms, each metal atom being linked to three other metal centers through single (three metal atoms involved) and double (two metal atoms involved) dca bridges exhibiting the mu-1,5 coordination mode. The isostructural complexes [M(dca)2(2,9-dmphen)]n (9-12) also have a sheetlike structure, the metal atoms in each layer being linked by two single and one double mu-1,5-dca units, as in 1-8. However, the topology of the network in 9-12 is different from that in 1-8 because of the different arrangement of the two single mu-1,5 dca bridges: cis in 1-8 versus trans in 9-12. The magnetic study of compounds 1-12 in the temperature range of 1.9-290 K has revealed the occurrence of weak ferromagnetic (M = Ni) and antiferromagnetic interactions (M = Mn, Fe, and Co). The different magnetic behavior in 1-12 was analyzed in the light of their structures, and the values of the magnetic interactions were compared to those of related systems. PMID:16749825

  13. Comparison of Muscle Transcriptome between Pigs with Divergent Meat Quality Phenotypes Identifies Genes Related to Muscle Metabolism and Structure

    PubMed Central

    Damon, Marie; Wyszynska-Koko, Joanna; Vincent, Annie; Hérault, Frédéric; Lebret, Bénédicte

    2012-01-01

    Background Meat quality depends on physiological processes taking place in muscle tissue, which could involve a large pattern of genes associated with both muscle structural and metabolic features. Understanding the biological phenomena underlying muscle phenotype at slaughter is necessary to uncover meat quality development. Therefore, a muscle transcriptome analysis was undertaken to compare gene expression profiles between two highly contrasted pig breeds, Large White (LW) and Basque (B), reared in two different housing systems themselves influencing meat quality. LW is the most predominant breed used in pig industry, which exhibits standard meat quality attributes. B is an indigenous breed with low lean meat and high fat contents, high meat quality characteristics, and is genetically distant from other European pig breeds. Methodology/Principal Findings Transcriptome analysis undertaken using a custom 15 K microarray, highlighted 1233 genes differentially expressed between breeds (multiple-test adjusted P-value<0.05), out of which 635 were highly expressed in the B and 598 highly expressed in the LW pigs. No difference in gene expression was found between housing systems. Besides, expression level of 12 differentially expressed genes quantified by real-time RT-PCR validated microarray data. Functional annotation clustering emphasized four main clusters associated to transcriptome breed differences: metabolic processes, skeletal muscle structure and organization, extracellular matrix, lysosome, and proteolysis, thereby highlighting many genes involved in muscle physiology and meat quality development. Conclusions/Significance Altogether, these results will contribute to a better understanding of muscle physiology and of the biological and molecular processes underlying meat quality. Besides, this study is a first step towards the identification of molecular markers of pork quality and the subsequent development of control tools. PMID:22470472

  14. Nectar robbery by a hermit hummingbird: association to floral phenotype and its influence on flowers and network structure.

    PubMed

    Maruyama, Pietro Kiyoshi; Vizentin-Bugoni, Jeferson; Dalsgaard, Bo; Sazima, Ivan; Sazima, Marlies

    2015-07-01

    Interactions between flowers and their visitors span the spectrum from mutualism to antagonism. The literature is rich in studies focusing on mutualism, but nectar robbery has mostly been investigated using phytocentric approaches focused on only a few plant species. To fill this gap, we studied the interactions between a nectar-robbing hermit hummingbird, Phaethornis ruber, and the array of flowers it visits. First, based on a literature review of the interactions involving P. ruber, we characterized the association of floral larceny to floral phenotype. We then experimentally examined the effects of nectar robbing on nectar standing crop and number of visits of the pollinators to the flowers of Canna paniculata. Finally, we asked whether the incorporation of illegitimate interactions into the analysis affects plant-hummingbird network structure. We identified 97 plant species visited by P. ruber and found that P. ruber engaged in floral larceny in almost 30% of these species. Nectar robbery was especially common in flowers with longer corolla. In terms of the effect on C. paniculata, the depletion of nectar due to robbery by P. ruber was associated with decreased visitation rates of legitimate pollinators. At the community level, the inclusion of the illegitimate visits of P. ruber resulted in modifications of how modules within the network were organized, notably giving rise to a new module consisting of P. ruber and mostly robbed flowers. However, although illegitimate visits constituted approximately 9% of all interactions in the network, changes in nestedness, modularity, and network-level specialization were minor. Our results indicate that although a flower robber may have a strong effect on the pollination of a particular plant species, the inclusion of its illegitimate interactions has limited capacity to change overall network structure. PMID:25740333

  15. A Complex Structural Variation on Chromosome 27 Leads to the Ectopic Expression of HOXB8 and the Muffs and Beard Phenotype in Chickens.

    PubMed

    Guo, Ying; Gu, Xiaorong; Sheng, Zheya; Wang, Yanqiang; Luo, Chenglong; Liu, Ranran; Qu, Hao; Shu, Dingming; Wen, Jie; Crooijmans, Richard P M A; Carlborg, Örjan; Zhao, Yiqiang; Hu, Xiaoxiang; Li, Ning

    2016-06-01

    Muffs and beard (Mb) is a phenotype in chickens where groups of elongated feathers gather from both sides of the face (muffs) and below the beak (beard). It is an autosomal, incomplete dominant phenotype encoded by the Muffs and beard (Mb) locus. Here we use genome-wide association (GWA) analysis, linkage analysis, Identity-by-Descent (IBD) mapping, array-CGH, genome re-sequencing and expression analysis to show that the Mb allele causing the Mb phenotype is a derived allele where a complex structural variation (SV) on GGA27 leads to an altered expression of the gene HOXB8. This Mb allele was shown to be completely associated with the Mb phenotype in nine other independent Mb chicken breeds. The Mb allele differs from the wild-type mb allele by three duplications, one in tandem and two that are translocated to that of the tandem repeat around 1.70 Mb on GGA27. The duplications contain total seven annotated genes and their expression was tested during distinct stages of Mb morphogenesis. A continuous high ectopic expression of HOXB8 was found in the facial skin of Mb chickens, strongly suggesting that HOXB8 directs this regional feather-development. In conclusion, our results provide an interesting example of how genomic structural rearrangements alter the regulation of genes leading to novel phenotypes. Further, it again illustrates the value of utilizing derived phenotypes in domestic animals to dissect the genetic basis of developmental traits, herein providing novel insights into the likely role of HOXB8 in feather development and differentiation. PMID:27253709

  16. A Complex Structural Variation on Chromosome 27 Leads to the Ectopic Expression of HOXB8 and the Muffs and Beard Phenotype in Chickens

    PubMed Central

    Wang, Yanqiang; Luo, Chenglong; Liu, Ranran; Qu, Hao; Shu, Dingming; Wen, Jie; Crooijmans, Richard P. M. A.; Zhao, Yiqiang; Hu, Xiaoxiang; Li, Ning

    2016-01-01

    Muffs and beard (Mb) is a phenotype in chickens where groups of elongated feathers gather from both sides of the face (muffs) and below the beak (beard). It is an autosomal, incomplete dominant phenotype encoded by the Muffs and beard (Mb) locus. Here we use genome-wide association (GWA) analysis, linkage analysis, Identity-by-Descent (IBD) mapping, array-CGH, genome re-sequencing and expression analysis to show that the Mb allele causing the Mb phenotype is a derived allele where a complex structural variation (SV) on GGA27 leads to an altered expression of the gene HOXB8. This Mb allele was shown to be completely associated with the Mb phenotype in nine other independent Mb chicken breeds. The Mb allele differs from the wild-type mb allele by three duplications, one in tandem and two that are translocated to that of the tandem repeat around 1.70 Mb on GGA27. The duplications contain total seven annotated genes and their expression was tested during distinct stages of Mb morphogenesis. A continuous high ectopic expression of HOXB8 was found in the facial skin of Mb chickens, strongly suggesting that HOXB8 directs this regional feather-development. In conclusion, our results provide an interesting example of how genomic structural rearrangements alter the regulation of genes leading to novel phenotypes. Further, it again illustrates the value of utilizing derived phenotypes in domestic animals to dissect the genetic basis of developmental traits, herein providing novel insights into the likely role of HOXB8 in feather development and differentiation. PMID:27253709

  17. Extended Pre-Transit Structures and the Exosphere Detected for HD189733b in Optical Hydrogen Balmer Line Absorption

    NASA Astrophysics Data System (ADS)

    Redfield, Seth; Cauley, P. Wilson; Jensen, Adam G.; Barman, Travis; Endl, Michael; Cochran, William

    2015-12-01

    We present two separate observations of HD189733b in the three strongest hydrogen Balmer lines (H-alpha, H-beta, and H-gamma), with HiRES on Keck I that show definitive in-transit absorption, confirming the detection with the HET by Jensen et al. (2012), as well as, significant pre-transit absorption. Recently, pre-transit absorption in UV metal transitions of the hot Jupiter exoplanets HD 189733b and WASP12-b have been interpreted as being caused by material compressed in a planetary bow shock, however our observations are the first to densely time-sample and redundantly detect these extended planetary structures. While our first observations (obtained in 2013 and presented in Cauley et al. 2015), were consistent with a bow shock, our subsequent observation taken in August 2015 show pre-transit absorption but with a pattern that is inconsistent with the 2013 model. Instead, the observations indicate significant variability in the strength and timing of the pre-transit absorption. We also find differences in the strength of the in-transit exospheric absorption as well. These changes could be indicative of variability in the extreme stellar wind properties found at just 8 stellar radii, which could drive the extended atmospheric interaction between star and planet. The pre-transit absorption in 2013 was first observed 65 minutes prior to transit (corresponding to a linear distance of ~7 planetary radii), although it could have started earlier. The pre-transit signal in 2015, which is well sampled, is first detected 165 minutes prior to transit (a linear distance of ~17 planetary radii). The line shape of the pre-transit feature and the shape of the time series absorption provide the strongest constraints on the morphology and physical characteristics of extended structures around the exoplanet. The absorption strength observed in the Balmer lines indicates an optically thick, but physically small, geometry. If part of this extended structure is a bow shock mediated

  18. Growth in Turface® clay permits root hair phenotyping along the entire crown root in cereal crops and demonstrates that root hair growth can extend well beyond the root hair zone.

    PubMed

    Goron, Travis L; Watts, Sophia; Shearer, Charles; Raizada, Manish N

    2015-01-01

    In cereal crops, root hairs are reported to function within the root hair zone to carry out important roles in nutrient and water absorption. Nevertheless, these single cells remain understudied due to the practical challenges of phenotyping these delicate structures in large cereal crops growing on soil or other growth systems. Here we present an alternative growth system for examining the root hairs of cereal crops: the use of coarse Turface® clay alongside fertigation. This system allowed for root hairs to be easily visualized along the entire lengths of crown roots in three different cereal crops (maize, wheat, and finger millet). Surprisingly, we observed that the root hairs in these crops continued to grow beyond the canonical root hair zone, with the most root hair growth occurring on older crown root segments. We suggest that the Turface® fertigation system may permit a better understanding of the changing dynamics of root hairs as they age in large plants, and may facilitate new avenues for crop improvement below ground. However, the relevance of this system to field conditions must be further evaluated in other crops. PMID:25889276

  19. Variational-method-based higher order mode analysis extendible to realistic tapered disk-loaded structures

    NASA Astrophysics Data System (ADS)

    Wang, L. F.; Lin, Y. Z.; Higo, T.

    2002-04-01

    In order to obtain high luminosity and energy efficiency in future linear colliders, most designs for e + and e - collisions in the TeV range will use multi-bunch operation. Therefore, the study of higher order modes excited by previous bunches in the train becomes very important for the optimal design of the accelerator components. Many designs have used tapered disk-loaded waveguides for acceleration. Various numerical methods have been used for the modal analysis of the structure. In this paper, a high-precision eigenmode-computation analysis based on a variational method will be discussed. It allows for rounding the edge of a disk hole without any approximation in shape treatment and calculates the exactly synchronous modes. It converges much faster than the mesh-based computer code SUPERFISH. Good agreement was observed between the results of the variational method and those of other methods.

  20. OpenMx 2.0: Extended Structural Equation and Statistical Modeling.

    PubMed

    Neale, Michael C; Hunter, Michael D; Pritikin, Joshua N; Zahery, Mahsa; Brick, Timothy R; Kirkpatrick, Robert M; Estabrook, Ryne; Bates, Timothy C; Maes, Hermine H; Boker, Steven M

    2016-06-01

    The new software package OpenMx 2.0 for structural equation and other statistical modeling is introduced and its features are described. OpenMx is evolving in a modular direction and now allows a mix-and-match computational approach that separates model expectations from fit functions and optimizers. Major backend architectural improvements include a move to swappable open-source optimizers such as the newly written CSOLNP. Entire new methodologies such as item factor analysis and state space modeling have been implemented. New model expectation functions including support for the expression of models in LISREL syntax and a simplified multigroup expectation function are available. Ease-of-use improvements include helper functions to standardize model parameters and compute their Jacobian-based standard errors, access to model components through standard R $ mechanisms, and improved tab completion from within the R Graphical User Interface. PMID:25622929

  1. A framework for performance measurement in university using extended network data envelopment analysis (DEA) structures

    NASA Astrophysics Data System (ADS)

    Kashim, Rosmaini; Kasim, Maznah Mat; Rahman, Rosshairy Abd

    2015-12-01

    Measuring university performance is essential for efficient allocation and utilization of educational resources. In most of the previous studies, performance measurement in universities emphasized the operational efficiency and resource utilization without investigating the university's ability to fulfill the needs of its stakeholders and society. Therefore, assessment of the performance of university should be separated into two stages namely efficiency and effectiveness. In conventional DEA analysis, a decision making unit (DMU) or in this context, a university is generally treated as a black-box which ignores the operation and interdependence of the internal processes. When this happens, the results obtained would be misleading. Thus, this paper suggest an alternative framework for measuring the overall performance of a university by incorporating both efficiency and effectiveness and applies network DEA model. The network DEA models are recommended because this approach takes into account the interrelationship between the processes of efficiency and effectiveness in the system. This framework also focuses on the university structure which is expanded from the hierarchical to form a series of horizontal relationship between subordinate units by assuming both intermediate unit and its subordinate units can generate output(s). Three conceptual models are proposed to evaluate the performance of a university. An efficiency model is developed at the first stage by using hierarchical network model. It is followed by an effectiveness model which take output(s) from the hierarchical structure at the first stage as a input(s) at the second stage. As a result, a new overall performance model is proposed by combining both efficiency and effectiveness models. Thus, once this overall model is realized and utilized, the university's top management can determine the overall performance of each unit more accurately and systematically. Besides that, the result from the network

  2. The Star Formation History and Extended Structure of the Hercules Milky Way Satellite

    NASA Astrophysics Data System (ADS)

    Sand, David J.; Olszewski, Edward W.; Willman, Beth; Zaritsky, Dennis; Seth, Anil; Harris, Jason; Piatek, Slawomir; Saha, Abi

    2009-10-01

    We present imaging of the recently discovered Hercules Milky Way satellite and its surrounding regions to study its structure, star formation history and to thoroughly search for signs of disruption. We robustly determine the distance, luminosity, size, and morphology of Hercules utilizing a bootstrap approach to characterize our uncertainties. We derive a distance to Hercules via a comparison to empirical and theoretical isochrones, finding a best match with the isochrone of M92, which yields a distance of 133 ± 6 kpc. As previous studies have found, Hercules is very elongated, with epsilon = 0.67 ± 0.03 and a half-light radius of rh sime 230 pc. Using the color-magnitude-fitting package StarFISH, we determine that Hercules is old (>12 Gyr) and metal-poor ([Fe/H] ~ -2.0), with a spread in metallicity, in agreement with previous spectroscopic work. This result is robust with respect to slight variations in the distance to Hercules and mismatches between the observed Hercules color-magnitude diagram and theoretical isochrones. We infer a total absolute magnitude of MV = -6.2 ± 0.4. Our innovative search for external Hercules structure both in the plane of the sky and along the line of sight yields some evidence that Hercules is embedded in a larger stream of stars. A clear stellar extension is seen to the northwest with several additional candidate stellar overdensities along the position angle of Hercules out to ~35' (~1.3 kpc). While the association of any of the individual stellar overdensities with Hercules is difficult to determine, we do show that the summed color-magnitude diagram of all three is consistent with Hercules' stellar population. Finally, we estimate that any change in the distance to Hercules across its face is at most ~6 kpc, and the data are consistent with Hercules being at the same distance throughout. Based on data acquired using the Large Binocular Telescope (LBT). The LBT is an international collaboration among institutions in the US

  3. Extended Fine Structure Studies of Surface Reactions of Oxygen and Potassium on ALUMINUM(111)

    NASA Astrophysics Data System (ADS)

    Kim, Eungsoo

    1992-01-01

    The photoemission EXAFS (PEXAFS) technique was applied to determine the surface structures of Al(111) resulting from oxidation, potassium adsorption, and coadsorption of oxygen and potassium. Various elastic photopeaks, and the bulk and surface plasmon loss peaks were used. This technique has proved to be a powerful tool for the surface study because of its chemical sensitivity and surface sensitivity. In clean Al(111) the first and second nearest distances of Al-Al we obtained using the Al 2p elastic photopeak and plasmon loss peaks agree with the bulk values and, hence, no evidence of surface relaxation is found within experimental uncertainty. In the initial oxidation of Al(111), at the exposure of 50L oxygen, the 1.4 eV characteristic chemical shift of the chemisorbed phase was observed. Using the unshifted Al 2p and O 2s photopeaks, the Al-O, Al-Al, and O-O interatomic distances were determined. These results suggest that the oxygen atoms exist in the three-fold hollow sites above the Al surface. This is the first EXAFS measurement using the O 2s edge. With 1000L exposure of oxygen the photoemission study showed a 2.7 eV chemical shift due to an oxide-like phase. By using the unshifted and shifted Al 2p photopeaks, the Al-O and Al-Al distances were determined. These results indicate that the oxygen atoms are located at the octahedral sites below the surface, that is, the alpha -Al_2O_3 (corundum)-like phase is formed. For the potassium adsorption study, 0.2 monolayer (ML) and 1 ML of K were deposited at room temperature. The LEED pattern of the 1 ML K deposit shows a (surd 3 x surd3)R30^ circ structure. Using the Al 2p and K 3p photopeaks, the Al-Al, Al-K, and K-K distances were determined. These results suggest that the K is not highly ionic and tends toward metallic as the coverage increases. Furthermore we find cluster formation of potassium atoms at low coverage, and the observed LEED pattern agrees well with the PEXAFS results. With 10L of oxygen exposure

  4. A unique tetrameric structure of deer plasma haptoglobin--an evolutionary advantage in the Hp 2-2 phenotype with homogeneous structure.

    PubMed

    Lai, I H; Lin, Kung-Yu; Larsson, Mikael; Yang, Ming Chi; Shiau, Chuen-Huei; Liao, Ming-Huei; Mao, Simon J T

    2008-03-01

    Similar to blood types, human plasma haptoglobin (Hp) is classified into three phenotypes: Hp 1-1, 2-1 and 2-2. They are genetically inherited from two alleles Hp 1 and Hp 2 (represented in bold), but only the Hp 1-1 phenotype is found in almost all animal species. The Hp 2-2 protein consists of complicated large polymers cross-linked by alpha2-beta subunits or (alpha2-beta)n (where n>or=3, up to 12 or more), and is associated with the risk of the development of diabetic, cardiovascular and inflammatory diseases. In the present study, we found that deer plasma Hp mimics human Hp 2, containing a tandem repeat over the alpha-chain based on our cloned cDNA sequence. Interestingly, the isolated deer Hp is homogeneous and tetrameric, i.e. (alpha-beta)4, although the locations of -SH groups (responsible for the formation of polymers) are exactly identical to that of human. Denaturation of deer Hp using 6 m urea under reducing conditions (143 mmbeta-mercaptoethanol), followed by renaturation, sustained the formation of (alpha-beta)4, suggesting that the Hp tetramers are not randomly assembled. Interestingly, an alpha-chain monoclonal antibody (W1), known to recognize both human and deer alpha-chains, only binds to intact human Hp polymers, but not to deer Hp tetramers. This implies that the epitope of the deer alpha-chain is no longer exposed on the surface when Hp tetramers are formed. We propose that steric hindrance plays a major role in determining the polymeric formation in human and deer polymers. Phylogenetic and immunochemical analyses revealed that the Hp 2 allele of deer might have arisen at least 25 million years ago. A mechanism involved in forming Hp tetramers is proposed and discussed, and the possibility is raised that the evolved tetrameric structure of deer Hp might confer a physiological advantage. PMID:18298795

  5. Multiresistant Uropathogenic Escherichia coli from a Region in India Where Urinary Tract Infections Are Endemic: Genotypic and Phenotypic Characteristics of Sequence Type 131 Isolates of the CTX-M-15 Extended-Spectrum-β-Lactamase-Producing Lineage

    PubMed Central

    Hussain, Arif; Ewers, Christa; Nandanwar, Nishant; Guenther, Sebastian; Jadhav, Savita; Wieler, Lothar H.

    2012-01-01

    Escherichia coli sequence type 131 (O25b:H4), associated with the CTX-M-15 extended-spectrum beta-lactamases (ESBLs) and linked predominantly to the community-onset antimicrobial-resistant infections, has globally emerged as a public health concern. However, scant attention is given to the understanding of the molecular epidemiology of these strains in high-burden countries such as India. Of the 100 clinical E. coli isolates obtained by us from a setting where urinary tract infections are endemic, 16 ST131 E. coli isolates were identified by multilocus sequence typing (MLST). Further, genotyping and phenotyping methods were employed to characterize their virulence and drug resistance patterns. All the 16 ST131 isolates harbored the CTX-M-15 gene, and half of them also carried TEM-1; 11 of these were positive for blaOXA groups 1 and 12 for aac(6′)-Ib-cr. At least 12 isolates were refractory to four non-beta-lactam antibiotics: ciprofloxacin, gentamicin, sulfamethoxazole-trimethoprim, and tetracycline. Nine isolates carried the class 1 integron. Plasmid analysis indicated a large pool of up to six plasmids per strain with a mean of approximately three plasmids. Conjugation and PCR-based replicon typing (PBRT) revealed that the spread of resistance was associated with the FIA incompatibility group of plasmids. Pulsed-field gel electrophoresis (PFGE) and genotyping of the virulence genes showed a low level of diversity among these strains. The association of ESBL-encoding plasmid with virulence was demonstrated in transconjugants by serum assay. None of the 16 ST131 ESBL-producing E. coli strains were known to synthesize carbapenemase enzymes. In conclusion, our study reports a snapshot of the highly virulent/multiresistant clone ST131 of uropathogenic E. coli from India. This study suggests that the ST131 genotypes from this region are clonally evolved and are strongly associated with the CTX-M-15 enzyme, carry a high antibiotic resistance background, and have

  6. High structural resolution hydroxyl radical protein footprinting reveals an extended Robo1-heparin binding interface.

    PubMed

    Li, Zixuan; Moniz, Heather; Wang, Shuo; Ramiah, Annapoorani; Zhang, Fuming; Moremen, Kelley W; Linhardt, Robert J; Sharp, Joshua S

    2015-04-24

    Interaction of transmembrane receptors of the Robo family and the secreted protein Slit provides important signals in the development of the central nervous system and regulation of axonal midline crossing. Heparan sulfate, a sulfated linear polysaccharide modified in a complex variety of ways, serves as an essential co-receptor in Slit-Robo signaling. Previous studies have shown that closely related heparin octasaccharides bind to Drosophila Robo directly, and surface plasmon resonance analysis revealed that Robo1 binds more tightly to full-length unfractionated heparin. For the first time, we utilized electron transfer dissociation-based high spatial resolution hydroxyl radical protein footprinting to identify two separate binding sites for heparin interaction with Robo1: one binding site at the previously identified site for heparin dp8 and a second binding site at the N terminus of Robo1 that is disordered in the x-ray crystal structure. Mutagenesis of the identified N-terminal binding site exhibited a decrease in binding affinity as measured by surface plasmon resonance and heparin affinity chromatography. Footprinting also indicated that heparin binding induces a minor change in the conformation and/or dynamics of the Ig2 domain, but no major conformational changes were detected. These results indicate a second low affinity binding site in the Robo-Slit complex as well as suggesting the role of the Ig2 domain of Robo1 in heparin-mediated signal transduction. This study also marks the first use of electron transfer dissociation-based high spatial resolution hydroxyl radical protein footprinting, which shows great utility for the characterization of protein-carbohydrate complexes. PMID:25752613

  7. High Structural Resolution Hydroxyl Radical Protein Footprinting Reveals an Extended Robo1-Heparin Binding Interface*

    PubMed Central

    Li, Zixuan; Moniz, Heather; Wang, Shuo; Ramiah, Annapoorani; Zhang, Fuming; Moremen, Kelley W.; Linhardt, Robert J.; Sharp, Joshua S.

    2015-01-01

    Interaction of transmembrane receptors of the Robo family and the secreted protein Slit provides important signals in the development of the central nervous system and regulation of axonal midline crossing. Heparan sulfate, a sulfated linear polysaccharide modified in a complex variety of ways, serves as an essential co-receptor in Slit-Robo signaling. Previous studies have shown that closely related heparin octasaccharides bind to Drosophila Robo directly, and surface plasmon resonance analysis revealed that Robo1 binds more tightly to full-length unfractionated heparin. For the first time, we utilized electron transfer dissociation-based high spatial resolution hydroxyl radical protein footprinting to identify two separate binding sites for heparin interaction with Robo1: one binding site at the previously identified site for heparin dp8 and a second binding site at the N terminus of Robo1 that is disordered in the x-ray crystal structure. Mutagenesis of the identified N-terminal binding site exhibited a decrease in binding affinity as measured by surface plasmon resonance and heparin affinity chromatography. Footprinting also indicated that heparin binding induces a minor change in the conformation and/or dynamics of the Ig2 domain, but no major conformational changes were detected. These results indicate a second low affinity binding site in the Robo-Slit complex as well as suggesting the role of the Ig2 domain of Robo1 in heparin-mediated signal transduction. This study also marks the first use of electron transfer dissociation-based high spatial resolution hydroxyl radical protein footprinting, which shows great utility for the characterization of protein-carbohydrate complexes. PMID:25752613

  8. Extended structure and fate of the nucleus in Henize 2-10

    SciTech Connect

    Nguyen, Dieu D.; Seth, Anil C.; Den Brok, Mark; Reines, Amy E.; Sand, David; McLeod, Brian E-mail: aseth@astro.utah.edu E-mail: areines@nrao.edu E-mail: bmcleod@cfa.harvard.edu

    2014-10-10

    We investigate the structure and nuclear region of the black hole (BH) hosting galaxy Henize 2-10. Surface brightness profiles are analyzed using Magellan/Megacam g- and r-band images. Excluding the central starburst, we find a best-fit two-component Sérsic profile with n {sub in} ∼ 0.6, r {sub eff,} {sub in} ∼ 260 pc and n {sub out} ∼ 1.8, r ∼ 1 kpc. Integrating out to our outermost data point (100'' ∼ 4.3 kpc), we calculate M{sub g} = –19.2 and M{sub r} = –19.8. The corresponding enclosed stellar mass is M {sub *} ∼ (10 ± 3) × 10{sup 9} M {sub ☉}, ∼3 × larger than previous estimates. Apart from the central ≲500 pc, with blue colors and an irregular morphology, the galaxy appears to be an early-type system. The outer color is quite red, (g – r){sub 0} = 0.75, suggesting a dominant old population. We study the nuclear region of the galaxy using archival Gemini/NIFS K-band adaptive optics spectroscopy and Hubble Space Telescope imaging. We place an upper limit on the BH mass of ∼10{sup 7} M {sub ☉} from the NIFS data, consistent with that from the M {sub BH}-radio-X-ray fundamental plane. No coronal lines are seen, but a Brγ source is located at the position of the BH with a luminosity consistent with the X-ray emission. The starburst at the center of Henize 2-10 has led to the formation of several super star clusters, which are within ∼100 pc of the BH. We examine the fate of the nucleus by estimating the dynamical masses and dynamical friction timescales of the clusters. The most massive clusters (∼10{sup 6} M {sub ☉}) have τ{sub dyn} ≲ 200 Myr, and thus Henize 2-10 may represent a rare snapshot of nuclear star cluster formation around a preexisting massive BH.

  9. Phenotypic and Molecular Characterization of Antimicrobial Resistance in Klebsiella spp. Isolates from Companion Animals in Japan: Clonal Dissemination of Multidrug-Resistant Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae

    PubMed Central

    Harada, Kazuki; Shimizu, Takae; Mukai, Yujiro; Kuwajima, Ken; Sato, Tomomi; Usui, Masaru; Tamura, Yutaka; Kimura, Yui; Miyamoto, Tadashi; Tsuyuki, Yuzo; Ohki, Asami; Kataoka, Yasushi

    2016-01-01

    The emergence of antimicrobial resistance in Klebsiella spp., including resistance to extended-spectrum cephalosporins (ESC) and fluoroquinolones, is of great concern in both human and veterinary medicine. In this study, we investigated the prevalence of antimicrobial resistance in a total of 103 Klebsiella spp. isolates, consisting of Klebsiella pneumoniae complex (KP, n = 89) and K. oxytoca (KO, n = 14) from clinical specimens of dogs and cats in Japan. Furthermore, we characterized the resistance mechanisms, including extended-spectrum β-lactamase (ESBL), plasmid-mediated AmpC β-lactamase (PABL), and plasmid-mediated quinolone resistance (PMQR); and assessed genetic relatedness of ESC-resistant Klebsiella spp. strains by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Antimicrobial susceptibility testing demonstrated that resistance rates to ampicillin, cephalothin, enrofloxacin, ciprofloxacin, trimethoprim/sulfamethoxazole, cefotaxime, gentamicin, tetracycline, chloramphenicol, amoxicillin-clavulanic acid, and cefmetazole were 98.1, 37.9, 37.9, 35.9, 35.0, 34.0, 31.1, 30.1, 28.2, 14.6, and 6.8%, respectively. Phenotypic testing detected ESBLs and/or AmpC β-lactamases in 31 of 89 (34.8%) KP isolates, but not in KO isolates. Resistances to 5 of the 12 antimicrobials tested, as well as the three PMQRs [qnrB, qnrS, and aac(6′)-Ib-cr], were detected significantly more frequently in ESBL-producing KP, than in non-ESBL-producing KP and KO. The most frequent ESBL was CTX-M-15 (n = 13), followed by CTX-M-14 (n = 7), CTX-M-55 (n = 6), SHV-2 (n = 5), CTX-M-2 (n = 2), and CTX-M-3 (n = 2). Based on the rpoB phylogeny, all ESBL-producing strains were identified as K. pneumoniae, except for one CTX-M-14-producing strain, which was identified as K. quasipneumoniae. All of AmpC β-lactamase positive isolates (n = 6) harbored DHA-1, one of the PABLs. Based on MLST and PFGE analysis, ST15 KP clones producing CTX-M-2, CTX-M-15, CTX-M-55, and

  10. Phenotypic and Molecular Characterization of Antimicrobial Resistance in Klebsiella spp. Isolates from Companion Animals in Japan: Clonal Dissemination of Multidrug-Resistant Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae.

    PubMed

    Harada, Kazuki; Shimizu, Takae; Mukai, Yujiro; Kuwajima, Ken; Sato, Tomomi; Usui, Masaru; Tamura, Yutaka; Kimura, Yui; Miyamoto, Tadashi; Tsuyuki, Yuzo; Ohki, Asami; Kataoka, Yasushi

    2016-01-01

    The emergence of antimicrobial resistance in Klebsiella spp., including resistance to extended-spectrum cephalosporins (ESC) and fluoroquinolones, is of great concern in both human and veterinary medicine. In this study, we investigated the prevalence of antimicrobial resistance in a total of 103 Klebsiella spp. isolates, consisting of Klebsiella pneumoniae complex (KP, n = 89) and K. oxytoca (KO, n = 14) from clinical specimens of dogs and cats in Japan. Furthermore, we characterized the resistance mechanisms, including extended-spectrum β-lactamase (ESBL), plasmid-mediated AmpC β-lactamase (PABL), and plasmid-mediated quinolone resistance (PMQR); and assessed genetic relatedness of ESC-resistant Klebsiella spp. strains by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Antimicrobial susceptibility testing demonstrated that resistance rates to ampicillin, cephalothin, enrofloxacin, ciprofloxacin, trimethoprim/sulfamethoxazole, cefotaxime, gentamicin, tetracycline, chloramphenicol, amoxicillin-clavulanic acid, and cefmetazole were 98.1, 37.9, 37.9, 35.9, 35.0, 34.0, 31.1, 30.1, 28.2, 14.6, and 6.8%, respectively. Phenotypic testing detected ESBLs and/or AmpC β-lactamases in 31 of 89 (34.8%) KP isolates, but not in KO isolates. Resistances to 5 of the 12 antimicrobials tested, as well as the three PMQRs [qnrB, qnrS, and aac(6')-Ib-cr], were detected significantly more frequently in ESBL-producing KP, than in non-ESBL-producing KP and KO. The most frequent ESBL was CTX-M-15 (n = 13), followed by CTX-M-14 (n = 7), CTX-M-55 (n = 6), SHV-2 (n = 5), CTX-M-2 (n = 2), and CTX-M-3 (n = 2). Based on the rpoB phylogeny, all ESBL-producing strains were identified as K. pneumoniae, except for one CTX-M-14-producing strain, which was identified as K. quasipneumoniae. All of AmpC β-lactamase positive isolates (n = 6) harbored DHA-1, one of the PABLs. Based on MLST and PFGE analysis, ST15 KP clones producing CTX-M-2, CTX-M-15, CTX-M-55, and

  11. Evidence of the nature of core-level photoemission satellites using angle-resolved photoemission extended fine structure

    SciTech Connect

    Moler, E.J.; Kellar, S.A.; Huff, W.R.A.

    1997-04-01

    The authors present a unique method of experimentally determining the angular momentum and intrinsic/extrinsic origin of core-level photoemission satellites by examining the satellite diffraction pattern in the Angle Resolved Photoemission Extended Fine Structure (ARPEFS) mode. They show for the first time that satellite peaks not associated with chemically differentiated atomic species display an ARPEFS intensity oscillation. They present ARPEFS data for the carbon 1s from ({radical}3x{radical}3)R30 CO/Cu(111) and p2mg(2xl)CO/Ni(110), nitrogen 1s from c(2x2) N{sub 2}/Ni(100), cobalt 1s from p(1x1)Co/Cu(100), and nickel 3p from clean nickel (111). The satellite peaks and tails of the Doniach-Sunjic line shapes in all cases exhibit ARPEFS curves which indicate an angular momentum identical to the main peak and are of an intrinsic nature.

  12. Anharmonicity of the Bending and Stretching Vibrations Observed in Extended X-Ray Absorption Fine Structure of Tetrahedral Molecules

    NASA Astrophysics Data System (ADS)

    Yokoyama, Toshihiko; Yonamoto, Yoshiki; Ohta, Toshiaki

    1996-12-01

    We have measured and analyzed the temperature dependence of extended X-ray absorption fine structure (EXAFS) spectra of tetrahedral systems MBr4 ( M=C, Si, Ge). The EXAFS analysis by means of the cumulant expansion technique enables one to obtain information about force constants including the third-order anharmonicity. The second-order cumulants obtained experimentally are in excellent agreement with the values expected by the vibrational data and the third-order cumulants have been determined successfully. For the first nearest neighbor (NN) Br M shells the stretching motions are apparently dominant to describe EXAFS, while for the second NN Br Br shell the bending modes are found to contribute significantly to the cumulants especially for the third-order anharmonicity. The obtained force constants are compared to each other and the origin of observed bending anharmonicity is discussed.

  13. Applications of extended X-ray absorption fine-structure spectroscopy to studies of bimetallic nanoparticle catalysts.

    PubMed

    Frenkel, Anatoly I

    2012-12-21

    Extended X-ray absorption fine structure (EXAFS) spectroscopy has been used to study short range order in heterometallic alloys for almost four decades. In this critical review, experimental, theoretical and data analytical approaches are revisited to examine their power, and limitations, in studies of bimetallic nanocatalysts. This article covers the basics of EXAFS experiments, data analysis, and modelling of nanoscale clusters. It demonstrates that, in the best case scenario, quantitative information about the nanocatalyst's size, shape, details of core-shell architecture, as well as static and dynamic disorder in metal-metal bond lengths can be obtained. The article also emphasizes the main challenge accompanying such insights: the need to account for the statistical nature of the EXAFS technique, and discusses corrective strategies. PMID:22833100

  14. A Search for Structure in PAH Emission in Extended Sources at 3.3 and 3.4 Microns

    NASA Technical Reports Server (NTRS)

    Bregman, Jesse; Temi, P.; Rank, D. M.; Sloan, G. C.; Schultz, A. S. B.; Witteborn, Fred C. (Technical Monitor)

    1994-01-01

    We have observed three extended sources of the infrared emission features associated with polycyclic aromatic hydrocarbons (PAHs), using a 128x128 InSb array mounted on the 1.5 m NASA/Steward telescope on Mt. Lemmon. We used a CVF (1.5% bandpass) to isolate the emission from the 3.29 and 3.40 microns PAH features in NGC 1333 #3, Sharpless 106, and the Orion Bar. In all three sources, the 3.29 and 3.40 microns emission features arise from the same regions, but show decidedly different structure. We are analyzing the images to determine the relationship of the 3.40 microns feature to the main feature at 3.29 microns. The 3.40 microns feature may be a vibrational overtone of the 3.29 microns feature, or it may arise from attached molecular sidegroups.

  15. Extended x-ray absorption fine structure spectroscopy in Co{sub 0.013}NbSe{sub 2}.

    SciTech Connect

    Weber, F.; Castellan, J.-P.; Rosenkranz, S.; Osborn, R.; Rosenmann, D.; Iavarone, M.; Materials Science Division

    2010-01-01

    We present a study of the local environment of the Co atom in single crystalline Co{sub x}NbSe{sub 2}, x = 0.013, via Extended X-ray Absorption Fine Structure (EXAFS) measurements at the Co K-edge (7.7 keV) at various temperatures. Co intercalation quickly suppresses superconductivity and the charge-density wave (CDW) present in pure NbSe{sub 2}. In order to study the effect of impurities on superconducting and CDW states one has to verify the random distribution of the intercalated atoms in contrast to possible clustering which could lead to additional, e.g. magnetic, interactions in the case of Co intercalation. Our measurements show that the Co atoms are indeed randomly distributed in Co{sub 0.013}NbSe{sub 2}.

  16. Topolology-symmetry law of structure of natural titanosilicate micas and related heterophyllosilicates based on the extended OD theory: Structure prediction

    NASA Astrophysics Data System (ADS)

    Belokoneva, E. L.; Topnikova, A. P.; Aksenov, S. M.

    2015-01-01

    A topology-symmetry analysis of the structures in the family of titanosilicate micas and related heterophyllosilicates based on the extended OD theory reveals their kinship with the family of rhodezite, delhayelite, and other minerals that had been analyzed earlier by distinguishing sheets common for all the structures. Like in the family studied earlier, the structural variety of a more complex titanosilicate family is determined by different local symmetries of sheets. Sheets consist of central O layers of edge-sharing octahedra and H layers formed by tetrahedra connected into diortho groups and Ti(Nb,Fe) semioctahedra (octahedra). Three patterns of connection of O and H layers correspond to sheet symmetry P2/ m, P21/ m, and . Various symmetry modes of sheet connection in the structures are analyzed. Hypothetical structures, including structures with a higher degree of disorder, which can be found in nature or obtained by crystal synthesis, are deduced. Factors responsible for structural variety, including the existence of two main sheet varieties (with P2/ m and P21/ m symmetry) are considered a consequence of the difference in the chemism of the mineral formation medium.

  17. Metabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophila

    PubMed Central

    Williams, Stephanie; Dew-Budd, Kelly; Davis, Kristen; Anderson, Julie; Bishop, Ruth; Freeman, Kenda; Davis, Dana; Bray, Katherine; Perkins, Lauren; Hubickey, Joana; Reed, Laura K.

    2015-01-01

    Genetic and environmental factors influence complex disease in humans, such as metabolic syndrome, and Drosophila melanogaster serves as an excellent model in which to test these factors experimentally. Here we explore the modularity of endophenotypes with an in-depth reanalysis of a previous study by Reed et al. (2014), where we raised 20 wild-type genetic lines of Drosophila larvae on four diets and measured gross phenotypes of body weight, total sugar, and total triglycerides, as well as the endophenotypes of metabolomic and whole-genome expression profiles. We then perform new gene expression experiments to test for conservation of phenotype-expression correlations across different diets and populations. We find that transcript levels correlated with gross phenotypes were enriched for puparial adhesion, metamorphosis, and central energy metabolism functions. The specific metabolites L-DOPA and N-arachidonoyl dopamine make physiological links between the gross phenotypes across diets, whereas leucine and isoleucine thus exhibit genotype-by-diet interactions. Between diets, we find low conservation of the endophenotypes that correlate with the gross phenotypes. Through the follow-up expression study, we found that transcript-trait correlations are well conserved across populations raised on a familiar diet, but on a novel diet, the transcript-trait correlations are no longer conserved. Thus, physiological canalization of metabolic phenotypes breaks down in a novel environment exposing cryptic variation. We cannot predict the physiological basis of disease in a perturbing environment from profiles observed in the ancestral environment. This study demonstrates that variation for disease traits within a population is acquired through a multitude of physiological mechanisms, some of which transcend genetic and environmental influences, and others that are specific to an individual’s genetic and environmental context. PMID:26530416

  18. Metabolomic and Gene Expression Profiles Exhibit Modular Genetic and Dietary Structure Linking Metabolic Syndrome Phenotypes in Drosophila.

    PubMed

    Williams, Stephanie; Dew-Budd, Kelly; Davis, Kristen; Anderson, Julie; Bishop, Ruth; Freeman, Kenda; Davis, Dana; Bray, Katherine; Perkins, Lauren; Hubickey, Joana; Reed, Laura K

    2015-12-01

    Genetic and environmental factors influence complex disease in humans, such as metabolic syndrome, and Drosophila melanogaster serves as an excellent model in which to test these factors experimentally. Here we explore the modularity of endophenotypes with an in-depth reanalysis of a previous study by Reed et al. (2014), where we raised 20 wild-type genetic lines of Drosophila larvae on four diets and measured gross phenotypes of body weight, total sugar, and total triglycerides, as well as the endophenotypes of metabolomic and whole-genome expression profiles. We then perform new gene expression experiments to test for conservation of phenotype-expression correlations across different diets and populations. We find that transcript levels correlated with gross phenotypes were enriched for puparial adhesion, metamorphosis, and central energy metabolism functions. The specific metabolites L-DOPA and N-arachidonoyl dopamine make physiological links between the gross phenotypes across diets, whereas leucine and isoleucine thus exhibit genotype-by-diet interactions. Between diets, we find low conservation of the endophenotypes that correlate with the gross phenotypes. Through the follow-up expression study, we found that transcript-trait correlations are well conserved across populations raised on a familiar diet, but on a novel diet, the transcript-trait correlations are no longer conserved. Thus, physiological canalization of metabolic phenotypes breaks down in a novel environment exposing cryptic variation. We cannot predict the physiological basis of disease in a perturbing environment from profiles observed in the ancestral environment. This study demonstrates that variation for disease traits within a population is acquired through a multitude of physiological mechanisms, some of which transcend genetic and environmental influences, and others that are specific to an individual's genetic and environmental context. PMID:26530416

  19. Antibacterial activities and structure-activity relationships of a panel of 48 compounds from Kenyan plants against multidrug resistant phenotypes.

    PubMed

    Omosa, Leonidah K; Midiwo, Jacob O; Mbaveng, Armelle T; Tankeo, Simplice B; Seukep, Jackson A; Voukeng, Igor K; Dzotam, Joachim K; Isemeki, John; Derese, Solomon; Omolle, Ruth A; Efferth, Thomas; Kuete, Victor

    2016-01-01

    In the current study forty eight compounds belonging to anthraquinones, naphthoquinones, benzoquinones, flavonoids (chalcones and polymethoxylated flavones) and diterpenoids (clerodanes and kauranes) were explored for their antimicrobial potential against a panel of sensitive and multi-drug resistant Gram-negative and Gram-positive bacteria. The minimal inhibitory concentration (MIC) determinations on the tested bacteria were conducted using modified rapid INT colorimetric assay. To evaluate the role of efflux pumps in the susceptibility of Gram-negative bacteria to the most active compounds, they were tested in the presence of phenylalanine arginine β-naphthylamide (PAβN) (at 30 µg/mL) against selected multidrug resistance (MDR) bacteria. The anthraquinone, emodin, naphthaquinone, plumbagin and the benzoquinone, rapanone were active against methicillin resistant Staphylococcus aureus (MRSA) strains of bacteria with MIC values ranging from 2 to 128 μg/mL. The structure activity relationships of benzoquinones against the MDR Gram-negative phenotype showed antibacterial activities increasing with increase in side chain length. In the chalcone series the presence of a hydroxyl group at C3' together with a methoxy group and a second hydroxyl group in meta orientation in ring B of the chalcone skeleton appeared to be necessary for minimal activities against MRSA. In most cases, the optimal potential of the active compounds were not attained as they were extruded by bacterial efflux pumps. However, the presence of the PAβN significantly increased the antibacterial activities of emodin against Gram-negative MDR E. coli AG102, 100ATet; K. pneumoniae KP55 and KP63 by >4-64 g/mL. The antibacterial activities were substantially enhanced and were higher than those of the standard drug, chloramphenicol. These data clearly demonstrate that the active compounds, having the necessary pharmacophores for antibacterial activities, including some quinones and chalcones are

  20. Probing the Limits of Conventional Extended X-ray Absorption Fine Structure Analysis Using Thiolated Gold Nanoparticles.

    PubMed

    Chill, Samuel T; Anderson, Rachel M; Yancey, David F; Frenkel, Anatoly I; Crooks, Richard M; Henkelman, Graeme

    2015-04-28

    We present a method for quantifying the accuracy of extended X-ray absorption fine structure (EXAFS) fitting models. As a test system, we consider the structure of bare Au147 nanoparticles as well as particles bound with thiol ligands, which are used to systematically vary disorder in the atomic structure of the nanoparticles. The accuracy of the fitting model is determined by comparing two distributions of bond lengths: (1) a direct average over a molecular dynamics (MD) trajectory using forces and energies from density functional theory (DFT) and (2) a fit to the theoretical EXAFS spectra generated from that same trajectory. Both harmonic and quasi-harmonic EXAFS fitting models are used to characterize the first-shell Au-Au bond length distribution. The harmonic model is found to significantly underestimate the coordination number, disorder, and bond length. The quasi-harmonic model, which includes the third cumulant of the first-shell bond length distribution, yields accurate bond lengths, but incorrectly predicts a decrease in particle size and little change in the disorder with increasing thiol ligands. A direct analysis of the MD data shows that the particle surfaces become much more disordered with ligand binding, and the high disorder is incorrectly interpreted by the EXAFS fitting models. Our DFT calculations compare well with experimental EXAFS measurements of Au nanoparticles, synthesized using a dendrimer encapsulation technique, showing that systematic errors in EXAFS fitting models apply to nanoparticles 1-2 nm in size. Finally we show that a combination of experimental EXAFS analysis with candidate models from DFT is a promising strategy for a more accurate determination of nanoparticle structures. PMID:25853740

  1. Differentiation of biological hydroxyapatite compounds by infrared spectroscopy, x-ray diffraction and extended x-ray absorption fine structure

    NASA Astrophysics Data System (ADS)

    Chassot, E.; Oudadesse, H.; Irigaray, J.; Curis, E.; Bénazeth, S.; Nicolis, I.

    2001-12-01

    Pure hydroxyapatite (HAP) and HAP doped with 800 ppm of zinc were implanted in cortical bone of femur diaphysis of ovines [J. L. Irigaray et al., Mater. Clin. Appl. 28, 399 (1999)]. We observed that the doped HAP was better resorbed than pure HAP. The first hypothesis is that zinc acts as a stimulator on macrophage cells and improves quantity and quality of osteoblast cells. The second hypothesis is that zinc yields HAP structure that is better resorbed in biological field. For our experiment we used HAP doped with 3000 ppm of zinc in order to have a good sensitivity. In the present work, chemical studies by inductively coupled plasma absorption emission spectrometry, x ray diffraction, and infrared were carried out to determine the composition of major and trace elements in the doped hydroxyapatite, and the crystallographic structure. These studies can indicate possible modifications induced by the insertion of zinc. We used the extended x-ray absorption fine structure experimental station of LURE (Orsay, France) to try to clarify the atomic surroundings of zinc in doped HAP structure and transformations induced in initial lattice. Despite the low zinc concentration, we got good quality fluorescence mode spectra. These spectra showed medium range order of the material that is consistent with its crystalline form. To perform the analysis, we compared the result obtained with another models like β tricalcium phosphate and we created theoretical models of zinc in substitution of calcium in order to reproduce as well as possible the experimental spectrum. After this study, only two models are coherent with experimental spectrum, zinc in substitution of calcium in site I and zinc in the interstice between the two hydroxydes.

  2. Synthesis, Structures, and Properties of π-Extended Double Helicene: A Combination of Planar and Nonplanar π-Systems.

    PubMed

    Fujikawa, Takao; Segawa, Yasutomo; Itami, Kenichiro

    2015-06-24

    The synthesis, structures, and properties of a π-extended double helicene 1 are described. This double helicene 1 was synthesized by a four-fold oxidative C-H biphenylation of naphthalene followed by the Scholl reaction or via five steps including the Suzuki-Miyaura cross-coupling reaction and the Scholl reaction. Due to the two helical substructures, 1 has three isomers, i.e., two enantiomers in a twisted form [(P,P) and (M,M)] and one diastereoisomer in a meso form. X-ray crystallographic analysis of the twisted isomers (twisted-1) revealed a tightly offset packing pattern of (P,P)- and (M,M)-twisted isomers, affording a three-dimensional lamellar stacking structure. A high isomerization barrier (43.5 kcal mol(-1)) and the relative thermal stability of twisted-1 isomer over meso-1 by 0.9 kcal mol(-1) were estimated by DFT calculations. The three isomers were successfully separated by chiral HPLC and characterized by circular dichroism spectroscopy as well as by TD-DFT studies. Electronic state variation resulting from the molecular geometry difference between the two diastereoisomers (twisted-1 and meso-1) was observed by UV-vis absorption and fluorescence spectra. PMID:26028308

  3. Dosage effect of high-amylose modifier gene(s) on the starch structure of maize amylose-extender mutant.

    PubMed

    Jiang, Hongxin; Campbell, Mark; Wu, Yusheng; Du, Shuangkui; Srichuwong, Sathaporn; Jane, Jay-Lin

    2015-01-21

    The objective of this study was to investigate how dosages of high-amylose modifier (HAM) gene(s) affected the structure of maize amylose extender (ae) mutant starch. GEMS-0067 (G), a homozygous mutant of ae and the HAM gene(s), and H99ae (H), an ae single mutant, were self-pollinated or inter-crossed to produce maize endosperms of G/G, G/H, H/G, and H/H with 3, 2, 1, and 0 doses of HAM gene(s), respectively. Endosperm starch was fractionated into amylopectin, amylose, and intermediate component (IC) of large and small molecular weights using 1-butanol precipitation of amylose followed by gel-permeation chromatography. Increases in the dosage of HAM gene(s) from 0 to 3 decreased the amylopectin content. The HAM-gene dosage significantly changed the branch chain-length of small-molecular-weight IC, but had little effect on the branch chain-length distributions of amylopectin and large-molecular-weight IC and the molecular structure of amylose. PMID:25495144

  4. Amyloid-β-Anti-Amyloid-β Complex Structure Reveals an Extended Conformation in the Immunodominant B-Cell Epitope

    SciTech Connect

    Miles, Luke A; Wun, Kwok S; Crespi, Gabriela A.N.; Fodero-Tavoletti, Michelle T; Galatis, Denise; Bagley, Christopher J; Beyreuther, Konrad; Masters, Colin L; Cappai, Roberto; McKinstry, William J; Barnham, Kevin J; Parker, Michael W

    2008-04-29

    Alzheimer's disease (AD) is the most common form of dementia. Amyloid-β (Aβ) peptide, generated by proteolytic cleavage of the amyloid precursor protein, is central to AD pathogenesis. Most pharmaceutical activity in AD research has focused on Aβ, its generation and clearance from the brain. In particular, there is much interest in immunotherapy approaches with a number of anti-Aβ antibodies in clinical trials. We have developed a monoclonal antibody, called WO2, which recognises the Aβ peptide. To this end, we have determined the three-dimensional structure, to near atomic resolution, of both the antibody and the complex with its antigen, the Aβ peptide. The structures reveal the molecular basis for WO2 recognition and binding of Aβ. The Aβ peptide adopts an extended, coil-like conformation across its major immunodominant B-cell epitope between residues 2 and 8. We have also studied the antibody-bound Aβ peptide in the presence of metals known to affect its aggregation state and show that WO2 inhibits these interactions. Thus, antibodies that target the N-terminal region of Aβ, such as WO2, hold promise for therapeutic development.

  5. Amyloid-β-Anti-Amyloid-β Complex Structure Reveals an Extended Conformation in the Immunodominant B-Cell Epitope

    SciTech Connect

    Miles, Luke A; Wun, Kwok S; Crespi, Gabriela A.N.; Fodero-Tavoletti, Michelle T; Galatis, Denise; Bagley, Christopher J; Beyreuther, Konrad; Masters, Colin L; Cappai, Roberto; McKinstry, William J; Barnham, Kevin J; Parker, Michael W

    2012-04-17

    Alzheimer's disease (AD) is the most common form of dementia. Amyloid-β (Aβ) peptide, generated by proteolytic cleavage of the amyloid precursor protein, is central to AD pathogenesis. Most pharmaceutical activity in AD research has focused on Aβ, its generation and clearance from the brain. In particular, there is much interest in immunotherapy approaches with a number of anti-Aβ antibodies in clinical trials. We have developed a monoclonal antibody, called WO2, which recognises the Aβ peptide. To this end, we have determined the three-dimensional structure, to near atomic resolution, of both the antibody and the complex with its antigen, the Aβ peptide. The structures reveal the molecular basis for WO2 recognition and binding of Aβ. The Aβ peptide adopts an extended, coil-like conformation across its major immunodominant B-cell epitope between residues 2 and 8. We have also studied the antibody-bound Aβ peptide in the presence of metals known to affect its aggregation state and show that WO2 inhibits these interactions. Thus, antibodies that target the N-terminal region of Aβ, such as WO2, hold promise for therapeutic development.

  6. Crystal chemistry and application development of uranyl extended structure and nanoscale materials and actinyl ion-substituted mineral phases

    NASA Astrophysics Data System (ADS)

    Wylie, Ernest M.

    The worldwide use of nuclear energy presents both significant advantages and challenges for society. Actinide research seeks to address these challenges and drive advancement in the fields of nuclear science and engineering. Here, key aspects of the fuel cycle are examined from both a fundamental and an applications-based perspective. Hydrothermal, ionothermal, room-temperature evaporation, and liquid diffusion synthesis techniques and single-crystal X-ray diffraction were used to study the structures of 18 uranyl compounds and six actinyl-doped mineral phases. These compounds represent a diverse group ranging from unique molecular clusters to novel and known extended structures isolated from aqueous and ionic liquid media. Ultrafiltration techniques were utilized to separate uranyl peroxide nanoclusters from complex aqueous solutions. Inductively coupled plasma optical emission spectroscopy and mass spectrometry were used to quantify elemental distributions in the feed and permeate solutions while Raman spectroscopy, small-angle X-ray scattering, and electrospray ionization mass spectrometry were used to define the characteristics of the cluster species across a range different solution conditions.

  7. Genetic Structure Associated with blaOXA-18, Encoding a Clavulanic Acid-Inhibited Extended-Spectrum Oxacillinase▿

    PubMed Central

    Naas, Thierry; Namdari, Fatemeh; Bogaerts, Pierre; Huang, Te-Din; Glupczynski, Youri; Nordmann, Patrice

    2008-01-01

    The genetic environment of the blaOXA-18 gene encoding a peculiar clavulanic acid-inhibitable Ambler class D extended-spectrum β-lactamase was determined from the prototype OXA-18-producing Pseudomonas aeruginosa MUS clinical isolate. An 8.2-kb genomic DNA fragment containing blaOXA-18 was cloned from P. aeruginosa MUS. Although most oxacillinases are located in integrons, blaOXA-18 lacked gene cassette-specific features. It was bracketed by two duplicated sequences containing ISCR19, a novel insertion sequence of the ISCR family of mobile elements; ΔintI1, a truncated integrase gene; and a truncated Δaac6′-Ib gene cassette. It is likely that ISCR19 was at the origin of the blaOXA-18 gene mobilization by a rolling-circle transposition event followed by homologous recombination. Furthermore, analysis of the cloned genomic DNA fragment revealed the presence of the integron-containing blaOXA-20 gene. Concomitantly, three P. aeruginosa clinical isolates, displaying a synergy image as determined by double-disk diffusion tests on cloxacillin-containing plates, were isolated from three patients hospitalized in different wards over a 9-month period at the Saint-Luc University hospital (Brussels, Belgium). These isolates were positive by PCR for blaOXA-18 and blaOXA-20 genes, genetically related to P. aeruginosa MUS as determined by pulsed-field gel electrophoresis, and carried the same blaOXA-18/blaOXA-20-associated genetic structures. This report characterized the genetic elements likely at the origin of blaOXA-18 gene mobilization in P. aeruginosa and suggests the spread of oxacillin-type extended-spectrum β-lactamases in P. aeruginosa at the Saint-Luc University hospital of Brussels, Belgium. PMID:18663027

  8. Genetic resources for phenotyping

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phenotyping of structured populations, along with molecular genotyping, will be essential for marker development in peanut. This research is essential for making the peanut genome sequence and genomic tools useful to breeders because it makes the connection between genes, gene markers, genetic maps...

  9. Structural and Dynamic Characterization of the C313Y Mutation in Myostatin Dimeric Protein, Responsible for the “Double Muscle” Phenotype in Piedmontese Cattle

    PubMed Central

    Bongiorni, Silvia; Valentini, Alessio; Chillemi, Giovanni

    2016-01-01

    The knowledge of the molecular effects of the C313Y mutation, responsible for the “double muscle” phenotype in Piedmontese cattle, can help understanding the actual mechanism of phenotype determination and paves the route for a better modulation of the positive effects of this economic important phenotype in the beef industry, while minimizing the negative side effects, now inevitably intersected. The structure and dynamic behavior of the active dimeric form of Myostatin in cattle was analyzed by means of three state-of-the-art Molecular Dynamics simulations, 200-ns long, of wild-type and C313Y mutants. Our results highlight a role for the conserved Arg333 in establishing a network of short and long range interactions between the two monomers in the wild-type protein that is destroyed upon the C313Y mutation even in a single monomer. Furthermore, the native protein shows an asymmetry in residue fluctuation that is absent in the double monomer mutant. Time window analysis on further 200-ns of simulation demonstrates that this is a characteristic behavior of the protein, likely dependent on long range communications between monomers. The same behavior, in fact, has already been observed in other mutated dimers. Finally, the mutation does not produce alterations in the secondary structure elements that compose the characteristic TGF-β cystine-knot motif. PMID:26904102

  10. Structural analysis of polymer-protected Pd/Pt bimetallic clusters as dispersed catalysts by using extended x-ray absorption fine structure spectroscopy

    SciTech Connect

    Toshima, Naoki; Harada, Masafumi; Yonezawa, Tetsu; Kushihashi, Kakuta; Asakura, Kiyotaka )

    1991-09-19

    Extended X-ray absorption fine structure (EXAFS) was applied to the determination of the structure of colloidal dispersions of the poly (N-vinyl-2-pyrrolidone)-protected palladium/platinum bimetallic clusters, which work as the catalysts for selective partial hydrogenation of 1,3-cyclooctadiene to cyclooctene. The catalytic activity was found to depend on the structure of the bimetallic clusters. The EXAFS data on the Pd/Pt (4/1) bimetallic clusters, which are the most active catalysts, indicate a Pt core structure, in which the 42 Pd atoms are on the surface of the cluster particle and 13 Pt atoms are at the center of the particle, forming a core. In contrast, the Pd/Pt (1/1) bimetallic clusters are suggested to have a modified Pt core structure, in which 28 Pt atoms connect directly with each other, being located both in the core and on the surface, and 27 Pd atoms form three islands on the surface of the cluster particle. These bimetallic clusters work as active catalysts for selective hydrogenation of olefins, selective partial hydrogenation of diene to monoene, and visible light-induced hydrogen generation from water.

  11. Local structure and polarization resistance of Ce doped SrMnO{sub 3} using extended x-ray fine structure analysis

    SciTech Connect

    Ryu, Jiseung; Lee, Heesoo

    2014-09-15

    Changes to the local structure of Sr and Mn atoms in Sr{sub 1−x}Ce{sub x}MnO{sub 3} (SCM) according to increasing Ce content and the effect of the structural change on the polarization resistance of SCM were investigated. The reduction of manganese was confirmed by the absorption edge shift of the Mn K-edge toward lower energies. The noise of oscillation in extended X-ray absorption fine structure k{sup 3}χ data at Mn K-edge reveals the distortion of the local structure of Mn atoms, and the peak that indicates the bonding length of Mn-O, Sr/Ce, and -Mn decreased with the addition of Ce content in Fourier transformations of the Mn K-edge. The distortion of the local structure at Mn atoms was affected by the reduced manganese ions having larger ionic radii than Mn{sup 4+}. Meanwhile, few distortions of local atomic structures of Sr atoms occurred, and the average nearest neighboring distances of Sr-O and Sr-Mn are ∼2.13 Å and ∼2.95 Å, respectively. The average bonding lengths of the Ce-O and Ce-Mn increased because the ionic radius of substituted Ce ion with 12 coordination number is smaller than that of Sr ion, which leads the reduction of Mn ions and the distortion of local structure at the substituted A-site. Therefore, we reasoned that the distortion of the local atomic structure at Mn atoms in MnO{sub 6} and Ce atoms in A-site is one of the causes for interrupting oxygen ion transfers as a geometric factor, which results in an increase in the polarization resistance of SCM within the Ce composition range from 10 mol. % to 30 mol. %.

  12. The solution structures of native and patient monomeric human IgA1 reveal asymmetric extended structures: implications for function and IgAN disease

    PubMed Central

    Hui, Gar Kay; Wright, David W.; Vennard, Owen L.; Rayner, Lucy E.; Pang, Melisa; Yeo, See Cheng; Gor, Jayesh; Molyneux, Karen; Barratt, Jonathan; Perkins, Stephen J.

    2015-01-01

    Native IgA1, for which no crystal structure is known, contains an O-galactosylated 23-residue hinge region that joins its Fab and Fc regions. IgA nephropathy (IgAN) is a leading cause of chronic kidney disease in developed countries. Because IgA1 in IgAN often has a poorly O-galactosylated hinge region, the solution structures of monomeric IgA1 from a healthy subject and three IgAN patients with four different O-galactosylation levels were studied. Analytical ultracentrifugation showed that all four IgA1 samples were monomeric with similar sedimentation coefficients, s020,w. X-ray scattering showed that the radius of gyration (Rg) slightly increased with IgA1 concentration, indicating self-association, although their distance distribution curves, P(r), were unchanged with concentration. Neutron scattering indicated similar Rg values and P(r) curves, although IgA1 showed a propensity to aggregate in heavy water buffer. A new atomistic modelling procedure based on comparisons with 177000 conformationally-randomized IgA1 structures with the individual experimental scattering curves revealed similar extended Y-shaped solution structures for all four differentially-glycosylated IgA1 molecules. The final models indicated that the N-glycans at Asn263 were folded back against the Fc surface, the C-terminal tailpiece conformations were undefined and hinge O-galactosylation had little effect on the solution structure. The solution structures for full-length IgA1 showed extended hinges and the Fab and Fc regions were positioned asymmetrically to provide ample space for the functionally-important binding of two FcαR receptors to its Fc region. Whereas no link between O-galactosylation and the IgA1 solution structure was detected, an increase in IgA1 aggregation with reduced O-galactosylation may relate to IgAN. PMID:26268558

  13. Structural aberration of the X chromosome in a patient with gonadal dysgenesis: an approach to karyotype-phenotype correlation.

    PubMed Central

    Varella-Garcia, M; Tajara, E H; Gagliardi, A R

    1981-01-01

    An 18-year-old female with some stigmata of pure dysgenesis had a chromosome constitution of 46,X,dir dup(X) (pter leads to q27: :q21 leads to qter). The abnormal chromosome was always late replicating. The clinical and cytogenetic picture is compared with that of patients with X;X translocation and some problems of karyotype-phenotype correlation are discussed. Images PMID:7241547

  14. Studies of vibrational properties in Ga stabilized delta-Pu by extended X-ray absorption fine structure

    SciTech Connect

    Allen, P.G.; Henderson, A.L.; Sylwester, E.R.; Turchi, P.E.A.; Shen, T.H.; Gallegos, G.F.; Booth, C.H.

    2002-02-14

    Temperature dependent extended x-ray absorption fine structure (EXAFS) spectra were measured for a 3.3 at. % Ga stabilized Pu alloy over the range T= 20 - 300 K. EXAFS data were acquired at both the Ga K-edge and the Pu L{sub III} edge. Curve-fits were performed to the first shell interactions to obtain pair-distance distribution widths, {sigma}, as a function of temperature. The temperature dependence of {sigma}(T) was accurately modeled using a correlated-Debye model for the lattice vibrational properties, suggesting Debye-like behavior in this material. Using this formalism, we obtain pair-specific correlated-Debye temperatures, {Theta}{sub cD}, of 110.7 {+-} 1.7 K and 202.6 {+-} 3.7 K, for the Pu-Pu and Ga-Pu pairs, respectively. The result for the Pu-{Theta}{sub cD} value compares well with previous vibrational studies on {delta}-Pu. In addition, our results represent the first unambiguous determination of Ga-specific vibrational properties in Pu-Ga alloys, i.e, {Theta}{sub cD} for the Ga-Pu pair. Because the Debye temperature can be related to a measure of the lattice stiffness, these results indicate the Ga-Pu bonds are significantly stronger than the Pu-Pu bonds. This effect has important implications for lattice stabilization mechanisms in these alloys.

  15. The solution structure of bis(phenazine-1-carboxamide)-DNA complexes: MLN 944 binding corrected and extended.

    PubMed

    Serobian, Andre; Thomas, Donald S; Ball, Graham E; Denny, William A; Wakelin, Laurence P G

    2014-11-01

    MLN 944 is a bisintercalating DNA-binding antitumor agent known to be a template inhibitor of transcription. Previous (1) H NMR studies of its d(ATGCAT)2 complex concluded that its phenazine chromophores are protonated. However, we find that this is not so, which has important consequences for the charged state of the ligand, for the orientation of its 1-carboxamide group in the complex, and for the details of the interaction of its protonated interchromophore linker with the DNA base pairs. Here, we report a corrected solution structure of the MLN 944-d(ATGCAT)2 complex, and extend the study to complexes with d(TATGCATA)2 , and d(TACGCGTA)2 , using a variety of (1) H and (31) P NMR methods and molecular dynamics simulations employing the AMBER 12 force field. We find that for all three complexes MLN 944 binds as a dication, in which the chromophores are uncharged, in the DNA major groove spanning the central 2 GC base pairs in a manner that maintains the dyad symmetry of the DNA. The carboxamide group lies in the plane of the chromophore, its NH making hydrogen bonding interactions with the phenazine N10 nitrogen, and the protonated linkers form hydrogen bonds with the O6 atom of guanine. The dynamics simulations reveal extensive solvent interactions involving the linker amines, the carboxamide group, and the DNA bases. PMID:24898663

  16. How do students with dyslexia perform in extended matching questions, short answer questions and observed structured clinical examinations?

    PubMed

    Gibson, Sandra; Leinster, Samuel

    2011-08-01

    There are an increasing number of students with learning difficulties attending university, and currently much debate about the suitability and ability of students with dyslexia at both medical school and once they graduate into clinical practice. In this study we describe the performance of students with dyslexia compared to fellow students in extended matching questions (EMQ), short answer question (SAQ) and observed structured clinical examinations (OSCE) and discuss the implications of differences identified. End of year assessment results for 5 cohorts of medical students were analysed. Students with dyslexia did less well overall in all assessment types in year 1 but this difference was not evident in later years. Dyslexic students who were allowed extra time in written assessments did better than dyslexic students who did not have their assessment concessions in place. When station type within OSCE assessments was analysed students with dyslexia did less well in both examination skills and data interpretation stations in years 1, 2 & 3. In conclusion, differences in performance in written assessments are only evident early in training and may be partly due to delayed adjustment to medical school or implementation of assessment concessions. Performance in individual OSCE stations is dependent on station type. Why students with specific learning difficulties (SpLDs) perform less well in examination skills and data analysis OSCE stations requires further investigation. PMID:21249518

  17. A novel mutation in FHL1 in a family with X-linked scapuloperoneal myopathy: phenotypic spectrum and structural study of FHL1 mutations

    PubMed Central

    Chen, Dong-Hui; Raskind, Wendy H.; Parson, William W.; Sonnen, Joshua A.; Vu, Tiffany; Zheng, YunLin; Matsushita, Mark; Wolff, John; Lipe, Hillary; Bird, Thomas D.

    2010-01-01

    An X-linked myopathy was recently associated with mutations in the four-and-a-half-LIM domains 1 (FHL1) gene. We identified a family with late onset, slowly progressive weakness of scapuloperoneal muscles in three brothers and their mother. A novel missense mutation in the LIM2 domain of FHL1 (W122C) co-segregated with disease in the family. The phenotype was less severe than that in other reported families. Muscle biopsy revealed myopathic changes with FHL1 inclusions that were ubiquitin- and desmin-positive. This mutation provides additional evidence for X-linked myopathy caused by a narrow spectrum of mutations in FHL1, mostly in the LIM2 domain. Molecular dynamics (MD) simulations of the newly identified mutation and five previously published missense mutations in the LIM2 domain revealed no major distortions of the protein structure or disruption of zinc binding. There were, however, increases in the nonpolar, solvent-accessible surface area in one or both of two clusters of residues, suggesting that the mutant proteins have a variably increased propensity to aggregate. Review of the literature shows a wide range of phenotypes associated with mutations in FHL1. However, recognizing the typical scapuloperoneal phenotype and X-linked inheritance pattern will help clinicians arrive at the correct diagnosis. PMID:20633900

  18. Belief propagation in genotype-phenotype networks.

    PubMed

    Moharil, Janhavi; May, Paul; Gaile, Daniel P; Blair, Rachael Hageman

    2016-03-01

    Graphical models have proven to be a valuable tool for connecting genotypes and phenotypes. Structural learning of phenotype-genotype networks has received considerable attention in the post-genome era. In recent years, a dozen different methods have emerged for network inference, which leverage natural variation that arises in certain genetic populations. The structure of the network itself can be used to form hypotheses based on the inferred direct and indirect network relationships, but represents a premature endpoint to the graphical analyses. In this work, we extend this endpoint. We examine the unexplored problem of perturbing a given network structure, and quantifying the system-wide effects on the network in a node-wise manner. The perturbation is achieved through the setting of values of phenotype node(s), which may reflect an inhibition or activation, and propagating this information through the entire network. We leverage belief propagation methods in Conditional Gaussian Bayesian Networks (CG-BNs), in order to absorb and propagate phenotypic evidence through the network. We show that the modeling assumptions adopted for genotype-phenotype networks represent an important sub-class of CG-BNs, which possess properties that ensure exact inference in the propagation scheme. The system-wide effects of the perturbation are quantified in a node-wise manner through the comparison of perturbed and unperturbed marginal distributions using a symmetric Kullback-Leibler divergence. Applications to kidney and skin cancer expression quantitative trait loci (eQTL) data from different mus musculus populations are presented. System-wide effects in the network were predicted and visualized across a spectrum of evidence. Sub-pathways and regions of the network responded in concert, suggesting co-regulation and coordination throughout the network in response to phenotypic changes. We demonstrate how these predicted system-wide effects can be examined in connection with

  19. Geometric Structure Determination of N694C Lipoxygenase: a Comparative Near-Edge X-Ray Absorption Spectroscopy And Extended X-Ray Absorption Fine Structure Study

    SciTech Connect

    Sarangi, R.; Hocking, R.K.; Neidig, M.L.; Benfatto, M.; Holman, T.R.; Solomon, E.I.; Hodgson, K.O.; Hedman, B.

    2009-05-27

    The mononuclear nonheme iron active site of N694C soybean lipoxygenase (sLO1) has been investigated in the resting ferrous form using a combination of Fe-K-pre-edge, near-edge (using the minuit X-ray absorption near-edge full multiple-scattering approach), and extended X-ray absorption fine structure (EXAFS) methods. The results indicate that the active site is six-coordinate (6C) with a large perturbation in the first-shell bond distances in comparison to the more ordered octahedral site in wild-type sLO1. Upon mutation of the asparigine to cystiene, the short Fe-O interaction with asparigine is replaced by a weak Fe-(H{sub 2}O), which leads to a distorted 6C site with an effective 5C ligand field. In addition, it is shown that near-edge multiple scattering analysis can give important three-dimensional structural information, which usually cannot be accessed using EXAFS analysis. It is further shown that, relative to EXAFS, near-edge analysis is more sensitive to partial coordination numbers and can be potentially used as a tool for structure determination in a mixture of chemical species.

  20. Adsorption site and structure determination of c(2x2) N{sub 2}/Ni(100) using angle-resolved photoemission extended fine structure

    SciTech Connect

    Moler, E.J.; Kellar, S.A.; Huff, W.R.A.

    1997-04-01

    The authors have determined the atomic spatial structure of c(2x2) N2Ni(100) with Angle-Resolved Photoemission Extended Fine Structure (ARPEFS) from the nitrogen 1s core level using monochromatized x-rays from beamline 6.1 at SSRL and beamline 9.3.2 at the ALS. The chemically shifted N 1s peak intensities were summed together to obtain ARPEFS curves for both nitrogen atoms in the molecule. They used a new, highly-optimized program based on the Rehr-Albers scattering matrix formalism to find the adsorption site and to quantitatively determine the bond-lengths. The nitrogen molecule stands upright at an atop site, with a N-Ni bond length of 2.25(1) {angstrom}, a N-N bond length of 1.10(7) {angstrom}, and a first layer Ni-Ni spacing of 1.76(4) {angstrom}. The shake-up peak shows an identical ARPEFS diffraction pattern, confirming its intrinsic nature and supporting a previous use of this feature to decompose the peak into contributions from the chemically inequivalent nitrogen atoms. Comparison to a previously published theoretical treatment of N-N-Ni and experimental structures of analogous adsorbate systems demonstrates the importance of adsorbate-adsorbate interactions in weakly chemisorbed systems.

  1. The determination of interfacial structure and phase transitions in Al/Cu and Al/Ni interfaces by means of surface extended x-ray absorption fine structure

    SciTech Connect

    Barrera, E.V. . Dept. of Mechanical Engineering and Materials Science); Heald, S.M. )

    1991-01-01

    Surface extended x-ray absorption fine structure (SEXAFS) was used to investigate the interfacial conditions of Al/Cu and Al/Ni shallow buried interfaces. Previous studies using glancing angle extended x-ray absorption fine structure, x-ray reflectivity, photoemission, and SEXAFS produced conflicting results as to whether or not the interfaces between Al and Cu and Al and Ni were reacted upon room temperature deposition. In this study polycrystalline bilayers of Al/Cu and Al/Ni and trilayers of Al/Cu/Al and Al/Ni/Al were deposited on tantalum foil at room temperature in ultra high vacuum and analyzed to evaluate the reactivity of these systems on a nanometer scale. It become overwhelming apparent that the interfacial phase reactions were a function of the vacuum conditions. Samples deposited with the optimum vacuum conditions showed reaction products upon deposition at room temperature which were characterized by comparisons to standards and by least squares fitting the be CuAl{sub 2} and NiAl{sub 3} respectively. The results of this study that the reacted zone thicknesses were readily dependent on the deposition parameters. For both Al on Cu and Al on Ni as well as the metal on Al conditions 10{Angstrom} reaction zones were observed. These reaction zones were smaller than that observed for bilayers of Al on Cu (30{Angstrom}) and Al on Ni (60{Angstrom}) where deposition rates were much higher and samples were much thicker. The reaction species are evident by SEXAFS, where the previous photoemission studies only indicated that changes had occurred. Improved vacuum conditions as compared to the earlier experiments is primarily the reason reactions on deposition were seen in this study as compared to the earlier SEXAFS studies.

  2. The determination of interfacial structure and phase transitions in Al/Cu and Al/Ni interfaces by means of surface extended x-ray absorption fine structure

    SciTech Connect

    Barrera, E.V.; Heald, S.M.

    1991-12-31

    Surface extended x-ray absorption fine structure (SEXAFS) was used to investigate the interfacial conditions of Al/Cu and Al/Ni shallow buried interfaces. Previous studies using glancing angle extended x-ray absorption fine structure, x-ray reflectivity, photoemission, and SEXAFS produced conflicting results as to whether or not the interfaces between Al and Cu and Al and Ni were reacted upon room temperature deposition. In this study polycrystalline bilayers of Al/Cu and Al/Ni and trilayers of Al/Cu/Al and Al/Ni/Al were deposited on tantalum foil at room temperature in ultra high vacuum and analyzed to evaluate the reactivity of these systems on a nanometer scale. It become overwhelming apparent that the interfacial phase reactions were a function of the vacuum conditions. Samples deposited with the optimum vacuum conditions showed reaction products upon deposition at room temperature which were characterized by comparisons to standards and by least squares fitting the be CuAl{sub 2} and NiAl{sub 3} respectively. The results of this study that the reacted zone thicknesses were readily dependent on the deposition parameters. For both Al on Cu and Al on Ni as well as the metal on Al conditions 10{Angstrom} reaction zones were observed. These reaction zones were smaller than that observed for bilayers of Al on Cu (30{Angstrom}) and Al on Ni (60{Angstrom}) where deposition rates were much higher and samples were much thicker. The reaction species are evident by SEXAFS, where the previous photoemission studies only indicated that changes had occurred. Improved vacuum conditions as compared to the earlier experiments is primarily the reason reactions on deposition were seen in this study as compared to the earlier SEXAFS studies.

  3. The Genomic and Phenotypic Diversity of Schizosaccharomyces pombe

    PubMed Central

    Jeffares, Daniel C.; Rallis, Charalampos; Rieux, Adrien; Speed, Doug; Převorovský, Martin; Mourier, Tobias; Marsellach, Francesc X.; Iqbal, Zamin; Lau, Winston; Cheng, Tammy M.K.; Pracana, Rodrigo; Mülleder, Michael; Lawson, Jonathan L.D.; Chessel, Anatole; Bala, Sendu; Hellenthal, Garrett; O’Fallon, Brendan; Keane, Thomas; Simpson, Jared T.; Bischof, Leanne; Tomiczek, Bartlomiej; Bitton, Danny A.; Sideri, Theodora; Codlin, Sandra; Hellberg, Josephine E.E.U.; van Trigt, Laurent; Jeffery, Linda; Li, Juan-Juan; Atkinson, Sophie; Thodberg, Malte; Febrer, Melanie; McLay, Kirsten; Drou, Nizar; Brown, William; Hayles, Jacqueline; Carazo Salas, Rafael E.; Ralser, Markus; Maniatis, Nikolas; Balding, David J.; Balloux, Francois; Durbin, Richard; Bähler, Jürg

    2015-01-01

    Natural variation within species reveals aspects of genome evolution and function. The fission yeast Schizosaccharomyces pombe is an important model for eukaryotic biology, but researchers typically use one standard laboratory strain. To extend the utility of this model, we surveyed the genomic and phenotypic variation in 161 natural isolates. We sequenced the genomes of all strains, revealing moderate genetic diversity (π = 3 ×10−3) and weak global population structure. We estimate that dispersal of S. pombe began within human antiquity (~340 BCE), and ancestors of these strains reached the Americas at ~1623 CE. We quantified 74 traits, revealing substantial heritable phenotypic diversity. We conducted 223 genome-wide association studies, with 89 traits showing at least one association. The most significant variant for each trait explained 22% of variance on average, with indels having higher effects than SNPs. This analysis presents a rich resource to examine genotype-phenotype relationships in a tractable model. PMID:25665008

  4. A combined fit of total scattering and extended x-ray absorption fine structure data for local-structure determination in crystalline materials

    SciTech Connect

    Proffen, Thomas E; Krayzman, Victor; Levin, Igor; Tucker, Matt

    2009-01-01

    Reverse Monte Carlo (RMC) refinements of local structure using a simultaneous fit of X-ray/neutron total scattering and extended X-ray absorption fine structure (EXAFS) data were developed to incorporate an explicit treatment of both single- and multiple-scattering contributions to EXAFS. The refinement algorithm, implemented as an extension to the public domain computer software RMCProfile, enables accurate modeling of EXAFS over distances encompassing several coordination shells around the absorbing species. The approach was first tested on Ni, which exhibits extensive multiple scattering in EXAFS, and then applied to perovskite-like SrAl{sub 1/2}Nb{sub 1/2}O{sub 3}. This compound crystal1izes with a cubic double-perovskite structure but presents a challenge for local-structure determination using a total pair-distribution function (PDF) alone because of overlapping peaks of the constituent partial PDFs (e.g. Al-O and Nb-O or Sr-O and O-O). The results obtained here suggest that the combined use of the total scattering and EXAFS data provides sufficient constraints for RMC refinements to recover fine details of local structure in complex perovskites. Among other results, it was found that the probability density distribution for Sr in SrAl{sub 1/2}Nb{sub 1/2}O{sub 3} adopts T{sub d} point-group symmetry for the Sr sites, determined by the ordered arrangement of Al and Nb, as opposed to a spherical distribution commonly assumed in traditional Rietveld refinements.

  5. Molecular structures and solvation of free monomeric and dimeric ferriheme in aqueous solution: insights from molecular dynamics simulations and extended X-ray absorption fine structure spectroscopy.

    PubMed

    Kuter, David; Streltsov, Victor; Davydova, Natalia; Venter, Gerhard A; Naidoo, Kevin J; Egan, Timothy J

    2014-10-20

    CHARMM force field parameters have been developed to model nonprotein bound five-coordinate ferriheme (ferriprotoporphyrin IX) species in aqueous solution. Structures and solvation were determined from molecular dynamics (MD) simulations at 298 K of monomeric [HO-ferriheme](2-), [H2O-ferriheme](-), and [H2O-ferriheme](0); π-π dimeric [(HO-ferriheme)2](4-), [(H2O-ferriheme)(HO-ferriheme)](3-), [(H2O-ferriheme)2](2-), and [(H2O-ferriheme)2](0); and μ-oxo dimeric [μ-(ferriheme)2O](4-). Solvation of monomeric species predominated around the axial ligand, meso-hydrogen atoms of the porphyrin ring (Hmeso), and the unligated face. Existence of π-π ferriheme dimers in aqueous solution was supported by MD calculations where such dimers remained associated over the course of the simulation. Porphyrin rings were essentially coplanar. In these dimers major and minor solvation was observed around the axial ligand and Hmeso positions, respectively. In μ-oxo ferriheme, strong solvation of the unligated face and bridging oxide ligand was observed. The solution structure of the μ-oxo dimer was investigated using extended X-ray absorption fine structure (EXAFS) spectroscopy. The EXAFS spectrum obtained from frozen solution was markedly different from that recorded on dried μ-oxo ferriheme solid. Inclusion of five solvent molecules obtained from spatial distribution functions in the structure generated from MD simulation was required to produce acceptable fits to the EXAFS spectra of the dimer in solution, while the solid was suitably fitted using the crystal structure of μ-oxo ferriheme dimethyl ester which included no solvent molecules. PMID:25275882

  6. Three deaf mice: mouse models for TECTA-based human hereditary deafness reveal domain-specific structural phenotypes in the tectorial membrane

    PubMed Central

    Legan, P. Kevin; Goodyear, Richard J.; Morín, Matías; Mencia, Angeles; Pollard, Hilary; Olavarrieta, Leticia; Korchagina, Julia; Modamio-Hoybjor, Silvia; Mayo, Fernando; Moreno, Felipe; Moreno-Pelayo, Miguel-Angel; Richardson, Guy P.

    2014-01-01

    Tecta is a modular, non-collagenous protein of the tectorial membrane (TM), an extracellular matrix of the cochlea essential for normal hearing. Missense mutations in Tecta cause dominant forms of non-syndromic deafness and a genotype–phenotype correlation has been reported in humans, with mutations in different Tecta domains causing mid- or high-frequency hearing impairments that are either stable or progressive. Three mutant mice were created as models for human Tecta mutations; the TectaL1820F,G1824D/+ mouse for zona pellucida (ZP) domain mutations causing stable mid-frequency hearing loss in a Belgian family, the TectaC1837G/+ mouse for a ZP-domain mutation underlying progressive mid-frequency hearing loss in a Spanish family and the TectaC1619S/+ mouse for a zonadhesin-like (ZA) domain mutation responsible for progressive, high-frequency hearing loss in a French family. Mutations in the ZP and ZA domains generate distinctly different changes in the structure of the TM. Auditory brainstem response thresholds in the 8–40 kHz range are elevated by 30–40 dB in the ZP-domain mutants, whilst those in the ZA-domain mutant are elevated by 20–30 dB. The phenotypes are stable and no evidence has been found for a progressive deterioration in TM structure or auditory function. Despite elevated auditory thresholds, the Tecta mutant mice all exhibit an enhanced tendency to have audiogenic seizures in response to white noise stimuli at low sound pressure levels (≤84 dB SPL), revealing a previously unrecognised consequence of Tecta mutations. These results, together with those from previous studies, establish an allelic series for Tecta unequivocally demonstrating an association between genotype and phenotype. PMID:24363064

  7. Structural characterization of (H sub x Re sub 3 (CO) sub 12 ) sup x-3 (x = 2, 3) by extended x-ray absorption fine structure spectroscopy

    SciTech Connect

    Van Zon, F.B.M.; Koningsberger, D.C. ); Kirlin, P.S.; Gates, B.C. )

    1989-03-23

    Extended x-ray absorption fine structure (EXAFS) measurements on the ReL{sub III} edge have been used to elucidate the structures of H{sub 3}ReP{sub 3}(CO){sub 12} and (H{sub 2}Re{sub 3}(CO){sub 12}){sup {minus}}. The data analysis is based on empirically determined EXAFS functions, including that of Os{sub 3}(CO){sub 12}, to account for the multiple scattering effects characteristic of metal carbonyls. The results confirm the presence of a triangular Re{sub 3} skeleton in each cluster, with the Re-Re bonds in the neutral cluster being of equal length (3.285 {angstrom}). The disorder in the Re-Re shell characterizing the anionic cluster indicates that not all the Re-Re bonds are of equal length, which implies the presence of bridging hydride ligands associated with the longer Re-Re bonds. Comparison of the EXAFS data with published x-ray diffraction data characterizing (HRe{sub 3}(CO){sub 12}){sup 2{minus}} shows a trend of decreasing Re-C distances and increasing C-O distances with increasing negative charge on the cluster, which is explained by {pi}-back-bonding.

  8. Dark Filaments, Clouds and Cores: A Multiband IR Study of the Early Stages of Star Formation in Extended Structures

    NASA Astrophysics Data System (ADS)

    Smith, Howard

    Star formation typically begins in cold, dark clouds that are not spherically symmetric, but elongated as infrared dark clouds or long linear filaments. Their star-forming characteristics are thought to be sensitive to the geometries. We propose a systematic, detailed study of a sample of 168 of these dark clouds spanning a wide range of parameters using new archival data from Herschel and Spitzer. Archival Herschel photometry in particular enables for the first time a sensitive, systematic study of the full far-infrared continuum of these objects. We have distance determinations and ancillary molecule line measurements for all of our sources. Ten-band photometry (from 3.5um to 500um) will let us determine the luminosities, spectral energy distributions (SEDs), and estimate masses of these cold structures as functions of their star-formation activity. We will produce dust temperature and optical depth maps that will enable statistical studies of filaments and their cores; we expect statistics on over 500 protostellar cores. Our selected sources span a range of physical conditions: distances from 1 to 8 kpc, lengths from 0.1 to 80 pc, aspect ratios from below 2 to above 8, nominal core masses from about 1 to 500 Mo, and a range of geometries including linear, branching, hub-filament, and network configurations. We plan to use the extended Robitaille YSO models and SUNRISE radiative transfer models for prestellar cores to analyze a generic set of the most common objects, and then test their applicability across the sample. We will also bring other data to bear (WISE; 2MASS, millimeter) as is useful. We address three current, multi-faceted problems: (1) What are the density, temperature and optical depth structures of filaments and their cores? How do these parameters vary spatially for cores and the inter-core regions? How do these parameters correlate to filamentary or environmental properties? (2) What is the statistical distribution of these properties; in

  9. Genetic Structure Is Associated with Phenotypic Divergence in Floral Traits and Reproductive Investment in a High-Altitude Orchid from the Iron Quadrangle, Southeastern Brazil

    PubMed Central

    Leles, Bruno; Chaves, Anderson V.; Russo, Philip; Batista, João A. N.; Lovato, Maria Bernadete

    2015-01-01

    Knowledge of the role of Neotropical montane landscapes in shaping genetic connectivity and local adaptation is essential for understanding the evolutionary processes that have shaped the extraordinary species diversity in these regions. In the present study, we examined the landscape genetics, estimated genetic diversity, and explored genetic relationships with morphological variability and reproductive strategies in seven natural populations of Cattleya liliputana (Orchidaceae). Nuclear microsatellite markers were used for genetic analyses. Spatial Bayesian clustering and population-based analyses revealed significant genetic structuring and high genetic diversity (He = 0.733 ± 0.03). Strong differentiation was found between populations over short spatial scales (FST = 0.138, p < 0.001), reflecting the landscape discontinuity and isolation. Monmonier´s maximum difference algorithm, Bayesian analysis on STRUCTURE and principal component analysis identified one major genetic discontinuity between populations. Divergent genetic groups showed phenotypic divergence in flower traits and reproductive strategies. Increased sexual reproductive effort was associated with rock outcrop type and may be a response to adverse conditions for growth and vegetative reproduction. Here we discuss the effect of restricted gene flow, local adaptation and phenotypic plasticity as drivers of population differentiation in Neotropical montane rock outcrops. PMID:25756994

  10. The stay-green phenotype of TaNAM-RNAi wheat plants is associated with maintenance of chloroplast structure and high enzymatic antioxidant activity.

    PubMed

    Checovich, Mariana L; Galatro, Andrea; Moriconi, Jorge I; Simontacchi, Marcela; Dubcovsky, Jorge; Santa-María, Guillermo E

    2016-07-01

    TaNAM transcription factors play an important role in controlling senescence, which in turn, influences the delivery of nitrogen, iron and other elements to the grain of wheat (Triticum aestivum) plants, thus contributing to grain nutritional value. While lack or diminished expression of TaNAMs determines a stay-green phenotype, the precise effect of these factors on chloroplast structure has not been studied. In this work we focused on the events undergone by chloroplasts in two wheat lines having either control or diminished TaNAM expression due to RNA interference (RNAi). It was found that in RNAi plants maintenance of chlorophyll levels and maximal photochemical efficiency of photosystem II were associated with lack of chloroplast dismantling. Flow cytometer studies and electron microscope analysis showed that RNAi plants conserved organelle ultrastructure and complexity. It was also found that senescence in control plants was accompanied by a low leaf enzymatic antioxidant activity. Lack of chloroplast dismantling in RNAi plants was associated with maintenance of protein and iron concentration in the flag leaf, the opposite being observed in control plants. These data provide a structural basis for the observation that down regulation of TaNAMs confers a functional stay-green phenotype and indicate that the low export of iron and nitrogen from the flag leaf of these plants is concomitant, within the developmental window studied, with lack of chloroplast degradation and high enzymatic antioxidant activity. PMID:27061370

  11. Structural in silico dissection of the collagen V interactome to identify genotype-phenotype correlations in classic Ehlers-Danlos Syndrome (EDS).

    PubMed

    Paladin, Lisanna; Tosatto, Silvio C E; Minervini, Giovanni

    2015-12-21

    Collagen V mutations are associated with Elhers-Danlos syndrome (EDS), a group of heritable collagenopathies. Collagen V structure is not available and the disease-causing mechanism is unclear. To address this issue, we manually curated missense mutations suspected to promote classic type EDS (cEDS) insurgence from the literature and performed a genotype-phenotype correlation study. Further, we generated a homology model of the collagen V triple helix to evaluate the pathogenic effects. The resulting structure was used to map known protein-protein interactions enriched with in silico predictions. An interaction network model for collagen V was created. We found that cEDS heterogeneous manifestations may be explained by the involvement in two different extracellular matrix pathways, related to cell adhesion and tissue repair or cell differentiation, growth and apoptosis. PMID:26608033

  12. The structure and ionization of the extended emission-line filaments surrounding the QSO MR 2251-178

    SciTech Connect

    Macchetto, F.; Colina, L.; Golombek, D.; Perryman, M.A.C.; Di Serego Alighieri, S. ESA, Astrophysics Div., Noordwijk ESA, Space Telescope European Coordinating Facility, Garching )

    1990-06-01

    This paper presents new VLA radio maps, at 6 cm and 20 cm, of the QSO MR 2251-178, together with deep high-spatial-resolution images in the O II forbidden 3727-A line in the O III forbidden 5007-A line, and H-alpha emission lines, showing the presence of extended emission-line filaments surrounding the MR 2251-178. The morphology of the circumnuclear emission-line regions and an extended system of filaments in different ionization states are shown. The physical characteristics, such as luminosities, densities, mass, and ionization parameters of different filaments are derived. 48 refs.

  13. Effect of Extender and Equilibration Time on Post Thaw Motility and Chromatin Structure of Buffalo Bull (Bubalus Bubalis) Spermatozoa

    PubMed Central

    Shahverdi, Abdolhossain; Rastegarnia, Abdolreza; Rezaei Topraggaleh, Tohid

    2014-01-01

    Objective The aim of the present study was to investigate the effects of four equilibration times (2, 4, 8 and 16 hours) and two extenders (tris or Bioxcell®) on cryopreservation of buffalo semen. Materials and Methods In this experimental study, split pooled ejaculates (n=4), possessing more than 70% visual sperm motility were divided in two aliquots and diluted in Bioxcell® and tris-citric egg yolk (TCE) extenders. Semen was cooled to 4°C within 2 hours, equilibrated at 4°C for 2, 4, 8 and 16 hours, then transferred into 0.5 ml French straws, and frozen in a programmable cell freezer before being plunged into liquid nitrogen. Postthaw motility characteristics, plasma membrane integrity, acrosome morphology and DNA integrity of the buffalo sperm were studied after thawing. Results There were significant interactions between equilibration times and extenders for sperm motility and membrane integrity. Post thaw sperm motility (PMOT), progressive motile spermatozoa (PROG), plasma membrane integrity (PMI) and normal apical ridge (NAR) measures were lower for sperm equilibrated for 2 hours in both TCE and Bioxcell® extender compared to others equilibration times. PMOT, PMI and NAR for sperm equilibrated for 4, 8 and 16 hours showed no significant differences in either extender, although PROG measures were superior in Bioxcell®compared to TCE at all equilibration times (p<0.05). Kinematic parameters such as average path velocity, curvilinear velocity and linearity in the Bioxcell®extender were superior to those in the TCE extender studied. In contrast to motility and viability, the DNA integrity of post thaw spermatozoa remained unaffected by different equilibration times. Conclusion Equilibration time is necessary for preservation of the motility and integrity of buffalo sperm membranes. Equilibration times of over than 2 hours resulted in the greatest preservation of total semen parameters during cryopreservation. There were no significant interactions between

  14. New dicyano cyclometalated compounds containing Pd(II)-Tl(I) bonds as building blocks in 2D extended structures: synthesis, structure, and luminescence studies.

    PubMed

    Sicilia, Violeta; Forniés, Juan; Fuertes, Sara; Martín, Antonio

    2012-10-15

    New mixed metal complexes [PdTl(C^N)(CN)(2)] [C^N = 7,8-benzoquinolinate (bzq, 3); 2-phenylpyridinate (ppy, 4)] have been synthesized by reaction of their corresponding precursors (NBu(4))[Pd(C^N)(CN)(2)] [C^N = bzq (1), ppy (2)] with TlPF(6). Compounds 3 and 4 were studied by X-ray diffraction, showing the not-so-common Pd(II)-Tl(I) bonds. Both crystal structures exhibit 2-D extended networks fashioned by organometallic "PdTl(C^N)(CN)(2)" units, each one containing a donor-acceptor Pd(II)-Tl(I) bond, which are connected through additional Tl···N≡C contacts and weak Tl···π (bzq) contacts in the case of 3. Solid state emissions are red-shifted compared with those of the precursors and have been assigned to metal-metal'-to-ligand charge transfer (MM'LCT [d/s σ*(Pd,Tl) → π*(C^N)]) mixed with some intraligand ((3)IL[π(C^N) → π*(C^N)]) character. In diluted solution either at room temperature or 77 K, the Pd-Tl bond is no longer retained as confirmed by mass spectrometry, NMR, and UV-vis spectroscopic techniques. PMID:22998590

  15. Full-potential theoretical investigations of electron inelastic mean free paths and extended x-ray absorption fine structure in molybdenum.

    PubMed

    Chantler, C T; Bourke, J D

    2014-04-01

    X-ray absorption fine structure (XAFS) spectroscopy is one of the most robust, adaptable, and widely used structural analysis tools available for a range of material classes from bulk solids to aqueous solutions and active catalytic structures. Recent developments in XAFS theory have enabled high-accuracy calculations of spectra over an extended energy range using full-potential cluster modelling, and have demonstrated particular sensitivity in XAFS to a fundamental electron transport property-the electron inelastic mean free path (IMFP). We develop electron IMFP theory using a unique hybrid model that simultaneously incorporates second-order excitation losses, while precisely accounting for optical transitions dictated by the complex band structure of the solid. These advances are coupled with improved XAFS modelling to determine wide energy-range absorption spectra for molybdenum. This represents a critical test case of the theory, as measurements of molybdenum K-edge XAFS represent the most accurate determinations of XAFS spectra for any material. We find that we are able to reproduce an extended range of oscillatory structure in the absorption spectrum, and demonstrate a first-time theoretical determination of the absorption coefficient of molybdenum over the entire extended XAFS range utilizing a full-potential cluster model. PMID:24651638

  16. Using an Advanced Computational Laboratory Experiment to Extend and Deepen Physical Chemistry Students' Understanding of Atomic Structure

    ERIC Educational Resources Information Center

    Hoffman, Gary G.

    2015-01-01

    A computational laboratory experiment is described, which involves the advanced study of an atomic system. The students use concepts and techniques typically covered in a physical chemistry course but extend those concepts and techniques to more complex situations. The students get a chance to explore the study of atomic states and perform…

  17. Characterization of Maize Amylose-Extender (ae) Mutant Starches. Part I: Relationship Between Resistant Starch Contents and Molecular Structures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endosperm starches were isolated from kernels of seven maize amylose-extender (ae) lines. The resistant starch (RS) contents, measured using AOAC method 991.43, showed that three new ae-mutant starch lines developed by the USDA-ARS Germplasm Enhancement (GEM) and Truman State University had larger R...

  18. The Effects of X Chromosome Loss on Neuroanatomical and Cognitive Phenotypes During Adolescence: a Multi-modal Structural MRI and Diffusion Tensor Imaging Study.

    PubMed

    Xie, Sheng; Zhang, Zhixin; Zhao, Qiuling; Zhang, Jiaying; Zhong, Suyu; Bi, Yanchao; He, Yong; Pan, Hui; Gong, Gaolang

    2015-09-01

    The absence of all or part of one X chromosome in female humans causes Turner's syndrome (TS), providing a unique "knockout model" to investigate the role of the X chromosome in neuroanatomy and cognition. Previous studies have demonstrated TS-associated brain differences; however, it remains largely unknown 1) how the brain structures are affected by the type of X chromosome loss and 2) how X chromosome loss influences the brain-cognition relationship. Here, we addressed these by investigating gray matter morphology and white matter connectivity using a multimodal MRI dataset from 34 adolescent TS patients (13 mosaic and 21 nonmosaic) and 21 controls. Intriguingly, the 2 TS groups exhibited significant differences in surface area in the right angular gyrus and in white matter integrity of the left tapetum of corpus callosum; these data support a link between these brain phenotypes and the type of X chromosome loss in TS. We further showed that the X chromosome modulates specific brain-cognition relationships: thickness and surface area in multiple cortical regions are positively correlated with working-memory performance in controls but negatively in TS. These findings provide novel insights into the X chromosome effect on neuroanatomical and cognitive phenotypes and highlight the role of genetic factors in brain-cognition relationships. PMID:24770708

  19. Microbial structural diversity estimated by dilution-extinction of phenotypic traits and T-RFLP analysis along a land-use intensification gradient

    NASA Technical Reports Server (NTRS)

    Gomez, Elena del V.; Garland, Jay L.; Roberts, Michael S.

    2004-01-01

    The present work tested whether the relationship between functional traits and inoculum density reflected structural diversity in bacterial communities from a land-use intensification gradient applying a mathematical model. Terminal restriction fragment length polymorphism (T-RFLP) analysis was also performed to provide an independent assessment of species richness. Successive 10-fold dilutions of a soil suspension were inoculated onto Biolog GN(R) microplates. Soil bacterial density was determined by total cell and plate counts. The relationship between phenotypic traits and inoculum density fit the model, allowing the estimation of maximal phenotypic potential (Rmax) and inoculum density (KI) at which Rmax will be half-reduced. Though Rmax decreased with time elapsed since clearing of native vegetation, KI remained high in two of the disturbed sites. The genetic pool of bacterial community did not experience a significant reduction, but the active fraction responding in the Biolog assay was adversely affected, suggesting a reduction in the functional potential. c2004 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.

  20. Integration of genome and phenotypic scanning gives evidence of genetic structure in Mesoamerican common bean (Phaseolus vulgaris L.) landraces from the southwest of Europe.

    PubMed

    Santalla, M; De Ron, A M; De La Fuente, M

    2010-05-01

    Southwestern Europe has been considered as a secondary centre of genetic diversity for the common bean. The dispersal of domesticated materials from their centres of origin provides an experimental system that reveals how human selection during cultivation and adaptation to novel environments affects the genetic composition. In this paper, our goal was to elucidate how distinct events could modify the structure and level of genetic diversity in the common bean. The genome-wide genetic composition was analysed at 42 microsatellite loci in individuals of 22 landraces of domesticated common bean from the Mesoamerican gene pool. The accessions were also characterised for phaseolin seed protein and for nine allozyme polymorphisms and phenotypic traits. One of this study's important findings was the complementary information obtained from all the polymorphisms examined. Most of the markers found to be potentially under the influence of selection were located in the proximity of previously mapped genes and quantitative trait loci (QTLs) related to important agronomic traits, which indicates that population genomics approaches are very efficient in detecting QTLs. As it was revealed by outlier simple sequence repeats, loci analysis with STRUCTURE software and multivariate analysis of phenotypic data, the landraces were grouped into three clusters according to seed size and shape, vegetative growth habit and genetic resistance. A total of 151 alleles were detected with an average of 4 alleles per locus and an average polymorphism information content of 0.31. Using a model-based approach, on the basis of neutral markers implemented in the software STRUCTURE, three clusters were inferred, which were in good agreement with multivariate analysis. Geographic and genetic distances were congruent with the exception of a few putative hybrids identified in this study, suggesting a predominant effect of isolation by distance. Genomic scans using both markers linked to genes affected

  1. Fine-Mapping and Phenotypic Analysis of the Ity3 Salmonella Susceptibility Locus Identify a Complex Genetic Structure

    PubMed Central

    Khan, Rabia T.; Yuki, Kyoko E.; Malo, Danielle

    2014-01-01

    Experimental animal models of Salmonella infections have been widely used to identify genes important in the host immune response to infection. Using an F2 cross between the classical inbred strain C57BL/6J and the wild derived strain MOLF/Ei, we have previously identified Ity3 (Immunity to Typhimurium locus 3) as a locus contributing to the early susceptibility of MOLF/Ei mice to infection with Salmonella Typhimurium. We have also established a congenic strain (B6.MOLF-Ity/Ity3) with the MOLF/Ei Ity3 donor segment on a C57BL/6J background. The current study was designed to fine map and characterize functionally the Ity3 locus. We generated 12 recombinant sub-congenic strains that were characterized for susceptibility to infection, bacterial load in target organs, cytokine profile and anti-microbial mechanisms. These analyses showed that the impact of the Ity3 locus on survival and bacterial burden was stronger in male mice compared to female mice. Fine mapping of Ity3 indicated that two subloci contribute collectively to the susceptibility of B6.MOLF-Ity/Ity3 congenic mice to Salmonella infection. The Ity3.1 sublocus controls NADPH oxidase activity and is characterized by decreased ROS production, reduced inflammatory cytokine response and increased bacterial burden, thereby supporting a role for Ncf2 (neutrophil cytosolic factor 2 a subunit of NADPH oxidase) as the gene underlying this sublocus. The Ity3.2 sub-locus is characterized by a hyperresponsive inflammatory cytokine phenotype after exposure to Salmonella. Overall, this research provides support to the combined action of hormonal influences and complex genetic factors within the Ity3 locus in the innate immune response to Salmonella infection in wild-derived MOLF/Ei mice. PMID:24505352

  2. Spatial genetic structure patterns of phenotype-limited and boundary-limited expanding populations: a simulation study.

    PubMed

    Dai, Qiang; Zhan, Xiangjiang; Lu, Bin; Fu, Jinzhong; Wang, Qian; Qi, Dunwu

    2014-01-01

    Range expansions may create a unique spatial genetic pattern characterized by alternate genetically homogeneous domains and allele frequency clines. Previous attempts to model range expansions have mainly focused on the loss of genetic diversity during expansions. Using individual-based models, we examined spatial genetic patterns under two expansion scenarios, boundary-limited range expansions (BLRE) and phenotype-limited range expansions (PhLRE). Our simulation revealed that the genetic diversity within populations lost quickly during the range expansion, while the genetic difference accumulated between populations. Consequently, accompanying the expansions, the overall diversity featured a slow decrease. Specifically, during BLREs, high speed of boundary motion facilitated the maintenance of total genetic diversity and sharpened genetic clines. Very slight constraints on boundary motion of BLREs drastically narrowed the homogeneous domains and increased the allele frequency fluctuations from those levels exhibited by PhLREs. Even stronger constraints, however, surprisingly brought the width of homogeneous domains and the allele frequency fluctuations back to the normal levels of PhLREs. Furthermore, high migration rates maintained a higher total genetic diversity than low ones did during PhLREs. Whereas, the total genetic diversities during BLREs showed a contrary pattern: higher when migration was low than those when migration was high. Besides, the increase of migration rates helped maintain a greater number of homogeneous domains during PhLREs, but their effects on the number of homogeneous domains during BLREs were not monotonous. Previous studies have showed that the homogenous domains can merge to form a few broad domains as the expansion went on, leading to fewer homogeneous domains. Our simulations, meanwhile, revealed that the range expansions could also rebuild homogeneous domains from the clines during the range expansion. It is possible that that the

  3. Genomic Structure of Three Phenotypically Different Isolates of Peach Latent Mosaic Viroid: Implications of the Existence of Constraints Limiting the Heterogeneity of Viroid Quasispecies

    PubMed Central

    Ambrós, S.; Hernández, C.; Desvignes, J. C.; Flores, R.

    1998-01-01

    The peach latent mosaic viroid (PLMVd) is used to study the interactions between a viroid containing hammerhead ribozymes and its natural host, peach. To gain insight into the molecular basis of the phenotypic effects observed upon viroid infection, sequence variants from three PLMVd isolates that differ in symptom expression on the peach indicator GF-305 have been characterized. Analysis of the primary structures of a total of 29 different sequence variants derived from a severe and two latent isolates has revealed a large number of polymorphic positions in the viroid molecule. The variability pattern indicates that preservation of the stability of both hammerhead structures and conservation of a branched secondary structure of the viroid molecule may be factors limiting sequence heterogeneity in PLMVd. Moreover, compensatory mutations in two hairpin loops of the proposed secondary structure, suggesting that a pseudoknot-like interaction may exist between them, have also been observed. Phylogenetic analysis has allowed the allocation of PLMVd molecules into three major groups. This clustering does not strictly correlate with the source isolate from which the variants were obtained, providing insights into the complex mixture of molecules which make up each isolate. Bioassays of individual PLMVd sequence variants on GF-305 peach seedlings have shown that the biological properties of the PLMVd isolates may be correlated with both the complexity of their viroid populations and the presence of specific sequence variants. PMID:9696836

  4. Multiple Interactions across the Surface of the gp120 Core Structure Determine the Global Neutralization Resistance Phenotype of Human Immunodeficiency Virus Type 1

    PubMed Central

    Bouma, Peter; Leavitt, Maria; Zhang, Peng Fei; Sidorov, Igor A.; Dimitrov, Dimiter S.; Quinnan, Gerald V.

    2003-01-01

    Resistance to neutralization is an important characteristic of primary isolates of human immunodeficiency virus type 1 (HIV-1) that relates to the potential for successful vaccination to prevent infection and use of immunotherapeutics for treatment of established infection. In order to further elucidate mechanisms responsible for neutralization resistance, we studied the molecular mechanisms that determine the resistance of the primary virus isolate of the strain HIV-1 MN to neutralization by soluble CD4 (sCD4). As is the case for the global neutralization resistance phenotype, sCD4 resistance depended upon sequences in the amino-terminal heptad repeat region of gp41 (HR1), as well as on multiple functional interactions within the envelope complex. The functional interactions that determined the resistance included interactions between the variable loop 1 and 2 (V1/V2) region and sequences in or near the CD4 binding site (CD4bs) and with the V3 loop. Additionally, the V3 loop region was found to interact functionally with sequences in the outer domain of gp120, distant from the CD4bs and coreceptor-binding site, as well as with a residue thought to be located centrally in the coreceptor-binding site. These and previous results provide the basis for a model by which functional signals that determine the neutralization resistance, high-infectivity phenotype depend upon interactions occurring across the surface of the gp120 core structure and involving variable loop structures and gp41. This model should be useful in efforts to define epitopes that may be important for primary virus neutralization. PMID:12829845

  5. [Plasticity of the cellular phenotype].

    PubMed

    Chneiweiss, Hervé

    2011-01-01

    The tragical consequences of the Hiroshima and Nagasaki atomic bombs in 1945 were to lead to the discovery of hematopoietic stem cells and their phenotypic plasticity, in response to environmental factors. These concepts were much later extended to the founding cells of other tissues. In the following collection of articles, the mechanisms underlying this plasticity, at the frontiers of developmental biology and oncology, are illustrated in the case of various cell types of neural origin and of some tumours. PMID:21501574

  6. Trust-region based instantaneous optimal semi-active control of long-span spatially extended structures with MRF-04K damper

    NASA Astrophysics Data System (ADS)

    Lin, Wei; Li, Zhongxian; Ding, Yang

    2008-12-01

    In the field of civil engineering, magneto rheological fluid (MRF) damper-based semi-active control systems have received considerable attention for use in protecting structures from natural hazards such as strong earthquakes and high winds. In this paper, the MRF damper-based semi-active control system is applied to a long-span spatially extended structure and its feasibility is discussed. Meanwhile, a trust-region method based instantaneous optimal semi-active control algorithm (TIOC) is proposed to improve the performance of the semi-active control system in a multiple damper situation. The proposed TIOC describes the control process as a bounded constraint optimization problem, in which an optimal semiactive control force vector is solved by the trust-region method in every control step to minimize the structural responses. A numerical example of a railway station roof structure installed with MRF-04K dampers is presented. First, a modified Bouc-Wen model is utilized to describe the behavior of the selected MRF-04K damper. Then, two semi-active control systems, including the well-known clipped-optimal controller and the proposed TIOC controller, are considered. Based on the characteristics of the long-span spatially extended structure, the performance of the control system is evaluated under uniform earthquake excitation and travelling-wave excitation with different apparent velocities. The simulation results indicate that the MR fluid damper-based semi-active control systems have the potential to mitigate the responses of full-scale long-span spatially extended structures under earthquake hazards. The superiority of the proposed TIOC controller is demonstrated by comparing its control effectiveness with the clipped-optimal controller for several different cases.

  7. Inter and intra-population phenotypic and genotypic structuring in the European whitefish Coregonus lavaretus, a rare freshwater fish in Scotland.

    PubMed

    Adams, C E; Bean, C W; Dodd, J A; Down, A; Etheridge, E C; Gowans, A R D; Hooker, O; Knudsen, R; Lyle, A A; Winfield, I J; Præbel, K

    2016-02-01

    This study revealed between-lake genetic structuring between Coregonus lavaretus collected from the only two native populations of this species in Scotland, U.K. (Lochs Eck and Lomond) evidenced by the existence of private alleles (12 in Lomond and four in Eck) and significant genetic differentiation (FST = 0·056) across 10 microsatellite markers. Juvenile C. lavaretus originating from eggs collected from the two lakes and reared in a common-garden experiment showed clear phenotypic differences in trophic morphology (i.e. head and body shape) between these populations indicating that these characteristics were, at least partly, inherited. Microsatellite analysis of adults collected from different geographic regions within Loch Lomond revealed detectable and statistically significant but relatively weak genetic structuring (FST = 0·001-0·024) and evidence of private alleles related to the basin structure of the lake. Within-lake genetic divergence patterns suggest three possibilities for this observed pattern: (1) differential selection pressures causing divergence into separate gene pools, (2) a collapse of two formerly divergent gene pools and (3) a stable state maintained by balancing selection forces resulting from spatial variation in selection and lake heterogeneity. Small estimates of effective population sizes for the populations in both lakes suggest that the capacity of both populations to adapt to future environmental change may be limited. PMID:26748995

  8. Al K-edge extended fine structures in X-ray emission spectra of aluminum metal and aluminum oxide measured by an electron probe microanalyzer (EPMA)

    NASA Astrophysics Data System (ADS)

    Tanuma, S.; Nishio, M.

    1998-03-01

    The radiative Auger satellite peaks of Al Kα for aluminum metal and aluminum oxide were measured over a small area using an electron probe microanalyzer (EPMA). The oscillation was found to be similar to the extended X-ray absorption fine structure (EXAFS) in the EPMA spectra, oscillation which was recently discovered by Hayashi et al. (1997) in the X-ray fluorescence (XRF) spectra. The measured EXAFS spectra with EPMA are in good agreement with those by Hayashi et al., but here the oscillation structure could be obtained in a few minutes over a small area by using EPMA.

  9. Spinor extended Lorentz-force-like equations as consequence of a spinorial structure of space-time

    NASA Astrophysics Data System (ADS)

    Buitrago, J.; Hajjawi, S.

    2007-02-01

    As previously shown, the special relativistic dynamical equation of the Lorentz force type can be regarded as a consequence of a succession of space-time dependent infinitesimal Lorentz boosts and rotations. This insight indicates that the Lorentz-Force-like equation has a fundamental meaning in physics. We show how this result may be spinorially obtained starting out from the application of an infinitesimal element of SL(2,C) to the individual spinors, which are regarded here as being more fundamental objects than four-vectors. In this way we get a set of new dynamical spinor equations inducing the extended Lorentz-Force-like equation in the Minkowski space-time and geometrically obtain the spinor form of the electromagnetic field tensor. The term extended refers to the dynamics of some additional degrees of freedom that may be associated with the intrinsic spin, namely, with the dynamics of three spacelike mutually orthogonal four-vectors, all of them orthogonal to the linear four-momentum of the object under consideration that finally, in the particle's proper frame, are identified with the generators of SU(2).

  10. Multivariate Analysis of Genotype-Phenotype Association.

    PubMed

    Mitteroecker, Philipp; Cheverud, James M; Pavlicev, Mihaela

    2016-04-01

    With the advent of modern imaging and measurement technology, complex phenotypes are increasingly represented by large numbers of measurements, which may not bear biological meaning one by one. For such multivariate phenotypes, studying the pairwise associations between all measurements and all alleles is highly inefficient and prevents insight into the genetic pattern underlying the observed phenotypes. We present a new method for identifying patterns of allelic variation (genetic latent variables) that are maximally associated-in terms of effect size-with patterns of phenotypic variation (phenotypic latent variables). This multivariate genotype-phenotype mapping (MGP) separates phenotypic features under strong genetic control from less genetically determined features and thus permits an analysis of the multivariate structure of genotype-phenotype association, including its dimensionality and the clustering of genetic and phenotypic variables within this association. Different variants of MGP maximize different measures of genotype-phenotype association: genetic effect, genetic variance, or heritability. In an application to a mouse sample, scored for 353 SNPs and 11 phenotypic traits, the first dimension of genetic and phenotypic latent variables accounted for >70% of genetic variation present in all 11 measurements; 43% of variation in this phenotypic pattern was explained by the corresponding genetic latent variable. The first three dimensions together sufficed to account for almost 90% of genetic variation in the measurements and for all the interpretable genotype-phenotype association. Each dimension can be tested as a whole against the hypothesis of no association, thereby reducing the number of statistical tests from 7766 to 3-the maximal number of meaningful independent tests. Important alleles can be selected based on their effect size (additive or nonadditive effect on the phenotypic latent variable). This low dimensionality of the genotype-phenotype map

  11. Structured three-dimensional co-culture of mesenchymal stem cells with meniscus cells promotes meniscal phenotype without hypertrophy.

    PubMed

    Cui, Xiaofeng; Hasegawa, Akihiko; Lotz, Martin; D'Lima, Darryl

    2012-09-01

    Menisci play a crucial role in weight distribution, load bearing, shock absorption, lubrication, and nutrition of articular cartilage within the knee joint. Damage to the meniscus typically does not heal spontaneously due to its partial avascular nature. Partial or complete meniscectomy is a common clinical treatment of the defective meniscus. However, this procedure ultimately leads to osteoarthritis due to increased mechanical stress to the articular cartilage. Meniscus tissue engineering offers a promising solution for partial or complete meniscus deficiency. Mesenchymal stem cells (MSC) have the potential to differentiate into meniscal fibrochondrocyte as well as deliver trophic effects to the differentiated cells. This study tested the feasibility of using MSC co-cultured with mature meniscal cells (MC) for meniscus tissue engineering. Structured cell pellets were created using MC and MSC at varying ratios (100:0, 75:25, 50:50, 25:75, and 0:100) and cultured with or without transforming growth factor-beta 3 supplemented chondrogenic media for 21 days. The meniscal and hypertrophic gene expression, gross appearance and structure of the pellets, meniscus extracellular matrix (ECM), histology and immunohistochemistry of proteoglycan and collagen were evaluated. Co-culture of MC with MSC at 75:25 demonstrated highest levels of collagen type I and glycosaminoglycans (GAG) production, as well as the lowest levels of hypertrophic genes, such as COL10A1 and MMP13. All co-culture conditions showed better meniscus ECM production and hypertrophic inhibition as compared to MSC culture alone. The collagen fiber bundles observed in the co-cultures are important to produce heterogenic ECM structure of meniscus. In conclusion, co-culturing MC and MSC is a feasible and efficient approach to engineer meniscus tissue with enhanced ECM production without hypertrophy. PMID:22422555

  12. Conceptual and Data-based Investigation of Genetic Influences and Brain Asymmetry: A Twin Study of Multiple Structural Phenotypes

    PubMed Central

    Eyler, Lisa T.; Vuoksimaa, Eero; Panizzon, Matthew S.; Fennema-Notestine, Christine; Neale, Michael C.; Chen, Chi-Hua; Jak, Amy; Franz, Carol E.; Lyons, Michael J.; Thompson, Wesley K.; Spoon, Kelly M.; Fischl, Bruce; Dale, Anders M.; Kremen, William S.

    2014-01-01

    Right–left regional cerebral differences are a feature of the human brain linked to functional abilities, aging, and neuro-developmental and mental disorders. The role of genetic factors in structural asymmetry has been incompletely studied. We analyzed data from 515 individuals (130 monozygotic twin pairs, 97 dizygotic pairs, and 61 unpaired twins) from the Vietnam Era Twin Study of Aging to answer three questions about genetic determinants of brain structural asymmetry: First, does the magnitude of heritability differ for homologous regions in each hemisphere? Despite adequate power to detect regional differences, heritability estimates were not significantly larger in one hemisphere versus the other, except left > right inferior lateral ventricle heritability. Second, do different genetic factors influence left and right hemisphere size in homologous regions? Inter-hemispheric genetic correlations were high and significant; in only two subcortical regions (pallidum and accumbens) did the estimate statistically differ from 1.0. Thus, there was little evidence for different genetic influences on left and right hemisphere regions. Third, to what extent do genetic factors influence variability in left–right size differences? There was no evidence that variation in asymmetry (i.e., the size difference) of left and right homologous regions was genetically determined, except in pallidum and accumbens. Our findings suggest that genetic factors do not play a significant role in determining individual variation in the degree of regional cortical size asymmetries measured with MRI, although they may do so for volume of some subcortical structures. Despite varying interpretations of existing left–right, we view the present results as consistent with previous findings. PMID:24283492

  13. Structural and stratigraphic evolution of the Iberia and Newfoundland hyper-extended rifted margins: A quantitative modeling approach

    NASA Astrophysics Data System (ADS)

    Mohn, Geoffroy; Karner, Garry; Manatschal, Gianreto; Johnson, Christopher

    2014-05-01

    Rifted margins develop through polyphased extensional events leading eventually to break-up. Of particular interests are the stratigraphic and subsidence evolutions of these polyphased rift events. In this contribution, we investigate the spatial and temporal evolution of the Iberia-Newfoundland rift system from the Permian, post-orogenic development of European crust to early Cretaceous break-up on the continental lithosphere between Iberia and Newfoundland. Based on seismic reflection and refraction and ODP drill data combined with a kinematic and flexural model for the deformation of the lithosphere, we explore the general tectono-stratigraphic evolution of Iberia-Newfoundland rift system and its relationship to repeated lithospheric thinning events. Our results emphasize the kinematic and isostatic interactions engendered by the distinct distribution, amplitude and depth-partitioning of extensional events that allowed the formation of the Iberia-Newfoundland rift system. The initial stratigraphic record is controlled by Permian, post-orogenic topographic erosion, lithospheric thinning, and its subsequent thermal re-equilibration that lead to a regional subsidence characterized by non-marine to marine sedimentation. During late Triassic and early Jurassic time, extensional deformation was characterized by broadly-distributed depth uniform thinning related to minor thinning of the crust. From the Late Jurassic onward, extensional deformation was progressively localized and associated with depth-dependent thinning that finally lead to the formation of hyper-extended domains pre-dating the Late Aptian/Early Albian break-up of the Iberia-Newfoundland continental lithosphere. In particular, extension was diachronous, propagating in severity from south to north - while the southern Iberian margin was undergoing significant thinning in the Tithonian-early Berriasian, the northern margin (i.e., Galicia Bank) had yet to start rifting. Break-up is likewise diachronous

  14. An extended velocity projection method for estimating the subsurface current and density structure for coastal plume regions: An application to the Chesapeake Bay outflow plume

    NASA Astrophysics Data System (ADS)

    Gangopadhyay, Avijit; Shen, Colin Y.; Marmorino, George O.; Mied, Richard P.; Lindemann, Gloria J.

    2005-07-01

    We describe a method for estimating subsurface current and density structure in a coastal region dominated by a plume from a set of surface observations of velocity and density. A detailed application of the method is shown via a case study of the Chesapeake Bay in November 1997. The proposed technique relies on developing a 'plume feature model' from theoretical models and past synoptic observational data sets, and incorporating the feature model into the previously developed velocity projection method [J. Geophys. Res. 106 (2001) 6973] to obtain subsurface current structure within the Ekman layer depth. The primary feature model parameters include the location and extent of the frontal boundary, a simplified gravity current structure, and the spatial gradient of salinity across the frontal head of the plume, which are inferred from remote sensing or minimal strategic in situ observations. For the Chesapeake Bay case study, we show how the proposed method, referred to as 'extended velocity projection', can produce estimates of plume current structure consistent with available ADCP profiles. We assess the sensitivity of the results to feature model parameters, and identify the resolution of spatial salinity gradient as being particularly important. The difference between the density-stratified estimate and the ADCP data can be used to calibrate and improve the zero-order dynamic feature model parameters. This synergistic approach with the extended velocity projection method should be applicable to other coastal plumes and possibly other shallow water features.

  15. Structural basis for heterogeneous phenotype of ERG11 dependent Azole resistance in C.albicans clinical isolates.

    PubMed

    Debnath, Surajit; Addya, Soma

    2014-01-01

    Correlating antifungal Azole drug resistance and mis-sense mutations of ERG11 has been paradoxical in pathogenic yeast Candida albicans. Amino acid substitutions (single or multiple) are frequent on ERG11, a membrane bound enzyme of Ergosterol biosynthesis pathway. Presence or absence of mutations can not sufficiently predict susceptibility. To analyze role of mis-sense mutations on Azole resistance energetically optimized, structurally validated homology model of wild C.albicans ERG11 using eukaryotic template was generated. A Composite Search Approach is proposed to identify vital residues for interaction at 3D active site. Structural analysis of catalytic groove, dynamics of substrate access channels and proximity of Heme prosthetic group characterized ERG11 active site. Several mis-sense mutations of ERG11 reported in C.albicans clinical isolates were selected through a stringent criterion and modeled. ERG11 mutants subsequently subjected to a four tier comparative biophysical analysis. This study indicates (i) critical interactions occur with residues at anterior part of 3D catalytic groove and substitution of these vital residues alters local geometry causing considerable change in catalytic pocket dimension. (ii) Substitutions of vital residues lead to confirmed resistance in clinical isolates that may be resultant to changed geometry of catalytic pocket. (iii)These substitutions also impart significant energetic changes on C.albicans ERG11 and (iv) include detectable dynamic fluctuations on the mutants. (v)Mis-sense mutations on the vital residues of the active site and at the vicinity of Heme prosthetic group are less frequent compared to rest of the enzyme. This large scale mutational study can aid to characterize the mutants in clinical isolates. PMID:25512882

  16. The impact of herbicide-resistant rice technology on phenotypic diversity and population structure of United States weedy rice.

    PubMed

    Burgos, Nilda Roma; Singh, Vijay; Tseng, Te Ming; Black, Howard; Young, Nelson D; Huang, Zhongyun; Hyma, Katie E; Gealy, David R; Caicedo, Ana L

    2014-11-01

    The use of herbicide-resistant (HR) Clearfield rice (Oryza sativa) to control weedy rice has increased in the past 12 years to constitute about 60% of rice acreage in Arkansas, where most U.S. rice is grown. To assess the impact of HR cultivated rice on the herbicide resistance and population structure of weedy rice, weedy samples were collected from commercial fields with a history of Clearfield rice. Panicles from each weedy type were harvested and tested for resistance to imazethapyr. The majority of plants sampled had at least 20% resistant offspring. These resistant weeds were 97 to 199 cm tall and initiated flowering from 78 to 128 d, generally later than recorded for accessions collected prior to the widespread use of Clearfield rice (i.e. historical accessions). Whereas the majority (70%) of historical accessions had straw-colored hulls, only 30% of contemporary HR weedy rice had straw-colored hulls. Analysis of genotyping-by-sequencing data showed that HR weeds were not genetically structured according to hull color, whereas historical weedy rice was separated into straw-hull and black-hull populations. A significant portion of the local rice crop genome was introgressed into HR weedy rice, which was rare in historical weedy accessions. Admixture analyses showed that HR weeds tend to possess crop haplotypes in the portion of chromosome 2 containing the ACETOLACTATE SYNTHASE gene, which confers herbicide resistance to Clearfield rice. Thus, U.S. HR weedy rice is a distinct population relative to historical weedy rice and shows modifications in morphology and phenology that are relevant to weed management. PMID:25122473

  17. An environment-dependent interatomic potential for silicon carbide: calculation of bulk properties, high-pressure phases, point and extended defects, and amorphous structures.

    PubMed

    Lucas, G; Bertolus, M; Pizzagalli, L

    2010-01-27

    An interatomic potential has been developed to describe interactions in silicon, carbon and silicon carbide, based on the environment-dependent interatomic potential (EDIP) (Bazant et al 1997 Phys. Rev. B 56 8542). The functional form of the original EDIP has been generalized and two sets of parameters have been proposed. Tests with these two potentials have been performed for many properties of SiC, including bulk properties, high-pressure phases, point and extended defects, and amorphous structures. One parameter set allows us to keep the original EDIP formulation for silicon, and is shown to be well suited for modelling irradiation-induced effects in silicon carbide, with a very good description of point defects and of the disordered phase. The other set, including a new parametrization for silicon, has been shown to be efficient for modelling point and extended defects, as well as high-pressure phases. PMID:21386297

  18. DISCOVERY OF EXTENDED AND VARIABLE RADIO STRUCTURE FROM THE GAMMA-RAY BINARY SYSTEM PSR B1259-63/LS 2883

    SciTech Connect

    Moldon, Javier; Ribo, Marc; Paredes, Josep M.; Johnston, Simon; Deller, Adam T.

    2011-05-01

    PSR B1259-63 is a 48 ms pulsar in a highly eccentric 3.4 year orbit around the young massive star LS 2883. During the periastron passage the system displays transient non-thermal unpulsed emission from radio to very high energy gamma rays. It is one of the three galactic binary systems clearly detected at TeV energies, together with LS 5039 and LS I +61 303. We observed PSR B1259-63 after the 2007 periastron passage with the Australian Long Baseline Array at 2.3 GHz to trace the milliarcsecond (mas) structure of the source at three different epochs. We have discovered extended and variable radio structure. The peak of the radio emission is detected outside the binary system near periastron, at projected distances of 10-20 mas (25-45 AU assuming a distance of 2.3 kpc). The total extent of the emission is {approx}50 mas ({approx}120 AU). This is the first observational evidence that non-accreting pulsars orbiting massive stars can produce variable extended radio emission at AU scales. Similar structures are also seen in LS 5039 and LS I +61 303, in which the nature of the compact object is unknown. The discovery presented here for the young non-accreting pulsar PSR B1259-63 reinforces the link with these two sources and supports the presence of pulsars in these systems as well. A simple kinematical model considering only a spherical stellar wind can approximately trace the extended structures if the binary system orbit has a longitude of the ascending node of {Omega} {approx} -40{sup 0} and a magnetization parameter of {sigma} {approx} 0.005.

  19. Extended electron energy loss fine structure simulation of the local boron environment in sodium aluminoborosilicate glasses containing gadolinium

    SciTech Connect

    Qian, Morris; Li, Hong; Li, Liyu ); Strachan, Denis M. )

    2003-10-15

    Gadolinium can be dissolved in sodium-alumino-borosilicate glasses up to 47 wt% in a baseline borosilicate glass (mol%) 20 B2O3, 5 Al2O3, 60 SiO2,and 20 Na2O. Understanding of Gd dissolution in borosilicate melts is important in glass formulation optimization. Electron energy loss fine structure (ELFS) spectroscopy is chosen, which provides well resolved local atomic structure information for both amorphous and crystalline materials with high sensitivity to low Z elements such as Al, B, Na, O, and Si where the x-ray absorption fine structure (XAFS) technique faces experimental difficulty. In this study, we report our results of boron K-edge ELFS study. Two borosilicate glass samples with 30 and 47 mass% Gd2O3, B20Gd30 and B20Gd47were chosen for B K-edge ELFS study. EEL spectra were acquired on a Philips 430 TEM equipped with Gatan PEELS system 666 and EL/P 2.1 software with Custom function AcqLong. The ELFS data analysis was performed using UWELFS, UWXAFS and FEFF software. From our Gd solubility study, the local structure of Gd in the borate environment possibly resembles double chain structure found in crystalline Gd(BO2)3 as proposed by Chakraborty et al. The B/Gd ratio's in both glasses are smaller then 3, which means the excess Gd atoms in the Si-sites would be 17 and 60 mol% of the total Gd atoms, respectively according to the model, yet the local environment of borate sites saturated with Gd should be remained. To verity above hypothesis, the double chain structure model was applied to fit boron K-edge. The model was shown to well fit experimental boron K-edge EELS spectra for both glasses with some degree of distance distortion which is understandable in amorphous structure. Therefore, it is very likely that Gd stabilized in borate sites has a local structure resembling the double chain Gd(BO2)3 structure as proposed by our solubility study and literature.

  20. Structure-Property Characterization of the Crinkle-Leaf Peach Wood Phenotype: A Future Model System for Wood Properties Research?

    NASA Astrophysics Data System (ADS)

    Wiedenhoeft, Alex C.; Arévalo, Rafael; Ledbetter, Craig; Jakes, Joseph E.

    2016-08-01

    Nearly 400 million years of evolution and field-testing by the natural world has given humans thousands of wood types, each with unique structure-property relationships to study, exploit, and ideally, to manipulate, but the slow growth of trees makes them a recalcitrant experimental system. Variations in wood features of two genotypes of peach (Prunus persica L.) trees, wild-type and crinkle-leaf, were examined to elucidate the nature of weak wood in crinkle-leaf trees. Crinkle-leaf is a naturally-occurring mutation in which wood strength is altered in conjunction with an easily observed `crinkling' of the leaves' surface. Trees from three vigor classes (low growth rate, average growth rate, and high growth rate) of each genotype were sampled. No meaningful tendency of dissimilarities among the different vigor classes was found, nor any pattern in features in a genotype-by-vigor analysis. Wild-type trees exhibited longer vessels and fibers, wider rays, and slightly higher specific gravity. Neither cell wall mechanical properties measured with nanoindentation nor cell wall histochemical properties were statistically or observably different between crinkle-leaf and wild-type wood. The crinkle-leaf mutant has the potential to be a useful model system for wood properties investigation and manipulation if it can serve as a field-observable vegetative marker for altered wood properties.

  1. Thermal and magnetic anomalies of α-iron: an exploration by extended x-ray absorption fine structure spectroscopy and synchrotron x-ray diffraction

    NASA Astrophysics Data System (ADS)

    Boccato, Silvia; Sanson, Andrea; Kantor, Innokenty; Mathon, Olivier; Dyadkin, Vadim; Chernyshov, Dmitry; Carnera, Alberto; Pascarelli, Sakura

    2016-09-01

    The local structure and dynamics of α-iron have been investigated by extended x-ray absorption fine structure (EXAFS) spectroscopy and x-ray diffraction (XRD) in order to shed light on some thermal and magnetic anomalies observed in the last decades. The quantitative EXAFS analysis of the first two coordination shells reveals a peculiar local vibrational dynamics of α-iron: the second neighbor distance exhibits anharmonicity and vibrational anisotropy larger than the first neighbor distance. We search for possible distortions of the bcc structure to justify the unexplained magnetostriction anomalies of α-iron and provide a value for the maximum dislocation of the central Fe atom. No thermal anomalies have been detected from the current XRD data. On the contrary, an intriguing thermal anomaly at about 150 K, ascribed to a stiffening of the Fe–Fe bonds, was found by EXAFS.

  2. Thermal and magnetic anomalies of α-iron: an exploration by extended x-ray absorption fine structure spectroscopy and synchrotron x-ray diffraction.

    PubMed

    Boccato, Silvia; Sanson, Andrea; Kantor, Innokenty; Mathon, Olivier; Dyadkin, Vadim; Chernyshov, Dmitry; Carnera, Alberto; Pascarelli, Sakura

    2016-09-01

    The local structure and dynamics of α-iron have been investigated by extended x-ray absorption fine structure (EXAFS) spectroscopy and x-ray diffraction (XRD) in order to shed light on some thermal and magnetic anomalies observed in the last decades. The quantitative EXAFS analysis of the first two coordination shells reveals a peculiar local vibrational dynamics of α-iron: the second neighbor distance exhibits anharmonicity and vibrational anisotropy larger than the first neighbor distance. We search for possible distortions of the bcc structure to justify the unexplained magnetostriction anomalies of α-iron and provide a value for the maximum dislocation of the central Fe atom. No thermal anomalies have been detected from the current XRD data. On the contrary, an intriguing thermal anomaly at about 150 K, ascribed to a stiffening of the Fe-Fe bonds, was found by EXAFS. PMID:27385480

  3. Identification of benzopyrone as a common structural feature in compounds with anti-inflammatory activity in a zebrafish phenotypic screen

    PubMed Central

    Robertson, Anne L.; Ogryzko, Nikolay V.; Henry, Katherine M.; Loynes, Catherine A.; Foulkes, Matthew J.; Meloni, Marco M.; Wang, Xingang; Ford, Christopher; Jackson, Malcolm; Ingham, Philip W.; Wilson, Heather L.; Farrow, Stuart N.; Solari, Roberto; Flower, Roderick J.; Jones, Simon; Whyte, Moira K. B.

    2016-01-01

    ABSTRACT Neutrophils are essential for host defence and are recruited to sites of inflammation in response to tissue injury or infection. For inflammation to resolve, these cells must be cleared efficiently and in a controlled manner, either by apoptosis or reverse migration. If the inflammatory response is not well-regulated, persistent neutrophils can cause damage to host tissues and contribute to the pathogenesis of chronic inflammatory diseases, which respond poorly to current treatments. It is therefore important to develop drug discovery strategies that can identify new therapeutics specifically targeting neutrophils, either by promoting their clearance or by preventing their recruitment. Our recent in vivo chemical genetic screen for accelerators of inflammation resolution identified a subset of compounds sharing a common chemical signature, the bicyclic benzopyrone rings. Here, we further investigate the mechanisms of action of the most active of this chemical series, isopimpinellin, in our zebrafish model of neutrophilic inflammation. We found that this compound targets both the recruitment and resolution phases of the inflammatory response. Neutrophil migration towards a site of injury is reduced by isopimpinellin and this occurs as a result of PI3K inhibition. We also show that isopimpinellin induces neutrophil apoptosis to drive inflammation resolution in vivo using a new zebrafish reporter line detecting in vivo neutrophil caspase-3 activity and allowing quantification of flux through the apoptotic pathway in real time. Finally, our studies reveal that clinically available ‘cromones’ are structurally related to isopimpinellin and have previously undescribed pro-resolution activity in vivo. These findings could have implications for the therapeutic use of benzopyrones in inflammatory disease. PMID:27079522

  4. Identification of benzopyrone as a common structural feature in compounds with anti-inflammatory activity in a zebrafish phenotypic screen.

    PubMed

    Robertson, Anne L; Ogryzko, Nikolay V; Henry, Katherine M; Loynes, Catherine A; Foulkes, Matthew J; Meloni, Marco M; Wang, Xingang; Ford, Christopher; Jackson, Malcolm; Ingham, Philip W; Wilson, Heather L; Farrow, Stuart N; Solari, Roberto; Flower, Roderick J; Jones, Simon; Whyte, Moira K B; Renshaw, Stephen A

    2016-06-01

    Neutrophils are essential for host defence and are recruited to sites of inflammation in response to tissue injury or infection. For inflammation to resolve, these cells must be cleared efficiently and in a controlled manner, either by apoptosis or reverse migration. If the inflammatory response is not well-regulated, persistent neutrophils can cause damage to host tissues and contribute to the pathogenesis of chronic inflammatory diseases, which respond poorly to current treatments. It is therefore important to develop drug discovery strategies that can identify new therapeutics specifically targeting neutrophils, either by promoting their clearance or by preventing their recruitment. Our recent in vivo chemical genetic screen for accelerators of inflammation resolution identified a subset of compounds sharing a common chemical signature, the bicyclic benzopyrone rings. Here, we further investigate the mechanisms of action of the most active of this chemical series, isopimpinellin, in our zebrafish model of neutrophilic inflammation. We found that this compound targets both the recruitment and resolution phases of the inflammatory response. Neutrophil migration towards a site of injury is reduced by isopimpinellin and this occurs as a result of PI3K inhibition. We also show that isopimpinellin induces neutrophil apoptosis to drive inflammation resolution in vivo using a new zebrafish reporter line detecting in vivo neutrophil caspase-3 activity and allowing quantification of flux through the apoptotic pathway in real time. Finally, our studies reveal that clinically available 'cromones' are structurally related to isopimpinellin and have previously undescribed pro-resolution activity in vivo These findings could have implications for the therapeutic use of benzopyrones in inflammatory disease. PMID:27079522

  5. Photoluminescence and structural studies on extended defect evolution during high-temperature processing of ion-implanted epitaxial silicon

    NASA Astrophysics Data System (ADS)

    Giri, P. K.; Coffa, S.; Raineri, V.; Privitera, V.; Galvagno, G.; La Ferla, A.; Rimini, E.

    2001-04-01

    Low-temperature photoluminescence (PL) spectroscopy, in conjunction with transmission electron microscopy (TEM) and optical microscopy (OM) have been carried out to investigate the origin of radiative recombination from various extended defects that evolve during high-temperature processing of ion-implanted epitaxial silicon. From PL studies on N2-annealed samples, we provide spectroscopic evidence of precipitation of the implanted impurities well below the solid-solubility limit. This result is being supported by observations from secondary ion mass spectrometry and spreading resistance profiling of the implanted ions. Cross sectional TEM analyses on these samples reveal <111>-oriented precipitates located in a region containing a high dislocation density. Postimplantation annealing in oxygen ambient results in the formation of dislocations and oxidation-induced stacking faults (OISF). A systematic analysis of PL spectra on different-implanted and preannealed samples, in conjunction with TEM and OM analyses, reveals that the conventionally observed dislocation-related D1 and D2 lines in the PL spectrum is not a characteristic of the OISF, but of the dislocations only. It is shown that the OISF acts as a nonradiative channel for luminescence in silicon. Various other sources of nonradiative channels in silicon are also presented and the efficacy of photoluminescence technique in the characterization of process-induced defects in silicon is discussed.

  6. Rats subjected to extended L-tryptophan restriction during early postnatal stage exhibit anxious-depressive features and structural changes.

    PubMed

    Zhang, Limei; Guadarrama, Leyla; Corona-Morales, Aleph A; Vega-Gonzalez, Arturo; Rocha, Luisa; Escobar, Alfonso

    2006-06-01

    Serotonin transmission dysfunction has been suggested to play an important role in depression and anxiety. This study reports the results of a series of experiments in which rats were subjected to extended maize-based tortilla diets during early postnatal stages. This diet contains only approximately 20% of the L-tryptophan in normal diets of laboratory rodents. Compared with controls, experimental rats displayed a significant increase of immobility counts in the forced swimming test and exhibited anxiety-like behavior in the elevated plus maze test after 1 month of diet treatment. Low levels of serotonin contents were found in prefrontal cortex, striatum, hippocampus, and brainstem using high-performance liquid chromatography. Immunocytochemical reactions against 5-Bromo-2'-deoxyuridine revealed a significant decrease in the proliferation rate for the subgranular zone of dentate gyrus. c-Fos expression after the forced swimming test was found reduced in prefrontal cortex, dentate gyrus, CA1, and hilus of hippocampus and amygdala. Moreover, dendrite arbor atrophy and decreased spine density were evident in Golgi-Cox-impregnated CA1 pyramidal neurons. Abnormal dendrite swelling in dentate gyrus granule cells was also observed. These findings indicate an involvement of hyposerotoninergia in emotional disturbance produced by L-tryptophan restriction during critical developmental stages and suggest that neuroplasticity changes might underlie these changes. PMID:16783166

  7. Structure of a novel dodecaheme cytochrome c from Geobacter sulfurreducens reveals an extended 12 nm protein with interacting hemes.

    SciTech Connect

    Pokkuluri, P. R.; Londer, Y. Y.; Duke, N. E. C.; Pessanha, M.; Yang, X.; Orshonsky, V.; Orshonsky, L.; Erickson, J.; Zagyansky, Y.; Salgueiro, C. A.; Schiffer, M.

    2011-04-01

    Multiheme cytochromes c are important in electron transfer pathways in reduction of both soluble and insoluble Fe(III) by Geobacter sulfurreducens. We determined the crystal structure at 3.2 {angstrom} resolution of the first dodecaheme cytochrome c (GSU1996) along with its N-terminal and C-terminal hexaheme fragments at 2.6 and 2.15 {angstrom} resolution, respectively. The macroscopic reduction potentials of the full-length protein and its fragments were measured. The sequence of GSU1996 can be divided into four c{sub 7}-type domains (A, B, C and D) with homology to triheme cytochromes c{sub 7}. In cytochromes c{sub 7} all three hemes are bis-His coordinated, whereas in c{sub 7}-type domains the last heme is His-Met coordinated. The full-length GSU1996 has a 12 nm long crescent shaped structure with the 12 hemes arranged along a polypeptide to form a 'nanowire' of hemes; it has a modular structure. Surprisingly, while the C-terminal half of the protein consists of two separate c{sub 7}-type domains (C and D) connected by a small linker, the N-terminal half of the protein has two c{sub 7}-type domains (A and B) that form one structural unit. This is also observed in the AB fragment. There is an unexpected interaction between the hemes at the interface of domains A and B, which form a heme-pair with nearly parallel stacking of their porphyrin rings. The hemes adjacent to each other throughout the protein are within van der Waals distance which enables efficient electron exchange between them. For the first time, the structural details of c{sub 7}-type domains from one multiheme protein were compared.

  8. The genomic and phenotypic diversity of Schizosaccharomyces pombe.

    PubMed

    Jeffares, Daniel C; Rallis, Charalampos; Rieux, Adrien; Speed, Doug; Převorovský, Martin; Mourier, Tobias; Marsellach, Francesc X; Iqbal, Zamin; Lau, Winston; Cheng, Tammy M K; Pracana, Rodrigo; Mülleder, Michael; Lawson, Jonathan L D; Chessel, Anatole; Bala, Sendu; Hellenthal, Garrett; O'Fallon, Brendan; Keane, Thomas; Simpson, Jared T; Bischof, Leanne; Tomiczek, Bartlomiej; Bitton, Danny A; Sideri, Theodora; Codlin, Sandra; Hellberg, Josephine E E U; van Trigt, Laurent; Jeffery, Linda; Li, Juan-Juan; Atkinson, Sophie; Thodberg, Malte; Febrer, Melanie; McLay, Kirsten; Drou, Nizar; Brown, William; Hayles, Jacqueline; Carazo Salas, Rafael E; Ralser, Markus; Maniatis, Nikolas; Balding, David J; Balloux, Francois; Durbin, Richard; Bähler, Jürg

    2015-03-01

    Natural variation within species reveals aspects of genome evolution and function. The fission yeast Schizosaccharomyces pombe is an important model for eukaryotic biology, but researchers typically use one standard laboratory strain. To extend the usefulness of this model, we surveyed the genomic and phenotypic variation in 161 natural isolates. We sequenced the genomes of all strains, finding moderate genetic diversity (π = 3 × 10(-3) substitutions/site) and weak global population structure. We estimate that dispersal of S. pombe began during human antiquity (∼340 BCE), and ancestors of these strains reached the Americas at ∼1623 CE. We quantified 74 traits, finding substantial heritable phenotypic diversity. We conducted 223 genome-wide association studies, with 89 traits showing at least one association. The most significant variant for each trait explained 22% of the phenotypic variance on average, with indels having larger effects than SNPs. This analysis represents a rich resource to examine genotype-phenotype relationships in a tractable model. PMID:25665008

  9. Structure of the Brachydanio Rerio Polo-Like Kinase 1 (Plk1) Catalytic Domain in Complex With An Extended Inhibitor Targeting the Adaptive Pocket of the Enzyme

    SciTech Connect

    Elling, R.A.; Fucini, R.V.; Hanan, E.J.; Barr, K.J.; Zhu, J.; Paulvannan, K.; Yang, W.; Romanowski, M.J.

    2009-05-18

    Polo-like kinase 1 (Plk1) is a member of the Polo-like kinase family of serine/threonine kinases involved in the regulation of cell-cycle progression and cytokinesis and is an attractive target for the development of anticancer therapeutics. The catalytic domain of this enzyme shares significant primary amino-acid homology and structural similarity with another mitotic kinase, Aurora A. While screening an Aurora A library of ATP-competitive compounds, a urea-containing inhibitor with low affinity for mouse Aurora A but with submicromolar potency for human and zebrafish Plk1 (hPlk1 and zPlk1, respectively) was identified. A crystal structure of the zebrafish Plk1 kinase domain-inhibitor complex reveals that the small molecule occupies the purine pocket and extends past the catalytic lysine into the adaptive region of the active site. Analysis of the structures of this protein-inhibitor complex and of similar small molecules cocrystallized with other kinases facilitates understanding of the specificity of the inhibitor for Plk1 and documents for the first time that Plk1 can accommodate extended ATP-competitive compounds that project toward the adaptive pocket and help the enzyme order its activation segment.

  10. Extended Vofire algorithm for fast transient fluid-structure dynamics with liquid-gas flows and interfaces

    NASA Astrophysics Data System (ADS)

    Faucher, Vincent; Kokh, Samuel

    2013-05-01

    The present paper is dedicated to the simulation of liquid-gas flows with interfaces in the framework of fast transient fluid-structure dynamics. The two-fluid interface is modelled as a discontinuity surface in the fluid property. We use an anti-dissipative Finite-Volume discretization strategy for unstructured meshes in order to capture the position of the interface within a thin diffused volume. This allows to control the numerical diffusion of the artificial mixing between components and provide an accurate capture of complex interface motions. This scheme is an extension of the Vofire numerical solver. We propose specific developments in order to handle flows that involved high density ratio between liquid and gas. The resulting scheme capabilities are validated on basic examples and also tested against large scale fluid-structure test derived from the MARA 10 experiment. All simulations are performed using EUROPLEXUS fast transient dynamics software.

  11. An extended inner-outer factorisation algorithm based on the structure of a transfer function matrix inverse

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Zhao, Chunhui; He, Xing; Zhang, Weidong

    2016-05-01

    In this paper, the structure feature of the inverse of a multi-input/multi-output square transfer function matrix is explored. Instead of complicated advanced mathematical tools, we only use basic results of complex analysis in the analysing procedure. By employing the Laurent expression, an elegant structure form of the expansion is obtained for the transfer function matrix inverse. This expansion form is the key of deriving an analytical solution to the inner-outer factorisation for both stable plants and unstable plants. Different from other computation algorithm, the obtained inner-outer factorisation is given in an analytical form. The solution is exact and without approximation. Numerical examples are provided to verify the correctness of the obtained results.

  12. Research Investigation Directed Toward Extending the Useful Range of the Electromagnetic Spectrum. [atomic spectra and electronic structure of alkali metals

    NASA Technical Reports Server (NTRS)

    Hartmann, S. R.; Happer, W.

    1974-01-01

    The report discusses completed and proposed research in atomic and molecular physics conducted at the Columbia Radiation Laboratory from July 1972 to June 1973. Central topics described include the atomic spectra and electronic structure of alkali metals and helium, molecular microwave spectroscopy, the resonance physics of photon echoes in some solid state systems (including Raman echoes, superradiance, and two photon absorption), and liquid helium superfluidity.

  13. Three-dimensional structure of a peptide extending from one end of a class I MHC binding site.

    PubMed

    Collins, E J; Garboczi, D N; Wiley, D C

    1994-10-13

    Class I major histocompatibility complex (MHC) molecules present peptides to CD8+ T cells for immunological surveillance (reviewed in ref. 1). The structures of complexes of class I MHC molecules with octamer, nonamer and decamer peptides determined until now show a common binding mode, with both peptide termini bound in conserved pockets at the ends of the peptide binding site. Length variations were accommodated by the peptide bulging or zig-zagging in the middle. Here we describe the structure of a decamer peptide which binds with the carboxy-terminal residue positioned outside the peptide binding site. Several protein side chains have rearranged to allow the peptide to exit. The structure suggests that even longer peptides could bind. The energetic effect of the altered mode of binding has been assessed by measuring the stability of the complex to thermal denaturation. Peptides bound in this novel manner are stable at physiological temperature, raising questions about their role in T-cell recognition and their production by proteolytic processing. PMID:7935798

  14. An example of phenotypic adherence to the island rule? - Anticosti gray jays are heavier but not structurally larger than mainland conspecifics.

    PubMed

    Strickland, Dan; Norris, D Ryan

    2015-09-01

    The island rule refers to the tendency of small vertebrates to become larger when isolated on islands and the frequent dwarfing of large forms. It implies genetic control, and a necessary linkage, of size and body-mass differences between insular and mainland populations. To examine the island rule, we compared body size and mass of gray jays (Perisoreus canadensis) on Anticosti Island, Québec, located in the Gulf of St. Lawrence, with three mainland populations (2 in Québec and 1 in Ontario). Although gray jays on Anticosti Island were ca 10% heavier, they were not structurally larger, than the three mainland populations. This suggests that Anticosti jays are not necessarily genetically distinct from mainland gray jays and that they may have achieved their greater body masses solely through packing more mass onto mainland-sized body frames. As such, they may be the first-known example of a proposed, purely phenotypic initial step in the adherence to the island rule by an insular population. Greater jay body mass is probably advantageous in Anticosti's high-density, intensely competitive social environment that may have resulted from the island's lack of mammalian nest predators. PMID:26380697

  15. An example of phenotypic adherence to the island rule? – Anticosti gray jays are heavier but not structurally larger than mainland conspecifics

    PubMed Central

    Strickland, Dan; Norris, D Ryan

    2015-01-01

    The island rule refers to the tendency of small vertebrates to become larger when isolated on islands and the frequent dwarfing of large forms. It implies genetic control, and a necessary linkage, of size and body-mass differences between insular and mainland populations. To examine the island rule, we compared body size and mass of gray jays (Perisoreus canadensis) on Anticosti Island, Québec, located in the Gulf of St. Lawrence, with three mainland populations (2 in Québec and 1 in Ontario). Although gray jays on Anticosti Island were ca 10% heavier, they were not structurally larger, than the three mainland populations. This suggests that Anticosti jays are not necessarily genetically distinct from mainland gray jays and that they may have achieved their greater body masses solely through packing more mass onto mainland-sized body frames. As such, they may be the first-known example of a proposed, purely phenotypic initial step in the adherence to the island rule by an insular population. Greater jay body mass is probably advantageous in Anticosti's high-density, intensely competitive social environment that may have resulted from the island's lack of mammalian nest predators. PMID:26380697

  16. Extended electron energy loss fine structure simulation of the local boron environment in sodium aluminoborosilicate glasses containing gadolinium

    SciTech Connect

    Qian, Morris; Li, Hong; Li, Liyu ); Strachan, Denis M. )

    2003-12-01

    Phase separation in sodium-aluminoborosilicate glasses was systematically studied as a function of Gd2O3 concentration with transmission electron microscopy (TEM), energy dispersive x-ray spectroscopy (EDS), and electron energy loss spectroscopy (EELS) methods. Gadolinium-induced phase separation in the three systems can be consistently explained by proposing that Gd cations partition to the borate-rich environments and subsequent agglomeration of the Gd-borate moieties, or short-range ordered structural groups, in the glass. Agglomeration of the Gd-borate rich environments is further discussed within the context of excess metal oxides,[Na2O]ex or[Al2O3]ex=|Na2O - Al2O3|, and excess B2O3,[B2O3]ex, available for incorporating Gd cations. Results showed that agglomeration of the Gd-borate rich environments occurred at a much lower Gd2O3 concentration in the glass without[Na2O]ex or[Al2O3]ex and at a significantly higher Gd2O3 concentration in the glass with either[Na2O]ex or[Al2O3]ex. Assuming 1BO4 : 1Gd : 2BO3 (based on literature-reported Gd-metaborate structure) as a local Gd-borate environment in glass, we introduced the saturation index of boron, SI[B]= Gd2O3/(1/3[B2O3]ex), to examine the glass susceptibility to Gd-induced phase separation for all three alkali-aluminoborosilicate systems. While our results have provided some insight to the glass structure, they also provide insight to the mechanism by which the metal oxide is dissolved into the melt. This appears to occur predominantly through boron complexation of the metal oxide.

  17. ELECTRONIC STRUCTURE CALCULATIONS FOR PrFe4P12 FILLED SKUTTERUDITE USING EXTENDED HUCKEL TIGHT-BINDING METHOD

    NASA Astrophysics Data System (ADS)

    GALVAN, DONALD H.

    To gain insight into the electronic properties of PrFe4P12 filled skutterudite, band electronic structure calculations, total and projected density of states, crystal orbital overlap population and Mulliken population analysis were performed. The energy bands yield a semi-metallic behavior with a direct gap (at Γ) of 0.02 eV. Total and Projected Density of States provided information of the contribution from each orbital of each atom to the total Density of States. Moreover, the bonding strength between some atoms within the unit cell was obtained. Mulliken Population Analysis suggests ionic behavior for this filled skutterudite.

  18. Mapping kiloparsec-scale structures in the extended H I disc of the galaxy UGC 000439 by H I 21-cm absorption

    NASA Astrophysics Data System (ADS)

    Dutta, R.; Gupta, N.; Srianand, R.; O'Meara, J. M.

    2016-03-01

    We study the properties of H I gas in the outer regions (˜2r25) of a spiral galaxy, UGC 00439 (z = 0.017 69), using H I 21-cm absorption towards different components of an extended background radio source, J0041-0043 (z = 1.679). The radio source exhibits a compact core coincident with the optical quasar and two lobes separated by ˜7 kpc, all at an impact parameter ˜25 kpc. The H I 21-cm absorption detected towards the southern lobe is found to extend over ˜2 kpc2. The absorbing gas shows sub-kpc-scale structures with the line-of-sight velocities dominated by turbulent motions. Much larger optical depth variations over 4-7 kpc scale are revealed by the non-detection of H I 21-cm absorption towards the radio core and the northern lobe, and the detection of Na I and Ca II absorption towards the quasar. This could reflect a patchy distribution of cold gas in the extended H I disc. We also detect H I 21-cm emission from UGC 00439 and two other galaxies within ˜150 kpc to it, that probably form an interacting group. However, no H I 21-cm emission from the absorbing gas is detected. Assuming a linear extent of ˜4 kpc, as required to cover both the core and the southern lobe, we constrain the spin temperature ≲ 300 K for the absorbing gas. The kinematics of the gas and the lack of signatures of any ongoing in situ star formation are consistent with the absorbing gas being at the kinematical minor axis and corotating with the galaxy. Deeper H I 21-cm observations would help to map in greater detail both the large- and small-scale structures in the H I gas associated with UGC 00439.

  19. Seismic structure of the extended continental crust in the Yamato Basin, Japan Sea, from ocean bottom seismometer survey

    NASA Astrophysics Data System (ADS)

    Nakahigashi, Kazuo; Shinohara, Masanao; Yamada, Tomoaki; Uehira, Kenji; Mochizuki, Kimihiro; Kanazawa, Toshihiko

    2013-05-01

    We present the result of a seismic experiment conducted using ocean bottom seismometers and an airgun in the Yamato Basin, of the Japan Sea. The Japan Sea is one of the most well-studied back-arc basins in the western Pacific. The Japan Sea is believed to have been formed by back-arc opening. However, the timing and formation processes of the opening of individual basins in and around the Japan Sea are not clear. To reveal the crustal structure of the Yamato Basin it is important to consider the formation process of the Japan Sea. Therefore, we conducted a seismic survey and estimated the P-wave seismic velocity structure beneath the 170-km profile using a 2-D ray-tracing method. A layer with a P-wave velocity of 3.4-4.0 km/s underlies the sedimentary sections, which is thought to consist of a sill-and-sediment complex. The upper crust below the profile varies greatly in thickness. The thickness of the upper crust is 3.5 km in the thinnest part and 7 km in the thickest part. The thickness of the lower crust is approximately 8 km and is relatively constant over the profile. The total thickness of the crust is approximately 15 km including the sedimentary layer. The distribution of P-wave velocities and the thickness indicate that the crust in the Yamato Basin is neither a typical continental nor a typical oceanic crust. From the point of view of seismic velocity, the obtained structure is more similar to a continental crust than to an oceanic crust. The large lateral thickness variation in the upper crust and the uniform thickness of the lower crust suggest that the crust in the study area was formed by rifting/extension of continental crust during the opening of the Japan Sea. The margins of the continent or of island arcs can be divided into two types: volcanic rifted margins and non-volcanic rifted margins. Volcanic rifted margins are normally classified by the presence of a high-velocity body in the lower crust. At the volcanic rifted margin, the high

  20. Extended x-ray absorption fine structure measurements on radio frequency magnetron sputtered HfO2 thin films deposited with different oxygen partial pressures.

    PubMed

    Maidul Haque, S; Nayak, C; Bhattacharyya, Dibyendu; Jha, S N; Sahoo, N K

    2016-03-20

    Two sets of HfO2 thin film have been deposited by the radio frequency magnetron sputtering technique at various oxygen partial pressures, one set without any substrate bias and another set with a 50 W pulsed dc substrate bias. The films have been characterized by extended x-ray absorption fine structure (EXAFS) measurements at the Hf L3 edge, and the structural information obtained from analysis of the EXAFS data has been used to explain the macroscopic behavior of the refractive index obtained from spectroscopic ellipsometry measurements. It has been observed that the variation of refractive index with oxygen partial pressure depends on the Hf-Hf bond length for the set of films deposited without substrate bias, while for the other set of films deposited with pulsed dc substrate bias, it depends on the oxygen coordination of the nearest neighbor shell surrounding Hf sites. PMID:27140550

  1. Combined small-angle x-ray scattering/extended x-ray absorption fine structure study of coated Co nanoclusters in bis(2-ethylhexyl)sulfosuccinate

    NASA Astrophysics Data System (ADS)

    Longo, A.; Giordano, F.; Giannici, F.; Martorana, A.; Portale, G.; Ruggirello, A.; Turco Liveri, V.

    2009-06-01

    Chemically stable cobalt nanostructures have been prepared with Co(II) reduction in the confined space of cobalt bis(2-ethylhexyl)sulfosuccinate, Co(AOT)2, reverse micelles dispersed in n-heptane. The reaction was carried out by adding a solution of sodium borohydride in ethanol (1% weight) to a 0.2M micellar solution of Co(AOT)2 in n-heptane at a reductant to Co(II) molar ratio of 4. This procedure involves the rapid formation of surfactant-coated Co nanoparticles followed by their slow separation as nanostructures embedded in a sodium bis(2-ethylhexyl)sulfosuccinate matrix. The resulting composites, characterized by extended x-ray absorption fine structure and small-angle x-ray scattering, showed the presence of subnanometer sized cobalt nanoparticles aggregated together to form elongated structures coated by the surfactant molecules.

  2. In-situ extended X-ray absorption fine structure study of electrostriction in Gd doped ceria

    SciTech Connect

    Korobko, Roman; Wachtel, Ellen; Lubomirsky, Igor; Lerner, Alyssa; Li, Yuanyuan; Frenkel, Anatoly I.

    2015-01-26

    Studying electric field-induced structural changes in ceramics is challenging due to the very small magnitude of the atomic displacements. We used differential X-ray absorption spectroscopy, an elementally specific and spatially sensitive method, to detect such changes in Gd-doped ceria, recently shown to exhibit giant electrostriction. We found that the large electrostrictive stress generation can be associated with a few percent of unusually short Ce-O chemical bonds that change their length and degree of order under an external electric field. The remainder of the lattice is reduced to the role of passive spectator. This mechanism is fundamentally different from that in electromechanically active materials currently in use.

  3. Deep seismic structure and tectonics of northern Alaska: Crustal-scale duplexing with deformation extending into the upper mantle

    USGS Publications Warehouse

    Fuis, G.S.; Murphy, J.M.; Lutter, W.J.; Moore, T.E.; Bird, K.J.; Christensen, N.I.

    1997-01-01

    Seismic reflection and refraction and laboratory velocity data collected along a transect of northern Alaska (including the east edge of the Koyukuk basin, the Brooks Range, and the North Slope) yield a composite picture of the crustal and upper mantle structure of this Mesozoic and Cenozoic compressional orogen. The following observations are made: (1) Northern Alaska is underlain by nested tectonic wedges, most with northward vergence (i.e., with their tips pointed north). (2) High reflectivity throughout the crust above a basal decollement, which deepens southward from about 10 km depth beneath the northern front of the Brooks Range to about 30 km depth beneath the southern Brooks Range, is interpreted as structural complexity due to the presence of these tectonic wedges, or duplexes. (3) Low reflectivity throughout the crust below the decollement is interpreted as minimal deformation, which appears to involve chiefly bending of a relatively rigid plate consisting of the parautochthonous North Slope crust and a 10- to 15-km-thick section of mantle material. (4) This plate is interpreted as a southward verging tectonic wedge, with its tip in the lower crust or at the Moho beneath the southern Brooks Range. In this interpretation the middle and upper crust, or all of the crust, is detached in the southern Brooks Range by the tectonic wedge, or indentor: as a result, crust is uplifted and deformed above the wedge, and mantle is depressed and underthrust beneath this wedge. (5) Underthrusting has juxtaposed mantle of two different origins (and seismic velocities), giving rise to a prominent sub-Moho reflector. Copyright 1997 by the American Geophysical Union.

  4. Significant progress in solution of nonlinear equations at displacement of structure and heat transfer extended surface by new AGM approach

    NASA Astrophysics Data System (ADS)

    Akbari, M. R.; Ganji, D. D.; Nimafar, M.; Ahmadi, A. R.

    2014-12-01

    In this paper, we aim to promote the capability of solving two complicated nonlinear differential equations: 1) Static analysis of the structure with variable cross section areas and materials with slope-deflection method; 2) the problem of one dimensional heat transfer with a logarithmic various surface A( x) and a logarithmic various heat generation G( x) with a simple and innovative approach entitled "Akbari-Ganji's method" (AGM). Comparisons are made between AGM and numerical method, the results of which reveal that this method is very effective and simple and can be applied for other nonlinear problems. It is significant that there are some valuable advantages in this method and also most of the differential equations sets can be answered in this manner while in other methods there is no guarantee to obtain the good results up to now. Brief excellences of this method compared to other approaches are as follows: 1) Differential equations can be solved directly by this method; 2) without any dimensionless procedure, equation(s) can be solved; 3) it is not necessary to convert variables into new ones. According to the aforementioned assertions which are proved in this case study, the process of solving nonlinear equation(s) is very easy and convenient in comparison to other methods.

  5. Cocrystal Structures of Primed Side-Extending α-Ketoamide Inhibitors Reveal Novel Calpain-Inhibitor Aromatic Interactions

    SciTech Connect

    Qian,J.; Cuerrier, D.; Davies, P.; Li, Z.; Powers, J.; Campbell, R.

    2008-01-01

    Calpains are intracellular cysteine proteases that catalyze the cleavage of target proteins in response to Ca2+ signaling. When Ca2+ homeostasis is disrupted, calpain overactivation causes unregulated proteolysis, which can contribute to diseases such as postischemic injury and cataract formation. Potent calpain inhibitors exist, but of these many cross-react with other cysteine proteases and will need modification to specifically target calpain. Here, we present crystal structures of rat calpain 1 protease core ({mu}I-II) bound to two a-ketoamide-based calpain inhibitors containing adenyl and piperazyl primed-side extensions. An unexpected aromatic-stacking interaction is observed between the primed-side adenine moiety and the Trp298 side chain. This interaction increased the potency of the inhibitor toward {mu}I-II and heterodimeric m-calpain. Moreover, stacking orients the adenine such that it can be used as a scaffold for designing novel primed-side address regions, which could be incorporated into future inhibitors to enhance their calpain specificity.

  6. Extended lifetime railgap switch

    SciTech Connect

    Cohn, D.B.; Mendoza, P.J.

    1988-02-02

    In a railgap switch of the type having an elongate blade electrode made of conductive material, an elongate housing made of insulating material for supporting the blade electrode and plate electrode in opposed relation extending in the same direction with the blade centered over the plate and separated therefrom by a gap, and a gas filling the housing and the gap, the gas being selected to breakdown and switch from a highly insulative state to a highly conductive state upon application of a high voltage across the blade and plate electrodes, the improvement is described comprising: forming the blade with laterally extending transverse wing portions at the edge of the blade and adjacent the gap so as to extend in spaced parallel relation to the surface of the plate, the blade generally following the contour thereof to form an inverted T-shape structure with the wing portions extending transversely of the elongate dimension of the blade. The wing portions terminating in a pair of spaced parallel edges extending along the elongate direction of the blade to thereby create two spaced elongate edges along which arcs form serving to divide the erosion effects of discharge between them, the current through each edge being one-half of that in single-edge devices with ablation wear reduced accordingly to give significantly larger switch lifetime. The blade and wing portions limiting ablation erosion of the edges in a direction generally align with the plate contour so that the edge-to-plate separation remains substantially constant.

  7. Naturally Extended CT · AG Repeats Increase H-DNA Structures and Promoter Activity in the Smooth Muscle Myosin Light Chain Kinase Gene▿

    PubMed Central

    Han, Yoo-Jeong; de Lanerolle, Primal

    2008-01-01

    Naturally occurring repeat sequences capable of adopting H-DNA structures are abundant in promoters of disease-related genes. In support of this, we found (CT)22 · (AG)22 repeats in the promoter of smooth muscle myosin light chain kinase (smMLCK), a key regulator of vascular smooth muscle function. We also found an insertion mutation that adds another six pairs of CT · AG repeats and increases smMLCK promoter activity in spontaneously hypertensive rats (SHR). Therefore, we used the smMLCK promoters from normotensive and hypertensive rats as a model system to determine how CT · AG repeats form H-DNA, an intramolecular triplex, and regulate promoter activity. High-resolution mapping with a chemical probe selective for H-DNA showed that the CT · AG repeats adopt H-DNA structures at a neutral pH. Importantly, the SHR promoter forms longer H-DNA structures than the promoter from normotensive rats. Reconstituting nucleosomes on the promoters, in vitro, showed no difference in nucleosome positioning between the two promoters. However, chromatin immunoprecipitation analyses revealed that histone acetylations are greater in the hypertensive promoter. Thus, our findings suggest that the extended CT · AG repeats in the SHR promoter increase H-DNA structures, histone modifications, and promoter activity of the smMLCK, perhaps contributing to vascular disorders in hypertension. PMID:17991897

  8. Extending Structural Analyses of the Rosenberg Self-Esteem Scale to Consider Criterion-Related Validity: Can Composite Self-Esteem Scores Be Good Enough?

    PubMed

    Donnellan, M Brent; Ackerman, Robert A; Brecheen, Courtney

    2016-01-01

    Although the Rosenberg Self-Esteem Scale (RSES) is the most widely used measure of global self-esteem in the literature, there are ongoing disagreements about its factor structure. This methodological debate informs how the measure should be used in substantive research. Using a sample of 1,127 college students, we test the overall fit of previously specified models for the RSES, including a newly proposed bifactor solution (McKay, Boduszek, & Harvey, 2014 ). We extend previous work by evaluating how various latent factors from these structural models are related to a set of criterion variables frequently studied in the self-esteem literature. A strict unidimensional model poorly fit the data, whereas models that accounted for correlations between negatively and positively keyed items tended to fit better. However, global factors from viable structural models had similar levels of association with criterion variables and with the pattern of results obtained with a composite global self-esteem variable calculated from observed scores. Thus, we did not find compelling evidence that different structural models had substantive implications, thereby reducing (but not eliminating) concerns about the integrity of the self-esteem literature based on overall composite scores for the RSES. PMID:26192536

  9. 1-3-A Resolution Structure of Human Glutathione S-Transferase With S-Hexyl Glutathione Bound Reveals Possible Extended Ligandin Binding Site

    SciTech Connect

    Trong, I.Le; Stenkamp, R.E.; Ibarra, C.; Atkins, W.M.; Adman, E.T.

    2005-08-22

    Cytosolic glutathione S-transferases (GSTs) play a critical role in xenobiotic binding and metabolism, as well as in modulation of oxidative stress. Here, the high-resolution X-ray crystal structures of homodimeric human GSTA1-1 in the apo form and in complex with S-hexyl glutathione (two data sets) are reported at 1.8, 1.5, and 1.3A respectively. At this level of resolution, distinct conformations of the alkyl chain of S-hexyl glutathione are observed, reflecting the nonspecific nature of the hydrophobic substrate binding site (H-site). Also, an extensive network of ordered water, including 75 discrete solvent molecules, traverses the open subunit-subunit interface and connects the glutathione binding sites in each subunit. In the highest-resolution structure, three glycerol moieties lie within this network and directly connect the amino termini of the glutathione molecules. A search for ligand binding sites with the docking program Molecular Operating Environment identified the ordered water network binding site, lined mainly with hydrophobic residues, suggesting an extended ligand binding surface for nonsubstrate ligands, the so-called ligandin site. Finally, detailed comparison of the structures reported here with previously published X-ray structures reveal a possible reaction coordinate for ligand-dependent conformational changes in the active site and the C-terminus.

  10. Imputing Phenotypes for Genome-wide Association Studies.

    PubMed

    Hormozdiari, Farhad; Kang, Eun Yong; Bilow, Michael; Ben-David, Eyal; Vulpe, Chris; McLachlan, Stela; Lusis, Aldons J; Han, Buhm; Eskin, Eleazar

    2016-07-01

    Genome-wide association studies (GWASs) have been successful in detecting variants correlated with phenotypes of clinical interest. However, the power to detect these variants depends on the number of individuals whose phenotypes are collected, and for phenotypes that are difficult to collect, the sample size might be insufficient to achieve the desired statistical power. The phenotype of interest is often difficult to collect, whereas surrogate phenotypes or related phenotypes are easier to collect and have already been collected in very large samples. This paper demonstrates how we take advantage of these additional related phenotypes to impute the phenotype of interest or target phenotype and then perform association analysis. Our approach leverages the correlation structure between phenotypes to perform the imputation. The correlation structure can be estimated from a smaller complete dataset for which both the target and related phenotypes have been collected. Under some assumptions, the statistical power can be computed analytically given the correlation structure of the phenotypes used in imputation. In addition, our method can impute the summary statistic of the target phenotype as a weighted linear combination of the summary statistics of related phenotypes. Thus, our method is applicable to datasets for which we have access only to summary statistics and not to the raw genotypes. We illustrate our approach by analyzing associated loci to triglycerides (TGs), body mass index (BMI), and systolic blood pressure (SBP) in the Northern Finland Birth Cohort dataset. PMID:27292110

  11. Downregulation of Cinnamoyl-Coenzyme A Reductase in Poplar: Multiple-Level Phenotyping Reveals Effects on Cell Wall Polymer Metabolism and Structure[W

    PubMed Central

    Leplé, Jean-Charles; Dauwe, Rebecca; Morreel, Kris; Storme, Véronique; Lapierre, Catherine; Pollet, Brigitte; Naumann, Annette; Kang, Kyu-Young; Kim, Hoon; Ruel, Katia; Lefèbvre, Andrée; Joseleau, Jean-Paul; Grima-Pettenati, Jacqueline; De Rycke, Riet; Andersson-Gunnerås, Sara; Erban, Alexander; Fehrle, Ines; Petit-Conil, Michel; Kopka, Joachim; Polle, Andrea; Messens, Eric; Sundberg, Björn; Mansfield, Shawn D.; Ralph, John; Pilate, Gilles; Boerjan, Wout

    2007-01-01

    Cinnamoyl-CoA reductase (CCR) catalyzes the penultimate step in monolignol biosynthesis. We show that downregulation of CCR in transgenic poplar (Populus tremula × Populus alba) was associated with up to 50% reduced lignin content and an orange-brown, often patchy, coloration of the outer xylem. Thioacidolysis, nuclear magnetic resonance (NMR), immunocytochemistry of lignin epitopes, and oligolignol profiling indicated that lignin was relatively more reduced in syringyl than in guaiacyl units. The cohesion of the walls was affected, particularly at sites that are generally richer in syringyl units in wild-type poplar. Ferulic acid was incorporated into the lignin via ether bonds, as evidenced independently by thioacidolysis and by NMR. A synthetic lignin incorporating ferulic acid had a red-brown coloration, suggesting that the xylem coloration was due to the presence of ferulic acid during lignification. Elevated ferulic acid levels were also observed in the form of esters. Transcript and metabolite profiling were used as comprehensive phenotyping tools to investigate how CCR downregulation impacted metabolism and the biosynthesis of other cell wall polymers. Both methods suggested reduced biosynthesis and increased breakdown or remodeling of noncellulosic cell wall polymers, which was further supported by Fourier transform infrared spectroscopy and wet chemistry analysis. The reduced levels of lignin and hemicellulose were associated with an increased proportion of cellulose. Furthermore, the transcript and metabolite profiling data pointed toward a stress response induced by the altered cell wall structure. Finally, chemical pulping of wood derived from 5-year-old, field-grown transgenic lines revealed improved pulping characteristics, but growth was affected in all transgenic lines tested. PMID:18024569

  12. Loss of β1-integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype

    PubMed Central

    Kanasaki, Keizo; Yu, Weiqun; von Bodungen, Maximilian; Larigakis, John D.; Kanasaki, Megumi; Ayala de la Pena, Francisco; Kalluri, Raghu; Hill, Warren G.

    2013-01-01

    Bladder urothelium senses and communicates information about bladder fullness. However, the mechanoreceptors that respond to tissue stretch are poorly defined. Integrins are mechanotransducers in other tissues. Therefore, we eliminated β1-integrin selectively in urothelium of mice using Cre-LoxP targeted gene deletion. β1-Integrin localized to basal/intermediate urothelial cells by confocal microscopy. β1-Integrin conditional-knockout (β1-cKO) mice lacking urothelial β1-integrin exhibited down-regulation and mislocalization of α3- and α5-integrins by immunohistochemistry but, surprisingly, had normal morphology, permeability, and transepithelial resistance when compared with Cre-negative littermate controls. β1-cKO mice were incontinent, as judged by random urine leakage on filter paper (4-fold higher spotting, P<0.01; 2.5-fold higher urine area percentage, P<0.05). Urodynamic function assessed by cystometry revealed bladder overfilling with 80% longer intercontractile intervals (P<0.05) and detrusor hyperactivity (3-fold more prevoid contractions, P<0.05), but smooth muscle contractility remained intact. ATP secretion into the lumen was elevated (49 vs. 22 nM, P<0.05), indicating abnormal filling-induced purinergic signaling, and short-circuit currents (measured in Ussing chambers) revealed 2-fold higher stretch-activated ion channel conductances in response to hydrostatic pressure of 1 cmH2O (P<0.05). We conclude that loss of integrin signaling from urothelium results in incontinence and overactive bladder due to abnormal mechanotransduction; more broadly, our findings indicate that urothelium itself directly modulates voiding.—Kanasaki, K., Yu, W., von Bodungen, M., Larigakis, J. D., Kanasaki, M., Ayala de la Pena, F., Kalluri, R., Hill, W.G. Loss of β1-integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype. PMID:23395910

  13. Analysis of photosynthetic picoeukaryote community structure along an extended Ellett Line transect in the northern North Atlantic reveals a dominance of novel prymnesiophyte and prasinophyte phylotypes

    NASA Astrophysics Data System (ADS)

    Kirkham, Amy R.; Jardillier, Ludwig E.; Holland, Ross; Zubkov, Mikhail V.; Scanlan, Dave J.

    2011-07-01

    Photosynthetic picoeukaryotes (PPEs) of a size <3 μm can contribute significantly to primary production. Here, PPE community structure was analysed along an extended Ellett Line transect, an area in the North Atlantic well studied by physical oceanographers but largely neglected in the field of microalgal ecology. Distribution patterns of specific PPE classes were determined using dot-blot hybridization analysis, while the taxonomic composition of specific PPE classes was revealed by phylogenetic analysis of plastid 16S rRNA gene sequences. In addition, we performed fluorescent in situ hybridization (FISH) analysis of seawater samples collected along the transect to provide a PCR-independent survey of class level PPE distribution patterns. We found the PPE community was dominated by members of the Prymnesiophyceae, Prasinophyceae and Mamiellophyceae. Interestingly, phylogenetic analysis revealed several novel Prymnesiophyceae and Prasinophyceae phylotypes (with only 85-96% identity to neighbouring sequences) within lineages for which cultured counterparts are unknown.

  14. The fate of silver ions in the photochemical synthesis of gold nanorods: an extended X-ray absorption fine structure analysis.

    PubMed

    Giannici, Francesco; Placido, Tiziana; Curri, Maria Lucia; Striccoli, Marinella; Agostiano, Angela; Comparelli, Roberto

    2009-12-14

    Water-soluble gold nanorods (Au NRs) were synthesized using a silver-ion mediated photochemical route under UV irradiation. Extended X-ray Absorption Fine Structure (EXAFS) measurements on the Ag K-edge were performed on samples obtained at different Ag/Au ratios and at increasing irradiation times in order to investigate the fate of silver ions during the growth of Au NRs. EXAFS measurements allowed to probe the chemical state and the local environment of silver in the final product. Experimental data suggest that Ag atoms are placed on top of the Au particles as metallic Ag(0), while no significant contribution to the EXAFS spectra comes from AgBr or other Ag(+) based species. The reported results strongly support the deposition of Ag(0) islands on the (110) surfaces of the Au particles, thus driving the anisotropic growth via the (111) surfaces. PMID:19921074

  15. Phenotypes and Genotypes of Old and Contemporary Porcine Strains Indicate a Temporal Change in the S. aureus Population Structure in Pigs

    PubMed Central

    Espinosa-Gongora, Carmen; Moodley, Arshnee; Lipinska, Urszula; Broens, Els M.; Hermans, Katleen; Butaye, Patrick; Devriese, Luc A.; Haesebrouck, Freddy; Guardabassi, Luca

    2014-01-01

    Introduction Staphylococcus aureus sequence type ST398 has recently gained attention due to the spread of methicillin-resistant strains among people exposed to livestock. The aim of this study was to explore temporal changes in the population structure of S. aureus in pigs over the last 40 years with particular reference to the occurrence of ST398. Methods We analysed a unique collection of 91 porcine strains isolated in six countries between 1973 and 2009 using a biotyping scheme described in the 1970's in combination with spa typing and multi-locus sequence typing (MLST). The collection comprised 32 historical isolates from 1973–1974 (n = 19) and from 1991–2003 (n = 13), and 59 contemporary isolates from 2004–2009. The latter isolates represented the most common MLST types (ST1, ST9, ST97 and ST433) and spa types isolated from pigs in Europe. Results and Discussion S. aureus sequence type ST398 was not found among old isolates from the 1970's or from 1991–2003, suggesting that this lineage was absent or present at low frequencies in pigs in the past. This hypothesis is supported by the observed association of ST398 with the ovine ecovar, which was not described in pigs by studies carried out in the 1970's. In addition, various phenotypic and genotypic differences were observed between old and contemporary isolates. Some biotypes commonly reported in pigs in the 1970's were either absent (human ecovar) or rare (biotype A) among contemporary isolates. Nine clonal lineages found among old porcine isolates are occasionally reported in pigs today (ST8, ST30, ST97, ST387, ST1092, ST2468) or have never been described in this animal host (ST12, ST133, ST1343). These results indicate that the population structure of porcine S. aureus has changed over the last 40 years and confirm the current theory that S. aureus ST398 does not originate from pigs. PMID:25000530

  16. The Bactofilin Cytoskeleton Protein BacM of Myxococcus xanthus Forms an Extended β-Sheet Structure Likely Mediated by Hydrophobic Interactions

    PubMed Central

    Xie, Kefang; Engelhardt, Harald; Bosch, Jürgen; Hoiczyk, Egbert

    2015-01-01

    Bactofilins are novel cytoskeleton proteins that are widespread in Gram-negative bacteria. Myxococcus xanthus, an important predatory soil bacterium, possesses four bactofilins of which one, BacM (Mxan_7475) plays an important role in cell shape maintenance. Electron and fluorescence light microscopy, as well as studies using over-expressed, purified BacM, indicate that this protein polymerizes in vivo and in vitro into ~3 nm wide filaments that further associate into higher ordered fibers of about 10 nm. Here we use a multipronged approach combining secondary structure determination, molecular modeling, biochemistry, and genetics to identify and characterize critical molecular elements that enable BacM to polymerize. Our results indicate that the bactofilin-determining domain DUF583 folds into an extended β-sheet structure, and we hypothesize a left-handed β-helix with polymerization into 3 nm filaments primarily via patches of hydrophobic amino acid residues. These patches form the interface allowing head-to-tail polymerization during filament formation. Biochemical analyses of these processes show that folding and polymerization occur across a wide variety of conditions and even in the presence of chaotropic agents such as one molar urea. Together, these data suggest that bactofilins are comprised of a structure unique to cytoskeleton proteins, which enables robust polymerization. PMID:25803609

  17. An extended-X-ray-absorption-fine-structure study of freeze-dried and solution ovotransferrin. Evidence for water co-ordination at the metal-binding sites.

    PubMed Central

    Hasnain, S S; Evans, R W; Garratt, R C; Lindley, P F

    1987-01-01

    Our previous extended-X-ray-absorption-fine-structure (e.x.a.f.s.) study has shown that the probable iron environment in chicken ovotransferrin involves two low-Z ligands (consistent with phenolate linkages) at 0.185(1) nm and four low-Z ligands at 0.204(1) nm [Garratt, Evans, Hasnain & Lindley (1986) Biochem. J. 233, 479-484]. Herein we provide additional information from the e.x.a.f.s. and near-edge structure suggestive of a decrease in the co-ordination number of ovotransferrin-bound iron upon freeze-drying. These effects are reversible, and exposure of the freeze-dried material to a humid atmosphere results in reversion to the solution spectra. Progressive rehydration was monitored by using e.p.r. spectroscopy and was confirmed by recording the high-resolution X-ray-absorption near-edge structure (x.a.n.e.s.). The results suggest the presence of a labile water molecule at the iron-binding sites of ovotransferrin in solution. PMID:2827627

  18. Polyradical Character of Triangular Non-Kekulé Structures, Zethrenes, p-Quinodimethane-Linked Bisphenalenyl, and the Clar Goblet in Comparison: An Extended Multireference Study.

    PubMed

    Das, Anita; Müller, Thomas; Plasser, Felix; Lischka, Hans

    2016-03-10

    In this work, two different classes of polyaromatic hydrocarbon (PAH) systems have been investigated in order to characterize the amount of polyradical character and to localize the specific regions of chemical reactivity: (a) the non-Kekulé triangular structures phenalenyl, triangulene and a π-extended triangulene system with high-spin ground state and (b) PAHs based on zethrenes, p-quinodimethane-linked bisphenalenyl, and the Clar goblet containing varying polyradical character in their singlet ground state. The first class of structures already have open-shell character because of their high-spin ground state, which follows from the bonding pattern, whereas for the second class the open-shell character is generated either because of the competition between the closed-shell quinoid Kekulé and the open-shell singlet biradical resonance structures or the topology of the π-electron arrangement of the non-Kekulé form. High-level ab initio calculations based on multireference theory have been carried out to compute singlet-triplet splitting for the above-listed compounds and to provide insight into their chemical reactivity based on the polyradical character by means of unpaired densities. Unrestricted density functional theory and Hartree-Fock calculations have been performed for comparison also in order to obtain better insight into their applicability to these types of complicated radical systems. PMID:26859789

  19. Polyradical Character of Triangular Non-Kekulé Structures, Zethrenes, p-Quinodimethane-Linked Bisphenalenyl, and the Clar Goblet in Comparison: An Extended Multireference Study

    PubMed Central

    2016-01-01

    In this work, two different classes of polyaromatic hydrocarbon (PAH) systems have been investigated in order to characterize the amount of polyradical character and to localize the specific regions of chemical reactivity: (a) the non-Kekulé triangular structures phenalenyl, triangulene and a π-extended triangulene system with high-spin ground state and (b) PAHs based on zethrenes, p-quinodimethane-linked bisphenalenyl, and the Clar goblet containing varying polyradical character in their singlet ground state. The first class of structures already have open-shell character because of their high-spin ground state, which follows from the bonding pattern, whereas for the second class the open-shell character is generated either because of the competition between the closed-shell quinoid Kekulé and the open-shell singlet biradical resonance structures or the topology of the π-electron arrangement of the non-Kekulé form. High-level ab initio calculations based on multireference theory have been carried out to compute singlet–triplet splitting for the above-listed compounds and to provide insight into their chemical reactivity based on the polyradical character by means of unpaired densities. Unrestricted density functional theory and Hartree–Fock calculations have been performed for comparison also in order to obtain better insight into their applicability to these types of complicated radical systems. PMID:26859789

  20. Temporal abstraction-based clinical phenotyping with Eureka!

    PubMed

    Post, Andrew R; Kurc, Tahsin; Willard, Richie; Rathod, Himanshu; Mansour, Michel; Pai, Akshatha Kalsanka; Torian, William M; Agravat, Sanjay; Sturm, Suzanne; Saltz, Joel H

    2013-01-01

    Temporal abstraction, a method for specifying and detecting temporal patterns in clinical databases, is very expressive and performs well, but it is difficult for clinical investigators and data analysts to understand. Such patterns are critical in phenotyping patients using their medical records in research and quality improvement. We have previously developed the Analytic Information Warehouse (AIW), which computes such phenotypes using temporal abstraction but requires software engineers to use. We have extended the AIW's web user interface, Eureka! Clinical Analytics, to support specifying phenotypes using an alternative model that we developed with clinical stakeholders. The software converts phenotypes from this model to that of temporal abstraction prior to data processing. The model can represent all phenotypes in a quality improvement project and a growing set of phenotypes in a multi-site research study. Phenotyping that is accessible to investigators and IT personnel may enable its broader adoption. PMID:24551400

  1. Temporal Abstraction-based Clinical Phenotyping with Eureka!

    PubMed Central

    Post, Andrew R.; Kurc, Tahsin; Willard, Richie; Rathod, Himanshu; Mansour, Michel; Pai, Akshatha Kalsanka; Torian, William M.; Agravat, Sanjay; Sturm, Suzanne; Saltz, Joel H.

    2013-01-01

    Temporal abstraction, a method for specifying and detecting temporal patterns in clinical databases, is very expressive and performs well, but it is difficult for clinical investigators and data analysts to understand. Such patterns are critical in phenotyping patients using their medical records in research and quality improvement. We have previously developed the Analytic Information Warehouse (AIW), which computes such phenotypes using temporal abstraction but requires software engineers to use. We have extended the AIW’s web user interface, Eureka! Clinical Analytics, to support specifying phenotypes using an alternative model that we developed with clinical stakeholders. The software converts phenotypes from this model to that of temporal abstraction prior to data processing. The model can represent all phenotypes in a quality improvement project and a growing set of phenotypes in a multi-site research study. Phenotyping that is accessible to investigators and IT personnel may enable its broader adoption. PMID:24551400

  2. Low-temperature adsorption of H2S on Ni(001) studied by near-edge- and surface-extended-x-ray-absorption fine structure

    NASA Astrophysics Data System (ADS)

    McGrath, R.; MacDowell, A. A.; Hashizume, T.; Sette, F.; Citrin, P. H.

    1989-11-01

    The adsorption of H2S on Ni(001) has been studied with surface-extended x-ray-absorption fine structure and near-edge x-ray-absorption fine structure (NEXAFS) using the AT&T Bell Laboratories X15B beamline at the National Synchrotron Light Source. At 95 K and full saturation coverage, ~0.45 monolayer (ML) of S atoms in fourfold-hollow sites are produced, characteristic of room-temperature adsorption, accompanied by ~0.05 ML of oriented molecular H2S. Both these atomic and molecular chemisorbed species are buried under ~0.9 ML of disordered physisorbed H2S. No evidence for HS is found. Above 190 K the two molecular H2S phases desorb, leaving only dissociated S. These findings differ from previously reported interpretations of data obtained with high-resolution electron-energy-loss spectroscopy. They also exemplify the utility of NEXAFS for identifying and quantifying atomic and molecular surface species even when their difference involves only H and the two species coexist.

  3. Mosaic structure of p1658/97, a 125-kilobase plasmid harboring an active amplicon with the extended-spectrum beta-lactamase gene blaSHV-5.

    PubMed

    Zienkiewicz, M; Kern-Zdanowicz, I; Gołebiewski, M; Zyliñska, J; Mieczkowski, P; Gniadkowski, M; Bardowski, J; Cegłowski, P

    2007-04-01

    Escherichia coli isolates recovered from patients during a clonal outbreak in a Warsaw, Poland, hospital in 1997 produced different levels of an extended-spectrum beta-lactamase (ESBL) of the SHV type. The beta-lactamase hyperproduction correlated with the multiplication of ESBL gene copies within a plasmid. Here, we present the complete nucleotide sequence of plasmid p1658/97 carried by the isolates recovered during the outbreak. The plasmid is 125,491 bp and shows a mosaic structure in which all modules constituting the plasmid core are homologous to those found in plasmids F and R100 and are separated by segments of homology to other known regions (plasmid R64, Providencia rettgeri genomic island R391, Vibrio cholerae STX transposon, Klebsiella pneumoniae or E. coli chromosomes). Plasmid p1658/97 bears two replication systems, IncFII and IncFIB; we demonstrated that both are active in E. coli. The presence of an active partition system (sopABC locus) and two postsegregational killing systems (pemIK and hok/sok) indicates that the plasmid should be stably maintained in E. coli populations. The conjugative transfer is ensured by the operons of the tra and trb genes. We also demonstrate that the plasmidic segment undergoing amplification contains the blaSHV-5 gene and is homologous to a 7.9-kb fragment of the K. pneumoniae chromosome. The amplicon displays the structure of a composite transposon of type I. PMID:17220406

  4. Extended x-ray absorption fine structure and micro-Raman spectra of Bridgman grown Cd1-xZnxTe ternary alloys

    NASA Astrophysics Data System (ADS)

    Talwar, Devki N.; Feng, Zhe Chuan; Lee, Jyh-Fu; Becla, P.

    2014-03-01

    We have performed low-temperature micro-Raman scattering and extended x-ray absorption fine-structure (EXAFS) measurements on the Bridgman-grown bulk zinc-blende Cd1-x Zn x Te (1.0 ≧̸ x ≧̸ 0.03) ternary alloys to comprehend their structural and lattice dynamical properties. The micro-Raman results are carefully appraised to authenticate the classical two-phonon mode behavior insinuated by far-infrared (FIR) reflectivity study. The composition-dependent EXAFS experiments have revealed a bimodal distribution of the nearest-neighbor bond lengths—its analysis by first-principles bond-orbital model enabled us to estimate the lattice relaxations around Zn/Cd atoms in CdTe/ZnTe to help evaluate the necessary force constant variations for constructing the impurity-perturbation matrices. The simulated results of impurity vibrational modes by average-t-matrix Green’s function (ATM-GF) theory has put our experimental findings of the gap mode ˜153 cm-1 near x ≈ 1 on a much firmer ground.

  5. Extended x-ray absorption fine structure measurements on asymmetric bipolar pulse direct current magnetron sputtered Ta(2)O(5) thin films.

    PubMed

    Maidul Haque, S; Sagdeo, Pankaj R; Shinde, D D; Misal, J S; Jha, S N; Bhattacharyya, D; Sahoo, N K

    2015-08-01

    Tantalum pentoxide (Ta2O5) thin films have been deposited on fused silica substrates using a novel asymmetric bipolar DC magnetron sputtering technique under a mixed ambient of oxygen and argon. Films have been prepared at different oxygen-to-argon ratios, and the sputtering ambient and optical properties of the films have been investigated by spectroscopic ellipsometry, while the structural analysis of the films has been carried out by grazing incidence x-ray diffraction and extended x-ray absorption fine structure (EXAFS) measurements. The concentration of oxygen and tantalum in the Ta2O5 films has been estimated by Rutherford backscattering spectrometry (RBS). The variation of the optical constants of the films with changes in deposition parameters has been explained in the light of the change in average Ta-O bond lengths and oxygen coordination around Ta sites as obtained from EXAFS measurements. The trend in variation of the oxygen-to-tantalum ratio in the films obtained from RBS measurement, as a function of oxygen partial pressure used during sputtering, is found to follow the trend in variation of the oxygen coordination number around Ta sites obtained from EXAFS measurement. PMID:26368089

  6. Angle-resolved photoemission extended fine structure of the Ni 3p, Cu 3s, and Cu 3p core levels of the respective clean (111) surfaces

    SciTech Connect

    Huff, W.R. |; Chen, Y.; Kellar, S.A.; Moler, E.J. |; Hussain, Z.; Huang, Z.Q.; Zheng, Y.; Shirley, D.A.

    1997-07-01

    We report a non-s initial-state angle-resolved photoemission extended fine-structure (ARPEFS) study of clean surfaces for the purpose of further understanding the technique. The surface structure sensitivity of ARPEFS applied to clean surfaces and to arbitrary initial states is studied using normal photoemission data taken from the Ni 3p core levels of a Ni(111) single crystal and the Cu 3s and the Cu 3p core levels of a Cu(111) single crystal. The Fourier transforms of these clean surface data are dominated by backscattering. Unlike the s initial-state data, the p initial-state data show a peak in the Fourier transform corresponding to in-plane scattering from the six nearest neighbors to the emitter. Evidence was seen for single-scattering events from the same plane as the emitters and double-scattering events. Using a recently developed, multiple-scattering calculation program, ARPEFS data from clean surfaces and from p initial states can be modeled to high precision. Although there are many layers of emitters when measuring photoemission from a clean surface, test calculations show that the ARPEFS signal is dominated by photoemission from atoms in the first two crystal layers. Thus ARPEFS applied to clean surfaces is sensitive to surface reconstruction. The best-fit calculation for clean Ni(111) indicates an expansion of the first two layers. {copyright} {ital 1997} {ital The American Physical Society}

  7. Estimation method of state-of-charge for lithium-ion battery used in hybrid electric vehicles based on variable structure extended kalman filter

    NASA Astrophysics Data System (ADS)

    Sun, Yong; Ma, Zilin; Tang, Gongyou; Chen, Zheng; Zhang, Nong

    2016-03-01

    Since the main power source of hybrid electric vehicle(HEV) is supplied by the power battery, the predicted performance of power battery, especially the state-of-charge(SOC) estimation has attracted great attention in the area of HEV. However, the value of SOC estimation could not be greatly precise so that the running performance of HEV is greatly affected. A variable structure extended kalman filter(VSEKF)-based estimation method, which could be used to analyze the SOC of lithium-ion battery in the fixed driving condition, is presented. First, the general lower-order battery equivalent circuit model(GLM), which includes column accumulation model, open circuit voltage model and the SOC output model, is established, and the off-line and online model parameters are calculated with hybrid pulse power characteristics(HPPC) test data. Next, a VSEKF estimation method of SOC, which integrates the ampere-hour(Ah) integration method and the extended Kalman filter(EKF) method, is executed with different adaptive weighting coefficients, which are determined according to the different values of open-circuit voltage obtained in the corresponding charging or discharging processes. According to the experimental analysis, the faster convergence speed and more accurate simulating results could be obtained using the VSEKF method in the running performance of HEV. The error rate of SOC estimation with the VSEKF method is focused in the range of 5% to 10% comparing with the range of 20% to 30% using the EKF method and the Ah integration method. In Summary, the accuracy of the SOC estimation in the lithium-ion battery cell and the pack of lithium-ion battery system, which is obtained utilizing the VSEKF method has been significantly improved comparing with the Ah integration method and the EKF method. The VSEKF method utilizing in the SOC estimation in the lithium-ion pack of HEV can be widely used in practical driving conditions.

  8. Novel phenotypes of prediabetes?

    PubMed

    Häring, Hans-Ulrich

    2016-09-01

    This article describes phenotypes observed in a prediabetic population (i.e. a population with increased risk for type 2 diabetes) from data collected at the University hospital of Tübingen. We discuss the impact of genetic variation on insulin secretion, in particular the effect on compensatory hypersecretion, and the incretin-resistant phenotype of carriers of the gene variant TCF7L2 is described. Imaging studies used to characterise subphenotypes of fat distribution, metabolically healthy obesity and metabolically unhealthy obesity are described. Also discussed are ectopic fat stores in liver and pancreas that determine the phenotype of metabolically healthy and unhealthy fatty liver and the recently recognised phenotype of fatty pancreas. The metabolic impact of perivascular adipose tissue and pancreatic fat is discussed. The role of hepatokines, particularly that of fetuin-A, in the crosstalk between these organs is described. Finally, the role of brain insulin resistance in the development of the different prediabetes phenotypes is discussed. PMID:27344314

  9. Structural basis for the extended substrate spectrum of AmpC BER and structure-guided discovery of the inhibition activity of citrate against the class C β-lactamases AmpC BER and CMY-10.

    PubMed

    Na, Jung Hyun; Cha, Sun Shin

    2016-08-01

    AmpC BER is an extended substrate spectrum class C β-lactamase with a two-amino-acid insertion in the R2 loop compared with AmpC EC2. The crystal structures of AmpC BER (S64A mutant) and AmpC EC2 were determined. Structural comparison of the two proteins revealed that the insertion increases the conformational flexibility of the R2 loop. Two citrate molecules originating from the crystallization solution were observed in the active site of the S64A mutant. One citrate molecule makes extensive interactions with active-site residues that are highly conserved among class C β-lactamases, whereas the other one is weakly bound. Based on this structural observation, it is demonstrated that citrate, a primary metabolite that is widely used as a food additive, is a competitive inhibitor of two class C β-lactamases (AmpC BER and CMY-10). Consequently, the data indicate enhancement of the flexibility of the R2 loop as an operative strategy for molecular evolution of extended-spectrum class C β-lactamases, and also suggest that the citrate scaffold is recognized by the active sites of class C β-lactamases. PMID:27487828

  10. Measurement of the Neutron (3He) Spin Structure at Low Q2 and the Extended Gerasimov-Drell-Hearn Sum Rule

    SciTech Connect

    Kominis, Ioannis

    2001-01-31

    This thesis presents the results of E-94010, an experiment at Thomas Jefferson National Accelerator Facility (TJNAF) designed to study the spin structure of the neutron at low momentum transfer, and to test the “extended” Gerasimov-Drell-Hearn (GDH) sum rule. The first experiment of its kind, it was performed in experimental Hall-A of TJNAF using a new polarized 3He facility. It has recently been shown that the GDH sum rule and the Bjorken sum rule are both special examples of a more general sum rule that applies to polarized electron scattering off nucleons. This generalized sum rule, due to Ji and Osborne, reduces to the GDH sum rule at Q2 = 0 and to the Bjorken sum rule at Q2 >> 1 GeV2. By studying the Q2 evolution of the extended GDH sum, one learns about the transition from quark-like behavior to hadronic-like behavior. We measured inclusive polarized cross sections by scattering high energy polarized electrons off the new TJNAF polarized 3He target with both longitudinal and transverse target orientations. The high density 3He target, based on optical pumping and spin exchange, was used as an effective neutron target. The target maintained a polarization of about 35% at beam currents as high as 151tA. We describe the precision 3He polarimetry leading to a systematic uncertainty of the target polarization of 4% (relative). A strained GaAs photocathode was utilized in the polarized electron gun, which provided an electron beam with a polarization of about 70%, known to 3% (relative). By using six different beam energies (between 0.86 and 5.06 GeV) and a fixed scattering angle of 15.5°, a wide kinematic coverage was achieved, with 0.02 GeV2< Q2 <1 GcV2 and 0.5 GeV< W < 2.5 GeV for the squared momentum transfer and invariant mass, respectively. From the measured cross sections we extract the 3He spin structure functions He and g1e Finally, we determine the extended GDH sum for the range 0.1 GeV2< Q2 <1 GeV2 for 3He and the neutron.

  11. The extended structure of the dwarf irregular galaxies Sextans A and Sextans B. Signatures of tidal distortion in the outskirts of the Local Group

    NASA Astrophysics Data System (ADS)

    Bellazzini, M.; Beccari, G.; Fraternali, F.; Oosterloo, T. A.; Sollima, A.; Testa, V.; Galleti, S.; Perina, S.; Faccini, M.; Cusano, F.

    2014-06-01

    We present a detailed study of the stellar and H i structure of the dwarf irregular galaxies Sextans A and Sextans B, members of the NGC 3109 association. We use newly obtained deep (r ≃ 26.5) and wide-field g and r photometry to extend the surface brightness (SB) profiles of the two galaxies down to μV ≃ 31.0 mag/arcsec2. We find that both galaxies are significantly more extended than previously traced with surface photometry, out to ~4 kpc from their centres along their major axes. Older stars are found to have more extended distribution than younger populations. We obtain the first estimate of the mean metallicity for the old stars in Sex B, from the colour distribution of the red giant branch, ⟨[Fe/H]⟩ = -1.6. The SB profiles show significant changes of slope and cannot be fitted with a single Sérsic model. Both galaxies have HI discs as massive as their respective stellar components. In both cases the H i discs display solid-body rotation with maximum amplitude of ~50 km s-1 (albeit with significant uncertainty due to the poorly constrained inclination), implying a dynamical mass ~109 M⊙, a mass-to-light ratio M / LV ~ 25, and a dark-to-baryonic mass ratio of ~10. The distribution of the stellar components is more extended than the gaseous disc in both galaxies. We find that the main, approximately round, stellar body of Sex A is surrounded by an elongated low-SB stellar halo that can be interpreted as a tidal tail, similar to that found in another member of the same association (Antlia). We discuss these, as well as other evidence of tidal disturbance, in the framework of a past passage of the NGC 3109 association close to the Milky Way, which has been hypothesised by several authors and is also supported by the recently discovered filamentary configuration of the association itself. Appendices are available in electronic form at http://www.aanda.orgTable of stellar photometry is only available at the CDS via anonymous ftp to http

  12. Phenotypic switching in bacteria

    NASA Astrophysics Data System (ADS)

    Merrin, Jack

    Living matter is a non-equilibrium system in which many components work in parallel to perpetuate themselves through a fluctuating environment. Physiological states or functionalities revealed by a particular environment are called phenotypes. Transitions between phenotypes may occur either spontaneously or via interaction with the environment. Even in the same environment, genetically identical bacteria can exhibit different phenotypes of a continuous or discrete nature. In this thesis, we pursued three lines of investigation into discrete phenotypic heterogeneity in bacterial populations: the quantitative characterization of the so-called bacterial persistence, a theoretical model of phenotypic switching based on those measurements, and the design of artificial genetic networks which implement this model. Persistence is the phenotype of a subpopulation of bacteria with a reduced sensitivity to antibiotics. We developed a microfluidic apparatus, which allowed us to monitor the growth rates of individual cells while applying repeated cycles of antibiotic treatments. We were able to identify distinct phenotypes (normal and persistent) and characterize the stochastic transitions between them. We also found that phenotypic heterogeneity was present prior to any environmental cue such as antibiotic exposure. Motivated by the experiments with persisters, we formulated a theoretical model describing the dynamic behavior of several discrete phenotypes in a periodically varying environment. This theoretical framework allowed us to quantitatively predict the fitness of dynamic populations and to compare survival strategies according to environmental time-symmetries. These calculations suggested that persistence is a strategy used by bacterial populations to adapt to fluctuating environments. Knowledge of the phenotypic transition rates for persistence may provide statistical information about the typical environments of bacteria. We also describe a design of artificial

  13. Extended conformal algebras

    NASA Astrophysics Data System (ADS)

    Bouwknegt, Peter

    1988-06-01

    We investigate extensions of the Virasoro algebra by a single primary field of integer or halfinteger conformal dimension Δ. We argue that for vanishing structure constant CΔΔΔ, the extended conformal algebra can only be associative for a generic c-value if Δ=1/2, 1, 3/2, 2 or 3. For the other Δ<=5 we compute the finite set of allowed c-values and identify the rational solutions. The case CΔΔΔ≠0 is also briefly discussed. I would like to thank Kareljan Schoutens for discussions and Sander Bais for a careful reading of the manuscript.

  14. Extended structures and new infinite-dimensional hidden symmetries for the Einstein Maxwell-dilaton-axion theory with multiple vector fields

    NASA Astrophysics Data System (ADS)

    Gao, Ya-Jun

    2005-01-01

    A so-called extended elliptical-complex (EEC) function method is proposed and used to further study the Einstein Maxwell-dilaton-axion theory with p vector fields (EMDA-p theory, for brevity) for p = 1,2,ldots . An Ernst-like 2^{k+1}× 2^{k+1}(k = [(p+1)/2]) matrix EEC potential is introduced and the motion equations of the stationary axisymmetric EMDA-p theory are written as a so-called Hauser Ernst-like self-dual relation for the EEC matrix potential. In particular, for the EMDA-2 theory, two Hauser Ernst-type EEC linear systems are established and based on their solutions some new parametrized symmetry transformations are explicitly constructed. These hidden symmetries are verified to constitute an infinite-dimensional Lie algebra, which is the semidirect product of the Kac Moody algebra su(2,2)⊗ R(t,t^{-1}) and Virasoro algebra (without centre charges). These results show that the studied EMDA-p theories possess very rich symmetry structures and the EEC function method is necessary and effective.

  15. Extended consecutive modal pushover procedure for estimating seismic responses of one-way asymmetric plan tall buildings considering soil-structure interaction

    NASA Astrophysics Data System (ADS)

    Tehrani, Mohammad Hadikhan; Khoshnoudian, Faramarz

    2014-09-01

    Performance based design becomes an effective method for estimating seismic demands of buildings. In asymmetric plan tall building the effects of higher modes and torsion are crucial. The consecutive modal pushover (CMP) procedure is one of the procedures that consider these effects. Also in previous studies the influence of soil-structure interaction (SSI) in pushover analysis is ignored. In this paper the CMP procedure is modified for one-way asymmetric plan mid and high-rise buildings considering SSI. The extended CMP (ECMP) procedure is proposed in order to overcome some limitations of the CMP procedure. In this regard, 10, 15 and 20 story buildings with asymmetric plan are studied considering SSI assuming three different soil conditions. Using nonlinear response history analysis under a set of bidirectional ground motion; the exact responses of these buildings are calculated. Then the ECMP procedure is evaluated by comparing the results of this procedure with nonlinear time history results as an exact solution as well as the modal pushover analysis procedure and FEMA 356 load patterns. The results demonstrate the accuracy of the ECMP procedure.

  16. Real-time object recognition in multidimensional images based on joined extended structural tensor and higher-order tensor decomposition methods

    NASA Astrophysics Data System (ADS)

    Cyganek, Boguslaw; Smolka, Bogdan

    2015-02-01

    In this paper a system for real-time recognition of objects in multidimensional video signals is proposed. Object recognition is done by pattern projection into the tensor subspaces obtained from the factorization of the signal tensors representing the input signal. However, instead of taking only the intensity signal the novelty of this paper is first to build the Extended Structural Tensor representation from the intensity signal that conveys information on signal intensities, as well as on higher-order statistics of the input signals. This way the higher-order input pattern tensors are built from the training samples. Then, the tensor subspaces are built based on the Higher-Order Singular Value Decomposition of the prototype pattern tensors. Finally, recognition relies on measurements of the distance of a test pattern projected into the tensor subspaces obtained from the training tensors. Due to high-dimensionality of the input data, tensor based methods require high memory and computational resources. However, recent achievements in the technology of the multi-core microprocessors and graphic cards allows real-time operation of the multidimensional methods as is shown and analyzed in this paper based on real examples of object detection in digital images.

  17. Local vibrational dynamics of hematite (α-Fe{sub 2}O{sub 3}) studied by extended x-ray absorption fine structure and molecular dynamics

    SciTech Connect

    Sanson, A.; Mathon, O.; Pascarelli, S.

    2014-06-14

    The local vibrational dynamics of hematite (α-Fe{sub 2}O{sub 3}) has been investigated by temperature-dependent extended x-ray absorption fine structure spectroscopy and molecular dynamics simulations. The local dynamics of both the short and long nearest-neighbor Fe–O distances has been singled out, i.e., their local thermal expansion and the parallel and perpendicular mean-square relative atomic displacements have been determined, obtaining a partial agreement with molecular dynamics. No evidence of the Morin transition has been observed. More importantly, the strong anisotropy of relative thermal vibrations found for the short Fe–O distance has been related to its negative thermal expansion. The differences between the local dynamics of short and long Fe–O distances are discussed in terms of projection and correlation of atomic motion. As a result, we can conclude that the short Fe–O bond is stiffer to stretching and softer to bending than the long Fe–O bond.

  18. Extended X-ray absorption fine structure investigation of Sn local environment in strained and relaxed epitaxial Ge1-xSnx films

    NASA Astrophysics Data System (ADS)

    Gencarelli, F.; Grandjean, D.; Shimura, Y.; Vincent, B.; Banerjee, D.; Vantomme, A.; Vandervorst, W.; Loo, R.; Heyns, M.; Temst, K.

    2015-03-01

    We present an extended X-ray absorption fine structure investigation of the local environment of Sn atoms in strained and relaxed Ge1-xSnx layers with different compositions. We show that the preferred configuration for the incorporation of Sn atoms in these Ge1-xSnx layers is that of a α-Sn defect, with each Sn atom covalently bonded to four Ge atoms in a classic tetrahedral configuration. Sn interstitials, Sn-split vacancy complexes, or Sn dimers, if present at all, are not expected to involve more than 2.5% of the total Sn atoms. This finding, along with a relative increase of Sn atoms in the second atomic shell around a central Sn atom in Ge1-xSnx layers with increasing Sn concentrations, suggests that the investigated materials are homogeneous random substitutional alloys. Within the accuracy of the measurements, the degree of strain relaxation of the Ge1-xSnx layers does not have a significant impact on the local atomic surrounding of the Sn atoms. Finally, the calculated topological rigidity parameter a** = 0.69 ± 0.29 indicates that the strain due to alloying in Ge1-xSnx is accommodated via bond stretching and bond bending, with a slight predominance of the latter, in agreement with ab initio calculations reported in literature.

  19. Nearest-neighbor nitrogen and oxygen distances in the iron(II)-DNA complex studied by extended X-ray absorption fine structure

    NASA Astrophysics Data System (ADS)

    Bertoncini, Clelia R. A.; Meneghini, Rogerio; Tolentino, Helio

    2010-11-01

    In mammalian cells, DNA-bound Fe(II) reacts with H 2O 2 producing the highly reactive hydroxyl radical ( rad OH) in situ. Since rad OH attacks nearby DNA residue generating oxidative DNA damage, many questions have arisen regarding iron-DNA complex formations and their implication in pre-malignant mutations and aging. In this work, a solid sample of Fe(II)-DNA complex containing one Fe(II) per 10 nucleotides was analyzed from extended X-ray absorption fine structure (EXAFS) spectra collected in a synchrotron radiation light source. Best fitting parameters of the EXAFS signal for the first two shells provide evidence of five oxygen atoms at 1.99 ± 0.02 Å and one nitrogen atom at 2.20 ± 0.02 Å in the inner coordination sphere of the Fe(II)-DNA complex. Considering that both purine base moieties bearing nitrogen atoms are prone to chelate iron, these results are consistent with the previously observed lower levels of DNA damage in cytosine nucleotides relative to adenine and guanine sites in cells under more physiological conditions of Fe(II) Fenton reaction.

  20. Structure-biological function relationship extended to mitotic arrest-deficient 2-like protein Mad2 native and mutants-new opportunity for genetic disorder control.

    PubMed

    Avram, Speranta; Milac, Adina; Mernea, Maria; Mihailescu, Dan; Putz, Mihai V; Buiu, Catalin

    2014-01-01

    Overexpression of mitotic arrest-deficient proteins Mad1 and Mad2, two components of spindle assembly checkpoint, is a risk factor for chromosomal instability (CIN) and a trigger of many genetic disorders. Mad2 transition from inactive open (O-Mad2) to active closed (C-Mad2) conformations or Mad2 binding to specific partners (cell-division cycle protein 20 (Cdc20) or Mad1) were targets of previous pharmacogenomics studies. Here, Mad2 binding to Cdc20 and the interconversion rate from open to closed Mad2 were predicted and the molecular features with a critical contribution to these processes were determined by extending the quantitative structure-activity relationship (QSAR) method to large-size proteins such as Mad2. QSAR models were built based on available published data on 23 Mad2 mutants inducing CIN-related functional changes. The most relevant descriptors identified for predicting Mad2 native and mutants action mechanism and their involvement in genetic disorders are the steric (van der Waals area and solvent accessible area and their subdivided) and energetic van der Waals energy descriptors. The reliability of our QSAR models is indicated by significant values of statistical coefficients: Cross-validated correlation q2 (0.53-0.65) and fitted correlation r2 (0.82-0.90). Moreover, based on established QSAR equations, we rationally design and analyze nine de novo Mad2 mutants as possible promoters of CIN. PMID:25411801

  1. Extended X- ray absorption fine structure study at the K-edge of copper in mixed ligand complexes having benzimidazole as one of the ligands

    NASA Astrophysics Data System (ADS)

    Hinge, V. K.; Joshi, S. K.; Nitin Nair, N.; Singh Verma, Vikram; Shrivastava, B. D.; Prasad, J.; Srivastava, K.

    2014-09-01

    Extended X-ray absorption fine structure (EXAFS) spectra have been studied at the K-edge of copper in some of its biologically important complexes, viz., [Cu(BzImH)4X2] and [Cu(BzIm)2], where X= Cl, Br, 1/2SO4, ClO4, NO3, and BzIm = Benzimidazolato anion. The spectra have been recorded using a bent crystal 0.4 m Cauchois-type transmission spectrograph. The positions of EXAFS maxima and minima have been used to determine the bond lengths in the complexes with the help of three different methods, namely, Levy's, Lytle's and Lytle, Sayers and Stern's (L.S.S.) methods. The phase uncorrected bond lengths have also been determined from Fourier transforms of the experimental spectra. The results obtained from these methods have been discussed and it has been found that the results obtained by L.S.S. method are comparable with the results obtained by Fourier transformation method and that these two methods give phase uncorrected bond lengths.

  2. Lead Is Not Off Center in PbTe: The Importance of r-Space Phase Information in Extended X-Ray Absorption Fine Structure Spectroscopy

    NASA Astrophysics Data System (ADS)

    Keiber, T.; Bridges, F.; Sales, B. C.

    2013-08-01

    PbTe is a well-known thermoelectric material. Recent x-ray total scattering studies suggest that Pb moves off center along 100 in PbTe, by ˜0.2Å at 300 K, producing a split Pb-Te pair distribution. We present an extended x-ray absorption fine structure spectroscopy (EXAFS) study of PbTe (and Tl doped PbTe) to determine if Pb or Te is off center. EXAFS provides sensitive r- or k-space phase information which can differentiate between a split peak for the Pb-Te distribution (indicative of off-center Pb) and a thermally broadened peak. We find no evidence for a split peak for Pb-Te or Te-Pb. At 300 K, the vibration amplitude for Pb-Te (or Te-Pb) is large; this thermally induced disorder is indicative of weak bonds, and the large disorder is consistent with the low thermal conductivity at 300 K. We also find evidence of an anharmonic potential for the nearest Pb-Te bonds, consistent with the overall anharmonicity found for the phonon modes. This effect is modeled by a “skew” factor (C3) which significantly improves the fit of the Pb-Te and Te-Pb peaks for the high temperature EXAFS data; C3 becomes significant above approximately 150-200 K. The consequences of these results will be discussed.

  3. Structure of GES-1 at Atomic Resolution: Insights Into the Evolution of Carbapenamase Activity in the Class a Extended-Spectrum Beta-Lactamases

    SciTech Connect

    Smith, C.A.; Caccamo, M.; Kantardjieff, K.A.; Vakulenko, S.; /Notre Dame U.

    2007-10-08

    The structure of the class A extended-spectrum {beta}-lactamase GES-1 from Klebsiella pneumoniae has been determined to 1.1 Angstrom resolution. GES-1 has the characteristic active-site disulfide bond of the carbapenemase family of {beta}-lactamases and has a structure that is very similar to those of other known carbapenemases, including NMC-A, SME-1 and KPC-2. Most residues implicated in the catalytic mechanism of this class of enzyme are present in the GES-1 active site, including Ser70, which forms a covalent bond with the carbonyl C atom of the {beta}-lactam ring of the substrate during the formation of an acyl-enzyme intermediate, Glu166, which is implicated as both the acylation and deacylation base, and Lys73, which is also implicated as the acylation base. A water molecule crucial to catalysis is observed in an identical location as in other class A {beta}-lactamases, interacting with the side chains of Ser70 and Glu166. One important residue, Asn170, also normally a ligand for the hydrolytic water, is missing from the GES-1 active site. This residue is a glycine in GES-1 and the enzyme is unable to hydrolyze imipenem. This points to this residue as being critically important in the hydrolysis of this class of {beta}-lactam substrate. This is further supported by flexible-docking studies of imipenem with in silico-generated Gly170Asn and Gly170Ser mutant GES-1 enzymes designed to mimic the active sites of imipenem-hydrolyzing point mutants GES-2 and GES-5.

  4. Reduced Extended MHD

    NASA Astrophysics Data System (ADS)

    Morrison, P. J.; Abdelhamid, H. M.; Grasso, D.; Hazeltine, R. D.; Lingam, M.; Tassi, E.

    2015-11-01

    Over the years various reduced fluid models have been obtained for modeling plasmas, with the goal of capturing important physics while maintaining computability. Such models have included the physics contained in various generalizations of Ohm's law, including Hall drift and electron inertia. In a recent publication it was shown that full 3D extended MHD is a Hamiltonian system by finding its noncanonical Poisson bracket. Subsequently, this bracket was shown to be derivable from that for Hall MHD by a series of remarkable transformations, which greatly simplifies the proof of the Jacobi identity and allows one to immediately obtain generalizations of the helicity and cross helicity. In this poster we use this structure to obtain exact reduced fluid models with the effects of full two-fluid theory. Results of numerical computations of collisionless reconnection using an exact reduced 4-field model will be presented and analytical comparisons of mode structure of previous reduced models will be made.

  5. Macrophage phenotypes in atherosclerosis.

    PubMed

    Colin, Sophie; Chinetti-Gbaguidi, Giulia; Staels, Bart

    2014-11-01

    Initiation and progression of atherosclerosis depend on local inflammation and accumulation of lipids in the vascular wall. Although many cells are involved in the development and progression of atherosclerosis, macrophages are fundamental contributors. For nearly a decade, the phenotypic heterogeneity and plasticity of macrophages has been studied. In atherosclerotic lesions, macrophages are submitted to a large variety of micro-environmental signals, such as oxidized lipids and cytokines, which influence the phenotypic polarization and activation of macrophages resulting in a dynamic plasticity. The macrophage phenotype spectrum is characterized, at the extremes, by the classical M1 macrophages induced by T-helper 1 (Th-1) cytokines and by the alternative M2 macrophages induced by Th-2 cytokines. M2 macrophages can be further classified into M2a, M2b, M2c, and M2d subtypes. More recently, additional plaque-specific macrophage phenotypes have been identified, termed as Mox, Mhem, and M4. Understanding the mechanisms and functional consequences of the phenotypic heterogeneity of macrophages will contribute to determine their potential role in lesion development and plaque stability. Furthermore, research on macrophage plasticity could lead to novel therapeutic approaches to counteract cardiovascular diseases such as atherosclerosis. The present review summarizes our current knowledge on macrophage subsets in atherosclerotic plaques and mechanism behind the modulation of the macrophage phenotype. PMID:25319333

  6. Extending quantum mechanics entails extending special relativity

    NASA Astrophysics Data System (ADS)

    Aravinda, S.; Srikanth, R.

    2016-05-01

    The complementarity between signaling and randomness in any communicated resource that can simulate singlet statistics is generalized by relaxing the assumption of free will in the choice of measurement settings. We show how to construct an ontological extension for quantum mechanics (QMs) through the oblivious embedding of a sound simulation protocol in a Newtonian spacetime. Minkowski or other intermediate spacetimes are ruled out as the locus of the embedding by virtue of hidden influence inequalities. The complementarity transferred from a simulation to the extension unifies a number of results about quantum non-locality, and implies that special relativity has a different significance for the ontological model and for the operational theory it reproduces. Only the latter, being experimentally accessible, is required to be Lorentz covariant. There may be certain Lorentz non-covariant elements at the ontological level, but they will be inaccessible at the operational level in a valid extension. Certain arguments against the extendability of QM, due to Conway and Kochen (2009) and Colbeck and Renner (2012), are attributed to their assumption that the spacetime at the ontological level has Minkowski causal structure.

  7. In vivo structure-function studies of human hepatic lipase: the catalytic function rescues the lean phenotype of HL-deficient (hl−/−) mice

    PubMed Central

    Chen, Jeffrey; Kaiyala, Karl J; Lam, Jennifer; Agrawal, Nalini; Nguyen, Lisa; Ogimoto, Kayoko; Spencer, Dean; Morton, Gregory J; Schwartz, Michael W; Dichek, Helén L

    2015-01-01

    The lean body weight phenotype of hepatic lipase (HL)–deficient mice (hl−/−) suggests that HL is required for normal weight gain, but the underlying mechanisms are unknown. HL plays a unique role in lipoprotein metabolism performing bridging as well as catalytic functions, either of which could participate in energy homeostasis. To determine if both the catalytic and bridging functions or the catalytic function alone are required for the effect of HL on body weight, we studied (hl−/−) mice that transgenically express physiologic levels of human (h)HL (with catalytic and bridging functions) or a catalytically-inactive (ci)HL variant (with bridging function only) in which the catalytic Serine 145 was mutated to Alanine. As expected, HL activity in postheparin plasma was restored to physiologic levels only in hHL-transgenic mice (hl−/−hHL). During high-fat diet feeding, hHL-transgenic mice exhibited increased body weight gain and body adiposity relative to hl−/−ciHL mice. A similar, albeit less robust effect was observed in female hHL-transgenic relative to hl−/−ciHL mice. To delineate the basis for this effect, we determined cumulative food intake and measured energy expenditure using calorimetry. Interestingly, in both genders, food intake was 5–10% higher in hl−/−hHL mice relative to hl−/−ciHL controls. Similarly, energy expenditure was ∼10% lower in HL-transgenic mice after adjusting for differences in total body weight. Our results demonstrate that (1) the catalytic function of HL is required to rescue the lean body weight phenotype of hl−/− mice; (2) this effect involves complementary changes in both sides of the energy balance equation; and (3) the bridging function alone is insufficient to rescue the lean phenotype of hl−/−ciHL mice. PMID:25862097

  8. Cosmological dynamics of extended chameleons

    NASA Astrophysics Data System (ADS)

    Tamanini, Nicola; Wright, Matthew

    2016-04-01

    We investigate the cosmological dynamics of the recently proposed extended chameleon models at both background and linear perturbation levels. Dynamical systems techniques are employed to fully characterize the evolution of the universe at the largest distances, while structure formation is analysed at sub-horizon scales within the quasi-static approximation. The late time dynamical transition from dark matter to dark energy domination can be well described by almost all extended chameleon models considered, with no deviations from ΛCDM results at both background and perturbation levels. The results obtained in this work confirm the cosmological viability of extended chameleons as alternative dark energy models.

  9. Topological defects in extended inflation

    NASA Technical Reports Server (NTRS)

    Copeland, Edmund J.; Kolb, Edward W.; Liddle, Andrew R.

    1990-01-01

    The production of topological defects, especially cosmic strings, in extended inflation models was considered. In extended inflation, the Universe passes through a first-order phase transition via bubble percolation, which naturally allows defects to form at the end of inflation. The correlation length, which determines the number density of the defects, is related to the mean size of bubbles when they collide. This mechanism allows a natural combination of inflation and large scale structure via cosmic strings.

  10. Speciation and localization of Zn in the hyperaccumulator Sedum alfredii by extended X-ray absorption fine structure and micro-X-ray fluorescence.

    PubMed

    Lu, Lingli; Liao, Xingcheng; Labavitch, John; Yang, Xiaoe; Nelson, Erik; Du, Yonghua; Brown, Patrick H; Tian, Shengke

    2014-11-01

    Differences in metal homeostasis among related plant species can give important information of metal hyperaccumulation mechanisms. Speciation and distribution of Zn were investigated in a hyperaccumulating population of Sedum alfredii by using extended X-ray absorption fine structure and micro-synchrotron X-ray fluorescence (μ-XRF), respectively. The hyperaccumulator uses complexation with oxygen donor ligands for Zn storage in leaves and stems, and variations in the Zn speciation was noted in different tissues. The dominant chemical form of Zn in leaves was most probably a complex with malate, the most prevalent organic acid in S. alfredii leaves. In stems, Zn was mainly associated with malate and cell walls, while Zn-citrate and Zn-cell wall complexes dominated in the roots. Two-dimensional μ-XRF images revealed age-dependent differences in Zn localization in S. alfredii stems and leaves. In old leaves of S. alfredii, Zn was high in the midrib, margin regions and the petiole, whereas distribution of Zn was essentially uniform in young leaves. Zinc was preferentially sequestered by cells near vascular bundles in young stems, but was highly localized to vascular bundles and the outer cortex layer of old stems. The results suggest that tissue- and age-dependent variations of Zn speciation and distribution occurred in the hyperaccumulator S. alfredii, with most of the Zn complexed with malate in the leaves, but a shift to cell wall- and citric acid-Zn complexes during transportation and storage in stems and roots. This implies that biotransformation in Zn complexation occurred during transportation and storage processes in the plants of S. alfredii. PMID:25306525

  11. Metal incorporation in sputter-deposited MoS{sub 2} films studied by extended x-ray adsorption fine structure

    SciTech Connect

    Lince, J.R.; Hilton, M.R.; Bommannavar, A.S.

    1995-08-01

    Solid lubricant films produced by cosputtering metals with MoS{sub 2} and by forming metal/MoS{sub 2} multilayers are being planned for use in the next generation of solid lubricated devices on spacecraft, including gimbal and sensor bearings, actuators, and sliding electrical contacts. The films exhibit increased densities and wear lives compared to films without additives, but the mechanism of density enhancement is not well understood. The extended x-ray absorption fine structure (EXAFS) technique is ideal for elucidating the structure of these poorly crystalline films. We analyzed MoS{sub 2} films cosputtered with 0, 2, and 10% Ni, as well as Ni/MoS{sub 2} and Au(Pd)/MoS{sub 2} multilayer films. The results obtained at the Mo-K absorption edge showed that the metal-containing films comprised predominantly the same nanocrystalline phases present in similar films without added metals: pure MoS{sub 2} and a MoS{sub 2{minus}{ital x}}O{sub {ital x}} phase. MoS{sub 2{minus}{ital x}}O{sub {ital x}} is isostructural with MoS{sub 2}, with O atoms substituting for S atoms in the MoS{sub 2} crystal lattice. For all Ni-containing films, EXAFS data obtained at the Ni--K absorption edge showed that the Ni had not chemically reacted with the MoS{sub 2{minus}{ital x}}O{sub {ital x}} and MoS{sub 2}, but formed a disordered NiO{sub {ital x}} phase. However, Ni-cosputtered films showed decreasing Mo--Mo bond lengths in the MoS{sub 2{minus}{ital x}}O{sub {ital x}} phase with increasing Ni content, probably due to preferential oxidation of Ni compared to MoS{sub 2}. EXAFS of these Ni-cosputtered films showed only a small decrease in short-range order with Ni content, while x-ray diffraction showed a concurrent large decrease in long-range order. The results indicate that film densification in Ni-cosputtered films is caused by NiO{sub {ital x}} formation at the edges of nucleating MoS{sub 2{minus}{ital x}}O{sub {ital x}} /MoS{sub 2} crystallites.

  12. Surface complexation and precipitate geometry for aqueous Zn(II) sorption on ferrihydrite I: X-ray absorption extended fine structure spectroscopy analysis

    USGS Publications Warehouse

    Waychunas, G.A.; Fuller, C.C.; Davis, J.A.

    2002-01-01

    "Two-line" ferrihydrite samples precipitated and then exposed to a range of aqueous Zn solutions (10-5 to 10-3 M), and also coprecipitated in similar Zn solutions (pH 6.5), have been examined by Zn and Fe K-edge X-ray absorption spectroscopy. Typical Zn complexes on the surface have Zn-O distances of 1.97(0.2) A?? and coordination numbers of about 4.0(0.5), consistent with tetrahedral oxygen coordination. This contrasts with Zn-O distances of 2.11(.02) A?? and coordination numbers of 6 to 7 in the aqueous Zn solutions used in sample preparation. X-ray absorption extended fine structure spectroscopy (EXAFS) fits to the second shell of cation neighbors indicate as many as 4 Zn-Fe neighbors at 3.44(.04) A?? in coprecipitated samples, and about two Zn-Fe neighbors at the same distance in adsorption samples. In both sets of samples, the fitted coordination number of second shell cations decreases as sorption density increases, indicating changes in the number and type of available complexing sites or the onset of competitive precipitation processes. Comparison of our results with the possible geometries for surface complexes and precipitates suggests that the Zn sorption complexes are inner sphere and at lowest adsorption densities are bidentate, sharing apical oxygens with adjacent edge-sharing Fe(O,OH)6 octahedra. Coprecipitation samples have complexes with similar geometry, but these are polydentate, sharing apices with more than two adjacent edge-sharing Fe(O,OH)6 polyhedra. The results are inconsistent with Zn entering the ferrihydrite structure (i.e., solid solution formation) or formation of other Zn-Fe precipitates. The fitted Zn-Fe coordination numbers drop with increasing Zn density with a minimum of about 0.8(.2) at Zn/(Zn + Fe) of 0.08 or more. This change appears to be attributable to the onset of precipitation of zinc hydroxide polymers with mainly tetrahedral Zn coordination. At the highest loadings studied, the nature of the complexes changes further

  13. Prediction of microbial phenotypes based on comparative genomics

    PubMed Central

    2015-01-01

    The accessibility of almost complete genome sequences of uncultivable microbial species from metagenomes necessitates computational methods predicting microbial phenotypes solely based on genomic data. Here we investigate how comparative genomics can be utilized for the prediction of microbial phenotypes. The PICA framework facilitates application and comparison of different machine learning techniques for phenotypic trait prediction. We have improved and extended PICA's support vector machine plug-in and suggest its applicability to large-scale genome databases and incomplete genome sequences. We have demonstrated the stability of the predictive power for phenotypic traits, not perturbed by the rapid growth of genome databases. A new software tool facilitates the in-depth analysis of phenotype models, which associate expected and unexpected protein functions with particular traits. Most of the traits can be reliably predicted in only 60-70% complete genomes. We have established a new phenotypic model that predicts intracellular microorganisms. Thereby we could demonstrate that also independently evolved phenotypic traits, characterized by genome reduction, can be reliably predicted based on comparative genomics. Our results suggest that the extended PICA framework can be used to automatically annotate phenotypes in near-complete microbial genome sequences, as generated in large numbers in current metagenomics studies. PMID:26451672

  14. Extended cooperative control synthesis

    NASA Technical Reports Server (NTRS)

    Davidson, John B.; Schmidt, David K.

    1994-01-01

    This paper reports on research for extending the Cooperative Control Synthesis methodology to include a more accurate modeling of the pilot's controller dynamics. Cooperative Control Synthesis (CCS) is a methodology that addresses the problem of how to design control laws for piloted, high-order, multivariate systems and/or non-conventional dynamic configurations in the absence of flying qualities specifications. This is accomplished by emphasizing the parallel structure inherent in any pilot-controlled, augmented vehicle. The original CCS methodology is extended to include the Modified Optimal Control Model (MOCM), which is based upon the optimal control model of the human operator developed by Kleinman, Baron, and Levison in 1970. This model provides a modeling of the pilot's compensation dynamics that is more accurate than the simplified pilot dynamic representation currently in the CCS methodology. Inclusion of the MOCM into the CCS also enables the modeling of pilot-observation perception thresholds and pilot-observation attention allocation affects. This Extended Cooperative Control Synthesis (ECCS) allows for the direct calculation of pilot and system open- and closed-loop transfer functions in pole/zero form and is readily implemented in current software capable of analysis and design for dynamic systems. Example results based upon synthesizing an augmentation control law for an acceleration command system in a compensatory tracking task using the ECCS are compared with a similar synthesis performed by using the original CCS methodology. The ECCS is shown to provide augmentation control laws that yield more favorable, predicted closed-loop flying qualities and tracking performance than those synthesized using the original CCS methodology.

  15. Structural Analysis of the Mn(IV)/Fe(III) Cofactor of Chlamydia trachomatis Ribonucleotide Reductase by Extended X-ray Absorption Fine Structure Spectroscopy and Density Functional Theory Calculations

    PubMed Central

    Younker, Jarod M.; Krest, Courtney M.; Jiang, Wei; Krebs, Carsten; Bollinger, J. Martin; Green, Michael T.

    2009-01-01

    The class Ic ribonucleotide reductase from Chlamydia trachomatis (Ct) uses a stable Mn(IV)/Fe(III) cofactor to initiate nucleotide reduction by a free-radical mechanism. Extended X-ray absorption fine structure (EXAFS) spectroscopy and density functional theory (DFT) calculations are used to postulate a structure for this cofactor. Fe and Mn K-edge EXAFS data yield an intermetallic distance of ~2.92 Å. The Mn data also suggest the presence of a short 1.74 Å Mn—O bond. These metrics are compared to the results of DFT calculations on 12 cofactor models derived from the crystal structure of the inactive Fe2(III/III) form of the protein. Models are differentiated by the protonation states of their bridging and terminal OHX ligands as well as the location of the Mn(IV) ion (site 1 or 2). The models that agree best with experimental observation feature a µ-1,3-carboxylate bridge (E120), terminal solvent (H2O/OH) to site 1, one µ-O bridge, and one µ-OH bridge. The site-placement of the metal ions cannot be discerned from the available data. PMID:18937466

  16. Structural Analysis of the Mn(IV)/Fe(III) Cofactor of Chlamydia Trachomatis Ribonucleotide Reductase By Extended X-Ray Absorption Fine Structure Spectroscopy And Density Functional Theory Calculations

    SciTech Connect

    Younker, J.M.; Krest, C.M.; Jiang, W.; Krebs, C.; Bollinger, J.M.Jr.; Green, M.T.

    2009-05-28

    The class Ic ribonucleotide reductase from Chlamydia trachomatis (C{bar A}) uses a stable Mn(lV)/ Fe(lll) cofactor to initiate nucleotide reduction by a free-radical mechanism. Extended X-ray absorption fine structure (EXAFS) spectroscopy and density functional theory (DFT) calculations are used to postulate a structure for this cofactor. Fe and Mn K-edge EXAFS data yield an intermetallic distance of -2.92 {angstrom}. The Mn data also suggest the presence of a short 1.74 {angstrom} Mn-O bond. These metrics are compared to the results of DFT calculations on 12 cofactor models derived from the crystal structure of the inactive Fe2(lll/ III) form of the protein. Models are differentiated by the protonation states of their bridging and terminal OH{sub x} ligands as well as the location of the Mn(lV) ion (site 1 or 2). The models that agree best with experimental observation feature a{mu}-1, 3-carboxylate bridge (E120), terminal solvent (H{sub 2}O/OH) to site 1, one {mu}-O bridge, and one {mu}-OH bridge. The site-placement of the metal ions cannot be discerned from the available data.

  17. Clonal Structure, Extended-Spectrum β-Lactamases, and Acquired AmpC-Type Cephalosporinases of Escherichia coli Populations Colonizing Patients in Rehabilitation Centers in Four Countries

    PubMed Central

    Izdebski, R.; Baraniak, A.; Fiett, J.; Adler, A.; Kazma, M.; Salomon, J.; Lawrence, C.; Rossini, A.; Salvia, A.; Vidal Samso, J.; Fierro, J.; Paul, M.; Lerman, Y.; Malhotra-Kumar, S.; Lammens, C.; Goossens, H.; Hryniewicz, W.; Brun-Buisson, C.; Carmeli, Y.

    2013-01-01

    The prospective project MOSAR was conducted in five rehabilitation units: the Berck Maritime Hôpital (Berck, France), Fondazione Santa Lucia (Rome, Italy), Guttmann Institute (GI; Barcelona, Spain), and Loewenstein Hospital and Tel-Aviv Souraski Medical Center (TA) (Tel-Aviv, Israel). Patients were screened for carriage of Enterobacteriaceae resistant to expanded-spectrum cephalosporins (ESCs) from admission until discharge. The aim of this study was to characterize the clonal structure, extended-spectrum β-lactamases (ESBLs), and acquired AmpC-like cephalosporinases in the Escherichia coli populations collected. A total of 376 isolates were randomly selected. The overall number of sequence types (STs) was 76, including 7 STs that grouped at least 10 isolates from at least three centers each, namely, STs 10, 38, 69, 131, 405, 410, and 648. These clones comprised 65.2% of all isolates, and ST131 alone comprised 41.2%. Of 54 STs observed only in one center, some STs played a locally significant role, like ST156 and ST393 in GI or ST372 and ST398 in TA. Among 16 new STs, five arose from evolution within the ST10 and ST131 clonal complexes. ESBLs and AmpCs accounted for 94.7% and 5.6% of the ESC-hydrolyzing β-lactamases, respectively, being dominated by the CTX-M-like enzymes (79.9%), followed by the SHV (13.5%) and CMY-2 (5.3%) types. CTX-M-15 was the most prevalent β-lactamase overall (40.6%); other ubiquitous enzymes were CTX-M-14 and CMY-2. Almost none of the common clones correlated strictly with one β-lactamase; although 58.7% of ST131 isolates produced CTX-M-15, the clone also expressed nine other enzymes. A number of clone variants with specific pulsed-field gel electrophoresis and ESBL types were spread in some locales, potentially representing newly emerging E. coli epidemic strains. PMID:23114774

  18. Down Syndrome: Cognitive Phenotype

    ERIC Educational Resources Information Center

    Silverman, Wayne

    2007-01-01

    Down syndrome is the most prevalent cause of intellectual impairment associated with a genetic anomaly, in this case, trisomy of chromosome 21. It affects both physical and cognitive development and produces a characteristic phenotype, although affected individuals vary considerably with respect to severity of specific impairments. Studies…

  19. Spatial structure determination of ({radical}3 x {radical}3)R30{degrees} and (1.5 x 1.5)R18{degrees}CO on Cu(111) using angle-resolved photoemission extended fine structure

    SciTech Connect

    Moler, E.J.; Kellar, S.A.; Huff, W.R.A.

    1997-04-01

    The authors report a study of the spatial structure of ({radical}3 x {radical}3)R30{degrees} (low coverage) and (1.5 x 1.5)R18{degrees} (intermediate coverage) CO adsorbed on Cu(111), using the Angle-Resolved Photoemission Extended Fine Structure (ARPEFS) technique at beamline 9.3.2 at the Advanced Light Source. The CO molecule adsorbs on an atop site for both adsorption phases. Full multiple-scattering spherical-wave (MSSW) calculations were used to extract the C-Cu. bond length and the first Cu-Cu layer spacing for each adsorption phase. The authors find that the C-Cu bond length remains unchanged with increasing coverage, but the 1st Cu-Cu layer spacing contracts at the intermediate coverage. They calculate the bending mode force constant in the (1.5 x 1.5)R18{degrees} phase to be K{sub {delta}} = 2.2 (1) x 10{sup {minus}12} dyne-cm/rad from their experimentally determined bond lengths combined with previously published infra-red absorption frequencies.

  20. Correlation functions for extended mass galaxy clusters

    NASA Astrophysics Data System (ADS)

    Iqbal, Naseer; Ahmad, Naveel; Hamid, Mubashir; Masood, Tabasum

    2012-07-01

    The phenomenon of clustering of galaxies on the basis of correlation functions in an expanding Universe is studied by using equation of state, taking gravitational interaction between galaxies of extended nature into consideration. The partial differential equation for the extended mass structures of a two-point correlation function developed earlier by Iqbal, Ahmad & Khan is studied on the basis of assigned boundary conditions. The solution for the correlation function for extended structures satisfies the basic boundary conditions, which seem to be sufficient for understanding the phenomena, and provides a new insight into the gravitational clustering problem for extended mass structures.

  1. State of the Art. A structural and functional assessment of the lung via multidetector-row computed tomography: phenotyping chronic obstructive pulmonary disease.

    PubMed

    Hoffman, Eric A; Simon, Brett A; McLennan, Geoffrey

    2006-08-01

    With advances in multidetector-row computed tomography (MDCT), it is now possible to image the lung in 10 s or less and accurately extract the lungs, lobes, and airway tree to the fifth- through seventh-generation bronchi and to regionally characterize lung density, texture, ventilation, and perfusion. These methods are now being used to phenotype the lung in health and disease and to gain insights into the etiology of pathologic processes. This article outlines the application of these methodologies with specific emphasis on chronic obstructive pulmonary disease. We demonstrate the use of our methods for assessing regional ventilation and perfusion and demonstrate early data that show, in a sheep model, a regionally intact hypoxic pulmonary vasoconstrictor (HPV) response with an apparent inhibition of HPV regionally in the presence of inflammation. We present the hypothesis that, in subjects with pulmonary emphysema, one major contributing factor leading to parenchymal destruction is the lack of a regional blunting of HPV when the regional hypoxia is related to regional inflammatory events (bronchiolitis or alveolar flooding). If maintaining adequate blood flow to inflamed lung regions is critical to the nondestructive resolution of inflammatory events, the pathologic condition whereby HPV is sustained in regions of inflammation would likely have its greatest effect in the lung apices where blood flow is already reduced in the upright body posture. PMID:16921136

  2. Evolving phenotypic networks in silico.

    PubMed

    François, Paul

    2014-11-01

    Evolved gene networks are constrained by natural selection. Their structures and functions are consequently far from being random, as exemplified by the multiple instances of parallel/convergent evolution. One can thus ask if features of actual gene networks can be recovered from evolutionary first principles. I review a method for in silico evolution of small models of gene networks aiming at performing predefined biological functions. I summarize the current implementation of the algorithm, insisting on the construction of a proper "fitness" function. I illustrate the approach on three examples: biochemical adaptation, ligand discrimination and vertebrate segmentation (somitogenesis). While the structure of the evolved networks is variable, dynamics of our evolved networks are usually constrained and present many similar features to actual gene networks, including properties that were not explicitly selected for. In silico evolution can thus be used to predict biological behaviours without a detailed knowledge of the mapping between genotype and phenotype. PMID:24956562

  3. Extender for securing a closure

    DOEpatents

    Thomas, II, Patrick A.

    2012-10-02

    An apparatus for securing a closure such as door or a window that opens and closes by movement relative to a fixed structure such as a wall or a floor. Many embodiments provide a device for relocating a padlock from its normal location where it secures a fastener (such as a hasp) to a location for the padlock that is more accessible for locking and unlocking the padlock. Typically an extender is provided, where the extender has a hook at a first end that is disposed through the eye of the staple of the hasp, and at an opposing second end the extender has an annulus, such as a hole in the extender or a loop or ring affixed to the extender. The shackle of the padlock may be disposed through the annulus and may be disposed through the eye of a second staple to secure the door or window in a closed or open position. Some embodiments employ a rigid sheath to enclose at least a portion of the extender. Typically the rigid sheath has an open state where the hook is exposed outside the sheath and a closed state where the hook is disposed within the sheath.

  4. Structural characterization of Bi{sub 2}Te{sub 3} and Sb{sub 2}Te{sub 3} as a function of temperature using neutron powder diffraction and extended X-ray absorption fine structure techniques

    SciTech Connect

    Mansour, A. N.; Wong-Ng, W.; Huang, Q.; Tang, W.; Thompson, A.; Sharp, J.

    2014-08-28

    The structure of Bi{sub 2}Te{sub 3} (Seebeck coefficient Standard Reference Material (SRM™ 3451)) and the related phase Sb{sub 2}Te{sub 3} have been characterized as a function of temperature using the neutron powder diffraction (NPD) and the extended X-ray absorption fine structure (EXAFS) techniques. The neutron structural studies were carried out from 20 K to 300 K for Bi{sub 2}Te{sub 3} and from 10 K to 298 K for Sb{sub 2}Te{sub 3}. The EXAFS technique for studying the local structure of the two compounds was conducted from 19 K to 298 K. Bi{sub 2}Te{sub 3} and Sb{sub 2}Te{sub 3} are isostructural, with a space group of R3{sup ¯}m. The structure consists of repeated quintuple layers of atoms, Te2-M-Te1-M-Te2 (where M = Bi or Sb) stacking along the c-axis of the unit cell. EXAFS was used to examine the bond distances and static and thermal disorders for the first three shells of Bi{sub 2}Te{sub 3} and Sb{sub 2}Te{sub 3} as a function of temperature. The temperature dependencies of thermal disorders were analyzed using the Debye and Einstein models for lattice vibrations. The Debye and Einstein temperatures for the first two shells of Bi{sub 2}Te{sub 3} are similar to those of Sb{sub 2}Te{sub 3} within the uncertainty in the data. However, the Debye and Einstein temperatures for the third shell of Bi-Bi are significantly lower than those of the third shell of Sb-Sb. The Einstein temperature for the third shell is consistent with a soft phonon mode in both Bi{sub 2}Te{sub 3} and Sb{sub 2}Te{sub 3}. The lower Einstein temperature of Bi-Bi relative to Sb-Sb is consistent with the lower value of thermal conductivity of Bi{sub 2}Te{sub 3} relative to Sb{sub 2}Te{sub 3}.

  5. Specific temperature-induced perturbations of secondary mRNA structures are associated with the cold-adapted temperature-sensitive phenotype of influenza A virus

    PubMed Central

    Chursov, Andrey; Kopetzky, Sebastian J.; Leshchiner, Ignaty; Kondofersky, Ivan; Theis, Fabian J.; Frishman, Dmitrij; Shneider, Alexander

    2012-01-01

    For decades, cold-adapted, temperature-sensitive (ca/ts) strains of influenza A virus have been used as live attenuated vaccines. Due to their great public health importance it is crucial to understand the molecular mechanism(s) of cold adaptation and temperature sensitivity that are currently unknown. For instance, secondary RNA structures play important roles in influenza biology. Thus, we hypothesized that a relatively minor change in temperature (32–39°C) can lead to perturbations in influenza RNA structures and, that these structural perturbations may be different for mRNAs of the wild type (wt) and ca/ts strains. To test this hypothesis, we developed a novel in silico method that enables assessing whether two related RNA molecules would undergo (dis)similar structural perturbations upon temperature change. The proposed method allows identifying those areas within an RNA chain where dissimilarities of RNA secondary structures at two different temperatures are particularly pronounced, without knowing particular RNA shapes at either temperature. We identified such areas in the NS2, PA, PB2 and NP mRNAs. However, these areas are not identical for the wt and ca/ts mutants. Differences in temperature-induced structural changes of wt and ca/ts mRNA structures may constitute a yet unappreciated molecular mechanism of the cold adaptation/temperature sensitivity phenomena. PMID:22995831

  6. PRIMARY CILIARY DYSKINESIA: DIAGNOSTIC AND PHENOTYPIC FEATURES

    EPA Science Inventory

    Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormalities in ciliary structure/function. We hypothesized that the major clinical and biologic phenotypic markers of the disease could be evaluated by studying a cohort of subjects suspected of having PCD. ...

  7. Rapamycin extends murine lifespan but has limited effects on aging

    PubMed Central

    Neff, Frauke; Flores-Dominguez, Diana; Ryan, Devon P.; Horsch, Marion; Schröder, Susanne; Adler, Thure; Afonso, Luciana Caminha; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Garrett, Lillian; Hans, Wolfgang; Hettich, Moritz M.; Holtmeier, Richard; Hölter, Sabine M.; Moreth, Kristin; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Rozman, Jan; Naton, Beatrix; Ordemann, Rainer; Adamski, Jerzy; Beckers, Johannes; Bekeredjian, Raffi; Busch, Dirk H.; Ehninger, Gerhard; Graw, Jochen; Höfler, Heinz; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Stypmann, Jörg; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabe de Angelis, Martin; Ehninger, Dan

    2013-01-01

    Aging is a major risk factor for a large number of disorders and functional impairments. Therapeutic targeting of the aging process may therefore represent an innovative strategy in the quest for novel and broadly effective treatments against age-related diseases. The recent report of lifespan extension in mice treated with the FDA-approved mTOR inhibitor rapamycin represented the first demonstration of pharmacological extension of maximal lifespan in mammals. Longevity effects of rapamycin may, however, be due to rapamycin’s effects on specific life-limiting pathologies, such as cancers, and it remains unclear if this compound actually slows the rate of aging in mammals. Here, we present results from a comprehensive, large-scale assessment of a wide range of structural and functional aging phenotypes, which we performed to determine whether rapamycin slows the rate of aging in male C57BL/6J mice. While rapamycin did extend lifespan, it ameliorated few studied aging phenotypes. A subset of aging traits appeared to be rescued by rapamycin. Rapamycin, however, had similar effects on many of these traits in young animals, indicating that these effects were not due to a modulation of aging, but rather related to aging-independent drug effects. Therefore, our data largely dissociate rapamycin’s longevity effects from effects on aging itself. PMID:23863708

  8. Extended chameleon models

    NASA Astrophysics Data System (ADS)

    Brax, Philippe; Tamanini, Nicola

    2016-05-01

    We extend the chameleon models by considering scalar-fluid theories where the coupling between matter and the scalar field can be represented by a quadratic effective potential with density-dependent minimum and mass. In this context, we study the effects of the scalar field on Solar System tests of gravity and show that models passing these stringent constraints can still induce large modifications of Newton's law on galactic scales. On these scales we analyze models which could lead to a percent deviation of Newton's law outside the virial radius. We then model the dark matter halo as a Navarro-Frenk-White profile and explicitly find that the fifth force can give large contributions around the galactic core in a particular model where the scalar field mass is constant and the minimum of its potential varies linearly with the matter density. At cosmological distances, we find that this model does not alter the growth of large scale structures and therefore would be best tested on galactic scales, where interesting signatures might arise in the galaxy rotation curves.

  9. Large-scale objective phenotyping of 3D facial morphology

    PubMed Central

    Hammond, Peter; Suttie, Michael

    2012-01-01

    Abnormal phenotypes have played significant roles in the discovery of gene function, but organized collection of phenotype data has been overshadowed by developments in sequencing technology. In order to study phenotypes systematically, large-scale projects with standardized objective assessment across populations are considered necessary. The report of the 2006 Human Variome Project meeting recommended documentation of phenotypes through electronic means by collaborative groups of computational scientists and clinicians using standard, structured descriptions of disease-specific phenotypes. In this report, we describe progress over the past decade in 3D digital imaging and shape analysis of the face, and future prospects for large-scale facial phenotyping. Illustrative examples are given throughout using a collection of 1107 3D face images of healthy controls and individuals with a range of genetic conditions involving facial dysmorphism. PMID:22434506

  10. Decomposing Phenotype Descriptions for the Human Skeletal Phenome

    PubMed Central

    Groza, Tudor; Hunter, Jane; Zankl, Andreas

    2013-01-01

    Over the course of the last few years there has been a significant amount of research performed on ontology-based formalization of phenotype descriptions. The intrinsic value and knowledge captured within such descriptions can only be expressed by taking advantage of their inner structure that implicitly combines qualities and anatomical entities. We present a meta-model (the Phenotype Fragment Ontology) and a processing pipeline that enable together the automatic decomposition and conceptualization of phenotype descriptions for the human skeletal phenome. We use this approach to showcase the usefulness of the generic concept of phenotype decomposition by performing an experimental study on all skeletal phenotype concepts defined in the Human Phenotype Ontology. PMID:23440304

  11. Rational elicitation of cold-sensitive phenotypes.

    PubMed

    Baliga, Chetana; Majhi, Sandipan; Mondal, Kajari; Bhattacharjee, Antara; VijayRaghavan, K; Varadarajan, Raghavan

    2016-05-01

    Cold-sensitive phenotypes have helped us understand macromolecular assembly and biological phenomena, yet few attempts have been made to understand the basis of cold sensitivity or to elicit it by design. We report a method for rational design of cold-sensitive phenotypes. The method involves generation of partial loss-of-function mutants, at either buried or functional sites, coupled with selective overexpression strategies. The only essential input is amino acid sequence, although available structural information can be used as well. The method has been used to elicit cold-sensitive mutants of a variety of proteins, both monomeric and dimeric, and in multiple organisms, namely Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanogaster This simple, yet effective technique of inducing cold sensitivity eliminates the need for complex mutations and provides a plausible molecular mechanism for eliciting cold-sensitive phenotypes. PMID:27091994

  12. Experimental validation of an extended Jones matrix calculus model to study the 3D structural orientation of the collagen fibers in articular cartilage using polarization-sensitive optical coherence tomography

    PubMed Central

    Kasaragod, Deepa K.; Lu, Zenghai; Jacobs, James; Matcher, Stephen J.

    2012-01-01

    We report results to verify a theoretical framework to analyze the 3D depth-wise structural organization of collagen fibers in articular cartilage using polarization-sensitive optical coherence tomography. Apparent birefringence data obtained from multi-angle measurements using a time domain polarization-sensitive optical coherence tomography system has been compared with simulated data based on the extended Jones matrix calculus. Experimental data has been shown to agree with the lamellar model previously proposed for the cartilage microstructure based on scanning electron microscopy data. This tool could have potential application in mapping the collagen structural orientation information of cartilage non-invasively during arthroscopy. PMID:22435087

  13. Bioimaging for quantitative phenotype analysis.

    PubMed

    Chen, Weiyang; Xia, Xian; Huang, Yi; Chen, Xingwei; Han, Jing-Dong J

    2016-06-01

    With the development of bio-imaging techniques, an increasing number of studies apply these techniques to generate a myriad of image data. Its applications range from quantification of cellular, tissue, organismal and behavioral phenotypes of model organisms, to human facial phenotypes. The bio-imaging approaches to automatically detect, quantify, and profile phenotypic changes related to specific biological questions open new doors to studying phenotype-genotype associations and to precisely evaluating molecular changes associated with quantitative phenotypes. Here, we review major applications of bioimage-based quantitative phenotype analysis. Specifically, we describe the biological questions and experimental needs addressable by these analyses, computational techniques and tools that are available in these contexts, and the new perspectives on phenotype-genotype association uncovered by such analyses. PMID:26850283

  14. Logo and Extended Definition.

    ERIC Educational Resources Information Center

    Desilets, Brendan J.

    1986-01-01

    Describes use of the programing language "Logo" and the Apple II computer to teach high school students how to write extended definitions. By defining procedures in Logo for drawing simple geometric patterns, students learn that good definition requires precision, rewriting and, in complex tasks, recursion, an aspect of extended definition…

  15. Extended or Restricted Childhood?

    ERIC Educational Resources Information Center

    Richards, Colin

    2005-01-01

    This article discusses the Government's proposals for "extended" primary schools, an important element in the recently-published five-year plan for education. The author expresses concern that extended primary schools will not provide a variety of experiences, including "play" experiences for young children.

  16. Quantum extended supersymmetries

    NASA Astrophysics Data System (ADS)

    Grigore, D. R.; Scharf, G.

    2004-09-01

    We analyse some quantum multiplets associated with extended supersymmetries. We study in detail the general form of the causal (anti)commutation relations. The condition of positivity of the scalar product imposes severe restrictions on the (quantum) model. It is problematic if one can find out quantum extensions of the standard model with extended supersymmetries.

  17. Extended conformal field theories

    NASA Astrophysics Data System (ADS)

    Taormina, Anne

    1990-08-01

    Some extended conformal field theories are briefly reviewed. They illustrate how non minimal models of the Virasoro algebra (c≥1) can become minimal with respect to a larger algebra. The accent is put on N-extended superconformal algebras, which are relevant in superstring compactification.

  18. Recovery act. Characterizing structural controls of EGS-candidate and conventional geothermal reservoirs in the Great Basin. Developing successful exploration strategies in extended terranes

    SciTech Connect

    Faulds, James

    2015-06-25

    We conducted a comprehensive analysis of the structural controls of geothermal systems within the Great Basin and adjacent regions. Our main objectives were to: 1) Produce a catalogue of favorable structural environments and models for geothermal systems. 2) Improve site-specific targeting of geothermal resources through detailed studies of representative sites, which included innovative techniques of slip tendency analysis of faults and 3D modeling. 3) Compare and contrast the structural controls and models in different tectonic settings. 4) Synthesize data and develop methodologies for enhancement of exploration strategies for conventional and EGS systems, reduction in the risk of drilling non-productive wells, and selecting the best EGS sites.

  19. Two-fermion-four-boson description of Hg198 within the Uν(6/12)⊗Uπ(6/4) extended nuclear structure supersymmetry

    NASA Astrophysics Data System (ADS)

    Bernards, C.; Heinze, S.; Jolie, J.; Fransen, C.; Linnemann, A.; Radeck, D.

    2009-05-01

    Using the Uν(6/12)⊗Uπ(6/4) extended supersymmetry, we constructed the energy spectrum and electromagnetic transition properties of the supermultiplet member Hg198 with two proton fermions coupled to a neutron boson core. Consistency between the supersymmetric interacting boson fermion fermion approximation (IBFFA) description and the F-spin symmetric interacting boson approximation (IBA-2) description is shown for this two-fermion-N-boson multiplet member. The data of a γγ angular correlation experiment using the HORUS cube γ-ray spectrometer—determining new multipole mixing ratios, level spins, γ transitions, and energy states—shows quite a good agreement, also for the low-energy part of the spectrum, when comparing theoretical predictions and experimental data. This is contrary to the usual assumption that a two-fermion-N-boson constellation should describe just the excited two-quasiparticle states.

  20. Structural profiling of lipopolysaccharide glycoforms expressed by non-typeable Haemophilus influenzae: phenotypic similarities between NTHi strain 162 and the genome strain Rd.

    PubMed

    Schweda, Elke K H; Landerholm, Malin K; Li, Jianjun; Richard Moxon, E; Richards, James C

    2003-11-14

    Non-typeable Haemophilus influenzae (NTHi) is a significant cause of otitis media in children. We have employed single and multiple step electrospray ionization mass spectrometry (ESIMS) and NMR spectroscopy to profile and elucidate lipopolysaccharide (LPS) structural types expressed by NTHi strain 162, a strain obtained from an epidemiological study in Finland. ESIMS on O-deacylated LPS (LPS-OH) and core oligosaccharide (OS) samples of LPS provided information on the composition and relative abundance of glycoforms differing in the number of hexoses linked to the conserved inner-core element, L-alpha-D-Hepp-(1-->2)-[PEtn-->6]-L-alpha-D-Hepp-(1-->3)-L-alpha-D-Hepp-(1-->5)-[PPEtn-->4]-alpha-Kdop-(2-->6)-Lipid A of H. influenzae LPS. The strain examined was found to elaborate Hex2 to Hex5 LPS glycoform populations having structures identical to those observed for H. influenzae strain Rd [Risberg, A.; Masoud, H.; Martin, A.; Richards, J.C.; Moxon, E.R.; Schweda, E.K.H. Eur. J. Biochem. 1999, 261, 171-180], the strain for which the complete genome has been sequenced. In addition, sialyllactose-containing glycoforms previously identified in strain Rd as well as several NTHi strains, were identified as minor components. Multiple step tandem ESIMS (MS(n)) on dephosphorylated and permethylated OS provided information on the arrangement of glycoses within the major population of glycoforms and on the existence of additional isomeric glycoforms. Minor Hex1 and Hex6 glycoforms were detected and characterized where the Hex6 glycoform was comprised of a dihexosamine-containing pentasaccharide chain attached at the proximal heptose residue of the inner-core unit. LPS structural motifs present in the NTHi strain 162 are expressed by a genetically diverse set of disease causing isolates, providing the basis for a vaccine strategy against NTHi otitis media. PMID:14670731

  1. Intermediate phenotypes and biomarkers of treatment outcome in major depressive disorder

    PubMed Central

    Leuchter, Andrew F.; Hunter, Aimee M.; Krantz, David E.; Cook, Ian A.

    2014-01-01

    Major depressive disorder (MDD) is a pleomorphic illness originating from gene x environment interactions. Patients with differing symptom phenotypes receive the same diagnosis and similar treatment recommendations without regard to genomics, brain structure or function, or other physiologic or psychosocial factors. Using this present approach, only one third of patients enter remission with the first medication prescribed, and patients may take longer than 1 year to enter remission with repeated trials. Research to improve treatment effectiveness recently has focused on identification of intermediate phenotypes (IPs) that could parse the heterogeneous population of patients with MDD into subgroups with more homogeneous responses to treatment. Such IPs could be used to develop biomarkers that could be applied clinically to match patients with the treatment that would be most likely to lead to remission. Putative biomarkers include genetic polymorphisms, RNA and protein expression (transcriptome and proteome), neurotransmitter levels (metabolome), additional measures of signaling cascades, oscillatory synchrony, neuronal circuits and neural pathways (connectome), along with other possible physiologic measures. All of these measures represent components of a continuum that extends from proximity to the genome to proximity to the clinical phenotype of depression, and there are many levels along this continuum at which useful IPs may be defined. Because of the highly integrative nature of brain systems and the complex neurobiology of depression, the most useful biomarkers are likely to be those with intermediate proximity both to the genome and the clinical phenotype of MDD. Translation of findings across the spectrum from genotype to phenotype promises to better characterize the complex disruptions in signaling and neuroplasticity that accompany MDD, and ultimately to lead to greater understanding of the causes of depressive illness. PMID:25733956

  2. Intermediate phenotypes and biomarkers of treatment outcome in major depressive disorder.

    PubMed

    Leuchter, Andrew F; Hunter, Aimee M; Krantz, David E; Cook, Ian A

    2014-12-01

    Major depressive disorder (MDD) is a pleomorphic illness originating from gene x environment interactions. Patients with differing symptom phenotypes receive the same diagnosis and similar treatment recommendations without regard to genomics, brain structure or function, or other physiologic or psychosocial factors. Using this present approach, only one third of patients enter remission with the first medication prescribed, and patients may take longer than 1 year to enter remission with repeated trials. Research to improve treatment effectiveness recently has focused on identification of intermediate phenotypes (IPs) that could parse the heterogeneous population of patients with MDD into subgroups with more homogeneous responses to treatment. Such IPs could be used to develop biomarkers that could be applied clinically to match patients with the treatment that would be most likely to lead to remission. Putative biomarkers include genetic polymorphisms, RNA and protein expression (transcriptome and proteome), neurotransmitter levels (metabolome), additional measures of signaling cascades, oscillatory synchrony, neuronal circuits and neural pathways (connectome), along with other possible physiologic measures. All of these measures represent components of a continuum that extends from proximity to the genome to proximity to the clinical phenotype of depression, and there are many levels along this continuum at which useful IPs may be defined. Because of the highly integrative nature of brain systems and the complex neurobiology of depression, the most useful biomarkers are likely to be those with intermediate proximity both to the genome and the clinical phenotype of MDD. Translation of findings across the spectrum from genotype to phenotype promises to better characterize the complex disruptions in signaling and neuroplasticity that accompany MDD, and ultimately to lead to greater understanding of the causes of depressive illness. PMID:25733956

  3. Evidence of tandem repeat and extra thiol-groups resulted in the polymeric formation of bovine haptoglobin: a unique structure of Hp 2-2 phenotype.

    PubMed

    Lai, Yi An; Lai, I Hsiang; Tseng, Chi Feng; Lee, James; Mao, Simon J T

    2007-11-30

    Human plasma Hp is classified as 1-1, 2-1, and 2-2. They are inherited from two alleles Hp 1 and Hp 2, but there is only Hp 1 in almost all the animal species. Hp 2-2 molecule is extremely large and heterogeneous associated with the development of inflammatory-related diseases. In this study, we expressed entire bovine Hp in E. coli as a alphabeta linear form. Interestingly, the antibodies prepared against this form could recognize the subunit of native Hp. In stead of a complicated column method, the antibody was able to isolate bovine Hp via immunoaffinity and gel-filtration columns. The isolated Hp is polymeric containing two major molecular forms (660 and 730 kDa). Their size and hemoglobin binding complex are significantly larger than that of human Hp 2-2. The amino-acid sequence deducted from the nucleotide sequence is similar to human Hp 2 containing a tandem repeat over the alpha chain. Thus, the Hp 2 allele is not unique in human. We also found that there is one additional -SH group (Cys-97) in bovine alpha chain with a total of 8 -SH groups, which may be responsible for the overall polymeric structure that is markedly different from human Hp 2-2. The significance of the finding and its relationship to structural evolution are also discussed. PMID:18047801

  4. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data.

    PubMed

    Köhler, Sebastian; Doelken, Sandra C; Mungall, Christopher J; Bauer, Sebastian; Firth, Helen V; Bailleul-Forestier, Isabelle; Black, Graeme C M; Brown, Danielle L; Brudno, Michael; Campbell, Jennifer; FitzPatrick, David R; Eppig, Janan T; Jackson, Andrew P; Freson, Kathleen; Girdea, Marta; Helbig, Ingo; Hurst, Jane A; Jähn, Johanna; Jackson, Laird G; Kelly, Anne M; Ledbetter, David H; Mansour, Sahar; Martin, Christa L; Moss, Celia; Mumford, Andrew; Ouwehand, Willem H; Park, Soo-Mi; Riggs, Erin Rooney; Scott, Richard H; Sisodiya, Sanjay; Van Vooren, Steven; Wapner, Ronald J; Wilkie, Andrew O M; Wright, Caroline F; Vulto-van Silfhout, Anneke T; de Leeuw, Nicole; de Vries, Bert B A; Washingthon, Nicole L; Smith, Cynthia L; Westerfield, Monte; Schofield, Paul; Ruef, Barbara J; Gkoutos, Georgios V; Haendel, Melissa; Smedley, Damian; Lewis, Suzanna E; Robinson, Peter N

    2014-01-01

    The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have developed logical definitions for 46% of all HPO classes using terms from ontologies for anatomy, cell types, function, embryology, pathology and other domains. This allows interoperability with several resources, especially those containing phenotype information on model organisms such as mouse and zebrafish. Here we describe the updated HPO database, which provides annotations of 7,278 human hereditary syndromes listed in OMIM, Orphanet and DECIPHER to classes of the HPO. Various meta-attributes such as frequency, references and negations are associated with each annotation. Several large-scale projects worldwide utilize the HPO for describing phenotype information in their datasets. We have therefore generated equivalence mappings to other phenotype vocabularies such as LDDB, Orphanet, MedDRA, UMLS and phenoDB, allowing integration of existing datasets and interoperability with multiple biomedical resources. We have created various ways to access the HPO database content using flat files, a MySQL database, and Web-based tools. All data and documentation on the HPO project can be found online. PMID:24217912

  5. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data

    PubMed Central

    Köhler, Sebastian; Doelken, Sandra C.; Mungall, Christopher J.; Bauer, Sebastian; Firth, Helen V.; Bailleul-Forestier, Isabelle; Black, Graeme C. M.; Brown, Danielle L.; Brudno, Michael; Campbell, Jennifer; FitzPatrick, David R.; Eppig, Janan T.; Jackson, Andrew P.; Freson, Kathleen; Girdea, Marta; Helbig, Ingo; Hurst, Jane A.; Jähn, Johanna; Jackson, Laird G.; Kelly, Anne M.; Ledbetter, David H.; Mansour, Sahar; Martin, Christa L.; Moss, Celia; Mumford, Andrew; Ouwehand, Willem H.; Park, Soo-Mi; Riggs, Erin Rooney; Scott, Richard H.; Sisodiya, Sanjay; Vooren, Steven Van; Wapner, Ronald J.; Wilkie, Andrew O. M.; Wright, Caroline F.; Vulto-van Silfhout, Anneke T.; de Leeuw, Nicole; de Vries, Bert B. A.; Washingthon, Nicole L.; Smith, Cynthia L.; Westerfield, Monte; Schofield, Paul; Ruef, Barbara J.; Gkoutos, Georgios V.; Haendel, Melissa; Smedley, Damian; Lewis, Suzanna E.; Robinson, Peter N.

    2014-01-01

    The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have developed logical definitions for 46% of all HPO classes using terms from ontologies for anatomy, cell types, function, embryology, pathology and other domains. This allows interoperability with several resources, especially those containing phenotype information on model organisms such as mouse and zebrafish. Here we describe the updated HPO database, which provides annotations of 7,278 human hereditary syndromes listed in OMIM, Orphanet and DECIPHER to classes of the HPO. Various meta-attributes such as frequency, references and negations are associated with each annotation. Several large-scale projects worldwide utilize the HPO for describing phenotype information in their datasets. We have therefore generated equivalence mappings to other phenotype vocabularies such as LDDB, Orphanet, MedDRA, UMLS and phenoDB, allowing integration of existing datasets and interoperability with multiple biomedical resources. We have created various ways to access the HPO database content using flat files, a MySQL database, and Web-based tools. All data and documentation on the HPO project can be found online. PMID:24217912

  6. A codon change in beta-tubulin which drastically affects microtubule structure in Drosophila melanogaster fails to produce a significant phenotype in Saccharomyces cerevisiae.

    PubMed

    Praitis, V; Katz, W S; Solomon, F

    1991-09-01

    The relative uniformity of microtubule ultrastructure in almost all eukaryotic cells is thought to be a consequence of the conserved elements of tubulin sequence. In support of this idea, a mutation in a beta-tubulin gene of Drosophila melanogaster, occurring at a highly conserved position, produces U-shaped microtubules, suggesting a defect in either nucleation or packing during assembly (M. T. Fuller, J. H. Caulton, J. A. Hutchens, T. C. Kaufman, and E. C. Raff, J. Cell Biol. 104:385-394, 1987, and J. E. Rudolph, M. Kimble, H. D. Hoyle, M. A. Subler, and E. C. Raff, Mol. Cell. Biol. 7:2231-2242, 1987). Surprisingly, we find that introducing the same mutation into the sole beta-tubulin gene of Saccharomyces cerevisiae has virtually no consequences for microtubule structure or function in that organism. PMID:1908555

  7. The Impact of Herbicide-Resistant Rice Technology on Phenotypic Diversity and Population Structure of United States Weedy Rice1[W][OPEN

    PubMed Central

    Burgos, Nilda Roma; Singh, Vijay; Tseng, Te Ming; Black, Howard; Young, Nelson D.; Huang, Zhongyun; Hyma, Katie E.; Gealy, David R.; Caicedo, Ana L.

    2014-01-01

    The use of herbicide-resistant (HR) Clearfield rice (Oryza sativa) to control weedy rice has increased in the past 12 years to constitute about 60% of rice acreage in Arkansas, where most U.S. rice is grown. To assess the impact of HR cultivated rice on the herbicide resistance and population structure of weedy rice, weedy samples were collected from commercial fields with a history of Clearfield rice. Panicles from each weedy type were harvested and tested for resistance to imazethapyr. The majority of plants sampled had at least 20% resistant offspring. These resistant weeds were 97 to 199 cm tall and initiated flowering from 78 to 128 d, generally later than recorded for accessions collected prior to the widespread use of Clearfield rice (i.e. historical accessions). Whereas the majority (70%) of historical accessions had straw-colored hulls, only 30% of contemporary HR weedy rice had straw-colored hulls. Analysis of genotyping-by-sequencing data showed that HR weeds were not genetically structured according to hull color, whereas historical weedy rice was separated into straw-hull and black-hull populations. A significant portion of the local rice crop genome was introgressed into HR weedy rice, which was rare in historical weedy accessions. Admixture analyses showed that HR weeds tend to possess crop haplotypes in the portion of chromosome 2 containing the ACETOLACTATE SYNTHASE gene, which confers herbicide resistance to Clearfield rice. Thus, U.S. HR weedy rice is a distinct population relative to historical weedy rice and shows modifications in morphology and phenology that are relevant to weed management. PMID:25122473

  8. Reprogramming of fibroblast nuclei in cloned bovine embryos involves major structural remodeling with both striking similarities and differences to nuclear phenotypes of in vitro fertilized embryos

    PubMed Central

    Popken, Jens; Brero, Alessandro; Koehler, Daniela; Schmid, Volker J; Strauss, Axel; Wuensch, Annegret; Guengoer, Tuna; Graf, Alexander; Krebs, Stefan; Blum, Helmut; Zakhartchenko, Valeri; Wolf, Eckhard; Cremer, Thomas

    2014-01-01

    Nuclear landscapes were studied during preimplantation development of bovine embryos, generated either by in vitro fertilization (IVF), or generated as cloned embryos by somatic cell nuclear transfer (SCNT) of bovine fetal fibroblasts, using 3-dimensional confocal laser scanning microscopy (3D-CLSM) and structured illumination microscopy (3D-SIM). Nuclear landscapes of IVF and SCNT embryonic nuclei were compared with each other and with fibroblast nuclei. We demonstrate that reprogramming of fibroblast nuclei in cloned embryos requires changes of their landscapes similar to nuclei of IVF embryos. On the way toward the 8-cell stage, where major genome activation occurs, a major lacuna, enriched with splicing factors, was formed in the nuclear interior and chromosome territories (CTs) were shifted toward the nuclear periphery. During further development the major lacuna disappeared and CTs were redistributed throughout the nuclear interior forming a contiguous higher order chromatin network. At all stages of development CTs of IVF and SCNT embryonic nuclei were built up from chromatin domain clusters (CDCs) pervaded by interchromatin compartment (IC) channels. Quantitative analyses revealed a highly significant enrichment of RNA polymerase II and H3K4me3, a marker for transcriptionally competent chromatin, at the periphery of CDCs. In contrast, H3K9me3, a marker for silent chromatin, was enriched in the more compacted interior of CDCs. Despite these striking similarities, we also detected major differences between nuclear landscapes of IVF and cloned embryos. Possible implications of these differences for the developmental potential of cloned animals remain to be investigated. We present a model, which integrates generally applicable structural and functional features of the nuclear landscape. PMID:25482066

  9. Intramolecular phenotypic capacitance in a modular RNA molecule

    PubMed Central

    Hayden, Eric J.; Bendixsen, Devin P.; Wagner, Andreas

    2015-01-01

    Phenotypic capacitance refers to the ability of a genome to accumulate mutations that are conditionally hidden and only reveal phenotype-altering effects after certain environmental or genetic changes. Capacitance has important implications for the evolution of novel forms and functions, but experimentally studied mechanisms behind capacitance are mostly limited to complex, multicomponent systems often involving several interacting protein molecules. Here we demonstrate phenotypic capacitance within a much simpler system, an individual RNA molecule with catalytic activity (ribozyme). This naturally occurring RNA molecule has a modular structure, where a scaffold module acts as an intramolecular chaperone that facilitates folding of a second catalytic module. Previous studies have shown that the scaffold module is not absolutely required for activity, but dramatically decreases the concentration of magnesium ions required for the formation of an active site. Here, we use an experimental perturbation of magnesium ion concentration that disrupts the folding of certain genetic variants of this ribozyme and use in vitro selection followed by deep sequencing to identify genotypes with altered phenotypes (catalytic activity). We identify multiple conditional mutations that alter the wild-type ribozyme phenotype under a stressful environmental condition of low magnesium ion concentration, but preserve the phenotype under more relaxed conditions. This conditional buffering is confined to the scaffold module, but controls the catalytic phenotype, demonstrating how modularity can enable phenotypic capacitance within a single macromolecule. RNA’s ancient role in life suggests that phenotypic capacitance may have influenced evolution since life’s origins. PMID:26401020

  10. The evolution of phenotypic correlations and ‘developmental memory’

    PubMed Central

    Watson, Richard A.; Wagner, Günter P.; Pavlicev, Mihaela; Weinreich, Daniel M.; Mills, Rob

    2014-01-01

    Development introduces structured correlations among traits that may constrain or bias the distribution of phenotypes produced. Moreover, when suitable heritable variation exists, natural selection may alter such constraints and correlations, affecting the phenotypic variation available to subsequent selection. However, exactly how the distribution of phenotypes produced by complex developmental systems can be shaped by past selective environments is poorly understood. Here we investigate the evolution of a network of recurrent non-linear ontogenetic interactions, such as a gene regulation network, in various selective scenarios. We find that evolved networks of this type can exhibit several phenomena that are familiar in cognitive learning systems. These include formation of a distributed associative memory that can ‘store’ and ‘recall’ multiple phenotypes that have been selected in the past, recreate complete adult phenotypic patterns accurately from partial or corrupted embryonic phenotypes, and ‘generalise’ (by exploiting evolved developmental modules) to produce new combinations of phenotypic features. We show that these surprising behaviours follow from an equivalence between the action of natural selection on phenotypic correlations and associative learning, well-understood in the context of neural networks. This helps to explain how development facilitates the evolution of high-fitness phenotypes and how this ability changes over evolutionary time. PMID:24351058

  11. Intramolecular phenotypic capacitance in a modular RNA molecule.

    PubMed

    Hayden, Eric J; Bendixsen, Devin P; Wagner, Andreas

    2015-10-01

    Phenotypic capacitance refers to the ability of a genome to accumulate mutations that are conditionally hidden and only reveal phenotype-altering effects after certain environmental or genetic changes. Capacitance has important implications for the evolution of novel forms and functions, but experimentally studied mechanisms behind capacitance are mostly limited to complex, multicomponent systems often involving several interacting protein molecules. Here we demonstrate phenotypic capacitance within a much simpler system, an individual RNA molecule with catalytic activity (ribozyme). This naturally occurring RNA molecule has a modular structure, where a scaffold module acts as an intramolecular chaperone that facilitates folding of a second catalytic module. Previous studies have shown that the scaffold module is not absolutely required for activity, but dramatically decreases the concentration of magnesium ions required for the formation of an active site. Here, we use an experimental perturbation of magnesium ion concentration that disrupts the folding of certain genetic variants of this ribozyme and use in vitro selection followed by deep sequencing to identify genotypes with altered phenotypes (catalytic activity). We identify multiple conditional mutations that alter the wild-type ribozyme phenotype under a stressful environmental condition of low magnesium ion concentration, but preserve the phenotype under more relaxed conditions. This conditional buffering is confined to the scaffold module, but controls the catalytic phenotype, demonstrating how modularity can enable phenotypic capacitance within a single macromolecule. RNA's ancient role in life suggests that phenotypic capacitance may have influenced evolution since life's origins. PMID:26401020

  12. Building Extended Families

    ERIC Educational Resources Information Center

    McKain, Barbara; McKain, Michael

    1970-01-01

    Discusses need for dissolution of the couple" relationship with substitution of the extended family which would permit each member to maintain individuality and to function on own merit. Suggests group living as preferable alternative. (CJ)

  13. Protein expression and genetic structure of the coral Porites lobata in an environmentally extreme Samoan back reef: Does host genotype limit phenotypic plasticity?

    USGS Publications Warehouse

    Barshis, D.J.; Stillman, J.H.; Gates, R.D.; Toonen, R.J.; Smith, L.W.; Birkeland, C.

    2010-01-01

    The degree to which coral reef ecosystems will be impacted by global climate change depends on regional and local differences in corals' susceptibility and resilience to environmental stressors. Here, we present data from a reciprocal transplant experiment using the common reef building coral Porites lobata between a highly fluctuating back reef environment that reaches stressful daily extremes, and a more stable, neighbouring forereef. Protein biomarker analyses assessing physiological contributions to stress resistance showed evidence for both fixed and environmental influence on biomarker response. Fixed influences were strongest for ubiquitin-conjugated proteins with consistently higher levels found in back reef source colonies both pre and post-transplant when compared with their forereef conspecifics. Additionally, genetic comparisons of back reef and forereef populations revealed significant population structure of both the nuclear ribosomal and mitochondrial genomes of the coral host (FST = 0.146 P < 0.0001, FST = 0.335 P < 0.0001 for rDNA and mtDNA, respectively), whereas algal endosymbiont populations were genetically indistinguishable between the two sites. We propose that the genotype of the coral host may drive limitations to the physiological responses of these corals when faced with new environmental conditions. This result is important in understanding genotypic and environmental interactions in the coral algal symbiosis and how corals may respond to future environmental changes. ?? 2010 Blackwell Publishing Ltd.

  14. Dicyanometallates as Model Extended Frameworks

    PubMed Central

    2016-01-01

    We report the structures of eight new dicyanometallate frameworks containing molecular extra-framework cations. These systems include a number of hybrid inorganic–organic analogues of conventional ceramics, such as Ruddlesden–Popper phases and perovskites. The structure types adopted are rationalized in the broader context of all known dicyanometallate framework structures. We show that the structural diversity of this family can be understood in terms of (i) the charge and coordination preferences of the particular metal cation acting as framework node, and (ii) the size, shape, and extent of incorporation of extra-framework cations. In this way, we suggest that dicyanometallates form a particularly attractive model family of extended frameworks in which to explore the interplay between molecular degrees of freedom, framework topology, and supramolecular interactions. PMID:27057759

  15. Dicyanometallates as Model Extended Frameworks.

    PubMed

    Hill, Joshua A; Thompson, Amber L; Goodwin, Andrew L

    2016-05-11

    We report the structures of eight new dicyanometallate frameworks containing molecular extra-framework cations. These systems include a number of hybrid inorganic-organic analogues of conventional ceramics, such as Ruddlesden-Popper phases and perovskites. The structure types adopted are rationalized in the broader context of all known dicyanometallate framework structures. We show that the structural diversity of this family can be understood in terms of (i) the charge and coordination preferences of the particular metal cation acting as framework node, and (ii) the size, shape, and extent of incorporation of extra-framework cations. In this way, we suggest that dicyanometallates form a particularly attractive model family of extended frameworks in which to explore the interplay between molecular degrees of freedom, framework topology, and supramolecular interactions. PMID:27057759

  16. EHR Big Data Deep Phenotyping

    PubMed Central

    Lenert, L.; Lopez-Campos, G.

    2014-01-01

    Summary Objectives Given the quickening speed of discovery of variant disease drivers from combined patient genotype and phenotype data, the objective is to provide methodology using big data technology to support the definition of deep phenotypes in medical records. Methods As the vast stores of genomic information increase with next generation sequencing, the importance of deep phenotyping increases. The growth of genomic data and adoption of Electronic Health Records (EHR) in medicine provides a unique opportunity to integrate phenotype and genotype data into medical records. The method by which collections of clinical findings and other health related data are leveraged to form meaningful phenotypes is an active area of research. Longitudinal data stored in EHRs provide a wealth of information that can be used to construct phenotypes of patients. We focus on a practical problem around data integration for deep phenotype identification within EHR data. The use of big data approaches are described that enable scalable markup of EHR events that can be used for semantic and temporal similarity analysis to support the identification of phenotype and genotype relationships. Conclusions Stead and colleagues’ 2005 concept of using light standards to increase the productivity of software systems by riding on the wave of hardware/processing power is described as a harbinger for designing future healthcare systems. The big data solution, using flexible markup, provides a route to improved utilization of processing power for organizing patient records in genotype and phenotype research. PMID:25123744

  17. Aspergillus parasiticus SU-1 genome sequence, predicted chromosome structure, and comparative gene expression under aflatoxin-inducing conditions: evidence that differential expression contributes to species phenotype.

    PubMed

    Linz, John E; Wee, Josephine; Roze, Ludmila V

    2014-08-01

    The filamentous fungi Aspergillus parasiticus and Aspergillus flavus produce the carcinogenic secondary metabolite aflatoxin on susceptible crops. These species differ in the quantity of aflatoxins B1, B2, G1, and G2 produced in culture, in the ability to produce the mycotoxin cyclopiazonic acid, and in morphology of mycelia and conidiospores. To understand the genetic basis for differences in biochemistry and morphology, we conducted next-generation sequence (NGS) analysis of the A. parasiticus strain SU-1 genome and comparative gene expression (RNA sequence analysis [RNA Seq]) analysis of A. parasiticus SU-1 and A. flavus strain NRRL 3357 (3357) grown under aflatoxin-inducing and -noninducing culture conditions. Although A. parasiticus SU-1 and A. flavus 3357 are highly similar in genome structure and gene organization, we observed differences in the presence of specific mycotoxin gene clusters and differential expression of specific mycotoxin genes and gene clusters that help explain differences in the type and quantity of mycotoxins synthesized. Using computer-aided analysis of secondary metabolite clusters (antiSMASH), we demonstrated that A. parasiticus SU-1 and A. flavus 3357 may carry up to 93 secondary metabolite gene clusters, and surprisingly, up to 10% of the genome appears to be dedicated to secondary metabolite synthesis. The data also suggest that fungus-specific zinc binuclear cluster (C6) transcription factors play an important role in regulation of secondary metabolite cluster expression. Finally, we identified uniquely expressed genes in A. parasiticus SU-1 that encode C6 transcription factors and genes involved in secondary metabolism and stress response/cellular defense. Future work will focus on these differentially expressed A. parasiticus SU-1 loci to reveal their role in determining distinct species characteristics. PMID:24951444

  18. Reannotation and extended community resources for the genome of the non-seed plant Physcomitrella patens provide insights into the evolution of plant gene structures and functions

    PubMed Central

    2013-01-01

    Background The moss Physcomitrella patens as a model species provides an important reference for early-diverging lineages of plants and the release of the genome in 2008 opened the doors to genome-wide studies. The usability of a reference genome greatly depends on the quality of the annotation and the availability of centralized community resources. Therefore, in the light of accumulating evidence for missing genes, fragmentary gene structures, false annotations and a low rate of functional annotations on the original release, we decided to improve the moss genome annotation. Results Here, we report the complete moss genome re-annotation (designated V1.6) incorporating the increased transcript availability from a multitude of developmental stages and tissue types. We demonstrate the utility of the improved P. patens genome annotation for comparative genomics and new extensions to the cosmoss.org resource as a central repository for this plant “flagship” genome. The structural annotation of 32,275 protein-coding genes results in 8387 additional loci including 1456 loci with known protein domains or homologs in Plantae. This is the first release to include information on transcript isoforms, suggesting alternative splicing events for at least 10.8% of the loci. Furthermore, this release now also provides information on non-protein-coding loci. Functional annotations were improved regarding quality and coverage, resulting in 58% annotated loci (previously: 41%) that comprise also 7200 additional loci with GO annotations. Access and manual curation of the functional and structural genome annotation is provided via the http://www.cosmoss.org model organism database. Conclusions Comparative analysis of gene structure evolution along the green plant lineage provides novel insights, such as a comparatively high number of loci with 5’-UTR introns in the moss. Comparative analysis of functional annotations reveals expansions of moss house-keeping and metabolic genes

  19. A group 6 late embryogenesis abundant protein from common bean is a disordered protein with extended helical structure and oligomer-forming properties.

    PubMed

    Rivera-Najera, Lucero Y; Saab-Rincón, Gloria; Battaglia, Marina; Amero, Carlos; Pulido, Nancy O; García-Hernández, Enrique; Solórzano, Rosa M; Reyes, José L; Covarrubias, Alejandra A

    2014-11-14

    Late embryogenesis-abundant proteins accumulate to high levels in dry seeds. Some of them also accumulate in response to water deficit in vegetative tissues, which leads to a remarkable association between their presence and low water availability conditions. A major sub-group of these proteins, also known as typical LEA proteins, shows high hydrophilicity and a high percentage of glycine and other small amino acid residues, distinctive physicochemical properties that predict a high content of structural disorder. Although all typical LEA proteins share these characteristics, seven groups can be distinguished by sequence similarity, indicating structural and functional diversity among them. Some of these groups have been extensively studied; however, others require a more detailed analysis to advance in their functional understanding. In this work, we report the structural characterization of a group 6 LEA protein from a common bean (Phaseolus vulgaris L.) (PvLEA6) by circular dichroism and nuclear magnetic resonance showing that it is a disordered protein in aqueous solution. Using the same techniques, we show that despite its unstructured nature, the addition of trifluoroethanol exhibited an intrinsic potential in this protein to gain helicity. This property was also promoted by high osmotic potentials or molecular crowding. Furthermore, we demonstrate that PvLEA6 protein is able to form soluble homo-oligomeric complexes that also show high levels of structural disorder. The association between PvLEA6 monomers to form dimers was shown to occur in plant cells by bimolecular fluorescence complementation, pointing to the in vivo functional relevance of this association. PMID:25271167

  20. A Group 6 Late Embryogenesis Abundant Protein from Common Bean Is a Disordered Protein with Extended Helical Structure and Oligomer-forming Properties*

    PubMed Central

    Rivera-Najera, Lucero Y.; Saab-Rincón, Gloria; Battaglia, Marina; Amero, Carlos; Pulido, Nancy O.; García-Hernández, Enrique; Solórzano, Rosa M.; Reyes, José L.; Covarrubias, Alejandra A.

    2014-01-01

    Late embryogenesis-abundant proteins accumulate to high levels in dry seeds. Some of them also accumulate in response to water deficit in vegetative tissues, which leads to a remarkable association between their presence and low water availability conditions. A major sub-group of these proteins, also known as typical LEA proteins, shows high hydrophilicity and a high percentage of glycine and other small amino acid residues, distinctive physicochemical properties that predict a high content of structural disorder. Although all typical LEA proteins share these characteristics, seven groups can be distinguished by sequence similarity, indicating structural and functional diversity among them. Some of these groups have been extensively studied; however, others require a more detailed analysis to advance in their functional understanding. In this work, we report the structural characterization of a group 6 LEA protein from a common bean (Phaseolus vulgaris L.) (PvLEA6) by circular dichroism and nuclear magnetic resonance showing that it is a disordered protein in aqueous solution. Using the same techniques, we show that despite its unstructured nature, the addition of trifluoroethanol exhibited an intrinsic potential in this protein to gain helicity. This property was also promoted by high osmotic potentials or molecular crowding. Furthermore, we demonstrate that PvLEA6 protein is able to form soluble homo-oligomeric complexes that also show high levels of structural disorder. The association between PvLEA6 monomers to form dimers was shown to occur in plant cells by bimolecular fluorescence complementation, pointing to the in vivo functional relevance of this association. PMID:25271167

  1. Pseudomonas Aeruginosa Resistance Phenotypes and Phenotypic Highlighting Methods

    PubMed Central

    BĂLĂŞOIU, MARIA; BĂLĂŞOIU, A.T.; MĂNESCU, RODICA; AVRAMESCU, CARMEN; IONETE, OANA

    2014-01-01

    Pseudomonas aeruginosa genus bacteria are well known for their increased drug resistance (phenotypic ang genotypic resistance). The most important resistance mechanisms are: enzyme production, reduction of pore expression, reduction of the external membrane proteins expression, efflux systems, topoisomerase mutations. These mechanisms often accumulate and lead to multidrug ressitance strains emergence. The most frequent acquired resistance mechanisms are betalactamase-type enzyme production (ESBLs, AmpC, carbapenemases), which determine variable phenotypes of betalactamines resistance, phenotypes which are associated with aminoglycosides and quinolones resistance. The nonenzymatic drug resistance mechanisms are caused by efflux systems, pore reduction and penicillin-binding proteins (PBP) modification, which are often associated to other resistance mechanisms. Phenotypic methods used for testing these mechanisms are based on highlighting these phenotypes using Kirby Bauer antibiogram, clinical breakpoints, and “cut off” values recommended by EUCAST 2013 standard, version 3.1. PMID:25729587

  2. Web-based phenotyping for Tourette Syndrome: Reliability of common co-morbid diagnoses.

    PubMed

    Darrow, Sabrina M; Illmann, Cornelia; Gauvin, Caitlin; Osiecki, Lisa; Egan, Crystelle A; Greenberg, Erica; Eckfield, Monika; Hirschtritt, Matthew E; Pauls, David L; Batterson, James R; Berlin, Cheston M; Malaty, Irene A; Woods, Douglas W; Scharf, Jeremiah M; Mathews, Carol A

    2015-08-30

    Collecting phenotypic data necessary for genetic analyses of neuropsychiatric disorders is time consuming and costly. Development of web-based phenotype assessments would greatly improve the efficiency and cost-effectiveness of genetic research. However, evaluating the reliability of this approach compared to standard, in-depth clinical interviews is essential. The current study replicates and extends a preliminary report on the utility of a web-based screen for Tourette Syndrome (TS) and common comorbid diagnoses (obsessive compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD)). A subset of individuals who completed a web-based phenotyping assessment for a TS genetic study was invited to participate in semi-structured diagnostic clinical interviews. The data from these interviews were used to determine participants' diagnostic status for TS, OCD, and ADHD using best estimate procedures, which then served as the gold standard to compare diagnoses assigned using web-based screen data. The results show high rates of agreement for TS. Kappas for OCD and ADHD diagnoses were also high and together demonstrate the utility of this self-report data in comparison previous diagnoses from clinicians and dimensional assessment methods. PMID:26054936

  3. Serine protease activity and residual LEKTI expression determine phenotype in Netherton syndrome.

    PubMed

    Hachem, Jean-Pierre; Wagberg, Fredrik; Schmuth, Matthias; Crumrine, Debra; Lissens, Willy; Jayakumar, Arumugam; Houben, Evi; Mauro, Theodora M; Leonardsson, Göran; Brattsand, Maria; Egelrud, Torbjorn; Roseeuw, Diane; Clayman, Gary L; Feingold, Kenneth R; Williams, Mary L; Elias, Peter M

    2006-07-01

    Mutations in the SPINK5 gene encoding the serine protease (SP) inhibitor, lymphoepithelial-Kazal-type 5 inhibitor (LEKTI), cause Netherton syndrome (NS), a life-threatening disease, owing to proteolysis of the stratum corneum (SC). We assessed here the basis for phenotypic variations in nine patients with "mild", "moderate", and "severe" NS. The magnitude of SP activation correlated with both the barrier defect and clinical severity, and inversely with residual LEKTI expression. LEKTI co-localizes within the SC with kallikreins 5 and 7 and inhibits both SP. The permeability barrier abnormality in NS was further linked to SC thinning and proteolysis of two lipid hydrolases (beta-glucocerebrosidase and acidic sphingomyelinase), with resultant disorganization of extracellular lamellar membranes. SC attenuation correlated with phenotype-dependent, SP activation, and loss of corneodesmosomes, owing to desmoglein (DSG)1 and desmocollin (DSC)1 degradation. Although excess SP activity extended into the nucleated layers in NS, degrading desmosomal mid-line structures with loss of DSG1/DSC1, the integrity of the nucleated epidermis appears to be maintained by compensatory upregulation of DSG3/DSC3. Maintenance of sufficient permeability barrier function for survival correlated with a compensatory acceleration of lamellar body secretion, providing a partial permeability barrier in NS. These studies provide a mechanistic basis for phenotypic variations in NS, and describe compensatory mechanisms that permit survival of NS patients in the face of unrelenting SP attack. PMID:16601670

  4. Why Quantification Matters: Characterization of Phenotypes at the Drosophila Larval Neuromuscular Junction.

    PubMed

    Sanhueza, Mario; Kubasik-Thayil, Anisha; Pennetta, Giuseppa

    2016-01-01

    Most studies on morphogenesis rely on qualitative descriptions of how anatomical traits are affected by the disruption of specific genes and genetic pathways. Quantitative descriptions are rarely performed, although genetic manipulations produce a range of phenotypic effects and variations are observed even among individuals within control groups. Emerging evidence shows that morphology, size and location of organelles play a previously underappreciated, yet fundamental role in cell function and survival. Here we provide step-by-step instructions for performing quantitative analyses of phenotypes at the Drosophila larval neuromuscular junction (NMJ). We use several reliable immuno-histochemical markers combined with bio-imaging techniques and morphometric analyses to examine the effects of genetic mutations on specific cellular processes. In particular, we focus on the quantitative analysis of phenotypes affecting morphology, size and position of nuclei within the striated muscles of Drosophila larvae. The Drosophila larval NMJ is a valuable experimental model to investigate the molecular mechanisms underlying the structure and the function of the neuromuscular system, both in health and disease. However, the methodologies we describe here can be extended to other systems as well. PMID:27213489

  5. Why Quantification Matters: Characterization of Phenotypes at the Drosophila Larval Neuromuscular Junction

    PubMed Central

    Pennetta, Giuseppa

    2016-01-01

    Most studies on morphogenesis rely on qualitative descriptions of how anatomical traits are affected by the disruption of specific genes and genetic pathways. Quantitative descriptions are rarely performed, although genetic manipulations produce a range of phenotypic effects and variations are observed even among individuals within control groups. Emerging evidence shows that morphology, size and location of organelles play a previously underappreciated, yet fundamental role in cell function and survival. Here we provide step-by-step instructions for performing quantitative analyses of phenotypes at the Drosophila larval neuromuscular junction (NMJ). We use several reliable immuno-histochemical markers combined with bio-imaging techniques and morphometric analyses to examine the effects of genetic mutations on specific cellular processes. In particular, we focus on the quantitative analysis of phenotypes affecting morphology, size and position of nuclei within the striated muscles of Drosophila larvae. The Drosophila larval NMJ is a valuable experimental model to investigate the molecular mechanisms underlying the structure and the function of the neuromuscular system, both in health and disease. However, the methodologies we describe here can be extended to other systems as well. PMID:27213489

  6. Extended x-ray absorption fine structure study of MnFeP0.56Si0.44 compound

    NASA Astrophysics Data System (ADS)

    Li, Ying-Jie; Haschaolu, W.; Wurentuya; Song, Zhi-Qiang; Ou, Zhi-Qiang; Tegus, O.; Nakai, Ikuo

    2015-08-01

    The MnFeP0.56Si0.44 compound is investigated by x-ray diffraction, magnetic measurements, and x-ray absorption fine structure spectroscopy. It crystallizes in Fe2P-type structure with the lattice parameters a = b = 5.9823(0) Å and c = 3.4551(1) Å and undergoes a first-order phase transition at the Curie temperature of 255 K. The Fe K edge and Mn K edge x-ray absorption fine structure spectra show that Mn atoms mainly reside at 3g sites, while 3f sites are occupied by Fe atoms. The distances between the absorbing Fe atom and the first and second nearest neighbor Fe atoms in a 3f-layer shift from 2.65 Å and 4.01 Å in the ferromagnetic state to 2.61 Å and 3.96 Å in the paramagnetic phase. On the other hand, the distance between the 3g-layer and 3f-layer changes a little as 2.66 Å-2.73 Å below the Curie temperature and 2.68 Å-2.75 Å above it. Project supported by the National Natural Science Foundation of China (Grant Nos. 51461035, 51161017, and 11404176), the Scientific Research Projects of the Higher Educational Department of Inner Mongolian Autonomous Region (Grant No. NJZZ14033). The XAFS measurement was performed under the approval of Photon Factory Program Advisory Committee (Proposal Nos. 2012G095 an